bluuebunny/crossref_metadata_2025 huggingface dataset:
High Resolution Manometry Guidance During Laparoscopic Fundoplication in Pediatric Surgically “Fragile” Patients: Preliminary Report
Authors: Caruso Anna Maria , Milazzo Mario , Tulone Vincenzo , Acierno Carlo , Girgenti Vincenza , Amoroso Salvatore , Bommarito Denisia , Calcaterra Valeria , Pelizzo Gloria
Published: November 2020

Background: High resolution manometry (HRM), has been recently introduced in clinical practice to detect esophageal intraluminal pressure and esophageal motor function. We evaluated the feasibility and usefulness of intraoperative esophageal HRM during antireflux laparoscopic procedures in pediatric cases with neurological impairment (NI) or esophageal atresia (EA). Methods: From January to November 2019, seven children (5 NI, 2 EA) with gastroesophageal reflux (GER) were enrolled. Data on intraoperative pressure changes of the esophagogastric junction (EGJ) and postoperative follow-up data were collected. Results: Average preoperative LES pressures were not significantly different from postoperative pressures. A sliding hernia was detected in all patients as evidenced by EGJ double peak pressures. Hernia correction after esophageal traction was complete in 71.4% of the patients, and residual hernia (<2 cm) was detected in 28.6%. Postoperative EGJ pressures were higher compared to preoperative sphincteric pressures (p < 0.001); in NI patients, higher postoperative values were noted compared to EA (p = 0.05). No sliding hernia and/or GER relapses were recorded. Two patients reported dysphagia postoperatively. Conclusions: Intraoperative HRM may optimize esophageal pressure changes during laparoscopic fundoplication. Further studies are needed to confirm the usefulness of a tailored surgical approach to reduce postoperative complications.
Anthropometric Assessment of Nepali Children Institutionalized in Orphanages
Authors: Fernández Lucía , Rubini Ana , Soriano Jose M. , Aldás-Manzano Joaquín , Blesa Jesús
Published: November 2020

Nepal is among the world’s poorest countries, and it is the third-poorest country in the South Asian region. Asia has the largest number of orphans in the world; in Nepal there are around 13,281 orphan children. The objective of this study is to evaluate the growth status of institutionalized children in Nepal through the analyses of anthropometric measures. The sample was Nepalese children aged 4 to 17, obtained from two different orphanages: in the first one, children with physical and mental disabilities coexist with children without any conditions. In the second one, there were no subjects with disabilities. Significant evidence of an association between mental and physical disability in institutionalized children and undernutrition (wasting and stunting) was found in this study. There is also weak but significant evidence of a relationship between underweight and being male. The study could help reaching a better understanding of growth status of institutionalized children in Nepal.
A Novel Method for the Evaluation of the Long-Term Stability of Cream Formulations Containing Natural Oils
Authors: Adejokun Deborah Adefunke , Dodou Kalliopi
Published: November 2020

This aim of this study is to prepare four novel oil-in-water creams from 100% naturally sourced oil ingredients such as jojoba, baobab and coconut oil, and compare the effect of the oils on the physico-chemical properties of the creams and their short- and long-term stability. Four 100 g each oil-in-water active containing creams and their controls (without the active ingredient) were formulated and stored in eight separate glass jars. The short-term stability of the creams was assessed via phase separation resistance, pH, microscopic size analysis, globule size, zeta potential, conductivity and microbial challenge evaluation after 8, 14 and 28 days, under three different storage temperature conditions (4 °C, 25 °C and 40 °C) and at ambient relative humidity. Model creams IA, IB, IIA, and IIB containing 1:1 of jojoba and baobab oil mix, all had good shelf-life or stability at the end of the 28 days after storage at 4 °C, 25 °C and 40 °C, compared to models IIIA, IVA and pairs. The long-term stability of creams stored at 25 °C for 28 days, was subsequently assessed using the Dynamic Vapor Sorption system. Model creams IB, IIB, IA and IIA showed the lowest percentage moisture loss or change in mass during a period of desorption steps. Therefore, the creams containing a mixture of jojoba and baobab oils are capable of retaining moisture easily for an extended period of time when compared to the creams containing jojoba and coconut oil or baobab and coconut oil combinations, thus they were proven to be the best products in terms of stability and quality. The stability ranking of the creams using the novel DVS method was in congruence with the results from the short-term stability experiments. This novel DVS method can, therefore, be generically applied in the cosmetic, food and pharmaceutical industries for the evaluation of the long-term stability of semisolids.
Bus Dynamic Travel Time Prediction: Using a Deep Feature Extraction Framework Based on RNN and DNN
Authors: Yuan Yuan , Shao Chunfu , Cao Zhichao , He Zhaocheng , Zhu Changsheng , Wang Yimin , Jang Vlon
Published: November 2020

