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Open AccessEditorial
Sleeping Sickness at the Crossroads
Trop. Med. Infect. Dis. 2020, 5(2), 57; https://doi.org/10.3390/tropicalmed5020057 (registering DOI) - 08 Apr 2020
Abstract
Human African trypanosomiasis (HAT; sleeping sickness) is a disease with truly historic dimensions. Its maximum possible distribution corresponds to the range of tsetse flies, which covers an area of eight million km2 between 14° North and 20° South latitude on the African [...] Read more.
Human African trypanosomiasis (HAT; sleeping sickness) is a disease with truly historic dimensions. Its maximum possible distribution corresponds to the range of tsetse flies, which covers an area of eight million km2 between 14° North and 20° South latitude on the African continent. (...) Full article
Open AccessFeature PaperArticle
A Phosphite Dehydrogenase Variant with Promiscuous Access to Nicotinamide Cofactor Pools Sustains Fast Phosphite-Dependent Growth of Transplastomic Chlamydomonas reinhardtii
Plants 2020, 9(4), 473; https://doi.org/10.3390/plants9040473 (registering DOI) - 08 Apr 2020
Abstract
Heterologous expression of the NAD+-dependent phosphite dehydrogenase (PTXD) bacterial enzyme from Pseudomonas stutzerii enables selective growth of transgenic organisms by using phosphite as sole phosphorous source. Combining phosphite fertilization with nuclear expression of the ptxD transgene was shown to be an [...] Read more.
Heterologous expression of the NAD+-dependent phosphite dehydrogenase (PTXD) bacterial enzyme from Pseudomonas stutzerii enables selective growth of transgenic organisms by using phosphite as sole phosphorous source. Combining phosphite fertilization with nuclear expression of the ptxD transgene was shown to be an alternative to herbicides in controlling weeds and contamination of algal cultures. Chloroplast expression of ptxD in Chlamydomonas reinhardtii was proposed as an environmentally friendly alternative to antibiotic resistance genes for plastid transformation. However, PTXD activity in the chloroplast is low, possibly due to the low NAD+/NADP+ ratio, limiting the efficiency of phosphite assimilation. We addressed the intrinsic constraints of the PTXD activity in the chloroplast and improved its catalytic efficiency in vivo via rational mutagenesis of key residues involved in cofactor binding. Transplastomic lines carrying a mutagenized PTXD version promiscuously used NADP+ and NAD+ for converting phosphite into phosphate and grew faster compared to those expressing the wild type protein. The modified PTXD enzyme also enabled faster and reproducible selection of transplastomic colonies by directly plating on phosphite-containing medium. These results allow using phosphite as selective agent for chloroplast transformation and for controlling biological contaminants when expressing heterologous proteins in algal chloroplasts, without compromising on culture performance. Full article
(This article belongs to the collection Feature Papers in Plant Physiology and Metabolism)
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Open AccessArticle
Research on Novel Control Strategy for Grid-Connected Inverter Suitable for Wide-Range Grid Impedance Variation
Electronics 2020, 9(4), 623; https://doi.org/10.3390/electronics9040623 (registering DOI) - 08 Apr 2020
Abstract
With the higher penetration of renewable energy, the influence of grid equivalent distribution cable impedance on grid-connected inverter stability is attracting increasing attention. In order to suppress the interaction between grid distribution cable impedance and output impedance of the grid-connected system, the active [...] Read more.
