bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicles from Human Teeth Stem Cells Trigger ATP Release and Promote Migration of Human Microglia through P2X4 Receptor/MFG-E8-Dependent Mechanisms
Authors: Jonavičė Ugnė , Romenskaja Diana , Kriaučiūnaitė Karolina , Jarmalavičiūtė Akvilė , Pajarskienė Justina , Kašėta Vytautas , Tunaitis Virginijus , Malm Tarja , Giniatullin Rashid , Pivoriūnas Augustas
Published: October 2021

Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate the neuroinflammatory response of microglia remains largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on immortalized human microglial cells. We found that EVs induced a rapid increase in intracellular Ca2+ and promoted significant ATP release in microglial cells after 20 min of treatment. Boyden chamber assays revealed that EVs promoted microglial migration by 20%. Pharmacological inhibition of different subtypes of purinergic receptors demonstrated that EVs activated microglial migration preferentially through the P2X4 receptor (P2X4R) pathway. Proximity ligation and co-immunoprecipitation assays revealed that EVs promote association between milk fat globule-epidermal growth factor-factor VIII (MFG-E8) and P2X4R proteins. Furthermore, pharmacological inhibition of αVβ3/αVβ5 integrin suppressed EV-induced cell migration and formation of lipid rafts in microglia. These results demonstrate that EVs promote microglial motility through P2X4R/MFG-E8-dependent mechanisms. Our findings provide novel insights into the molecular mechanisms through which EVs target human microglia that may be exploited for the development of new therapeutic strategies targeting disease-associated neuroinflammation.
Ectopic Endometrium: The Pathologist’s Perspective
Authors: Camboni Alessandra , Marbaix Etienne
Published: October 2021

Endometriosis and adenomyosis are two frequent diseases closely linked, characterized by ectopic endometrium. Despite their benign nature, endometriosis and adenomyosis impair women’s quality of life by causing pain and infertility and an increase in the incidence of gynecological malignancies has been reported. Since the first description of ectopic endometrium in 1860, different attempts have been made to describe, classify and understand the origin of these diseases. Several theories have been proposed to describe the pathogenic mechanism leading to the development of adenomyosis or endometriosis. However, all the hypotheses show some limitations in explaining all the different aspects and manifestations of these diseases. Despite the remarkable progress made over recent years, the pathogeneses of endometriosis and adenomyosis remain unclear. Moreover, because of the lack of standardized protocols and diagnostic criteria in pathology practice it is difficult to study and to classify these disorders. The goal of this review is to summarize the pathological aspects of adenomyosis and endometriosis, spanning a historical perspective to newly reported data.
Natural Resources Resistance to Tomato Spotted Wilt Virus (TSWV) in Tomato (Solanum lycopersicum)
Authors: Qi Shiming , Zhang Shijie , Islam Md. Monirul , El-Sappah Ahmed H. , Zhang Fei , Liang Yan
Published: October 2021

Tomato spotted wilt virus (TSWV) is one of the most destructive diseases affecting tomato (Solanum lycopersicum) cultivation and production worldwide. As defenses against TSWV, natural resistance genes have been identified in tomato, including Sw-1a, Sw-1b, sw-2, sw-3, sw-4, Sw-5, Sw-6, and Sw-7. However, only Sw-5 exhibits a high level of resistance to the TSWV. Thus, it has been cloned and widely used in the breeding of tomato with resistance to the disease. Due to the global spread of TSWV, resistance induced by Sw-5 decreases over time and can be overcome or broken by a high concentration of TSWV. How to utilize other resistance genes and identify novel resistance resources are key approaches for breeding tomato with resistance to TSWV. In this review, the characteristics of natural resistance genes, natural resistance resources, molecular markers for assisted selection, and methods for evaluating resistance to TSWV are summarized. The aim is to provide a theoretical basis for identifying, utilizing resistance genes, and developing tomato varieties that are resistant to TSWV.
Synthesis, In Silico Prediction and In Vitro Evaluation of Antimicrobial Activity, DFT Calculation and Theoretical Investigation of Novel Xanthines and Uracil Containing Imidazolone Derivatives
Authors: El-Kalyoubi Samar , Agili Fatimah , Zordok Wael A. , El-Sayed Ashraf S. A.
Published: October 2021

