bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation Mode of the O–H Bond in Betanidin, pKa-Clusterization Prediction, and Molecular Interactions via Shape Theory and DFT Methods
Authors: Ramírez-Velásquez Iliana María , Bedoya-Calle Álvaro H. , Vélez Ederley , Caro-Lopera Francisco J.
Published: February 2023

Betanidin (Bd) is a nitrogenous metabolite with significant bioactive potential influenced by pH. Its free radical scavenging activity and deprotonation pathway are crucial to studying its physicochemical properties. Motivated by the published discrepancies about the best deprotonation routes in Bd, this work explores all possible pathways for proton extractions on that molecule, by using the direct approach method based on pKa. The complete space of exploration is supported by a linear relation with constant slope, where the pKa is written in terms of the associated deprotonated molecule energy. The deprotonation rounds 1, …, 6 define groups of parallel linear models with constant slope. The intercepts of the models just depend on the protonated energy for each round, and then the pKa can be trivially ordered and explained by the energy. We use the direct approximation method to obtain the value of pKa. We predict all possible outcomes based on a linear model of the energy and some related verified assumptions. We also include a new measure of similarity or dissimilarity between the protonated and deprotonated molecules, via a geometric–chemical descriptor called the Riemann–Mulliken distance (RMD). The RMD considers the cartesian coordinates of the atoms, the atomic mass, and the Mulliken charges. After exploring the complete set of permutations, we show that the successive deprotonation process does not inherit the local energy minimum and that the commutativity of the paths does not hold either. The resulting clusterization of pKa can be explained by the local acid and basic groups of the BD, and the successive deprotonation can be predicted by using the chemical explained linear models, which can avoid unnecessary optimizations. Another part of the research uses our own algorithm based on shape theory to determine the protein’s active site automatically, and molecular dynamics confirmed the results of the molecular docking of Bd in protonated and anionic form with the enzyme aldose reductase (AR). Also, we calculate the descriptors associated with the SET and SPLET mechanisms.
Expression of Acetabular Labral Vascular Endothelial Growth Factor and Nerve Growth Factor Is Directly Associated with Hip Osteoarthritis Pain: Investigation by Immunohistochemical Staining
Authors: Sato Yoshihiro , Tetsunaga Tomonori , Yamada Kazuki , Kawamura Yoshi , Yoshida Aki , Ozaki Toshifumi
Published: February 2023

The acetabular labrum enhances hip joint stability and plays a key role in osteoarthritis (OA) progression. Labral nerve endings contribute to hip OA pain. Moreover, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are associated with pain. Consequently, we analysed VEGF and NGF expression levels in the labrum and their roles in OA. Labra obtained from OA patients were stained immunohistochemically, and labral cells were cultured and subjected to a reverse transcription (RT)–polymerase chain reaction (PCR) to analyse VEGF and NGF mRNA expression. VEGF and NGF expression were compared in each region of the labrum. Correlations between VEGF and NGF expression and age, body mass index, Kellgren–Lawrence grade, Harris Hip Score, the visual analogue scale (VAS), and Krenn score were analysed, and the RT-PCR confirmed the findings. VEGF and NGF expression were high on the labral articular side, negatively correlated with the Krenn score, and positively correlated with the VAS in early OA. VEGF and NGF mRNA expression increased significantly in patients with severe pain and decreased significantly in severely degenerated labra. In early OA, VEGF and NGF expression in the acetabular labrum was associated with the occurrence of hip pain; therefore, these factors could be effective targets for pain management.
The Effects of Sirolimus and Magnesium on Primary Human Coronary Endothelial Cells: An In Vitro Study
Authors: Fedele Giorgia , Castiglioni Sara , Maier Jeanette A. M. , Locatelli Laura
Published: February 2023

Drug eluting magnesium (Mg) bioresorbable scaffolds represent a novel paradigm in percutaneous coronary intervention because Mg-based alloys are biocompatible, have adequate mechanical properties and can be resorbed without adverse events. Importantly, Mg is fundamental in many biological processes, mitigates the inflammatory response and is beneficial for the endothelium. Sirolimus is widely used as an antiproliferative agent in drug eluting stents to inhibit the proliferation of smooth muscle cells, thus reducing the occurrence of stent restenosis. Little is known about the potential interplay between sirolimus and Mg in cultured human coronary artery endothelial cells (hCAEC). Therefore, the cells were treated with sirolimus in the presence of different concentrations of extracellular Mg. Cell viability, migration, barrier function, adhesivity and nitric oxide synthesis were assessed. Sirolimus impairs the viability of subconfluent, but not of confluent cells independently from the concentration of Mg in the culture medium. In confluent cells, sirolimus inhibits migration, while it cooperates with Mg in exerting an anti-inflammatory action that might have a role in preventing restenosis and thrombosis.
The Intracellular and Secreted Sides of Osteopontin and Their Putative Physiopathological Roles
Authors: Bastos Ana Clara Santos da Fonseca , Gomes Amanda Vitória Pampolha , Silva Gabriela Ribeiro , Emerenciano Mariana , Ferreira Luciana Bueno , Gimba Etel Rodrigues Pereira
Published: February 2023

