bluuebunny/crossref_metadata_2025 huggingface dataset:
Behind Closed Gates: The Barriers to Self-Expression and Publication for Australian Young Adult Authors of OwnVoices Fiction
Authors: Booth Emily , Narayan Bhuva
Published: May 2021

This article based on an empirical study of Australian authors argues that, despite the OwnVoices movement gathering momentum in Australia, there are still barriers and limitations for authors from marginalised communities within the Australian publishing industry. This is due to power imbalances in publishing spaces which silence marginalised writers, limiting the availability of their books to teenage readers.
The Relationship between Formal Education and Non‑Formal Education: A Descriptive and Analytical Review of the Publications about Astronomy Education in Journals and Events Related to Science Teaching in the Brazilian Context
Authors:   Postgraduate Program in Science Education, Federal University of Itajubá (UNIFEI), Itajubá, Minas Gerais, Brazil, Menezes Isadora Moutinho Carvalho A. , Ovigli Daniel Fernando Bovolenta ,   Department of Science Education, Mathematics and Technologies, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, Colombo Junior Pedro Donizete ,   Department of Science Education, Mathematics and Technologies, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
Published: May 2021

The present research aims to analyze the publications related to astronomy education that discusses the interface between formal education (FE) and non-FE (NFE) at scientific events and a journal in the Brazilian context. These events were the National Symposium on Astronomy Education, the National Meeting on Research in Science Education (ENPEC), and the National Symposium on Physics Teaching. We also analyzed the journal “Latin American Journal of Astronomy Education” (RELEA). The objective was to understand how the approach between FE and NFE in the teaching of astronomy is constructed. The delimitation of the analyses covering the period 2001–2014 coincided with the constitution of Area 46 by the Coordination of Improvement of Higher Education Personnel (CAPES), which regulates postgraduate programs in Brazil. In a theoretical-methodological aspect, the ideas of content analysis proposed by Bardin (2011) were adopted. Among the results, we observed that few studies dealt with the relationship between FE and NFE; however, almost half of them occurred in institutions commonly classified as FE (i.e., schools), and the actions were mediated by teachers. Among the main activities, we highlight the observations the sky, guided tours, and play activities, with more than 60% of the activities going through three moments proposed by Allard et al. (1994): Before, during, and after the accomplishment of the activity in a non-formal space. The results found in this research can foster reflections about teacher training courses since more and more NFE spaces are present in teaching-learning processes, but little has been done to associate FE and NFE in teaching practice. We discuss what difficulties are faced by teachers to approach FE and NFE.
Türkiye’deki Doğrudan Yabancı Yatırımların Kadın İstihdamına Etkisi
Authors: Tekin İpek , Aktakas Başak Gül
Published: May 2021

Bu çalışmada Türkiye’ye yönelik doğrudan yabancı yatırımların (DYY) kadın istihdamı üzerindeki etkisinin farklı sektörler bazında analiz edilmesi amaçlanmaktadır. 2004-2012 dönemi için yıllık verilerin kullanıldığı çalışmada, yöntem olarak dinamik panel veri analiz tekniği uygulanmıştır. Analiz sonuçlarına göre, DYY’lerin kadın istihdamı üzerindeki etkisi negatif iken, Gayri Safi Yurtiçi Hasıla (GSYİH)’nın etkisi pozitiftir. Söz konusu çalışmanın alan yazınına katkısı, Türkiye’deki DYY’lerin toplam istihdam düzeyinden ziyade kadın istihdam düzeyi üzerindeki etkisinin sektörel olarak incelenmesidir.
Kentler Toplumsal Cinsiyetsiz Değildir: Türkiye’de Kentsel Mekânın Üretiminin Feminist Bir Eleştirisi
Authors: Yüceşahin M. Murat , Yazgan Pınar
Published: May 2021

Feministlerin öne sürdüğü gibi; çağdaş kentler ve onların sosyo-mekânsal yapıları, sanayi sonrası toplumlarda ev ve iş, kamusal ve özel mekânın ayrışmasını takiben üretim ve yeniden üretim sorumluluklarının toplumsal cinsiyete göre bölünmüş olmasından ötürü toplumsal cinsiyet eşitsizliklerini (kadınların aleyhine olacak şekilde) sürdürülmesinde ve yeniden üretiminde önemli bir yere sahiptir. Feminist coğrafya araştırmaları kadınların günlük yaşamlarında karşılaştıkları mekânsal kısıtları ve kentin bölgelerine erişim zorluklarını araştırmaktadır. İlgili alanyazında, çevrenin erkek bakış açısıyla ve neoliberal kent politikalarının kendine özgü doğası vasıtasıyla bizatihi erkekler tarafından planlanmakta olduğunu öne sürülmektedir. Bu çalışma, Türkiye özelinde, kentlerin cinsiyetlenmiş mekânları hakkındaki tartışmalara eleştirel feminist analizle katkı sağlamayı amaçlamaktadır. Çalışmada erkek egemen çevrenin küresel ve yereldeki mekânsal süreçleri incelenerek cinsiyetci bakış açısının inşa edilmiş çevrenin tasarımında ve yönetiminde Türkiye kentlerini biçimlendirme tarzı eleştirel söylem analiziyle ele alınmaktadır. Analiz bulguları neoliberal dönüşüm ve buna bağlı kentsel politikaların cinsiyetlenmiş kentsel mekânın üretiminde önemli bir rol üstlendiği ve ayrıca bireylerin kentsel alanlara kullanım ve erişimindeki cinsiyet eşitsizliklerini meşrulaştırdığına işaret etmektedir.
Müslüman Ülkelerde Toplumsal Cinsiyet Eşitliği Politikalarının Karşılaştırmalı Analizi
Authors: Ertan Senem
Published: May 2021

