COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever and control inflammation. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

Measurements of optical properties have been used for decades to study particle distributions in the ocean. They have been found useful to constrain suspended mass concentration as well as particle-related properties such as size, composition, packing (particle porosity or density) and settling velocity. Optical properties, however, provide measurements that are biased, as certain particles (based on size, composition, shape or packing) contribute to a specific property more than others. Here we study this issue both theoretically as well as by contrasting different optical properties collected simultaneously in a bottom boundary layer, to highlight the utility of such measurements as well as the biases we are likely to encounter using different optical properties to study suspended particles. In particular, we investigate the possibility to infer settling velocity from vertical profiles of optical measurements, finding that the effects of aggregation dynamics can seldom be ignored.

In this paper, we will revisit the derivation of Heisenberg's uncertainty principle. We will see how the Heisenberg principle collapses at the Planck scale by introducing a minor modification. The beauty of our suggested modification is that it does not change the main equations in quantum mechanics; it only gives them a Planck scale limit where uncertainty collapses. We suspect that Einstein could have been right after all, when he stated, ``God does not throw dice." His now-famous saying was an expression of his skepticism towards the concept that quantum randomness could be the ruling force, even at the deepest levels of reality. Here we will explore the quantum realm with a fresh perspective, by re-deriving the Heisenberg principle in relation to the Planck scale. We will show how this idea also leads to an upper boundary on uncertainty, in addition to the lower boundary. These upper and lower boundaries are identical for the Planck mass particle; in fact, they are zero, and this highlights the truly unique nature of the Planck mass particle. Further, there may be a close connection between light and the Planck mass particle: In our model, the standard relativistic energy momentum relation also seems to apply to light, while in modern physics light generally stands outside the standard relativistic momentum energy relation. We will also suggest a new way to look at elementary particles, where mass and time are closely related, consistent with some of the recent work in experimental physics. Our model leads to a new time operator that does not appear to be in conflict with the Pauli objection. This indicates that both mass and momentum come in quanta, which are perfectly correlated to an internal Compton `clock' frequency in elementary particles.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

In this paper, we first discuss the research status and application progress of the finite element method and the smoothed particle method. By analyzing the advantages of the smoothed particle method and the finite element method, a new coupling algorithm, namely FEM-SPH algorithm, is proposed. By the method of comparison, it shows that finite element method and SPH method in the simulation of large deformation problems each have advantages and disadvantages, the finite element method smoothed particle coupling algorithm is effective to achieve the performance of high computational efficiency and can naturally simulate large deformation problems across. In the process of calculation, the large deformation unit can be freely into an algorithm to facilitate the calculation accuracy and efficiency of three methods of numerical simulation. Through the study found, FEM-SPH algorithm not only overcome the defect of smooth particle tensile instability, but also overcomes the problem of low efficiency of finite element computation. To further test the FEM-SPH algorithm has advantages in the practical engineering, we have carried out the actual test to the example of the super high speed collision, concluded that, since the target of most of the computational domain is always finite element, smoothed particle focused only in contact with the projectile and target of local area, particle number is not much, the whole calculation process just ten minutes, computational efficiency has been greatly improved, at the same time in the simulation of large deformation, the advantage is very obvious .This provides a criterion for the actual project, depending on the specific material deformation mode and choose a more appropriate conversion algorithm.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don’t suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients’ health after the active phase of the infection is over.

Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cell line than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC₅₀ values against these cancer cells were approximately 10000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity.

This paper presents the results of an experimental investigation about target detecting with passive sonar in Persian Gulf. Detecting propagated sounds in the water is one of the basic challenges of the researchers in sonar field. This challenge will be complex in shallow water (like Persian Gulf) and noise less vessels. Generally, in passive sonar the targets are detected by sonar equation (with constant threshold) which increase the detection error in shallow water. Purpose of this study is proposed a new method for detecting targets in passive sonars using adaptive threshold. In this method, target signal (sound) is processed in time and frequency domain. For classifying, Bayesian classification is used and prior distribution is estimated by Maximum Likelihood algorithm. Finally, target was detected by combining the detection points in both domains using LMS adaptive filter. Results of this paper has showed that proposed method has improved true detection rate about 27% compare other the best detection method.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

In this paper we report a new development on the numerical model for aluminum-steam combustion. This model is based on diffusion flame of continuum regime and the thermal equilibrium between the particle and the flow field, which can be used to calculate the aluminum particle combustion model for two phase calculation conditions. The model prediction is in good agreement with the experimental data. A new type of vortex combustor was proposed for the combustion of aluminum and steam, and the mathematical model of the two phase reacting flow with in this combustor was established. The turbulence effects are modeled using the Reynolds Stress Model (RSM) with Linear Pressure-Strain approach, and the Eddy-Dissipation model is used to simulate the gas phase combustion. Aluminum particles are injected into the vortex combustor and form a swirling flow around the chamber and their trajectories are traced using the Discrete Phase Model (DPM). The simulation results show that the vortex combustor can achieve high efficient combustion of aluminum and steam. The influencing factors, such as the eccentric distance of the inlet of aluminum particles, particle size and steam inlet diameter, etc., are studied. The work described in this paper represents an attempt to the design of a vortex combustor in order to increase aluminum combustion efficiency.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

This study was aimed at investigating the effects of roasting and cryogenic milling on particle size, water solubility, and amount of bioactive components in ginseng root. Samples were pulverized by cryogenic milling, and one treatment condition was selected for each size range (10-50 μm, and >50 μm). The selected samples were roasted at different temperatures (160-200 °C) followed by cryogenic milling. Powdered samples were analyzed for their physicochemical characteristics. Results revealed that roasted samples exhibited significantly smaller particle size than controls (not roasted, p<0.05), and the particle size of roasted samples decreased with increase in roasting temperature until flocculation occurred around 180-190 °C. With decrease in particle size of ginseng; water solubility index, antioxidant activity, total polyphenol content, and total polysaccharide content were observed to increase. Ginseng samples showed an increasing trend in antioxidant activity with decreasing particle size (p>0.05) with significantly higher values for all roasted samples compared to the controls (p<0.05). Non-polar ginsenosides such as Rg2(S), Rg2(R), Rg3(S), Rg3(R), and Rh1(S) showed an increase in temperature-dependent manner. This study revealed that roasting at certain temperature range with cryogenic milling has positive effects on ginseng by reducing its particle size, and increasing water solubility and bioactive components.

The greenhouse gases and air pollution generated by extensive energy use have exacerbated climate change. An electric-bus (e-bus) transportation system favors reducing pollution and carbon emissions. This study analyzed the minimization of construction costs for an all battery-swapping public e-bus transportation system. A simulation was conducted according to existing timetables and routes. Daytime charging was incorporated during the hours of operation; the two parameters of the daytime charging scheme were the residual battery capacity and battery-charging energy during various intervals of daytime peak electricity hours. The parameters were optimized using three algorithms: particle swarm optimization (PSO), a genetic algorithm (GA), and a PSO–GA. This study observed the effects of optimization on cost changes (e.g., number of e-buses, on-board battery capacity, number of extra batteries, charging facilities, and energy consumption) and compared the plug-in and battery-swapping e-bus systems. The results revealed that daytime charging can reduce the construction costs of both systems. In contrast to the other two algorithms, the PSO–GA yielded the most favorable optimization results for the charging scheme. Finally, according to the cases investigated and the parameters of this study, the construction cost of the plug-in e-bus system was lower than that of the battery-swapping e-bus system.

