Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

Philip Morris International (PMI) has developed the Population Health Impact Model (PHIM) to quantify, in the absence of epidemiological data, the effects of marketing a candidate modified risk tobacco product (cMRTP) on the public health of a whole population. Various simulations were performed to understand the harm reduction impact on the U.S. population over a 20-year period under various scenarios. The overall reduction in smoking attributable deaths (SAD) over the 20-year period was estimated as 934,947 if smoking completely went away and between 516,944 and 780,433 if cMRTP use completely replaces smoking. The reduction in SADs was estimated as 172,458 for the World Health Organization (WHO) 2025 Target and between 70,274 and 90,155 for the gradual cMRTP uptake. Combining the scenarios (WHO 2025 Target and cMRTP uptake), the reductions were between 256,453 and 268,796, depending on the cMRTP effective dose. These results show how a cMRTP can reduce overall population harm additionally to existing tobacco control efforts.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

Daily rainfall data was collected for the arid district of Ananthapuramu, Andhra Pradesh state, India from 1981 to 2016 at the sub-district level and aggregated to monthly, annual and seasonal rainfall totals and the number of rainy days. The objective of this study is to evaluate the homogeneity, trend, and trend change points in the rainfall data. After quality checks and homogeneity analysis, a total of 27 rain gauge locations were considered for trend analysis. A serial correlation test was applied to all the time series to identify serially independent series. Non-Parametric Mann-Kendall test and Spearman’s rank correlation tests were applied to serially independent series. The magnitude of the trend was calculated using Sen’s slope method. For the data influenced by serial correlation, various modified versions of Mann-Kendall tests (Pre-Whitening, Trend Free Pre-Whitening, Bias Corrected Pre-Whitening and two variants of Variance Correction Approaches) were applied. A significant increasing summer rainfall trend is observed in 6 out of 27 stations. Significant decreasing trends are observed at two stations in the south-west monsoon season and at two stations in the north-east monsoon season. To identify the trend change-points in the time series, distribution-free Cumulative SUM test and sequential Mann-Kendall tests were applied. Two open-source library packages were developed in R language namely, ‘modifiedmk’ and ‘trendchange’ to implement the statistical tests mentioned in this paper. The study will benefit water resource management, drought mitigation, socio-economic development and sustainable agricultural planning in the region.

Terms related to gradients of scalar fields are introduced as scalar products into the formulation of entropy. A Lagrange density is then formulated by adding constraints based on known conservation laws. Applying the Lagrange formalism to the resulting Lagrange density leads to the Poisson equation of gravitation and also includes terms being related to curvature of space. The formalism further leads to terms possibly explaining nonlinear extensions known from modified Newtonian dynamics approaches. The article concludes with a short discussion of the presented methodology and provides an outlook on other phenomena, which might be tackled using this new approach.

The time symmetry of T_c = CT is redefined based on the 4-D Euclidean space. The time inversion symmetry of T_c = CT changes the signs of the charge (q) and absolute time (ct) of the particle. The P symmetry changes the signs of the space momenta and handedness of the particle. The T_c symmetry changes the signs of the time momentum (P_t=E/c) and charges. The handedness are classified as the left-handedness and right-handedness on the 3-D space. The charges (|q| = cDt) and energies (E= cDtDV) of the particles are originated from the upward warping (q>0) and downward warping (q<0) of the particles along the time axis. The evolution of our matter universe with P_t > 0 since the big bang can be interpreted based on the CTP symmetry with the partner antimatter universe with p_t < 0. The photon space is called as the vacuum space. Then the E and M waves are the space fluctuations, and the gravitational G wave is the time fluctuations. And the E, M and G fields are newly explained. The zero E and M fields of the photon space indicates that the photon space and gamma ray are the 2EM waves. The rest mass energy of the particle is the 4-D space volume of the warped photon space. In the present work, the quantum wave function is considered as the 4-D vector with the space wave function and time axis wave function in the 4-D Euclidean space. The warped photon space corresponds to the squared wave function which is the probability density. It is concluded that, in the quantum mechanics, the imaginary number concept is introduced in the quantum wave functions instead of the time axis component of the 4-D wave function vector. The left-handed neutrino puzzle is explained from the handedness partner relation with the right-handed dark matters. Finally, the modified Lorentz transformations derived in the 4-D Euclidean space are compared with the Lorentz transformations of the special and general relativity theories in the 4-D Minkowski space.

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

The role of the Renin-Angiotensin-Aldosterone System (RAAS) in Corona Virus Disease 2019 (COVID-19) infection has become a controversial topic of discussion. RAAS inhibitors, such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs), which are used to treat cardiovascular diseases, have been implicated in potentially increasing cell surface levels of ACE2. ACE2 is the host receptor for COVID-19 that was discovered in Wuhan, China in December 2019. Since December, COVID-19 has transmitted rapidly across the world and has become a global pandemic. COVID-19 is similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) with the first case reported in Saudi Arabia in September 2012. COVID-19, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is also similar to SARS-CoV, which first infected humans in the Guangdong province of southern China in 2002, and caused an epidemic between November 2002 and July 2003. Both SARS-CoV and COVID-19 use ACE2 to enter host cells. ACE2 is primarily expressed in the mouth, lung, heart, esophagus, kidney, bladder, and intestines, and is a component of RAAS, which serves to maintain vascular tone and blood volume. Inhibition or activation of other components of RAAS has been shown to directly increase or decrease the expression and/or activity of ACE2. Furthermore, RAAS-targeting therapeutics, such as ACE inhibitors and ARBs, have also been shown to regulate the expression and/or activity of ACE2, albeit in animal models. Although these changes in ACE2 have been demonstrated only in animal models, there is no evidence that administration of RAAS-targeting therapeutics to humans for the treatment of hypertension, diabetes, and other cardiovascular diseases (e.g., myocardial infarction and heart failure) causes changes in ACE2 expression. Nor is there clinical evidence that RAAS-targeting therapeutics augment COVID-19 infection, morbidity, or mortality. However, clinical evidence does suggest that ACE2 expression may protect against respiratory distress caused by a variety of noxious agents. This review attempts to provide a balanced overview of the potential role of RAAS in regulating ACE2, and the role of ACE2 during COVID-19 infection. Evidence is provided to show that the expression of ACE2 may mediate both positive and negative outcomes, depending on the timing of ACE2 expression.

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

Three kinds of inorganic alkali are introduced into tetraethylenepentamine (TPEA) and polyethyleneimine (PEI) modified MCM-41 as the CO2 adsorbents. FT-IR and TGA are used to characterize the surface groups and the thermal stability of adsorbents. Chemical titration method is used to measure the alkali amounts of adsorbents. Thermo-gravimetric analysis with 10%CO2/N2 as the simulated flue gas is used to test the CO2 adsorption performance of adsorbents. The results show that all three kinds of inorganic alkali containing adsorbents exhibit promoted CO2 adsorption capability than traditional TPEA and PEI modified samples. Ca(OH)2 and PEI modified samples exhibit the highest adsorption capacity and stable regeneration property. The introduction of inorganic alkali changes the chemical adsorption mechanism between CO2 and increases the effective alkali amounts due to its hydroxyl groups. The CO2 adsorption capacities have a linear dependence relation with the alkali amounts of adsorbents, indicating that alkali amount is a critical factor for novel adsorbents exploring.