Travel time data is an important factor for evaluating the performance of a public transport system. In terms of time and space within the nature of uncertainty, bus travel time is dynamic and flexible. Since the change of traffic status is periodic, contagious or even sudden, the changing mechanism of that is a hidden mode. Therefore, bus travel time prediction is a challenging problem in intelligent transportation system (ITS). Allowing for a large amount of traffic data can be collected at present but lack of precisely-conducting, it is still worth exploring how to extract feature sets that can accurately predict bus travel time from these data. Hence, a feature extraction framework based on the deep learning models were developed to reflect the state of bus travel time. First, the study introduced different historical stages of bus signaling time, taxi speed, the stop identity (ID) of spatial characteristics, and real-time possible arrival time, signified by fourteen spatiotemporal characteristic values. Then, an embedding network is proposed to leverage a wide and deep structure to mate the spatial and temporal data. In order to meet the temporal dependence requirements, an attention mechanism for a Recurrent Neural Network (RNN) was designed in this research in order to capture the temporal information. Finally, a Deep Neural Networks (DNN) was implemented in this research in order to achieve the dynamic bus travel time prediction. Two case studies of Guangzhou and Shenzhen were tested. The results showed that the performance of the algorithm was more efficient than that of the traditional machine-learning model and promoted by 4.82% compared to the deep neural network applied to the initial feature space. Moreover, the study visualized the weighted cost of attention on the bus’s travel time features during a certain running state. Therefore, the study demonstrated the proposed model enabled to understand the characteristic data of transit travel time with visualization.
Explaining the Diffusion of Energy-Efficient Lighting in India: A Technology Innovation Systems Approach
Authors: Mir Danish Ahmad , Doll Christopher N.H. , Lindner Robert , Parray Muhammad Tabish
Published: November 2020

Electricity consumption from lighting accounts for about 15% of total power demand and 5–6% of greenhouse gas emissions in developing countries. It is therefore a promising avenue to achieve considerable energy savings through technological innovation and upgrading. India has been very successful in recent years with a nationwide roll-out of modern light-emitting diode (LED) applications. This study uses the framework of technology innovation systems to identify the actors, institutions, and processes behind the diffusion of this technology. Our findings indicate that national innovation strategies, along with low-carbon technology (LCT) transfer policies, helped to bring down the cost of LED lamps in a rapidly expanding domestic market. Based on the findings, we further explore lessons for broader issues of low-carbon technology transfer and suggest an emerging intermediate step between north–south and south–south technology transfer.
Frequency-Domain Modeling of Harmonic Interactions in Voltage-Source Inverters with Closed-Loop Control
Authors: John Malte , Mertens Axel
Published: November 2020

Power electronic converters, together with their loads, sources, and controls, form a coupled system that includes many nonlinear interactions, for instance due to pulse-width modulation (PWM) and feedback control. In this paper we develop a complete, nonlinear modeling approach for voltage-source inverters in the frequency domain, taking into account the harmonic components introduced into the system from the inputs and from the nonlinear digital PWM. The most important contribution is a method for analyzing how these harmonics propagate through the nonlinear system in steady state. To enable this, an analytic model of PWM with arbitrary, multiple-frequency input is necessary. A revised model of Asymmetrical regularly-sampled double-edge PWM (AD-PWM) is proposed and its incorporation into the system model regarding sampling effects is discussed. The resulting nonlinear equation system is numerically and simultaneously solved, yielding the spectra of all relevant signals in the converter. The results are validated with time-domain simulations and with measurements, proving the effectiveness of the proposed approach.
Polymer Electrolyte Fuel Cell Degradation Mechanisms and Their Diagnosis by Frequency Response Analysis Methods: A Review
Authors: Sorrentino Antonio , Sundmacher Kai , Vidakovic-Koch Tanja
Published: November 2020