Recycling waste products is an environmental-friendly activity that can bring benefits to accompany, saving manufacturing costs and improving economic efficiency. For the beer industry, recycling bottles can reduce manufacturing costs and reduce the industry's carbon footprint. This paper presents a model for a multi-objective collection-distribution center location and allocation problem in a closed loop supply chain for the beer industry, in which the objective is to minimize total costs and transportation pollution. Uncertainties in the form of randomness and fuzziness are jointly handled in this paper to ensure a more practical problem solution, for which returned bottle sand unusable bottles are considered fuzzy random variables. A heuristic algorithm based on priority-based global-local-neighbor particle swarm optimization (pb-glnPSO) is applied to ensure reliable solutions for this NP-hard problem. A case study on a beer operation company is conducted to illustrate the application of the proposed model and demonstrate the priority-based global-local-neighbor particle swarm optimization.

Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.

In this paper, an in-wheel vibration absorber for In-wheel-motor electric vehicle (IWM EV) is designed, and a comprehensive control strategy of in-wheel absorber and vehicle suspension is proposed to improve vehicle ride comfort. The proposed in-wheel vibration absorber, designed for suppressing the motor vibration, is composed of a spring and a controllable damper. The values of in-wheel spring stiffness and damper initial coefficient are determined by using the improved particle swarm optimization (IPSO) algorithm, which is carried on the typical driving condition. To deal with the negative interaction effects between vehicle suspension and in-wheel absorber, the linear quadratic regulator (LQR) algorithm is utilized to control suspension damper, and the fuzzy PID method is utilized to control in-wheel damper. Based on the four evaluation indexes including vehicle body vertical acceleration, suspension dynamic deflection, wheel dynamic load and motor wallop, the simulation results show that, the proposed LQR control of suspension effectively improves vehicle ride comfort, and the fuzzy PID control of in-wheel damper exhibits superior performance of motor vibration suppressing in comparison to conventional electric wheel.

A reinforcement learning algorithm is proposed to improve the accuracy of short-term load forecasting (STLF) in this article. The proposed model integrates radial basis function neural network (RBFNN), support vector regression (SVR), and adaptive annealing learning algorithm (AALA). In the proposed methodology, firstly, the initial structure of RBFNN is determined by using SVR. Then, an AALA with time-varying learning rates is used to optimize the initial parameters of SVR-RBFNN (AALA-SVR-RBFNN). In order to overcome the stagnation for searching optimal RBFNN, a particle swarm optimization (PSO) is applied to simultaneously find promising learning rates in AALA. Finally, the short-term load demands are predicted by using the optimal RBFNN. The performance of the proposed methodology is verified on the actual load dataset from Taiwan Power Company (TPC). Simulation results reveal that the proposed AALA-SVR-RBFNN can achieve a better load forecasting precision as compared to various RBFNNs.

In the war against the COVID-19 pandemic, the world is experiencing severe resource constraints. Although transmission routes are well understood, we suspect that they cause different disease consequences. We evaluate them in different forms to understand how they affect infection rates and disease severity. In determining how they affect disease outcome, we evaluated target tissue vulnerability, functional role, defense mechanisms, viral concentration, infection vicinity to target vital tissue, and host factors. We found that direct lung infection is the most lethal transmission route followed by bronchi infection. Transmissions by physical contacts, foods, and blood by low viral concentration (as expected in normal human activities) pose lower or much lower risks unless the infection is followed by subsequent lung exposures. After adding transmission route, treatment timings, and improper treatments into the list of known risk factors, we found that death rate and disability rate for young or healthy persons are nearly zero. We show that population based medical model improperly shifts nominal death rate from few vulnerable people to the population resulting in unnecessary population panic, and such panic is responsible for shutting down human activities and the world economy. Finally, we examined limitations in population-based mitigating measures and proposed for governmental and private adoption community guidelines, which are mainly to enable vulnerable people avoid exposures, prevent non-vulnerable people from serving as viral transmitters, get rid of high-risk exposure modes in working environment, improve safety for people in buses, ships and planes, and reduce death and disability rates for infected people.

This article provides a systematic review of the crosslinking strategies used to produce microgel particles in microfluidic chips. Various ionic crosslinking methods for gelation of charged pol-ymers are discussed, including external gelation via crosslinkers dissolved or dispersed in the oil phase, internal gelation methods using crosslinkers added to the dispersed phase in their non-active forms, such as chelating agents, photo-acid generators, sparingly soluble or slowly hydrolyzing compounds, and methods involving competitive ligand exchange, rapid mixing of polymer and crosslinking streams, and merging polymer and crosslinker droplets. Covalent crosslinking methods using enzymatic oxidation of modified biopolymers, photo-polymerization of crosslinkable monomers or polymers, and thiol-ene “click” reactions are also discussed, as well as the methods based on sol-gel transitions of stimuli responsive polymers triggered by pH or temperature change. In addition to homogeneous microgel particles, the production of structurally heterogeneous particles such as composite hydrogel particles entrapping droplet interface bi-layers, core-shell particles, organoids, and Janus particles are also discussed. Microfluidics offers the ability to precisely tune chemical composition, size, shape, surface morphology, and internal structure of microgels by bringing in contact multiple fluid streams in a highly controlled fashion using versatile channel geometries and flow configurations and allowing controlled crosslinking.

Planck’s constant and the gravitational constant are comprised of more fundamental quantities of length, mass, and time. Reformulating traditional equations in terms of these fundamental units offers a more granular view of the physical transformations encoded in the equations of physics. The composite structure of h and G conceals a simple model in which maximum unit potentials are reduced by dimensionless proportionality operators. Natural symmetries correlate the three unit dimensions, yielding predictable quantities of physical dynamics. Insights are organized into a New Foundations Model of physics that reformulates traditional constants and equations in elementary form. The New Foundations Model offers a common language for describing quantum mechanical, gravitational, and electromagnetic phenomena.

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

The development of computational acoustics allows simulation of sound generation and propagation in complex environment. In particular, meshfree methods are widely used to solve acoustics problems through arbitrarily distributed field points and approximation smoothness flexibility. As a Lagrangian meshfree method, smoothed particle hydrodynamics (SPH) method reduce the difficulty in solving problems with deformable boundaries, complex topologies, or multiphase medium. The traditional SPH method has been applied in acoustic simulation. This study presents the corrective smoothed particle method (CSPM), which is a combination of SPH kernel estimate and Taylor series expansion. The CSPM is introduced as a Lagrangian approach to improve accuracy in solving acoustic wave equations in the time domain. Moreover, a boundary treatment technique based on the hybrid meshfree and finite difference time domain (FDTD) method is proposed to represent different acoustic boundaries with particles. To model sound propagation in pipes with different boundaries, soft, rigid, and absorbing boundary conditions are built with this technique. Numerical results show that the CSPM algorithm is consistent and demonstrates convergence with exact solutions. Main computational parameters are discussed, and different boundary conditions are validated to be effective for benchmark problems in computational acoustics.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

We conducted many model simulations to understand the causes of the damages of coronavirus (COVID-19) to lung tissue and constructed a diagram showing apparent viral reproduction, immune response and damage accumulation curves. We found that lung damages include virus-caused damage, tissue damage caused by immune responses and tissue damage caused by accumulated wastes. The virus-caused damage is proportional to the phase lag between the viral reproduction curve and the delayed adaptive immune response curve, while waste-induced damage is attributed to imbalance in removing viral, cellular and metabolic by-products. We found that treatment strategies should slow down viral reproduction and speed up immune response, and improve blood micro-circulation in the lungs. Consistent with the strategies, measures are taken to void direct lung infection, strengthen innate responses, promote immune responses, dilute viral concentration in lung tissue, maintain waste removal balance, protect heart and kidneys, control other infections, avoid allergic reactions and other inflammation, etc. We show that medical, dietary, emotional, lifestyle, environmental, mechanical factors, etc. may be simultaneously used to mitigate lung damages and prove that multiple factor health optimization method is magnitudes more powerful than a single factor treatment. Such a method does not depend on molecular specificity and can be used in parallel to antiviral drugs.