Kadın hakları ve toplumsal cinsiyet eşitliği konuları tartışıldığında, Batılı bilim insanlarının Müslüman ülkeleri birleşmiş tek bir kültür olarak görme eğilimleri vardır. Söz konusu eğilim ve savların sorgulandığı bu makalede, aynı zamanda, İslamiyet’i toplumsal cinsiyet eşitliğine karşı kuvvetli bir engel olarak gören birtakım fikirlere de eleştirel bir yaklaşım getirilerek, Müslüman ülkelerde toplumsal cinsiyet eşitliği politikaları arasındaki farklılıklar incelenmektedir. Bu amaçla bu çalışmada dünyadaki toplumsal cinsiyet eşitliği politikalarının kapsamını ölçmek için oluşturulmuş yeni ve orijinal kadın politikası ölçekleri kullanılmıştır. Bu ölçekler, 20 tanesi Müslüman olmak üzere toplam 84 ülkedeki toplumsal cinsiyet eşitliği politikalarını, karşılaştırmalı bir bakış açısıyla incelemeyi mümkün kılmıştır. Bu çalışmanın analizleri Müslüman ülkelerdeki toplumsal cinsiyet eşitliği politikaları arasında önemli farklılıklar olduğunu göstermektir. Bunun yanında, bu çalışmanın sunduğu ampirik deliller, Müslüman ülkelerin Müslüman olmayan ülkelere oranla genel olarak daha kötü toplumsal cinsiyet eşitliği politikaları ürettiklerini de göstermektedir
Yalçın Tosun Öykülerinde LGBTİ Kimliklerin İnşası
Authors: Abdal Göksenin
Published: May 2021

Yalçın Tosun, öykülerinde, toplumsal cinsiyet kavramını birçok açıdan ele alarak verili toplumsal cinsiyet rollerini tartışmaya açmıştır. Yazar; geleneksel ataerkil kadınlık ve erkeklik rollerini, toplumsal baskı mekanizmalarını, basmakalıp düşünceleri öykülerinde işler. Bu çalışmanın amacı, Yalçın Tosun’un öykülerinde LGBTİ kimlik unsurlarının ele alınış biçimlerini ve inşa edilme yollarını analiz etmektir.. Bu hususta, yazarın kitaplarından seçilen ve LGBTİ cinsel kimliklere dair yansımalar içeren dört öyküye (Kıpırtılı Bir Yorgan, Madam Marini’nin Tamamlanmış Bir Resmi, Kucak Delisi, Siyah Külot) odaklanılmıştır. Bu çalışma sonucunda, Yalçın Tosun’un öykülerinde LGBTİ cinsel kimliklerin, ayrımcılık mekanizmalarından uzakta ele alındığı ve LGBTİ kimliklerinin etkin bir biçimde yansıtıldığı ve geleneksel ataerkil kadınlık ve erkeklik rollerinin yapı-bozuma uğratılarak yeniden inşa edilme olanaklarının ortaya koyulduğu görülmüştür.
Designing and Testing of a System for Aerosolization and Recovery of Viable Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Theoretical and Engineering Considerations
Authors: Li Peiyang , Koziel Jacek A. , Zimmerman Jeffrey J. , Hoff Steven J. , Zhang Jianqiang , Cheng Ting-Yu , Yim-Im Wannarat , Lee Myeongseong , Chen Baitong , Jenks William S.
Published: May 2021

Porcine reproductive and respiratory syndrome virus (PRRSV) infections cause significant economic losses to swine producers every year. Aerosols containing infectious PRRSV are an important route of transmission, and proper treatment of air could mitigate the airborne spread of the virus within and between barns. Previous bioaerosol studies focused on the microbiology of PRRSV aerosols; thus, the current study addressed the engineering aspects of virus aerosolization and collection. Specific objectives were to (1) build and test a virus aerosolization system, (2) achieve a uniform and repeatable aerosol generation and collection throughout all replicates, (3) identify and minimize sources of variation, and (4) verify that the collection system (impingers) performed similarly. The system for virus aerosolization was built and tested (Obj. 1). The uniform airflow distribution was confirmed using a physical tracer (<12% relative standard deviation) for all treatments and sound engineering control of flow rates (Obj. 2). Theoretical uncertainty analyses and mass balance calculations showed <3% loss of air mass flow rate between the inlet and outlet (Obj. 3). A comparison of TCID50values among impinger fluids showed no statistical difference between any two of the three trials (p-value = 0.148, 0.357, 0.846) (Obj. 4). These results showed that the readiness of the system for research on virus aerosolization and treatment (e.g., by ultraviolet light), as well as its potential use for research on other types of airborne pathogens and their mitigation on a laboratory scale.
Somite Compartments in Amphioxus and Its Implications on the Evolution of the Vertebrate Skeletal Tissues
Authors: Yong Luok Wen , Lu Tsai-Ming , Tung Che-Huang , Chiou Ruei-Jen , Li Kun-Lung , Yu Jr-Kai
Published: May 2021

