bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Simulation of a Special Class of Time-Inhomogeneous Diffusion Processes
Authors: Giorno Virginia , Nobile Amelia G.
Published: April 2021

General methods to simulate probability density functions and first passage time densities are provided for time-inhomogeneous stochastic diffusion processes obtained via a composition of two Gauss–Markov processes conditioned on the same initial state. Many diffusion processes with time-dependent infinitesimal drift and infinitesimal variance are included in the considered class. For these processes, the transition probability density function is explicitly determined. Moreover, simulation procedures are applied to the diffusion processes obtained starting from Wiener and Ornstein–Uhlenbeck processes. Specific examples in which the infinitesimal moments include periodic functions are discussed.
Influence of Impulse Disturbances on Oscillations of Nonlinearly Elastic Bodies
Authors: Andrukhiv Andriy , Sokil Mariia , Sokil Bohdan , Fedushko Solomiia , Syerov Yuriy , Karovic Vincent , Klynina Tetiana
Published: April 2021

A method for studying the effect of impulse perturbation on the longitudinal oscillations of a homogeneous constant cross-section of the body and the elastic properties of a material which satisfies the essentially nonlinear law of elasticity has been developed. A mathematical model of the process is presented, which is an equation of hyperbolic type with a small parameter at the discrete right-hand side. The latter expresses the effect of impulse perturbation on the oscillatory process. As for the boundary conditions considered in the work, they are classic of the first, second and third genera. The methodology is based on: the principle of oscillation frequency in nonlinear systems with many degrees of freedom and distributed parameters; basic provisions of asymptotic methods of nonlinear mechanics; the idea of using special periodic Ateb-functions to construct solutions of some classes of nonlinear differential equations; properties of completeness and orthonormality of functions that describe the forms of oscillations of undisturbed motion. In general, the above allowed to obtain relations that describe for the first approximation the defining parameters of the oscillations of an elastic body. Their peculiarity is that even for undisturbed motion, the natural frequency of oscillations depends on the amplitude, and therefore, under the action of a periodic (over time) pulse force on the elastic body, both resonant and nonresonant processes are possible in the latter. It, in contrast to an elastic body with linear or quasilinear elastic properties of the body is determined not only by its basic physical and mechanical properties, but also by the amplitude of oscillations. As a special case, the oscillations of the body under the action of a constant periodic momentum perturbation are considered. It is shown that for the nonresonant case for the first approximation it does not affect the laws of change of amplitude and frequency of the process. As for the resonant is the amplitude of origin through the main resonance significantly depends not only on the speed but also on the points of action of the pulsed perturbation. Moreover, the closer the point of application of the pulsed force to the middle of the elastic body under boundary conditions of the first kind is greater (for boundary conditions of the second kind closer to the end).
Functional Symmetry and Statistical Depth for the Analysis of Movement Patterns in Alzheimer’s Patients
Authors: Nieto-Reyes Alicia , Battey Heather , Francisci Giacomo
Published: April 2021

Black-box techniques have been applied with outstanding results to classify, in a supervised manner, the movement patterns of Alzheimer’s patients according to their stage of the disease. However, these techniques do not provide information on the difference of the patterns among the stages. We make use of functional data analysis to provide insight on the nature of these differences. In particular, we calculate the center of symmetry of the underlying distribution at each stage and use it to compute the functional depth of the movements of each patient. This results in an ordering of the data to which we apply nonparametric permutation tests to check on the differences in the distribution, median and deviance from the median. We consistently obtain that the movement pattern at each stage is significantly different to that of the prior and posterior stage in terms of the deviance from the median applied to the depth. The approach is validated by simulation.
Reliability Measures and Profit Exploration of Windmill Water-Pumping Systems Incorporating Warranty and Two Types of Repair
Authors: Goyal Nupur , Ram Mangey , Kumar Akshay , Bisht Soni , Klochkov Yury
Published: April 2021

Wind energy is a kind of renewable energy that plays a significant role in remote areas for pumping water. The windmill is also used to generate electricity. The windmill is also known as a wind pump when it is used for pumping water. In this work, the authors proposed a complex hybrid model of an example of combined system (windmill, rechargeable battery and pumping system) to evaluate the system’s performance. System performance was affected by system degradation due to system failure. These factors also affected the profit of the user. Two types of repair facilities for continuous and satisfactory performance of the system were assumed. To illustrate the system modeling using the Gumbel–Hougaard family of the copula, numerical examples were used for the exploration of Markov results of the reliability measures and the profit of the system with the warranty period, with this also being demonstrated graphically.
Population-Based COVID-19 Screening in Mexico: Assessment of Symptoms and Their Weighting in Predicting SARS-CoV-2 Infection
Authors: Martinez-Fierro Margarita L , Diaz-Lozano Martha , Alvarez-Zuñiga Claudia , Ramirez-Hernandez Leticia A , Araujo-Espino Roxana , Trejo-Ortiz Perla M , Mollinedo-Montaño Fabiana E , Ortiz-Castro Yolanda , Vazquez-Reyes Sodel , Velasco-Elizondo Perla , Garcia-Esquivel Lidia , Araujo-Conejo Arturo , Garza-Veloz Idalia
Published: April 2021