Alkali Silica Reaction (ASR) is known to be a serious problem for concrete worldwide, especially in high humidity and high temperature regions. ASR is a slow process that develops over years to decades and it is influenced by changes in environmental and loading conditions of the structure. The problem becomes even more complicated if one recognizes that other phenomena like creep and shrinkage are coupled with ASR. This results in synergistic mechanisms that can not be easily understood without a comprehensive computational model. In this paper, coupling between creep, shrinkage and ASR is modeled within the Lattice Discrete Particle Model (LDPM) framework. In order to achieve this, a multi-physics formulation is used to compute the evolution of temperature, humidity, cement hydration, and ASR in both space and time, which is then used within physics-based formulations of cracking, creep and shrinkage. The overall model is calibrated and validated on the basis of experimental data available in the literature. Results show that even during free expansions (zero macroscopic stress), a significant degree of coupling exists because ASR induced expansions are relaxed by meso-scale creep driven by self-equilibriated stresses at the meso-scale. This explains and highlights the importance of considering ASR and other time dependent aging and deterioration phenomena at an appropriate length scale in coupled modeling approaches.

Particle Swarm Optimization (PSO) is a metaheuristic global optimization paradigm that has gained prominence in the last two decades due to its ease of application in unsupervised, complex multidimensional problems which cannot be solved using traditional deterministic algorithms. The canonical particle swarm optimizer is based on the flocking behavior and social co-operation of birds and fish schools and draws heavily from the evolutionary behavior of these organisms. This paper serves to provide a thorough survey of the PSO algorithm with special emphasis on the development, deployment and improvements of its most basic as well as some of the very recent state–of-the-art implementations. Concepts and directions on choosing the inertia weight, constriction factor, cognition and social weights and perspectives on convergence, parallelization, elitism, niching and discrete optimization as well as neighborhood topologies are outlined. Hybridization attempts with other evolutionary and swarm paradigms in selected applications are covered and an up-to-date review is put forward for the interested reader.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

Nature-inspired algorithms are very popular tools for solving optimization problems inspired by nature. However, there is no guarantee that optimal solution can be obtained using a randomly selected algorithm. As such, the problem can be addressed using trial and error via the use of different optimization algorithms. Therefore, the proposed study in this paper analyzes the time-complexity and efficacy of some nature-inspired algorithms which includes Artificial Bee Colony, Bat Algorithm and Particle Swarm Optimization. For each algorithm used, experiments were conducted several times with iterations and comparative analysis was made. The result obtained shows that Artificial Bee Colony outperformed other algorithms in terms of the quality of the solution, Particle Swarm Optimization is time efficient while Artificial Bee Colony yield a worst case scenario in terms of time complexity.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

The biophysical consequences of nanoscale curvature have been challenging to resolve due to size-dependent membrane behavior and the experimental resolution limits imposed by optical diffraction. Recent advances in nanoengineering and super-resolution techniques have enabled new capabilities for creating and observing curvature. In particular, draping supported lipid bilayers over lithographically patterned substrates provides a model system for endocytic pits. The experiments and simulations presented below describe the possible detection of membrane curvature through fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), single particle tracking (SPT), and polarized localization microscopy (PLM). FRAP and FCS depend on diffraction-limited illumination and detection. In particular, a simulation of FRAP shows no effects on lipids diffusion due to a 50 nm diameter membrane bud at any stage in the budding process. Simulated FCS demonstrated small effects due to a 50 nm radius membrane bud that was amplified with curvature-dependent lipid mobility changes. However, PLM and SPT achieve sub-diffraction-limited resolution of membrane budding and lipid mobility through the identification of the single-lipid positions with ≤15 nm spatial and ≤20 ms temporal resolution. By mapping the single-lipid step lengths to locations on the membrane, the effects of curvature on lipid behavior have been resolved.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

This study analyzes the correlation between the lifetime and the rest energy of the unstable particle states with a lifetime greater than the zeptosecond (10⁻²¹ s), using data available from the Particle Data Group. This set of states seems to be divided into three groups, in each of which the two quantities can be correlated through a remarkably accurate power law. Although this fact does not represent anything new compared to the predictions of the Standard Model, it nevertheless reveals an unexpected order structure in the set of particle decays, emerging from such predictions.

Smoothed particle hydrodynamics (SPH) is regarded as a pure Lagrangian approach, which can solve fluid dynamics problems without the creation of mesh. In this paper, a paralleled SPH solver is developed to solve particle-based computational acoustics (PCA). The aim of this paper is to study the feasibility of using SPH to solve acoustic problems and to improve the efficiency of solving processes by paralleling some procedures on GPU during calculating. A stand SPH code running serially in a CPU is proposed to solve wave equation. This is a wave propagating in a two-dimensional domain. After finishing the computation, the results are compared with the theoretical solutions and they agree well. So its feasibility is verified. There are two main methods for searching neighbor particles: all-pair search method and linked-list search method. Both methods are used in different codes to simulate an identical problem and their runtimes are compared to investigate their searching efficiencies. The runtime results show that linked-list search method has a higher efficiency, which can save a lot of searching time when simulating problems with huge amounts of particles. Furthermore, the percentages of different procedures’ runtimes in a simulation are also discussed to find the most consuming one. Then, some codes are modified to run in different GPUs and their runtimes are compared with those of serial ones on a CPU. Runtime results show that the paralleled algorithm can be more than 80 times faster than the serial one. The result shows that GPU paralleled SPH computing can achieve desirable accuracy and speed in solving acoustic problems.

Real-time energy management of a converter-based microgrid is difficult to determine optimal operating points of a storage system in order to save costs and minimise energy waste. This complexity arises due to time-varying electricity prices, stochastic energy sources and power demand. Many countries have imposed real-time electricity pricing to efficiently control demand side management. This paper presents a particle swarm optimisation (PSO) for the application of real-time energy management to find optimal battery controls of a community microgrid. The modification of the PSO consists in altering the cost function to better model the battery charging/discharging operations. As optimal control is performed by formulating a cost function, it is suitably analysed and then a dynamic penalty function in order to obtain the best cost function is proposed. Several case studies with different scenarios are conducted to determine the effectiveness of the proposed cost function. The proposed cost function can reduce operational cost by 12% as compared to the original cost function over a time horizon of 96 hours. Simulation results reveal the suitability of applying the regularised PSO algorithm with the proposed cost function, which can be adjusted according to the need of the community, for real-time energy management.

Meshfree particle method, which is always regarded as a pure Lagrangian approach, is easily represented complicated domain topologies, moving boundaries, and multiphase media. Solving acoustic problems with the mesfree particle method forms a branch of the acoustic wave modeling field, namely, particle-based computational acoustics (PCA). The aim of this paper is to improve the accuracy of using the PCA method to solve two-dimensional acoustic problems, and realize the particle representation with a hybrid meshfree and finite-difference time-domain (FDTD) method for acoustic boundary conditions at both the plane and curved surface. As a widely used Lagrangian meshfree method, the smoothed particle hydrodynamics (SPH) based on the support domain and the kernel function has developed rapidly in recent years. The traditional SPH method is easily implements parallel processing and has been applied in sound wave simulation. As a corrective method with higher accuracy than SPH, the acoustic propagation and scattering in the time domain is simulated with the corrective smoothed particle method (CSPM). Moreover, a hybrid meshfree-FDTD boundary treatment technique is utilized to represent different acoustic boundaries in the Lagrangian approach. In this boundary treatment technique, the parameter value of virtual particles is obtained with the FDTD method, which concerns truncation errors based on the Tayler series expansion. Soft, rigid, and Mur’s absorbing boundary conditions are developed to simulate sound waves in finite and infinite domain. Results of modeling acoustic propagation and scattering show that CSPM is accurate and convergence with exact solutions, and different acoustic boundaries are validated to be effective in the computation.

