bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficiency of Biocidal Silica Nanosystems for the Conservation of Stone Monuments: Comparative In Vitro Tests against Epilithic Green Algae
Authors: Bartoli Flavia , Zuena Martina , Sodo Armida , Caneva Giulia
Published: July 2021

In the last decade, worldwide research has focused on innovative natural biocides and the development of organic and inorganic nanomaterials for long-lasting reliability. In this work, the biocide effects of two different biocides encapsulated in two different silica nanosystems for a multifunctional coating have been performed through in vitro tests, by using Chlorococcum sp. as a common stone biodeteriogen. Zosteric sodium salt (ZS), a green biocide, was compared with the commercial biocide, 2-mercaptobenzothiazole (MBT), widely used in the treatment of cultural heritage. The analyzed systems are the following: silica nanocapsules (NC) and silica nanoparticles (MNP) not loaded with biocides, two nanosystems loaded with ZS and MBT, and free biocides. The qualitative and quantitative evaluations of biocide efficiency were performed periodically, analyzing pigment autofluorescence to discriminate between active and inactive/dead cells. The analyses showed multiple differences. All the nanocontainers presented an initial reduction in chlorophyll’s autofluorescence. For the free biocide, the results highlighted higher efficiency for MBT than ZS. Finally, the nanosystems loaded with the different biocides highlighted a higher activity for nanocontainers loaded with the commercial biocide than the green product, and better efficiency for MNP in comparison with NC.
Dose Calculation Algorithms for External Radiation Therapy: An Overview for Practitioners
Authors: De Martino Fortuna , Clemente Stefania , Graeff Christian , Palma Giuseppe , Cella Laura
Published: July 2021

Radiation therapy (RT) is a constantly evolving therapeutic technique; improvements are continuously being introduced for both methodological and practical aspects. Among the features that have undergone a huge evolution in recent decades, dose calculation algorithms are still rapidly changing. This process is propelled by the awareness that the agreement between the delivered and calculated doses is of paramount relevance in RT, since it could largely affect clinical outcomes. The aim of this work is to provide an overall picture of the main dose calculation algorithms currently used in RT, summarizing their underlying physical models and mathematical bases, and highlighting their strengths and weaknesses, referring to the most recent studies on algorithm comparisons. This handy guide is meant to provide a clear and concise overview of the topic, which will prove useful in helping clinical medical physicists to perform their responsibilities more effectively and efficiently, increasing patient benefits and improving the overall quality of the management of radiation treatment.
Numerical Study of RC Beams Strengthened with Fe-Based Shape Memory Alloy Strips Using the NSM Method
Authors: Yeon Yeong-Mo , Hong Ki-Nam , Lee Sugyu , Ji Sang-Won
Published: July 2021

This paper presents a finite element (FE) analysis for predicting the flexural behavior of reinforced concrete (RC) beams strengthened with Fe-based shape memory alloy (Fe-SMA) strips using a near surface mounted (NSM) method. Experimental results reported in the literature were used to verify the proposed FE model. FE analyses were conducted using OpenSees, a general-purpose structural FE analysis program. The RC beam specimens were modeled using a nonlinear beam-column element and a fiber element. The Concrete 02 model, Steel 01 model, and Pinching 04 model were applied to the concrete, steel reinforcement, and Fe-SMA strip in the fiber element, respectively, and the FE analysis was carried out in a displacement control method based on the Newton-Raphson method. The FE model of this study accurately predicted the initial crack load, yield load, and ultimate load. From parametric analyses, it was concluded that an increase in the compressive strength of the concrete increases the ductility of the specimen, and an increase in the level of recovery stress on the Fe-SMA strip increases the initial stiffness of the specimen.
Carbon Nanostructures Decorated with Titania: Morphological Control and Applications
Authors: Cringoli Maria Cristina , Perathoner Siglinda , Fornasiero Paolo , Marchesan Silvia
Published: July 2021

Nanostructured titania (TiO2) is the most widely applied semiconducting oxide for a variety of purposes, and it is found in many commercial products. The vast majority of uses rely on its photo-activity, which, upon light irradiation, results in excited states that can be used for diverse applications. These range from catalysis, especially for energy or environmental remediation, to medicine—in particular, to attain antimicrobial surfaces and coatings for titanium implants. Clearly, the properties of titania are enhanced when working at the nanoscale, thanks to the increasingly active surface area. Nanomorphology plays a key role in the determination of the materials’ final properties. In particular, the nucleation and growth of nanosized titania onto carbon nanostructures as a support is a hot topic of investigation, as the nanocarbons not only provide structural stability but also display the ability of electronic communication with the titania, leading to enhanced photoelectronic properties of the final materials. In this concise review, we present the latest progress pertinent to the use of nanocarbons as templates to tailor nanostructured titania, and we briefly review the most promising applications and future trends of this field.
The Impact of Earthquakes on Apartment Owners and Renters in Te Whanganui-a-Tara (Wellington) Aotearoa New Zealand
Authors: Blake Denise , Becker Julia S. , Hodgetts Darrin , Elwood Kenneth J.
Published: July 2021