Mineralized skeletal tissues of vertebrates are an evolutionary novelty within the chordate lineage. While the progenitor cells that contribute to vertebrate skeletal tissues are known to have two embryonic origins, the mesoderm and neural crest, the evolutionary origin of their developmental process remains unclear. Using cephalochordate amphioxus as our model, we found that cells at the lateral wall of the amphioxus somite express SPARC (a crucial gene for tissue mineralization) and various collagen genes. During development, some of these cells expand medially to surround the axial structures, including the neural tube, notochord and gut, while others expand laterally and ventrally to underlie the epidermis. Eventually these cell populations are found closely associated with the collagenous matrix around the neural tube, notochord, and dorsal aorta, and also with the dense collagen sheets underneath the epidermis. Using known genetic markers for distinct vertebrate somite compartments, we showed that the lateral wall of amphioxus somite likely corresponds to the vertebrate dermomyotome and lateral plate mesoderm. Furthermore, we demonstrated a conserved role for BMP signaling pathway in somite patterning of both amphioxus and vertebrates. These results suggest that compartmentalized somites and their contribution to primitive skeletal tissues are ancient traits that date back to the chordate common ancestor. The finding of SPARC-expressing skeletal scaffold in amphioxus further supports previous hypothesis regarding SPARC gene family expansion in the elaboration of the vertebrate mineralized skeleton.
Modeling Neurological Disorders in 3D Organoids Using Human-Derived Pluripotent Stem Cells
Authors: Bose Raj , Banerjee Soumyabrata , Dunbar Gary L.
Published: May 2021

Modeling neurological disorders is challenging because they often have both endogenous and exogenous causes. Brain organoids consist of three-dimensional (3D) self-organizing brain tissue which increasingly is being used to model various aspects of brain development and disorders, such as the generation of neurons, neuronal migration, and functional networks. These organoids have been recognized as important in vitro tools to model developmental features of the brain, including neurological disorders, which can provide insights into the molecular mechanisms involved in those disorders. In this review, we describe recent advances in the generation of two-dimensional (2D), 3D, and blood-brain barrier models that were derived from induced pluripotent stem cells (iPSCs) and we discuss their advantages and limitations in modeling diseases, as well as explore the development of a vascularized and functional 3D model of brain processes. This review also examines the applications of brain organoids for modeling major neurodegenerative diseases and neurodevelopmental disorders.
Timing Does Matter: Nerve-Mediated HDAC1 Paces the Temporal Expression of Morphogenic Genes During Axolotl Limb Regeneration
Authors: Wang Mu-Hui , Hsu Chia-Lang , Wu Cheng-Han , Chiou Ling-Ling , Tsai Yi-Tzang , Lee Hsuan-Shu , Lin Shau-Ping
Published: May 2021

Sophisticated axolotl limb regeneration is a highly orchestrated process that requires highly regulated gene expression and epigenetic modification patterns at precise positions and timings. We previously demonstrated two waves of post-amputation expression of a nerve-mediated repressive epigenetic modulator, histone deacetylase 1 (HDAC1), at the wound healing (3 days post-amputation; 3 dpa) and blastema formation (8 dpa onward) stages in juvenile axolotls. Limb regeneration was profoundly inhibited by local injection of an HDAC inhibitor, MS-275, at the amputation sites. To explore the transcriptional response of post-amputation axolotl limb regeneration in a tissue-specific and time course-dependent manner after MS-275 treatment, we performed transcriptome sequencing of the epidermis and soft tissue (ST) at 0, 3, and 8 dpa with and without MS-275 treatment. Gene Ontology (GO) enrichment analysis of each coregulated gene cluster revealed a complex array of functional pathways in both the epidermis and ST. In particular, HDAC activities were required to inhibit the premature elevation of genes related to tissue development, differentiation, and morphogenesis. Further validation by Q-PCR in independent animals demonstrated that the expression of 5 out of 6 development- and regeneration-relevant genes that should only be elevated at the blastema stage was indeed prematurely upregulated at the wound healing stage when HDAC1 activity was inhibited. WNT pathway-associated genes were also prematurely activated under HDAC1 inhibition. Applying a WNT inhibitor to MS-275-treated amputated limbs partially rescued HDAC1 inhibition, resulting in blastema formation defects. We propose that post-amputation HDAC1 expression is at least partially responsible for pacing the expression timing of morphogenic genes to facilitate proper limb regeneration.
Epigenetic Regulation in Hydra: Conserved and Divergent Roles
Authors: Pillai Anirudh , Gungi Akhila , Reddy Puli Chandramouli , Galande Sanjeev
Published: May 2021