Classically, osteopontin (OPN) has been described as a secreted glycophosprotein. Indeed, most data concerning its physiological and pathological roles are mainly related to the secreted OPN (sOPN). However, there are several instances in which intracellular OPN (iOPN) has been described, presenting some specific roles in distinct experimental models, such as in the immune system, cancer cells, and neurological disorders. We herein aimed to highlight and discuss some of these secreted and intracellular roles of OPN and their putative clinical and biological impacts. Moreover, by consolidating data from the OPN protein database, we also analyzed the occurrence of signal peptide (SP) sequences and putative subcellular localization, especially concerning currently known OPN splicing variants (OPN-SV). Comprehending the roles of OPN in its distinct cellular and tissue environments may provide data regarding the additional applications of this protein as biomarkers and targets for therapeutic purposes, besides further describing its pleiotropic roles.
The Role of Genetics in the Development and Pharmacotherapy of Depression and Its Impact on Drug Discovery
Authors: Zięba Agata , Matosiuk Dariusz , Kaczor Agnieszka A.
Published: February 2023

Complex disorders, such as depression, remain a mystery for scientists. Although genetic factors are considered important for the prediction of one’s vulnerability, it is hard to estimate the exact risk for a patient to develop depression, based only on one category of vulnerability criteria. Genetic factors also regulate drug metabolism, and when they are identified in a specific combination, may result in increased drug resistance. A proper understanding of the genetic basis of depression assists in the development of novel promising medications and effective disorder management schemes. This review aims to analyze the recent literature focusing on the correlation between specific genes and the occurrence of depression. Moreover, certain aspects targeting a high drug resistance identified among patients suffering from major depressive disorder were highlighted in this manuscript. An expected direction of future drug discovery campaigns was also discussed.
Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Authors: Martelli Alberto M. , Paganelli Francesca , Truocchio Serena , Palumbo Carla , Chiarini Francesca , McCubrey James A.
Published: February 2023

The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL.
The Molecular Mechanisms of Systemic Sclerosis-Associated Lung Fibrosis
Authors: Mouawad Joe E. , Feghali-Bostwick Carol
Published: February 2023

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has the highest mortality rate among the rheumatic diseases. One of the hallmarks of SSc is fibrosis, which may develop systemically, affecting the skin and virtually any visceral organ in the body. Fibrosis of the lungs leads to interstitial lung disease (ILD), which is currently the leading cause of death in SSc. The identification of effective treatments to stop or reverse lung fibrosis has been the main challenge in reducing SSc mortality and improving patient outcomes and quality of life. Thus, understanding the molecular mechanisms, altered pathways, and their potential interactions in SSc lung fibrosis is key to developing potential therapies. In this review, we discuss the diverse molecular mechanisms involved in SSc-related lung fibrosis to provide insights into the altered homeostasis state inherent to this fatal disease complication.
Expression Patterns of Serotonin Receptors 5-HT1A, 5-HT2A, and 5-HT3A during Human Fetal Lung Development
Authors: Nikolić Jelena , Vukojević Katarina , Šoljić Violeta , Mišković Josip , Orlović Vlaho Martina , Saraga-Babić Mirna , Filipović Natalija
Published: February 2023

We analyzed the expression of the serotonin receptors 5-HT1A, 5-HT2A, and 5-HT3A at four different stages of fetal lung development from 12 to 40 weeks of gestation, divided into four groups: the pseudoglandular stage (12–16th week of development; n = 8), the canalicular stage (16th–26th week of development; n = 7), the saccular stage (26th-36th week of development; n = 5), and the alveolar stage (36th–40th week of development; n = 5). The strongest expression of all three receptor types was found in the epithelium of the proximal airways during the pseudoglandular, canalicular, and saccular stages and in a vascular wall. 5-HT1A was also strongly expressed in the smooth muscle cells of the proximal airway. Vascular smooth muscle cells and endothelium occasionally showed a strong expression of 5-HT1A and 5-HT2A. In the alveolar stage, the expression of 5-HT1A, 5-HT2A, and 5-HT3A was detected in both type I (p1) and type II (p2) pneumocytes, with a stronger expression in p2. A significant decrease in percent the 5-HT2A area and in the integrated density was observed at the alveolar stage. On the other hand, a significant decrease in the percentage area but an increase in the integrated density was observed for 5-HT3A toward the alveolar stage, suggesting that a smaller number of cells expressed 5-HT3A but that they (p1 and p2) significantly increased their 5-HT3A expression at the alveolar stage. The results presented provided us with new data on the development and function of the serotonin system in the human fetal lung and gave us insight into their possible involvement in the pathogenesis of lung pathology, particularly that characteristic of the neonatal period.
Ameliorating Effects of Vitamin K2 on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
Authors: Hu Shouna , Ma Yan , Xiong Ke , Wang Yanrong , Liu Yajun , Sun Yongye , Yang Yuexin , Ma Aiguo
Published: February 2023