With the higher penetration of renewable energy, the influence of grid equivalent distribution cable impedance on grid-connected inverter stability is attracting increasing attention. In order to suppress the interaction between grid distribution cable impedance and output impedance of the grid-connected system, the active damping strategy is often used. When a capacitive current loop is used, the damping coefficient increases with the grid impedance increasing. However, the excessive damping coefficient will cause the unstable operation of the system. In order to enhance the robustness of the system, a novel control strategy which is suitable for wide-range grid impedance variation is proposed. In this strategy, the capacitor current inner loop is combined with the grid current inner loop, and grid voltage feedforward is included. Since the virtual impedance, active damping and voltage feed-forward are normalized, the changing tendency of the damping coefficient of the grid-current inner loop is opposite to that of capacitor current inner-loop. The overall damping coefficient of the system remains relatively constant when the grid impedance changes, and this effectively suppresses the resonance of the system. In this paper, the method is analyzed and the parameters are designed and optimized. Finally, the simulation and experiment are presented to verify the analysis. Full article
(This article belongs to the Section Power Electronics)
Open AccessArticle
Electromagnetic Loss Analysis of a Linear Motor System Designed for a Free-Piston Engine Generator
Electronics 2020, 9(4), 621; https://doi.org/10.3390/electronics9040621 - 08 Apr 2020
Abstract
A free-piston engine generator is a new type of power generating device, which has the advantages of high efficiency and simple structure. In this paper, a linear motor system composed of a moving-coil linear motor with axial magnetized magnets and a H-bridge pulse-width [...] Read more.
A free-piston engine generator is a new type of power generating device, which has the advantages of high efficiency and simple structure. In this paper, a linear motor system composed of a moving-coil linear motor with axial magnetized magnets and a H-bridge pulse-width modulation (PWM) rectifier is designed for portable free-piston engine generators. Based on the finite-element model of the motor and physical model of the rectifier, the combined electromagnetic model is presented and then validated by the prototype-tested results. The electromagnetic processes of the linear motor system are simulated. The electromagnetic losses during the standard working cycle are analyzed. Under the rated reciprocating frequency of 50 Hz and the rated reciprocating stroke of 36 mm, the mechanical-to-electrical energy conversion efficiency of 86.3% can be obtained by the linear motor system, which meets the requirement of portable free-piston engine generators. Full article
(This article belongs to the Section Systems & Control Engineering)
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Open AccessReview
Methionine Dependence of Cancer
Biomolecules 2020, 10(4), 568; https://doi.org/10.3390/biom10040568 (registering DOI) - 08 Apr 2020
Abstract
Tumorigenesis is accompanied by the reprogramming of cellular metabolism. The shift from oxidative phosphorylation to predominantly glycolytic pathways to support rapid growth is well known and is often referred to as the Warburg effect. However, other metabolic changes and acquired needs that distinguish [...] Read more.
Tumorigenesis is accompanied by the reprogramming of cellular metabolism. The shift from oxidative phosphorylation to predominantly glycolytic pathways to support rapid growth is well known and is often referred to as the Warburg effect. However, other metabolic changes and acquired needs that distinguish cancer cells from normal cells have also been discovered. The dependence of cancer cells on exogenous methionine is one of them and is known as methionine dependence or the Hoffman effect. This phenomenon describes the inability of cancer cells to proliferate when methionine is replaced with its metabolic precursor, homocysteine, while proliferation of non-tumor cells is unaffected by these conditions. Surprisingly, cancer cells can readily synthesize methionine from homocysteine, so their dependency on exogenous methionine reflects a general need for altered metabolic flux through pathways linked to methionine. In this review, an overview of the field will be provided and recent discoveries will be discussed. Full article
(This article belongs to the Special Issue Targeting Tumor Metabolism: From Mechanisms to Therapies)
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Open AccessArticle
High Temperature Oxidation and Thermal Shock Properties of La2Zr2O7 Thermal Barrier Coatings Deposited on Nickel-Based Superalloy by Laser-Cladding
Coatings 2020, 10(4), 370; https://doi.org/10.3390/coatings10040370 (registering DOI) - 08 Apr 2020
Abstract
In order to reduce the difficulty and cost of manufacturing and improve the high temperature oxidation and thermal shock properties of nickel-based superalloy, a thin La2Zr2O7 thermal barrier coating without bond coat was successfully prepared by laser-cladding using [...] Read more.