Apartment dwelling is on the increase in many cities in Aotearoa New Zealand, including those in earthquake-prone regions. Hence it is important that people working in disaster management and housing improve their understanding on how the living situations of apartment dwellers influence their disaster management practices. This knowledge is crucial for efforts to promote safety and preparedness. This paper explores what enables and constrains apartment dwellers in their ability to prepare for an earthquake. Eighteen people were interviewed who resided in Te Whanganui-a-Tara (Wellington) two years after the 2016 7.8 magnitude (Mw) Kaikōura earthquake. Of central concern was people’s ability to prepare for disasters and access knowledge about building and structural safety and how this knowledge mattered to what apartment dwellers were able to prepare for. We found that the agency to prepare was dependent on whether people owned or rented their dwellings. We report on participant accounts of dealing with body corporations, landlords, emergency kits, other emergency items, and evacuation plans.
Improved Surprise Adequacy Tools for Corner Case Data Description and Detection
Authors: Ouyang Tinghui , Marco Vicent Sanz , Isobe Yoshinao , Asoh Hideki , Oiwa Yutaka , Seo Yoshiki
Published: July 2021

Facing the increasing quantity of AI models applications, especially in life- and property-related fields, it is crucial for designers to construct safety- and security-critical systems. As a major factor affecting the safety of AI models, corner case data and its related description/detection techniques are important in the AI design phase and quality assurance. In this paper, inspired by surprise adequacy (SA), a tool having advantages on capture data behaviors, we developed three modified versions of distance-based-SA (DSA) for detecting corner cases in classification problems. Through the experiment analysis on MNIST, CIFAR, and industrial example data, the feasibility and usefulness of the proposed tools on corner case data detection are verified. Moreover, Qualitative and quantitative experiments validated that the developed DSA tools can achieve improved performance in describing corner cases’ behaviors.
Gamma, Fast Neutron, Proton, and Alpha Shielding Properties of Borate Glasses: A Closer Look on Lead (II) Oxide and Bismuth (III) Oxide Reinforcement
Authors: ALMisned Ghada , Tekin Huseyin O. , Kavaz Esra , Bilal Ghaida , Issa Shams A.M. , Zakaly Hesham M.H. , Ene Antoaneta
Published: July 2021

The purpose of this research was to investigate the shielding characteristics of high-amount heavy metal oxide and Eu3+-activated borate glasses based on 10La2O3–50HMO–(40–x) B2O3–xEu2O3 (x = 0, 0.5, 1, 2, and HMO = PbO, Bi2O3). Critical gamma radiation attenuation characteristics, particularly mass attenuation coefficients of investigated heavy metal oxide glass samples, were determined using Monte Carlo simulations and the Phy-x/PSD software. Following that, we looked at the half-value layer, mean free path, effective atomic number, and build-up factors across a broad energy range (0.015–15 MeV). According to the study’s results, the addition of Eu2O3 enhanced the mass attenuation coefficient and effective atomic number, while reducing the half-value layer, mean free path, and accumulation factors. In terms of gamma radiation attenuation, the LBi50BEu glass system surpassed the LPb50BEu glass system in terms of overall shielding properties against nuclear radiation. Additionally, the heavy metal oxide glass’ efficacy as a neutron shield was determined using fast neutron removal cross-sections (ΣR). LBi50BEu2 glass was shown to be more effective in preventing the penetration of charged particle radiation.
Preparation and Properties of Wood Plastic Composites with Desirable Features Using Poplar and Five Recyclable Plastic Wastes
Authors: Yu Qinghan , Wang Yang , Ye Haoran , Sheng Yequan , Shi Yang , Zhang Minglong , Fan Wei , Yang Rui , Xia Changlei , Ge Shengbo
Published: July 2021

This study evaluated the mechanical and hydrophobic properties of wood plastic composites (WPC) prepared by the hot molding approach incorporating five different recycled plastics and poplar flour. The WPC showed excellent tensile strength (36.9 MPa) and flexural strength (44.7 MPa) associated with good hydrophobicity, and the excellent properties of WPC could be due to the application of hot pressing which improved the amount of hydroxyl groups and reduced the crystallinity of WPC. The WPC also revealed a strong and hydrostable structure and negligible emission of formaldehyde during the preparation process. Overall, the WPC could be used to substitute traditional wood-based panels as potential furniture material, hence achieving sustainable utilization of plastic wastes.
BengaliNet: A Low-Cost Novel Convolutional Neural Network for Bengali Handwritten Characters Recognition
Authors: Sayeed Abu , Shin Jungpil , Hasan Md. Al Mehedi , Srizon Azmain Yakin , Hasan Md. Mehedi
Published: July 2021