Transitions in gene regulatory processes responsible for the emergence of specialized cell types and spatiotemporal regulation of developmental signaling prior to the divergence of Cnidaria and Bilateria are poorly understood. As a sister group of Bilateria, the phylum Cnidaria can provide significant insights into these processes. Among the cnidarians, hydrae have been studied for >250 years to comprehend the mechanisms underlying their unique immortality and robust regenerative capacity. Studies on Hydra spp. and other pre-bilaterians alike have advanced our understanding of the evolutionary underpinnings governing eumetazoan tissue development, homeostasis, and regeneration. In addition to its regenerative potential, Hydra exhibits continuously active axial patterning due to its peculiar tissue dynamics. These distinctive physiological processes necessitate large scale gene expression changes that are governed by the multitude of epigenetic mechanisms operating in cells. This review highlights the contemporary knowledge of epigenetic regulation in Hydra with contemporary studies from other members of Cnidaria, as well as the interplay between regulatory mechanisms wherever demonstrated. The studies covered in the scope of this review reveal both ancestral and divergent roles played by conserved epigenetic mechanisms with emphasis on transcriptional regulation. Additionally, single-cell transcriptomics data was mined to predict the physiological relevance of putative gene regulatory components, which is in agreement with published findings and yielded insights into the possible functions of the gene regulatory mechanisms that are yet to be deciphered in Hydra, such as DNA methylation. Finally, we delineate potentially rewarding epigenetics research avenues that can further leverage the unique biology of Hydra.
Pharmacophore Modelling-Based Drug Repurposing Approaches for SARS-CoV-2 Therapeutics
Authors: Rampogu Shailima , Lee Keun Woo
Published: May 2021

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating effect globally with no effective treatment. The swift strategy to find effective treatment against coronavirus disease 2019 (COVID-19) is to repurpose the approved drugs. In this pursuit, an exhaustive computational method has been used on the DrugBank compounds targeting nsp16/nsp10 complex (PDB code: 6W4H). A structure-based pharmacophore model was generated, and the selected model was escalated to screen DrugBank database, resulting in three compounds. These compounds were subjected to molecular docking studies at the protein-binding pocket employing the CDOCKER module available with the Discovery Studio v18. In order to discover potential candidate compounds, the co-crystallized compound S-adenosyl methionine (SAM) was used as the reference compound. Additionally, the compounds remdesivir and hydroxycholoroquine were employed for comparative docking. The results have shown that the three compounds have demonstrated a higher dock score than the reference compounds and were upgraded to molecular dynamics simulation (MDS) studies. The MDS results demonstrated that the three compounds, framycetin, kanamycin, and tobramycin, are promising candidate compounds. They have represented a stable binding mode at the targets binding pocket with an average protein backbone root mean square deviation below 0.3 nm. Additionally, they have prompted the hydrogen bonds during the entire simulations, inferring that the compounds have occupied the active site firmly. Taken together, our findings propose framycetin, kanamycin, and tobramycin as potent putative inhibitors for COVID-19 therapeutics.
Latent Cytomegalovirus Reactivation in Patients With Liver Failure: A 10-Year Retrospective Case-Control Study, 2011-2020
Authors: Yang Qingluan , Zhou Zhe , Yang Xuefang , Chen Yuming , Liu Aiping , Zhang Bingyan , Shao Lingyun , Zheng Jianming , Zhang Wenhong
Published: May 2021

Background

The aim of this study was to explore potential risk factors for cytomegalovirus (CMV) reactivation and their impact on liver failure patient outcomes.

Methods

A 10-year retrospective case–control study was conducted in adult participants, who were diagnosed with liver failure and had undergone CMV DNA tests. CMV reactivation cases were matched with controls at a 2:1 ratio based on age, sex, and year of admission. Univariate and multivariate analyses were used to explore risk factors for CMV reactivation.

Results

Between January 2011 and April 2020, 198 adult patients with liver failure and available CMV DNA test results were enrolled into the study. Among them, 33 patients had detectable CMV DNA in their plasma (16.7%). Clinical manifestations and liver function were comparable between the CMV reactivation and non-reactivation groups. However, CMV reactivation may triple mortality in patients with liver failure. We found that nearly 50% of patients in the CMV-positive group received glucocorticoids, compared to 13.6% in the CMV-negative group (P=0.000). The median total glucocorticoid dose included 836.5 mg of methylprednisolone (IQR 308.7-1259.0 mg) in the CMV-positive group, which was significantly higher than that in the CMV-negative group. A multivariate analysis revealed that glucocorticoid use significantly increased the risk of CMV reactivation (adjusted OR, 4.84; 95% CI, 1.61–14.49; P=0.005). Patients with CMV reactivation tended to be associated with higher white cell counts (adjusted OR, 1.21; 95% CI, 1.08–1.36; P=0.002).

Conclusions

High intravenous glucocorticoid doses may be the most important risk factor for CMV reactivation in liver failure.
Exosomes Derived From Alveolar Epithelial Cells Promote Alveolar Macrophage Activation Mediated by miR-92a-3p in Sepsis-Induced Acute Lung Injury
Authors: Liu Fen , Peng Wei , Chen Jiaquan , Xu Zeyao , Jiang Rong , Shao Qiang , Zhao Ning , Qian Kejian
Published: May 2021