Background and Objectives: Sentinel surveillance in the early stage of the COVID-19 pandemic in Mexico represented a significant cost reduction and was useful in estimating the population infected with SARS-CoV-2. However, it also implied that many patients were not screened and therefore had no accurate diagnosis. In this study, we carried out a population-based SARS-CoV-2 screening in Mexico to evaluate the COVID-19-related symptoms and their weighting in predicting SARS-CoV-2 infection. We also discuss this data in the context of the operational definition of suspected cases of COVID-19 established by the Mexican Health Authority’s consensus. Materials and Methods: One thousand two hundred seventy-nine subjects were included. They were screened for SARS-CoV-2 using RT-PCR. The weighting of COVID-19 symptoms in predicting SARS-CoV-2 infection was evaluated statistically. Results: Three hundred and twenty-five patients were positive for SARS-CoV-2 and 954 were negative. Fever, asthenia, dysgeusia, and oxygen saturation predicted SARS-CoV-2 infection (odds ratios ranged from 1.74 to 4.98; p < 0.05). The percentage of asymptomatic COVID-19 patients was 36% and only 38.15% met the Mexican operational definition. Cq-values for the gene N of SARS-CoV-2 were significantly higher in asymptomatic subjects than in the groups of COVID-19 patients with neurological, respiratory, and/or musculoskeletal manifestations (p < 0.05). Conclusions: Dysgeusia, fever, and asthenia increased the odds of a positive result for COVID-19 1.74–4.98-fold among the study population. Patients with neurological, respiratory, and/or musculoskeletal manifestations had higher viral loads at COVID-19 diagnosis than those observed in asymptomatic patients. A high percentage of the participants in the study (61.85%) did not meet the operational definition for a suspected case of COVID-19 established by the Mexican Health Authority’s consensus, representing a high percentage of the population that could have remained without a COVID-19 diagnosis, so becoming a potential source of virus spread.
Innovative Gas-Liquid Membrane Contactor Systems for Carbon Capture and Mineralization in Energy Intensive Industries
Authors: Asimakopoulou Akrivi , Koutsonikolas Dimitrios , Kastrinaki Georgia , Skevis George
Published: April 2021

CO2 mineralization is an alternative to conventional geological storage and results in permanent carbon storage as a solid, with no need for long-term monitoring and no requirements for significant energy input. Novel technologies for carbon dioxide capture and mineralization involve the use of gas-liquid membrane contactors for post-combustion capture. The scope of the present study is to investigate the application of hollow fiber membrane contactor technology for combined CO2 capture from energy-intensive industry flue gases and CO2 mineralization, in a single-step multiphase process. The process is also a key enabler of the circular economy for the cement industry, a major contributor in global industrial CO2 emissions, as CaCO3 particles, obtained through the mineralization process, can be directed back into the cement production as fillers for partially substituting cement in high-performance concrete. High CO2 capture efficiency is achieved, as well as CaCO3 particles of controlled size and crystallinity are synthesized, in every set of operating parameters employed. The intensified gas-liquid membrane process is assessed by calculating an overall process mass transfer coefficient accounting for all relevant mass transfer resistances and the enhanced mass transfer due to reactive conditions on the shell side. The obtained nanocomposite particles have been extensively characterized by DLS, XRD, TGA, SEM, TEM, and FTIR studies, revealing structured aggregates (1–2 μm average aggregate size) consisting of cubic calcite when the contactor mode is employed.
A Review of Damage, Void Evolution, and Fatigue Life Prediction Models
Authors: Lee Hsiao Wei , Basaran Cemal
Published: April 2021

Degradation, damage evolution, and fatigue models in the literature for various engineering materials, mostly metals and composites, are reviewed. For empirical models established under the framework of Newtonian mechanics, Gurson–Tvergaard–Needleman (GTN) type model, Johnson-Cook (J-C) type damage model, microplasticity model, some other micro-mechanism based damage models, and models using irreversible entropy as a metric with an empirical evolution function are thoroughly discussed. For Physics-based models, the development and applications of unified mechanics theory is reviewed.
Underwater Laser Welding of Pure Ti: Oxidation and Hardening Behaviors
Authors: Luo Manlelan , Wei Pengyu , Li Quanhong , Hu Renzhi , Huang Anguo , Pang Shengyong
Published: April 2021