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives 2a-c as a key intermediate. The corresponding xanthine 3-5 and imidazolone derivatives 6-13 were obtained via reaction of oxazolone derivative 2a-c with 5,6-diaminouracils 1a-e under various conditions. Xanthine compounds 3-5 were obtained by cyclocondensation of 5,6-diaminouracils 1a-c with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils 1a-e were reacted with oxazolones 2a-c in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives 6-13. Furthermore, Schiff base of compounds 14-16 were obtained by condensing 5,6-diaminouracils 1a,b,e with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR, 1H-, 13C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds 3, 6, 13 and 16 displayed the highest activity against Escherichia coli as revealed from the IC50 values (1.8–1.9 µg/mL). The compound 16 displayed a significant antifungal activity against Candia albicans (0.82 µg/mL), Aspergillus flavus (1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds 3, 12, 13 and 16 exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound 12 showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation.
Recent Advances in CRISPR/Cas9-Based Genome Editing Tools for Cardiac Diseases
Authors: Schreurs Juliët , Sacchetto Claudia , Colpaert Robin M. W. , Vitiello Libero , Rampazzo Alessandra , Calore Martina
Published: October 2021

In the past two decades, genome editing has proven its value as a powerful tool for modeling or even treating numerous diseases. After the development of protein-guided systems such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), which for the first time made DNA editing an actual possibility, the advent of RNA-guided techniques has brought about an epochal change. Based on a bacterial anti-phage system, the CRISPR/Cas9 approach has provided a flexible and adaptable DNA-editing system that has been able to overcome several limitations associated with earlier methods, rapidly becoming the most common tool for both disease modeling and therapeutic studies. More recently, two novel CRISPR/Cas9-derived tools, namely base editing and prime editing, have further widened the range and accuracy of achievable genomic modifications. This review aims to provide an overview of the most recent developments in the genome-editing field and their applications in biomedical research, with a particular focus on models for the study and treatment of cardiac diseases.
MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease
Authors: Waseem Rashid , Anwar Saleha , Khan Shama , Shamsi Anas , Hassan Md. Imtaiyaz , Anjum Farah , Shafie Alaa , Islam Asimul , Yadav Dharmendra Kumar
Published: October 2021

Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (K = 0.8 × 107 M−1), subsequently inhibiting its activity (IC50 = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.
MPA_Pathway_Tool: User-Friendly, Automatic Assignment of Microbial Community Data on Metabolic Pathways
Authors: Walke Daniel , Schallert Kay , Ramesh Prasanna , Benndorf Dirk , Lange Emanuel , Reichl Udo , Heyer Robert
Published: October 2021

Taxonomic and functional characterization of microbial communities from diverse environments such as the human gut or biogas plants by multi-omics methods plays an ever more important role. Researchers assign all identified genes, transcripts, or proteins to biological pathways to better understand the function of single species and microbial communities. However, due to the versality of microbial metabolism and a still-increasing number of newly biological pathways, linkage to standard pathway maps such as the KEGG central carbon metabolism is often problematic. We successfully implemented and validated a new user-friendly, stand-alone web application, the MPA_Pathway_Tool. It consists of two parts, called ‘Pathway-Creator’ and ‘Pathway-Calculator’. The ‘Pathway-Creator’ enables an easy set-up of user-defined pathways with specific taxonomic constraints. The ‘Pathway-Calculator’ automatically maps microbial community data from multiple measurements on selected pathways and visualizes the results. The MPA_Pathway_Tool is implemented in Java and ReactJS.
Anti-Allergic and Anti-Inflammatory Effects of Neferine on RBL-2H3 Cells
Authors: Chiu Kuan-Ming , Hung Yen-Ling , Wang Su-Jane , Tsai Yi-Ju , Wu Nan-Lin , Liang Cher-Wei , Chang Der-Chen , Hung Chi-Feng
Published: October 2021

Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.
Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening
Authors: Martín-Nalda Andrea , Rivière Jacques G. , Català-Besa Mireia , García-Prat Marina , Parra-Martínez Alba , Martínez-Gallo Mónica , Colobran Roger , Argudo-Ramírez Ana , Marín-Soria Jose Luis , García-Villoria Judit , Alonso Laura , Arranz-Amo Jose Antonio , la Marca Giancarlo , Soler-Palacín Pere
Published: October 2021

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP deficiency was detected by TREC analysis.
Cybersecurity Awareness Framework for Academia
Authors: Khader Mohammed , Karam Marcel , Fares Hanna
Published: October 2021