Acute lung injury (ALI) induced by sepsis is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. The exact mechanism by which the initial mediator of alveolar epithelial cells (AECs) induces inflammation remains elusive. Here we investigated the roles of AEC-derived exosomes in AM activation and sepsis-induced ALI in vivo and in vitro. Cecal ligation and puncture (CLP) was utilized to establish septic lung injury model in rats. The effect of exosomal inhibition by intratracheal GW4869 administration on lung injury was investigated. To assess the effects of AEC-derived exosomes on ALI, we treated the rat alveolar epithelial cell line RLE-6TN with LPS to induce cell damage. Exosomes from conditioned medium of LPS-treated AECs (LPS-Exos) were isolated by ultracentrifugation. The miRNAs in LPS-Exos were screened by miRNA expression profile analysis. The effects of miR-92a-3p on the function of AMs were studied. We found that intratracheal GW4869 administration ameliorated lung injury following CLP-induced ALI. LPS-Exos were taken up by AMs and activated these cells. Consistently, administration of LPS-Exos in rats significantly aggravated pulmonary inflammation and alveolar permeability. Moreover, miR-92a-3p was enriched in LPS-Exos and could be delivered to AMs. Inhibition of miR-92a-3p in AECs diminished the proinflammatory effects of LPS-Exos in vivo and in vitro. Mechanistically, miR-92a-3p activates AMs along with pulmonary inflammation. This process results in activation of the NF-κB pathway and downregulation of PTEN expression, which was confirmed by a luciferase reporter assay. In conclusion, AEC-derived exosomes activate AMs and induce pulmonary inflammation mediated by miR-92a-3p in ALI. The present findings revealed a previously unidentified role of exosomal miR-92a-3p in mediating the crosstalk between injured AEC and AMs. miR-92a-3p in AEC exosomes might represent a novel diagnostic biomarker for ALI, which may lead to a new therapeutic approach.
Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese ob/ob Mice
Authors: Saito Akimichi , Ishimori Naoki , Tokuhara Satoshi , Homma Tsuneaki , Nishikawa Mikito , Iwabuchi Kazuya , Tsutsui Hiroyuki
Published: May 2021

The infiltration and activation of macrophages as well as lymphocytes within the aorta contribute to the pathogenesis of abdominal aortic aneurysm (AAA). Invariant natural killer T (iNKT) cells are unique subset of T lymphocytes and have a crucial role in atherogenesis. However, it remains unclear whether iNKT cells also impact on the development of AAA. Ob/ob mice were administered angiotensin II (AngII, 1,000 ng/kg/min) or phosphate-buffered saline (PBS) by osmotic minipumps for 4 weeks and further divided into 2 groups; α-galactosylceramide (αGC; PBS-αGC; n = 5 and AngII-αGC; n = 12), which specifically activates iNKT cells, and PBS (PBS-PBS; n = 10, and AngII-PBS; n = 6). Maximal abdominal aortic diameter was comparable between PBS-PBS and PBS-αGC, and was significantly greater in AngII-PBS than in PBS-PBS. This increase was significantly attenuated in AngII-αGC without affecting blood pressure. αGC significantly enhanced iNKT cell infiltration compared to PBS-PBS. The ratio of F4/80-positive macrophages or CD3-positive T lymphocytes area to the lesion area was significantly higher in AngII-PBS than in PBS-PBS, and was significantly decreased in AngII-αGC. Gene expression of M2-macrophage specific markers, arginase-1 and resistin-like molecule alpha, was significantly greater in aortic tissues from AngII-αGC compared to AngII-PBS 1 week after AngII administration, and this increase was diminished at 4 weeks. Activation of iNKT cells by αGC can attenuate AngII-mediated AAA in ob/ob mice via inducing anti-inflammatory M2 polarized state. Activation of iNKT cells by the bioactive lipid αGC may be a novel therapeutic target against the development of AAA.
Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis
Authors: Büttner Petra , Feistner Lukas , Lurz Philipp , Thiele Holger , Hutcheson Joshua D. , Schlotter Florian
Published: May 2021

Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.
Hypertension-Mediated Organ Damage Correlates With Serum Homocysteine Level in Community-Dwelling Elderly Chinese: The North Shanghai Study
Authors: Ren Zhongyuan , Zhang Jun , Yu Shikai , Zhao Song , Tang Jiamin , Zheng Yixing , Meng Weilun , Xu Chong , Zhang Yi , Xu Yawei
Published: May 2021

Introduction: Serum homocysteine (Hcy) level is associated with cardiocerebrovascular disease. However, the relationship between Hcy and hypertension-mediated organ damage (HMOD) in non-hospitalized residents has not been elucidated. We aimed to investigate the association of HMOD with Hcy in elderly Chinese.

Methods: One thousand seven hundred and forty-four community-dwelling elderly Chinese (age ≥65 years) participated in the Northern Shanghai Study from Jun. 2014 to Aug. 2015. Hyperhomocysteinemia (HHcy) was defined as serum Hcy ≥15 mmol/L, and HMOD was estimated as arterial stiffness [carotid-femoral pulse wave velocity (CF-PWV) and ankle-brachial index (ABI)], cardiac impairment [left ventricular (LV) hypertrophy and LV diastolic dysfunction], and renal dysfunction [estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio]. Linear and logistic regression models were built to explore the associations of HMOD with Hcy.

Results: Among 1,744 participants, 632 (36.2%) were diagnosed as HHcy. HHcy group had more men (61.2 vs. 35.3%), with higher age (73.7 ± 6.7 vs. 70.4 ± 5.3 years) and BMI (24.2 ± 3.4 vs. 23.7 ± 3.5 kg/m2). Linear regression analysis showed that serum Hcy level was positively associated CF-PWV and negatively associated with ABI and eGFR. By logistic regression, HHcy was significantly associated with abnormal CF-PWV [odds ratio (OR) = 1.53, 95% confidence interval (CI) 1.08–2.16] and ABI (OR = 1.55, 95% CI 1.17–2.04), and decreased eGFR (OR = 7.09, 95% CI 4.03–12.47) after adjustment for covariates. Moreover, similar associations of serum Hcy level with CF-PWV and eGFR were observed in subgroups by gender and hypertensive state.