The local dry underwater laser welding of cp-Ti, with air as an assisting gas, and in a simulated underwater facility was researched, aiming to find a viable and economical method for repairing titanium alloy underwater vehicles in situ in the future. Macro-morphology, microstructure, and microhardness of the cp-Ti laser welds, as a function of welding parameters, were experimentally characterized. The oxidation and hardening behaviors of the welds were also studied in detail. It was found that local dry underwater laser welding with air assisted blowing is feasible for obtaining a complete and glossy weld. Compared with a weld in atmosphere, the cross-section morphology of the weld was almost unaffected by the special underwater welding environment. The weld presented a three-layer structure. High temperature and high pressure water vapor and local blowing are the direct causes of weld oxidation, and porosity defects further aggravate the oxidation behavior. The oxygen-enriched areas were mostly concentrated in the top area of the weld center and near the fusion zone, because of the higher number of grain boundaries and phase boundaries. In addition, the partial oxidation caused by local blowing and water vapor atmosphere, and also the higher strength acicular martensite caused by the rapid cooling effect of water, will lead to weld hardening. However, adjusting the welding process parameters, such as increasing the welding speed, can effectively reduce the microhardness of the weld. Our findings can provide an understanding of the influence of water environment on underwater laser welding, and verify the feasibility of a more economical method for the in situ repair of large underwater facilities.
First Genome-Scale Metabolic Model of Dolosigranulum pigrum Confirms Multiple Auxotrophies
Authors: Renz Alina , Widerspick Lina , Dräger Andreas
Published: April 2021

Dolosigranulum pigrum is a quite recently discovered Gram-positive coccus. It has gained increasing attention due to its negative correlation with Staphylococcus aureus, which is one of the most successful modern pathogens causing severe infections with tremendous morbidity and mortality due to its multiple resistances. As the possible mechanisms behind its inhibition of S. aureus remain unclear, a genome-scale metabolic model (GEM) is of enormous interest and high importance to better study its role in this fight. This article presents the first GEM of D. pigrum, which was curated using automated reconstruction tools and extensive manual curation steps to yield a high-quality GEM. It was evaluated and validated using all currently available experimental data of D. pigrum. With this model, already predicted auxotrophies and biosynthetic pathways could be verified. The model was used to define a minimal medium for further laboratory experiments and to predict various carbon sources’ growth capacities. This model will pave the way to better understand D. pigrum’s role in the fight against S. aureus.
Cavity-BOX SOI: Advanced Silicon Substrate with Pre-Patterned BOX for Monolithic MEMS Fabrication
Authors: Kluba Marta Maria , Li Jian , Parkkinen Katja , Louwerse Marcus , Snijder Jaap , Dekker Ronald
Published: April 2021

Several Silicon on Insulator (SOI) wafer manufacturers are now offering products with customer-defined cavities etched in the handle wafer, which significantly simplifies the fabrication of MEMS devices such as pressure sensors. This paper presents a novel cavity buried oxide (BOX) SOI substrate (cavity-BOX) that contains a patterned BOX layer. The patterned BOX can form a buried microchannels network, or serve as a stop layer and a buried hard-etch mask, to accurately pattern the device layer while etching it from the backside of the wafer using the cleanroom microfabrication compatible tools and methods. The use of the cavity-BOX as a buried hard-etch mask is demonstrated by applying it for the fabrication of a deep brain stimulation (DBS) demonstrator. The demonstrator consists of a large flexible area and precisely defined 80 µm-thick silicon islands wrapped into a 1.4 mm diameter cylinder. With cavity-BOX, the process of thinning and separating the silicon islands was largely simplified and became more robust. This test case illustrates how cavity-BOX wafers can advance the fabrication of various MEMS devices, especially those with complex geometry and added functionality, by enabling more design freedom and easing the optimization of the fabrication process.
Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival
Authors: Murata Takayuki
Published: April 2021

The immune system has evolved as a complex and efficient means of coping with extrinsic materials, such as pathogens and toxins, as well as intrinsic abnormalities, such as cancers. Although rapid and timely activation of the immune system is obviously important, regulated downregulation of the system is almost as significant as activation to prevent runaway immunity, such as allergies and hypercytokinemia. Therefore, the immune checkpoint programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is beneficial for the host. On the other hand, pathogens have evolved to evade host immunity by taking advantage of the PD-1/PD-L1 pathway. This review is focused on human herpesviruses, such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV), which cause various types of disorders, and their relationships with the PD-1/PD-L1 pathway. Understanding such relationships will be useful for developing preventative and therapeutic methods for disorders caused by herpesviruses.
Gut Microbiota Dynamics, Growth Performance, and Gut Morphology in Broiler Chickens Fed Diets Varying in Energy Density with or without Bacitracin Methylene Disalicylate (BMD)
Authors: Adewole Deborah , Akinyemi Fisayo
Published: April 2021