Several experimental techniques involving dynamic electrical variables are used to study the complex behaviour of polymer electrolyte membrane fuel cells in order to improve performance and durability. Among them, electrochemical impedance spectroscopy (EIS) is one of the most employed methods. Like any frequency response analysis (FRA) methodology, EIS enables one to separate the contribution of many processes to performance losses. However, it fails to identify processes with a similar time constant and the interpretation of EIS spectra is often ambiguous. In the last decade, alternative FRA methodologies based on non-electrical inputs and/or outputs have been developed. These studies were mainly driven by requirements for a better diagnosis of polymer electrolyte membrane fuel cells (PEMFCs) faulty operation conditions as well as better component and material design. In this contribution, a state-of-the-art EIS and novel FRA techniques for PEMFC diagnosis are summarised. First, common degradation mechanisms and their causes are discussed. A mathematical framework based on linear system theory of time invariant systems is described in order to explain the theoretical implications of the use of different input/output configurations. In relation to this, the concepts and potential are depicted as well as the problematic aspects and future prospective of these diagnostic approaches.
High-Performance Anion Exchange Chromatography with Pulsed Amperometric Detection (HPAEC–PAD) and Chemometrics for Geographical and Floral Authentication of Honeys from Southern Italy (Calabria region)
Authors: Carabetta Sonia , Di Sanzo Rosa , Campone Luca , Fuda Salvatore , Rastrelli Luca , Russo Mariateresa
Published: November 2020

High-performance anion exchange chromatography with pulsed amperometric detection (HPAEC–PAD) combined with chemometric analysis was developed to describe, for the first time, the sugar profile of sixty-one honeys of different botanical origin produced in southern Italy (Calabria Region). The principal component and linear discriminant analysis used to describe the variability of sugar data were able to discriminate the honeys according to their botanical origin with a correlation index higher than 90%. For the purpose of the robustness of the conclusions of this study, the analytical advantages of the HPAEC–PAD method have been statistically demonstrated compared to the official Italian HPLC–RI method (Refractive Index detection). Finally, as the characterization of the floral and geographical origin of honey became an important issue due to high consumer demand, 13 acacia honeys originating from Europe and China were studied by using the same method. By chemometric method it was possible to discriminate the different geographical origin with an index of 100%. All results proved the possibility to identify the sugar profile obtained by HPAEC–PAD combined with a robust statistical analysis, as a tool of authentication.
What Is the Color of Milk and Dairy Products and How Is It Measured?
Authors: Milovanovic Bojana , Djekic Ilija , Miocinovic Jelena , Djordjevic Vesna , Lorenzo Jose M. , Barba Francisco J. , Mörlein Daniel , Tomasevic Igor
Published: November 2020

Exactly six-hundred (600) scientific articles that report milk and milk products’ color results in scientific journals in the last couple of decades were reviewed. Thereof, the greatest part of the articles derived from Europe (36.3%) and Asia (29.5%). The greatest share of researchers used Minolta colorimeters (58.8%), while 26.3% of them used Hunter devices. Most reports were on cheese (31.0%) followed by fermented products (21.2%). Moreover, the highest number of papers reported color data of milk and milk products made from cow’s milk (44.81%). As expected, goat’s cheese was the brightest (L* = 87.1), while cow’s cheese was the yellowest (b* = 17.4). Most importantly, it appeared that color research results reported were often impossible to replicate or to interpret properly because of incomplete description of the methodology. In some of the manuscripts reviewed, illuminant source (61.0%), aperture size (93.8%), observer angle, and number of readings (over 70% of all cases) were not reported. It is therefore critical to set rules regarding the description of the methodology for (milk) color research articles in order to ensure replicability and/or comparison of studies.
Thermodynamic Constraints on the Non-Baryonic Dark Matter Gas Composing Galactic Halos
Authors: Hofmeister Anne M.
Published: November 2020

To explain rotation curves of spiral galaxies through Newtonian orbital models, massive halos of non-baryonic dark matter (NBDM) are commonly invoked. The postulated properties are that NBDM interacts gravitationally with baryonic matter, yet negligibly interacts with photons. Since halos are large, low-density gaseous bodies, their postulated attributes can be tested against classical thermodynamics and the kinetic theory of gas. Macroscopic models are appropriate because these make few assumptions. NBDM–NBDM collisions must be elastic to avoid the generation of light, but this does not permit halo gas temperature to evolve. If no such collisions exist, then the impossible limit of absolute zero would be attainable since the other available energy source, radiation, does not provide energy to NBDM. The alternative possibility, an undefined temperature, is also inconsistent with basic thermodynamic principles. However, a definable temperature could be attained via collisions with baryons in the intergalactic medium since these deliver kinetic energy to NBDM. In this case, light would be produced since some proportion of baryon collisions are inelastic, thereby rendering the halo detectable. Collisions with baryons are unavoidable, even if NBDM particles are essentially point masses. Note that <0.0001 × the size of a proton is needed to avoid scattering with γ-rays, the shortest wavelength used to study halos. If only elastic collisions exist, NBDM gas would collapse to a tiny, dense volume (zero volume for point masses) during a disturbance—e.g., cosmic rays. NBDM gas should occupy central galactic regions, not halos, since self-gravitating objects are density stratified. In summary, properties of NBDM halos as postulated would result in violations of thermodynamic laws and in a universe unlike that observed.
Public Healthcare: Citizen’s Preferences in Spain
Authors: Prieto-Herraez Silvia , González-Arteaga Teresa , Calle Rocío de Andrés
Published: November 2020

