bluuebunny/crossref_metadata_2025 huggingface dataset:
Signalling switches maintain intercellular communication in the vascular endothelium
Authors: Buckley Charlotte , Lee Matthew D. , Zhang Xun , Wilson Calum , McCarron John G.
Published: April 2024

Background and Purpose

The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co‐ordination centre that controls a wide range of vascular functions including the regulation of blood pressure and blood flow. To co‐ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved.

Experimental Approach

Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels.

Key Results

Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3‐induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C‐dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation.

Conclusion and Implications

These results show that signalling switches underlie endothelial cell‐to‐cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.
Leaf traits and leaf‐to‐air temperature differences in tropical plants suggest variability in thermoregulatory capacities across elevations
Authors: Pedraza Sara
Published: April 2024

Plant thermoregulation is essential for understanding the potential effects of climate change on terrestrial ecosystems. This study provides evidence indicating variation of leaf functional traits and leaf‐to‐air temperature across the elevation gradient. These results support the existence of distinct plant adaptations for thermoregulation across different elevation zones.

Abstract in Spanish is available with online material.
Choosing Among Undesirable Options: Children Consider Desirability of Available Choices in Evaluation of Socially Mindful Actions
Authors: Li Sixian , Zhao Xin
Published: April 2024

Previous studies show that adults and children evaluate the act of leaving a choice for others as prosocial, and have termed such actions as socially mindful actions. The current study investigates how the desirability of the available options (i.e., whether the available options are desirable or not) may influence adults’ and children's evaluation of socially mindful actions. Children (N = 120, 4‐ to 6‐year‐olds) and adults (N = 124) were asked to evaluate characters selecting items for themselves from a set of three items—two identical items and one unique item—in a way that either leaves a choice (two diverse items) or leaves no choice (two identical items) for the next person (i.e., the beneficiary). We manipulated whether the available options were either desirable or undesirable (i.e., damaged). We found that adults’ and 6‐year‐olds’ evaluation of socially mindful actions is moderated by the desirability of the options. Although they evaluate the act of leaving a choice for others as nicer than the act of leaving no choice both when the choosing options are desirable and when they are undesirable, the discrepancy in the evaluation becomes significantly smaller when the choosing options are undesirable. We also found that inference of the beneficiary's feeling underlies social evaluation of the actor leaving a choice (or not). These findings suggest that children consider both the diversity of options left and the desirability of the available options in understanding and evaluating socially mindful acts.
A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects
Authors: Gao Xianglei , Di Yujing , Lv Yuan , Luan Yingcai , Xiong Yang , Xu Yuli , Li Yusheng , Guo Linfeng , Li Xiaoping , Deng Li , Zhuang Yulei , Hou Jie
Published: April 2024

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single‐center, randomized, open, single‐dose, parallel‐controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17‐day observation period after administration, and a 7‐day safety follow‐up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration‐time curve from zero time to the estimated infinite time (AUC0–∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0–∞ geometric mean ratios were 102.9%–122.0% and 97.1%–116.9%, respectively, which were both within the range of 80.00%–125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.
Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy
Authors: Al‐Zuhairy Ali , Jakobsen Johannes , Krarup Christian
Published: April 2024

Background

To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3–37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow‐up.

Results

At follow‐up, the Z‐score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment‐free period of 0.3 years (0.2–0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z‐scores (0.9–17.0, p = 0.06) was observed in five patients with a treatment‐free period of 4.0 years (0.9–9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow‐up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss.

Conclusion

Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.
A family reunion of “clinical cousins”: Attachment and emotion in four family‐oriented therapy models
Authors: Sabey Allen K. , Lafrance Adele , Furrow James , Diamond Guy , Hughes Daniel
Published: April 2024