Cybersecurity is a multifaceted global phenomenon representing complex socio-technical challenges for governments and private sectors. With technology constantly evolving, the types and numbers of cyberattacks affect different users in different ways. The majority of recorded cyberattacks can be traced to human errors. Despite being both knowledge- and environment-dependent, studies show that increasing users’ cybersecurity awareness is found to be one of the most effective protective approaches. However, the intangible nature, socio-technical dependencies, constant technological evolutions, and ambiguous impact make it challenging to offer comprehensive strategies for better communicating and combatting cyberattacks. Research in the industrial sector focused on creating institutional proprietary risk-aware cultures. In contrast, in academia, where cybersecurity awareness should be at the core of an academic institution’s mission to ensure all graduates are equipped with the skills to combat cyberattacks, most of the research focused on understanding students’ attitudes and behaviors after infusing cybersecurity awareness topics into some courses in a program. This work proposes a conceptual Cybersecurity Awareness Framework to guide the implementation of systems to improve the cybersecurity awareness of graduates in any academic institution. This framework comprises constituents designed to continuously improve the development, integration, delivery, and assessment of cybersecurity knowledge into the curriculum of a university across different disciplines and majors; this framework would thus lead to a better awareness among all university graduates, the future workforce. This framework may be adjusted to serve as a blueprint that, once adjusted by academic institutions to accommodate their missions, guides institutions in developing or amending their policies and procedures for the design and assessment of cybersecurity awareness.
Arabic Offensive and Hate Speech Detection Using a Cross-Corpora Multi-Task Learning Model
Authors: Aldjanabi Wassen , Dahou Abdelghani , Al-qaness Mohammed A. A. , Elaziz Mohamed Abd , Helmi Ahmed Mohamed , Damaševičius Robertas
Published: October 2021

As social media platforms offer a medium for opinion expression, social phenomena such as hatred, offensive language, racism, and all forms of verbal violence have increased spectacularly. These behaviors do not affect specific countries, groups, or communities only, extending beyond these areas into people’s everyday lives. This study investigates offensive and hate speech on Arab social media to build an accurate offensive and hate speech detection system. More precisely, we develop a classification system for determining offensive and hate speech using a multi-task learning (MTL) model built on top of a pre-trained Arabic language model. We train the MTL model on the same task using cross-corpora representing a variation in the offensive and hate context to learn global and dataset-specific contextual representations. The developed MTL model showed a significant performance and outperformed existing models in the literature on three out of four datasets for Arabic offensive and hate speech detection tasks.
GC/TOF-MS-Based Metabolomics Reveals Altered Metabolic Profiles in Wood-Feeding Termite Coptotermes formosanus Shiraki Digesting the Weed Mikania micrantha Kunth
Authors: Wu Wenjing , Hou Yahui , Zhang Shijun , Chen Yong , Zeng Wenhui , Li Zhiqiang
Published: October 2021

Effective approaches to exploiting the biomass of the abundant invasive weed Mikania micrantha Kunth are limited. Termites have been a focus of significant attention as mediators of biomass-processing owing to their ability to digest lignocellulose. Here, the GC/TOF-MS approach was employed to assess the effects of a diet composed of M. micrantha leaves on Coptotermes formosanus workers, with the growth performance of these workers also being assessed. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. A total of 62 differentially abundant metabolites and nine significantly affected pathways were found when comparing termites fed M. micrantha leaves to pinewood. Key metabolites, including carbohydrates, polyols, 4-hydroxyphenylacetic acid, and their related metabolic pathways, suggested that termites can digest and utilize M. micrantha-derived lignocellulose. However, changes in the tryptophan metabolism, tyrosine metabolism, and sphingolipid metabolism suggest an adverse effect of M. micrantha leaves on antioxidant activity and signal transduction in termites. Overall, this study identified the key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites.
Advanced Power Generation Using a Nitrogen Turbine Engine Instead of a Conventional Injection Steam Turbine Engine
Authors: Vattanapuripakorn Wenich , Khannam Khomson , Sonsupap Sathapon , Kaewkhiaw Prachakon , Tongsantia Umakorn , Sarasamkan Jiradanai , Bubphachot Bopit
Published: October 2021