As it is the seventh most-spoken language and fifth most-spoken native language in the world, the domain of Bengali handwritten character recognition has fascinated researchers for decades. Although other popular languages i.e., English, Chinese, Hindi, Spanish, etc. have received many contributions in the area of handwritten character recognition, Bengali has not received many noteworthy contributions in this domain because of the complex curvatures and similar writing fashions of Bengali characters. Previously, studies were conducted by using different approaches based on traditional learning, and deep learning. In this research, we proposed a low-cost novel convolutional neural network architecture for the recognition of Bengali characters with only 2.24 to 2.43 million parameters based on the number of output classes. We considered 8 different formations of CMATERdb datasets based on previous studies for the training phase. With experimental analysis, we showed that our proposed system outperformed previous works by a noteworthy margin for all 8 datasets. Moreover, we tested our trained models on other available Bengali characters datasets such as Ekush, BanglaLekha, and NumtaDB datasets. Our proposed architecture achieved 96–99% overall accuracies for these datasets as well. We believe our contributions will be beneficial for developing an automated high-performance recognition tool for Bengali handwritten characters.
A Multi-Nuclear MAS-NMR Study on the Structural Properties of Silicalite-1 Zeolite Synthesized Using N- and P-Based Organic Structure Directing Agents
Authors: Martinez-Ortigosa Joaquin , Simancas Jorge , Vidal-Moya Jose A. , Rey Fernando , Valencia Susana , Blasco Teresa
Published: July 2021

The nature of organic structure directing agents (OSDAs) is of paramount importance in the final properties of zeolites, particularly the framework and porosity. Recently, the use of P-containing OSDAs has been employed for new zeolites, but there is little discussion compared to their analogues N-OSDAs. The main objective of this work is the characterization of pure silica MFI zeolite (silicalite-1) prepared by the dual-template route with tetrapropylammonium (TPA), tetrapropylphosphonium (TPP) cations, and mixtures thereof aiming to understand by advanced NMR methods how the nature of the organic influences the physico-chemical properties of the zeolite. Silicalite-1 has been successfully synthesized using the dual-template procedure with TPA and TPP molecules. Both OSDAs are incorporated into the zeolite without any specific preference, differently to that observed before for the TEA/TEP system, and homogenously mixed inside of the zeolite voids. The presence of TPP leads to the incorporation of less F, raising the concentration of Q3-defective sites in the silicalite-1 zeolites. Detailed NMR results indicate that those structural defects are close to the –CH3 group of the entrapped OSDAs in the zeolite and these defects consist of at least two silanol groups stabilizing the Si-O- species, which is responsible for the charge balancing.
A Study on a Prediction Model of E-Bike Expansion Degree at Irregular Signalized Intersections
Authors: Tan Ting , Ma Jianxiao , Yang Zhen , Zhu Mengyue , Zong Chenhong , Li Hao
Published: July 2021

The deviations of straight-going traffic at irregular signalized intersections lead to obvious expansion characteristics of e-bikes. This situation increases the possibility of collisions between motor vehicles and e-bikes. In order to study the change of expansion degree of straight-going e-bike at irregular signalized intersections, the video trajectory extraction technology is used to obtain relevant data of e-bikes during green light release periods at irregular signalized intersections. In addition, we combined the flow and spacing characteristics of e-bikes and used a clustering method to analyze the release stage and release groups. Therefore, the Group 1 of e-bikes in the early green light release was determined to be the main research object of expansion degree. According to the static and dynamic factors, a prediction model for the expansion degree of straight-going e-bikes at irregular signalized intersections was established based on the beetle antennae search–back propagation (BAS-BP) neural network model. Finally, the evaluation indexes were compared and analyzed before and after the beetle antennae search (BAS) algorithm optimization. The results showed that the BAS-BP neural network prediction model was better than that of the back propagation (BP) neural network. The results could provide a theoretical reference for improving the efficiency of mixed traffic flow at irregular signalized intersections.
Outpatient Total Hip Arthroplasty: A Meta-Analysis
Authors: Migliorini Filippo , Cipollaro Lucio , Cuozzo Francesco , Oliva Francesco , Marino Andrea Valerio , Maffulli Nicola
Published: July 2021

Introduction: Outpatient total hip arthroplasty (THA) is increasingly popular. This meta-analysis investigated the potential advantages of outpatient regimes for THA. Methods: This study followed the PRISMA guidelines. PubMed, Web of Science, Google Scholar, Embase, and Scopus databases were accessed in June 2021. All clinical studies investigating outpatient THA were considered. The outcomes of interest were pain, infection, mortality, revision, dislocation, readmission rates, and deep vein thrombosis (DVT). Results: Data from 102,839 patients were included. A total of 52% (153,168 of 102,839 patients) were women. The mean age of patients was 62.6 ± 4.6 years, the mean BMI was 29.1 ± 1.8 kg/m2. Good comparability was found in age, BMI, and gender (p > 0.1). No difference was found in pain (p = 0.4), infections (p = 0.9), mortality (p = 0.9), rate of revision (p = 0.1), dislocation (p = 0.9), and readmission (p = 0.8). The outpatient group demonstrated a greater rate of DVT (OR 3.57; 95% CI 2.47 to 5.18; p < 0.0001). Conclusions: In selected patients, outpatient THA can be performed safely with optimal outcomes comparable with inpatient THA. Clear and comprehensive pre-operative planning should involve a multi-disciplinary group composed of orthopaedic surgeons, anaesthesia and rehabilitation specialists, and physiotherapists. Each centre performing outpatient THA should implement continuous homecoming welfare activity, to supervise physiotherapy and monitor anticoagulant therapy.
Are Shell Strength Phenotypic Traits in Mussels Associated with Species Alone?
Authors: Carboni Stefano , Evans Sarah , Tanner K. Elizabeth , Davie Andrew , Bekaert Michaël , Fitzer Susan C.
Published: July 2021