Attachment theory and the science of emotion provide a strong foundation for intervention at the family system level. Four therapeutic models in particular, Attachment‐Based Family Therapy, Emotion‐Focused Family Therapy, Dyadic Developmental Psychotherapy, and Emotionally Focused Family Therapy, demonstrate how a broad and accurate view of attachment relationships and emotion can be utilized to effectively intervene for a variety of presenting problems in a relational and empathic way for all involved. This paper continues a conversation that began at the Summit for Attachment and Emotion in Family Therapy in 2021 and aims to foster openness, collaboration, and affirmation between four different models of family therapy with shared theoretical roots. The presenters at the Summit and the authors of this paper view similarities across these models as validating and differences as opportunities to serve more families in unique ways, learning from one another's creativity to promote healing within families in the most effective and efficient ways possible. The paper frames the value of attachment theory and emotion science for family therapy, discusses the importance of learning from a variety of models with shared theoretical roots, presents brief summaries of the four models presented at the Summit, compares the models for similarities and complementarities, and shares highlights from each of the presenters from the Summit.
Sonochemical synthesis of CeO2 nanoparticles with high photocatalytic and antibacterial activities under visible light
Authors: Zeng Shenghui , Shui Anze , Yu Hulei , He Chao
Published: April 2024

Cerium oxide (CeO2), one of the most significant heterogeneous catalysts, has attracted extensive research interest. Herein, ultrafine spherical CeO2 with a diameter of 5 nm is successfully synthesized within a reaction time of 25 min by a simple and environmentally friendly sonochemical method without any additional oxidants or high temperature and pressure conditions, and 50 nm spherical CeO2 was obtained by heat treating the 5 nm spherical CeO2 in 400°C air atmosphere condition for 3 h. By controlling the ultrasonic condition, a specific surface area of up to 194.2 m2/g and a bandgap as low as 2.2 eV are achieved in the CeO2 nanoparticles without any heat treatment. Further study has shown that the as‐prepared spherical CeO2 without heat treatment exhibits remarkable photocatalytic and antibacterial activities under visible light conditions. The study is beneficial for energy conservation in fabricating ultrafine photocatalytic and antibacterial nanomaterials.
An integrated analysis of the anticarcinogenic role of forkhead box protein 1 in oesophageal squamous cell carcinoma
Authors: Ye Guanzhi , Pan Gaojian , Zhu Xiaolei , Li Ning , Liu Hongming , Geng Guojun , Jiang Jie
Published: April 2024

Forkhead box protein 1 (FOXP1) serves as a tumour promoter or suppressor depending on different cancers, but its effect in oesophageal squamous cell carcinoma has not been fully elucidated. This study investigated the role of FOXP1 in oesophageal squamous cell carcinoma through bioinformatics analysis and experimental verification. We determined through public databases that FOXP1 expresses low in oesophageal squamous cell carcinoma compared with normal tissues, while high expression of FOXP1 indicates a better prognosis. We identified potential target genes regulated by FOXP1, and explored the potential biological processes and signalling pathways involved in FOXP1 in oesophageal squamous cell carcinoma through GO and KEGG enrichment, gene co‐expression analysis, and protein interaction network construction. We also analysed the correlation between FOXP1 and tumour immune infiltration levels. We further validated the inhibitory effect of FOXP1 on the proliferation of oesophageal squamous cell carcinoma cells through CCK‐8, colony formation and subcutaneous tumour formation assays. This study revealed the anticarcinogenic effect of FOXP1 in oesophageal squamous cell carcinoma, which may serve as a novel biological target for the treatment of tumour.
From Menace to Mundane: Moral Hazard and the Politics of the European Central Bank's Government Bond Purchases
Authors: Chang Michele , Howarth David , Pierret Laura
Published: April 2024

During the Eurozone's sovereign debt crisis, the ideational consensus that shaped the foundation of Economic and Monetary Union (EMU) was destabilized by disagreement on unconventional monetary policies (UMPs), specifically government bond purchases. In the ECB's 2021 strategy review, however, UMPs were confirmed as standard elements of the European Central Bank's (ECB) toolbox. What happened? One argument frequently presented to question the legitimacy of UMPs is that they undermine the prior objective of the EMU of avoiding moral hazard. We analyse the politics of UMPs by focusing upon how top officials in four major Eurozone central banks have discursively constructed the relationship between the ECB's purchase of sovereign debt and moral hazard. We find that top central bank officials aligned to a large degree on the non‐necessary causal relationship between government bond purchases and moral hazard, which reinforced its legitimacy and eventual acceptance as ‘conventional’.
Risk factors for inadequate bowel preparation before colonoscopy: A meta‐analysis
Authors: Feng Lina , Guan Jialun , Dong Ruonan , Zhao Kai , Zhang Mingyu , Xia Suhong , Zhang Yu , Chen Liping , Xiao Fang , Liao Jiazhi
Published: April 2024

Objective

This meta‐analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP).

Methods

We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals.

