bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Coelenterazine Analogue to Reveal Bioluminescent Reaction of Human Serum Albumin
Authors: Nishihara Ryo , Niwa Kazuki , Tomita Tatsunosuke , Kurita Ryoji
Published: April 2021

This chapter describes the design of an imidazopyrazinone-type luciferin named as HuLumino1 by us and investigation of its luminescence properties. This luciferin was designed to generate bioluminescence by human serum albumin (HSA) rather than by luciferase derived from luminous organisms. HuLumino1 was developed by modifying a methoxy-terminated alkyl chain to the C-6 position and eliminating a benzyl group at the C-8 position of coelenterazine. To clarify the basis of light emission by HSA, the detailed kinetic properties of the HuLumino1/HSA pair were investigated using a calibrated luminometer. The enzymatic oxidation of HuLumino1 was observed only in the presence of HSA. Results of HSA quantification experiments using HuLumino1 agreed with less than 5% differences with those of enzyme-linked immunosorbent assays, suggesting HuLumino1 could be used for quantitative analysis of HSA levels in serum samples without any pretreatments. These results demonstrate the advantages of the coelenterazine analogue as a bioluminescence reagent to detect non-labeled proteins, which generally do not function as enzymes.
Tiny Blind Assistive Humanoid Robot
Authors: Ganguly Amrita , Paul Bijan
Published: April 2021

In today’s world, individuals show more enthusiasm for robotics and aim to depend upon humanoid robots for multiple purposes. It has implementations in a wide range of sectors such as- in atomic plants, house management, government foundations and even astro stations. Our research-based project is elucidating robotics with a tiny humanoid robot following the human structure to make gestures like strolling, dancing, and detecting objects near it. It has been achieved using Arduino Nano (Atmega 328P), Servo motors SG90 working on the conception of servomechanism and the Ultrasonic sensor to identify obstacles and restrain the Robot from going ahead. The aim is to fabricate a bigger humanoid robot that will serve our general public and make our life simpler. The Robot has eventual utilize in marketing, entertainment and helping the visually impaired to move from one place to another. This project can also be a great apparatus for future research works and alteration.
Design Thinking Applications in Physical Activity and Exercise Literacy
Authors: Georgiadis Emmanouil
Published: April 2021

Various theoretical models of Health Literacy (HL) discuss its importance for behaviour change, supporting long-term health and disease prevention. During the 21st century Physical Activity (PA), Exercise and Sedentariness (SD) have received an increased priority over other health indices for quality of life purposes due to their central importance over metabolic conditions and their comorbidities. This review aims to conceptualise the main issues and challenges of Physical Inactivity (PI) and SD through the new proposals of Design Thinking (DT) which is considered one of the most promising pathways in health promotion. DT is prioritising empathy for service users, brings together collaborative multidisciplinary teams and provides the opportunity to assess various solutions via iterative practices. This chapter: A. provides a review over the efficacy of health promotion strategies during the current era and the urgency of behaviour change in PA and SD for various population segments. B. Explains how HL links self-care practices to PA and SD habits. And C. Presents DT as a new layout for supporting the exploration and feasibility of more active lifestyles for overall health and quality of life.
The genus Phantolabis (Diptera: Limoniidae) new to the Palearctic: description of a new species and re-definition of the genus
Authors: Pilipenko Valentin E.
Published: April 2021

A new crane fly species from the genus Phantolabis Alexander, 1956, active in the cold season and previously known by a single, eastern Nearctic species, is described from Primorsky Krai of the Russian Far East. A revised definition of the genus is given.
SS-MSC2 Process cruise/mooring service 2020
Authors: Fer Ilker , Skogseth Ragnheid , Astad Sine Sara , Baumann Till , Elliott Fiona , Falck Eva , Gawinski Christine , Kolås Eivind Hugaas
Published: April 2021

The cruise GOS 2020113 (6 October 2020 Longyearbyen, 27 October 2020 Tromsø) aboard the Research Vessel G.O. SARS is a mooring service/deployment and process studies cruise of the Nansen LEGACY project.
Hematological and cytochemical characteristics of peripheral blood cells in the argus snakehead (Ophiocephalus argus Cantor)
Authors: Wang Xue , Wu Zhengjie , Wu Shengmei , Chen Xianxian , Hanif Misbah , Zhang Shengzhou
Published: April 2021

Background

The argus snakehead (Ophiocephalus argus Cantor) is a highly nutritious, freshwater, cultured bony fish with a high economic value. The health of the fish is closely related to its blood cells, which are critical for oxygen transport, natural defense, and immunity. We investigated the morphometry, microstructure, and cytochemical characteristics of the peripheral blood cells of O. argus. Our results may provide the basic reference values needed to monitor the health of this fish for large-scale cultivation.

Methods

The number of blood cells in O. argus were counted on a hemocytometer and their size was measured using a micrometer under light microscope. The morphology and classification of the blood cells were studied using Wright’s staining and the cytochemical characteristics were studied using seven chemical stains including peroxidase (POX), Sudan black B (SBB), periodic acid-Schiff (PAS), acid phosphatase (ACP), alkaline phosphatase (ALP), chloroacetic acid AS-D naphthol esterase (AS-D), and α-naphthol acetate esterase (α-NAE).