In order to reduce the difficulty and cost of manufacturing and improve the high temperature oxidation and thermal shock properties of nickel-based superalloy, a thin La2Zr2O7 thermal barrier coating without bond coat was successfully prepared by laser-cladding using La2Zr2O7 powders on a nickel-based superalloy substrate. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) methods were used to characterize the microstructure of the coating. The high temperature oxidation and thermal shock properties of the coating were evaluated by the air isothermal oxidation method at 1100 °C for 110 h and thermal cycling method at 25~1100 °C, respectively. The results show that the coating is mainly composed of La2Zr2O7 phase. The oxidation weight gain rate of the coating is about two-thirds of that of the substrate, and the first crack thermal shock lifetime of the coating is about 1.67 times of that of the substrate. The oxidation products of the coating are mainly Fe2O3, Cr2O3, NiCr2O4, Nb2O5 and La2Zr2O7. The existence of La2Zr2O7 phase in the coating is the main reason for the improvement of its oxidation resistance at 1100 °C and its thermal shock resistance at 25~1100 °C. Full article
(This article belongs to the Special Issue Surface Treatment by Laser-Assisted Techniques)
Open AccessArticle
Equilibria in DPPC-Diosgenin and DPPC-Diosgenin Acetate Bilayer Lipid Membranes: Interfacial Tension and Microelectrophoretic Studies
Coatings 2020, 10(4), 368; https://doi.org/10.3390/coatings10040368 (registering DOI) - 08 Apr 2020
Abstract
Interactions between components of model lipid membranes (spherical lipid bilayers and liposomes) are investigated here. Parameters characterizing equilibria in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin (Dio) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin acetate (DAc) membrane systems have been determined. The interfacial tension measurement of spherical [...] Read more.
Interactions between components of model lipid membranes (spherical lipid bilayers and liposomes) are investigated here. Parameters characterizing equilibria in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin (Dio) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin acetate (DAc) membrane systems have been determined. The interfacial tension measurement of spherical lipid bilayers was based on the Young-Laplace’s equation using a homemade computer-controlled device. We assume a 1:1 complex in the DPPC-Dio and DPPC-DAc membrane systems. The parameters A 3 1 , the surface concentration of lipid membranes formed from these complexes, γ 3 , the interfacial tension of such membranes, and, K, the constant stability of these complexes were calculated. Microelectrophoresis was used for examinations of the surface charge density of lipid membranes. The values were obtained here from electrophoretic mobility data applying Smoluchowsky’s equation. The effect of pH (pH ranged of 2 to 10) on the electrolyte solution and the compositions of the membranes was analyzed. The obtained results indicate that the modification of DPPC membranes with both Dio and DAc causes changes in surface charge density values and shifts of the isoelectric point. Full article
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Open AccessArticle
Assessing the Productivity of Common Bean in Intercrop with Maize across Agro-Ecological Zones of Smallholder Farms in the Northern Highlands of Tanzania
Agriculture 2020, 10(4), 117; https://doi.org/10.3390/agriculture10040117 - 08 Apr 2020
Abstract
Common bean (Phaseolus vulgaris L.) is an important grain legume for food and cash of the smallholder farmers worldwide. However, the total potential benefits to be derived from the common bean as a source of food and income, its complementarities with non-legume [...] Read more.
Common bean (Phaseolus vulgaris L.) is an important grain legume for food and cash of the smallholder farmers worldwide. However, the total potential benefits to be derived from the common bean as a source of food and income, its complementarities with non-legume food crops, and significance to the environment are underexploited. Intensification of common bean could provide approaches that offer new techniques to better manage and monitor globally complex systems of sustainable food production. Therefore, this study tried to assess the productivity of common bean bushy varieties when are involved as part of an intercrop with maize (Zea mays L.) in varying agro-ecological zones. The factors evaluated were the cropping seasons/years (S) (2015 and 2016), agro-ecological zones (A) above sea level (lower 843 m, middle 1051 m, upper 1743 m), and cropping systems (C) (sole, intercrop). The data collected were the total biomass, number of pods per plant and seeds per pod, 100-seed weight as yield components, and grain yield. Bean and maize grain yields were used to calculate the partial (P) and total land equivalent ratio (LER). Results indicated that the main effects of S, A, C, and the interaction effects of S × A, S × C, S × A × C were significant on bean grain yields. Interactions of S × A × C were also significant on all measured variables. Results also indicated that continuous intercropping of bean with maize over two cropping seasons resulted in the increase of bean grain yields from 1.5 to 2.3 t ha−1 in the lower altitude, 2.0 to 2.3 t ha−1 in the middle altitude, and 1.8 to 2.9 t ha−1 in the upper altitude. Land utilization advantage of intercrops over monocultures yielded a total LER of 1.58, whereas the average partial land equivalent ratio (PLER) of individual beans was 1.53. Full article
(This article belongs to the Special Issue Productivity, Efficiency, and Sustainability in Agriculture)
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Open AccessArticle
Adaptive Human–Machine Evaluation Framework Using Stochastic Gradient Descent-Based Reinforcement Learning for Dynamic Competing Network
Appl. Sci. 2020, 10(7), 2558; https://doi.org/10.3390/app10072558 (registering DOI) - 08 Apr 2020
Abstract
Complex problems require considerable work, extensive computation, and the development of effective solution methods. Recently, physical hardware- and software-based technologies have been utilized to support problem solving with computers. However, problem solving often involves human expertise and guidance. In these cases, accurate human [...] Read more.