Mussels often hybridise to form the Mytilus species complex comprised of M. edulis and M. galloprovincialis as the main species cultivated in Europe and, where their geographical distribution overlaps, the species M. trossulus. It has been suggested that M. trossulus have a weaker shell than the UK native M. edulis and hybridisation reduces farmed mussel yields and overall fitness. Here, we investigate the hypothesised link between species and shell weakness, employing multi-locus genotyping combined with measurements of six different phenotypes indicative of shell strength (shell thickness, flexural strength, Young’s modulus, Vicker’s hardness, fracture toughness, calcite and aragonite crystallographic orientation). Historic evidence from shell strength studies assumed species designation based on geographical origin, single locus DNA marker or allozyme genetic techniques that are limited in their ability to discern hybrid individuals. Single nucleotide polymorphic markers have now been developed with the ability to better distinguish between the species of the complex and their hybrids. Our study indicates that shell strength phenotypic traits are less associated with species than previously thought. The application of techniques outlined in this study challenges the historic influence of M. trossulus hybridisation on mussel yields and opens up potential for the environment to determine mussel shell fitness.
Tracking the Endogenous Dynamics of the Solfatara Volcano (Campi Flegrei, Italy) through the Analysis of Ground Thermal Image Temperatures
Authors: Cusano Paola , Caputo Teresa , De Lauro Enza , Falanga Mariarosaria , Petrosino Simona , Sansivero Fabio , Vilardo Giuseppe
Published: July 2021

In the last decades, thermal infrared ground-based cameras have become effective tools to detect significant spatio-temporal anomalies in the hydrothermal/volcanic environment, possibly linked to impending eruptions. In this paper, we analyzed the temperature time-series recorded by the ground-based Thermal Infrared Radiometer permanent network of INGV-OV, installed inside the Solfatara-Pisciarelli area, the most active fluid emission zones of the Campi Flegrei caldera (Italy). We investigated the temperatures’ behavior in the interval 25 June 2016–29 May 2020, with the aim of tracking possible endogenous hydrothermal/volcanic sources. We performed the Independent Component Analysis, the time evolution estimation of the spectral power, the cross-correlation and the Changing Points’ detection. We compared the obtained patterns with the behavior of atmospheric temperature and pressure, of the time-series recorded by the thermal camera of Mt. Vesuvius, of the local seismicity moment rate and of the CO2 emission flux. We found an overall influence of exogenous, large scale atmospheric effect, which dominated in 2016–2017. Starting from 2018, a clear endogenous forcing overcame the atmospheric factor, and dominated strongly soil temperature variations until the end of the observations. This paper highlights the importance of monitoring and investigating the soil temperature in volcanic environments, as well as the atmospheric parameters.
A Comparison of HWRF Six-Hourly 4DEnVar and Hourly 3DEnVar Assimilation of Inner Core Tail Dopper Radar Observations for the Prediction of Hurricane Edouard (2014)
Authors: Davis Benjamin , Wang Xuguang , Lu Xu
Published: July 2021

Six-hourly three-dimensional ensemble variational (3DEnVar) (6H-3DEnVar) data assimilation (DA) assumes constant background error covariance (BEC) during a six-hour DA window and is, therefore, unable to account for temporal evolution of the BEC. This study evaluates the one-hourly 3DEnVar (1H-3DEnVar) and six-hourly 4DEnVar (6H-4DEnVar) DA methods for the analyses and forecasts of hurricanes with rapidly evolving BEC. Both methods account for evolving BEC in a hybrid EnVar DA system. In order to compare these methods, experiments are conducted by assimilating inner core Tail Doppler Radar (TDR) wind for Hurricane Edouard (2014) and by running the Hurricane Weather Research and Forecasting (HWRF) model. In most metrics, 1H-3DEnVar and 6H-4DEnVar analyses and forecasts verify better than 6H-3DEnVar. 6H-4DEnVar produces better thermodynamic analyses than 1H-3DEnVar. Radar reflectivity shows that 1H-3DEnVar produces better structure forecasts. For the first 24–48 h of the intensity forecast, 6H-4DEnVar forecast performs better than 1H-3DEnVar verified against the best track. Degraded 1H-3DEnVar forecasts are found to be associated with background storm center location error as a result of underdispersive ensemble storm center spread. Removing location error in the background improves intensity forecasts of 1H-3DEnVar.
Assimilation of Leaf Area Index and Soil Water Index from Satellite Observations in a Land Surface Model in Hungary
Authors: Tóth Helga , Szintai Balázs
Published: July 2021