Results

The peripheral blood cells in O. argus can be classified as erythrocytes, leukocytes, and thrombocytes; of which, females had 2.9597 million/mm3, 88,400/mm3, and 43,600/mm3, respectively, and males had 3.0105 million/mm3, 105,500/mm3, and 34,000/mm3, respectively. Leukocytes consisted of neutrophils, monocytes, large lymphocytes, and small lymphocytes. Eosinophils and basophils were not found. Monocytes were the most numerous leukocytes identified, followed by neutrophils and small lymphocytes, while large lymphocytes were the least frequently identified. Cytochemical staining showed that erythrocytes were only positive for PAS staining. Neutrophils were strongly positive for POX, SBB, and ACP, and positive for all the other cytochemical stains. Monocytes were positive for PAS and α-NAE and were weakly positive for ACP and AS-D staining. Large lymphocytes were positive for PAS and were weakly positive for ALP, AS-D, and α-NAE staining. Small lymphocytes were positive for PAS and weakly positive for AS-D and α-NAE staining. Thrombocytes were positive for PAS and were weakly positive for ACP and AS-D, but negative for the remaining cytochemical stains. The morphology of peripheral blood cells in O. argus was generally similar to that of other fish species, while the cytochemical staining patterns showed clear species specificity.
Application of thermal comfort assessment models to indoor areas near glazed walls – experimental evaluation
Authors:   Polytechnic Institute of Viseu, School of Technology and Management (Portugal), Figueiredo Freitas Oliveira António Manuel , Corvacho Helena ,   CONSTRUCT- LFC, University of Porto, Faculty of Engineering (portugal)
Published: April 2021

In this paper, some of the results of an experimental study are presented. Its purpose was to better understand the impact of glazing on thermal comfort of users of indoor spaces (living and working), especially in the areas near glazed walls. Glazed elements, such as windows and glazed doors, allow visual access to the outdoor environment and the entrance of natural light and solar heat gains but they are often the cause of unwanted heat losses and gains and are disturbing elements in obtaining thermal comfort, both in global terms and in what concerns local discomfort due to radiant asymmetries and/or air draughts. Furthermore, solar radiation directly affecting users in the vicinity of glazing can also cause discomfort. These disturbances are recognized by users, both on cold winter days and on hot summer days. To assess thermal comfort or thermal neutrality of a person in a particular indoor space, it is important to know their location within that space. Thus, in order to adequately assess thermal comfort in the areas near the glazing, the indoor thermal environment must be characterized for this specific location. In this study, two indoor spaces (a classroom and an office-room) of a school building were monitored at different periods of the year. The measurements of the environmental parameters were performed both in the center of the rooms and in the areas near the glazing. Five models of thermal comfort assessment were then applied to the results, in order to compare the comfort conditions between the two studied locations and to evaluate the applicability of these models to the areas close to glazed walls. It was observed there was clearly a greater variability of comfort conditions in the vicinity of the glazed walls when compared to the center of the rooms. The application of thermal comfort assessment models to the two studied rooms was able to reveal the differences between the two compared locations within each space. It was also possible to show the effect of incoming solar radiation and the influence of the geometry of the spaces and of the ratio between glazed area and floor area by comparing the results for both spaces. The assessment model proposed by LNEC (Portuguese National Laboratory of Civil Engineering) proved to be the most adapted to Portuguese users’ habits.
Performance of ambient and freezing-thawing cured metazeolite and slag based geopolymer composites against elevated temperatures
Authors:   Yldiz Technical University (Turkey), Aygörmez Yurdakul
Published: April 2021

Today, geopolymer has an important place in producing sustainable alternative products by consuming less energy. This paper researches the elevated-temperature behavior of metazeolite (MZ) and slag (S) based geopolymer composites, reinforced by polyvinyl alcohol fiber (PVA) (at 0.3%, 0.6% and 0.9% by volume), and basalt fiber (B) (at 0.3%, 0.6% and 0.9% by volume). The curing was carried out at room temperature for up to 7 days and then the freeze-thaw test was applied as a curing method for up to 28 days. Slag was used alongside metazeolite to solve the problem of delayed setting time with its high Ca content. After 7 days, the damp environment provided by the freeze-thaw curing ensured the preservation of the compact structure and the continuation of geopolymerization. The resulting geopolymer composites were exposed to temperatures of 250, 500, and 750 oC. The flexural and compressive strengths, microstructure (FT-IR, XRD, SEM, TGA-DTA, and micro-CT analyzes), ultrasonic pulse velocity (UPV), visual inspection, and weight-losses of the geopolymers were examined to evaluate their behavior. According to the results, it was observed that geopolymer samples maintained their stability after 750oC. In this way, a sustainable geopolymer composite was produced by using less energy.
The effect of calcite and blast furnace slag on the rheology properties of self-compacting concrete in meso and macro scales
Authors:   Amasya University, Architecture Faculty, Architecture Department, Amasya, (Turkey), Gokce Murat , Şimşek Osman ,   Gazi University, Faculty of Technology, Civil Engineering Department (Turkey)
Published: April 2021