Ulcerative colitis (UC) is a chronic recurrent inflammatory illness of the gastrointestinal system. The purpose of this study was to explore the alleviating effect of vitamin K2 (VK2) on UC, as well as its mechanism. C57BL/6J mice were given 3% DSS for seven days to establish UC, and they then received VK2 (15, 30, or 60 mg/kg·bw) and 5-aminosalicylic acid (100 mg/kg·bw) for two weeks. We recorded the clinical signs, body weights, colon lengths, and histological changes during the experiment. We detected the inflammatory factor expressions using enzyme-linked immunosorbent assay (ELISA) kits, and we detected the tight junction proteins using Western blotting. We analyzed the intestinal microbiota alterations and short-chain fatty acids (SCFAs) using 16S rRNA sequencing and targeted metabolomics. According to the results, VK2 restored the colon lengths, improved the colonic histopathology, reduced the levels of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6), and boosted the level of the immunosuppressive cytokine IL-10 in the colon tissues of the colitis mice. Moreover, VK2 promoted the expression of mucin and tight junction proteins (such as occludin and zonula occludens-1) in order to preserve the intestinal mucosal barrier function and prevent UC in mice. Additionally, after the VK2 intervention, the SCFAs and SCFA-producing genera, such as Eubacterium_ruminantium_group and Faecalibaculum, were elevated in the colon. In conclusion, VK2 alleviated the DSS-induced colitis in the mice, perhaps by boosting the dominant intestinal microflora, such as Faecalibaculum, by reducing intestinal microflora dysbiosis, and by modulating the expression of SCFAs, inflammatory factors, and intestinal barrier proteins.
Salivary Polyamines Help Detect High-Risk Patients with Pancreatic Cancer: A Prospective Validation Study
Authors: Nose Daisuke , Sugimoto Masahiro , Muta Tsuneo , Miura Shin-Ichiro
Published: February 2023

Pancreatic cancer is one of the most malignant cancer types and has a poor prognosis. It is often diagnosed at an advanced stage because of the absence of typical symptoms. Therefore, it is necessary to establish a screening method for the early detection of pancreatic cancer in high-risk individuals. This is a prospective validation study conducted in a cohort of 1033 Japanese individuals (male, n = 467, age = 63.3 ± 11.5 years; female, n = 566, age = 64.2 ± 10.6 years) to evaluate the use of salivary polyamines for screening pancreatic diseases and cancers. Patients with pancreatic cancer were not included; however, other pancreatic diseases were treated as positive cases for accuracy verification. Of the 135 individuals with elevated salivary polyamine markers, 66 had pancreatic diseases, such as chronic pancreatitis and pancreatic cysts, and 1 had gallbladder cancer. These results suggest that the salivary polyamine panel is a useful noninvasive pancreatic disease screening tool.
Plant Metabolites Affect Fusarium proliferatum Metabolism and In Vitro Fumonisin Biosynthesis
Authors: Lalak-Kańczugowska Justyna , Witaszak Natalia , Waśkiewicz Agnieszka , Bocianowski Jan , Stępień Łukasz
Published: February 2023

Fusarium proliferatum is a common hemi-biotrophic pathogen that infect a wide range of host plants, often leading to substantial crop loss and yield reduction. F. proliferatum synthesizes various mycotoxins, and fumonisins B are the most prevalent. They act as virulence factors and specific effectors that elicit host resistance. The effects of selected plant metabolites on the metabolism of the F. proliferatum strain were analyzed in this study. Quercetin-3-glucoside (Q-3-Glc) and kaempferol-3-rutinoside (K-3-Rut) induced the pathogen’s growth, while DIMBOA, isorhamnetin-3-O-rutinoside (Iso-3-Rut), ferulic acid (FA), protodioscin, and neochlorogenic acid (NClA) inhibited fungal growth. The expression of seven F. proliferatum genes related to primary metabolism and four FUM genes was measured using RT-qPCR upon plant metabolite addition to liquid cultures. The expression of CPR6 and SSC1 genes was induced 24 h after the addition of chlorogenic acid (ClA), while DIMBOA and protodioscin reduced their expression. The transcription of FUM1 on the third day of the experiment was increased by all metabolites except for Q-3-Glc when compared to the control culture. The expression of FUM6 was induced by protodioscin, K-3-Rut, and ClA, while FA and DIMBOA inhibited its expression. FUM19 was induced by all metabolites except FA. The highest concentration of fumonisin B1 (FB1) in control culture was 6.21 µg/mL. Protodioscin did not affect the FB content, while DIMBOA delayed their synthesis/secretion. Flavonoids and phenolic acids displayed similar effects. The results suggest that sole metabolites can have lower impacts on pathogen metabolism and mycotoxin synthesis than when combined with other compounds present in plant extracts. These synergistic effects require additional studies to reveal the mechanisms behind them.
The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment
Authors: Papadakos Stavros P. , Dedes Nikolaos , Gkolemi Nikolina , Machairas Nikolaos , Theocharis Stamatios
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC) is a major concern for health care systems worldwide, since its mortality remains unaltered despite the surge in cutting-edge science. The EPH/ephrin signaling system was first investigated in the 1980s. EPH/ephrins have been shown to exert bidirectional signaling and cell-to-cell communication, influencing cellular morphology, adhesion, migration and invasion. Recent studies have highlighted the critical role of the EPH/ephrin system in various physiologic processes, including cellular proliferation, survival, synaptic plasticity and angiogenesis. Thus, it has become evident that the EPH/ephrin signaling system may have compelling effects on cell homeostasis that contribute to carcinogenesis. In particular, the EPH/ephrins have an impact on pancreatic morphogenesis and development, whereas several EPHs and ephrins are altered in PDAC. Several clinical and preclinical studies have attempted to elucidate the effects of the EPH/ephrin pathway, with multilayered effects on PDAC development. These studies have highlighted its highly promising role in the diagnosis, prognosis and therapeutic management of PDAC. The aim of this review is to explore the obscure aspects of the EPH/ephrin system concerning the development, physiology and homeostasis of the pancreas.
Masked Face Recognition System Based on Attention Mechanism
Authors: Wang Yuming , Li Yu , Zou Hua
Published: February 2023