This paper analyzes the stability of citizens’ preferences on public healthcare services in Spain. Nowadays, the increasing privatization of some healthcare services and the rapid emergence of private hospitals have caused changes in people’s preferences on public healthcare systems. This paper focuses on analyzing the preferences of Spaniards on their healthcare system over time under the assumption that citizens’ preferences are represented by complete pre-orders. Data for this study were collected from the Spanish Health Barometer survey, and they were searched from 1995 until 2018. The results show that preferences on the public healthcare system are very stable along time.
Antibiofilm Activity on Candida albicans and Mechanism of Action on Biomembrane Models of the Antimicrobial Peptide Ctn[15–34]
Authors: Aguiar Francisca Lidiane Linhares de , Santos Nuno C. , de Paula Cavalcante Carolina Sidrim , Andreu David , Baptista Gandhi Radis , Gonçalves Sónia
Published: November 2020

Ctn[15–34], the C-terminal fragment of crotalicidin, an antimicrobial peptide from the South American rattlesnake Crotalus durissus terrificus venom, displays remarkable anti-infective and anti-proliferative activities. Herein, its activity on Candida albicans biofilms and its interaction with the cytoplasmic membrane of the fungal cell and with a biomembrane model in vitro was investigated. A standard C. albicans strain and a fluconazole-resistant clinical isolate were exposed to the peptide at its minimum inhibitory concentration (MIC) (10 µM) and up to 100 × MIC to inhibit biofilm formation and its eradication. A viability test using XTT and fluorescent dyes, confocal laser scanning microscopy, and atomic force microscopy (AFM) were used to observe the antibiofilm effect. To evaluate the importance of membrane composition on Ctn[15–34] activity, C. albicans protoplasts were also tested. Fluorescence assays using di-8-ANEPPS, dynamic light scattering, and zeta potential measurements using liposomes, protoplasts, and C. albicans cells indicated a direct mechanism of action that was dependent on membrane interaction and disruption. Overall, Ctn[15–34] showed to be an effective antifungal peptide, displaying antibiofilm activity and, importantly, interacting with and disrupting fungal plasma membrane.
Review of PIP2 in Cellular Signaling, Functions and Diseases
Authors: Mandal Kalpana
Published: November 2020

Phosphoinositides play a crucial role in regulating many cellular functions, such as actin dynamics, signaling, intracellular trafficking, membrane dynamics, and cell–matrix adhesion. Central to this process is phosphatidylinositol bisphosphate (PIP2). The levels of PIP2 in the membrane are rapidly altered by the activity of phosphoinositide-directed kinases and phosphatases, and it binds to dozens of different intracellular proteins. Despite the vast literature dedicated to understanding the regulation of PIP2 in cells over past 30 years, much remains to be learned about its cellular functions. In this review, we focus on past and recent exciting results on different molecular mechanisms that regulate cellular functions by binding of specific proteins to PIP2 or by stabilizing phosphoinositide pools in different cellular compartments. Moreover, this review summarizes recent findings that implicate dysregulation of PIP2 in many diseases
Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations
Authors: Atienza-Navarro Isabel , Alves-Martinez Pilar , Lubian-Lopez Simon , Garcia-Alloza Monica
Published: November 2020

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most important complications of the preterm newborn. Since these children are born at a critical time in brain development, they can develop short and long term neurological, sensory, cognitive and motor disabilities depending on the severity of the GM-IVH. In addition, hemorrhage triggers a microglia-mediated inflammatory response that damages the tissue adjacent to the injury. Nevertheless, a neuroprotective and neuroreparative role of the microglia has also been described, suggesting that neonatal microglia may have unique functions. While the implication of the inflammatory process in GM-IVH is well established, the difficulty to access a very delicate population has lead to the development of animal models that resemble the pathological features of GM-IVH. Genetically modified models and lesions induced by local administration of glycerol, collagenase or blood have been used to study associated inflammatory mechanisms as well as therapeutic targets. In the present study we review the GM-IVH complications, with special interest in inflammatory response and the role of microglia, both in patients and animal models, and we analyze specific proteins and cytokines that are currently under study as feasible predictors of GM-IVH evolution and prognosis.
Ensemble-Based Analysis of the Dynamic Allostery in the PSD-95 PDZ3 Domain in Relation to the General Variability of PDZ Structures
Authors: Dudola Dániel , Hinsenkamp Anett , Gáspári Zoltán
Published: November 2020