In this study, the effects of blast furnace slag (BFS) and calcite on rheological properties of self-compacting concrete (SSC) in meso and macro scales were investigated. During the preparation of replicate samples, while BFS was replaced with the cement at the rate of 10%, 20%, 30%, and 40% by weight, calcite was added to the cement at the rate of 10%, 15%, 20%, and 25% by weight. The rheological properties (plastic viscosity and yield point) and mini-slump flow values of the cement paste prepared in meso scales were determined. The fresh flow consistency of concrete prepared in macro-scale was tested with L-box flowing test. As a result, upon evaluating the rheological parameters of the pastes according to the Bingham model, while the pastes with a plastic viscosity value close to 1 Pa·s (±100 MPa·s) and a mini-slump flow rate higher than 200 mm were observed to be more resistant to segregation and form a homogeneous flow consistency, their L-box flowing rates were determined to be homogeneous and high. Ideal SSCs were made by adding 20% and 25% calcite to 30% BFS and 40% BFS replaced mixtures respectively in this study. It was also concluded that ideal SCC could be produced with paste mixtures having 1 Pa·s (±100 MPa·s) viscosity and mini-slump flow diameter higher than 200 mm. With the increase in calcite addition rates in SSCs, the passing rate for the L box test has increased
Future Trends in Cassava Production: Indicators and its Implications for Food Supply in Nigeria
Authors: Ikuemonisan Edamisan Stephen , Akinbola Adeyose Emmanuel
Published: April 2021

The growing demand for cassava and its products has continued to stretch the supply of cassava globally. Nigeria is a leading producer of cassava in the world yet, there are concerns that if appropriate policy strategies are not adopted to increase production, the current fragile situation of food insecurity in Nigeria may be worsened. Besides the increasing number of gigantic cassava-based industries spring up in Nigeria, the rapidly growing population of consumers is another factor that may further disrupt the relatively stable cassava market in Nigeria in the future. Therefore, “ceteris paribus”, the study determined the appropriate quantitative models to forecast the trends in cassava production indictors in Nigeria. Using the historical series (1961 – 2018), 12-year period (2019 -2030) forecasts were made for each of the production indicators as follows: 106 million tonnes (production output), 7.7 tonnes/ha (yield) and 9.6 million hectares (cropped area) in 2030. The study extrapolated the expected food supply from the expected production output in the forecast period using the 2014 FAO estimates of food supply per caput. Thus, in 2030, cassava food supply per caput was found to decline from 267 Kcal/capita/day in 2014 to 239 Kcal/capita/day. The study concludes that despite keeping the future demand of the growing cassava-based industries constant, cassava production is expected to continually increase but future food supply per caput would decline. However, the growing cassava-based industries globally is expected to hugely influence the future cassava market dynamics.
East African Community Regional Integration: Private Investment Implications
Authors: Mose Naftaly , Keino Irene , Yoganandan G. , Olaniyan Oladipo , Nyoni Thabani
Published: April 2021

The objective of regional integration is the attainment of long-run economic growth for member countries. Private investments are decisive in attaining this objective, given the high dependence of EAC member states on state-owned investment. This has been attributed to the economic policies implemented by the government which favors state-owned investment. Further, existing empirical studies have been unable to determine whether trade liberalization advances or obstructs the accumulation of private and foreign investment. This study, assuming a random effect assumption, attempts to estimate the private investment model in EAC member states using the panel least squares technique for the period 1981-2015. The panel random effect regression result reveals that East African Community regional integration has had a significant impact on private investment build-up owing to the presence of third-country investors not currently established inside the EAC region. This study, therefore, recommends any policy agenda aimed at deepening regional integration through guaranteeing an appropriate business environment for enabling free movement of factors of production, population, and goods and services.
Effect of Various Tillage Practices and Residue Retention on N, P and K Content in Seed and Straw of Different Wheat Varieties in Rice-wheat System
Authors: Malik Kapil , Lathwal O. P. , Dhaka A. K. , Jatana Mansukh Singh , Ravi .
Published: April 2021

A field trial was conducted at rice research station, Kaul (Kaithal) of CCSHAU, Hisar during the Rabi season to study theeffect of tillage practices and residue retention on nutrient content in seed and straw of different wheat varieties. The six wheat varieties viz; HD 2967, HD 3086, WH 1105, WH 711, WH 1124 and WH 1142 were grown under four tillage systems: turbo seeder with full residue retention, turbo seeder with intact residue, zero tillage with no residue and conventional tillage with no residue methods. The nitrogen (N), phosphorus (P) and potassium (K) content in seed and straw were not influenced by different sowing techniques during both the years but nitrogen content was significantly affected during second year of study. However, the maximum N, P and K content (%) in seed and straw of wheat was achieved with turbo seeder sowing wheat under full residue retention and minimum content was recorded in conventional tillage with no residue retention during both years. Among varieties, significant difference was observed in term of nitrogen and potassium content in seed and straw. WH 1105 recorded significantly higher N content (%) in grain while more N content (%) in straw was found in WH 1124 during 2018 and 2019. While K content (%) in seed was more in WH 711 which was at par with WH 1142 and WH 1105 whereas, K content(%)in straw was more in WH 1124 variety being at par with WH 1142 in both years of study. However, Phosphorus content (%) in grain and straw of different wheat varieties was not differed significantly during 2 years of experiment.In conclusion, the different sowing methods had non- significant effects on the nutrient content but varietal genotype of wheat had more influence nutrient content in seed and straw under different sowing techniques.
Assessing the Level of Satisfaction of Patients with TB-DOTS Implementation in Rural and Urban Centres of Selected Dots accredited facilities in Anambra State, Nigeria
Authors: Ohamaeme M. C. , Ilika F. , Aniagboso C. C. , Elendu M. U. , Aniemena C. R. , Eberendu I. G.
Published: April 2021

Background: This study assessed the level of satisfaction of patients with TB implementation in selected DOTS accredited facilities.