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C₁₆-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’_w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

Most of existing fuzzy forecasting models partition historical training time series into fuzzy time series and build fuzzy-trend logical relationship groups to generate forecasting rules. The determination process of intervals is complex and uncertainty. In this paper, we present a novel fuzzy forecasting model based on high-order fuzzy-fluctuation trends and the fuzzy-fluctuation logical relationships of the training time series. Firstly, we compare each data with the data of its previous day in historical training time series to generate a new fluctuation trend time series(FTTS). Then, fuzzify the FTTS into fuzzy-fluctuation time series(FFTS) according to the up, equal or down range and orientation of the fluctuations. Since the relationship between historical FFTS and the fluctuation trend of future is nonlinear, Particle Swarm Optimization (PSO) algorithm is employed to estimate the required parameters. Finally, use the acquired parameters to forecast the future fluctuations. In order to compare the performance of the proposed model with that of the other models, we apply the proposed method to forecast the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) time series datasets. The experimental results and the comparison results show that the proposed method can be successfully applied in stock market forecasting or such kinds of time series. We also apply the proposed method to forecast Shanghai Stock Exchange Composite Index (SHSECI) to verify its effectiveness and universality.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

The present study aims to investigate radiation doses from Computed Tomography Pulmonary Angiography (CTPA) examinations based on the patient’s size and to estimate the probability of cancer risk induced from the examination. Data from 100 patients who had undergone CTPA examinations, such as scanning acquisition parameters, patient demography, as well as radiation dose exposure, were collected and analysed. All subjects which aged above 18 y/o were scanned using a Philips Brilliance 128 multi-detector CT (MDCT) scanner. The mean dose value for Volume Computed Tomography Dose Index (CTDI_vol), Dose-Length Product (DLP) and effective dose (E) were 11.06 ± 7.17 mGy, 400.38 ± 259.10 mGy.cm and 8.68 ± 5.47 mSv respectively. In addition, with respective of patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89, 13.70 ± 9.04 and 22.29 ± 7.35, respectively. Cancer risk per million procedure was calculated based on te recommendation by the International Commission on Radiological Protection Publication 103 report. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. In conclusion, CTDI_vol underestimated, and SSDE was more accurate in describing the radiation dose. Lung and breast with larger lung effective diameter received the highest dose exposure which increase the probability of the cancer risk. Therefore, it is important to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

Coffee is regarded as the highly consumed beverage throughout the world and has established a key spot in the world economy as an important commodity for trading. In general, they are produced by brewing their roasted and ground beans, which release aromatic coffee; as well as produce an equivalent amount of spent coffee grounds (SCG). Previously, they were discarded as wastes or used as natural pest repellent or garden fertilizer; however, in recent times, are valorized into biofuels owing to their high calorific value. In fact, SCG briquettes have gained wide attention for supplying energy renewably, especially to the rising energy demand; and also have been identified as an effective measure to reduce their pollution. With this in mind, this present chapter focuses on reviewing the availability and chemistry involved in these SCG wastes, pre-treatments and preparations required for their briquetting, compacting techniques followed, and fuel characteristics of their briquettes, from various available works of literature. Here, their availability showcases the amount of SCG wastes generated with respect to time and consumption, wherein understanding their chemistry helps in deciding the pre-treatments necessary for their briquetting. Meanwhile, preparation techniques briefs about the necessary pre-treatments undertaken before compaction by different researchers; and the fuel characteristics define the physicochemical and mechanical properties of their briquettes, developed using various compaction methods. Besides, combustion behaviors of these briquettes are explained in terms of their burning characteristics and emission levels, as reported in literatures; which help in deciding their suitability as a replacement for existing fossil coal. Eventually, all the reported data were in accordance with their permissible standards and suggested these SCG as a highly renewable solid biofuel.

To enable purposeful design and implementation of automated concrete technologies, precise assessment and prediction of the complex material flow at various stages of the process chain are necessary. This paper investigates the intermediate stage of the extrusion and deposition processes in extrusion-based 3D-concrete-printing, using a numerical model based on the Particle Finite Element Method (PFEM). In PFEM, due to the Lagrangian description of motion, remeshing algorithms and the alpha shape method are used to track the free surface during large deformation scenarios. The Bingham constitutive model was used for describing the rheological behaviour of fresh concrete. This model is validated by comparing the numerically predicted layer geometries with those obtained from laboratory 3D printing experiments. Extensive parametric studies were then conducted using the numerical simulation, delineating the influence of process and material parameters on the layer geometries, the dynamic surface forces generated under the extrusion nozzle and the inter-layer interactions.

The precise prediction of air contaminant dispersion is essential to the air quality monitoring and the emergency management of the contaminant gases leakage incidents in the chemical industry park. The conventional atmospheric dispersion models can seldom give precise prediction due to inaccurate input parameters. In order to improve the prediction accuracy of dispersion model, two data assimilation methods (i.e. one is merely based on the typical particle filter while the other is a combination of particle filter and expectation-maximization algorithm) are proposed to assimilate the UAV observations into the atmospheric dispersion model. Two emission cases are taken into consideration, the difference between which is the different dimensions of state variables. To test the performances of the proposed methods, experiments corresponding to the two emission cases are designed and implemented. The results show that the particle filter can effectively estimate the model parameters and improve the accuracy of model prediction when the dimension of state variables is low. In contrast, when the dimension of state variables becomes higher, the method of particle filter combining expectation-maximization algorithm performs better in the parameter estimation accuracy and warm-up time. Therefore, the data assimilation methods are able to effectively support the air quality monitoring and emergency management in chemical industry parks.

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged >75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. The findings of this descriptive study indicated that air pollution may have a role with regard to the risk of lung and bladder cancers, limited to women aged ≥ 75 years. Such increased risk warrants further analytical investigations.

COVID-19 is a severe global problem, and AI can play a significant role in preventing losses by monitoring and detecting infected persons in early-stage. This paper aims to propose a high-speed and accurate fully-automated method to detect COVID-19 from the patient's CT scan images. We introduce a new dataset that contains 48260 CT scan images from 282 normal persons and 15589 images from 95 patients with COVID-19 infections. At the first stage, this system runs our proposed image processing algorithm to discard those CT images that inside the lung is not properly visible in them. This action helps to reduce the processing time and false detections. At the next stage, we introduce a novel method for increasing the classification accuracy of convolutional networks. We implemented our method using the ResNet50V2 network and a modified feature pyramid network alongside our designed architecture for classifying the selected CT images into COVID-19 or normal with higher accuracy than other models. After running these two phases, the system determines the condition of the patient using a selected threshold. We are the first to evaluate our system in two different ways. In the single image classification stage, our model achieved 98.49% accuracy on more than 7996 test images. At the patient identification phase, the system correctly identified almost 234 of 245 patients with high speed. We also investigate the classified images with the Grad-CAM algorithm to indicate the area of infections in images and evaluate our model classification correctness.

Aims TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employing combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC. Method A549 and HCC-15 cells were used in experimental design. Cell viability was determined by morphological image, crystal violet staining and MTT assay. Apoptosis was evaluated by LDH assay, Annexin V and DAPI staining. Autophagy and apoptosis indicator protein were examined by western blotting. TEM and puncta assay were carried out to evaluate the autophagy. MTP and ROS activity were evaluated by JC-1 and H₂DCFDA staining. Findings Resveratrol is a polyphenolic compound capable of activation of tumor suppressor p53 and its pro-apoptotic modulator PUMA. Herein, we showed the p53-independent apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in NSCLC, resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells with a co-treatment of resveratrol and TRAIL assessed by the loss of MMP, ROS generations which resulting the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis in NSCLC. Significance Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the effective TRAIL-based cancer therapy regimen.