Results

A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta‐analyses of observational studies revealed that three preparation‐related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation‐related factors (preparation‐to‐colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta‐analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate.

Conclusions

We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation‐related elements were more strongly associated with IBP. These findings may help clinicians identify high‐risk individuals and provide guidance for IBP prevention.
Valorization of waste seashells as bioadsorbent for sunflower oil bleaching
Authors: Seçilmiş Şakir Selçuk
Published: April 2024

In this study, the performance of waste seashells (SS) in adsorbing color and oxidation parameters during the bleaching process of sunflower oil was evaluated and compared with that of commercial clay. Seashell activation methods included microwave treatment (900 W for 30 min), acid treatment (7 N H2SO4), and a combination of both. Interestingly, the unactivated SS demonstrated superior adsorption performance compared with the activated SS. SS, which have the ability to eliminate color pigments like chlorophyll and carotenoid, were found to be effective in this regard. However, their effectiveness in reducing the peroxide and p‐anisidine value was not as successful as that of commercial clay. Free acidity content remained constant across all treatments. SS emerged as a cost‐effective alternative adsorbent, promising in preventing environmental pollution. Their use signifies a valuable contribution to sustainability. This study sheds light on SS potential as an eco‐friendly solution in industrial processes, warranting further exploration and application.

Practical applications

Biowaste valorization is a process that involves converting organic waste materials into valuable products, energy, or resources, instead of simply disposing of them in landfills or incinerating them. This approach has gained significance owing to its potential to address environmental, economic, and social challenges. In this respect, this study presents that bioadsorbent obtained from waste SS can be utilized for bleaching of sunflower oil.
Effects of pretreatments involving ohmic heating and infrared radiation on the drying process of bananas using hot air
Authors: Zare Amir Hossein , Azadbakht Mohsen , Naseri Reza
Published: April 2024

Nowadays, the hot air drying process is the most widely used method for producing dried food and agricultural products due to its suitable investment and low operational costs. However, one of the disadvantages of drying with hot air is the prolonged drying time, which sometimes leads to serious damage to the quality characteristics of the resulting products, especially at high temperatures. Therefore, there is a need to find the most suitable conditions for producing high‐quality dried products. To conduct this experiment, after determining the desired number of samples, infrared preheating and ohmic heating were performed sequentially. In the first stage of preheating, the samples were placed in the ohmic heating device, and in the second stage, they were exposed to infrared radiation. Then, the samples were transferred to a hot air dryer for complete drying. The results showed that the antioxidant content increased with the increase in the thickness of the banana slices. Moreover, an increase in the drying temperature and the number of infrared lamps led to a reduction in the antioxidant content. The slices with less thickness and higher drying temperatures had the minimum phenol content. The maximum and minimum measured values of the total phenol content were 34.51 and 37.32, respectively. The range of variation in the solid soluble content was between 11.708% and 19.5437% Brix. In addition, at the same temperature values, an increase in the thickness of the banana slices resulted in a decrease in the solid soluble content of the samples. Furthermore, with an increase in the temperature for slices of the same thickness, the solid soluble content of the samples increased.

Practical applications

The purpose of this research is to evaluate the effect of the thickness factors of the sample pieces, the temperature of the hot air dryer along with ohmic heating pretreatments, and the infrared lamps in the hot air dryer on the quality indicators of banana.
Arabidopsis mRNA export factor MOS11: molecular interactions and role in abiotic stress responses
Authors: Rödel Amelie , Weig Ina , Tiedemann Sophie , Schwartz Uwe , Längst Gernot , Moehle Christoph , Grasser Marion , Grasser Klaus D.
Published: April 2024

Transcription and export (TREX) is a multi‐subunit complex that links synthesis, processing and export of mRNAs. It interacts with the RNA helicase UAP56 and export factors such as MOS11 and ALYs to facilitate nucleocytosolic transport of mRNAs. Plant MOS11 is a conserved, but sparsely researched RNA‐binding export factor, related to yeast Tho1 and mammalian CIP29/SARNP.

Using biochemical approaches, the domains of Arabidopsis thaliana MOS11 required for interaction with UAP56 and RNA‐binding were identified. Further analyses revealed marked genetic interactions between MOS11 and ALY genes. Cell fractionation in combination with transcript profiling demonstrated that MOS11 is required for export of a subset of mRNAs that are shorter and more GC‐rich than MOS11‐independent transcripts.