We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.

The paper presents an adaptation of numerical solution of first order linear differential equation in fuzzy environment. The numerical method is re-established and studied with fuzzy concept to estimate its uncertain parameters whose values are not precisely known. Demonstrations of fuzzy solutions of the governing methods are carried out by the approaches, namely Modified Runge Kutta method and Runge Kutta Merson method. The results are compared with the exact solution which is found using generalized Hukuhara derivative (gH-derivative) concepts. Additionally, different illustrative examples and an application in industry of the methods are also undertaken with the useful table and graph to show the usefulness for attained to the proposed approaches.

The three dimensional conformable time fractional Kadomtsev-Petviashvili and the conformable time fractional modified Kawahara equations are solved by implementing the Kudryashov's procedure. The corresponding wave transformation reduces both equations to some ODEs. Balancing the nonlinear and the highest order derivative terms gives the structure of the solutions in the finite series form. The useful symbolic tools are used to solve the resultant algebraic systems. The solutions are expressed in explicit forms.

The outbreak of a novel coronavirus (SARS-CoV2) associated with acute respiratory disease called COVID-19 marked the introduction of the third spillover of an animal CoV to humans in the last 2 decades. The SARS-CoV2 genome analysis with various bioinformatics tools revealed that it belongs to beta CoVs genera, with highly similar genome as bat coronavirus and receptor binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV2 is likely to be originated from bat derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further spike protein S1/S2 cleavage site of SARS-CoV2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV2, roles of virus proteins in pathogenesis, commonalities and differences between different corona viruses. We have also highlighted the evidences regarding the potential drugs and vaccine candidates with their modes of action to cope with this viral outbreak. Our review provides comprehensive up-dated information on molecular aspects of the SARS-CoV2.

Surface water distribution extracted from remote sensing data has been used in water resource assessment, coastal management, and environmental change studies. Traditional manual methods for extracting water bodies cannot satisfy the requirements for mass processing of remote sensing data; therefore, accurate automated extraction of such water bodies has remained a challenge. The histogram bimodal method (HBM) is a frequently used objective tool for threshold selection in image segmentation. The threshold is determined by seeking twin peaks, and the valley values between them; however, automatically calculating the threshold is difficult because complex surfaces and image noise which lead to not perfect twin peaks (single or multiple peaks). We developed an operational automated water extraction method, the modified histogram bimodal method (MHBM). The MHBM defines the threshold range of water extraction through mass static data; therefore, it does not require the identification of twin histogram peaks. It then seeks the minimum values in the threshold range to achieve automated threshold. We calibrated the MHBM for many lakes in China using Landsat 8 Operational Land Imager (OLI) images, for which the relative error (RE) and squared correlation coefficient (R2) for threshold accuracy were found to be 2.1% and 0.96, respectively. The RE and root-mean-square error (RMSE) for the area accuracy of MHBM were 0.59% and 7.4 km2. The results show that the MHBM could easily be applied to mass time-series remote sensing data to calculate water thresholds within water index images and successfully extract the spatial distribution of large water bodies automatically.

Presence of mutated genes strongly correlates with incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprit, we need to look at the biochemistry of cancer, with focus on enzymes which carry out any and all transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) which is tightly linked to tumor growth. Beside the circumstantial evidence that cancer is induced at its vulnerable active-site by various carcinogens, there exists experimental proof of its role in initiating retinoblastoma and HPV-related cervical cancers. Blocking the activity of RnR is a certain way to arrest cancer.

Metabolic enzymes are often targeted for drug development programs of metabolic diseases such as diabetes and its complications. Many secondary metabolites isolated from natural products have shown therapeutic action against these enzymes. However, some commercially available synthetic drugs have shown unfriendly impacts with various side effects. Thus, this research has focused on a comprehensive study of secondary metabolites showing better inhibitory activities towards metabolic enzymes such as α-amylase, α-glucosidase, aldose reductase, and lipase. Further receptor-based virtual screening was performed against the various secondary metabolites database designed in-silico. Using Gold combined with subsequent post-docking analyses, the score was obtained as methyl xestospongic ester (Gold score 65.83), 2,″4″-O-diacetylquercitrin (Gold score 65.15), kaempferol-3-O-neohesperidoside (Gold score 53.37) and isosalvianolic acid C methyl ester (Gold score 53.44) for lipase, aldol reductase, α-amylase, and α-glucosidase, respectively. Besides, vitexin and isovitexin for α-amylase; N-trans-Caffeoyl-tyramin for α-glucosidase; purpurolide F and schaftoside for lipase; acteoside and orientin for aldose reductase could be potential drugs for respective enzymes based on in-silico analyses, supported by experimental IC₅₀ values reported. They could bind to the competitive sites of the various targets of metabolic enzymes, and finally, toxicity analysis using ProTox-II was also performed.

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The K_i values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.

By using Modified simple equation method, we study the Cahn Allen equation which arises in many scientific applications such as mathematical biology, quantum mechanics and plasma physics. As a result, the existence of solitary wave solutions of the Cahn Allen equation is obtained. Exact explicit solutions interms of hyperbolic solutions of the associated Cahn Allen equation are characterized with some free parameters. Finally, the variety of structure and graphical representation make the dynamics of the equations visible and provides the mathematical foundation in mathematical biology, quantum mechanics and plasma physics.

Among the plant nutrients potassium (K) is one of the vital elements required for plant growth and physiology. Potassium is not only a constituent of plant structure but also plays regulatory function in several biochemical processes related to protein synthesis, carbohydrate metabolism, enzyme activation. There are several physiological processes like stomatal regulation and photosynthesis are dependent on K. In the recent decades K was found to provide abiotic stress tolerance. Under salt stress, K helps in maintaining ion homeostasis and regulation of osmotic balance. Under drought stress condition K regulates the stomatal opening and makes the plants adaptive to water deficit. Many reports provided the notion that K enhances the antioxidant defense in plants and therefore, protects the plants from oxidative stress under various environmental adversities. Also, it provides some cellular signaling alone or in association with other signaling molecules and phytohormones. Although a considerable progress in understanding K-induced abiotic stress tolerance in plants has been achieved the exact molecular mechanisms of such protections are still under research. In this review, we summarized the recent literature on the biological functions of K, its uptake, and translocation and its role in plant abiotic stress tolerance.

Exact solutions to conformable time fractional (3+1)- dimensional equations are derived by using the modified form of the Kudryashov method. The compatible wave transformation reduces the equations to an ODE with integer orders. The predicted solution of the finite series of a rational exponential function is substituted into this ODE. The resultant polynomial equation is solved by using algebraic operations. The method works for the Jimbo-Miwa, the Zakharov-Kuznetsov and the modified Zakharov-Kuznetsov equations in conformable time fractional forms. All the solutions are expressed in explicit forms.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

The exact solutions of some conformable time fractional PDEs are presented explicitly. The modified Kudryashov method is applied to construct the solutions to the conformable time fractional Regularized Long Wave-Burgers (RLW-Burgers, potential Korteweg-de Vries (KdV) and clannish random walker's parabolic (CRWP) equations. Initially, the predicted solution in the finite series of a rational form of an exponential function is substituted to the ODE generated from the conformable time fractional PDE by using wave transformation. The coefficients used in the finite series are determined by solving the algebraic system derived from the coefficients of the powers of the predicted solution.

Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40, and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters such as the area under the curve, C_max, and T_max varied according to the administered dose. AUC and C_max values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

This study investigated the effects of soil crust development on the underlying soil properties. The field sampling work was conducted in June 2016 in the Hobq Desert in Inner Mongolia, North China. Soil crust samples and 0–6, 6–12, 12–18, 18–24, 24–30 cm deep underlying soil samples were taken from five representative areas of different soil crust development stages. All samples were analyzed for physicochemical properties including water content, bulk density, aggregate content, organic matter content, enzyme activities, and microbial biomass carbon and nitrogen. The results showed that the thickness, water content, macroaggregate (>250 μm) content, organic matter content, microbial biomass and enzyme activities of the soil crusts gradually increased along the soil crust development gradient, while the bulk density of the soil crusts decreased. Meanwhile, the physicochemical and biological properties of the soils below the algal and moss crusts were significantly ameliorated when compared with the physical crust. Moreover, the amelioration effects were significant in the upper horizons (approx. 0–12 cm deep) and diminished quickly in the deeper soil layers.

Enzymes are in high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users. These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.

Fractional differential mathematical model unfolding the dynamics of the COVID-19 pandemic in India is presented and explored in this paper. The purpose of this study is to estimate the future outbreak of disease and potential control strategies using mathematical models in India as a whole country as well as in some of the states of the country. This model is calibrated based on reported cases of infections over the month of April 2020 in India. We have used iterative fractional complex transform method to find approximate solutions of the model having modified Riemann Liouville fractional differential operator. We have also carried out a comparative analysis between actual and estimated cumulative cases graphically, moreover, most sensitive parameters for basic reproduction number$(R_0)$ are computed and their effect on transmission dynamics of COVID-19 pandemic is investigated in detail.

That how to improve the sensitivity and the detection ability of the Large-caliber sensor is critical to satisfy the requirement of heavy vehicle wear condition monitoring. In this paper, we introduced the LC resonance principle to the design of sensor with large flow channel (7mm). The resonant exciting coil increases the impedance change of the exciting circuit caused by wear particles which magnify the current difference between the two exciting coils and improve the sensitivity of the sensor. The resonant induction coil greatly suppresses the interference signals and magnifies the weak induced electromotive force which is beneficial to enhance the detection ability. In order to boost the detectability for different materials particles, a phase controlled variable-frequency exciting system (PCVFES) was adopted to automatically switch the exciting frequency between 284kHz for ferromagnetic particles and 420KHz for non-ferromagnetic particles. For the weak signal detection, based on the essential characteristic of the signal, we apply a simpler method that modified lock-in amplifier (MLIA) rather than the conventional algorithms (Wavelet transform, EMD). Results show that using these methods the sensitivity and the detection ability of the sensor are significantly improved and the 75μm iron particles and 220μm copper particles were successfully detected which realizes the initial abnormal wear monitoring for the large flow project.

Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

Abstract: This paper is focusing on the stabilisation of soil using jute fibre as soil stabilizer. Stabilisation is the process of modifying the properties of a soil to improve its engineering performance and used it for a variety of engineering works. This study examines the potential of soil stabilization with jute fibre when it is cut into roughly 30mm lengths as stabilizer. The varying percentages like 0.5%, 1%, 1.5 and 2% of pieces of jute fibre were used and mixed it with soil. The laboratory tests such as California Bearing Ratio (CBR) test, modified compaction tests and direct shear strength tests have been conducted to observe the change in engineering properties of soil. On the basis of the experiments performed, it can be concluded that the stabilization of soil using 30mm pieces of jute as stabilizer improves the strength characteristics of the soil so that it becomes usable as one of the reinforcing material for the construction of roadways, parking areas, site development projects, airports and many other situations where sub-soils are not suitable for construction.

Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1^st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex₉GlcNAc₂ (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.

Inverse Sumudu transform multiple shifting properties are used to design methodology for solving ordinary differential equations. Then algorithm applied to solve Whittaker and Zettl equations to get their new exact solutions and profiles which shown through Maple complex graphicals. Table of inverse Sumudu transforms for elementary functions given for supporting the differential equations solving using inverse Sumudu transform.

: Nanotechnology options to road surface maintenance offers several advantages compared to traditionally used materials. The small particle sizer of hydrophobic Nano-Silane modified Nano-Polymers (NSNP) enables these nanotechnology products to deeply penetrate existing road surfaces, sealing micro-cracks and render surfacings to be water-resistant for extended periods of time. In comparison, traditionally used products contain minimum partial sizes of about 1 – 5 microns, that provide a superficial protection that wears off in a relatively short period of time. These traditional products are often associated with vehicle contamination while drying and requires the re-instatement of road markings. None of these disadvantages are associated with applicable NSNP technologies that are quick drying, with no vehicle contamination risks and is equivalent to a “clear-seal” requiring no reinstatement of road markings. In a similar vein, pot-hole repairs can be done using applicable, easy to use, pre-packed and treated pot-hole repair kits that are water-repellent and quick-drying at a fraction of the costs of conventional cold-mix products. Resurfacing using NME binder slurries can be done labour-intensively on a pre-treated NSNP surfacing, restoring cracked surfacing and providing a water-resistant long-lasting protective layer without the removal of existing cracked areas. The implementation of nanotechnology solutions for road surface maintenance operations is directly associated with ease of use, labour-intensive operations, prevention of considerable deterioration in riding quality due to removal and manual re-instatement of cracked surfaces, time and cost savings and a reduction in the risk of water damage to the sub-structure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

A recent breakthrough in preparation of immobilized enzyme based biocatalysts achieving highly enhanced enzymatic activities and stabilities has become a great alternative to conventional immobilization techniques. The functional hybrid nanobiocatalysts (FHNs) fabricated in this immobilization composed of organic components (amino acid, peptide, protein, enzyme and plant extract) and inorganic components (various metal ions) give flower-like morphology with narrow size distribution and porous structure. The enzyme incorporated FHNs exhibite greatly enhanced catalytic activities and stabilities compared to free and conventionally immobilized enzymes under various experimental conditions. In addition to that, the FHNs consisting of other organic components act as Fenton-like reagents and show peroxidase-like activity owing to presence of metal ions and porous structure in the FHNs. This report basically focuses on preparation, characterization, and bioanalytical applications of the FHNs and explain mechanism of the FHNs formation and thier enhanced activities and stabilities.