In this study, we attempted to verify the hypothesis that total metals bound to dust of different particle sizes may reflect pollution levels, but cannot predict its bioavailability and risks in human health assessments. Dust samples were collected using active sampling method; during the dry season months of November, 2014 to March, 2015 at different locations in Akure (7˚10ʹN and 5˚15ʹE). The samples were sorted into different particle sizes (< 10µm, 10 – 50 µm, >50µm), analyzed for some physicochemical properties and assessed for metals bioavailability using two-step physiological extraction method. The amount of metals (Cd, Cu, Cr, Ni, Pb, Zn and Mn) released in each particle sizes were determined using Perkin-Elmer 6000 Inductively Coupled Plasma - Atomic Emission Spectrometry (ICP-AES) analysis. The results showed that bioavailability of some metals (Cd, Ni, Pb, and Zn) decreases with increasing particle sizes, however, the reverse trend was observed for Mn, Cu and Fe concentrations. This may be attributed to some combination of physicochemical characteristics of the dust and metal speciation. Hence, it was concluded that metal bioaccessibility in dust can best be described by the knowledge of physicochemical characteristics. The exposure dose of the metals showed that cancer risks due to inhalation were very high when compared to other exposure routes (ingestion and dermal contact). The calculated non-cancer (HQ) and cancer risk (HI) for humans in the area showed values higher than unity, indicating possibility of the metals’ body burden.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

This paper proposes the use of non-uniform extended surfaces installed externally to the tubes of the radiation section of fired heaters, in order to obtain a better heat flux distribution to the coils. To this end, the heat transfer mechanisms present in such equipment were studied through computational fluid dynamics (CFD), using simplified geometries that represent typical sizes of fired heaters. Also, a simplified model for the combustion was considered. Although this model oversimplifies the physics of the problem, it was able to give satisfactory results for the parameters being optimized, considering the main objective of this paper, that is to minimize the non-uniformity of heat flux in the tubes of the radiant section of fired heaters. It was possible to obtain optimized geometric parameters for different types of extended surfaces evaluated, coupling the results of these models with the Particle Swarm optimization method through the use of a response surface technique,. The results indicate a significant improvement in the uniformity of the heat flux distribution to the tubes through the use of the proposed extended surfaces. Thus, this solution reveals to be an interesting alternative to reduce the risks of fluid degradation and coking formation. Future studies must investigate the non-uniformity of the heat flux due to the presence of the flame and consider the interaction between the reactive flow and the participating medium. Nevertheless, this paper presents some results that justify the optimization of such extended surfaces taking into consideration thermal radiation.

Here, applying the theory of the generalization of the Boltzmann constant in curved space-time, we will model the mechanism by which elementary particles are formed. We will determine the relationship between gravity and each of the elementary particles that form the standard model following analogies to that of stellar bodies. In order to achieve our goal, we will propose new models for photons, quarks and gluons; with this, we will demonstrate why there are stable and unstable elementary particles; why the first family of elementary particles forms hadrons and why the second and third families cannot form hadrons; why the fermions comply with the Pauli exclusion principle and why the bosons do not comply with the Pauli exclusion principle, etc. Finally, we will analyse the generalization of the ADS/CFT correspondence and propose a theory of everything (T.O.E.).

The distribution of noble metal nanoparticles in hydrogels are influencing their nanoplasmonic response and signal used for biosensor purposes. By controlling the particle distribution, it is possible to obtain new nanoplasmonic features with new sensing modalities. Particle distributions can be characterized by using volume-imaging methods such as the focused ion beam-scanning electron microscope (FIB-SEM) and the serial block-face scanning electron microscopy (SBFSEM) techniques . Since the pore structure of hydrogels is contained by the water absorbed in the polymer network it may pose challenges for volume-imaging based on electron microscope techniques since the sample must be in a vacuum chamber. The structure of hydrogels can be conserved by choosing appropriate preparation methods, which also depends on the composition of the hydrogel used. In this paper, we have prepared low-weight percentage hydrogels, with and without gold nanorods (GNR) for conventional SEM imaging by using two different drying techniques; (1) the critical point drying (CPD) technique and (2) hexamethyldisilazane (HMDS) drying of hydrogels. A qualitative characterization of the GNR-hydrogels was carried out to study the GNRs positioned in the polymer network. The effect of the two different drying methods on the hydrogel morphology were also compared. The use of HMDS as an alternative to the CPD has several advantages involving less parametrical variables for drying, involving less effort, being cost-effective, and requires no equipment use. In addition, choosing an optimized sample preparation method for SEM with optimized imaging parameters is highly important for obtaining accurate information about materials that is not correlated to artifacts. Hence, the results obtained from the preparation methods and SEM imaging parameters in this paper are useful for developing methods for mapping the metal particle distributions in micro-hydrogels by using FIB-SEM and SBFSEM techniques.

Silver nanoparticles (AgNPs) have been demonstrated to restrain bacterial growth while maintaining the minimal risk in development of bacterial resistance and human cell toxicity that conventional silver compounds exhibit. Several physical and chemical methods have been reported to synthesize AgNPs. However, these methods are expensive and involve heavy chemical reduction agents. An alternative approach to produce AgNPs in a cost-effective and environmentally friendly way employs a biological pathway using various plant extracts to reduce metal ions. The size control issue and the stability of nanoparticles remain some of the latest challenges in such methods. In this study, we used two different concentrations of fresh leaf extract of the plant Arbutus Unedo (LEA) as a reducing and stabilizing agent to produce two size variations of AgNPs. UV-Vis spectroscopy, Dynamic Light Scattering, Transmission Electron Microscopy and zeta potential were applied for the characterization of AgNPs. Both AgNP variations were evaluated for their antibacterial efficacy against the gram-negative species Escherichia coli and Pseudomonas aeruginosa, as well as the gram-positive species Bacillus subtilis and Staphylococcus epidermidis. Although significant differences have been achieved in the nanoparticles’ size by varying the plant extract concentration during synthesis, the antibacterial effect was almost similar.

To understand great disparities in disease outcomes between CIVID-19 patients, we explore infection and host responses in kinetics. From existing data, we deduced a model that the lungs are damaged by rapidly rising flow resistance as a result of retaining white blood cells in lung tissues. The retention of white blood cells is initially triggered by viral infection but aggravated by injuries caused by low temperature. Lungs are initially damaged by fluid leakage, rapidly followed by extruding blood into alveolar spaces. The step of blood extruding is predicted to take place in a very short time. Our simulations show that as little as 0.1% retention of white blood cells in the lungs can lead to their failure in 5 to 10 days. The small degrees of imbalance implies that this imbalance could be corrected by a large number of factors that are known to reduce flow resistance. The model implies that the top priority is maintaining blood micro-circulation and preserving organ functions in the entire disease course, especially after the virus has spread the whole lungs. From exploring a large number of hypothetical infection modes, we propose preventive, mitigating and treatment strategies for ultimately ending the pandemic. The first strategy is avoiding exposures that could result in widespread damages to lungs and taking post exposure mitigating measures that would reduce disease severity. The second strategy is reducing death rate and disability rate from the current levels to one tenth for infected patients by using multiple factors health optimization method. The double reduction strategies are expected to generate a series of chain reactions that favor mitigating or ending the pandemic. Some reactions include a big reduction of the amount of viral discharges from infected patients into the air, the avoidance of panic, chronic stress and emotional distress, and cross-infections which are expected in quarantines. The double reductions would have a final effect of ending the pandemic.