The central α‐helical domain of MOS11 proved essential for physical interaction with UAP56 and for RNA‐binding. MOS11 is involved in the nucleocytosolic transport of mRNAs that are upregulated under stress conditions and accordingly mos11 mutant plants turned out to be sensitive to elevated NaCl concentrations and heat stress.

Collectively, our analyses identify functional interaction domains of MOS11. In addition, the results establish that mRNA export is critically involved in the plant response to stress conditions and that MOS11 plays a prominent role at this.
Ethnic votes and parties' mobilization: A case study of New Zealand
Authors: Zhao Luna L.
Published: April 2024

The aim of this research is to investigate how ethnicity and political parties' mobilization efforts influence the voting preferences of migrants in electoral contexts. To achieve this, an empirical study was conducted, focusing on New Zealand's two major parties (New Zealand National and New Zealand Labour Party) and their mobilization practice targeting ethnic Chinese voters. This research adopted a mixed‐methods approach, involving conducting interviews with Chinese community leaders and surveys within the community. The quantitative findings establish a positive correlation between a party's mobilization efforts and the level of support from Chinese ethnic voters. Furthermore, the research underscores the importance of genuine targeting, emphasizing the recognition and addressing of the unique needs and concerns of ethnic minority communities, rather than engaging in mere tokenism.

Related Articles

Escaleras, Monica, Dukhong Kim, and Kevin M. Wagner. 2019. “You Are Who You Think You Are: Linked Fate and Vote Choices among Latino Voters.” Politics & Policy 47(5): 902–30. https://doi.org/10.1111/polp.12329.

McKay, Spencer. 2021. “The Politics of Referendum Rules: Evidence from New Zealand (1893–2016).” Politics & Policy 50(1): 137–53. https://doi.org/10.1111/polp.12445.

Stokes‐Brown, Atiya Kai. 2009. “The Hidden Politics of Identity: Racial Self‐Identification and Latino Political Engagement.” Politics & Policy 37(6): 1281–305. https://doi.org/10.1111/j.1747‐1346.2009.00220.x.
Kant's mature account of monads as objects in the idea
Authors: Betti Pierpaolo
Published: April 2024

In On a Discovery, Kant depicts monads as simple beings that are thought in the idea as the ground of appearances. He argues that his account of monads is partially in line with both Leibniz's monadology and his own critical philosophy. However, in the Critique of Pure Reason, Kant appears to depart from the monadologies of his predecessors. In this article, I make sense of Kant's late subscription to a version of Leibniz's monadology by arguing that Kant considers monads to be the objects represented through cosmological and psychological ideas posited by reason in its search for the unconditioned conditions of appearances. In particular, I point to what I take to be two instances of what Kant calls “objects in the idea” in the Critique of Pure Reason, namely (a) the substratum of matter qua ground of external appearances, and (b) the soul qua ground of internal appearances. Drawing on Kant's reply to Eberhard and the Transcendental Dialectic of the first Critique, I highlight the merely regulative—and yet fundamental—role that monads conceived as objects of reason play in Kant's critical philosophy.
Masculine, independent, and “not acting”: Hegemonic masculinity and femmephobia within an online community of queer men
Authors: Leeder George Frederick
Published: April 2024

This article focuses on queer men's relationship with hegemonic masculinity and femmephobia. The study was conducted with the aim of investigating how different understandings of masculinity and femininity can fuel femmephobia. Ten posts within the Reddit forum “r/gaybros” were analyzed, along with their 1356 collective comments. Within the analysis, the users of r/gaybros were found to define their expression of masculinity as independent and free from any societal constraints or expectations. To be masculine meant resisting the stereotype that associates queerness with femininity. Femininity was then understood as failing to reach this construction of masculinity and as vacuously conforming to the stereotype that queer men are feminine. Consequently, the users constructed masculinity and femininity in a complementary and hierarchical way. Not only do they devalue and regulate femininity, but the femmephobia that they reproduce is a necessary part of their understanding of masculinity. This article consequently argues that the users of r/gaybros constructed a local form of hegemonic masculinity which contrasts with previous research that understands gay men as capable of imitating hegemonic masculinity but ultimately excluded from its construction.
Absence of evidence of transfusion transmission risk of Creutzfeldt‐Jakob disease in the United States: Results froma 28‐year lookback study
Authors: Crowder Lauren A. , Dodd Roger Y. , Schonberger Lawrence B.
Published: April 2024

Background

For many years, there has been concern about the risk of transmission of classic forms of Creutzfeldt‐Jakob disease (CJD) by blood transfusion, particularly after the recognition of such transmission of variant CJD (vCJD). We report on a 28‐year lookback study of recipients of blood from donors who subsequently developed CJD.