Unavoidable exposure to radiosensitive normal tissues around cancerous tumor during the radiotherapy can cause side effects such as self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Nevertheless, clinical use of currently available radiation protective agents is limited because of their generic cytotoxicity. A study on radiation protective effect of delphinidin was conducted with proton-beam-exposed human colon cells (CCD-18Co). The measurement in changes of survival fractions of CCD-18Co with/without delphinidin administration at different radiation doses were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The changes in expression of reactive oxygen species (ROS) and in activities of antioxidant enzymes were measured by colorimetric assays using pertinent assay kits. The measurement of pro-apoptosis/pro-survival protein expressions using Western blot assay and the measurement of DNA damage using comet assay were also fulfilled to evaluate the molecular level of radiation damages in CCD-18Co cells. The experimental results revealed that the pre-administration of delphinidin regulated antioxidant enzymes, reduced ROS, decreased DNA damage, regulated pro-apoptosis/pro-survival proteins, and eventually reduced apoptosis of CCD-18Co cells. In conclusion, it is claimed that delphinidin is nontoxic natural radiation protective compound, and thus delphinidin can be used to protect normal colon tissues during the proton beam therapy.

Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.

The Sine-Gordon expansion method is implemented to construct exact solutions some conformable time fractional equations in Regularized Long Wave(RLW)-class. Compatible wave transform reduces the governing equation to classical ordinary differential equation. The homogeneous balance procedure gives the order of the predicted polynomial-type solution that is inspired from well-known Sine-Gordon equation. The substitution of this solution follows the previous step. Equating the coefficients of the powers of predicted solution leads a system of algebraic equations. The solution of resultant system for coefficients gives the necessary relations among the parameters and the coefficients to be able construct the solutions. Some solutions are simulated for some particular choices of parameters.

Plants have evolved tightly regulated strategies to adapt and acclimate to a changing environment to ensure their survival. Various environmental factors affect plant distribution, growth and yield. Low temperature belongs to those abiotic factors which significantly constrain range boundaries of plant species. Exposing plants to low but non-freezing temperature induces a multigenic processes termed cold acclimation, which finally results in an increased freezing tolerance. Cold acclimation comprises reprogramming of the transcriptome, proteome and metabolome and affects communication and signaling between subcellular organelles. Reprogramming of the central carbohydrate metabolism plays a key role in cold acclimation. This review summarizes current knowledge about the role of carbohydrate metabolism in plant cold acclimation. A focus is laid on subcellular metabolic reprogramming, its thermodynamic constraints under low temperature and mathematical modelling of metabolism.

New exact solutions to conformable time fractional EW and modified EW equations are constructed by using Sine-Gordon expansion approach. The fractional traveling wave transform and homogeneous balance have significant roles in the solution procedure. The predicted solution is of the form of some finite series of multiplication of powers of cos and sin functions. The relation among trigonometric and hyperbolic functions in sense of Sine-Gordon expansion gives opportunity to construct the solutions in terms of hyperbolic functions.

An expansion method based on time fractional Sine-Gordon equation is implemented to construct some real and complex valued exact solutions to the Korteweg-de Vries and modified Korteweg-de Vries equation in time fractional forms. Compatible fractional traveling wave transform plays a key role to be able to apply homogeneous balance technique to set the predicted solution. The relation between trigonometric and hyperbolic functions based on fractional Sine-Gordon equation allows to form the exact solutions with multiplication of powers of hyperbolic functions.

Ti64 alloy plays a significant role in the biomedical applications such as bioimplants for its excellent biocompatibility. Its usage can be further extended by improving the surface hardness and wear resistance. In this respect, laser surface glazing (LSG), an advanced surface modification technique, is very useful which can produce thin hardened surface layer and strong metallurgical bonding. Investigation of temporal and spatial temperature distributions of laser glazed surface of materials are essential because temperature plays significant role in achieving required surface properties. Therefore, in this study, a 3D Finite element analysis has been developed to perform transient thermal analysis of LSG for Ti64 alloy. The model investigated temperature distribution, depth of modified zone and heating and cooling. The results show that the peak temperature is attained 2095 K for 300 W laser power, 0.2 mm beam width and 0.15 ms residence time. Since this temperature is above the melting point (1933 K) of Ti64 alloy, the melt depth is calculated 22.5 μm. Furthermore, from the simulation results, the average heating and cooling rates are estimated 1.19×10⁷ Ks^-1 and 2.71×10⁶ Ks^-1 respectively which indicate the presence of hard phases in the modified zone.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.

Mass insect rearing can have a range of applications, for example in biological control of insects. Since the performance of released biological control agents determines efficacy, the competitive fitness of insects post release is a key variable. Here, we tested whether inoculation with a gut symbiont, Enterobacter cloacae, and gnotobiotic rearing of larvae could improve insect growth and male competitive fitness of a transgenic diamondback moth, which has shown variation in fitness when reared in different insectaries. All larvae were readily infected with the focal symbiont. Under gnotobiotic rearing pupal weights were reduced and there was a marginal reduction in larval survival. However, gnotobiotic rearing substantially improved the fitness of transgenic males. In addition, in gnotobiotic conditions, inoculation with the gut symbiont increased pupal weights and male fitness, increasing the proportion of transgenic progeny from 20 to 30% relative to symbiont-free insects. Gnotobiotic conditions may improve the fitness of transgenic males by excluding microbial contaminants, while symbiont inoculation could further improve fitness by providing additional protection against infections, or by normalizing insect physiology. The simple innovation of incorporating antibiotic into diet, and inoculating insects with symbiotic bacteria that are resistant to that antibiotic, could provide a readily transferable tool for other insect rearing systems.

Background: Post-operative pain and swelling are frequently observed after sinus lift procedures. The aim of the present study was a clinical evaluation of swelling and pain of two sinus lift different flaps technique measured through visual analogue scale (VAS), verbal rating scale (VRS) and infrared thermal imaging (i.e., thermography). Methods: A randomized controlled trial was conducted in fifteen patients treated for a total of 30 sinus randomly allotted into two groups. In patients of Group I, a triangular flap was performed, while in Group II modified triangular flap without anterior release was performed. Postoperative pain was scored by VAS and inflammation was recorded by VRS at 2, 4, 6 and 14 days. The facial temperature was recorded before and after sinus augmentation, at 2, 4, 6 day intervals for the first week and at 14 day, to check the course of healing. Results: In group I the pain intensity was recorded at 2 days after the surgery with a score of 38.67 ± 6.4 mm. Swelling was higher at 2 and 4 day, and it was absent at day 6. Facial temperature difference before and after the procedure was 3 (4.737 °C ± 0.37). In Group II the pain was lower than in Group I (p < 0,05). Swelling scored 2 on the first and second day, and it was reduced at day 4. After the second day the difference of temperature reduced significantly compared to day of surgery (0.77 °C), at 2 and 4 days no difference was registered. Conclusion: In conclusion based on the outcome of the present study, modified triangular flap can be used with success in sinus augmentation procedures and is to be preferred to trapezoidal flap.

This study aims to implement a SSDBI (single-stage differential boost inverter, SSDBI) applying in a single-stage BESS (battery energy storage system, BESS) topology, which can supply power from lower voltage battery module to AC load. Compared with the common two-stage topology, which has a two-stage converter and higher voltage battery module array, the single-stage topology can reduce the number of cells and components, and improve the power density. In addition, a modified SPWM control was proposed to reduce the control complexity of the SSDBI while improving the THD of the inverter. The modified SPWM control can reduce the duty ratio of the SSDBI and the stress on the components to improve the AC voltage output waveform and reduce the THD value about 2.654%.