In this study, a Land Data Assimilation System (LDAS) is applied over the Carpathian Basin at the Hungarian Meteorological Service to monitor the above-ground biomass, surface fluxes (carbon and water), and the associated root-zone soil moisture at the regional scale (spatial resolution of 8 km × 8 km) in quasi-real-time. In this system the SURFEX model is used, which applies the vegetation growth version of the Interactions between Soil, Biosphere and Atmosphere (ISBA-A-gs) photosynthesis scheme to describe the evolution of vegetation. SURFEX is forced using the outputs of the ALADIN numerical weather prediction model run operationally at the Hungarian Meteorological Service. First, SURFEX is run in an open-loop (i.e., no assimilation) mode for the period 2008–2015. Secondly, the Extended Kalman Filter (EKF) method is used to assimilate Leaf Area Index (LAI) Spot/Vegetation (until May 2014) and PROBA-V (from June 2014) and Soil Water Index (SWI) ASCAT/Metop satellite measurements. The benefit of LDAS is proved over the whole country and to a selected site in West Hungary (Hegyhátsál). It is demonstrated that the EKF can provide useful information both in wet and dry seasons as well. It is shown that the data assimilation is efficient to describe the inter-annual variability of biomass and soil moisture values. The vegetation development and the water and carbon fluxes vary from season to season and LDAS is a capable tool to monitor the variability of these parameters.
Critical Indices and Self-Similar Power Transform
Authors: Gluzman Simon
Published: July 2021

“Odd” factor approximants of the special form suggested by Gluzman and Yukalov (J. Math. Chem. 2006, 39, 47) are amenable to optimization by power transformation and can be successfully applied to critical phenomena. The approach is based on the idea that the critical index by itself should be optimized through the parameters of power transform to be calculated from the minimal sensitivity (derivative) optimization condition. The critical index is a product of the algebraic self-similar renormalization which contributes to the expressions the set of control parameters typical to the algebraic self-similar renormalization, and of the power transform which corrects them even further. The parameter of power transformation is, in a nutshell, the multiplier connecting the critical exponent and the correction-to-scaling exponent. We mostly study the minimal model of critical phenomena based on expansions with only two coefficients and critical points. The optimization appears to bring quite accurate, uniquely defined results given by simple formulas. Many important cases of critical phenomena are covered by the simple formula. For the longer series, the optimization condition possesses multiple solutions, and additional constraints should be applied. In particular, we constrain the sought solution by requiring it to be the best in prediction of the coefficients not employed in its construction. In principle, the error/measure of such prediction can be optimized by itself, with respect to the parameter of power transform. Methods of calculation based on optimized power-transformed factors are applied and results presented for critical indices of several key models of conductivity and viscosity of random media, swelling of polymers, permeability in two-dimensional channels. Several quantum mechanical problems are discussed as well.
TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus
Authors: Ramirez-Malule Howard , López-Agudelo Víctor , Gómez-Ríos David , Ochoa Silvia , Ríos-Estepa Rigoberto , Junne Stefan , Neubauer Peter
Published: July 2021

Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of β-lactamase enzymes. In this study, S. clavuligerus cultivated in 2D rocking bioreactor in fed-batch operation produced CA at comparable rates to those observed in stirred tank bioreactors. A reduced model of S. clavuligerus metabolism was constructed by using a bottom-up approach and validated using experimental data. The reduced model was implemented for in silico studies of the metabolic scenarios arisen during the cultivations. Constraint-based analysis confirmed the interrelations between succinate, oxaloacetate, malate, pyruvate, and acetate accumulations at high CA synthesis rates in submerged cultures of S. clavuligerus. Further analysis using shadow prices provided a first view of the metabolites positive and negatively associated with the scenarios of low and high CA production.
Optimization of a New Antihyperglycemic Formulation Using a Mixture of Linum usitatissimum L., Coriandrum sativum L., and Olea europaea var. sylvestris Flavonoids: A Mixture Design Approach
Authors: Mechchate Hamza , Ouedrhiri Wessal , Es-safi Imane , Amaghnouje Amal , Jawhari Fatima zahra , Bousta Dalila
Published: July 2021

Flavonoids are a class of natural chemicals with variable phenolic structures that have long been recognized for their health advantages, they have recently attracted researchers’ attention for treating diabetes and hyperglycemia. The goal of this research is to develop a novel antihyperglycemic formulation using a combination of three plant flavonoids: Linum usitatissimum L. seeds (FLU), Coriandrum sativum L. seeds (FCS), and Olea europaea var. sylvestris leaves (FOE) based on a mixture design experiment approach which generates the most effective ratio of each component in a mixture instead of the trial-and-error method. Prior to the test, sub-acute toxicity research was conducted to establish a safe and effective dosage. The Oral Glucose Tolerance Test (OGTT) was used to assess the antihyperglycemic impact of these extracts and their combinations in Swiss albino mice. The dose that showed efficacy and safety was 25 mg/kg, which was utilized in all formulations. According to the results, the binary and ternary combinations showed the most significant synergetic effects. The optimum combination with the most potent effect was 37% FLU, 20% FCS, and 43% FOE. This study’s mixture design and prediction model for glycemic variation (GV) may be utilized at an industrial level to develop a novel antidiabetic and antihyperglycemic formulation that is safe and effective.
Mutual Interactions between Brain States and Alzheimer’s Disease Pathology: A Focus on Gamma and Slow Oscillations
Authors: Byron Nicole , Semenova Anna , Sakata Shuzo
Published: July 2021

Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer’s disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.
Cannabinoids Accumulation in Hemp (Cannabis sativa L.) Plants under LED Light Spectra and Their Discrete Role as a Stress Marker
Authors: Islam Md. Jahirul , Ryu Byeong Ryeol , Azad Md. Obyedul Kalam , Rahman Md. Hafizur , Cheong Eun Ju , Lim Jung-Dae , Lim Young-Seok
Published: July 2021