An ever-increasing demand for electrical power and soaring levels of energy consumption around the world have led to an energy crisis. Thus, this paper aims to review the conventional technologies against those of newer developments in electrical power generation such as using nitrogen generators. The nitrogen generator method is most appealing as it is a seemingly free energy already existing in nature. A nitrogen generator with a 5000 (Nm3/h) capacity has the potential to be used to analyze gas composition and the results are compared with the gas composition of a conventional steam turbine, which is used to pressurize 6000 (kWh) injection steam turbines. The magnetic bearing must be installed in both systems to modify all centrifuged systems which reduces all energy consumption in all systems by more than 50%. Artificial intelligence is used with the machine to analyze and control nitrogen gas flow to provide a more precise evaluation resulting in a more efficient technology. It should further be noted that the nitrogen turbine is superior to the steam turbine because it does not require the burning of fossil fuel to generate power. Hence, it is crucial to modify conventional technologies to improve energy sustainability and begin the long task of tackling environmental issues.
Experimental Investigation of the Effect of a Combination of Active and Passive Cooling Mechanism on the Thermal Characteristics and Efficiency of Solar PV Module
Authors: Agyekum Ephraim Bonah , PraveenKumar Seepana , Alwan Naseer T. , Velkin Vladimir Ivanovich , Shcheklein Sergey E. , Yaqoob Salam J.
Published: October 2021

A photovoltaic (PV) module’s electrical efficiency depends on the operating temperature of the cell. Electrical efficiency reduces with increasing PV module temperature which is one of the drawbacks of this technology. This is due to the negative temperature coefficient of a PV module which decreases its voltage significantly while the current increases slightly. This study combines both active and passive cooling mechanisms to improve the electrical output of a PV module. A heat sink made up of aluminum fins and an ultrasonic humidifier were used to cool the panel. The ultrasonic humidifier was used to generate a humid environment at the rear side of the PV module. The cooling process in the study was able to reduce the temperature of the panel averagely by 14.61 °C. This reduction led to a 6.8% improvement in the electrical efficiency of the module. The average power of 12.23 W was recorded for the cooled panel against 10.87 W for the referenced module. In terms of water consumption, a total of 1.5 L was approximately consumed during the whole experimental process due to evaporation. In effect, the proposed cooling approach was demonstrated as effective.
Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients
Authors: Hsieh Tsu-Yi , Lin Yi-Ching , Hung Wei-Ting , Chen Yi-Ming , Wen Mei-Chin , Chen Hsin-Hua , Lin Wan-Yu , Hsieh Chia-Wei , Lin Ching-Tsai , Lai Kuo-Lung , Tang Kuo-Tung , Tseng Chih-Wei , Huang Wen-Nan , Chen Yi-Hsing , Tsai Shih-Chuan , Wu Yi-Da
Published: October 2021

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.
Loss of the Extracellular Matrix Protein DIG-1 Causes Glial Fragmentation, Dendrite Breakage, and Dendrite Extension Defects
Authors: Chong Megan K. , Cebul Elizabeth R. , Mizeracka Karolina , Heiman Maxwell G.
Published: October 2021

The extracellular matrix (ECM) guides and constrains the shape of the nervous system. In C. elegans, DIG-1 is a giant ECM component that is required for fasciculation of sensory dendrites during development and for maintenance of axon positions throughout life. We identified four novel alleles of dig-1 in three independent screens for mutants affecting disparate aspects of neuronal and glial morphogenesis. First, we find that disruption of DIG-1 causes fragmentation of the amphid sheath glial cell in larvae and young adults. Second, it causes severing of the BAG sensory dendrite from its terminus at the nose tip, apparently due to breakage of the dendrite as animals reach adulthood. Third, it causes embryonic defects in dendrite fasciculation in inner labial (IL2) sensory neurons, as previously reported, as well as rare defects in IL2 dendrite extension that are enhanced by loss of the apical ECM component DYF-7, suggesting that apical and basolateral ECM contribute separately to dendrite extension. Our results highlight novel roles for DIG-1 in maintaining the cellular integrity of neurons and glia, possibly by creating a barrier between structures in the nervous system.
Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering
Authors: Riedel Stefanie , Ward Daniel , Kudláčková Radmila , Mazur Karolina , Bačáková Lucie , Kerns Jemma G. , Allinson Sarah L. , Ashton Lorna , Koniezcny Robert , Mayr Stefan G. , Douglas Timothy E. L.
Published: October 2021

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications.
Polyamide/Poly(Amino Acid) Polymers for Drug Delivery
Authors: Boddu Sai H. S. , Bhagav Prakash , Karla Pradeep K. , Jacob Shery , Adatiya Mansi D. , Dhameliya Tejas M. , Ranch Ketan M. , Tiwari Amit K.
Published: October 2021