With the continuous development of deep learning, the face recognition field has also developed rapidly. However, with the massive popularity of COVID-19, face recognition with masks is a problem that is now about to be tackled in practice. In recognizing a face wearing a mask, the mask obscures most of the facial features of the face, resulting in the general face recognition model only capturing part of the facial information. Therefore, existing face recognition models are usually ineffective in recognizing faces wearing masks. This article addresses this problem in the existing face recognition model and proposes an improvement of Facenet. We use ConvNeXt-T as the backbone of the network model and add the ECA (Efficient Channel Attention) mechanism. This enhances the feature extraction of the unobscured part of the face to obtain more useful information, while avoiding dimensionality reduction and not increasing the model complexity. We design new face recognition models by investigating the effects of different attention mechanisms on face mask recognition models and the effects of different data set ratios on experimental results. In addition, we construct a large set of faces wearing masks so that we can efficiently and quickly train the model. Through experiments, our model proved to be 99.76% accurate for real faces wearing masks. A combined accuracy of 99.48% for extreme environments such as too high or lousy contrast and brightness.
Blockchain Data Availability Scheme with Strong Data Privacy Protection
Authors: Liu Xinyu , Ji Shan , Wang Xiaowan , Liu Liang , Ren Yongjun
Published: February 2023

Blockchain, with its characteristics of non-tamperability and decentralization, has had a profound impact on various fields of society and has set off a boom in the research and application of blockchain technology. However, blockchain technology faces the problem of data availability attacks during its application, which greatly limits the scope and domain of blockchain applications. One of the most advantageous researches to address this problem is the scalable data availability solution that integrates coding theory design into the Merkle tree promise. Based on this scheme, this paper combines a zero-knowledge accumulator with higher efficiency and security with local repair coding, and proposes a data availability scheme with strong dataset privacy protection. The scheme first encodes the data block information on the blockchain to ensure tamper-proof data, and then uses a zero-knowledge accumulator to store the encoded data block information. Its main purpose is to use zero-knowledge property to protect the accumulation set information stored in the accumulator from being leaked and to ensure that no other information about the accumulation set is revealed during the data transmission. It fundamentally reduces the possibility of attackers generating fraudulent information by imitating block data and further resists data availability attacks.
Transferring CNN Features Maps to Ensembles of Explainable Neural Networks
Authors: Bologna Guido
Published: February 2023

The explainability of connectionist models is nowadays an ongoing research issue. Before the advent of deep learning, propositional rules were generated from Multi Layer Perceptrons (MLPs) to explain how they classify data. This type of explanation technique is much less prevalent with ensembles of MLPs and deep models, such as Convolutional Neural Networks (CNNs). Our main contribution is the transfer of CNN feature maps to ensembles of DIMLP networks, which are translatable into propositional rules. We carried out three series of experiments; in the first, we applied DIMLP ensembles to a Covid dataset related to diagnosis from symptoms to show that the generated propositional rules provided intuitive explanations of DIMLP classifications. Then, our purpose was to compare rule extraction from DIMLP ensembles to other techniques using cross-validation. On four classification problems with over 10,000 samples, the rules we extracted provided the highest average predictive accuracy and fidelity. Finally, for the melanoma diagnostic problem, the average predictive accuracy of CNNs was 84.5% and the average fidelity of the top-level generated rules was 95.5%. The propositional rules generated from the CNNs were mapped at the input layer by squares in which the relevant data for the classifications resided. These squares represented regions of attention determining the final classification, with the rules providing logical reasoning.
Prediction of Composite Mechanical Properties: Integration of Deep Neural Network Methods and Finite Element Analysis
Authors: Gholami Kimia , Ege Faraz , Barzegar Ramin
Published: February 2023

