bluuebunny/crossref_metadata_2025 huggingface dataset:
Local resonance metamaterial-based integrated design for suppressing longitudinal and transverse waves in fluid-conveying pipes
Authors: Han Donghai , Jia Qi , Gao Yuanyu , Jin Qiduo , Fang Xin , Wen Jihong , Yu Dianlong
Published: September 2024

To solve the problem of low broadband multi-directional vibration control of fluid-conveying pipes, a novel metamaterial periodic structure with multi-directional wide bandgaps is proposed. First, an integrated design method is proposed for the longitudinal and transverse wave control of fluid-conveying pipes, and a novel periodic structure unit model is constructed for vibration reduction. Based on the bandgap vibration reduction mechanism of the acoustic metamaterial periodic structure, the material parameters, structural parameters, and the arrangement interval of the periodic structure unit are optimized. The finite element method (FEM) is used to predict the vibration transmission characteristics of the fluid-conveying pipe installed with the vibration reduction periodic structure. Then, the wave/spectrum element method (WSEM) and experimental test are used to verify the calculated results above. Lastly, the vibration attenuation characteristics of the structure under different conditions, such as rubber material parameters, mass ring material, and fluid-structure coupling effect, are analyzed. The results show that the structure can produce a complete bandgap of 46 Hz–75 Hz in the low-frequency band below 100 Hz, which can effectively suppress the low broadband vibration of the fluid-conveying pipe. In addition, a high damping rubber material is used in the design of the periodic structure unit, which realizes the effective suppression of each formant peak of the pipe, and improves the vibration reduction effect of the fluid-conveying pipe. Meanwhile, the structure has the effect of suppressing both bending vibration and longitudinal vibration, and effectively inhibits the transmission of transverse waves and longitudinal waves in the pipe. The research results provide a reference for the application of acoustic metamaterials in the multi-directional vibration control of fluid-conveying pipes.
Virtues of routine suprahyoid release during tracheal resection and anastomosis in patients with post intubation stenosis
Authors: Elsayed Hany Hasan , El-Nori Ahmed Anwar , Mostafa Ahmed , Elsayegh Mohamed Tarek , Bassiouny Samia , Refaat Ahmed , Elkahely Mohamed Attia , Zaki Mina
Published: September 2024

Postintubation tracheal stenosis is the most common cause of benign tracheal stenosis. Surgical treatment is more challenging in long-segment stenosis. Suprahyoid release can increase tracheal length resected without anastomotic tension in patients with post-intubation tracheal stenosis. Its effect on swallowing has not been objectively studied and this article aims to explore its virtues and potential complications in a tertiary center for airway surgery. A prospective cohort study was conducted on forty consecutive patients from June 2020 till December 2023. Patients of both genders had tracheal resection anastomosis surgery with routine suprahyoid muscle release for resected tracheal segment of more than 2.5 cm in length aiming to decrease the anastomotic tension. Within two weeks postoperatively, a video naso-laryngoscope was done on all the patients to detect any vocal cord disorders, then they were examined by video fluoroscopy swallowing study VFSS to detect swallowing problems. Follow up was done for 6 months postoperatively. 40 patients were studied. Twenty-five patients (62.5%) were males. 21 patients (52.5%) had a cricotracheal resection. VFSS was performed on 38 patients (two patients excluded for serious morbidity). Six (15.7%) and four (10.5%) patients had residual semisolid and solid food in the vallecula and pyriform fossa respectively during swallowing. Five patients (13%) out of eight patients with abnormal VFSS had aspiration and dysphagia. Video nasolaryngoscopy was done pre- and post-operatively and showed that 7 patients (17.5%) had unilateral vocal cord paralysis, two of them had the same lesion preoperatively. Two patients developed postoperative anastomotic complications. All symptoms of dysphagia improved within 3 weeks of the procedure and improvement persisted for 6 months. Suprahyoid muscle release had a considerable reversible drawback on the process of swallowing. Its routine use in high-risk patients requiring long segment tracheal resections could be considered.
Engineered Cancer Nanovaccines: A New Frontier in Cancer Therapy
Authors: Wang Yijie , Liu Congrui , Fang Chao , Peng Qiuxia , Qin Wen , Yan Xuebing , Zhang Kun
Published: September 2024

Vaccinations are essential for preventing and treating disease, especially cancer nanovaccines, which have gained considerable interest recently for their strong anti-tumor immune capabilities. Vaccines can prompt the immune system to generate antibodies and activate various immune cells, leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and surgery. To enhance the flexibility and targeting of vaccines, nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level, enabling more controlled and precise drug delivery to enhance immune responses. Cancer nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within nanomaterials. The small size of these nanomaterials allows for precise targeting of T cells, dendritic cells, or cancer cells, thereby eliciting a more potent anti-tumor response. In this paper, we focus on the classification of carriers for cancer nanovaccines, the roles of different target cells, and clinically tested cancer nanovaccines, discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation, while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.
Mesomorphic thermal stabilities and nonlinear optical properties of fluorine containing liquid crystals
Authors: Kumari P. Preethi , Bhattacharjee Debanjan , Sonali M. K. , Nayak Sandesha , Moorkoth Sudheer , Gupta Ashutosh , Angadiyavar Priya , Bhagavath Poornima
Published: September 2024