Complex problems require considerable work, extensive computation, and the development of effective solution methods. Recently, physical hardware- and software-based technologies have been utilized to support problem solving with computers. However, problem solving often involves human expertise and guidance. In these cases, accurate human evaluations and diagnoses must be communicated to the system, which should be done using a series of real numbers. In previous studies, only binary numbers have been used for this purpose. Hence, to achieve this objective, this paper proposes a new method of learning complex network topologies that coexist and compete in the same environment and interfere with the learning objectives of the others. Considering the special problem of reinforcement learning in an environment in which multiple network topologies coexist, we propose a policy that properly computes and updates the rewards derived from quantitative human evaluation and computes together with the rewards of the system. The rewards derived from the quantitative human evaluation are designed to be updated quickly and easily in an adaptive manner. Our new framework was applied to a basketball game for validation and demonstrated greater effectiveness than the existing methods. Full article
(This article belongs to the Section Applied Industrial Technologies)
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Open AccessArticle
Automatic Expanding Mandrel with Air Sensing Device: Design and Analysis
Appl. Sci. 2020, 10(7), 2551; https://doi.org/10.3390/app10072551 (registering DOI) - 08 Apr 2020
Abstract
In precision machining, expanding mandrels are used for jobs with close tolerances. An expanding mandrel consists of a tapered arbor or shaft, with a thin-slotted clamping sleeve or collet made of hardened steel. The internal tapered and external cylindrical surfaces are ground to [...] Read more.
In precision machining, expanding mandrels are used for jobs with close tolerances. An expanding mandrel consists of a tapered arbor or shaft, with a thin-slotted clamping sleeve or collet made of hardened steel. The internal tapered and external cylindrical surfaces are ground to a high degree of accuracy, and the mandrel expands to fit the internal bore of the workpiece. Expanding mandrels are, essentially, wedge mechanisms. This paper proposes an automatic expanding mandrel with a novel force transmission system for high stiffness within a novel air sensing system, which allows detection of the correct part position before starting machining. A computational model for determining the dynamic clamping force of the proposed mechanism is developed and implemented using MATLAB. This model considers the influence of the stiffness behaviors of the collet, force transmission structure and workpiece. Additionally, this paper presents the finite element method analyses which were conducted to check the proposed computational model. The amount of clamping force transmitted by a collet chuck holder depends strongly on: clearances, wedge angle, stiffness of the collet chuck holder and workpiece stiffness. Full article
(This article belongs to the Section Mechanical Engineering)
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Open AccessArticle
The Aqueous Extract from Ceratonia siliqua Leaves Protects Against 6-hydroxydopamine in Zebrafish: Understanding the Underlying Mechanism
Antioxidants 2020, 9(4), 304; https://doi.org/10.3390/antiox9040304 (registering DOI) - 08 Apr 2020
Abstract
Ceratonia siliqua L. is a Mediterranean medicinal plant traditionally cultivated for its ethnopharmacological benefits, such as antidiarrheal, antidiabetic, enhance acetylcholine, antioxidant, antiatherosclerotic, and for its possible anti-neurodegenerative potential. The aim of the present study was to evaluate the chemical composition, as well as [...] Read more.