Hemp adaptability through physiological and biochemical changes was studied under 10 LED light spectra and natural light in a controlled aeroponic system. Light treatments were imposed on 25 days aged seedlings for 16 h daily (300 µmol m−2 s−1) for 20 days. Plant accumulated highest Cannabidiol (CBD) in R7:B2:G1 light treatment, with relatively higher photosynthetic rate and lower reactive oxygen species, total phenol content, total flavonoid content, DPPH radical scavenging capacity, and antioxidant enzymatic activities. Tetrahydrocannabinol (THC) also accumulated at a higher level in white, R8:B2, and R7:B2:G1 light with less evidence of stress-modulated substances. These results indicated that CBD and THC have no or little relation with light-mediated abiotic stress in hemp plants. On the contrary, Tetrahydrocannabinolic acid (THCA) was accumulated higher in R6:B2:G1:FR1 and R5:B2:W2:FR1 light treatment along with lower photosynthetic rate and higher reactive oxygen species, total phenol content, total flavonoid content, DPPH radical scavenging capacity, and antioxidant enzymatic activities. However, Cannabidiolic acid (CBDA) was accumulated higher in R6:B2:G1:FR1 light treatment with higher stress-modulated substances and lower physiological traits. CBDA was also accumulated higher in R8:B2 and R7:B2:G1 light treatments with less evidence of stress-modulated substances. Besides, Greenlight influenced CBD and CBDA synthesis where FR and UV-A (along with green) play a positive and negative role in this process. Overall, the results indicated that the treatment R7:B2:G1 enhanced the medicinal cannabinoids most, and the role of THCA as a stress marker is more decisive in the hemp plant than in other cannabinoids under attributed light-mediated stress.
hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease
Authors: Thibault Patricia A. , Ganesan Aravindhan , Kalyaanamoorthy Subha , Clarke Joseph-Patrick W. E. , Salapa Hannah E. , Levin Michael C.
Published: July 2021

The hnRNP A/B family of proteins is canonically central to cellular RNA metabolism, but due to their highly conserved nature, the functional differences between hnRNP A1, A2/B1, A0, and A3 are often overlooked. In this review, we explore and identify the shared and disparate homeostatic and disease-related functions of the hnRNP A/B family proteins, highlighting areas where the proteins have not been clearly differentiated. Herein, we provide a comprehensive assembly of the literature on these proteins. We find that there are critical gaps in our grasp of A/B proteins’ alternative splice isoforms, structures, regulation, and tissue and cell-type-specific functions, and propose that future mechanistic research integrating multiple A/B proteins will significantly improve our understanding of how this essential protein family contributes to cell homeostasis and disease.
Specification and Evaluation of Plasticizer Migration Simulants for Human Blood Products: A Delphi Study
Authors: Thelliez Aurélie , Hénard Grégory , Delorme Bruno , Chatellier Sonia , Danel Cécile , Ducoroy Laurent , Dupont Annabelle , Garrigue Delphine , Genay Stéphanie , Goossens Jean-François , Goossens Laurence , Havet Coralie , Hecq Jean-Daniel , Maeght Caroline , Mendel Isabelle , Najdovski Tomé , Odou Pascal , Saint-Lorant Guillaume , Ung Alexandre , Lecoeur Marie , Décaudin Bertrand
Published: July 2021

Potentially toxic plasticizers are commonly added to polyvinyl chloride medical devices for transfusion in order to improve their flexibility and workability. As the plasticizers are not chemically bonded to the PVC, they can be released into labile blood products (LBPs) during storage. Ideally, LBPs would be used in laboratory studies of plasticizer migration from the medical device. However, short supply (i.e., limited stocks of human blood in collection centres) has prompted the development of specific simulants for each type of LBP in the evaluation of new transfusion devices. We performed a Delphi study with a multidisciplinary panel of 24 experts. In the first (qualitative) phase, the panel developed consensus definitions of the specification criteria to be met by each migration simulant. Next, we reviewed the literature on techniques for simulating the migration of plasticizers into LBPs. A questionnaire was elaborated and sent out to the experts, and the replies were synthesized in order to obtain a consensus. The qualitative study established specifications for each biological matrix (whole blood, red blood cell concentrate, plasma, and platelet concentrate) and defined the criteria required for a suitable LBP simulant. Ten criteria were suggested: physical and chemical characteristics, opacity, form, stability, composition, ability to mimic a particular clinical situation, ease and safety of use, a simulant–plastic interaction correlated with blood, and compatibility with analytical methods. The questionnaire data revealed a consensus on the use of natural products (such as pig’s blood) to mimic the four LBPs. Opinions diverged with regard to synthetic products. However, an isotonic solution and a rheological property modifier were considered to be of value in the design of synthetic simulants. Consensus reached by the Delphi group could be used as a database for the development of simulants used to assess the migration of plasticizers from PVC bags into LBPs.
FGF1 Fusions with the Fc Fragment of IgG1 for the Assembly of GFPpolygons-Mediated Multivalent Complexes Recognizing FGFRs
Authors: Poźniak Marta , Zarzycka Weronika , Porębska Natalia , Knapik Agata , Marczakiewicz-Perera Paulina , Zakrzewska Malgorzata , Otlewski Jacek , Opaliński Łukasz
Published: July 2021