Methods

Patients with diagnosed CJD and a history of blood donation were identified. Blood centers were asked to provide information about the distribution of the donations and consignees were requested to provide information about the recipients of the donations. Vital status of each available recipient was determined and, if deceased, the reported cause(s) of death were obtained primarily from the National Death Index. All recipients included in the study database contributed person‐time up to the last recorded review of vital status.

Results

There were 84 eligible donors who gave 3284 transfusable components, and it was possible to evaluate 1245 recipients, totaling 6495 person‐years of observation. The mean observation period per recipient was 5.5 years with a maximum of 51 years. No case of CJD or prion disease was reported among the recipient population.

Discussion

The study suggests that CJD may not be transfusion‐transmissible, a position in agreement with similar findings from two similar European reports amounting to an overall observation period of 15,500 person‐years. These studies have supported the conclusion that the risk, if any, of transmission of CJD by blood products is extremely small and remains theoretical.
A Decision Support Framework for Robust Multilevel Co-Design Exploration of Manufacturing Supply Networks
Authors: Baby Mathew , Guptan Akshay , Broussard Jacob , Allen Janet K. , Mistree Farrokh , Nellippallil Anand Balu
Published: April 2024

The design of a manufacturing supply network (MSN) requires the consideration of decisions made by different groups at multiple levels and their interactions that include potential conflicts. Decisions are typically made based on information from computational simulations that are abstractions of reality and, therefore, embody uncertainty. This necessitates focusing on design space exploration to identify robust satisficing solution sets that are relatively insensitive to uncertainty. Current frameworks that support robust satisficing design space exploration are limited by their capability to support the efficient exploration of multilevel design spaces simultaneously. In this paper, we present the Framework for Robust Multilevel Co-Design Exploration (FRoMCoDE), a decision support framework that allows designers to (i) model decision problems across multiple levels and their interactions, (ii) consider uncertainties in the decision problems, and (iii) visualize and systematically carry out simultaneous exploration of multilevel design spaces, termed co-design exploration. In FRoMCoDE, we combine the coupled-compromise Decision Support Problem construct, where a combination of the Preemptive and Archimedean formulations is used, with robust design constructs and interpretable-Self-Organizing Maps (iSOM)-based visualization to facilitate robust co-design. We use a steel MSN problem with decisions made at two levels to test the framework. Using the problem, we demonstrate FRoMCoDE's efficacy in supporting designers in (i) modeling multilevel decision problems and their interactions, considering the uncertainties, and (ii) the efficient co-design exploration of multilevel design spaces. FRoMCoDE is generic and supports designers in the robust co-design exploration of multilevel systems.
Analysis of Instantaneous Kinematic Properties Regarding the Shape of Robotic Mechanisms
Authors: Arikawa Keisuke
Published: April 2024

A theoretical framework for analyzing instantaneous kinematic properties regarding the shape of robotic mechanisms is proposed. Conventional research on kinematic analysis regarding the shape has been conducted with the primary goal of approximating a target shape. In contrast, this study does not set a target shape, and instantaneous kinematic properties regarding the shape formed by multiple reference links are analyzed. The properties provide information about the shape change that is easy to achieve and about the controllability of the shape. Furthermore, in contrast to the standard kinematic analysis of robot manipulators that assumes having a single hand link configuration with respect to the base link, the kinematic analysis in this study is free from this assumption. When analyzing instantaneous kinematic properties regarding the shape, it is crucial to decompose motions of reference links into rigid and nonrigid components. After formulating this decomposition, the Jacobian matrices that relate active joint velocities and nonrigid motions are defined. The indices of instantaneous kinematic properties regarding the shape are defined on the basis of the Jacobian matrices. Moreover, application examples using the defined indices are demonstrated.
Investigation of the Map Width Improvement in a Radially Reduced Diffuser Design Concept for a Centrifugal Compressor
Authors: McLaughlin Laura , Spence Stephen , Rusch Daniel , Stuart Charles , Geron Marco , So Kwok Kai , Fischer Magnus
Published: April 2024