Polymers have always played a critical role in the development of novel drug delivery systems by providing the sustained, controlled and targeted release of both hydrophobic and hydrophilic drugs. Among the different polymers, polyamides or poly(amino acid)s exhibit distinct features such as good biocompatibility, slow degradability and flexible physicochemical modification. The degradation rates of poly(amino acid)s are influenced by the hydrophilicity of the amino acids that make up the polymer. Poly(amino acid)s are extensively used in the formulation of chemotherapeutics to achieve selective delivery for an appropriate duration of time in order to lessen the drug-related side effects and increase the anti-tumor efficacy. This review highlights various poly(amino acid) polymers used in drug delivery along with new developments in their utility. A thorough discussion on anticancer agents incorporated into poly(amino acid) micellar systems that are under clinical evaluation is included.
Signal Retrieval from Non-Sinusoidal Intensity Modulations in X-ray and Neutron Interferometry Using Piecewise-Defined Polynomial Function
Authors: Pinzek Simon , Gustschin Alex , Neuwirth Tobias , Backs Alexander , Schulz Michael , Herzen Julia , Pfeiffer Franz
Published: October 2021

Grating-based phase-contrast and dark-field imaging systems create intensity modulations that are usually modeled with sinusoidal functions to extract transmission, differential-phase shift, and scatter information. Under certain system-related conditions, the modulations become non-sinusoidal and cause artifacts in conventional processing. To account for that, we introduce a piecewise-defined periodic polynomial function that resembles the physical signal formation process, modeling convolutions of binary periodic functions. Additionally, we extend the model with an iterative expectation-maximization algorithm that can account for imprecise grating positions during phase-stepping. We show that this approach can process a higher variety of simulated and experimentally acquired data, avoiding most artifacts.
Multi-Scale Convolutional Neural Network for Accurate Corneal Segmentation in Early Detection of Fungal Keratitis
Authors: Mayya Veena , Kamath Shevgoor Sowmya , Kulkarni Uma , Hazarika Manali , Barua Prabal Datta , Acharya U. Rajendra
Published: October 2021

Microbial keratitis is an infection of the cornea of the eye that is commonly caused by prolonged contact lens wear, corneal trauma, pre-existing systemic disorders and other ocular surface disorders. It can result in severe visual impairment if improperly managed. According to the latest World Vision Report, at least 4.2 million people worldwide suffer from corneal opacities caused by infectious agents such as fungi, bacteria, protozoa and viruses. In patients with fungal keratitis (FK), often overt symptoms are not evident, until an advanced stage. Furthermore, it has been reported that clear discrimination between bacterial keratitis and FK is a challenging process even for trained corneal experts and is often misdiagnosed in more than 30% of the cases. However, if diagnosed early, vision impairment can be prevented through early cost-effective interventions. In this work, we propose a multi-scale convolutional neural network (MS-CNN) for accurate segmentation of the corneal region to enable early FK diagnosis. The proposed approach consists of a deep neural pipeline for corneal region segmentation followed by a ResNeXt model to differentiate between FK and non-FK classes. The model trained on the segmented images in the region of interest, achieved a diagnostic accuracy of 88.96%. The features learnt by the model emphasize that it can correctly identify dominant corneal lesions for detecting FK.
Drk1, a Dimorphism Histidine Kinase, Contributes to Morphology, Virulence, and Stress Adaptation in Paracoccidioides brasiliensis
Authors: Marcos Caroline Maria , de Oliveira Haroldo Cesar , Assato Patrícia Akemi , Castelli Rafael Fernando , Fusco-Almeida Ana Marisa , Mendes-Giannini Maria José Soares
Published: October 2021

P. brasiliensis is a thermally dimorphic fungus belonging to Paracoccidioides complex, causative of a systemic, endemic mycosis limited to Latin American countries. Signal transduction pathways related to important aspects as surviving, proliferation according to the biological niches are linked to the fungal pathogenicity in many species, but its elucidation in P. brasiliensis remains poorly explored. As Drk1, a hybrid histidine kinase, plays regulators functions in other dimorphic fungi species, mainly in dimorphism and virulence, here we investigated its importance in P. brasilensis. We, therefore generated the respective recombinant protein, anti-PbDrk1 polyclonal antibody and a silenced strain. The Drk1 protein shows a random distribution including cell wall location that change its pattern during osmotic stress condition; moreover the P. brasiliensis treatment with anti-PbDrk1 antibody, which does not modify the fungus’s viability, resulted in decreased virulence in G. mellonella model and reduced interaction with pneumocytes. Down-regulating PbDRK1 yielded phenotypic alterations such as yeast cells with more elongated morphology, virulence attenuation in G. mellonella infection model, lower amount of chitin content, increased resistance to osmotic and cell wall stresses, and also caspofungin, and finally increased sensitivity to itraconazole. These observations highlight the importance of PbDrk1 to P. brasiliensis virulence, stress adaptation, morphology, and cell wall organization, and therefore it an interesting target that could help develop new antifungals.
Evidence for Lignocellulose-Decomposing Enzymes in the Genome and Transcriptome of the Aquatic Hyphomycete Clavariopsis aquatica
Authors: Heeger Felix , Bourne Elizabeth C. , Wurzbacher Christian , Funke Elisabeth , Lipzen Anna , He Guifen , Ng Vivian , Grigoriev Igor V. , Schlosser Dietmar , Monaghan Michael T.
Published: October 2021