FGFRs are cell surface receptors that, when activated by specific FGFs ligands, transmit signals through the plasma membrane, regulating key cellular processes such as differentiation, division, motility, metabolism and death. We have recently shown that the modulation of the spatial distribution of FGFR1 at the cell surface constitutes an additional mechanism for fine-tuning cellular signaling. Depending on the multivalent, engineered ligand used, the clustering of FGFR1 into diverse supramolecular complexes enhances the efficiency and modifies the mechanism of receptor endocytosis, alters FGFR1 lifetime and modifies receptor signaling, ultimately determining cell fate. Here, we present a novel approach to generate multivalent FGFR1 ligands. We functionalized FGF1 for controlled oligomerization by developing N- and C-terminal fusions of FGF1 with the Fc fragment of human IgG1 (FGF1-Fc and Fc-FGF1). As oligomerization scaffolds, we employed GFPpolygons, engineered GFP variants capable of well-ordered multivalent display, fused to protein G to ensure binding of Fc fragment. The presented strategy allows efficient assembly of oligomeric FGFR1 ligands with up to twelve receptor binding sites. We show that multivalent FGFR1 ligands are biologically active and trigger receptor clustering on the cell surface. Importantly, the approach described in this study can be easily adapted to oligomerize alternative growth factors to control the activity of other cell surface receptors.
A Novel Knowledge Distillation-Based Feature Selection for the Classification of ADHD
Authors: Khan Naseer Ahmed , Waheeb Samer Abdulateef , Riaz Atif , Shang Xuequn
Published: July 2021

Attention Deficit Hyperactivity Disorder (ADHD) is a brain disorder with characteristics such as lack of concentration, excessive fidgeting, outbursts of emotions, lack of patience, difficulty in organizing tasks, increased forgetfulness, and interrupting conversation, and it is affecting millions of people worldwide. There is, until now, not a gold standard test using which an ADHD expert can differentiate between an individual with ADHD and a healthy subject, making accurate diagnosis of ADHD a challenging task. We are proposing a Knowledge Distillation-based approach to search for discriminating features between the ADHD and healthy subjects. Learned embeddings from a large neural network, trained on the functional connectivity features, were fed to one hidden layer Autoencoder for reproduction of the embeddings using the same connectivity features. Finally, a forward feature selection algorithm was used to select a combination of most discriminating features between the ADHD and the Healthy Controls. We achieved promising classification results for each of the five individual sites. A combined accuracy of 81% in KKI, 60% Peking, 56% in NYU, 64% NI, and 56% OHSU and individual site wise accuracy of 72% in KKI, 60% Peking, 73% in NYU, 70% NI, and 71% OHSU were obtained using our extracted features. Our results also outperformed state-of-the-art methods in literature which validates the efficacy of our proposed approach.
NF-κB in Gastric Cancer Development and Therapy
Authors: Chaithongyot Supattra , Jantaree Phatcharida , Sokolova Olga , Naumann Michael
Published: July 2021

Gastric cancer is considered one of the most common causes of cancer-related death worldwide and, thus, a major health problem. A variety of environmental factors including physical and chemical noxae, as well as pathogen infections could contribute to the development of gastric cancer. The transcription factor nuclear factor kappa B (NF-κB) and its dysregulation has a major impact on gastric carcinogenesis due to the regulation of cytokines/chemokines, growth factors, anti-apoptotic factors, cell cycle regulators, and metalloproteinases. Changes in NF-κB signaling are directed by genetic alterations in the transcription factors themselves, but also in NF-κB signaling molecules. NF-κB actively participates in the crosstalk of the cells in the tumor micromilieu with divergent effects on the heterogeneous tumor cell and immune cell populations. Thus, the benefits/consequences of therapeutic targeting of NF-κB have to be carefully evaluated. In this review, we address recent knowledge about the mechanisms and consequences of NF-κB dysregulation in gastric cancer development and therapy.
Childhood Obesity-Related Mechanisms: MicroRNome and Transcriptome Changes in a Nested Case-Control Study
Authors: Kim Jin Hee , Kim Da Hae , Lim Youn-Hee , Shin Choong Ho , Lee Young Ah , Kim Bung-Nyun , Kim Johanna Inhyang , Hong Yun-Chul
Published: July 2021

Childhood obesity could contribute to adulthood obesity, leading to adverse health outcomes in adults. However, the mechanisms for how obesity is developed are still unclear. To determine the epigenome-wide and genome-wide expression changes related with childhood obesity, we compared microRNome and transcriptome levels as well as leptin protein levels in whole bloods of 12 obese and 24 normal children aged 6 years. miR-328-3p, miR-1301-3p, miR-4685-3p, and miR-6803-3p were negatively associated with all obesity indicators. The four miRNAs were also associated with 3948 mRNAs, and separate 475 mRNAs (185 among 3948 mRNAs) were associated with all obesity indicators. The 2533 mRNAs (64.2%) among the 3948 mRNAs and 286 mRNAs (60.2%) among the 475 mRNAs were confirmed as targets of the four miRNAs in public databases through miRWalk 2.0. Leptin protein was associated with miR-6803-3p negatively and all obesity indicators positively. Using DAVID bioinformatics resources 6.8, top three pathways for obesity-related gene set were metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. The top three obesity-related disease classes were metabolic, cardiovascular, and chemdependency. Our results support that childhood obesity could be developed through miRNAs-related epigenetic mechanism and, further, these obesity-related epigenetic changes could control the pathways related with the development of various diseases.
Structural and Functional Alterations in Mitochondria-Associated Membranes (MAMs) and in Mitochondria Activate Stress Response Mechanisms in an In Vitro Model of Alzheimer’s Disease
Authors: Fernandes Tânia , Resende Rosa , Silva Diana F. , Marques Ana P. , Santos Armanda E. , Cardoso Sandra M. , Domingues M. Rosário , Moreira Paula I. , Pereira Cláudia F.
Published: July 2021