The present study was conducted to evaluate the effects of dietary supplementation of tea polyphenol （TP） on serum hormone, serum enzyme activity, antioxidant-related and immune-related gene expression of laying hens under heat stress. A total of 288 Chinese yellow chicken (186 days old) were randomly distributed among two treatments, each of which included 6 replicates of 24 hens. Dietary treatments were that the basal diet was supplemented with 200 mg / kg tea polyphenol. The study lasted for 7 weeks, including 1 week of adaptation and 6 weeks of the formal test. The content of high-density lipoprotein cholesterol (HDL-C) and total protein (TP) in serum significantly decreased by dietary supplementation with tea polyphenol. Dietary tea polyphenol supplementation improved serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in treatments compared to the control. However, supplementation of tea polyphenol did not affect the activity of serum catalase (CAT). The results indicated that long-term feeding of tea polyphenols help to increase the amount of hormones (FSH, E2) associated with reproduction in laying hens and thus improve egg production. It also improved the immune function of laying hens in high temperature environments. Adding tea polyphenols to the diet can significantly increase the serum IgG, IgM content of the laying hens and can upregulate the IgA content. Dietary supplementation of tea polyphenols in the laying hens significantly increased the expression of antioxidant enzyme-related genes (SOD, CAT and GPX1) in the liver. Moreover, the addition of tea polyphenols significantly increased the expression of immune-related genes (Interferon-γ (INF-γ), Interleukin 2 (IL-2) and Interleukin 4 (IL-4)) in the spleen. It is concluded that addition of tea polyphenols has a positive effect on antioxidant activity and immune function of laying hens.

The space time fractional Korteweg-de Vries equation, modified Equal Width equation and Benney-Luke Equations are solved by using simple hyperbolic tangent Ansatz method. A simple compatible wave transformation in one dimension is employed to reduce the governing equations to integer ordered ODEs. Then, the ansatz approximation is used to derive exact solutions. Some illustrative examples are presented for some particular choices of parameters and derivative orders.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

In quantum approaches to consciousness, the authors try to propose a model and mechanism for the mind-brain interaction using modern physics and some quantum concepts which do not exist in the classical physics. The independent effect of mind on the brain has been one of the challenging issues in the history of science and philosophy. In some recent mind-brain interaction models, the direct influence of mind on matter is either not accepted (as in Stapp’s model) or not clear, and there have not been any clear mechanism for it (as in Penrose-Hameroff’s model or in Eccles’s model). In this manuscript we propose a model and mechanism for mind’s effect on the matter using an extended Bohmian quantum mechanics and Avicenna’s ideas. We show that mind and mental states can affect brain’s activity without any violation of physical laws. This is a mathematical and descriptive model which shows the possibility of providing a causal model for mind’s effect on matter. It is shown that this model guarantees the realistic philosophical constraints and respects the laws of nature. In addition, it is shown that it is in agreement with the Libet style experimental results and parapsychological data. To propose this model, we obtained a modified (non-unitary) Schrödinger equation via second quantization method which affects the particle through a modified quantum potential and a new term in the continuity equation. At the second quantized level, which is equivalent to quantum field theory level (QFT), we can use the path integral formalism of Feynman. We show that there are three methods to extend Bohmian QM via path integral formalism, which has different interpretations. By numerical simulation of trajectories in the two-slits experiment, we show their differences and choose one of these methods for our mind-brain model which can be the basis for explaining some phenomena which are not possible to explain in the standard Bohmian QM.

A new model of gravity is presented here similar to the earlier work of Verlinde on Emergent Gravity but without the use of Verlinde's main assumption on the nature of gravity as an entropic force using the First Law of Thermodynamics. Instead, the model will be shown to be consistent with the Second Law of Thermodynamics as used in Black Hole Physics. Moreover, it does not use the Equipartition Theorem such that there is no need to define a thermal bath enclosed within a holographic screen. The theory uses $E=NE_{p}$, for the total energy of a massive object where $E_{p}$ is the Planck Energy while $N$ is the number of Planck Energy to represent the maximum possible density of information that can reside in matter. The theory uses also the Holographic Principle as the basis for an information-theoretic approach to the nature of gravity. It is shown here that gravity emerges whenever there is an updating of the information within a given volume of space by the presence of matter.

In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.

We hypothesize that the reason severe COVID-19 is closely linked to a limited number of conditions such as obesity, hypertension, older age and diabetes is that these conditions are characterized by a pro-inflammatory state in general and an angiotensin converting enzyme-1-bias in particular. We review recent evidence that this pro-inflammatory state can be reversed via regular exercise and a healthy diet. Studies are suggested that could test this hypothesis.

Bottom-up systems biology entails the construction of kinetic models of cellular pathways by collecting kinetic information on the pathway components (e.g. enzymes) and collating this into a kinetic model, based for example on ordinary differential equations. This requires integration and data transfer between a variety of tools, ranging from data acquisition in kinetics experiments, to fitting and parameter estimation, to model construction, evaluation and validation. Here, we present a workflow that uses the Python programming language, specifically the modules from the SciPy stack, to facilitate this task. Starting from raw kinetics data, acquired either from spectrophotometric assays with microtitre plates or from NMR spectroscopy time courses, we demonstrate the fitting and construction of a kinetic model using scientific Python tools. The analysis takes place in a Jupyter notebook, which keeps all information related to a particular experiment together in one place and thus serves as an e-labbook, enhancing reproducibility and traceability. The Python programming language serves as an ideal foundation for this framework because it is powerful yet relatively easy to learn for the non-programmer, has a large library of scientific routines and active user community, is open-source and extensible, and many computational systems biology software tools are written in Python or have a Python API. Our workflow thus enables investigators to focus on the scientific problem at hand rather than worrying about data integration between disparate platforms.

Cyanobacteria (blue-green algae) may rapidly propagate under favorable conditions, forming dense blooms. As water blooms deteriorate, blue-green algae can generate potent toxins, potentially harmful to companion animals, wildlife, and even humans. One widely recognized cyanobacterial toxin is microcystin. This algal toxin has been implicated in surface waters globally, increasing liver cancer and/or disease risk amongst those who depend on sources prone to microcystin contamination. Interestingly, no study looked at weather conditions when connecting liver health outcomes to freshwater cyanotoxins. The purpose of this study was to determine if climate was an important determinant of liver mortality and total microcystins at the ecological level. Secondary data was used to evaluate the proposed hypothesis. Environmental data (CDC WONDER) and toxin data (USEPA) were used in multivariate regression analysis. Mean daily sunlight and total microcystins were significant predictors of age-adjusted chronic liver disease and cirrhosis death rates. Mean annual precipitation and mean daily max temperature were non-significant predictors. This study demonstrated how microcystins in combination with climate may increase liver mortality. The results can prompt others to study environmental exposures of terminal liver diseases, guiding environmental health and the water industry of human survival needs.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