PDZ domains are abundant interaction hubs found in a number of different proteins and they exhibit characteristic differences in their structure and ligand specificity. Their internal dynamics have been proposed to contribute to their biological activity via changes in conformational entropy upon ligand binding and allosteric modulation. Here we investigate dynamic structural ensembles of PDZ3 of the postsynaptic protein PSD-95, calculated based on previously published backbone and side-chain S2 order parameters. We show that there are distinct but interdependent structural rearrangements in PDZ3 upon ligand binding and the presence of the intramolecular allosteric modulator helix α3. We have also compared these rearrangements in PDZ1-2 of PSD-95 and the conformational diversity of an extended set of PDZ domains available in the PDB database. We conclude that although the opening-closing rearrangement, occurring upon ligand binding, is likely a general feature for all PDZ domains, the conformer redistribution upon ligand binding along this mode is domain-dependent. Our findings suggest that the structural and functional diversity of PDZ domains is accompanied by a diversity of internal motional modes and their interdependence.
Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?
Authors: D’Augustin Ostiane , Huet Sébastien , Campalans Anna , Radicella Juan Pablo
Published: November 2020

The most frequent DNA lesion resulting from an oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoG). 8-oxoG is a premutagenic base modification due to its capacity to pair with adenine. Thus, the repair of 8-oxoG is critical for the preservation of the genetic information. Nowadays, 8-oxoG is also considered as an oxidative stress-sensor with a putative role in transcription regulation. In mammalian cells, the modified base is excised by the 8-oxoguanine DNA glycosylase (OGG1), initiating the base excision repair (BER) pathway. OGG1 confronts the massive challenge that is finding rare occurrences of 8-oxoG among a million-fold excess of normal guanines. Here, we review the current knowledge on the search and discrimination mechanisms employed by OGG1 to find its substrate in the genome. While there is considerable data from in vitro experiments, much less is known on how OGG1 is recruited to chromatin and scans the genome within the cellular nucleus. Based on what is known of the strategies used by proteins searching for rare genomic targets, we discuss the possible scenarios allowing the efficient detection of 8-oxoG by OGG1.
Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases
Authors: Ryu Jae-Sung , Jeong Eun-Jeong , Kim Jong-Yeup , Park Soon Ju , Ju Won Seok , Kim Chang-Hyun , Kim Jang-Seong , Choo Young-Kug
Published: November 2020

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.
The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms
Authors: Beyer Hannes M. , Virtanen Salla I. , Aranko A. Sesilja , Mikula Kornelia M. , Lountos George T. , Wlodawer Alexander , Ollila O. H. Samuli , Iwaï Hideo
Published: November 2020

Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from Mycobacterium chimaera and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for trans-peptidyl and trans-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues.
Dietary Carbohydrates and Lipids in the Pathogenesis of Leaky Gut Syndrome: An Overview
Authors: Binienda Agata , Twardowska Agata , Makaro Adam , Salaga Maciej
Published: November 2020

This review summarizes the recent knowledge on the effects of dietary carbohydrates and lipids on the pathophysiology of leaky gut syndrome (LGS). Alterations in intestinal barrier permeability may lead to serious gastrointestinal (GI) disorders. LGS is caused by intestinal hyperpermeability due to changes in the expression levels and functioning of tight junctions. The influence of dietary habits on intestinal physiology is clearly visible in incidence rates of intestinal diseases in industrial and developing countries. Diseases which are linked to intestinal hyperpermeability tend to localize to Westernized countries, where a diet rich in fats and refined carbohydrates predominates. Several studies suggest that fructose is one of the key carbohydrates involved in the regulation of the intestinal permeability and its overuse may cause harmful effects, such as tight junction protein dysfunction. On the other hand, short chain fatty acids (mainly butyrate) at appropriate concentrations may lead to the reduction of intestinal permeability, which is beneficial in LGS. However, long chain fatty acids, including n-3 and n-6 polyunsaturated fatty acids have unclear properties. Some of those behave as components untightening and tightening the intestinal membrane.
An In Vitro Model to Investigate the Role of Helicobacter pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
Authors: Cuomo Paola , Papaianni Marina , Sansone Clementina , Iannelli Antonio , Iannelli Domenico , Medaglia Chiara , Paris Debora , Motta Andrea , Capparelli Rosanna
Published: November 2020