Methodology: A comparative cross-sectional analytic study involving rural and urban areas implementing DOTS for TB in Anambra State was done. A total of 354 respondents (177 per sub population) were enrolled in the study. By exit interview respondents were administered the questionnaire that bordered on services rendered and cost implications of accessing treatment at the facilities.

Results: A total of 162(91.5%) rural respondents were satisfied with appropriateness of working hours compared to 166(93.8%) participants in urban areas. Also 141(79.7%) respondents in rural areas were satisfied with waiting time compared to 155(87.6%) in urban areas and this was statistically significant p<0.004. For the cleanliness of the specimen bottle 138(77.8%) rural respondents compared to 148(83.6%) in urban areas were satisfied and this was statistically significant, p<0.001. Majority of the urban respondents 123(68.9%) were satisfied with respect offered by health workers compared to rural 114(64.4%), and this was also significant, p<0.000. Concerning cost incurred and information given by health workers more urban respondents 5(2.8%) were dissatisfied compared to rural 2(1.1%) though not statistically significant p= 0.378. However, satisfaction was slightly higher in urban (82.8%) compared to rural (80.8%) respondents, while the overall satisfaction in this study was 81.8%.

Conclusion: Patient`s satisfaction is a panacea for successful DOTS implementation. We therefore recommend that satisfaction could be improved by provision patient-centred requests such as provision of multivitamins, transport, food among others to help improve DOTS because it will encourage attendance and adherence with better outcomes.
Effect of Variable Viscosity and Thermal Conductivity on MHD Natural Convection Flow along a Vertical Flat Plate
Authors: Sarker Sree Pradip Kumer , Alam Md. M.
Published: April 2021

Free convection flow around a heated vertical flat plate in the presence of a magnetic field is very important from the technical standpoint, and several researchers have studied this issue. The effects of variable viscosity and thermal conductivity on Magneto-Hydrodynamics (MHD) free convection flow over an isothermal vertical plate immersed in a fluid with heat conduction will be studied in this study. The two-dimensional, laminar, and unsteady boundary layer equations are considered in this paper. Using relevant variables, simple governing equations are transformed into non-dimensional governing equations. The implicit finite difference scheme, also known as the Crank-Nicolson scheme, is used to solve these equations numerically. This research looks at viscous incompressible fluids with temperature-dependent viscosity and thermal conductivity. The effect of various parameters on velocity, temperature, local skin friction, and local heat transfer coefficient profiles will be shown in this study, and the results will be compared to those of other researchers. The current numerical results will be compared to the results of previously published works. Figures from the current thesis will be compared to those from previously published works. The outcomes result will be shown in graphs for various values of relevant physical parameters.
Epidemic Model and Mathematical Study of Impact of Vaccination for the Control of Malware in Computer Network
Authors: Chinebu Titus Ifeanyi , Udegbe Ikechukwu Valentine , Eberendu Adanma Cecilia
Published: April 2021

Malware remains a significant threat to computer network.  In this paper, we consideredthe problem which computer malware cause to personal computers with its control by proposing a compartmental model SVEIRS (Susceptible Vaccinated-Exposed-infected-Recovered-Susceptible) for malware transmission in computer network using nonlinear ordinary differential equation. Through the analysis of the model, the basic reproduction number  were obtained, and the malware free equilibrium was proved to be locally asymptotical stable if  is less than unity and globally asymptotically stable if Ro is less than some threshold using a Lyapunov function. Also, the unique endemic equilibrium exists under certain conditions and the model underwent backward bifurcation phenomenon. To illustrate our theoretical analysis, some numerical simulation of the system was performed with RungeKutta fourth order (KR4) method in Mathlab. This was used in analyzing the behavior of different compartments of the model and the results showed that vaccination and treatment is very essential for malware control.
A Study of Antioxidant and Anti-bacterial activities of Borassus flabellifer
Authors: Nayak Prashant , Sandeep D. S. , Hameed Aqib , Priya Sneh , Kumar Pankaj , Kumar Abhishek
Published: April 2021