Both macro and microprojectiles (e.g., interplanetary, interstellar and even intergalactic material) are seen as important vehicles for the exchange of potential (bio)material within our solar system as well as between stellar systems in our Galaxy. Accordingly, this requires estimates of the impact probabilities for different source populations of projectiles, including for intergalactic meteor particles which have received relatively little attention since considered as rare events (discrete occurrences that are statistically improbable due to their very infrequent appearance). We employ the simple but comprehensive model of intergalactic microprojectile capture by the gravity of exoplanets which enables us to estimate the map of collisional probabilities for an available sample of exoplanets in habitable zones around host stars. The model includes a dynamical description of the capture adopted from Mautner model of interstellar exchange of microparticles and changed for our purposes. We use statistical and information metrics to calculate probability map of intergalactic meteorite particle capture. Moreover, by calculating the entropy index map we estimate the concentration of these rare events. We further adopted a model from immigration theory, to show that the time dependent distribution of single molecule immigration of material indicates high survivability of the immigrated material taking into account birth and death processes on our planet. At present immigration of material can not be observationally constrained but it seems reasonable to think that it will be possible in the near future, and to use it along other proposed parameters for life sustainability on some planet.

This paper presents a multi-swarm PSO algorithm for the Quadratic Assignment Problem (QAP) implemented on the OpenCL platform. Our work was motivated by results of time efficiency tests performed for single-swarm algorithm implementation that showed clearly that the benefits of a parallel execution platform can be fully exploited provided the processed population is large. The described algorithm can be executed in two modes: with independent swarms or with migration. We discuss the algorithm construction as well as we report results of tests performed on several problem instances from the QAPLIB library. During the experiments the algorithm was configured to process large populations. This allowed us to collect statistical data related to values of goal function reached by individual particles. We use them to demonstrate on two test cases that although single particles seem to behave chaotically during the optimization process, when the whole population is analyzed, the probability that a particle will select a near-optimal solution grows.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

A novel metaheuristic optimization method is proposed based on an earthquake that is a geology phenomenon. The novel Earthquake Algorithm (EA) proposed, adapts the principle of propagation of geology waves P and S through the earth material composed by random density to ensure the dynamic balance between exploration and exploitation, in order to reach the best solution to optimization complex problems by searching for the optimum into the search space. The performance and validation of the EA are compared against the Bat Algorithm (BA) and the Particle Swarm Optimization (PSO) by using 10 diverse benchmark functions. In addition, an experimental engineering application is implemented to evaluate the proposed algorithm. Early results show a feasibility of the proposed method with a clearly constancy and stability. It is important highlight the fact that the main purpose of this paper is to present a new line of research, which is opened from the novel EA.

Quantitative structure-activity relationship (QSAR) model is adopted to study the relationship between the chemical and physical properties of various substances and the structure. Through QSAR studies, the internal relationship between the invisible structure and the activity can be obtained. In this paper, a novel chaos-enhanced accelerate particle swarm algorithm (CAPSO) is proposed, which is used to molecular descriptors screening and optimization of the weights of back propagation artificial neural network (BP ANN). Then, the QSAR model based on CAPSO and BP ANN is put forward, hereinafter referred to as CAPSO BP ANN model. The prediction experiment showed that the CAPSO algorithm is a reliable method for screening molecular descriptors and the five molecular descriptors obtained by CAPSO algorithm could well characterize the molecular structure of each compound in pKa prediction. The experimental results also showed the CAPSO BP ANN model has a good performance in predicting the pKa values of various compounds, the absolute mean relative error, root mean square error, and square correlation coefficient are respectively 0.5364, 0.0632, and 0.9438, indicating the higher prediction accuracy and correlation. The proposed hybrid intelligent model can be applied in all kinds of engineering design, prediction of physical and chemical properties and intelligent calculation.

Direct georeferencing of airborne pushbroom scanner data usually suffers from the limited precision of navigation sensors onboard of the aircraft. The bundle adjustment of images and orientation parameters, used to perform geocorrection of frame images during the post-processing phase, cannot be used for pushbroom cameras without difficulties: it relies on matching corresponding points between scan lines, which is not feasible in the absence of sufficient overlap and texture information. We address this georeferencing problem by equipping our aircraft with both a frame camera and a pushbroom scanner: the frame images and the navigation parameters measured by a couple GPS/Inertial Measurement Unit (IMU) are input to a bundle adjustment algorithm; the output orientation parameters are used to project the scan lines on a Digital Elevation Model (DEM) and on an orthophoto generated during the bundle adjustement step; using the image feature matching algorithm Speeded Up Robust Features (SURF), corresponding points between the image formed by the projected scan lines and the orthophoto are matched, and through a least-squares method, the boresight between the two cameras is estimated and included in the calculation of the projection; finally, using Particle Image Velocimetry (PIV) on the gradient image, the projection is deformed into a final image that fits the geometry of the orthophoto. We apply this algorithm to five test acquisitions over Lake Geneva region (Switzerland) and Lake Baikal region (Russia). The results are quantified in terms of Root Mean Square Error (RMSE) between matching points of the RGB orthophoto and the pushbroom projection. From a first projection where the Interior Orientation Parameters (IOP) are known with limited precision and the RMSE goes up to 41 pixels, our geocorrection estimates IOP, boresight and Exterior Orientation Parameters (EOP) and produces a new projection which RMSE with the reference orthophoto is around two pixels.

1) Background: Traditionally, complex biological products such as vaccines presented unique challenges to implementation of even rudimentary characterization packages; thus, the product was defined almost exclusively by its manufacturing process. The advances in technology and analytical tools allowed the application of more comprehensive characterization packages for products such as adsorbed combination vaccines, which contain several antigens in a single formulation to protect against more than one disease, and may contain adjuvants and excipients. Aluminum phosphate (AlPO4) is a well-established adjuvant for enhancing the uptake of vaccines and to induce robust immunity against pathogens. During manufacturing, adjuvant is mixed with protein antigens which may in turn impact their higher order structure and stability. 2) Methods: To study the structural changes of protein antigens after adsorption several analytical tools including DLS, FTIR, Fluorescence, LD, and SEM were used. 3) Results: the AlPO4 adjuvant suspension consists of small submicron particles that form a continuous porous surface. Secondary structure alpha-helix and beta-sheet content of DT and TT increased after adsorption to AlPO4 adjuvant, whereas no significant changes were noted for other protein antigens. Interactions were noted between AlPO4 adjuvant and DT, TT, and FHA. 4) Conclusions: here we report for the first time the use of SEM for the visualization of adsorbed multivalent vaccine components. A unique signature profile detected for each multivalent vaccine by FTIR can be used as a lean in-process test to verify vaccine product composition and identity prior to filling.

The COVID-19 pandemic has disrupted the supply chain for personal protective equipment (PPE) for medical professionals, including N95-type respiratory protective masks. To address this shortage, many have looked to the agility and accessibility of additive manufacturing (AM) systems to provide a democratized, decentralized solution to producing respirators with equivalent protection for last-resort measures. However, there are concerns about the viability and safety in deploying this localized download, print, and wear strategy. Several polymer-based AM processes produce porous parts, and inherent process variation between printers and materials also threaten the integrity of tolerances and seals within the printed respirator assembly. The goal of this paper is to quantitatively measure particle transmission through printed respirators of different designs, materials, and AM processes, and assess the viability of printed respirators as N95 equivalents. Results from this study show that respirators printed using desktop/industrial-scale fused filament fabrication processes and industrial-scale powder bed fusion processes have insufficient filtration efficiency at the size of the SARS-CoV-2 virus, even while assuming a perfect seal between the respirator and the user’s face. Almost all printed respirators provided <60% filtration efficiency at the 100-300 nm particle range. Only one respirator, printed on an industrial-scale fused filament fabrication system provided >90% efficiency as-printed. Post-processing procedures including cleaning, sealing surfaces, and reinforcing the filter cap seal generally improved performance, but no respirator sustained the filtration efficiency of an N95 respirator, which filters 95% of SARS-CoV-2 virus particles. Instead, the printed respirators showed similar performance to various cloth masks. While continued optimization of printing process parameters and design tolerances could be implemented to directly print respirators that provide the requisite 95% filtration efficiency, AM processes are not sufficiently reliable for widespread distribution and local production of N95-type respiratory protection without commensurate quality assurance processes in place. Certain design/printer/material combinations may provide sufficient protection for specific users, but the respirators should not be trusted without quantitative filtration efficiency testing. It is currently not advised to expect printed respirators originating from distributed designs to replicate performance across different printers and materials.