High-energy-density diet could increase body weight at the expense of the intestinal health of the animals. In order to optimize production without negatively influencing the gut health of chickens, dietary supplementation with bacitracin methylene disalicylate (BMD) is a common feeding strategy adopted to enhance production performance and intestinal health. Studies have suggested that BMD could improve chicken growth performance and gut health through modulation of the gut microbiota. The current study investigated the effect of BMD supplementation in a normal-energy (NE) or high-energy (HE) diet on growth performance, organ weights, jejunal morphology, and gut microbiota of broiler chickens at different growth stages. Birds were allocated to four treatments: normal-energy basal diet (NE-BAS), normal-energy BMD diet (NE-BMD), high-energy basal diet (HE-BAS), and high-energy BMD diet (HE-BMD). In the starter phase, body weight and body weight gain were reduced significantly (p < 0.05) in chickens fed HE diets compared to those fed NE diets. The FCR was significantly higher (p < 0.05) in birds fed HE-BMD diets in the starter phase but lower (p < 0.05) during the grower phase when compared to other treatments. Moreover, the relative bursa weight increased significantly (p = 0.0220) among birds that received HE diets. Birds fed HE-BMD had greater villus height (p = 0.054) than NE-BMD group. Among the chickens fed the HE diets, those that received BMD treatment had a significantly increased (p = 0.003) villus width (13.3% increase) compared to those that received the basal diet. Improved population of Firmicutes was observed in chickens fed HE-BMD diet when compared to HE-BAS. Our results imply that BMD may be more effective in improving intestinal health when supplemented in a high-energy diet for broiler chickens.
Li2(BH4)(NH2) Nanoconfined in SBA-15 as Solid-State Electrolyte for Lithium Batteries
Authors: Yang Qianyi , Lu Fuqiang , Liu Yulin , Zhang Yijie , Wang Xiujuan , Pang Yuepeng , Zheng Shiyou
Published: April 2021

Solid electrolytes with high Li-ion conductivity and electrochemical stability are very important for developing high-performance all-solid-state batteries. In this work, Li2(BH4)(NH2) is nanoconfined in the mesoporous silica molecule sieve (SBA-15) using a melting–infiltration approach. This electrolyte exhibits excellent Li-ion conduction properties, achieving a Li-ion conductivity of 5.0 × 10−3 S cm−1 at 55 °C, an electrochemical stability window of 0 to 3.2 V and a Li-ion transference number of 0.97. In addition, this electrolyte can enable the stable cycling of Li|Li2(BH4)(NH2)@SBA-15|TiS2 cells, which exhibit a reversible specific capacity of 150 mAh g−1 with a Coulombic efficiency of 96% after 55 cycles.
Towards Universal Stimuli-Responsive Drug Delivery Systems: Pillar[5]arenes Synthesis and Self-Assembly into Nanocontainers with Tetrazole Polymers
Authors: Shurpik Dmitriy N. , Makhmutova Lyaysan I. , Usachev Konstantin S. , Islamov Daut R. , Mostovaya Olga A. , Nazarova Anastasia A. , Kizhnyaev Valeriy N. , Stoikov Ivan I.
Published: April 2021

In this work, we have proposed a novel universal stimulus-sensitive nanosized polymer system based on decasubstituted macrocyclic structures—pillar[5]arenes and tetrazole-containing polymers. Decasubstituted pillar[5]arenes containing a large, good leaving tosylate, and phthalimide groups were first synthesized and characterized. Pillar[5]arenes containing primary and tertiary amino groups, capable of interacting with tetrazole-containing polymers, were obtained with high yield by removing the tosylate and phthalimide protection. According to the fluorescence spectroscopy data, a dramatic fluorescence enhancement in the pillar[5]arene/fluorescein/polymer system was observed with decreasing pH from neutral (pH = 7) to acidic (pH = 5). This indicates the destruction of associates and the release of the dye at a pH close to 5. The presented results open a broad range of opportunities for the development of new universal stimulus-sensitive drug delivery systems containing macrocycles and nontoxic tetrazole-based polymers.
Glucose Detection of 4-Mercaptophenylboronic Acid-Immobilized Gold-Silver Core-Shell Assembled Silica Nanostructure by Surface Enhanced Raman Scattering
Authors: Pham Xuan-Hung , Seong Bomi , Hahm Eunil , Huynh Kim-Hung , Kim Yoon-Hee , Kim Jaehi , Lee Sang Hun , Jun Bong-Hyun
Published: April 2021

The importance of glucose in many biological processes continues to garner increasing research interest in the design and development of efficient biotechnology for the sensitive and selective monitoring of glucose. Here we report on a surface-enhanced Raman scattering (SERS) detection of 4-mercaptophenyl boronic acid (4-MPBA)-immobilized gold-silver core-shell assembled silica nanostructure (SiO2@Au@Ag@4-MPBA) for quantitative, selective detection of glucose in physiologically relevant concentration. This work confirmed that 4-MPBA converted to 4-mercaptophenol (4-MPhOH) in the presence of H2O2. In addition, a calibration curve for H2O2 detection of 0.3 µg/mL was successfully detected in the range of 1.0 to 1000 µg/mL. Moreover, the SiO2@Au@Ag@4-MPBA for glucose detection was developed in the presence of glucose oxidase (GOx) at the optimized condition of 100 µg/mL GOx with 1-h incubation time using 20 µg/mL SiO2@Au@Ag@4-MPBA and measuring Raman signal at 67 µg/mL SiO2@Au@Ag. At the optimized condition, the calibration curve in the range of 0.5 to 8.0 mM was successfully developed with an LOD of 0.15 mM. Based on those strategies, the SERS detection of glucose can be achieved in the physiologically relevant concentration range and opened a great promise to develop a SERS-based biosensor for a variety of biomedicine applications.
Increased Crystallization of CuTCNQ in Water/DMSO Bisolvent for Enhanced Redox Catalysis
Authors: Hussain Zakir , Nafady Ayman , Anderson Samuel R. , Al-Enizi Abdullah M. , Alothman Asma A. , Ramanathan Rajesh , Bansal Vipul
Published: April 2021