Extracting the mechanical properties of a composite hydrogel; e.g., bioglass (BG)–collagen (COL), is often difficult due to the complexity of the experimental procedure. BGs could be embedded in the COL and thereby improve the mechanical properties of COL for bone tissue engineering applications. This paper proposed a deep-learning-based approach to extract the mechanical properties of a composite hydrogel directly from the microstructural images. Four datasets of various shapes of BGs (9000 2D images) generated by a finite element analysis showed that the deep neural network (DNN) model could efficiently predict the mechanical properties of the composite hydrogel, including the Young’s modulus and Poisson’s ratio. ResNet and AlexNet architecture were tuned to ensure the excellent performance and high accuracy of the proposed methods with R-values greater than 0.99 and a mean absolute error of the prediction of less than 7%. The results for the full dataset revealed that AlexNet had a better performance than ResNet in predicting the elastic material properties of BGs-COL with R-values of 0.99 and 0.97 compared to 0.97 and 0.96 for the Young’s modulus and Poisson’s ratio, respectively. This work provided bridging methods to combine a finite element analysis and a DNN for applications in diverse fields such as tissue engineering, materials science, and medical engineering.
Wideband Cascaded and Stacked Receiver Front-Ends Employing an Improved Clock-Strategy Technique
Authors: Abbasi Arash , Nabki Frederic
Published: February 2023

A wideband cascaded receiver and a stacked receiver using an improved clock strategy are proposed to support the software-defined radio (SDR). The improved clock strategy reduces the number of mixer switches and the number of LO clock paths required to drive the mixer switches. This reduces the dynamic power consumption. The cascaded receiver includes an inverter-based low-noise transconductance amplifier (LNTA) using a feed-forward technique to enhance the noise performance; a passive mixer; and an inverter-based transimpedance amplifier (TIA). The stacked receiver architecture is used to reduce the power consumption by sharing the current between the LNTA and the TIA from a single supply. It utilizes a wideband LNTA with a capacitor cross-coupled (CCC) common-gate (CG) topology, a passive mixer to convert the RF current to an IF current, an active inductor (AI) and a 1/f noise-cancellation (NC) technique to improve the noise performance, and a TIA to convert the IF current to an IF voltage at the output. Both cascaded and stacked receivers are simulated in 22 nm CMOS technology. The cascaded receiver achieves a conversion-gain from 26 dB to 36 dB, a double-sideband noise-figure (NFDSB) from 1.4 dB to 3.9 dB, S11<−10 dB and an IIP3 from −7.5 dBm to −10.5 dBm, over the RF operating band from 0.4 GHz to 12 GHz. The stacked receiver achieves a conversion-gain from 34.5 dB to 36 dB, a NFDSB from 4.6 dB to 6.2 dB, S11<−10 dB, and an IIP3 from −21 dBm to −17.5 dBm, over the RF operating band from 2.2 GHz to 3.2 GHz. The cascaded receiver consumes 11 m from a 1 V supply voltage, while the stacked receiver consumes 2.4 m from a 1.2 V supply voltage.
Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome
Authors: Ho Teresa T. , Noble Melissa , Tran Bao Anh , Sunjic Katlynd , Gupta Sheeba Varghese , Turgeon Jacques , Crutchley Rustin D.
Published: February 2023

Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome.
Spaces, Systems and Infrastructures: From Founding Visions to Emerging Approaches for the Productive Urban Landscape
Authors: Nasr Joe , Potteiger Matthew
Published: February 2023

The proliferation of urban agriculture on an array of urban spaces is one of the more visible responses to perceived failures of contemporary food systems. This paper seeks to identify fundamental strategies connected to food system change efforts, linking these with diverse attempts at designing and planning the productive city. It first situates the contemporary concept of the productive city within a broader historical dialogue of foundational figures in urban and regional planning, architecture, and landscape architecture for whom food production was a central component of future cities. Recently, a growing number of practitioners have theorized the need for integrating urban agriculture in urban design and planning. Across this spectrum of emerging theory and practice, we identify three approaches to designing productive cities. First, spatial design strategies identify new territories for food production. These offer the potential for systems design thinking that links the individual spaces of production to other sectors of food systems that extend across networks of spaces and multiple scales. Finally, both spatial and systems design involve strategies of designing productive infrastructures of soils, water, nutrients, and other essential flows. The engagement with spaces of production, food systems, and productive infrastructure opens up a range of challenges as well as opportunities for emerging forms of practice and design thinking for the productive city.
Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons
Authors: Hough Andrea , Criswell Connor , Faruk Asef , Cavanaugh Jane E. , Kolber Benedict J. , Tidgewell Kevin J.
Published: February 2023

Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.
Quantification of Age-Related Changes in the Lateral Organization of the Lipid Portion of the Intact Membranes Isolated from the Left and Right Eye Lenses of the Same Human Donor
Authors: Mainali Laxman , Raguz Marija , Subczynski Witold Karol
Published: February 2023