Conclusion: HMOD, particularly renal dysfunction and arterial stiffening, was significantly and independently associated with increased serum Hcy level in the elderly Chinese.

Clinical Trial Registration: [ClinicalTrial.gov], identifier [NCT02368938].
The Role of Long Non-coding RNAs in Sepsis-Induced Cardiac Dysfunction
Authors: Li Jiawen , Zhang Yulin , Zhang Donghui , Li Yifei
Published: May 2021

Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. The heart is one of the most commonly involved organs during sepsis, and cardiac dysfunction, which is usually indicative of an extremely poor clinical outcome, is a leading cause of death in septic cases. Despite substantial improvements in the understanding of the mechanisms that contribute to the origin and responses to sepsis, the prognosis of sepsis-induced cardiac dysfunction (SICD) remains poor and its molecular pathophysiological changes are not well-characterized. The recently discovered group of mediators known as long non-coding RNAs (lncRNAs) have presented novel insights and opportunities to explore the mechanisms and development of SICD and may provide new targets for diagnosis and therapeutic strategies. LncRNAs are RNA transcripts of more than 200 nucleotides with limited or no protein-coding potential. Evidence has rapidly accumulated from numerous studies on how lncRNAs function in associated regulatory circuits during SICD. This review outlines the direct evidence of the effect of lncRNAs on SICD based on clinical trials and animal studies. Furthermore, potential functional lncRNAs in SICD that have been identified in sepsis studies are summarized with a proven biological function in research on other cardiovascular diseases.
Bayesian Inference of Ice Softness and Basal Sliding Parameters at Langjökull
Authors: Gopalan Giri , Hrafnkelsson Birgir , Aðalgeirsdóttir Guðfinna , Pálsson Finnur
Published: May 2021

We develop Bayesian statistical models that are designed for the inference of ice softness and basal sliding parameters, important glaciological quantities. These models are applied to Langjökull, the second largest temperate ice cap in Iceland at about 900 squared kilometers in area. The models make use of a relationship between physical parameters and ice velocity as stipulated by a shallow ice approximation that is generally applicable to Langjökull. The posterior distribution for ice softness concentrates around 18.2 × 10−25s−1Pa−3; moreover, spatially varying basal sliding parameters are inferred allowing for the decomposition of velocity into a deformation component and a sliding component, with spatial variation consistent with previous studies. Bayesian computation is conducted with a Gibbs sampling approach. The paper serves as an example of statistical inference for ice softness and basal sliding parameters at temperate, shallow glaciers using surface velocity data.
Research on the Dispatching Rules of Inter-Basin Water Transfer Projects Based on the Two-Dimensional Scheduling Diagram
Authors: Cai Siyu , Sun Long , Liu Qingtao , Ji Yi , Wang Hao
Published: May 2021

Inter-basin water transfer projects play an important role in allocating water resources that vary both in temporal and spatial scale while supporting regional development. In the practical operation of inter-basin water transfer projects, high water level and less inflow runoff would result in water supply destruction, while low water level and more inflow runoff would cause abandoned water. How to play the compensation roles of hydrological characteristics and storage capacities of multi-reservoirs to maximize the utilization efficiency of water resources, the key is to select the basis for the decision-making of starting water transfer process. In this paper, we selected the “Datong-Huangshui” water transfer project as the research subject, analyzed the composition of the inter-basin water transfer system, and constructed a dispatching rule extraction model including water transfer rules, water diversion rules, and water supply rules. Then the NSGA-II was used to solve the multi-objective optimization model to obtain the Pareto frontier solution set of the dispatching rules. Finally, the optimal operation scheme was determined and discussed according to the scheduling scheme decision model. The model itself was based on the gray target model and prospect theory. We found that: (1) The optimal target frontier obtained by the two-dimensional scheduling diagram and the hedging rules for water supply was closer to the theoretical optimal frontier of the multi-objective problem. This result indicated that the two-dimensional scheduling diagram and the hedging rules for water supply could better guide the water diversion operation of inter-basin water transfer projects. (2) Based on the multi-objective optimal operation schemes set, the OPT scheme obtained by the scheduling scheme decision model using gray target model and prospect theory could generate 359 million Kwh. At the same time, it could guarantee 90% of municipal and industrial water supply and 85% of agricultural water supply.
Subjective Measure of Cognitive Load Depends on Participants’ Content Knowledge Level
Authors: Zu Tianlong , Munsell Jeremy , Rebello N. Sanjay
Published: May 2021