Controlling the kinetics of CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane) crystallization has been a major challenge, as CuTCNQ crystallizing on Cu foil during synthesis in conventional solvents such as acetonitrile simultaneously dissolves into the reaction medium. In this work, we address this challenge by using water as a universal co-solvent to control the kinetics of crystallization and growth of phase I CuTCNQ. Water increases the dielectric constant of the reaction medium, shifting the equilibrium toward CuTCNQ crystallization while concomitantly decreasing the dissolution of CuTCNQ. This allows more CuTCNQ to be controllably crystallized on the surface of the Cu foil. Different sizes of CuTCNQ crystals formed on Cu foil under different water/DMSO admixtures influence the solvophilicity of these materials. This has important implications in their catalytic performance, as water-induced changes in the surface properties of these materials can make them highly hydrophilic, which allows the CuTCNQ to act as an efficient catalyst as it brings the aqueous reactants in close vicinity of the catalyst. Evidently, the CuTCNQ synthesized in 30% (v/v) water/DMSO showed superior catalytic activity for ferricyanide reduction with 95% completion achieved within a few minutes in contrast to CuTCNQ synthesized in DMSO that took over 92 min.
Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Händel Mina Nicole , Rohde Jeanett Friis , Rimestad Marie Louise , Bandak Elisabeth , Birkefoss Kirsten , Tendal Britta , Lemcke Sanne , Callesen Henriette Edemann
Published: April 2021

Based on epidemiological and animal studies, the rationale for using polyunsaturated fatty acids (PUFAs) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD) seems promising. Here, the objective was to systematically identify and critically assess the evidence from clinical trials. The primary outcome was ADHD core symptoms. The secondary outcomes were behavioral difficulties, quality of life, and side effects. We performed a systematic search in Medline, Embase, Cinahl, PsycInfo, and the Cochrane Library up to June 2020. The overall certainty of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified 31 relevant randomized controlled trials including 1755 patients. The results showed no effect on ADHD core symptoms rated by parents (k = 23; SMD: −0.17; 95% CI: −0.32, −0.02) or teachers (k = 10; SMD: −0.06; 95% CI: −0.31, 0.19). There was no effect on behavioral difficulties, rated by parents (k = 7; SMD: −0.02; 95% CI: −0.17, 0.14) or teachers (k = 5; SMD: −0.04; 95% CI: −0.35, 0.26). There was no effect on quality of life (SMD: 0.01; 95% CI: −0.29, 0.31). PUFA did not increase the occurrence of side effects. For now, there seems to be no benefit of PUFA in ADHD treatment; however, the certainty of evidence is questionable, and thus no conclusive guidance can be made. The protocol is registered in PROSPERO ID: CRD42020158453.
Exploratory Space–Time Analyses of Reported Lyme Borreliosis Cases in France, 2016–2019
Authors: Fu Wen , Bonnet Camille , Figoni Julie , Septfons Alexandra , Métras Raphaëlle
Published: April 2021

In recent decades, the incidence of Lyme borreliosis (LB) in Europe seems to have increased, underpinning a growing public health concern. LB surveillance systems across the continent are heterogeneous, and the spatial and temporal patterns of LB reports have been little documented. In this study, we explored the spatio-temporal patterns of LB cases reported in France from 2016 to 2019, to describe high-risk clusters and generate hypotheses on their occurrence. The space–time K-function and the Kulldorf’s scan statistic were implemented separately for each year to evaluate space–time interaction between reported cases and searching clusters. The results show that the main spatial clusters, of radius size up to 97 km, were reported in central and northeastern France each year. In 2017–2019, spatial clusters were also identified in more southern areas (near the Alps and the Mediterranean coast). Spatio-temporal clustering occurred between May and August, over one-month to three-month windows in 2016–2017 and in 2018–2019. A strong spatio-temporal interaction was identified in 2018 within 16 km and seven days, suggesting a potential local and intense pathogen transmission process. Ongoing improved surveillance and accounting for animal hosts, vectors, meteorological factors and human behaviors are keys to further elucidate LB spatio-temporal patterns.
Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs
Authors: Silva Sara , Almeida António , Vale Nuno
Published: April 2021

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.
Endophytic Bacteria Enterobacter hormaechei Fabricated Silver Nanoparticles and Their Antimicrobial Activity
Authors: Monowar Tahmina , Rahman Md. Sayedur , Bhore Subhash J. , Sathasivam Kathiresan V.
Published: April 2021