Fungi are ecologically outstanding decomposers of lignocellulose. Fungal lignocellulose degradation is prominent in saprotrophic Ascomycota and Basidiomycota of the subkingdom Dikarya. Despite ascomycetes dominating the Dikarya inventory of aquatic environments, genome and transcriptome data relating to enzymes involved in lignocellulose decay remain limited to terrestrial representatives of these phyla. We sequenced the genome of an exclusively aquatic ascomycete (the aquatic hyphomycete Clavariopsis aquatica), documented the presence of genes for the modification of lignocellulose and its constituents, and compared differential gene expression between C. aquatica cultivated on lignocellulosic and sugar-rich substrates. We identified potential peroxidases, laccases, and cytochrome P450 monooxygenases, several of which were differentially expressed when experimentally grown on different substrates. Additionally, we found indications for the regulation of pathways for cellulose and hemicellulose degradation. Our results suggest that C. aquatica is able to modify lignin to some extent, detoxify aromatic lignin constituents, or both. Such characteristics would be expected to facilitate the use of carbohydrate components of lignocellulose as carbon and energy sources.
The Impact of Organizational Context on the Levels of Cross-Border E-Commerce Adoption in Chinese SMEs: The Moderating Role of Environmental Context
Authors: Abdulkarem Anaf , Hou Wenhua
Published: October 2021

With the rapid technological developments, cross-border e-commerce (CBEC) as a sector is also expanding rapidly. In the past couple of decades, China has become a major force in promoting and developing CBEC and, therefore, it was needed to explore the various antecedents and outcomes of Chinese CBEC to expand the understanding and existing CBEC scholarship. Ample studies have been conducted to understand the antecedents and outcomes of CBEC. However, limited studies have explored such variables which can mitigate the adoption of CBEC. With this background, this empirical study was focused on addressing this gap by studying the moderating role of environmental context between organizational context and the four levels of CBEC adoption with the help of a technology-organization-environment framework. SMEs operating in China were targeted for data collection, where data were collected through an online survey. A final sample size of 208 was recorded. It was found that the organizational context has a direct and positive impact on all four levels of CBEC adoption. Furthermore, the moderating role of environmental context on Level 1 and 2 was not supported. Finally, the moderating role of environmental context on Level 3 and 4 was supported by the data. It was concluded that the organizational context plays a significant role in shaping CBEC at all four levels, whereas the environmental context has the potential to mitigate the relationships between organizational context and CBEC Level 3 and 4.
Vaccine Hesitancy and Administrative Burden in the Australian National Immunisation Program: An Analysis of Twitter Discourse
Authors: Atkinson Christopher L. , Atkinson Allison M.
Published: October 2021

In Australia, the National Immunisation Program and its Standard Vaccination Schedule are administered by the Australian Government Department of Health. While the public vaccination program’s safety and worth are generally agreed upon by doctors and public health professionals, some continue to see vaccinations as a source of danger and harm. The burden of vaccination in order to receive public services aligns government and medical interests, but a less-than-trusting public may see conspiracy in such requirements, resulting in vaccine hesitancy. The media’s attention to the topic, and a tendency toward misinformation on the part of anti-government opinion leaders, necessitate additional exploration of the administrative burden of vaccinations in an increasingly complex policy environment, where public health benefits are weighed against individual freedom and belief. This paper examines vaccinations as a burden, with costs in compliance, learning, and psychological terms, using posts from the social networking site Twitter as a corpus for exploratory content analysis in the specific case of Australia and its requirements. It is worth considering whether the positive aspects messaged by public health professionals are successfully entering into the discourse on vaccinations.
Land Tenure Disputes and Resolution Mechanisms: Evidence from Peri-Urban and Nearby Rural Kebeles of Debre Markos Town, Ethiopia
Authors: Agegnehu Sayeh Kassaw , Dires Tilahun , Nega Worku , Mansberger Reinfried
Published: October 2021