H-bonded liquid crystals (HBLCs) are newly synthesized with PyBF viz., (4-pyridyl)-benzylidene-4′-fluoro aniline as the proton acceptor which is non-mesogenic and alkyloxy benzoic acids viz., nOBAs (n = 3, 12) as the mesogenic proton donors. The H-bond formed is confirmed by FTIR spectroscopy. Polarizing Optical Microscopy confirmed the H-bonded compound’s mesomorphic textures, and the thermal analysis is carried out using a Differential Scanning Calorimeter. The influence of fluorine atom on mesomorphic stability is studied. The nonlinear optical properties of the H-bonded compound is studied using DFT theoretical approach. This work supports the SDG-9 of the United Nations.

Graphical abstract
Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting
Authors: Iqbal Faiza , Barche Apurv , Shenoy Padmaja A. , Lewis Leslie Edward S. , Purkayastha Jayashree , Vandana K. E.
Published: September 2024

Background

The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit.

Methods

A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500 g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80⁰C for extraction of DNA and microbiome analysis.

Results

The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria.

Conclusion

Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.
The Shadow Prices of Voluntary Caregiving: Using Well-Being Panel Data to Estimate the Cost of Informal Care
Authors: McDonald Rebecca , Powdthavee Nattavudh
Published: September 2024

This article uses the well-being valuation (WV) approach to estimate and monetize the well-being impacts of informal care provision on caregivers. Using nationally representative longitudinal data from the UK, the British Household Panel Survey, we address two challenging methodological issues related to the economic valuation of informal care: (i) the anticipatory nature of informal care; and (ii) the sensitivity of income estimates used in valuation. We address the anticipatory issue by focusing on well-being impacts associated with caring for a relative who had recently suffered a serious accident. We use the fixed effects filtered (FEF) estimator to estimate a “time-invariant income” coefficient free from individual fixed effects bias, which helps to partially improve the quality of the income estimate as an alternative to using instrumental variables. This estimate is used in the calculation of shadow prices of informal care. Our estimates suggest that, focusing on the first year of unanticipated care provision, those experiencing the well-being losses from providing unanticipated informal care would be willing to pay approximately £13,167 on average to avoid it.
Provocation and the Reasonable Asian: Applying the Reasonable Person Standard to Asian Defendants Asserting the Provocation Defense
Authors: Hyun Kaitlyn
Published: September 2024

This Article examines the criminal law defense of provocation in the U.S., which employs an objective reasonable person standard, as applied to recent Asian immigrants. It discusses approaches taken in other countries and describes the cultural defense. The Article concludes with different possibilities for a hypothetical Asian defendant who was provoked: Improving education about U.S. laws as a preventative measure, using expert cultural witnesses at trial, and taking the defendant’s characteristics into consideration during the sentencing stage.
The Public Trust as an International Solution to Climate Inaction
Authors: LoPreiato Elizabeth
Published: September 2024

The public trust doctrine holds promise as a tool for combatting international climate inaction. A global public trust in the Earth’s atmosphere may be a feasible avenue for generating international cooperation in this issue. The public trust doctrine is a viable and underutilized mechanism of understanding our collaborative obligations with respect to natural resources. This Article looks to the historical origins and current presentations of public trusts to extract features which indicate its effectiveness and appeal for modern climate change applications. Additionally, it presents two circumstances under which a global public trust in the atmosphere could eventually develop.
Militant Moralism: The Hegemonic Consequences of German Content Moderation
Authors: Donaldson Connor
Published: September 2024

Germany’s content moderation law—NetzDG— is often the target of criticism in English-language scholarship as antithetical to Western notions of free speech and the First Amendment. The purpose of this Article is to encourage those engaged in the analysis of transatlantic content moderation schemes to consider how Germany’s self-ideation influences policy decisions. By considering what international relations scholars term ontological security, Germany’s aggressive forays into the content moderation space are better understood as an externalization of Germany’s ideation of itself, which rests upon an absolutist domestic moral and constitutional hierarchy based on the primacy of human dignity. Ultimately, this Article implores American scholars and lawmakers to consider the impact of this subconscious ideation when engaging with Germany and the European Union in an increasingly multi-polar cyberspace.
A Comparative Analysis of Defamation Law in the United States and Thailand’s Lèse–Majesté Law: Lessons from the Land of Smiles (But Where the King Never Smiles)
Authors: Kelling Christian Addams
Published: September 2024