The use of naturally available materials not conforming to traditional specifications or standards, in the base and sub-base layers of road pavement structures, stabilised with New-age (Nano) Modified Emulsions (NME), have been tested, implemented and successfully verified through Accelerated Pavement Testing (APT) in South Africa. This was made possible through the development and use of a design procedure addressing fundamental principles and based on scientific concepts, which are universally applicable. The understanding of and incorporation of the chemical interaction between the mineralogy of the materials and a NME stabilising agent (compatibility between the chemistry of the reactive agents and material mineralogy) into the design approach is key to achieving the required engineering properties. Stabilised materials evaluation is done using tests indicative of the basic engineering properties (physics) of compressive strengths, tensile strengths and durability. This article describes the basic materials design approach developed to ensure that organofunctional nano-silane modified emulsions can successfully be used for pavement layer construction utilising naturally available materials, at a low risk. The enablement of the use of naturally available materials in all pavement layers can have a considerable impact on the unit cost and life-cycle costs of road transportation infrastructure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

Interpolation is procedure that depends on spatial and/or statistical properties of analysed variable(s). It is special challenging task for data that included low number of samples, like dataset with less than 20 data. This problem is especially emphasized in the subsurface geological mapping, i.e. in the cases where data are taken solely from wells. Successful solutions of such mapping problems ask for knowledge about interpolation methods designed primarily for small datasets and dataset itself. Here are compared two methods, namely Inverse Distance Weighting and Modified Shepard’s Method, applied for three variables (porosity, permeability, thickness) measured in the Neogene sandstone hydrocarbon reservoirs (Northern Croatia). The results showed that pure cross-validation is not enough condition for appropriate map selection, but also geometrical features need to be considered, for datasets with less than 20 points.

Controlling Nutritional Status (CONUT) Score is useful for the nutritional screening. We aimed to explore whether the CONUT score may predict a 3-month functional outcome in hemorrhagic stroke (AHS). Totally, 349 patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. Poor functional outcomes were defined as the modified Rankin Scale (mRS) score of ≥ 3 at 3 months. A total of 328 patients (mean age, 60.4 ± 12.83 years; 66.8% male) were included, 172 (52.40%) patients at malnutrition risk and 104 (31.7%) patients with a poor prognosis. High-CONUT patients had lower total lymphocyte counts and total cholesterol levels than low-CONUT patients (p &lt; 0.001 and p = 0.012). At 3-month post discharge, patients with malnutrition risk had higher hospitalization costs (p = 0.021), lower Barthel Index (p = 0.001), and more infectious complications (p = 0.002) than those without, and there was a greater risk for poor functional outcomes in the high-CONUT compared with the low-CONUT patients at admission (adjusted odds ratio: 2.32, 95% confidence interval: 1.28-4.17). High-CONUT scores predict a 3-month poor prognosis in AHS, which may help identify the AHS patients who need additional nutritional managements.

Cyanobacterial mass developments in eutrophic ponds and lakes are a major concern for lake management, as many cyanobacteria produce a huge variety of toxic secondary metabolites, e.g. microcystins. The aim of this research was to culture a strain of the cyanobacterium Microcystis sp strain BM25, to observe its biomass production and to isolate and purify protease inhibitors from this cyanobacterial biomass. Different secondary metabolites were isolated following a standard bioassay-guideline. Isolation was performed, with an enzymatic protease assay as bioassay. High performance liquid chromatography was used to identify different fractions of secondary metabolite from the strain BM25. Moreover, protease homogenates were isolated from Daphnia magna in order to test the inhibitors against naturally occurring major digestive proteases trypsin and chymotrypsin. It was measured that 60% MeOH and the 80% MeOH C18-SPE fraction inhibits chymotrypsin activity 98% (6 nmol pNA min^-1 mg^-1) and 99 % (4 nmol pNA min^-1 mg^-1), respectively. In contrast, trypsin activity was not inhibited by methanolic extracts of this cyanobacterium strain.

The purpose of bovine colostrum, being the milk secreted by a cow after giving birth, is to transfer passive immunity to the calf. The calves have an insufficient immune system as they lack immunoglobulins (Igs). Subsequently, the supply of good quality bovine colostrum is obligatory. The quality of colostrum is classified by low bacterial counts and adequate Ig concentrations. Bacterial contamination can contain a variety of human pathogens or high counts of spoilage bacteria, which becomes more challenging with emerging use of bovine colostrum as food and food supplements. There is also a growing risk for the spread of zoonotic diseases originating from bovines. For this reason, processing based on heat treatment or other feasible techniques are required. This review provides an overview of literature on the microbial quality of bovine colostrum and processing methods to improve its microbial quality and keep its nutritional values as food. The highlights of this review are: high quality colostrum is a valuable raw material in food products and supplements, the microbial safety of bovine colostrum is increased using appropriate processing, suitable effective heat-treatment, which does not destroy the high nutrition value of colostrum, the heat treatment processes are cost-effective compared to other methods, and heat treatment can be performed in both small- and large-scale production

DNA origami has emerged in recent years as a powerful technique for designing and building 2D and 3D nanostructures. While the breadth of structures that have been produced is impressive, one of the remaining challenges, especially for DNA origami structures intended to carry out useful biomedical tasks in vivo, is to endow them with the ability to detect and respond to molecules of interest. Target molecules may be disease indicators or cell surface receptors, and the responses may include conformational changes leading to release of therapeutically relevant cargo. Nucleic acid aptamers are ideally suited to this task and are beginning to be used in DNA origami designs. In this review we consider examples of uses of DNA aptamers in DNA origami structures and summarise what is currently understood regarding aptamer-origami integration. We review three major roles for aptamers in such applications: protein immobilisation, triggering of structural transformation, and cell targeting. Finally, we consider future perspectives for DNA aptamer integration with DNA origami.

The potential of Neural Stem Cells (NSCs) to provide therapeutic benefit for a variety of neurological disorders, including brain malignancies, has been long recognized and has inspired many scientists to design, test and successfully demonstrate that NSCs are efficient and effective therapeutic agents. Glioblastoma, the deadliest form of primary brain tumor, despite extensive and sustained efforts to find better therapies, remains a disease without cure, with a median survival after diagnosis of less than two years. Treatment resistance in glioblastoma is in large part attributed to limitations in the delivery and distribution of therapeutic agents administered either systemically or directly into the tumor due to the highly invasive nature of this cancer and its abnormal intratumoral vasculature. Stem Cells (SCs) have an innate tumor-tropic migratory behavior, can be modified to deliver a variety of therapeutic agents and efficiently distribute their cargo into brain tumors, pursuing invading streams of tumor cells, deep into the brain parenchyma. Over the last twenty years, numerous preclinical trials have demonstrated the feasibility and efficacy of SCs as antiglioma agents, leading to the development of trials to test these therapies in the clinic. In this review we present and analyze these studies and discuss mechanisms underlying their beneficial effect, highlighting experimental progress, limitations and the emergence of promising new therapeutic avenues. We hope to increase awareness of the advantages of using SCs for the treatment of glioblastoma and inspire further studies that will lead to accelerated implementation of effective therapies.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

In this paper, we investigate the Hawking radiation process by using the quantum tunneling phenomenon of massive spin-1 (W-bosons) and spin-0 particles from (2+1) dimensional Black Hoke with quintessential and magnetic field. For this purpose, using Hamilton-Jacobi ansatz, we apply the WKB approximation to the field equations of massive charged vector particles. We get the required tunneling rate of radiated particles and obtain their corresponding Hawking temperature $T_h$. In order to study the quantum gravity effects, we utilize the generalized Proca and Klein-Gordan equations incorporating the generalized uncertainty principle (GUP) and recover the accompanying quantum corrected temperature $T'_{h}$.