In Ethiopia, like in other developing countries, land disputes are critical problems both in peri-urban and rural areas. Handling such disputes requires scientific and evidence-based interventions. This study analyzes the nature, types, and causes of land tenure disputes and the resolution mechanisms thereof in peri-urban and nearby rural kebeles of Debre Markos town. Interviews for the investigation were conducted with sample landholders and concerned legal experts in Debre Markos town’s peri-urban area and Gozamin Wereda of Amhara National Regional State in Ethiopia. Compared to rural areas, the incidence of land tenure disputes is high in peri-urban areas. The land tenure disputes identified in the study areas are boundary trespassing disputes, landholding disputes, land rental disagreements, divorce-related land disputes, bequeath disputes, parcel exchange disputes, and land use-related disputes. The land tenure disputes are resolved mainly by formal means such as court litigations and administrative decisions, or by informal means known as alternative dispute resolution mechanisms (ADRMs). In both study areas, negotiation, mediation/conciliation, and arbitration are the most frequently employed ADRMs. In particular, mediation plays a significant role in resolving symmetrical land tenure disputes both in peri-urban and rural areas.
Gradual Vowel Epenthesis in Urban Hijazi Arabic
Authors: Al-Mohanna Faisal M.
Published: October 2021

In this paper, vowel epenthesis in Urban Hijazi Arabic is analysed as a process of gradual structural build-up. Harmonic Serialism, a derivational framework of Optimality Theory, provides the theoretical foundation to illustrate the arguments. Rather than epenthesising an entire vowel all at once, featural structure progressively increases in successive steps. This accumulation continues until the required vowel quality is achieved. Specifically, the constraint hierarchy predicts high epenthetic vowels to occur in closed syllables and the low epenthetic vowel in open syllables. The same constraint hierarchy, however, is also expected to predict both gradual epenthesis and gradual deletion. In that regard, a seemingly paradoxical situation is created when the very same intermediate vowel quality is achieved through accumulation or attrition of featural structure. This particular vowel quality, in exactly the same environment, will have to continue gaining internal structure towards epenthesis or continue losing internal structure towards deletion. Eventually, identifying the path that the derivation takes to reach a certain vowel will help to resolve the issue.
The Expressive Function of the ni que Insubordinate Construction in Spanish
Authors: Martínez Caro Elena , Alba-Juez Laura
Published: October 2021

Authors such as Tyler Schnoebelen (on page 12 of his study Emotions are Relational: Positioning and the Use of Affective Linguistic Resources), suggest that in some languages (cf. Navajo), certain dependent clauses are frequently used independently to “mark emotional evaluation and background information”. Evans, in his work on insubordination and its uses, makes use of the term insubordination to refer to this phenomenon. Our study focuses on a particular insubordinate construction introduced by the sequence ni que in Spanish, as in the example [¡Una carta cada día!] Ni que yo fuese Umbral. (CORPES Corpus), used as an independent clause with a sociopragmatic meaning, which is different from that of its subordinate counterpart (cf. No escribiría una carta cada día ni que yo fuese Umbral). Our research questions ask about the potential for ni que to be used as a discourse marker fulfilling an expressive function when it introduces this type of construction, and the derived hypothesis is then oriented to test whether Schnoebelen’s observation about insubordinate constructions also applies to this Spanish construction. In order to test this hypothesis, we performed a functional discourse analysis of more than 2000 concordances (and their extended contexts) in Mark Davies’ Corpus del Español and the Real Academia CORPES XXI. Our findings show that the insubordinate construction differs in function and meaning from its subordinate counterpart, the former fulfilling an emotive function, often combined with other discourse–pragmatic functions, such as evaluation or the organization of discourse.
Monitoring 21st-Century Real-Time Language Change in Spanish Youth Speech
Authors: Roels Linde , De Latte Fien , Enghels Renata
Published: October 2021