Antimicrobial resistance (AMR), one of the greatest issues for humankind, draws special attention to the scientists formulating new drugs to prevent it. Great emphasis on the biological synthesis of silver nanoparticles (AgNPs) for utilization in single or combinatorial therapy will open up new avenues to the discovery of new antimicrobial drugs. The purpose of this study was to synthesize AgNPs following a green approach by using an endophytic bacterial strain, Enterobacter hormaechei, and to assess their antimicrobial potential against five pathogenic and four multidrug-resistant (MDR) microbes. UV-Vis spectroscopy, fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), and zeta potential (ζ) were used to characterize the synthesized AgNPs. Endophytic E. hormaechei-mediated AgNPs (Eh-AgNPs) were represented by a strong UV-Vis absorbance peak at 418 nm within 5 min, forming spherical and polydispersed nanoparticles in the size range of 9.91 nm to 92.54 nm. The Eh-AgNPs were moderately stable with a mean ζ value of −19.73 ± 3.94 mV. The presence of amine, amide, and hydroxyl functional groups was observed from FTIR analysis. In comparison to conventional antibiotics, the Eh-AgNPs were more effective against Bacillus cereus (ATCC 10876) and Candida albicans (ATCC 10231), exhibiting 9.14 ± 0.05 mm and 8.24 ± 0.05 mm zones of inhibition (ZOIs), respectively, while displaying effective inhibitory activity with ZOIs ranging from 10.98 ± 0.08 to 13.20 ± 0.07 mm against the MDR bacteria. Eh-AgNP synthesis was rapid and eco-friendly. The results showed that Eh-AgNPs are promising antimicrobial agents that can be used in the development and formulation of new drugs to curb the menace of antimicrobial resistance in pathogenic and MDR microbes.
β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles
Authors: Asela Isabel , Donoso-González Orlando , Yutronic Nicolás , Sierpe Rodrigo
Published: April 2021

Drugs are widely used as therapeutic agents; however, they may present some limitations. To overcome some of the therapeutic disadvantages of drugs, the use of β-cyclodextrin-based nanosponges (βCDNS) constitutes a promising strategy. βCDNS are matrices that contain multiple hydrophobic cavities, increasing the loading capacity, association, and stability of the included drugs. On the other hand, gold nanoparticles (AuNPs) are also used as therapeutic and diagnostic agents due to their unique properties and high chemical reactivity. In this work, we developed a new nanomaterial based on βCDNS and two therapeutic agents, drugs and AuNPs. First, the drugs phenylethylamine (PhEA) and 2-amino-4-(4-chlorophenyl)-thiazole (AT) were loaded on βCDNS. Later, the βCDNS–drug supramolecular complexes were functionalized with AuNPs, forming the βCDNS–PhEA–AuNP and βCDNS–AT–AuNP systems. The success of the formation of βCDNS and the loading of PhEA, AT, and AuNPs was demonstrated using different characterization techniques. The loading capacities of PhEA and AT in βCDNS were 90% and 150%, respectively, which is eight times higher than that with native βCD. The functional groups SH and NH2 of the drugs remained exposed and allowed the stabilization of the AuNPs, 85% of which were immobilized. These unique systems can be versatile materials with an efficient loading capacity for potential applications in the transport of therapeutic agents.
Public Attitudes towards Medicinal Waste and Medicines Reuse in a ‘Free Prescription’ Healthcare System
Authors: McRae David , Gould Abigail , Price-Davies Rebecca , Tagoe Jonathan , Evans Andrew , James Delyth H.
Published: April 2021

This study investigates public attitudes towards medicinal waste and medicines reuse within a ‘free prescription’ healthcare system. A quantitative online survey was employed in a sample drawn from the population of Wales, where prescription medicines have been ‘free’ since 2007. Qualitative interviews informed the content of the attitude statements with categorical or ordinal response options assigned. The questionnaire was hosted on the HealthWise Wales platform for 1 year from October 2017. Of the 5584 respondents, 67.2% had at least one medicine on repeat prescription. Overall, 89.1% held strong concerns about medicinal waste. High acceptance for the reuse of prescription medicines which have been returned unused by patients to pharmacies was reported for tablets (78.7%) and capsules (75.1%) if the medicine is checked by a pharmacist first (92.4% rated essential). Concerns identified related to tampering of packs (69.2%) and the need for hygienic storage (65.4%). However, those working in healthcare had less concern about the safety of reusing medicines. The level of public acceptance for the reuse of medication was higher than previously reported. This is the largest survey to capture these views to date, which has implications for the future design of medicines reuse schemes.
Broadband Absorption in Patterned Metal/Weakly-Absorbing-Spacer/Metal with Graded Photonic Super-Crystal
Authors: Kamau Steve , Hassan Safaa , Alnasser Khadijah , Zhang Hualiang , Cui Jingbiao , Lin Yuankun
Published: April 2021