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC₅₀ = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective.

BTB domain and CNC homology 1 (BACH1) is a highly expressed transcription factor in tumors including breast and lung, relative to their non-tumor tissues. BACH1 is known to regulate multiple physiological processes including heme homeostasis, oxidative stress response, senescence, cell cycle, and mitosis. In a tumor, BACH1 promotes invasion and metastasis of cancer cells, and the expression of BACH1 presents a poor outcome for cancer patients including breast cancer patients. Recent studies identified novel functional roles of BACH1 in the regulation of metabolic pathways in cancer cells. BACH1 inhibits mitochondrial metabolism through transcriptional suppression of mitochondrial membrane genes. In addition, BACH1 suppresses activity of pyruvate dehydrogenase (PDH), a key enzyme that converts pyruvate to acetyl-CoA for the citric acid (TCA) cycle through transcriptional activation of pyruvate dehydrogenase kinase (PDK). Moreover, BACH1 increases glucose uptake and lactate secretion in aerobic glycolysis through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3- phosphate dehydrogenase (GAPDH). Pharmacological or genetic inhibition of BACH1 could reprogramme metabolic pathways, subsequently rendering metabolic vulnerability of cancer cells. Furthermore, inhibition of BACH1 decreased antioxidant-induced glycolysis rates as well as reduced migration and invasion of cancer cells, suggesting BACH1 as a potentially useful cancer therapeutic target.

In this investigation magnetic γ-Al2O3 ceramic nanocomposite particles bearing epoxide functionality are prepared following a multistep process. The ultimate nanocomposite particles are named as γ-Al2O3/Fe3O4/SiO2/poly(glycidyl methacrylate (PGMA). The surface property is evaluated by carrying out the adsorption study of Remazol navy (RN), a model reactive azo dye, on both γ-Al2O3/Fe3O4/SiO2 and γ-Al2O3/Fe3O4/SiO2/PGMA nanocomposite particles. The adsorption is carried out at the point of zero charge (PZC) to neutralize the effect of particle surface charge. The adsorption rate is very fast, reached equilibrium (qe) value within five min. Due to mesoporous structure of silica layer γ-Al2O3/Fe3O4/SiO2 nanocomposite particles possessed relatively higher specific surface area and magnitude of adsorption is dependent on the total specific surface area. The introduction of epoxide functionality favored high adsorption capacity in mass per unit surface area. The adsorption process strictly followed Langmuir model. Thermodynamic equilibrium parameters implied that irrespective of surface functionality the adsorption process is spontaneous and exothermic. Pseudo-second-order rate kinetic model is more appropriate to explain the adsorption kinetics.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

In this paper, we implement a new method binary Particle Swarm Optimization (PSO) for solving the kidney exchange problem, which will improve the future decisions of kidney exchange programs. Because using a kidney exchange, we can help incompatible patient-donor couples to swap donors to receive a compatible kidney. Kidney paired donation programs provide an innovative approach for increasing the number of available kidneys. Further, we implementing binary particle swarm optimization in parallel with MATLAB with one, two, three and four threads and from the computations point of view, the authors compare the performance to reduce the running time for kidney exchange to match patients as fast as possible to help clinicians. Moreover, implementing binary particle swarm optimization in solving the kidney exchange problem is an effective method. The obtained results indicate that binary PSO outperforms other stochastic-based methods such as genetic algorithm, ant lion optimization, and efficient the number of resulting exchanges.

Quantum computing arrives. Preceded by Mādhava of Sangamagrāma and other Hindu mathematicians, around 1,500 CE, and our previous work, we show at least 4 quantum properties that are indeed universal in some number systems; here we use them to enable quantum computing. Using the sets B={0,1}, B^n, N, Z, Q, and Q*, one has +4 quantum properties that one can trust, as archetypes of easy communication to friends and foes, to ignoranti or cognoscenti, and for quantum consciousness. Therefore, this work applies to computer calculations, apps in cell phones, algebra, atoms, mathematics, physics, and the human mind.

Although energy management of a microgrid is generally performed using a day-ahead scheduling method, its effectiveness has been questioned by the research community due to the existence of high uncertainty in renewable power generation, power demand and electricity market. As a result, real-time energy management schemes are recently developed to minimise the operating cost of a microgrid while high uncertainty presents in the network. This paper develops modified particle swarm optimisation (MPSO) algorithms to solve optimisation problems of energy management schemes for a community microgrid and proposes a scheduling approach after taking into consideration high uncertainty to effectively minimise the operational cost of the microgrid. The optimisation problems are formulated for real-time and scheduling approaches, and solution methods are developed to solve the problems. It is observed that the scheduling program demonstrates superior performance in all the cases, including uncertainty in prediction, as compared to the other energy management approaches, although solutions have significant deviations due to prediction errors.

We consider partition functions, in the form of state sums, and associated probabilistic measures for aperiodic substrates described by model sets and their associated tiling spaces. We propose model set tiling spaces as microscopic models for small scales in the context of quantum gravity. Model sets possess special self-similarity properties that allow us to consider implications on large and observable scales from the underlying (non-ergodic) dynamics. In particular we consider the implication of the underlying aperiodic substrate for the well known problem of time in quantum gravity, and propose a correspondence between small and large scales, the so-called ergodic correspondence, that addresses the emergence of matter properties and spacetime structure. In the process we find a possible bound in the mass spectrum of fundamental particles.

Plant pathogens utilize effectors to subvert host cell biology for facilitating infection. However certain effectors, called as the avirulence proteins, trigger immune responses in the host. AvrPi54 is an avirulence protein from fungus Magnaporthe oryzae which induces the defense reactions in rice cells that contain Pi54 resistance gene. The characterization of such proteins and elucidation of their function facilitate the understanding of the mechanism of disease establishment. In present study, physiochemical properties of AvrPi54 were analysed using computational methods. We found that mature AvrPi54 is a small, hydrophobic and secretary protein with 134 amino acids. It is rich in small amino acids with no significant homology with other proteins in databases. The gene ORF was cloned in pET28a(+) vector and expressed in E. coli BL21(DE3)pLysS. The protein was purified using affinity chromatography. Transient expression of the gene in epidermal cells of onion bulb is a powerful tool to predict the subcellular localization in plant cells. We fused AvrPi54 to eYFP and transformed epidermal cell layer of onion bulb. Fused protein localized to the plasma membrane and nucleus of plant cells. Therefore, AvrPi54 might be functioning in the host cell as transcription factor or chromatin remodelling factor to modify pathogenesis-related processes.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

We review some properties of a relativistic classical massless charged particle with spin interacting with an external electromagnetic field. We give in particular a proper definition of kinetic energy and total energy, the latter being conserved when the external field is stationary. We find that the particle’s velocity may differ from c as a result of the spin - electromagnetic field interaction, without jeopardizing Lorentz invariance.