Ceratonia siliqua L. is a Mediterranean medicinal plant traditionally cultivated for its ethnopharmacological benefits, such as antidiarrheal, antidiabetic, enhance acetylcholine, antioxidant, antiatherosclerotic, and for its possible anti-neurodegenerative potential. The aim of the present study was to evaluate the chemical composition, as well as the cognitive-enhancing, anxiolytic, and antioxidant activities of the aqueous extract from C. siliqua (CsAE) leaves against 6-hydroxydopamine (6-OHDA) zebrafish Parkinson’s disease (PD) model. CsAE (0.1, 0.3, and 1 mg/L) was administered by immersion to zebrafish (Danio rerio) for eight consecutive days and one hour before each behavioral test of each day, while 6-OHDA (250 µM) treatment was supplied one day before the novel tank diving test (NTT). Qualitative and quantitative analyses were performed by the ultra-high-performance liquid chromatography (UHPLC) analysis. The memory performance was evaluated through the NTT and Y-maze tests. Additionally, the in vitro and in vivo antioxidant status and acetylcholinesterase (AChE) activity was also assessed. Our finds demonstrated that CsAE presented positive antioxidant and anti-AChE activities, which contributed to the improvement of cognitive function in the 6-OHDA zebrafish PD model. Full article
(This article belongs to the Special Issue Oxidative Stress, DNA Damage and Biological Clinical Effects)
Open AccessArticle
The Effect of Nanoparticle Shape and Microchannel Geometry on Fluid Flow and Heat Transfer in a Porous Microchannel
Symmetry 2020, 12(4), 591; https://doi.org/10.3390/sym12040591 (registering DOI) - 08 Apr 2020
Abstract
Microchannels are widely used in electrical and medical industries to improve the heat transfer of the cooling devices. In this paper, the fluid flow and heat transfer of water–Al2O3 nanofluids (NF) were numerically investigated considering the nanoparticle shape and different [...] Read more.
Microchannels are widely used in electrical and medical industries to improve the heat transfer of the cooling devices. In this paper, the fluid flow and heat transfer of water–Al2O3 nanofluids (NF) were numerically investigated considering the nanoparticle shape and different cross-sections of a porous microchannel. Spherical, cubic, and cylindrical shapes of the nanoparticle as well as circular, square, and triangular cross-sections of the microchannel were considered in the simulation. The finite volume method and the SIMPLE algorithm have been employed to solve the conservation equations numerically, and the k-ε turbulence model has been used to simulate the turbulence fluid flow. The models were simulated at Reynolds number ranging from 3000 to 9000, the nanoparticle volume fraction ranging from 1 to 3, and a porosity coefficient of 0.7. The results indicate that the average Nusselt number (Nuave) increases and the friction coefficient decreases with an increment in the Re for all cases. In addition, the rate of heat transfer in microchannels with triangular and circular cross-sections is reduced with growing Re values and concentration. The spherical nanoparticle leads to maximum heat transfer in the circular and triangular cross-sections. The heat transfer growth for these two cases are about 102.5% and 162.7%, respectively, which were obtained at a Reynolds number and concentration of 9000 and 3%, respectively. However, in the square cross-section, the maximum heat transfer increment was obtained using cylindrical nanoparticles, and it is equal to 80.2%. Full article
(This article belongs to the Special Issue Aero/Hydrodynamics and Symmetry 2020)
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Open AccessArticle
Timing Comparison of the Real-Time Operating Systems for Small Microcontrollers
Symmetry 2020, 12(4), 592; https://doi.org/10.3390/sym12040592 (registering DOI) - 08 Apr 2020
Abstract
In automatic systems used in the control and monitoring of industrial processes, fieldbuses with specific real-time requirements are used. Often, the sensors are connected to these fieldbuses through embedded systems, which also have real-time features specific to the industrial environment in which it [...] Read more.