Cognitive load theory (CLT) posits the classic view that cognitive load (CL) has three-components: intrinsic, extraneous and germane. Prior research has shown that subjective ratings are valid measures of different CL subtypes. To a lesser degree, how the validity of these subjective ratings depends on learner characteristics has not been studied. In this research, we explored the extent to which the validity of a specific set of subjective measures depends upon learners’ prior knowledge. Specifically, we developed an eight-item survey to measure the three aforementioned subtypes of CL perceived by participants in a testing environment. In the first experiment (N = 45) participants categorized the eight items into different groups based on similarity of themes. Most of the participants sorted the items consistent with a threefold construct of the CLT. Interviews with a subgroup (N = 13) of participants provided verbal evidence corroborating their understanding of the items that was consistent with the classic view of the CLT. In the second experiment (N = 139) participants completed the survey twice after taking a conceptual test in a pre/post setting. A principal component analysis (PCA) revealed a two-component structure for the survey when the content knowledge level of the participants was initially lower, but a three-component structure when the content knowledge of the participants was improved to a higher level. The results seem to suggest that low prior knowledge participants failed to differentiate the items targeting the intrinsic load from those measuring the extraneous load. In the third experiment (N = 40) participants completed the CL survey after taking a test consisting of problems imposing different levels of intrinsic and extraneous load. The results reveals that how participants rated on the CL survey was consistent with how each CL subtype was manipulated. Thus, the CL survey developed is decently effective measuring different types of CL. We suggest instructors to use this instrument after participants have established certain level of relevant knowledge.
Emerging Classes of Small Non-Coding RNAs With Potential Implications in Diabetes and Associated Metabolic Disorders
Authors: Jacovetti Cécile , Bayazit Mustafa Bilal , Regazzi Romano
Published: May 2021

Most of the sequences in the human genome do not code for proteins but generate thousands of non-coding RNAs (ncRNAs) with regulatory functions. High-throughput sequencing technologies and bioinformatic tools significantly expanded our knowledge about ncRNAs, highlighting their key role in gene regulatory networks, through their capacity to interact with coding and non-coding RNAs, DNAs and proteins. NcRNAs comprise diverse RNA species, including amongst others PIWI-interacting RNAs (piRNAs), involved in transposon silencing, and small nucleolar RNAs (snoRNAs), which participate in the modification of other RNAs such as ribosomal RNAs and transfer RNAs. Recently, a novel class of small ncRNAs generated from the cleavage of tRNAs or pre-tRNAs, called tRNA-derived small RNAs (tRFs) has been identified. tRFs have been suggested to regulate protein translation, RNA silencing and cell survival. While for other ncRNAs an implication in several pathologies is now well established, the potential involvement of piRNAs, snoRNAs and tRFs in human diseases, including diabetes, is only beginning to emerge. In this review, we summarize fundamental aspects of piRNAs, snoRNAs and tRFs biology. We discuss their biogenesis while emphasizing on novel sequencing technologies that allow ncRNA discovery and annotation. Moreover, we give an overview of genomic approaches to decrypt their mechanisms of action and to study their functional relevance. The review will provide a comprehensive landscape of the regulatory roles of these three types of ncRNAs in metabolic disorders by reporting their differential expression in endocrine pancreatic tissue as well as their contribution to diabetes incidence and diabetes-underlying conditions such as inflammation. Based on these discoveries we discuss the potential use of piRNAs, snoRNAs and tRFs as promising therapeutic targets in metabolic disorders.
The Interplay of Glucagon-Like Peptide-1 Receptor Trafficking and Signalling in Pancreatic Beta Cells
Authors: Marzook Amaara , Tomas Alejandra , Jones Ben
Published: May 2021

The glucagon-like peptide 1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) which mediates the effects of GLP-1, an incretin hormone secreted primarily from L-cells in the intestine and within the central nervous system. The GLP-1R, upon activation, exerts several metabolic effects including the release of insulin and suppression of appetite, and has, accordingly, become an important target for the treatment for type 2 diabetes (T2D). Recently, there has been heightened interest in how the activated GLP-1R is trafficked between different endomembrane compartments, controlling the spatial origin and duration of intracellular signals. The discovery of “biased” GLP-1R agonists that show altered trafficking profiles and selective engagement with different intracellular effectors has added to the tools available to study the mechanisms and physiological importance of these processes. In this review we survey early and recent work that has shed light on the interplay between GLP-1R signalling and trafficking, and how it might be therapeutically tractable for T2D and related diseases.
Diagnosis and Prediction for Loss of Coolant Accidents in Nuclear Power Plants Using Deep Learning Methods
Authors: She Jingke , Shi Tianzi , Xue Shiyu , Zhu Yan , Lu Shaofei , Sun Peiwei , Cao Huasong
Published: May 2021

A combination of Convolutional Neural Network (CNN), Long-Short Term Memory (LSTM), and Convolutional LSTM (ConvLSTM) is constructed in this work for the fault diagnosis and post-accident prediction for Loss of Coolant Accidents (LOCAs) in Nuclear Power Plants (NPPs). The advantages of ConvLSTM, such as effective feature determination and extraction, are applied to the classification of LOCA cases. The prediction accuracy is enhanced via the collaborative work of CNN and LSTM. Such a hybrid model is proved to be functional, accurate, and adaptive, offering quick accident judgment and a reliable decision basis for the emergency response purpose. It then allows NPPs to have an Artificial Intelligence (AI)-based solution for fault diagnosis and post-accident prediction.
BeO Utilization in Reactors for the Improvement of Extreme Reactor Environments - A Review
Authors: Li Kai , Qian Libo , Li Xiaojing , Ma Yu , Zhou Wenzhong
Published: May 2021