Often, an improvement in performance at one operating point in a compressor/turbine operating map will lead to a reduction in performance at another area. For example, improving the efficiency of a compressor at design point (DP) may result in a reduction of efficiency at other operating points or it may result in a reduced stable operating range. In order to reduce the compressor cost and weight, a 15% radial reduction was applied to the diffuser passage length of a high pressure ratio centrifugal compressor. The diffuser endwall was diverged to achieve an appropriate area ratio from diffuser inlet to outlet. Two different vane shapes were considered with the radially reduced diffuser passage. The first diffuser vane was a scaled version of the baseline airfoil vane shape and this was used to develop an understanding of the impact of the passage length reduction and diverging endwall. The second vane geometry was parameterized using an unconventional method derived from published literature and optimized to improve performance at DP. Increased losses were generated through the diffuser passages of the radially reduced designs, but this was compensated for by lower losses through the volute due to more desirable flow at volute inlet. As a result, the radially reduced designs not only matched the performance of the baseline configuration, but also succeeded in achieving a marginal efficiency improvement. Furthermore, despite not being one of the goals of the optimization procedure, an extension of the stable operating range of 36% and 20% at the highest speed condition was achieved for the scaled and optimized designs, respectively. The current study focuses on understanding the physical reasons that generated this significant enhancement to the compressor operating range. In order to acquire the desired understanding, experimental data is presented to validate the Computational Fluid Dynamics (CFD) model and a detailed numerical investigation is presented to explain the changes in the flow field within the radially reduced designs. The study focuses on low flow rate operating points, necessitating the use of an Unsteady Reynolds Averaged Navier-Stokes (URANS) approach to analyse the flow. Detailed scrutiny of the flow field revealed a secondary flow feature in the diffuser passage which resulted in higher diffuser passage losses at DP but stabilised the flow as it developed for lower mass flow rate operating points.
Strategies for High-Accuracy Measurements of Stage Efficiency for a Cooled Turbine
Authors: Rozman Maria , Berdanier Reid A. , Barringer Michael D. , Thole Karen A.
Published: April 2024

Gas turbines are used in a broad range of aerospace and land-based applications from power generation to aviation, and their usage is projected to continue to grow. It is therefore critical to improve turbine efficiency thereby reducing fuel consumption and carbon emissions. Demonstration of new efficiency-increasing technologies requires efficiency measurements that are accurate and repeatable. The Steady Thermal Aero Research Turbine (START) Laboratory at the Pennsylvania State University uses a unique 360-deg traversing system for temperature and pressure probes with redundant torque measurements to quantify thermal efficiency for a single-stage cooled test turbine. Flows in the full annulus have been analyzed and compared with subsector traverse segments centered at different circumferential positions to determine the appropriate sector size. The results from this investigation indicate that the full 360-deg measurement is recommended to minimize variation in calculated stage efficiencies. This study also compares the circumferential variations in thermodynamic and mechanical efficiency definitions, finding that the thermodynamic efficiency calculation results in a higher accuracy for full exit plane measurements. A statistical analysis was then performed to determine the number of 360-deg traverse measurements required to achieve a precision uncertainty at most that of the bias uncertainty. This study establishes guidelines to streamline experimental procedures by limiting the necessary test count per day per operating condition to five measurements for at most four test days. Following these procedures establishes a bias of ɛb = 0.19 points, resulting in a total uncertainty of at most ɛt = 0.32 points.
Posterior Covariance Matrix Approximations
Authors: Schmid Abigail C. , Andrews Stephen A.
Published: April 2024

The Davis equation of state (EOS) is commonly used to model thermodynamic relationships for high explosive (HE) reactants. Typically, the parameters in the EOS are calibrated, with uncertainty, using a Bayesian framework and Markov Chain Monte Carlo (MCMC) methods. However, MCMC methods are computationally expensive, especially for complex models with many parameters. This paper provides a comparison between MCMC and less computationally expensive Variational methods (Variational Bayesian and Hessian Variational Bayesian) for computing the posterior distribution and approximating the posterior covariance matrix based on heterogeneous experimental data. All three methods recover similar posterior distributions and posterior covariance matrices. This study demonstrates that for this EOS parameter calibration application, the assumptions made in the two Variational methods significantly reduce the computational cost but do not substantially change the results compared to MCMC.
Numerical Modeling and Dynamic Response Analysis of an End-Anchored Floating Bridge With a Damaged Pontoon Under Repair Operation
Authors: Cui Minghao , Cheng Zhengshun , Chen Peng , Moan Torgeir
Published: April 2024