The United States’ free speech regime, as codified in the First Amendment to the United States Constitution, comes with obvious contrasts to Thailand’s ill-famed lèse–majesté law—Section 112 of the Thai Criminal Code—which prohibits defamation or even truthful degradation of the Thai King and Royal Family. Recent scholarship has focused on such differences and has largely depicted the two regimes as diametric opposites. When viewing the First Amendment and Thailand’s lèse–majesté law in temporal isolation, the recent scholarly consensus has significant merit. However, by analyzing the two regimes over time, similarities arise suggesting that both regimes represent each respective country’s attempt to accommodate competing and changing values present within the respective countries.
Multistability of a long droplet in a capillary tube under transverse body force
Authors: Tan Dongwen , Zhou Xinping
Published: September 2024

Bistable states for a sufficiently large amount of liquid can appear in an eccentric capillary due to the eccentricity effect under zero gravity (J. Fluid Mech, vol. 863, 2019, pp. 364–385). A transverse body force, which can lead to rich physical phenomena of a droplet, may lead to multistable states (bistability, tristability and the likes) of a sufficiently large amount of liquid in a capillary. We theoretically investigate this situation in a circular or annular capillary tube under a transverse body force. The results show that there can be tristable (bistable) states in an annular (circular) capillary tube: an occluding configuration and two (one) non-occluding configurations. In the annular tube, for one of the non-occluding configurations, the gas–liquid interface in the middle cross-section of the droplet meets both the inner and outer walls of the tube (bridging configuration); for the other non-occluding configuration, the gas–liquid interface in the middle cross-section of the droplet does not meet the inner wall (non-bridging configuration). The multistability is dependent on the Bond number, the contact angle and the cross-sectional shape. The multistability cannot occur for a zero or very large Bond number. A hydrophilic condition (the contact angle smaller than 90°) contributes to the non-occluding non-bridging configuration, while the hydrophobic condition (the contact angle larger than 90°) contributes to the non-occluding bridging configuration (only for the annular capillary). For the annular capillary with a not-so-large contact angle, increasing the inner-to-outer radius ratio can lead to a larger range of Bond numbers, in which the multistability occurs.
Cenozoic climate change and the evolution of North American mammalian predator ecomorphology
Authors: Juhn Mark S. , Balisi Mairin A. , Doughty Evan M. , Friscia Anthony R. , Howenstine Aidan O. , Jacquemetton Christiane , Marcot Jonathan , Nugen Sarah , Van Valkenburgh Blaire
Published: September 2024

The trend of global cooling across the Cenozoic transformed the North American landscape from closed forest to more open grasslands, resulting in dietary adaptations in herbivores in response to shifting resources. In contrast, the material properties of the predator food source (muscle, skin, and bone) have remained constant over this transition, suggesting a corresponding lack of change in predator dietary adaptations. We investigated the North American mammalian predator fossil record using a tooth-shape metric and body mass, predicting that the former would exhibit stability. Instead, we found that mean molar morphology became more blade-like, with our tooth-shape metric sharply increasing in the late Eocene and remaining high from the Oligocene onward. Subsequent tests in extant carnivorans reveal taxa with more bladelike teeth are prevalent in more open environments. Our results reveal an unexpected functional shift among North American predators in response to large-scale environmental changes across the Cenozoic.
The Perils of Privacy and Passivity: Antidemocratic, Racist, and Antisemitic Sentiments in Postwar West Germany
Authors: Knatz Jonas
Published: September 2024

This article analyzes the affective economy of West Germany's postwar society. After delineating the intellectual history of the Frankfurt Institute for Social Research's “Gruppenexperiment,” which consisted of 137 group interviews with different segments of West German society, my article focuses on one transcript of a 1950 group discussion of young fashion-designer apprentices. Based on a close reading, I study how the younger generation in West Germany constructed a passive and privatist self-image in which they could both articulate their emotional dissociation from National Socialism while clinging to antidemocratic, racist, and antisemitic feelings in metamorphosed form. The micrological focus of the analysis of the group's emotions is balanced by a rereading of both Helmut Schelsky's study about the “skeptical generation” and texts by researchers associated with the Institute for Social Research who came to markedly different conclusions about the West German youth.
The Stomach Purifies All Foods: Jesus’ Anatomical Argument in Mark 7.18–19
Authors: Williams Logan
Published: September 2024

This article offers a new interpretation of καθαρίζων πάντα τὰ βρώματα in Mark 7.19c. After reviewing and offering some nuance to an emerging non-antinomian interpretation of 7.15a/18b, I turn to Mark 7.19c and argue that the phrase καθαρίζων πάντα τὰ βρώματα should be understood as a part of Jesus' speech in 7.18–19. Jesus’ argument, I suggest, is that ritually defiled food cannot defile humans through ingestion because humans purify all foods from ritual impurity through digestion. This reasoning depends on a widespread Jewish view that excrement is impervious to ritual impurity: because all excrement is pure, the stomach acts as a purifying agent that purifies all food from ritual impurity. I proffer that the common translation of Mark 7.19c – ‘Thus he declared all foods clean’ (NRSV) – should therefore be abandoned.
A Non-Manuscript of Papias of Hierapolis
Authors: Lincicum David
Published: September 2024