The present study was designed to estimate the antimicrobial and antioxidant activities of ethanolic and aqueous extract of Borassus flabellifer fruit, juice, leaves and sap. The antioxidant evaluation was carried out by various radical scavenging assays and antimicrobial activity by the disk diffusion method. For antibacterial activity, bacterial species such as Escherichia coli and Staphylococcus aureus were tested for all extracts. The extract showed moderate antioxidant activity when compared to the standard vitamin C. In both DPPH and nitric oxide oxide assay when related IC 50 value, ethanolic fruit extract showed promising results of 132 and 119  µg/mL respectively with ascorbic acid as standard which showed 25 and 35 µg/mL respectively. In Ferric Thiocyanate (FTC) Method and Thiobarbituric Acid (TBA) Method the radical scavenging activity of ethanolic fruit extract showed satisfactory results of 160 and 148 µg/mL ascorbic acid being the standard which showed 94 and 97 µg/mL respectively. The total flavonoid contents were 32.7 /100g for ethanolic sap extracts and 53.9/100g in aqueous extract of sap. The fruit juice extract showed maximum inhibition zone with 31.4 and 32.1 mm against E. coli and S.aureus correlated other extracts .Ethanolic and aqueous sap extracts zone of inhibition was 25.2 and 26.8 against E. coli and zone of inhibition was 28.3 against S.aureus in both ethanolic and aqueous sap. Ethanolic and aqueous leaves extracts zone of inhibition was 28.5 and 24.1 against E. coli. Ethanolic and aqueous leaves extracts zone of inhibition was 30.4 and 25.8 against S.aureus. Herein, the results suggest that the Borassus flabellifer plant extracts have potential antioxidant and antimicrobial properties.
Recent Advances in Development, Validation, and Exploitation of QSAR Models
Authors: Tropsha Alexander
Published: April 2021

Counting more than 45 years of intensive development and applications, QSAR modeling remains one of the major computational approaches for drug discovery and environmental chemical risk assessment. Recent developments in the field reflect the burgeoning growth of bioactivity and chemical databases. This growth provides a never‐ending impetus for the development of a growing body of QSAR models and their application for virtual screening to prioritize chemicals for experimental investigations. This article reviews recent and emerging trends in the QSAR modeling field with the emphasis on new approaches to chemical and biological data curation, model validation, virtual screening, and potential application of QSAR models by federal agencies for regulatory decision making.
NMR‐Based Screening and Drug Discovery
Authors: Craik David J. , Smith Phillippa A. , Clark Richard J.
Published: April 2021

NMR spectroscopy is a powerful technique for determining the structures of molecules in solution. It involves placing a sample in a strong homogeneous magnetic field and irradiating it with radiowaves of defined frequency. The emitted signals provide information about the local molecular environments of nuclei in the sample, from which structures can be derived. NMR can also be used for determining interactions between molecules and is particularly useful for determining the nature of binding interactions between ligands and macromolecules. This information is very important in drug design: by understanding how bioactive molecules interact with a target protein or nucleic acid it is, in principle, possible to design ligands with improved affinity and specificity that may make useful drug leads. In addition to this structure‐based approach to drug design NMR is also useful as a screening tool in drug discovery programs to identify ligands that bind to target macromolecules.
Modulation of the Androgen Receptor Axis
Authors: Mohler Michael L. , Dalton James T.
Published: April 2021

The androgen receptor (AR) mediates the endocrine functions of endogenous androgens like testosterone and exerts pleiotropic androgenic (male phenotype development, sexual function) and anabolic (growth and maintenance of musculoskeletal system) effects across most tissues. The AR‐axis, i.e. AR and its downstream effects, is extensively targeted to stimulate anabolism or treat prostatic diseases. Tissue‐selective, direct‐acting synthetic AR agonists are limited in scope by their inadequate separation of anabolic from untoward androgenic or virilizing effects and include FDA approved steroidal androgens (anabolic‐androgenic steroids) and investigational nonsteroidal selective AR modulators (SARMs). Gaining in popularity is testosterone replacement therapy in hypogonadal men. Antagonism of the AR‐axis is common in aging males with androgen‐dependent prostate hyperproliferation [prostate cancer or benign prostatic hyperplasia (BPH)]. Androgen ablation (indirect antagonism) and direct AR antagonism have been the mainstays of prostate cancer therapies for many decades including recent approvals. Indirect antagonists of the AR‐axis include gonadotropin‐releasing hormone agonists or antagonists (androgen‐deprivation therapy), which achieve systemic androgen and estrogen ablation for prostate or breast cancers as a monotherapy or sometimes in combination with steroidogenic enzyme (lyase) inhibitors. DHT‐dependent diseases are treated with 5α‐reductase to block intracrine production of DHT for male pattern baldness and BPH; whereas aromatase inhibitors block androgen metabolism to estrogen in breast cancer. Direct AR antagonists (antiandrogens) with improved potency and anti‐androgenic scope continue to be approved for prostate cancer. Research into innovative ways to directly or indirectly modulate the AR‐axis remains robust, suggesting new therapies will likely be introduced regularly for the foreseeable future.
Cholinergics/Anticholinergics
Authors: Griffith Robert , Dukat Malgorzata
Published: April 2021

This article covers classes of drugs and chemicals that act directly on muscarinic and nicotinic cholinergic receptors as agonists, antagonist, or allosteric modulators, together with an overview of the structures of muscarinic and nicotinic receptors. A brief history of the use of the small molecules muscarine, nicotine, and atropine to differentiate nicotinic and muscarinic receptors both of which respond to the neurotransmitter acetylcholine. This followed by discussion of the physical nature of the muscarinic G‐protein‐coupled‐receptor and the ligand‐gated‐ion‐channel nicotinic receptor. The structure–activity relationships of muscarinic agonists and antagonists are discussed with reference to attempts to develop of drugs selective for one of the five muscarinic receptors. Muscarinic antagonists are employed to treat disease states such as asthma, COPD, and overactive bladder. Muscarinic agonists have potential in the treatment of Alzheimer's disease. The structure–activity relationships of agonists and antagonists of nicotinic receptors are presented. Nicotinic agonists have been employed to assist in smoking cessation and have potential in treating Alzheimer's disease. Nicotinic antagonists have primarily been employed as neuromuscular blockers in surgery. The use of both positive and negative allosteric modulators of both muscarinic and nicotinic are discussed.
Antipsychotic Agents
Authors: Ablordeppey Seth , Ofori Edward
Published: April 2021