The continuous wave EPR spin-labeling method was used to evaluate age-related changes in the amounts of phospholipids (PLs) and cholesterol (Chol) in domains present in intact, cortical, and nuclear fiber cell plasma membranes isolated separately from the left and right eye lenses of the same human donor. The relative amounts of boundary plus trapped PLs were evaluated with the PL analog 12-doxylstearic acid spin label (12-SASL) and the relative amounts of trapped Chol with the Chol analog androstane spin label (ASL). The donors ranged in age from 15 to 70 years. Both the left and right eye lenses from donors aged 60, 65, and 70 years had nuclear cataracts; additionally, the right eye lens only of the 60-year-old donor had a cortical cataract. In transparent lenses, the relative amounts of boundary plus trapped PLs increase monotonously with donor age, and, at all ages, this amount was greater in nuclear compared with cortical membranes. Moreover, in transparent lenses, the relative amount of trapped Chol increases with age in nuclear membranes. However, the EPR spectrum of ASL from cortical membranes of 15- to 60-year-old donors shows only the weakly immobilized component assigned to ASL in the bulk plus Chol bilayer domain. Only the cortical membranes of 61- to 70-year-old donors contain both weakly and strongly immobilized components. The strongly immobilized component is assigned to ASL in trapped lipids. We speculate that the age of 60 years may be considered as a “threshold” for appearance of trapped lipids in cortical membranes. The relative amounts of boundary plus trapped PLs in lenses with nuclear cataracts is lower than that predicted from the tendency of the age-dependent increase observed for transparent lenses. The differences in amounts of lipids in the indicated left and right eye domains of each donor are smaller than the differences in single donors of a similar age.
Corrosion Wear of Hypereutectic High Chromium Cast Iron: A Review
Authors: Gong Liqiang , Fu Hanguang , Zhi Xiaohui
Published: February 2023

Hypereutectic High Chromium Cast Iron (HHCCI) is a new type of corrosion-wear-resistant material developed from ordinary high chromium cast iron by increasing the chromium and carbon content and is often used in abrasive environments where wear and corrosion interact. The corrosion wear resistance of the HHCCI is related to the number, size, shape and distribution of carbides and the microstructure of the matrix. This paper reviews the research progress in improving the corrosion wear resistance of HHCCI from various aspects such as primary carbide refinement, heat treatment, deep cooling treatment and alloying, etc. Among the methods of refining primary carbides are modification, semi-solid treatment and current pulse treatment. In addition, we also analyze the potential of Cr, V, Nb, Mo, Mn, W, Ni, Cu, Si, N and other alloying elements to improve the corrosion wear resistance of HHCCI. The mechanism for improving the corrosion wear resistance of HHCCI is also explored in depth and research contents worthy of attention are proposed to further improve the corrosion wear resistance of HHCCI. In the future, the author believes that modification + alloying + heat treatment is the most potential application method to improve the corrosion wear resistance of HHCCI. The corrosion wear resistance of HHCCI can be further improved by refining the primary carbide (such as adding rare earth, Ti and other modified elements) + heat treatment (with cryogenic treatment) to improve the strength + alloying (such as adding low-cost, high-potential alloy elements such as N and Si) to improve the corrosion wear resistance of the matrix.
Comparative Analysis of Volatile and Non-Volatile Metabolites Derived from Bacillus subtilis Strains Producing Different Levels of Biogenic Amines
Authors: Lee Kyuwon , Kwon Seo-Hee , Song Sumin , Lee Do-Yup , Park Min Kyung , Kim Young-Suk
Published: February 2023

Biogenic amines (BAs), which are mainly generated by the microbial decarboxylation of amino acids, are important nitrogen compounds in fermented foods because of their toxicology. However, amino acids, the precursors of BAs, also play an important role in generating volatile and non-volatile metabolites, which are strongly associated with quality indicators for foods. Bacillus subtilis is one of dominant fermentative microorganism in various fermented foods and is well known as a BA-producing bacterium. In this study, B. subtilis strains which have different BAs-producing capacities, higher level of BAs production strain (BH) and lower level of BAs production strain (BL), were applied to compare the formations of volatile and non-volatile metabolite profiles according to cultivation times. In this study, histamine, putrescine, and spermidine were detected in all strains, however, 2-phenylethylamine was detected only in BH. Partial least squares discriminant analysis (PLS-DA) was applied to investigate the difference of metabolic profiles according to strains. In BH, some amino acids (phenylalanine, leucine, and threonine) and related volatile metabolites (3-methylbutanoic acid, pyrazines, styrene, and 1H-indole) were produced higher levels. On the other hand, BL produced significantly higher contents of metabolites associated with metabolism of fatty acids and nucleotides. It is necessary to consider the formation of metabolites in terms of quality as well as that of BAs during fermentation.
Characterization of Peptaibols Produced by a Marine Strain of the Fungus Trichoderma endophyticum via Mass Spectrometry, Genome Mining and Phylogeny-Based Prediction
Authors: Castro Gleucinei S. , Sousa Thiago F. , da Silva Gilvan F. , Pedroso Rita C. N. , Menezes Kelly S. , Soares Marcos A. , Dias Gustavo M. , Santos Aline O. , Yamagishi Michel E. B. , Faria Jéssica V. , Januário Ana H. , Koolen Hector H. F.
Published: February 2023