Uncertainty has attached to a medieval library catalogue entry mentioning Papias cum sermonibus diversis at Stams Abbey. Most recent editors of Papias have suspected that it refers to the medieval lexicographer rather than the second-century Christian author of the same name. This note calls attention to a marginal citation in a Stams manuscript from the lexicographer that helps put to rest the hypothesis of a full Latin manuscript of Papias of Hierapolis.
Puppies and Pejoratives: Did Jesus Insult the Syrophoenician Woman (Mark 7.24-30)?
Authors: Croy N. Clayton
Published: September 2024

Jesus' response to the Syrophoenician woman in Mark 7.27 is sometimes seen as sexist, racist, or abusive. The force of his response depends in part on the diminutive form κυναριον, which is often dismissed as a faded diminutive that lacks true force. But a statistical, semantic, and contextual analysis of the word indicates that it does, in fact, have diminutive force in Mark 7:27. Because of this, the pejorative force found in direct insults employing the word ‘dog’ is lacking in Jesus' response. In addition to failing to recognise the diminutive force of κυναριον, interpreters sometimes assume a social context in which Jews routinely referred to Gentiles as dogs. Finally, the analogy that Jesus makes is often read allegorically, assuming that ‘children’ and ‘dogs’ have direct counterparts in ‘Jews’ and ‘Gentiles’. These assumptions are found to be dubious. The point of Jesus' analogy is about the proper order of events: children eat before the puppies; Jews receive the benefits of his ministry before Gentiles. The Syrophoenician woman outwits Jesus by arguing that the puppies may eat simultaneously with the children. The interpretive upshot is that Jesus' saying is unlikely to be misogynistic or abusive, but simply asserts Jewish priority, a priority that admits of exceptions and change.
Varicella vaccine effectiveness evaluation in Wuxi, China: A retrospective cohort study
Authors: Xiu Shixin , Xu Zhuping , Wang Xuwen , Zhang Li , Wang Qiang , Yang Min , Shen Yuan
Published: September 2024

Varicella is a vaccine-preventable infectious disease. Since 1 December 2018, the varicella vaccine has been included in the local Expanded Programme on Immunization (EPI) in Wuxi, China, and children born after 1 December 2014 are eligible for free vaccination. To evaluate the effect of varicella vaccination in Wuxi city, we selected 382 397 children born from 2012 to 2016 as subjects. Their disease data were obtained from the Chinese Disease Prevention and Control Information System, and their vaccination data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. The incidence of breakthrough varicella cases increased in the first 4 years and reached the peak in the fifth year. With the increase of vaccination rate, the incidence of varicella decreased significantly. The vaccine effectiveness (VE) was found to be 88.17%–95.78% for one dose and 98.65%–99.93% for two doses. Although the VE per dose decreased from 99.57% in the first year to 93.04% in the eighth year, it remained high. These findings confirmed the effectiveness of varicella vaccination in children, supported the use of a two-dose varicella vaccination strategy to achieve better protection, and provided important insights into the optimal vaccination strategy for varicella prevention in children.
Everything but the kitchen sink: The use of multiple hypothesis generation methods to investigate an outbreak of Salmonella Enteritidis associated with frozen profiteroles and eclairs
Authors: Smith Courtney R. , Taylor Marsha , Manore Anna J. W. , Hexemer April , Adhikari Bijay , Alexander David , Atkinson Robin , Chui Linda , Galanis Eleni , Gaulin Colette , Griffin Meghan , Honish Lance , Kearney Ashley , Mah Victor , McCormick Rachel , Murti Michelle
Published: September 2024

In December 2018, an outbreak of Salmonella Enteritidis infections was identified in Canada by whole-genome sequencing (WGS). An investigation was initiated to identify the source of the illnesses, which proved challenging and complex. Microbiological hypothesis generation methods included comparisons of Salmonella isolate sequence data to historical domestic outbreaks and international repositories. Epidemiological hypothesis generation methods included routine case interviews, open-ended centralized re-interviewing, thematic analysis of open-ended interview data, collection of purchase records, a grocery store site visit, analytic comparison to healthy control groups, and case–case analyses. Food safety hypothesis testing methods included food sample collection and analysis, and traceback investigations. Overall, 83 cases were identified across seven provinces, with onset dates from 6 November 2018 to 7 May 2019. Case ages ranged from 1 to 88 years; 60% (50/83) were female; 39% (22/56) were hospitalized; and three deaths were reported. Brand X profiteroles and eclairs imported from Thailand were identified as the source of the outbreak, and eggs from an unregistered facility were hypothesized as the likely cause of contamination. This study aims to describe the outbreak investigation and highlight the multiple hypothesis generation methods that were employed to identify the source.
Wire marking reduces bird collisions with a transmission powerline in western Belgium
Authors: Verbelen Dominique , Bovens Wim , Dwyer James F. , Swinnen Kristijn
Published: September 2024