Schizophrenia is one of the most severe diseases of the brain and is characterized by a spectrum of symptoms including positive, negative, and cognitive symptoms. Even though schizophrenia has a low worldwide prevalence (0.4–0.7%), it is one of the most devastating diseases of the central nervous system (CNS). Despite the immense studies on schizophrenia over the years, the exact cause of the disorder remains unknown. Therefore, morbidity studies and their outcomes for schizophrenia continue to rely on descriptive definitions spelled out in the Diagnostic and Statistical Manual of Mental Disorders‐fifth edition (DSM‐5). Current pharmacotherapy of the disease involves the use of antipsychotic agents that target CNS receptors including dopamine and serotonin receptor subtypes. Despite the success in the management of psychiatric illness most of the current antipsychotics are saddled with problems such as inefficacy across patient populations and disease domains and intolerable side effects that limit their widespread utility. Evolving paradigm shift in antipsychotic drug discovery efforts over the last decade has begun to address these issues opening the door for new hypotheses that integrate well‐known neurotransmitter systems with neuronal circuits. Recent advances in molecular biology and genetics are also paving the way for a better understanding of the etiology and pathophysiology of schizophrenia. In addition to reviewing currently used agents, this article will focus on the advances made to address the stated problems and highlight the paradigm shift in the antipsychotic drug discovery area.
Better left alone: Trying to control pasture grasses in untended rainforest plantings incurs multiple costs and delivers few benefits
Authors: Radford‐Smith Julian , Shoo Luke P. , Dwyer John M.
Published: April 2021

Rainforest revegetation projects often deliver suboptimal outcomes due to the recolonization of invasive pasture grasses, but little is known about the effects of grass reinvasion on the survival and growth of established saplings. Even less is known about the costs and benefits of controlling pasture grasses once they have reinvaded.

To address these knowledge gaps, we implemented a split‐plot grass control experiment in a 2‐year old subtropical rainforest restoration planting in South East Queensland, Australia, that was reinvaded by the exotic pasture grassChloris gayana.

Grass removal involved brush cutting around saplings, spraying herbicide and then laying 1 m2jute matting. The costs of implementing the treatment were recorded, and the survival, growth and physiological stress of treated and control saplings were monitored for 1 year.

Non‐target herbicide application reduced survival by 6.5% in treated saplings, affecting mainly smaller plants that were below the grass canopy at the onset of the experiment. Beyond this direct herbicide effect, smaller treated saplings were also more stressed (lower chlorophyll fluorescence) and had substantially lower survival after 1 year than untreated saplings of the same size. There was limited evidence that removing grass increased growth rates, even for saplings that were already taller than the grass canopy at the start of the experiment.

While the growth benefits of controlling grass may become more apparent with time, our results suggest that grass removal is not an effective management strategy in untended plantings due to the heightened risk of sapling mortality, coupled with the considerable labour and material costs.
A Highly Stable and Durable Capacitive Strain Sensor Based on Dynamically Super‐Tough Hydro/Organo‐Gels
Authors: Mo Funian , Huang Yan , Li Qing , Wang Zifeng , Jiang Ruijuan , Gai Weiming , Zhi Chunyi
Published: April 2021

Capacitive‐type strain sensors based on hydrogel ionic conductors have undergone rapid development benefited from their robust structure, drift‐free sensing, higher sensitivity, and precision. However, the unsatisfactory electro‐mechanical stability of the conventional hydrogel conductors, which are normally vulnerable to large deformation and severe mechanical impacts, remains a challenge. In addition, there is not enough research regarding the adhesiveness and mechanical properties of the dielectric layer, which is also critical for the mechanical adaptability of the whole device. Here, a dynamically super‐tough capacitive‐type strain sensor based on energy‐dissipative dual‐crosslinked hydrogel conductors and an organogel dielectric with high adhesive strength is developed. Combining with the mechanical advantages of the hydro/organo‐gels, the capacitive strain sensor exhibits high stretchability and superior linear dependence of sensitivity with a gauge factor of ≈0.8% at 100% strain. Moreover, the sensor displayed ultrastability against various severe mechanical stimuli that can even survive unprecedentedly from extremely catastrophic car run‐over by 20 times. With these synergistic mechanical advantages, the capacitive strain sensor is successfully applied as a highly‐reliable wearable sensing system to monitor diverse faint physiological signals and large‐range human motions.
Conjugated Polymer for Implantable Electronics toward Clinical Application
Authors: Liu Yuxin , Feig Vivian Rachel , Bao Zhenan
Published: April 2021