Helicobacter pylori (Hp) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the Hp cell filtrate (Hpcf) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer’s diseases, and cardiometabolic disease. Here, we demonstrate how Hp may modulate these traits. Hp induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by Hp. Furthermore, Hp modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the Hp toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how Hp may potentially manipulate them.
A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes
Authors: Shin Sun-Hye , Kim Hee-Yeon , Yoon Hee-Soo , Park Woo-Jae , Adams David R. , Pyne Nigel J. , Pyne Susan , Park Joo-Won
Published: November 2020

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis.
CaHsfA1d Improves Plant Thermotolerance via Regulating the Expression of Stress- and Antioxidant-Related Genes
Authors: Gai Wen-Xian , Ma Xiao , Li Yang , Xiao Jing-Jing , Khan Abid , Li Quan-Hui , Gong Zhen-Hui
Published: November 2020

Heat shock transcription factor (Hsf) plays an important role in regulating plant thermotolerance. The function and regulatory mechanism of CaHsfA1d in heat stress tolerance of pepper have not been reported yet. In this study, phylogenetic tree and sequence analyses confirmed that CaHsfA1d is a class A Hsf. CaHsfA1d harbored transcriptional function and predicted the aromatic, hydrophobic, and acidic (AHA) motif mediated function of CaHsfA1d as a transcription activator. Subcellular localization assay showed that CaHsfA1d protein is localized in the nucleus. The CaHsfA1d was transcriptionally up-regulated at high temperatures and its expression in the thermotolerant pepper line R9 was more sensitive than that in thermosensitive pepper line B6. The function of CaHsfA1d under heat stress was characterized in CaHsfA1d-silenced pepper plants and CaHsfA1d-overexpression Arabidopsis plants. Silencing of the CaHsfA1d reduced the thermotolerance of the pepper, while CaHsfA1d-overexpression Arabidopsis plants exhibited an increased insensitivity to high temperatures. Moreover, the CaHsfA1d maintained the H2O2 dynamic balance under heat stress and increased the expression of Hsfs, Hsps (heat shock protein), and antioxidant gene AtGSTU5 (glutathione S-transferase class tau 5) in transgenic lines. Our findings clearly indicate that CaHsfA1d improved the plant thermotolerance via regulating the expression of stress- and antioxidant-related genes.
Apelin-13 Protects Dopaminergic Neurons against Rotenone—Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation
Authors: Chen Peng , Wang Youcui , Chen Leilei , Song Ning , Xie Junxia
Published: November 2020

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain–gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPKα inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.
Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis
Authors: Skurikhin Evgenii , Nebolsin Vladimir , Widera Darius , Ermakova Natalia , Pershina Olga , Pakhomova Angelina , Krupin Vyacheslav , Pan Edgar , Zhukova Mariia , Novikov Fedor , Sandrikina Lubov , Morozov Sergey , Kubatiev Aslan , Dygai Alexander
Published: November 2020

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by interstitial fibrosis and progressive respiratory failure. Pirfenidone and nintedanib slow down but do not stop the progression of IPF. Thus, new compounds with high antifibrotic activity and simultaneously regenerative activity are an unmet clinical need. Recently, we showed that Treamid can help restoring the pancreas and testicular tissue in mice with metabolic disorders. We hypothesized that Treamid may be effective in antifibrotic therapy and regeneration of damaged lung tissue in pulmonary fibrosis. In this study, experiments were performed on male C57BL/6 mice with bleomycin-induced pulmonary fibrosis. We applied histological and immunohistochemical methods, ELISA, and assessed the expression of markers of endothelial and epithelial cells in primary cultures of CD31+ and CD326+ lung cells. Finally, we evaluated esterase activity and apoptosis of lung cells in vitro. Our data indicate that Treamid exhibits antifibrotic activity in mice with pulmonary fibrosis and has a positive effect on capillaries of the lungs. Treamid also increases the number of endothelial progenitor cells in the lungs of animals with pulmonary fibrosis. Lastly, Treamid increases esterase activity and decreases apoptosis of CD31+ lung cells in vitro. Based on these findings, we suggest that Treamid may represent a promising compound for the development of new antifibrotic agents, which are capable of stimulating regeneration of lung endothelium in IPF patients.
A Portable Compact System for Laser Speckle Correlation Imaging of Artworks Using Projected Speckle Pattern
Authors: Daffara Claudia , Marini Elisa
Published: November 2020