Trichoderma is recognized as a prolific producer of nonribosomal peptides (NRPs) known as peptaibols, which have remarkable biological properties, such as antimicrobial and anticancer activities, as well as the ability to promote systemic resistance in plants against pathogens. In this study, the sequencing of 11-, 14- and 15-res peptaibols produced by a marine strain of Trichoderma isolated from the ascidian Botrylloides giganteus was performed via liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Identification, based on multilocus phylogeny, revealed that our isolate belongs to the species T. endophyticum, which has never been reported in marine environments. Through genome sequencing and genome mining, 53 biosynthetic gene clusters (BGCs) were identified as being related to bioactive natural products, including two NRP-synthetases: one responsible for the biosynthesis of 11- and 14-res peptaibols, and another for the biosynthesis of 15-res. Substrate prediction, based on phylogeny of the adenylation domains in combination with molecular networking, permitted extensive annotation of the mass spectra related to two new series of 15-res peptaibols, which are referred to herein as “endophytins”. The analyses of synteny revealed that the origin of the 15-module peptaibol synthetase is related to 18, 19 and 20-module peptaibol synthetases, and suggests that the loss of modules may be a mechanism used by Trichoderma species for peptaibol diversification. This study demonstrates the importance of combining genome mining techniques, mass spectrometry analysis and molecular networks for the discovery of new natural products.
Changes in the Seasonality of Fire Activity and Fire Weather in Portugal: Is the Wildfire Season Really Longer?
Authors: Silva Pedro , Carmo Miguel , Rio João , Novo Ilda
Published: February 2023

The length of the fire season has not garnered much attention within the broad field of meteorological research on fire regime change. Fire weather research on the Iberian Peninsula is no exception in this case; there is no solid understanding on fire season lengthening in Portugal, although recent decades do suggest ongoing transitions. Based on a complete record of fire occurrence and burned area between 1980 and 2018, we first searched for consistent trends in the monthly distribution of fire activity. To determine day-scale changes, an exceedance date method based on annual cumulative burned area was developed. Results show an early onset of fire activity in a range of 23–50 days and no significant extension into autumn, suggesting that existing projections of the lengthening of the fire season in Portugal over the present century have been already achieved. Fire weather results show a trend in the cumulative Daily Severity Rating (DSR), with the last two decades (2000–2018) displaying an early build-up of meteorological fire danger in late spring and early summer. The detailed spatio-temporal analysis based on the daily Fire Weather Index (FWI) shows that June stands out with the largest increase (year-round) in days per month with an FWI above 38.3, the threshold above which fire conditions make suppression uncertain. This aggravated fire weather is likely sustaining early fire activity, thus contributing to a longer critical fire season.
A Cryostat Applicable to Long-Wavelength Light-Driven Scanning Probe Microscopy
Authors: Xiang Kui , Xie Caihong , Feng Qiyuan , Wang Ze , Dai Guangbin , Wang Jihao , Zhang Jing , Meng Wenjie , Hou Yubin , Lu Qingyou , Lu Yalin
Published: February 2023

Recently, there has been growing interest in using lightwave-driven scanning probe microscopy (LD-SPM) to break through the Abbe diffraction limit of focusing, yielding insight into various energy couplings and conversion processes and revealing the internal information of matter. We describe a compact and efficient optical cryostat designed for LD-SPM testing under magnetic fields. The exceptional multilayer radiation shielding insert (MRSI) forms an excellent temperature gradient when filled with heat conducting gas, which removes the requirement to install an optical window in the liquid helium cooling shell. This not only critically avoids the vibration and thermal drift caused by solid heat conduction but also minimizes light transmission loss. The application of gate valves and bellows allows a simpler and more effective replacement of the sample and working cell in the test cavity. ANSYS software is used for steady-state thermal analysis of the MRSI to obtain the temperature distribution and heat transfer rate, and the necessity of the flexible copper shielding strips is illustrated by the simulations. The topography and magnetic domain images of 45 nm-thick La0.67Ca0.33MnO3 thin films on NdGaO3(001) substrates under a magnetic field were obtained by a self-made lightwave-driven magnetic force microscope in this cryostat. The resolution and noise spectra during imaging reveal temperature stability and low vibration throughout the cryostat. The experience acquired during the development of this cryostat will help to establish cryostats of similar types for a variety of optic applications requiring the use of cryogenic temperatures.
A 53-µA-Quiescent 400-mA Load Demultiplexer Based CMOS Multi-Voltage Domain Low Dropout Regulator for RF Energy Harvester
Authors: Poongan Balamahesn , Rajendran Jagadheswaran , Yizhi Li , Mariappan Selvakumar , Parameswaran Pharveen , Kumar Narendra , Othman Masuri , Nathan Arokia
Published: February 2023