Owing to their excellent mechanical flexibility, mixed‐conducting electrical property, and extraordinary chemical turnability, conjugated polymers have been demonstrated to be an ideal bioelectronic interface to deliver therapeutic effect in many different chronic diseases. This review article summarizes the latest advances in implantable electronics using conjugated polymers as electroactive materials and identifies remaining challenges and opportunities for developing electronic medicine. Examples of conjugated polymer‐based bioelectronic devices are selectively reviewed in human clinical studies or animal studies with the potential for clinical adoption. The unique properties of conjugated polymers are highlighted and exemplified as potential solutions to address the specific challenges in electronic medicine.
Resonant Spin Transmission Mediated by Magnons in a Magnetic Insulator Multilayer Structure
Authors: Fan Yabin , Finley Joseph , Han Jiahao , Holtz Megan E. , Quarterman Patrick , Zhang Pengxiang , Safi Taqiyyah S. , Hou Justin T. , Grutter Alexander J. , Liu Luqiao
Published: April 2021

While being electrically insulating, magnetic insulators can behave as good spin conductors by carrying spin current with excited spin waves. So far, magnetic insulators are utilized in multilayer heterostructures for optimizing spin transport or to form magnon spin valves for reaching controls over the spin flow. In these studies, it remains an intensively visited topic as to what the corresponding roles of coherent and incoherent magnons are in the spin transmission. Meanwhile, understanding the underlying mechanism associated with spin transmission in insulators can help to identify new mechanisms that can further improve the spin transport efficiency. Here, by studying spin transport in a magnetic‐metal/magnetic‐insulator/platinum multilayer, it is demonstrated that coherent magnons can transfer spins efficiently above the magnon bandgap of magnetic insulators. Particularly the standing spin‐wave mode can greatly enhance the spin flow by inducing a resonant magnon transmission. Furthermore, within the magnon bandgap, a shutdown of spin transmission due to the blocking of coherent magnons is observed. The demonstrated magnon transmission enhancement and filtering effect provides an efficient method for modulating spin current in magnonic devices.
Solvent Annealing Enables 15.39% Efficiency All‐Small‐Molecule Solar Cells through Improved Molecule Interconnection and Reduced Non‐Radiative Loss
Authors: Ge Jinfeng , Hong Ling , Song Wei , Xie Lin , Zhang Jinsheng , Chen Zhenyu , Yu Kuibao , Peng Ruixiang , Zhang Xiaoli , Ge Ziyi
Published: April 2021

Post‐treatment is of great importance to form nanoscale phase‐separated morphology for all‐small‐molecule organic solar cells (ASM‐OSCs), while the reasons for the difference between thermal annealing (TA) and solvent annealing (SVA) remain unclear. In this work, the influences of TA and SVA (with three common solvents of THF, CS2, and CF) are systematically investigated based on BT‐2F:N3 through characterization of photovoltaic performance, molecular stacking, charge transfer, etc. The results indicate that: i) solvents with good solubility induce stronger molecular interaction than that of TA treatment, and thus endowing molecules with better mobility to migrate for crystallization and phase separation, which leads to better J‐aggregation and molecular interconnection. ii) Donor‐selectively dissolved CS2 is better for optimizing the donor domain for its suitable domain size, improved molecular interaction and interconnection, and reduced trap states. iii) CS2 imposes a small impact on N3 acceptors and thus alleviates the increment of non‐radiative recombination. As a result, CS2 SVA with unique multifunctions enables a PCE of 15.39% with simultaneously improved voltage (0.845 V) and fill factor (75.02%), which is much higher than 14.66% of TA treatment. Moreover, 15.39% efficiency is also the highest value in binary ASM‐OSCs.
Cover crop and minimum tillage effects on yield, irrigation water use, and net returns
Authors: Badon Thomas B. , Prince Czarnecki Joby M. , Krutz L. Jason , Shockley Jordan M. , Baker Beth H.
Published: April 2021

The addition of cover crops and minimum tillage to current row‐crop production practices in the mid‐southern United States could holistically improve the sustainability of these farming systems. This relatively short‐term study was conducted to determine if the addition of these practices into corn (Zea mays L.)–soybean [Glycine max (L.) Merr.] rotational systems in the region would decrease irrigation water use while improving yield, irrigation water use efficiency, and net returns above production costs. The effects of cover crops and minimum tillage on these parameters were investigated from 2017 to 2019 on six pairs of production fields in northwest Mississippi. A pair was created by dividing a single field that had been under uniform management into two fields that were land leveled and hydrologically separated with an earthen berm. Control fields were managed according to standard practices within the region, which include winter fallow and multiple tillage passes, whereas treatment fields were managed with winter cover crops and minimum tillage. The addition of cover crops and minimum tillage had no effect on yield (p = .09), irrigation water use efficiency (p = .38), or irrigation water applied (p = .83). The net economic return on average across all site years was a loss of US$233 ha–1. These results reflect the short study period as changes resulting from these practices often occur on a greater time scale. The value proposition for adoption of a cover crop–minimum tillage system will be challenging in the mid‐southern United States if potential benefits are to be expected in the early years of adoption.
Theoretical impact of the AT(N) framework on dementia using a community autopsy sample
Authors: Burke Bridget Teevan , Latimer Caitlin , Keene C. Dirk , Sonnen Joshua A. , McCormick Wayne , Bowen James D. , McCurry Susan M. , Larson Eric B. , Crane Paul K.
Published: April 2021