Collisions with powerlines affect birds worldwide, including countries such as Belgium where a nationwide model indicated high avian collision risk in the IJzerbroeken region (seasonally flooded riverside wetlands). Large numbers of waterbirds winter in this area, which is crossed by a 70-kV transmission line. To manage avian collision risk, the transmission system operator, Elia, installed AB Hammarprodukter’s FireFly™ FF line markers incorporating reflective, glow-in-the-dark, high contrast, and moving elements intended to increase the visibility of the transmission line to flying birds. We evaluated the effectiveness of FireFly line markers by comparing the numbers of avian carcasses found during 11 surveys annually in 2001 and 2018 (22 total surveys) before line markers were installed compared with 11 surveys conducted in 2021 after line marking. Before line marking, we found 30 avian carcasses attributable to collision in 2001 and 113 in 2018. After, we found six carcasses attributable to collision in 2021. In 2021, FireFly line markers correlated with a reduction in collision rate, depending on the pre-treatment year and species group, of at least 85% and up to 100%. The line was composed of two configurations, with half of the spans (two-thirds of the monitored line length) supported by tall pylons with shield wires, and half of the spans supported by shorter pylons without shield wires. After line marking, six collisions (100% in 2021) occurred on spans supported by tall pylons, and none (0%) occurred on spans supported by short pylons. Thus, in 2021, FireFly line markers correlated with an observed mortality reduction of at least 73% and up to 100%, depending on the configuration being considered. These findings suggest FireFly line markers substantially reduced wintering bird collisions in our study area.
Do Rubrics Enhance Self-Assessment Accuracy?
Authors: Krebs Rebecca , Waldeyer Julia , Rothstein Björn , Roelle Julian
Published: September 2024

Abstract: Rubrics are a widespread means to enhance task performance. However, in contrast to the question of whether rubrics effectively foster task performance, the question of why rubrics are effective has received relatively scarce attention. Frequently, researchers have assumed that rubrics help learners to accurately self-assess their task performance, paving the way for effective regulation and thereby enhancing task performance. The present experiment tests this potential mechanism. N = 118 students read a scientific article and were tasked with writing an abstract for it. Afterward, they self-assessed the quality of their abstracts, which, dependent on the experimental condition, was or was not supported by a rubric. Then, all learners could decide on which dimensions relevant to the quality of their abstracts they would like to receive further instruction. They could then revise their abstracts. We found that rubrics fostered self-assessment accuracy (lower bias and better absolute accuracy) but did not enhance the effectiveness of the subsequent regulation. We conclude that rubrics effectively enhance self-assessment accuracy but do not necessarily pave the way for effective regulation.
Nd Isotopic Equilibration During Channelized Melt Transport Through the Lithosphere: A Feasibility Study Using Idealized Numerical Models
Authors: Roy Mousumi , Farmer G. Lang , Malone Kellen
Published: September 2024

This study is motivated by the observed variability in trace element isotopic and chemical compositions of primitive (Si52 wt %) basalts in southwest North America (SWNA) during the Cenozoic transition from subduction to extension. Specifically, we focus on processes that may explain the enigmatic observation that in some localities, basalts with low Ta/Th, consistent with parental melts in a subduction setting, have signatures consistent with continental lithospheric mantle (CLM). In locations with the oldest CLM (Proterozoic and Archean), Cenozoic basalts with low Ta/Th have well below zero. We model channelized magma transport through the CLM using simple 1D transport models to explore the extent to which diffusive and reactive mass exchange can modify Nd isotopic compositions via open system melt‐wallrock interactions. For geologically reasonable channel spacings and volume fractions, we quantify the reactive assimilation rates required for incoming melt with a different than the wall‐rock to undergo a substantial isotopic shift during 10 km channelized melt transport. In the presence of grain boundaries, enhanced diffusion between melt‐rich channels and melt‐poor surrounding rock contributes to isotopic equilibration, however this effect is not enough to explain observations; our models suggest a significant contribution from reactive assimilation of wall‐rock. Additionally our models support the idea that the observed covariability in Ta/Th and in Cenozoic basalts cannot be attributed to transport alone and must also reflect the transition from subduction‐related to extension‐related parental melts in SWNA.
A functional parcellation of the whole brain in high-functioning individuals with autism spectrum disorder reveals atypical patterns of network organization
Authors: Persichetti Andrew S. , Shao Jiayu , Gotts Stephen J. , Martin Alex
Published: September 2024