In recent decades, youth language has become one of the preferred research areas in sociolinguistics, not only because of its non-normative nature but mostly because it is recognized as a catalyst for language change. Since adolescents aspire to create and safeguard an in-group identity, they constantly generate innovative linguistic forms. However, few studies have empirically monitored the speed at which linguistic innovations are introduced into youth language. This study explores the speed and nature of recent language change within Spanish youth language by conducting a corpus analysis in real time. Data of the contemporary CORMA corpus (Corpus Oral de Madrid, compiled between 2016 and 2019) are contrasted with the highly comparable data of the COLAm corpus (Corpus Oral de Lenguaje Adolescente de Madrid, compiled between 2003 and 2007). The study scrutinizes two typical phenomena of youth language, namely the use of intensifiers (e.g., super-, mazo) and vocatives (e.g., tío/tía, chaval/chavala). It is shown that changes occur at a more moderate speed than previously assumed and that the speed of change depends on the linguistic phenomenon under study. Additionally, the data suggest that more neutral forms remain quite stable over time, while the use of more expressive items shrinks or increases faster.
The Charter of Fundamental Rights of the European Union: The First Ten Years-New Challenges and Perspectives
Authors: Tzemos Vasileios G. , Margaritis Konstantinos
Published: October 2021

Since 1 December 2009, the time when the Treaty of Lisbon came into force, the Charter of Fundamental Rights of the European Union (hereinafter: the EU Charter, the Charter) has been formally included in the EU legal order as primary EU law [...]
Using a Modified SERVQUAL Approach to Assess the Quality of Supply Chain Services in Greek Online Supermarkets
Authors: Mitropoulou Anastasia D. , Tsoulfas Giannis T.
Published: October 2021

Background: The purpose of this paper is to study customer satisfaction concerning orders from online supermarkets, which have recently boomed to fulfil the increased needs of customers during the COVID-19 pandemic. The service quality, as well as aspects of the logistics efficiency, are being examined, and the gaps between the expectations of people using these services and their perceptions about the received services are being evaluated. Methods: A modified approach of the well-known model SERVQUAL is suggested and used in the case of Greek online supermarkets. Thus, an initial contribution of this paper is the formulation of a framework which can be used to assess the quality of B2C logistics services. Results: The results show that customers’ expectations are exceeding their experiential perceptions in all the examined fields, and therefore there is room for substantial improvement. The study identified areas in which supermarkets’ online shops are close to meeting customer expectations and areas in which they fall far short. Conclusions: Competition is expected to become more intense and efficient supply chains that provide services of high quality will have a determinant role to play. Moreover, online supermarkets will have to rethink of their omni-channel structures to maintain and increase their market share. This is of particular importance during turbulent times such as the ones we are experiencing now.
Naphthalen-2-yl 1-(benzamido(diethoxyphosphoryl)methyl)-1H-1,2,3-triazole-4-carboxylate
Authors: Fall Serigne Abdou Khadir , Hajib Sara , Karai Oumaima , Boukhssas Salaheddine , Aouine Younas , Akhazzane Mohamed , Labriti Brahim , Faraj Hassane , Alami Anouar
Published: October 2021

We have previously published new biheterocyclic phospohonic α-amino esters of the 1,2,3-triazole-benzimidazole and 1,2,3-triazole-carbazole type. The aim of the present paper was to describe a new phosponic aminoester bearing a triazole ring substituted in position 5 by an ester group. Thus, according to the same catalytic process used previously, the compound naphthalen-2-yl 1-(benzamido(diethoxyphosphoryl)methyl)-1H-1,2,3-triazole-4-carboxylate was synthesized with an excellent yield and high regioselectivity via the copper (I)-catalyzed alkyne–azide cycloaddition reaction (CuAAC), using diethyl (α-azido(benzamido)methyl)phosphonate (1) as a dipole and 2- naphthyl propiolate as a dipolarophile (2). The structure of the new compound was fully characterized by 1D (31P, 1H-, 13C-) and 2D (1H-1H and 1H-, 13C-) NMR spectroscopy, IR, and HRMS.
Influence of Dispersed Reinforcement on Mechanical Properties of Stabilized Soil
Authors: Miturski Maciej , Głuchowski Andrzej , Sas Wojciech
Published: October 2021

Stabilized soils are commonly used as part of pavement construction in highway engineering. The everyday use of this material makes it necessary to classify it. One of the basic methods of determining the mechanical properties of a material is the unconfined compressive strength (UCS) test, from which the material elasticity can be determined. The scope of the research included the design and making of soil mixtures stabilized with polypropylene fibers modified cement. This paper presents the effect of the amount of dispersed reinforcement on the maximum compressive strength, the secant modulus at half the ultimate stress (E50), the secant modulus at the ultimate stress (Es), and the tangent modulus (Et). The materials chapter characterizes the soil, cement, and dispersed reinforcement used. The test methods section describes the tests performed and the procedure for interpreting the results. The results section describes the relationship between elastic modulus and compressive strength. The discussion section compares the obtained results with the works of other authors. The work is concluded with a summary containing the most important conclusions resulting from the work.