The AT(N) research framework categorizes eight biomarker profiles using amyloid (A), tauopathy (T), and neurodegeneration (N), regardless of dementia status. We evaluated associations with dementia risk in a community‐based cohort by approximating AT(N) profiles using autopsy‐based neuropathology correlates, and considered cost implications for clinical trials for secondary prevention of dementia based on AT(N) profiles. We used Consortium to Establish a Registry for Alzheimer's Disease (moderate/frequent) to approximate A+, Braak stage (IV‐VI) for T+, and temporal pole lateral ventricular dilation for (N)+. Outcomes included dementia prevalence at death and incidence in the last 5 years of life. A+T+(N)+ was the most common profile (31%). Dementia prevalence ranged from 14% (A–T–[N]–) to 79% (A+T+[N]+). Between 8% (A+T–[N]–) and 68% (A+T+[N]–) of decedents developed incident dementia in the last 5 years of life. Clinical trials would incur substantial expense to characterize AT(N). Many people with biomarker‐defined preclinical Alzheimer's disease will never develop clinical dementia during life, highlighting resilience to clinical expression of AD neuropathologic changes and the need for improved tools for prediction beyond current AT(N) biomarkers.
Selectivity and Targeting of G‐Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics
Authors: Zhu Bo‐Chen , He Juan , Liu Wenting , Xia Xiao‐Yu , Liu Liu‐Yi , Liang Bing‐Bing , Yao Hua‐Gang , Liu Bing , Ji Liang‐Nian , Mao Zong‐Wan
Published: April 2021

G‐quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4‐DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF‐G4 (a promoter G4) shows that Pt1 matches 3′‐G‐tetrad of VEGF‐G4 through Cl−‐dissociation and loop rearrangement of VEGF‐G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate‐determining binding step, Cl−‐dissociation upon G4‐binding, is 2–3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4‐binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.
Ambiphilic Al−Cu Bonding
Authors: Liu Han‐Ying , Schwamm Ryan J. , Hill Michael S. , Mahon Mary F. , McMullin Claire L. , Rajabi Nasir A.
Published: April 2021

Copper‐alumanyl complexes, [LCu‐Al(SiNDipp)], where L=carbene=NHCiPr(N,N′‐diisopropyl‐4,5‐dimethyl‐2‐ylidene) andMe2CAAC (1‐(2,6‐diisopropylphenyl)‐3,3,5,5‐tetramethyl‐pyrrolidin‐2‐ylidene) and featuring unsupported Al−Cu bonds, have been prepared. Divergent reactivity observed with carbodiimides and CO2implies an ambiphilicity in the Cu–Al interaction that is dependent on the identity of the carbene co‐ligand.
Cyclic Diaryl λ3‐Bromanes as Original Aryne Precursors
Authors: Lanzi Matteo , Dherbassy Quentin , Wencel‐Delord Joanna
Published: April 2021

Despite the widespread application of hypervalent iodines, the corresponding λ3‐bromanes are less explored. Herein we report a general, safe, and high‐yielding strategy to access cyclic diaryl λ3‐bromanes. These unique compounds feature reactivity that is appealing and complementary to that of λ3‐iodanes, generating arynes under mild reaction conditions and in the presence of a weak base. Accordingly, formal meta‐selective transition‐metal‐free C–O and C–N couplings may be achieved. Mechanistic studies unambiguously support the aryne generation mechanism.
Synthesis of new 1,2,4‐triazole–(thio)semicarbazide hybrid molecules: Their tyrosinase inhibitor activities and molecular docking analysis
Authors: Gultekin Ergün , Bekircan Olcay , Kolcuoğlu Yakup , Akdemir Atilla
Published: April 2021

Tyrosinase inhibition is very important in controlling melanin synthesis. If melanin synthesis is not controlled in metabolism, an unwanted increase in melanin synthesis occurs. As melanin plays a role in the formation of skin color, its unusual levels cause some skin disorders such as pregnancy scars, age spots, and especially skin cancer (melanoma). However, the tyrosinase activity is also related to Parkinson's disease and some neurodegenerative diseases. For all these reasons, the medicinal as well as the cosmetic industries focus on research on tyrosinase inhibitors for the treatment of skin disorders and some neurodegenerative diseases. In this study, 32 new 1,2,4‐triazole–(thio)semicarbazide hybrid molecules (6a–p and 7a–p) were synthesized, starting from 4‐amino‐1‐pentyl‐3‐phenyl‐1H‐1,2,4‐triazole‐5(4H)‐one. These compounds were evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 6h, 6m, 6n, and 6p exhibited the most effective inhibitory activity, with IC50 values of 0.00162 ± 0.0109, 0.00166 ± 0.0217, 0.00165 ± 0.019, and 0.00197 ± 0.0063 μM, respectively, compared with kojic acid as the reference drug (IC50 = 14.09 ± 0.02 μM). Also, molecular docking analyses were performed to suggest possible binding poses for the ligands. As a result, derivatives 6h, 6m, 6n, and 6p can be used as promising tyrosinase inhibitor candidates in the medicinal, cosmetics, or food industries.