Researchers studying autism spectrum disorder (ASD) lack a comprehensive map of the functional network topography in the ASD brain. We used high-quality resting state functional MRI (rs-fMRI) connectivity data and a robust parcellation routine to provide a whole-brain map of functional networks in a group of seventy high-functioning individuals with ASD and a group of seventy typically developing (TD) individuals. The rs-fMRI data were collected using an imaging sequence optimized to achieve high temporal signal-to-noise ratio (tSNR) across the whole-brain. We identified functional networks using a parcellation routine that intrinsically incorporates internal consistency and repeatability of the networks by keeping only network distinctions that agree across halves of the data over multiple random iterations in each group. The groups were tightly matched on tSNR, in-scanner motion, age, and IQ. We compared the maps from each group and found that functional networks in the ASD group are atypical in three seemingly related ways: (1) whole-brain connectivity patterns are less stable across voxels within multiple functional networks, (2) the cerebellum, subcortex, and hippocampus show weaker differentiation of functional subnetworks, and (3) subcortical structures and the hippocampus are atypically integrated with the neocortex. These results were statistically robust and suggest that patterns of network connectivity between the neocortex and the cerebellum, subcortical structures, and hippocampus are atypical in ASD individuals.
Biological function of sialic acid and sialylation in human health and disease
Authors: Zhu Wengen , Zhou Yue , Guo Linjuan , Feng Shenghui
Published: September 2024

Sialic acids are predominantly found at the terminal ends of glycoproteins and glycolipids and play key roles in cellular communication and function. The process of sialylation, a form of post-translational modification, involves the covalent attachment of sialic acid to the terminal residues of oligosaccharides and glycoproteins. This modification not only provides a layer of electrostatic repulsion to cells but also serves as a receptor for various biological signaling pathways. Sialylation is involved in several pathophysiological processes. Given its multifaceted involvement in cellular functions, sialylation presents a promising avenue for therapeutic intervention. Current studies are exploring agents that target sialic acid residues on sialoglycans or the sialylation process. These efforts are particularly focused on the fields of cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. In this review, we aimed to summarize the biological functions of sialic acid and the process of sialylation, explore their roles in various pathophysiological contexts, and discuss their potential applications in the development of novel therapeutics.
Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii
Authors: Alexander P. J. , Oyama L. B. , Olleik H. , Godoy Santos F. , O’Brien S. , Cookson A. , Cochrane S. A. , Gilmore B. F. , Maresca M. , Huws S. A.
Published: September 2024

Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2–128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.
Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein
Authors: Kravec Marek , Šedo Ondrej , Nedvědová Jana , Micka Miroslav , Šulcová Marie , Zezula Nikodém , Gömöryová Kristína , Potěšil David , Sri Ganji Ranjani , Bologna Sara , Červenka Igor , Zdráhal Zbyněk , Harnoš Jakub , Tripsianes Konstantinos , Janke Carsten , Bařinka Cyril , Bryja Vítězslav
Published: September 2024

Polyglutamylation is a reversible posttranslational modification that is catalyzed by enzymes of the tubulin tyrosine ligase-like (TTLL) family. Here, we found that TTLL11 generates a previously unknown type of polyglutamylation that is initiated by the addition of a glutamate residue to the free C-terminal carboxyl group of a substrate protein. TTLL11 efficiently polyglutamylates the Wnt signaling protein Dishevelled 3 (DVL3), thereby changing the interactome of DVL3. Polyglutamylation increases the capacity of DVL3 to get phosphorylated, to undergo phase separation, and to act in the noncanonical Wnt pathway. Both carboxy-terminal polyglutamylation and the resulting reduction in phase separation capacity of DVL3 can be reverted by the deglutamylating enzyme CCP6, demonstrating a causal relationship between TTLL11-mediated polyglutamylation and phase separation. Thus, C-terminal polyglutamylation represents a new type of posttranslational modification, broadening the range of proteins that can be modified by polyglutamylation and providing the first evidence that polyglutamylation can modulate protein phase separation.
Assay Development and Screening Strategies for Epigenetic Targets
Authors: Brown Peter J.
Published: September 2024

The field of epigenetics has grown substantially in the last 20 years with the discovery of novel post-translational modifications (PTMs) and the expansion of substrates beyond chromatin. This growth has been matched by an increase in the sensitivity and diversity of in vitro and cellular assays which has enabled the rapid identification of tool compounds and characterization of their effects in cellular systems to further facilitate drug discovery. This chapter aims to introduce the newcomer to epigenetics to the screening strategies and assay formats commonly used for epigenetic targets.
Toward Understanding Pharmacological Modulation of DNA Methylation
Authors: Horton John R.
Published: September 2024