Both lung adenocarcinoma and SARS-CoV-2 infection could cause pulmonary inflammation. Angiotensin-converting enzyme 2, not only as the functional receptor of SARS-CoV-2 but also play key role in lung adenocarcinoma. To study the risk of SARS-CoV-2 infection in lung adenocarcinoma patients, mRNA and miRNA profiles were obtained from TCGA and GEO databases followed by bioinformatics analysis. A regulatory network which regards angiotensin-converting enzyme 2 as the center would be structured. In addition, via immunological analysis about key factors in lung adenocarcinoma patients, to explore the essential reasons for the susceptibility of SARS-CoV-2. Compared with normal tissue, angiotensin-converting enzyme 2 was increased in lung adenocarcinoma patients. Furthermore, a total of 7 differently expressed correlated mRNAs (ACE2, CXCL9, MMP12, IL6, AZU1, FCN3, HYAL1 and IRAK3) and 5 differently expressed correlated miRNAs (miR-125b-5p, miR-9-5p, miR-130b-5p, miR-381-3p and miR-421) were screened followed by enrichment analysis. Interestingly, toll-like receptor signaling pathway with the most frequent occurrence was enriched by mRNA (IL6) and miRNA (miR-125b-5p) sets simultaneously. Finally through comprehensive analysis, it was assumed that miR-125b-5p-ACE2-IL6 axis in the structured regulatory network could alter risk of SARS-CoV-2 infection in lung adenocarcinoma patients.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Gigantic particle accelerators, incredibly complex detectors, an antimatter factory and the discovery of the Higgs boson – this is part of what makes CERN famous. Only a few know that CERN also hosts the world largest Open Access initiative: SCOAP3. The Sponsoring Consortium for Open Access Publishing in Particle Physics (SCOAP3) started operation in 2014 and has since supported the publication of 19,000 Open Access articles in the field of particle physics, at no direct cost, nor burden, for individual authors worldwide. SCOAP3 is made possible by a 3,000-institute strong partnership, where libraries re-direct funds previously used for subscriptions to ’flip’ articles to ’gold Open Access’. With its recent expansion, the initiative now covers about 90% of the journal literature of the field. This article describes the economic principles of SCOAP3, the collaborative approach of the partnership, and finally summarizes financial results after four years of successful operation.

An analysis is presented of the possible existence of a second anomalous dipole moment of Dirac’s particle next to the angular one. It includes a discussion why, in spite of his own derivation, Dirac has doubted about its relevancy. It is shown why since then it has been overlooked and why it has vanished from leading textbooks. A critical survey is given on the reasons of its reject, including the failure of attempts to measure and the perceived violations of time reversal symmetry and chargeparity symmetry. It is emphasized that the anomalous electric dipole moment of the pointlike electron (AEDM) is fundamentally different from the quantum field type electric dipole moment of an electron (eEDM) as defined in the standard model of particle physics and that its measurement requires different instrumentation. A proposal has been described how to prove or disprove its existence by experiment. Moreover, by reference from literature, the possible impact is discussed in the nuclear domain and in the gravitational domain.

In the past 50 years, calorimeters have become the most important detectors in many particle physics experiments, especially experiments in colliding-beam accelerators at the energy frontier. In this paper, we describe and discuss a number of common misconceptions about these detectors, as well as the consequences of these misconceptions. We hope that it may serve as a useful source of information for young colleagues who want to familiarize themselves with these tricky instruments.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.

An optimal scheduling strategy for cooling, heating and power (CCHP) joint-power-supply system is proposed to improve energy utilization and minimize costs in this paper. Firstly, the mathematical model of CCHP system is established. Particle swarm optimization (PSO) is used to optimize the regularization coefficient C and the kernel parameter λ which can affect the prediction accuracy of KELM(PSO-KELM). Then PV generation and load prediction model are established by PSO-KELM. In order to jump out of local optimal solution, Cauchy variation is introduced in SFLA local update, and adaptive mutation operation is carried out on SFLA individuals. The predictions of PV generation and load power by PSO-KELM are imported into the objective function, and the microgrid dispatching model is solved by the improved SFLA algorithm. Compared with the traditional GA-KELM and KELM, PSO-KELM has faster convergence and prediction accuracy. Compared with the power supply division, the operation cost of the power grid is reduced by the proposed optimization dispatching strategy of CCHP micro-grid.

Recent changes in lung cancer care, including new approvals in first line and the introduction of high throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second and third generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated to the identification of new predictive markers.

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein are expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying G₂/M transition of the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with increased Wee1 and decreased Cdc25B expression, simultaneously. ChIP analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through the interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G₂/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G₂/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.

The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.

Lung adenocarcinoma with EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) resistance was reported to harbor higher ability of invasion and migration than those sensitive to EGFR-TKI, but the function of MMPs (matrix metalloproteinases) has not been explored in EGFR-TKI resistant lung adenocarcinoma. In this study, the correlation between immunohistochemical status of MMP-1 and clinicopathological factors were analyzed in 89 lung adenocarcinoma. We performed microarray, migration assay and invasion assay using EGFR-TKI sensitive cell lines and EGFR-TKI resistant cell lines. To clarify the mechanism of MMP-1 induction, we treated lung adenocarcinoma cells with EGF and rapamycin, performed phosphorylation antibody array and analyzed the correlation between MMP-1 expression and EGFR or mTOR (mammalian target of rapamycin) pathway. As a result, we firstly demonstrated that MMP-1 played an important role in migration and invasion abilities of EGFR-TKI resistant lung adenocarcinoma, and that mTOR pathway could be associated with an induction of MMP-1. We demonstrated the significant positive correlation between MMP-1 status in lung adenocarcinoma cells and the history of smoking, and the subtype of invasive mucinous adenocarcinoma. In conclusion, This study provides insights into the development of a possible alternative therapy manipulating MMP-1 and mTOR signaling pathway in EGFR-TKI resistant lung adenocarcinoma.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

Inertial microfluidics offers high throughput, label-free, easy to design, and cost-effective solutions and is a promising technique based on hydrodynamic forces (passive techniques) instead of external ones, which can be employed in lab-on-a-chip and micro-total-analysis-systems for focusing, manipulation, and separation of microparticles in chemical and biomedical applications. The current work, studies the focusing behavior of microparticles in an asymmetric curvilinear microchannel. For this purpose, focusing behavior, including position and band width, of microparticles of diameters of 10, 15 and 20 µm, which served as representatives of different cells, in an asymmetric curvilinear microchannel with curvature angle of 280° was experimentally studied at flow rates from 400 to 2700 µL/min (corresponding to Reynolds numbers between 30 and 205). The results revealed that the largest distance between focusing bands of 20 µm and 10 µm microparticles as well as between focusing bands of 15 µm and 10 µm was obtained at Reynolds number of 121. For the case of microparticles of diameters 20 µm and 15 µm, the largest distance was seen at Reynolds number of 144. The focusing band width became smaller in the asymmetric microchannel so that focusing could be more clearly observed in this configuration.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

Transport of hydrophobic drugs in the human body exhibits complications due to the low solubility of these compounds. With the purpose of enhancing the bioavailability and biodistribution of such drugs, recent studies have reported the use of amphiphilic molecules, such as phospholipids, for synthesis of nanoparticles or nanocapsules. Given that phospholipids can self–assemble in liposomes or micellar structures, they are ideal candidates to function as vehicles of hydrophobic molecules. In this work, we report mesoscopic simulations of nanoliposomes, constituted by lecithin and coated with a shell of chitosan. The stability of such structure and the efficiency of encapsulation of capsaicin, as well as the internal and superficial distribution of capsaicin and chitosan inside the nanoliposome were analyzed. The characterization of the system was carried out through density maps and the potentials of mean force for the lecithin–capsaicin, lecithin–chitosan and capsaicin–chitosan interactions. The results of these simulations show that chitosan is deposited on the surface of the nanoliposome, as has been reported in some experimental works. It was also observed that a nanoliposome of approximately 18 nm in diameter is stable during the simulation. The deposition behavior was found to be influenced by pattern of N-acetylation of chitosan.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

This paper presents a multifunctional reflective digital metasurface of arbitrary base based on voltage tunable liquid crystal (LC). The reflective digital metamaterial can be multiplexed for different desirable functions by properly biasing the LC for different code patterns. Simulation results of three significant functions, beam steering with a steering elevation angle 27° at 75 GHz, RCS reduction of at least 15dB along the incident direction, and beam shaping with different beam shapes have been presented to prove the concept.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.