It is challenging to realize the complete broadband absorption of near-infrared in thin optical devices. In this paper, we studied high light absorption in two devices: a stack of Au-pattern/insulator/Au-film and a stack of Au-pattern/weakly-absorbing-material/Au-film where the Au-pattern was structured in graded photonic super-crystal. We observed multiple-band absorption, including one near 1500 nm, in a stack of Au-pattern/spacer/Au-film. The multiple-band absorption is due to the gap surface plasmon polariton when the spacer thickness is less than 30 nm. Broadband absorption appears in the near-infrared when the insulator spacer is replaced by a weakly absorbing material. E-field intensity was simulated and confirmed the formation of gap surface plasmon polaritons and their coupling with Fabry–Pérot resonance.
CRISPR/Cas9 Targeted Mutagenesis for Functional Genetics in Maize
Authors: Hunter Charles T.
Published: April 2021

The CRISPR/Cas9-based system for targeted mutagenesis has become an indispensable tool for functional genetics in plants. CRISPR/Cas9 allows users to generate loss-of-function alleles in genes of interest with precision and in a simple-to-use system. This manuscript outlines important points to consider for experimental design and utilization of CRISPR/Cas9 in targeted mutagenesis in maize. It also introduces the pRGEB32-BAR vector modified for use in maize that allows simultaneous delivery of multiple gRNAs using a simple assembly. Vector selection, gRNA design, genetic strategies, and genotyping approaches are discussed, with an emphasis on achieving isolation of homozygous mutant plants in a time- and cost-efficient manner.
Natural Blues: Structure Meets Function in Anthocyanins
Authors: Houghton Alan , Appelhagen Ingo , Martin Cathie
Published: April 2021

Choices of blue food colourants are extremely limited, with only two options in the USA, synthetic blue no. 1 and no. 2, and a third available in Europe, patent blue V. The food industry is investing heavily in finding naturally derived replacements, with limited success to date. Here, we review the complex and multifold mechanisms whereby blue pigmentation by anthocyanins is achieved in nature. Our aim is to explain how structure determines the functionality of anthocyanin pigments, particularly their colour and their stability. Where possible, we describe the impact of progressive decorations on colour and stability, drawn from extensive but diverse physico-chemical studies. We also consider briefly how this understanding could be harnessed to develop blue food colourants on the basis of the understanding of how anthocyanins create blues in nature.
Oenothera laciniata Hill Extracts Exhibits Antioxidant Effects and Attenuates Melanogenesis in B16-F10 Cells via Downregulating CREB/MITF/Tyrosinase and Upregulating p-ERK and p-JNK
Authors: Ko Horng-Huey , Chang Yeo-Tzu , Kuo Yueh-Hsiung , Lin Chia-Hsuan , Chen Yih-Fung
Published: April 2021

Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and superoxide anion (O2−•), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities.
Ethnomedicinal Value of Antidiabetic Plants in Bangladesh: A Comprehensive Review
Authors: Rahman Md. Masudur , Uddin Md. Josim , Reza A. S. M. Ali , Tareq Abu Montakim , Emran Talha Bin , Simal-Gandara Jesus
Published: April 2021

The use of conventional drugs to treat metabolic disorders and the pathological consequences of diabetes further increases the complications because of the side effects, and is sometimes burdensome due to relatively higher costs and occasionally painful route of administration of these drugs. Therefore, shifting to herbal medicine may be more effective, economical, have fewer side effects and might have minimal toxicity. The present review amasses a list of ethnomedicinal plants of 143 species belonging to 61 families, from distinctive domestic survey literature, reported to have been used to treat diabetes by the ethnic and local people of Bangladesh. Leaves of the medicinal plants were found leading in terms of their use, followed by fruits, whole plants, roots, seeds, bark, stems, flowers, and rhizomes. This review provides starting information leading to the search for and use of indigenous botanical resources to discover bioactive compounds for novel hypoglycemic drug development.
Root-Derived Proteases as a Plant Tool to Access Soil Organic Nitrogen; Current Stage of Knowledge and Controversies
Authors: Adamczyk Bartosz
Published: April 2021

Anthropogenic deterioration of the global nitrogen (N) cycle emerges mainly from overuse of inorganic N fertilizers in nutrient-limited cropping systems. To counteract a further dysregulation of the N cycle, we need to improve plant nitrogen use efficiency. This aim may be reached via unravelling all plant mechanisms to access soil N, with special attention to the dominating high-molecular-mass N pool. Traditionally, we believe that inorganic N is the only plant-available N pool, however, more recent studies point to acquisition of organic N compounds, i.e., amino acids, short peptides, and proteins. The least known mechanism of plants to increase the N uptake is a direct increase of soil proteolysis via root-derived proteases. This paper provides a review of the knowledge about root-derived proteases and also controversies behind this phenomenon.
Plasma Mediated Chlorhexidine Immobilization onto Polylactic Acid Surface via Carbodiimide Chemistry: Antibacterial and Cytocompatibility Assessment
Authors: Ozaltin Kadir , Di Martino Antonio , Capakova Zdenka , Lehocky Marian , Humpolicek Petr , Saha Tomas , Vesela Daniela , Mozetic Miran , Saha Petr
Published: April 2021