Floating bridges face potential hazards due to ship collisions throughout their operational lifetime. In a situation where a pontoon is significantly damaged from an accident, a floating drydock may be used to compensate for the lost buoyancy and provide a dry atmosphere for operations. As the repair might take months, a primary concern is whether the repair can be in-site conducted without shutting down the road traffic. This study aims to investigate the feasibility of using a drydock for the repair. The numerical model of the in-operation damaged bridge is established for a comparative dynamic analysis with the intact end-anchored bridge. Eigenvalue analysis is conducted, and pendulum modes of oscillation are found with an eigen-period of around 15 s. The dynamic responses are analyzed through a series of fully coupled time-domain simulations under various environmental conditions. The results indicate that the standard deviation of the moment about the girder weak axis increases significantly at the damaged pontoon axis due to the excitation of low-frequency resonant response. Swell wave loads might induce dynamic amplification to the damaged bridge, even with a relatively small wave height. In addition, the internal stress of the bridge girder is investigated and found to be larger, especially, at the lower locations of the cross section. It is suggested that the responses can be managed by limiting the excitation of pendulum modes or providing special damping devices in practical engineering.
Planar microcoil arrays for in vitro cellular-level micromagnetic activation of neurons
Authors: Saha Renata , Benally Onri J. , Faramarzi Sadegh , Bloom Robert , Wu Kai , Tonini Denis , Shiao Maple , Keirstead Susan A. , Low Walter C. , Netoff Theoden I. , Wang Jian-Ping
Published: April 2024

In the treatment of neurodegenerative disorders, a potential cure at a single neuron cell resolution is still lacking. Micromagnetic neurostimulation, although in its infancy, is one of the most promising techniques that offer spatially selective activation of neurons through micrometer-sized coils or microcoils (μcoils). Time-varying current drives these μcoils and generates a time-varying magnetic field which in turn induces an electric field to activate the neural tissues. In this work, we report the design and fabrication of planar μcoil arrays, termed Magnetic Patch (MagPatch), for activating single neurons. Using numerical calculations on ANSYS-Maxwell and NEURON, we report an optimized MagPatch array design that exploits the directionality of the induced electric field from the μcoils to enhance spatial selectivity. Each μcoil has an outer dimension of 190 × 190 μm2 and one MagPatch array contains 8 μcoils. For proof-of-concept design and development, the MagPatch array has been fabricated on Si-substrates using Ti, Au, and Si3N4 to ensure preliminary biocompatibility. They were then encapsulated in Parylene-C, a waterproof, anti-leakage current coating, thereby ensuring basic surface biocompatibility. Human neuroblastoma cells were cultured directly on the surface encapsulated MagPatch, and calcium fluorescence imaging was used to assess cell functionality. The impact of scaling the dimensions of the μcoil in the MagPatch array on electrical characteristics, Q-factor, and thermal effects on neural tissues from these μcoils have also been discussed.
Contaminants in Dietary Supplements: Toxicity, Doping Risk, and Current Regulation
Authors: Zapata-Linares Jesús , Gervasini Guillermo
Published: April 2024

Athletes, both amateur and professional, often resort to the consumption of nutritional supplements without professional supervision and without being aware of the risks they may entail. We conducted an exhaustive literature search to determine the most common substances found as contaminants in dietary supplements. For each substance, we analyzed its mechanism of action, clinical indication, health risk, and putative use as doping agent. In addition, we evaluated the current regulation of these supplements. Contamination of nutritional supplements (accidental or intentional), especially with steroids and stimulants, is a hazardous situation. The prolonged consumption of these products without being aware of their composition can cause serious health risks and, in the case of professional athletes, a possible sanction for doping.
Optogenetically controlled inflammasome activation demonstrates two phases of cell swelling during pyroptosis
Authors: Nadjar Julien , Monnier Sylvain , Bastien Estelle , Huber Anne-Laure , Oddou Christiane , Bardoulet Léa , Leloup Hubert B. , Ichim Gabriel , Vanbelle Christophe , Py Bénédicte F. , Destaing Olivier , Petrilli Virginie
Published: April 2024

Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck–like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation. We demonstrated that inducing the light-sensitive oligomerization of ASC was sufficient to recapitulate the classical features of inflammasomes within minutes. This system showed that there were two phases of cell swelling during pyroptosis. This approach offers avenues for biophysical investigations into the intricate nature of cellular volume control and plasma membrane rupture during cell death.
TNF-α signals through ITK-Akt-mTOR to drive CD4
+
T cell metabolic reprogramming, which is dysregulated in rheumatoid arthritis
Authors: Bishop Emma L. , Gudgeon Nancy , Fulton-Ward Taylor , Stavrou Victoria , Roberts Jennie , Boufersaoui Adam , Tennant Daniel A. , Hewison Martin , Raza Karim , Dimeloe Sarah
Published: April 2024

Upon activation, T cells undergo metabolic reprogramming to meet the bioenergetic demands of clonal expansion and effector function. Because dysregulated T cell cytokine production and metabolic phenotypes coexist in chronic inflammatory disease, including rheumatoid arthritis (RA), we investigated whether inflammatory cytokines released by differentiating T cells amplified their metabolic changes. We found that tumor necrosis factor–α (TNF-α) released by human naïve CD4
+
T cells upon activation stimulated the expression of a metabolic transcriptome and increased glycolysis, amino acid uptake, mitochondrial oxidation of glutamine, and mitochondrial biogenesis. The effects of TNF-α were mediated by activation of Akt-mTOR signaling by the kinase ITK and did not require the NF-κB pathway. TNF-α stimulated the differentiation of naïve cells into proinflammatory T helper 1 (T
H
1) and T
H
17 cells, but not that of regulatory T cells. CD4
+
T cells from patients with RA showed increased TNF-α production and consequent Akt phosphorylation upon activation. These cells also exhibited increased mitochondrial mass, particularly within proinflammatory T cell subsets implicated in disease. Together, these findings suggest that T cell–derived TNF-α drives their metabolic reprogramming by promoting signaling through ITK, Akt, and mTOR, which is dysregulated in autoinflammatory disease.
Glia are powerhouses for sleep
Authors: Ferrarelli Leslie K.
Published: April 2024

Glia take up and detoxify neurotoxic lipids on a wake-sleep cycle, in turn promoting healthy sleep.
A novel member of drug/metabolite transporter (DMT) family efflux pump, SA00565, contributes to tetracycline antibiotics resistance in
Staphylococcus aureus
USA300
Authors: Li Daiyu , Ge Yan , Wang Ning , Shi Yun , Guo Gang , Zhang Jing , Zou Quanming , Liu Qiang
Published: April 2024

Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in
Staphylococcus aureus
. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of
sa00565
in resistance, we generated
sa00565
gene deletion mutant (Δ
sa00565
) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δ
sa00565
mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in
S. aureus
.

IMPORTANCE

In this study, we addressed the significance of drug efflux systems in multidrug resistance of
Staphylococcus aureus
, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δ
sa00565
mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in
S. aureus
, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.
Alkenone-derived estimates of Cretaceous pCO2
Authors: Si Weimin , Novak Joseph B. , Richter Nora , Polissar Pratigya , Ma Ruigang , Santos Ewerton , Nirenberg Jared , Herbert Timothy D. , Aubry Marie-Pierre
Published: April 2024

Alkenones are long-chain ketones produced by phytoplankton of the order Isochrysidales. They are widely used in reconstructing past sea surface temperatures, benefiting from their ubiquitous occurrence in the Cenozoic ocean. Carbon isotope fractionation (εp) between alkenones and dissolved inorganic carbon may also be used as a proxy for past atmospheric pCO2 and has provided continuous pCO2 estimates back to ca. 45 Ma. Here, an extended occurrence of alkenones from ca. 130 Ma is reported. We characterize the molecular structure and distribution of these Mesozoic alkenones and evaluate their potential phylogenetic relationship with Cenozoic alkenones. Using δ13C values of the C37 methyl alkenone (C37:2Me), the first alkenone-based pCO2 estimates for the Mesozoic are derived. These estimates suggest elevated pCO2 with a range of 548–4090 ppm (908 ppm median) during the super-greenhouse climate of the Early Cretaceous, in agreement with phytane-based pCO2 reconstructions. Finally, insights into the identity of the Cretaceous coccolithophores that possibly synthesized alkenones are also offered.