DNA methylation controls the proper development and functioning of all our cells. Aberrant DNA methylation can cause disease. The enzymes that carry out DNA methylation are known, and we are beginning to understand how they are highly regulated for the proper functioning of cells. Generally, DNA methylation turns off gene expression, depending on its context and the specific genomic location where it occurs. DNA hypermethylation by dysregulated enzymes inhibits the binding of transcription factors and regulatory proteins and affects other regulatory elements, as well as the important interplay with other epigenetic modifications, and results in switching off gene expression in the wrong cellular context. Some compounds that incorporate into DNA and interfere with DNA methylation catalysis are utilized as drugs, particularly for cancers. However, modern drug discovery techniques, increasing understanding of DNA methylation regulation, and knowledge obtained from three-dimensional structural information of the epigenetic apparatus have led to and will lead to compounds being discovered that can become better drugs with greater specificity.
Chemical Targeting of Histone Acetyltransferases
Authors: Liu Qi , Qi Aimee L. , Durbin Adam D. , Qi Jun
Published: September 2024

Histone acetyltransferases (HATs) are a class of enzymes that catalyze acetylation of the amino group on the lysine side chains of histones via their HAT domains. Acetylated lysine residues on histones are often associated with chromatin that is accessible to transcription factors and transcriptionally active loci. Given that transcription is often dysregulated in human diseases, particularly in cancers, HATs represent attractive targets for inhibitor and drug development. Many HAT domain-containing proteins are multi-domain proteins with functions extending beyond histone acetylation. Therefore, chemical strategies to inhibit their activity include targeting the HAT domain directly, targeting protein–protein interactions (PPIs) that regulate HAT activity, and targeting the whole protein for degradation as a means of inhibiting HAT activity, disrupting PPIs, and eliminating any other functions. All of these strategies are in current development and have yielded a variety of inhibitors and degraders that are used for mechanistic studies and, more recently, human clinical investigation. With the rapid development of chemical methods to target HAT proteins, we expect increasing mechanistic understanding and therapeutic insights into this class of proteins.
Histone Demethylases
Authors: Kales Stephen C. , Simeonov Anton
Published: September 2024

Histone methylation is a dynamic process that contributes to the control of gene expression by influencing chromatin structure. Since their initial discovery 20 years ago, histone demethylases have been shown to play a critical role in histone methylation and thus developmental, physiological, and pathological processes. Dysregulation of this class of enzymes has been linked to nearly all types of cancers but their complex interactions and elusive functions continue to impede therapeutic development. Here, we explore the demethylase family, its sub-families, and the great efforts to identify novel, specific inhibitors to understand their complex biological functions and therapeutic potential.
Targeting Histone Readers: Non-bromodomain Readers
Authors: Huang Xiaolei , Chen Yichang , Xiao Qin , Shang Xinci , Liu Yanli
Published: September 2024

Histone mark readers have diverse biological functions and dysregulation of these proteins is associated with various diseases. Targeting these readers through therapeutic interventions has become an exciting area of focus in drug discovery. Several modalities have been employed to develop inhibitors against these reader domains, including small molecules and peptides. The optimization of these inhibitors has greatly benefited from the use of structure-based design techniques. In this chapter, we will examine the discovery and development of therapeutics targeting histone non-bromodomain readers, including chromodomains, Tudor domains, PWWP domains, MBT domains, WD40 repeat domains, PHD fingers, and YEATS domains. For each target, we will briefly discuss its identification and biological/biochemical functions before delving into the discovery of inhibitors designed to target these domains. By modulating chromatin dynamics, such inhibitors have the potential to be used as therapeutics for a range of diseases, including cancer and neurological disorders. The search for inhibitors targeting each of these reader domains continues to be an active area of research.
Menin Inhibitors: Discovery, Development and Clinical Translation
Authors: Chen Dong , Ray Joshua , Cierpicki Tomasz , Grembecka Jolanta
Published: September 2024

The protein–protein interaction between menin and Mixed Lineage Leukemia 1 (MLL1) protein plays a critical role in a subset of acute leukemia, including leukemias with MLL1 translocations or mutations in the nucleophosmin (NPM1) gene, providing an opportunity for therapeutic intervention. Indeed, multiple small molecule inhibitors directly targeting menin to block its interactions with MLL1 were reported within the last decade. These compounds demonstrate pronounced anti-leukemic activity in pre-clinical models of MLL1-rearranged and NPM1-mutated leukemia, resulting in clinical translation of several of these compounds to acute leukemia patients. Discovery, development and early clinical data for the most promising menin inhibitors are discussed in this chapter.
Enantioselective synthesis of molecules with multiple stereogenic elements
Authors: Gaucherand Arthur , Yen-Pon Expédite , Domain Antoine , Bourhis Alix , Rodriguez Jean , Bonne Damien
Published: September 2024