In automatic systems used in the control and monitoring of industrial processes, fieldbuses with specific real-time requirements are used. Often, the sensors are connected to these fieldbuses through embedded systems, which also have real-time features specific to the industrial environment in which it operates. The embedded operating systems are very important in the design and development of embedded systems. A distinct class of these operating systems is real-time operating systems (RTOSs) that can be used to develop embedded systems, which have hard and/or soft real-time requirements on small microcontrollers (MCUs). RTOSs offer the basic support for developing embedded systems with applicability in a wide range of fields such as data acquisition, internet of things, data compression, pattern recognition, diversity, similarity, symmetry, and so on. The RTOSs provide basic services for multitasking applications with deterministic behavior on MCUs. The services provided by the RTOSs are task management and inter-task synchronization and communication. The selection of the RTOS is very important in the development of the embedded system with real-time requirements and it must be based on the latency in the handling of the critical operations triggered by internal or external events, predictability/determinism in the execution of the RTOS primitives, license costs, and memory footprint. In this paper, we measured and compared the timing performance for synchronization throughout an event, semaphore, and mailbox for the following RTOSs: FreeRTOS 9.0.0, FreeRTOS 10.2.0, rt-thread, Keil RTX, uC/OS-II, and uC/OS-III. For the experimental tests, we developed test applications for two MCUs: ARM Cortex™-M4 and ARM Cortex™-M0+ based MCUs. Full article
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Open AccessArticle
A Comprehensive Multi-Scenario Routing Algorithm Based on Fuzzy Control Theory in Opportunistic Social Network
Symmetry 2020, 12(4), 589; https://doi.org/10.3390/sym12040589 (registering DOI) - 08 Apr 2020
Abstract
With the flourishing of big data and the 5G era, the amount of data to be transmitted in the communication process is increasing, and end-to-end communication in traditional social networks has been unable to meet the current communication needs. Therefore, in order to [...] Read more.
With the flourishing of big data and the 5G era, the amount of data to be transmitted in the communication process is increasing, and end-to-end communication in traditional social networks has been unable to meet the current communication needs. Therefore, in order to improve the success rate of data forwarding, social networks propose that the sender of the message should reasonably choose the next hop node. However, existing routing and forwarding algorithms do not take into account nodes that are live in different scenarios, and the applicable next hop node metrics are also different. These algorithms only consider the forwarding preferences of the nodes during working hours and do not consider the forwarding preferences of the nodes during non-working hours. We propose a routing algorithm based on fuzzy decision theory, which aims at a more accurate decision on selecting the next hop. A routing and forwarding algorithm based on fuzzy decision is proposed in this paper. This algorithm symmetrical divides scenes in opportunistic social networks into working time and non-working time according to real human activity. In addition, metrics are designed symmetrically for these two scenarios. Simulation results demonstrate that, in the best case, the proposed scheme presents an average delivery ratio of 0.95 and reduces the average end-to-end delay and average overhead compared with the epidemic routing algorithm, the EIMSTalgorithm, the ICMT algorithm, and the FCNSalgorithm. Full article
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Open AccessArticle
Living at the Water’s Edge: A World-Wide Econometric Panel Estimation of Arable Water Footprint Drivers
Water 2020, 12(4), 1060; https://doi.org/10.3390/w12041060 (registering DOI) - 08 Apr 2020
Abstract
As part of the Sustainable Development Goal (SDG) for ensuring clean water and sanitation worldwide by 2030, SDG target 6.4 seeks to attain sustainable withdrawals of freshwater through efficiency gains with a view to relieving water stress in vulnerable populated areas. The water [...] Read more.