Artworks have a layered structure subjected to alterations caused by various factors. The monitoring of defects at sub-millimeter scale may be performed by laser interferometric techniques. The aim of this work was to develop a compact system to perform laser speckle imaging in situ for effective mapping of subsurface defects in paintings. The device was designed to be versatile with the possibility of optimizing the performance by easy parameters adjustment. The system exploits a laser speckle pattern generated through an optical diffuser and projected onto the artworks and image correlation techniques for the analysis of the speckle intensity pattern. A protocol for the optimal measurement was suggested, based on calibration curves for tuning the mean speckle size in the acquired intensity pattern. The system was validated in the analysis of detachments in an ancient painting model using a short pulse thermal stimulus to induce a surface deformation field and standard decorrelation algorithms for speckle pattern matching. The device is equipped with a compact thermal camera for preventing any overheating effects during the phase of the stimulus. The developed system represents a valuable nondestructive tool for artwork diagnostics, allowing the monitoring of subsurface defects in paintings in out-of-laboratory environment.
Decoupled Hydrodynamic Models and Their Outdoor Identification for an Unmanned Inland Cargo Vessel with Embedded Fully Rotatable Thrusters
Authors: Peeters Gerben , Van Baelen Senne , Yayla Gökay , Catoor Tim , Afzal Muhammad Raheel , Christofakis Christos , Louw Robrecht , Singh Yogang , Vanierschot Maarten , Boonen René , Slaets Peter
Published: November 2020

Expanding the automation level of the freshly introduced fleet of self-propelled Watertruck+ barges, which house fully-rotatable embedded thrusters, might increase their ability to compete with their less sustainable but dominating road-based alternatives. Hydrodynamic motion models, which reveal the manoeuvring capabilities of these barges, can serve as inputs for many pieces of this automation puzzle. No identified motion models or hydrodynamic data seem to be publicly available for the hull design and the novel actuation system configuration of these barges. Therefore, this study offers: (i) decoupled motion model structures for these barges for surge, sway, and yaw, with a focus on the thruster and damping models; (ii) two identification procedures to determine these motion models; (iii) all the experimental data, generated outdoors with a scale model barge to identify (i) based on (ii). In addition, the identified surge models were compared with both computational and empirical data. These comparisons offer more physical insights into the identified model structures and can aid in the model selection for which the desired complexity and accuracy evidently depend on their envisaged application. Finally, this methodology need not be limited to the vessel and actuation types utilised by us.
The Emergence of Second Language Categorisation of the English Article Construction
Authors: Zhao Helen
Published: November 2020

This study examines the emergent cognitive categorisation of the English article construction among second language (L2) learners. One hundred and fourteen Mandarin-L1 learners of English, divided into two L2 proficiency levels (low-to-intermediate and advanced), were measured by a computer-based cloze test for the accuracy and response time of appropriate use of English articles in sentential contexts. Results showed that when learners acquired the polysemous English article construction they demonstrated stronger competence in differentiating individual form-function mappings in the article construction. L2 learners’ patterns of article construction usage were shaped by semantic functions. Learners performed better on the definiteness category than on the non-definiteness categories, suggesting that learners were sensitive to the prototypicality of nominal grounding. Advanced learners demonstrated an increased sensitivity to semantic idiosyncrasy, but they lacked contextualised constructional knowledge. Competition among the functional categories and restructuring of functional categories are important ways of regularization that learners go through to acquire semantically complex systems such as articles.
How Does Pedagogical Flexibility in Curriculum Use Promote Mathematical Flexibility? An Exploratory Case Study
Authors: Lee Kyeong-Hwa , Na GwiSoo , Song Chang-Geun , Jung Hye-Yun
Published: November 2020

Flexibility has been increasingly valued in mathematics education to better prepare students for lives in the rapidly changing society of the future. Although there has been conjecture that teachers’ flexibility plays a substantial role in facilitating students’ mathematical flexibility, there has been little examination of how teachers can use a flexible curriculum to develop mathematical flexibility (MF) in authentic classroom environments. This paper elaborates the notion of flexible curriculum use, referred to as pedagogical flexibility (PF) in curriculum use, as the competence to expand pedagogical space and make alternative pedagogical decisions when planning and enacting a curriculum that differs from the routine practices provided in the intended and written curriculum. We develop a framework for PF in curriculum use to identify and characterize teachers’ curriculum use to promote MF. In an explorative case study with one middle school teacher, we analyzed what and how specific aspects of PF in curriculum use promote potential and actual MF in the learning of central tendency measures. Findings indicate that the teacher could expand his pedagogical space by carefully differentiating the pedagogical considerations of the curriculum and could find alternative approaches by making associative and reflective connections among them. This provides insight into how PF in curriculum use can promote students’ potential and actual MF.
Distributional Properties of Fluid Queues Busy Period and First Passage Times
Authors: Palmowski Zbigniew
Published: November 2020