The development of antibacterial materials has great importance in avoiding bacterial contamination and the risk of infection for implantable biomaterials. An antibacterial thin film coating on the surface via chemical bonding is a promising technique to keep native bulk material properties unchanged. However, most of the polymeric materials are chemically inert and highly hydrophobic, which makes chemical agent coating challenging Herein, immobilization of chlorhexidine, a broad-spectrum bactericidal cationic compound, onto the polylactic acid surface was performed in a multistep physicochemical method. Direct current plasma was used for surface functionalization, followed by carbodiimide chemistry to link the coupling reagents of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and N-Hydroxysuccinimide (NHs) to create a free bonding site to anchor the chlorhexidine. Surface characterizations were performed by water contact angle test, X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). The antibacterial activity was tested using Staphylococcus aureus and Escherichia coli. Finally, in vitro cytocompatibility of the samples was studied using primary mouse embryonic fibroblast cells. It was found that all samples were cytocompatible and the best antibacterial performance observed was the Chlorhexidine immobilized sample after NHs activation.
Modeling and Simulation in Capacity Degradation and Control of All-Solid-State Lithium Battery Based on Time-Aging Polymer Electrolyte
Authors: Fang Xuansen , He Yaolong , Fan Xiaomin , Zhang Dan , Hu Hongjiu
Published: April 2021

The prediction of electrochemical performance is the basis for long-term service of all-solid-state-battery (ASSB) regarding the time-aging of solid polymer electrolytes. To get insight into the influence mechanism of electrolyte aging on cell fading, we have established a continuum model for quantitatively analyzing the capacity evolution of the lithium battery during the time-aging process. The simulations have unveiled the phenomenon of electrolyte-aging-induced capacity degradation. The effects of discharge rate, operating temperature, and lithium-salt concentration in the electrolyte, as well as the electrolyte thickness, have also been explored in detail. The results have shown that capacity loss of ASSB is controlled by the decrease in the contact area of the electrolyte/electrode interface at the initial aging stage and is subsequently dominated by the mobilities of lithium-ion across the aging electrolyte. Moreover, reducing the discharge rate or increasing the operating temperature can weaken this cell deterioration. Besides, the thinner electrolyte film with acceptable lithium salt content benefits the durability of the ASSB. It has also been found that the negative effect of the aging electrolytes can be relieved if the electrolyte conductivity is kept being above a critical value under the storage and using conditions.
Optimization and Validation of Rancimat Operational Parameters to Determine Walnut Oil Oxidative Stability
Authors: Félix-Palomares Lucía , Donis-González Irwin R.
Published: April 2021

This study was performed to optimize and validate Rancimat (Metrohm Ltd., Herisau, Switzerland) operational parameters including temperature, air-flow, and sample weight to minimize Induction-Time (IT) and IT-Coefficient-of-Variation (CV), using Response Surface Methodology (RSM). According to a Box–Behnken experimental design, walnut oil equivalent to 3-, 6-, or 9-g was added to each reaction vessel and heated to 100, 110, or 120 °C, while an air-flow equal to 10-, 15-, or 20-L·h−1 was forced through the reaction vessels. A stationary point was found per response variable (IT and CV), and optimal parameters were defined considering the determined stationary points for both response variables at 100 °C, 25 L·h−1, and 3.9 g. Optimal parameters provided an IT of 5.42 ± 0.02 h with a CV of 1.25 ± 0.83%. RSM proved to be a useful methodology to find Rancimat operational parameters that translate to accurate and efficient values of walnut oil IT.
Everything but the Squeal: The Politics of Porcinity in the Livre des Propriétés des Choses
Authors: Gins Sven
Published: April 2021

Mediaeval encyclopaedias described nonhuman animals in terms of their corporeality and cosmic significance by combining zoological and theological knowledge. Such descriptions were therefore prescriptions of normative parameters for how animals were supposed to function within Christian society, rather than objective observations. As mediaeval conceptualisations of species were highly malleable, particular animals that shared no biological relation could be considered kin, and animals who behaved against their prescribed nature could become a different animal altogether. This paper investigates how several species were implicated in the mediaeval invention of what it meant to be (like) a pig. My counter-hegemonic reading of the Livre des propriétés des choses, a fifteenth-century French encyclopaedia, draws attention to how late mediaeval Christian scripts of porcinity simultaneously defined the nonhumanity of pigs and of ‘other’ humans. These render the idea of the pig inseparable from what it meant to be human. I contend that the Livre des propriétés des choses employs discourses of porcinity to self-define and -stabilise particular notions of human identity by debasing and othering human and nonhuman animals with seemingly porcine traits. Additionally, I underline how such fabrications of humanity are often mired in practices that devaluate and harm real animals, including other humans. Mediaeval studies need to further address the crucial roles of animal suffering in human history. This way, historians can add valuable insights to present debates about anthropocentrism and its devastating socio-ecological consequences.