As part of the Sustainable Development Goal (SDG) for ensuring clean water and sanitation worldwide by 2030, SDG target 6.4 seeks to attain sustainable withdrawals of freshwater through efficiency gains with a view to relieving water stress in vulnerable populated areas. The water footprint (WF) is a key metric to measure this concept, although the dynamics of the drivers of the WF through space and time remain relatively under-researched, whilst in foresight studies, the WF is often subject to simplistic assumptions. Thus, constructing a panel dataset of 130 countries and 156 crops for the period 2002–2016, this paper empirically assesses the sign and magnitude of WF drivers of agricultural crop activities, employing a careful selection of demographic, economic and climatic drivers. The study uncovers evidence of significant deviations in WF drivers across regions segmented by relative wealth, relating specifically to the stage of economic development and the presence (absence) of economies of scale, whilst we confirm that geographical coordinates have a major bearing on the climatic WF driver. Moreover, examining the temporal dimension, there is compelling evidence supporting a structural break in the role that technical progress exerted on the WF prior to, and in the wake of, the 2008 financial crisis. Full article
(This article belongs to the Special Issue Virtual Water Trade and Water Resources Economics)
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Open AccessFeature PaperArticle
Contribution of the Potassium Channels KV1.3 and KCa3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries
Cells 2020, 9(4), 913; https://doi.org/10.3390/cells9040913 (registering DOI) - 08 Apr 2020
Abstract
Collateral artery growth (arteriogenesis) involves the proliferation of vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Whereas the proliferation of ECs is directly related to shear stress, the driving force for arteriogenesis, little is known about the mechanisms of SMC proliferation. Here [...] Read more.
Collateral artery growth (arteriogenesis) involves the proliferation of vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Whereas the proliferation of ECs is directly related to shear stress, the driving force for arteriogenesis, little is known about the mechanisms of SMC proliferation. Here we investigated the functional relevance of the potassium channels KV1.3 and KCa3.1 for SMC proliferation in arteriogenesis. Employing a murine hindlimb model of arteriogenesis, we found that blocking KV1.3 with PAP-1 or KCa3.1. with TRAM-34, both interfered with reperfusion recovery after femoral artery ligation as shown by Laser-Doppler Imaging. However, only treatment with PAP-1 resulted in a reduced SMC proliferation. qRT-PCR results revealed an impaired downregulation of α smooth muscle-actin (αSM-actin) and a repressed expression of fibroblast growth factor receptor 1 (Fgfr1) and platelet derived growth factor receptor b (Pdgfrb) in growing collaterals in vivo and in primary murine arterial SMCs in vitro under KV1.3. blockade, but not when KCa3.1 was blocked. Moreover, treatment with PAP-1 impaired the mRNA expression of the cell cycle regulator early growth response-1 (Egr1) in vivo and in vitro. Together, these data indicate that KV1.3 but not KCa3.1 contributes to SMC proliferation in arteriogenesis. Full article
(This article belongs to the Special Issue Arteriogenesis and Therapeutic Neovascularization)
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Open AccessFeature PaperReview
Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses
Cells 2020, 9(4), 915; https://doi.org/10.3390/cells9040915 (registering DOI) - 08 Apr 2020
Abstract
Following fifteen years of research, neutrophil extracellular traps (NETs) are widely reported in a large range of inflammatory infectious and non-infectious diseases. Cumulating evidences from in vitro, in vivo and clinical diagnostics suggest that NETs may play a crucial role in inflammation and [...] Read more.
Following fifteen years of research, neutrophil extracellular traps (NETs) are widely reported in a large range of inflammatory infectious and non-infectious diseases. Cumulating evidences from in vitro, in vivo and clinical diagnostics suggest that NETs may play a crucial role in inflammation and autoimmunity in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Most likely, NETs contribute to breaking self-tolerance in autoimmune diseases in several ways. During this review, we discuss the current knowledge on how NETs could drive autoimmune responses. NETs can break self-tolerance by being a source of autoantigens for autoantibodies found in autoimmune diseases, such as anti-citrullinated protein antibodies (ACPAs) in RA, anti-dsDNA in SLE and anti-myeloperoxidase and anti-protein 3 in AAV. Moreover, NET components could accelerate the inflammatory response by mediating complement activation, acting as danger-associated molecular patterns (DAMPs) and inflammasome activators, for example. NETs also can activate other immune cells, such as B cells, antigen-presenting cells and T cells. Additionally, impaired clearance of NETs in autoimmune diseases prolongs the presence of active NETs and their components and, in this way, accelerate immune responses. NETs have not only been implicated as drivers of inflammation, but also are linked to resolution of inflammation. Therefore, NETs may be central regulators of inflammation and autoimmunity, serve as biomarkers, as well as promising targets for future therapeutics of inflammatory autoimmune diseases. Full article

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