Alzheimer’s disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-β (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events modulated by these subcellular domains. In this study, we characterized the structural and functional alterations at MAM, mitochondria, and ER/microsomes in a mouse neuroblastoma cell line (N2A) overexpressing the human amyloid precursor protein (APP) with the familial Swedish mutation (APPswe). Proteins levels were determined by Western blot, ER-mitochondria contacts were quantified by transmission electron microscopy, and Ca2+ homeostasis and mitochondria function were analyzed using fluorescent probes and Seahorse assays. In this in vitro AD model, we found APP accumulated in MAM and mitochondria, and altered levels of proteins implicated in ER-mitochondria tethering, Ca2+ signaling, mitochondrial dynamics, biogenesis and protein import, as well as in the stress response. Moreover, we observed a decreased number of close ER-mitochondria contacts, activation of the ER unfolded protein response, reduced Ca2+ transfer from ER to mitochondria, and impaired mitochondrial function. Together, these results demonstrate that several subcellular alterations occur in AD-like neuronal cells, which supports that the defective ER-mitochondria crosstalk is an important player in AD physiopathology.
Circulatory Inflammatory Mediators in the Prediction of Anti-Tuberculous Drug-Induced Liver Injury Using RUCAM for Causality Assessment
Authors: Ho Cheng-Maw , Chen Chi-Ling , Chang Chia-Hao , Lee Meng-Rui , Wang Jann-Yuan , Hu Rey-Heng , Lee Po-Huang
Published: July 2021

Background: Anti-tuberculous (TB) medications are common causes of drug-induced liver injury (DILI). Limited data are available on systemic inflammatory mediators as biomarkers for predicting DILI before treatment. We aimed to select predictive markers among potential candidates and to formulate a predictive model of DILI for TB patients. Methods: Adult active TB patients from a prospective cohort were enrolled, and all participants received standard anti-tuberculous treatment. Development of DILI, defined as ≥5× ULN for alanine transaminase or ≥2.6× ULN of total bilirubin with causality assessment (RUCAM, Roussel Uclaf causality assessment method), was regularly monitored. Pre-treatment plasma was assayed for 15 candidates, and a set of risk prediction scores was established using Cox regression and receiver-operating characteristic analyses. Results: A total of 19 (7.9%) in 240 patients developed DILI (including six carriers of hepatitis B virus) following anti-TB treatment. Interleukin (IL)-22 binding protein (BP), interferon gamma-induced protein 1 (IP-10), soluble CD163 (sCD163), IL-6, and CD206 were significant univariable factors associated with DILI development, and the former three were backward selected as multivariable factors, with adjusted hazards of 0.20 (0.07–0.58), 3.71 (1.35–10.21), and 3.28 (1.07–10.06), respectively. A score set composed of IL-22BP, IP-10, and sCD163 had an improved area under the curve of 0.744 (p < 0.001). Conclusions: Pre-treatment IL-22BP was a protective biomarker against DILI development under anti-TB treatment, and a score set by additional risk factors of IP-10 and sCD163 employed an adequate DILI prediction.
Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway
Authors: Shimada Hiroki , Yamazaki Yuto , Sugawara Akira , Sasano Hironobu , Nakamura Yasuhiro
Published: July 2021

The adrenal cortex produces steroid hormones as adrenocortical hormones in the body, secreting mineralocorticoids, glucocorticoids, and adrenal androgens, which are all considered essential for life. Adrenocortical tumors harbor divergent hormonal activity, frequently with steroid excess, and disrupt homeostasis of the body. Aldosterone-producing adenomas (APAs) cause primary aldosteronism (PA), and cortisol-producing adenomas (CPAs) are the primary cause of Cushing’s syndrome. In addition, adrenocortical carcinoma (ACC) is a highly malignant cancer harboring poor prognosis. Various genetic abnormalities have been reported, which are associated with possible pathogenesis by the alteration of intracellular signaling and activation of transcription factors. In particular, somatic mutations in APAs have been detected in genes encoding membrane proteins, especially ion channels, resulting in hypersecretion of aldosterone due to activation of intracellular calcium signaling. In addition, somatic mutations have been detected in those encoding cAMP-PKA signaling-related factors, resulting in hypersecretion of cortisol due to its driven status in CPAs. In ACC, mutations in tumor suppressor genes and Wnt-β-catenin signaling-related factors have been implicated in its pathogenesis. In this article, we review recent findings on the genetic characteristics and regulation of intracellular signaling and transcription factors in individual tumors.