This review explores the fascinating world of molecules featuring multiple stereogenic elements, unraveling the different strategies designed over the years for their enantioselective synthesis.
Two-dimensional direct Z-scheme AlN/GaS-SiP heterojunctions enhance photocatalytic hydrogen production from water: a DFT study
Authors: Gong Zeting , Yao Yongsheng , Liu Yaozhong , Liang Zheng , Li Junyao , Tang Zhenkun , Wei Xiaolin
Published: September 2024

We elucidate the method for determining type-II and direct Z-scheme heterojunctions from the perspective of dynamic simulation.
Synthesis of axially chiral thiourea by NHC-catalyzed desymmetrizative amidation
Authors: Wu Yingtao , Guan Xin , Jiao Kehan , Zhao Huaqiu , Li Mingrui , Sun Jiaqiong , Zheng Guangfan , Zhang Qian
Published: September 2024

NHC-catalyzed desymmetrization amidation of biaryl dialdehydes has been developed for NH-free axially chiral thiourea. Sequential kinetic resolution enhances the chirality induction of the desymmetrization strategy, expanding the applicable scope.
Efficient preconcentration of ultra-trace rhenium from geological materials via induced adsorption for accurate isotope analysis
Authors: Liu Yumeng , Chen Tianyu , Li Tao , Li Weiqiang , Hong Qingquan , Chen Jiubin
Published: September 2024

Preconcentration via induced adsorption achieves the quantitative recovery of Re and facilitates Re isotope analysis.
Dual-active Hf(iv)–organic framework for the detection of FOX-7 and as a heterogeneous catalyst for Knoevenagel condensation
Authors: Das Aniruddha , Chavda Dhruvil , Manna Moutusi , Das Asit Kumar
Published: September 2024

A dual-active MOF (CSMCRI-KNC′) was successfully employed for the detection of the explosive FOX-7 and as a heterogeneous catalyst for the synthesis of barbituric acid and its derivatives under mild conditions.
Fabrication and characterization of eco-friendly biocomposites from waste coconut spathe fabric for sustainable progress
Authors: Behera Diptiranjan , Pattnaik Shruti S. , Sanjibani Sukanya , Nayak Ganesh C. , Das Nigamananda , Behera Ajaya K.
Published: September 2024

Natural fiber-reinforced biocomposites offer sustainable alternatives to conventional plastics.
Ce-doped nanorod-like NiFe-MOF with coordination substitution based on in situ co-doping method for boosting the oxygen evolution reaction
Authors: Wei Xiao , Yu Shudi , Li Jie , Liu Tianpeng , Li Shujin , Hata Shinichi , Wu Zhengying , Shiraishi Yukihide , Du Yukou
Published: September 2024

In situ co-doped ion coordination substitution was used to prepare nanorod-like CeNi1.6Fe-MIL-53 with a high active site number and optimized electron and band structures for boosting effective water decomposition.
In situ formation of a Co-MOF/Ti–Fe2O3 photoanode for efficient photoelectrochemical water splitting
Authors: Ba Kaikai , Li Hongda , Zhang Kai , Lin Yanhong , Zhu Wanchun , Xie Tengfeng
Published: September 2024

The cocatalyst Co-MOF significantly enhances charge separation and transfer in the Ti–Fe2O3 photoanode, achieving a photocurrent density of 3.9 mA cm−2 at 1.23 V vs. RHE.
Audiological Characteristics of a Sample of Adults With Misophonia
Authors: Muñoz Karen , Woolley Mercedes G. , Velasquez Doris , Ortiz Diana , San Miguel Guadalupe G. , Petersen Julie M. , Twohig Michael P.
Published: September 2024

Purpose:

The aim of this study was to describe the audiological test results from a sample of 60 adults with self-reported misophonia.

Method:

Audiological testing was completed prior to participant randomization in a controlled trial for misophonia treatment. Participants completed the Inventory of Hyperacusis Symptoms Survey (IHS), the Tinnitus and Hearing Survey (THS), the Misophonia Questionnaire (MQ), and behavioral and objective audiometric measures.

Results:

Hearing thresholds were less than 25 dBHL for 97% of the participants. Loudness discomfort levels for tonal stimuli suggested hyperacusis in 25% of the sample. Total scores on the IHS indicated that 12% met the clinical cutoff for hyperacusis, and, on the THS, 27% experienced problems with tinnitus, 77% experienced problems with hearing, and 53% experienced problems with sound tolerance. On the MQ, 37% indicated mild levels of misophonia and 58% indicated moderate levels. For speech-in-noise testing, a mild signal-to-noise ratio loss was present for 15% of participants. Most of the participants had present distortion product otoacoustic emissions (DPOAEs).

Conclusions:

Audiological data on individuals with misophonia are lacking. In this article, we present results from audiological testing on 60 adults with self-reported misophonia. Most had normal peripheral hearing sensitivity based on pure-tone audiometry and DPOAE measures; some had difficulties with sound sensitivities and understanding speech-in-noise, self-report indicated problems with hyperacusis, tinnitus, and hearing difficulty.