Ceramic material is one of the essential materials used in reactors. Beryllium oxide ceramics have good high-temperature radiation stability, high density, high strength, and thermal conductivity at high temperatures, and the price of beryllium oxide is relatively moderate. This makes it more suitable for use as a reflector, moderator, and dispersion phase fuel matrix in a reactor. In recent years, beryllium oxide has attracted widespread attention due to its high hardness, high resistivity, high thermal conductivity, high melting point, and high radiation resistance. Because of its excellent mechanical properties, beryllium oxide materials also have a long history in the field of nuclear energy. Reactor extreme environments have become a significant challenge for optimizing reactor operation and safety performance. The utilization of beryllium oxide can significantly alleviate extreme reactor environments. According to research, the coupling of beryllium oxide material can effectively improve nuclear fuels' thermal conductivity, such as uranium dioxide. Beryllium oxide also has good radiation resistance and neutron scattering properties, which increases its applications in nuclear energy. The article comprehensively reviews the BeO utilization approaches in reactors to improve extreme reactor environments for current reactor operation and future reactor design optimization.
Ecological Risks of Heavy Metals and Microbiome Taxonomic Profile of a Freshwater Stream Receiving Wastewater of Textile Industry
Authors: Odubanjo Grace Olunike , Oyetibo Ganiyu Oladunjoye , Ilori Matthew Olusoji
Published: May 2021

Textile wastewater (TWW) contains toxic metals that are inimical to microbiome, aesthetic quality, and the health of the receiving freshwater. TWW-impacted freshwater (L2) was assessed for metals eco-toxicity and the consequent impact on microbiome taxonomic profile (MTP) compared to a pristine environment (L1). The conductivity (1750 μS/cm), chemical oxygen demand (2,110 mg/L), biochemical oxygen demand (850 mg/L), and salinity (5,250 mg/L) of L2 were far above the permissible limits. Mercury posed very high ecological risks in the water column of L2 as lead, arsenic, and copper exerted high risk in the sediment. The MTP of L2 revealed the dominance of Euryarchaeota (48.6%) and Bathyarchaeota (45.9%) among the Archaea. The relative abundances of Proteobacteria and Bacteroidetes increased from 38.3 to 2.0%, respectively, in the L1 ecosystem to 42.1 and 12.9%, correspondingly, in L2. Unclassified Eukarya_uc_p (50.4%) and Fungi_uc (16.0%) were key players among the fungi kingdom in L2. The impact of the TWW on the microbiome was evident with the extinction of 6,249, 32,272, and 10,029 species of archaea, bacteria, and fungi, respectively. Whereas, 35,157, 32,394, and 7,291 species of archaea, bacteria, and fungi, correspondingly, exclusively found in L2 were assumed to be invading resident communities that combined with dominant autochthonous strains in shaping the ecophysiology dynamics in TWW-impacted freshwater. While the sensitive microorganisms in L2 are suggested bio-indicators of TWW ecotoxicity, the emergent and dominant taxa are pivotal to natural attenuation processes in the contaminated ecosystem that could be adopted for biotechnological strategy in decommissioning the TWW-impacted freshwater.
Phylogenetic Patterns in Mouth Posture and Echolocation Emission Behavior of Phyllostomid Bats
Authors: Gessinger Gloria , Page Rachel , Wilfert Lena , Surlykke Annemarie , Brinkløv Signe , Tschapka Marco
Published: May 2021

While phyllostomid bats show an impressive range of feeding habits, most of them emit highly similar echolocation calls. Due to the presence of an often prominent noseleaf, it has long been assumed that all phyllostomids emit echolocation calls exclusively through the nostrils rather than through the mouth. However, photo evidence documents also phyllostomid bats flying with an opened mouth. We hypothesized that all phyllostomid species emit echolocation calls only through the nostrils and therefore fly consistently with a closed mouth, and that observations of an open mouth should be a rare and random behavior among individuals and species. Using a high-speed camera and standardized conditions in a flight cage, we screened 40 phyllostomid species. Behavior varied distinctly among the species and mouth posture shows a significant phylogenetic signal. Bats of the frugivorous subfamilies Rhinophyllinae and Carolliinae, the nectarivorous subfamilies Glossophaginae and Lonchophyllinae, and the sanguivorous subfamily Desmodontinae all flew consistently with open mouths. So did the animalivorous subfamilies Glyphonycterinae, Micronycterinae and Phyllostominae, with the notable exception of species in the omnivorous genus Phyllostomus, which consistently flew with mouths closed. Bats from the frugivorous subfamily Stenodermatinae also flew exclusively with closed mouths with the single exception of the genus Sturnira, which is the sister clade to all other stenodermatine species. Further, head position angles differed significantly between bats echolocating with their mouth closed and those echolocating with their mouths opened, with closed-mouth phyllostomids pointing only the nostrils in the direction of flight and open-mouth phyllostomids pointing both the nostrils and mouth gape in the direction of flight. Ancestral trait reconstruction showed that the open mouth mode is the ancestral state within the Phyllostomidae. Based on the observed behavioral differences, we suggest that phyllostomid bats are not all nasal emitters as previously thought and discuss possible reasons. Further experiments, such as selectively obstructing sound emission through nostrils or mouth, respectively, will be necessary to clarify the actual source, plasticity and ecological relevance of sound emission of phyllostomid bats flying with their mouths open.