Clean, fresh, and safe drinking water is essential to human health and well-being. Occasionally, chemical pollutants taint surface water quality used for consumption. Microcystins (MCs) are toxic heptapeptides produced by freshwater cyanobacteria. These secondary metabolites can reach hazardous concentrations, impairing surface drinking water supplies. Inconsistent screening of MCs is not uncommon in Florida waters as no provisional guidance value is established to protect public health. The occurrence of MCs in Lake Manatee and Lake Washington was monitored over the potential peak algae bloom season (June-August). An indirect competitive enzyme-linked immunosorbent assay (icELISA) quantified total MCs in two drinking water systems. Varied concentrations occurred between June and July, whereas concentrations peaked in August. Overall, MC prevalence was higher in Lake Manatee than Lake Washington. Colorimetric assays measured phosphate and nitrite in environmental water samples. Phosphate and nitrite concentrations strongly correlated with total MCs (p < 0.01). The results indicate the intrinsic nature of environmental MCs in surface drinking water supplies and the need to examine hepatotoxin dynamics to preserve drinking water quality in community served areas.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

Nano-scale organofunctional silanes have been developed, tested and successfully applied to protect stone buildings in Europe against climatic effects since the 1860s. The same nanotechnologies can also be used in pavement engineering to create strong chemical bonds between a stabilising agent and the material substrata. The attachment of the organofunctional silane to a material also makes the surface of the material hydrophobic, reducing future chemical weathering. These properties allow naturally available materials to be used in any pavement layer at a low risk. In the built environment, scientists soon determined that the successful use of an organo-silane depends on the type and condition of the stone to be treated. The same principles apply to the implementation of applicable nanotechnologies in pavement engineering. Understanding the basic chemistry determining the properties of the stabilising agent and the organofunctional modifying agent and the chemical interaction with the primary and secondary minerals of the material are essential for the successful application of these technologies in pavement engineering. This paper explains some basic chemistry which fundamentally influences engineering outputs that can be achieved using New-age (Nano) Modified Emulsions (NME) stabilising agents with naturally available material in all road pavement TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

The aim of the study was to assess the chemical and biochemical composition of heat-treated dates palm fruits (Phoenix dactylifera L.) cultivated in Algeria and stored under Modified Atmosphere Packaging (MAP). In this research, fresh dates palm fruits at harvest (Phoenix dactylifera L.) have been subjected at heat treatment at 55 ± 2°C for 20 min in a ventilated oven. The samples were packed in specific Polyethylene Terephthalate packaging (PET) bags with a thickness of 2.5 μm under MAP condition. The effect of this heat treatment on date fruits quality was investigated during 5 months of storage at room temperature storage (22 ± 1°C of temperature with 75 to 80% of relative humidity (RH), and 10 ± 1°C with 85 to 90% of RH). Chemical and biochemical composition of the samples were studied. Results indicated that during storage the Brix degree, protein, and vitamin C content changed significantly (p&lt;0.05). The major change was observed for lipid values varied from about 0.02 to 0.06% at 10°C, and 0.04 to 0.07% at 22°C for samples not heat-treated unpacked after 5 months of storage, these results represent a highly significant difference (p&lt;0.01). Harvesting at Tamr stage followed by treating the fruits with heat disinfestation packed in MAP, and storing at 10 ± 1°C showed to be a promising method for maintaining dates fruits storage quality.

A 9,10-phenanthrenequinone (PQ) was electrochemically polymerized on a graphite rod electrode using potential cycling. The electrode modified by poly-9,10-phenanthrenequinone (poly-PQ) was studied by means of cyclic voltammetry, electrochemical impedance spectroscopy, atomic force microscopy and scanning electron microscopy. The poly-PQ shows variations in growth pattern depending on the number of potential cycles for the initiation of polymerization. Formed poly-PQ layer demonstrates good electric conductivity, great electrochemical capacitance and unique oxidation/reduction properties, which are suitable for broad technological applications, including applicability in biosensors, supercapacitors, and in some other electrochemical systems.

Regression models form the core of the discipline of econometrics. One of the basic assumptions of classical linear regression model is that the values of the explanatory variables are fixed in repeated sampling. However, in most of the real life cases, particularly in economics the assumption of fixed regressors is not always tenable. Under a non-experimental or uncontrolled environment, the dependent variable is often under the influence of explanatory variables that are stochastic in nature. There is a huge literature related to stochastic regressors in various aspects. In this paper, a historical perspective on some of the works related to stochastic regressor is being tried to pen down based on literature search.

Water treatment efficiency of several filter media such as perlite, modified (silicated) perlite, zeolite and sand were studied on wastewater. This study contains 2 distinct experiments which the first one emphasize on the modified perlite’s performance in removing turbidity which has been gone through 3 phases including low turbidity model water, mid turbidity and high turbidity model water; the second experiment underlines the differentiation between 3 evolutionary material based on perlite which undergoes the filtration process with certain turbid model water. It was dedicated that modified perlite removed more than 90% of turbidity and it functions better than other materials with high turbidity (more than100 NTU). The experiments have been conducted with sodium silicate perlite, normal perlite and synthetic zeolite perlite in order to determine the optimized material which is able to be substituted with perlite in the filtration process.

Soil proteases are involved in the transformation of organic matter and thus influence the nutrient turnover in the ecosystem. Phytohormones, similarly to proteases, are synthesized and secreted into the soil by fungi and microorganisms and regulating their activity in the rhizosphere. The aim of our work was to find out how the presence of auxins, cytokinins, ethephone and chlorocholine chloride affects the activity of native soil proteases at the spruce tree stand. Auxins stimulated the native proteolytic activity in the spruce tree stand. Synthetic auxins most stimulated the activity of 2-naphthoxyacetic acid and the naturally occurring auxins of indole-3-acetic acid in the organic horizon of the spruce forest. Cytokinins, ethephone and chlorocholine chloride inhibited the activity of native soil proteases in the spruce tree stand. The highest inhibitory effect was found in ethephone and chlorocholine chloride. Overall, the negative effect of phytohormones on the activity of the native proteolytic activity may slow down the decomposition of organic matter and thus make plant nutrition more difficult. The outcomes of our work assist with understanding of the effect of substances produced by the rhizosphere on the activity of soil microorganisms and the soil nitrogen cycle.

In this paper, we revisit a modified version of the classical Whitehead's theory of gravity in which all possible bilinear forms are considered to define the corresponding metric. Although, this is a linear theory that fails to give accurate results for the most sophisticated predictions of general relativity, such as gravity waves, it can still provide a convenient framework to analyze some new phenomena in the Solar System. In particular, recent development in the accurate tracking of spacecraft and the ephemerides of planetary positions have revealed certain anomalies in relation with our standard paradigm for celestial mechanics. Among them the so-called flyby anomaly and the anomalous increase of the astronomical unit play a prominent role. In the first case the total energy of the spacecraft changes during the flyby and a secular variation of the semi-major axis of the planetary orbits is found in the second anomaly. For this to happen it seems that a net energy and angular momentum transfer is taken place among the orbiting and the central body. We evaluate the total transfer per revolution for a planet orbiting the Sun in order to predict the astronomical unit anomaly in the context of Whitehead's theory. This could lead to a more deeply founded hypothesis for an extended gravity model.