A low-power capacitorless demultiplexer-based multi-voltage domain low-dropout regulator (MVD-LDO) with 180 nm CMOS technology is proposed in this work. The MVD-LDO has a 1.5 V supply voltage headroom and regulates an output from four voltage domains ranging from 0.8 V to 1.4 V, with a high current efficiency of 99.98% with quiescent current of 53 µA with the aid of an integrated low-power demultiplexer controller which consumes only 68.85 pW. The fabricated chip has an area of 0.149 mm2 and can deliver up to 400 mA of current. The MVD-LDO’s line and load regulations are 1.85 mV/V and 0.0003 mV/mA for the low-output voltage domain and 3.53 mV/V and 0.079 mV/mA for the high-output voltage domain. The LDO consumes only 174.5 µW in standby mode, making it suitable for integrating with an RF energy harvester chip to power sensor nodes.
Mineral Characteristics and the Mineralization of Leptynite-Type Nb–Ta Ore Deposit in the Western Qilian Orogenic Belt
Authors: Yu Junpeng , Wu Yibu , Zhang Chunhui , Si Haojia , Si Dongze , Zhang Chengjun
Published: February 2023

A large Nb–Ta ore deposit was found in the Yushishan leptynite in the west Qilian Orogenic Belt (QOB). Based on a field geological survey and using a Mineral Liberation Analyser (MLA, including scanning electron microscopy (SEM) and energy-dispersive spectrometer (EDS)) methods, eight Nb minerals (fergusonite, polycrase, columbite, Nb-rutile, aeschynite, pyrochlore, microlite, and ilmenorutile) were found to occur in the leptynite. This accounted for approximately 69% of Nb, with fergusonite, polycrase, and columbite being the dominant phases. The other 17.90% Nb as a minor element was dispersed in titanium magnetite–maghemite, and another 13.00% Nb was dispersed in gangue minerals. Nb minerals are formed mainly by two metallogenesis stages. The first stage is magmatic genesis to form four Nb minerals, euhedral-subhedral fergusonite, polycrase, pyrochlore, and microlite, which are crystallized within or between primary minerals, such as quartz and feldspar. Late alteration phenomena are locally observed. The second stage is the hydrothermal genesis of columbite, anhedral fergusonite, Nb-rutile, and aeschynite, which are dispersed in the fissures of the wall rocks as irregular veins and lump assemblages. Meanwhile, they are closely associated with metasomatic chlorite, albite, and secondary quartz. Furthermore, direct metasomatism among different Nb minerals is also found at the local scale. The Nb percentage of these two Nb mineral mineralization types is approximately equal, which reflects two main mineralizing periods. The first stage of mineralization occurred in the Neoproterozoic Era (834–790 Ma). Magmatism of this period produced early niobium and formed fergusonite, polycrase, pyrochlore, microlite, and zircon. The initial enrichment of Nb, Ta, and other rare metals occurred during this stage. The second stage of mineralization occurred in the Caledonian period (490–455 Ma). Large-scale and intense tectonic–magmatic thermal events occurred in the western part of the QOB due to the plate subduction and convergence (510–450 Ma). Hydrothermal activity in this period formed columbite, fergusonite, Nb-rutile, and aeschynite. Moreover, rare metal elements in the Nb-bearing rocks activated and migrated at short distances, forming in situ Nb–Ta-rich ore deposits.
Carbonate U-Pb Geochronology and Clumped Isotope Constraints on the Origin of Hydrothermal Dolomites: A Case Study in the Middle Permian Qixia Formation, Sichuan Basin, South China
Authors: Zou Yu , You Donghua , Chen Bo , Yang Huamin , Tian Zhixing , Liu Dongna , Zhang Liyu
Published: February 2023

Reservoirs in the dolomites of the Middle Permian Qixia Formation in the Sichuan Basin are currently important oil and gas exploration objects in China. However, the questions concerning the sources of the dolomitized fluids and the control factors of the Qixia hydrothermal dolomites remain unclear. In this study, the original hydrothermal dolomites (the replacement dolomites (RDs) and saddle dolomites (SDs)) from the Qixia Formation in the southwestern Sichuan Basin (the PR1 well and Baoxing section) were mainly examined using novel in situ carbonate U-Pb dating with clumped isotopes (∆47). Our results show that the U-Pb ages of the latest SDs from the PR1 well (located in the middle zone of the Emeishan large igneous province (ELIP) and distanced from the Orogenic Belt of Longmenshan) are 257.9–251.0 Ma, coincident with the period of main activity of the ELIP. Combined with the previous U-Pb dating, we propose that the high-temperature T∆47 (82.2–108.4 °C and 127.5–205.9 °C) recorded for SDs from the PR1 well and Baoxing section may have responded to ELIP activity and Longmenshan orogeny activity, respectively. In addition, in the entire southwestern Sichuan Basin, the RDs and SDs yield similar δ13C and δ18O values, indicating that the dolomites were formed by hydrothermal fluids of similar sources, with marine hydrothermal fluids being a highly possible source. Finally, this study proposes a new hydrothermal dolomite genesis model for the Qixia Formation, emphasizing that the formation of hydrothermal dolomites mainly depends on the proximity to tectonic thermal events in space and time.