In this paper, I analyze the distributional properties of the busy period in an on-off fluid queue and the first passage time in a fluid queue driven by a finite state Markov process. In particular, I show that the first passage time has a IFR distribution and the busy period in the Anick-Mitra-Sondhi model has a DFR distribution.
Antibacterial Alkaloids and Polyketide Derivatives from the Deep Sea-Derived Fungus Penicillium cyclopium SD-413
Authors: Li Yan-He , Li Xiao-Ming , Li Xin , Yang Sui-Qun , Shi Xiao-Shan , Li Hong-Lei , Wang Bin-Gui
Published: November 2020

Nine secondary metabolites (1–9), including two new polyketide derivatives 9-dehydroxysargassopenilline A (4) and 1,2-didehydropeaurantiogriseol E (5), along with seven known related secondary metabolites (1–3 and 6–9), were isolated and identified from the deep sea-derived fungus Penicilliumcyclopium SD-413. Their structures were elucidated on the basis of 1D/2D NMR spectroscopic and mass spectrometric analysis and the absolute configurations were determined by the combination of NOESY correlations and time-dependent density functional (TDDFT) ECD calculations. Compounds 1–9 inhibited some pathogenic bacteria including Escherichia coli, E. ictaluri, Edwardsiella tarda, Micrococcus luteus, Vibrio anguillarum, and V. harveyi, with MIC (minimum inhibitory concentration) values ranging from 4 to 32 μg/mL.
The Evanescent GacS Signal
Authors: Latour Xavier
Published: November 2020

The GacS histidine kinase is the membrane sensor of the major upstream two-component system of the regulatory Gac/Rsm signal transduction pathway. This pathway governs the expression of a wide range of genes in pseudomonads and controls bacterial fitness and motility, tolerance to stress, biofilm formation, and virulence or plant protection. Despite the importance of these roles, the ligands binding to the sensor domain of GacS remain unknown, and their identification is an exciting challenge in this domain. At high population densities, the GacS signal triggers a switch from primary to secondary metabolism and a change in bacterial lifestyle. It has been suggested, based on these observations, that the GacS signal is a marker of the emergence of nutritional stress and competition. Biochemical investigations have yet to characterize the GacS signal fully. However, they portray this cue as a low-molecular weight, relatively simple and moderately apolar metabolite possibly resembling, but nevertheless different, from the aliphatic organic acids acting as quorum-sensing signaling molecules in other Proteobacteria. Significant progress in the development of metabolomic tools and new databases dedicated to Pseudomonas metabolism should help to unlock some of the last remaining secrets of GacS induction, making it possible to control the Gac/Rsm pathway.
Effect of Co-contamination by PAHs and Heavy Metals on Bacterial Communities of Diesel Contaminated Soils of South Shetland Islands, Antarctica
Authors: Gran-Scheuch Alejandro , Ramos-Zuñiga Javiera , Fuentes Edwar , Bravo Denisse , Pérez-Donoso José M.
Published: November 2020

Diesel oil is the main source of energy used in Antarctica. Since diesel is composed of toxic compounds such as polycyclic aromatic hydrocarbons (PAHs) and heavy metals, it represents a constant threat to the organisms inhabiting this continent. In the present study, we characterized the chemical and biological parameters of diesel-exposed soils obtained from King George Island in Antarctica. Contaminated soils present PAH concentrations 1000 times higher than non-exposed soils. Some contaminated soil samples also exhibited high concentrations of cadmium and lead. A 16S metagenome analysis revealed the effect of co-contamination on bacterial communities. An increase in the relative abundance of bacteria known as PAH degraders or metal resistant was determined in co-contaminated soils. Accordingly, the soil containing higher amounts of PAHs exhibited increased dehydrogenase activity than control soils, suggesting that the microorganisms present can metabolize diesel. The inhibitory effect on soil metabolism produced by cadmium was lower in diesel-contaminated soils. Moreover, diesel-contaminated soils contain higher amounts of cultivable heterotrophic, cadmium-tolerant, and PAH-degrading bacteria than control soils. Obtained results indicate that diesel contamination at King George island has affected microbial communities, favoring the presence of microorganisms capable of utilizing PAHs as a carbon source, even in the presence of heavy metals.