In this study, the effect of heat treatment was investigated to influence the occurrence of fracture during manufacturing process of Alloy B steel with boron contents as high as 130 ppm. As the content of boron increases, it affects the phase transformation temperature and texture. The development of {111}<uvw> components in the γ-fiber is affected depending on the austenite fraction after phase transformation. The Alloy B steel indicated that the increase in the boron content increased the α to γ phase transformation temperature such that sufficient transformation did not occur in the normalizing condition. The cracks occurred at the point of the transition from elastic to plastic deformation in the ND direction during the rolling process, thereby resulting in failure. Therefore, it is necessary to avoid the intermediate heat treatment condition in which γ-fiber does not fully develop, i.e., an imperfect normalization.

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

The constant ħ is elevated to a dynamical field, coupling to other fields, and itself, through the Lagrangian density derivative terms. The spatial and temporal dependence of ħ falls directly out of the field equations themselves. Three solutions are found: a free field with a tadpole term; a standing-wave non-propagating mode; a non-oscillating non-propagating mode. The first two could be quantized. The third corresponds to a zero-momentum classical field that naturally decays spatially to a constant with no ad-hoc terms added to the Lagrangian. An attempt is made to calibrate the constants in the third solution based on experimental data. The three fields are referred to as actons. It is tentatively concluded that the acton origin coincides with a massive body, or point of infinite density, though is not mass dependent. An expression for the positional dependence of Planck’s constant is derived from a field theory in this work that matches in functional form that of one derived from considerations of Local Position Invariance violation in GR in another paper by this author. Astrophysical and Cosmological interpretations are provided. A derivation is shown for how the integrand in the path integral exponent becomes Lc/ħ(r), where Lc is the classical action. The path that makes stationary the integral in the exponent is termed the “dominant” path, and deviates from the classical path systematically due to the position dependence of ħ. The meaning of variable ħ is seen to be related to the rate of time passage along each path increment. The changes resulting in the Euler-Lagrange equation, Newton’s first and second laws, Newtonian gravity, Friedmann equation with a Cosmological Constant, and the impact on gravitational radiation for the dominant path are shown and discussed.

Successful engineering of a microbial host for efficient production of a target product from a given substrate can be viewed as an extensive optimization task. Such a task involves the selection of high activity enzymes as well as their gene expression regulatory control elements (i.e., promoters and ribosome binding sites). Finally, there is also the need to tune expression of multiple genes along a heterologous pathway to relieve constraints from rate-limiting step and help reduce metabolic burden on cells from unnecessary over-expression of high activity enzymes. While the aforementioned tasks could be performed through combinatorial experiments, such an approach incurs significant cost, time and effort, which is a handicap that can be relieved by application of modern machine learning tools. Such tools could attempt to predict high activity enzymes from sequence, but they are currently most usefully applied in classifying strong promoters from weaker ones as well as combinatorial tuning of expression of multiple genes. This perspective reviews the application of machine learning tools to aid metabolic pathway optimization through identifying challenges in metabolic engineering that could be overcome with the help of machine learning tools.

At present there is a renewed interest in theories of ”modified” gravity. Here, under a more drastic modification enforced by Galilei group, we obtain a completely new gravitational structure, and which exists in addition to the already available general relativity of today. Correlated with this, we show that in addition, there is a new ”modified” quantum mechanics, in as much as it exists as an independent and new ”pure” non-relativistic quantum me- chanics, and which has no relativistic counterpart. This is in addition to the present quantum mechanics, where the relativistic and non-relativistic structures are counterparts of each other. The above holds, firstly due to the correlation between Galilei group and quantum mechanics. These math- ematical conclusions are consolidated by the fact that there exists a physical Majorana interaction between each neutron- proton pairs in nuclei. Galilei invariance of Majorana exchange in Majorana interaction, shows that the mass here is of pure gravitational nature, and which is immune to the other three forces. This makes an amazing connection between the gravitational force and the quantum mechanics. This pure gravitational mass would man- ifest itself as dark matter of the universe. It is our new modified gravity that generates the dark matter.

Angiotensin converting enzyme 2 (ACE2) is a key entry point of SARS-CoV-2 virus known to induce COVID-19. We have recently outlined the concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs, such as the intestine, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on the stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we confirmed the reduction of ACE2 also at the protein level. Present findings provide first evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

Abstract: This study aims to set up a system to evaluate nursing competencies in disaster preparedness for undergraduates and influencing factors in China. The evaluation system was established by using the modified Delphi. There were 3 phases in this study: 1) an environmental scan; 2) setting framework; 3) adjusting indicators based on the modified Delphi. The questionnaire for these undergraduates lied in their basic information and assessment of nursing competencies in disaster preparedness. Based on the survey, the average score of nursing competencies in disaster preparedness for undergraduate nursing students surveyed was 3.10 (out of 5). In addition, gender, grade, inhabitation, and disaster drills of the students were four factors affecting nursing competencies of undergraduates. This study indicates that the present nursing competencies in disaster preparedness for undergraduates are weak, and it is essential to strengthen nursing education in disaster preparedness for undergraduates.

The use of New-age (Nano) Modified Emulsions (NME) for the stabilisation of marginal materials for use in the upper-pavement layers of roads have been proven in laboratories, through Accelerated Pavement Tests (APT) and in practice. In addition, material design methods have been developed based on the scientific analysis of granular material mineralogy and the chemical interaction with the binder to design a material compatible NME stabilising agent for naturally available (often marginal) materials. However, the introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology enables the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In practice, few road construction projects are without any problems. The introduction of new-technologies obviously makes it an easy target to blame for any non-related problem that may arise during construction. This article aims to assist in pre-empting, recognising, preventing and resolving material or non-material related construction problems through the correct identification of the cause of the problem and recommending the best, most cost-effective way to correct any deficiencies on site.

olten salt reactors (MSRs) utilize salts as coolant or as the fuel and coolant together with fissile isotopes dissolved in the salt. It is necessary to therefore understand the behavior of the salts to effectively design, operate, and regulate such reactors, and thus there is a need for thermodynamic models for the salt systems. Molten salts, however, are difficult to represent as they exhibit short range order that is dependent on both composition and temperature. A widely useful approach is the modified quasichemical model in the quadruplet approximation that provides for consideration of first and second nearest neighbor coordination and interactions. Its use in the CALPHAD ap-proach to system modeling requires fitting parameters using standard thermodynamic data such as phase equilibria, heat capacity, and others. Shortcoming of the model is its inability to directly vary coordination numbers with composition or temperature. Another issue is the difficulty in fitting model parameters using regression methods without already having very good initial values. The proposed paper will discuss these issues and note some practical methods for the effective genera-tion of useful models.