The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19.

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

Crop-type mapping is an important intermediate step for cost-effective crop management at the field level, as an overview of all fields with a particular crop type can be used for monitoring or yield forecasting, for instance. Our study used a data set with 2400 fields and corresponding satellite observations from the federal state of Bavaria, Germany. The study classified corn, winter wheat, winter barley, sugar beet, potato, and winter rapeseed as the main crops grown in Upper Bavaria. We additionally experimented with a rejection class "Other", which summarised further crop types. Corresponding Sentinel-2 data included the normalised difference vegetation index (NDVI) and raw bands from 2016 to 2018 for each selected field. The influence of raw bands compared to NDVI was analysed and the classification algorithms, i.e. support vector machine (SVM) and random forest (RF), were compared. The study showed that the use of an index should be critically questioned and that raw bands provided a wider spectral bandwidth, which significantly improved the mapping of crop types. The results underline the use of RF with raw bands and achieved overall accuracies (OA) of up to 92%. We also predicted crop types in an unknown year with significantly different weather conditions and several months before the end of the growing season. Thus, the influence of climate anomalies and the accuracy depending on the time of prediction were assessed. The crop types of a test site and year without labels could be determined with an OA of up to 86%. The results demonstrate the usefulness of the proof-of-concept and its readiness for use in real applications.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Titania is one of the most comprehensively studied nanostructures due to its widespread applications in production of catalytic, gas- sensing and corrosion- resistance materials [1]. M-polynomial of nanotubes has been vastly investigated as it produces many degree-based topological indices which are numerical parameters capturing structural and chemical properties. These indices are used in the development of quantitative structure-activity relationships (QSARs) in which the biological activity and other properties of molecules are correlated with their structure like boiling point, stability, strain energy etc of chemical compounds. In this paper, we determine M-polynomials of single-walled titanium (SW TiO2) nanotubes and recover important topological degree based indices of them to theoretically judge these nanotubes. We also use Maple to plot surfaces associated to different types of single-walled titanium (SW TiO2) nanotubes.

Frost heave, which is the volumetric expansion of frozen soil, has great ecological significance, since it creates water storage spaces in soils at the beginning of the growing season in cold temperate forests. To understand the characteristics of frost heave in seasonally frozen soil and the factors that impact its extent, we investigated the frost heave rates of forest soil from different depths and with different soil moisture contents, using both lab-based simulation and in situ measurement in a broadleaved Korean pine forest in the Changbai Mountains (northeastern China). We found that frost heave was mainly affected by soil moisture content, soil type, and gravitational pressure. Frost heave rate increased linearly with soil moisture content, and for each 100% increase in soil moisture content, the frost heave rate increased by 41.6% (loam, upper layer), 17.2% (albic soil, middle layer), and 4.6% (loess, lower layer). Under the same soil moisture content, the frost heave rate of loam was highest, whereas that of loess was lowest, and the frost heave of the uppermost 15 cm, which is the biologically enriched layer, accounted for ~55% of the frost heave. As a result, we determined the empirical relationship between frost heave and freezing depth, which is important for interpreting the effects of frost heave on increases in the storage space of forest soils and for calculating changes in soil porosity.

We previously reported new superconductivity produced by an electrostatic field and a diffusion current in a semiconductor without refrigeration. In particular, the superconductivity was investigated theoretically and confirmed experimentally. Here, we determine that the derived superconducting quantum state can be reproduced in a capacitor. When circuits are formed with this new-type capacitor and diodes, a magnetic field is applied to the diodes’ depletion layer. The depletion layer is biased because of the conversion from the magnetic-field energy to electric-field energy, resulting in the diodes’ spontaneously emitting a current. Thus, the new-type capacitor is charged using no other energy source. This new phenomenon is described theoretically with assistance of initial experiments.

In this study, a graphene-doped porous silicon (G-doped/p-Si) substrate for low ppm H₂ gas detection by an inexpensive synthesis route was proposed as a potential noble graphene-based gas sensor material and to understand the sensing mechanism. The G-doped/p-Si gas sensor was synthesized by a simple capillary force-assisted solution dropping method on p-Si substrates, whose porosity was generated through an electrochemical etching process. G-doped/p-Si was fabricated with various graphene concentrations and exploited as a H₂ sensor operated at room temperature. The sensing mechanism of the sensor with/without graphene decoration on p-Si was proposed to elucidate the synergetic gas sensing effect generated from the interface between the graphene and p-type silicon.

Pure-compression shells have been the central topic in the form-finding of shells. This paper studies tension-compression mixed type shells by utilizing a NURBS-based isogeometric form-finding approach that analyzes Airy stress functions to expand the possible plan geometry. A complete set of smooth version graphic statics tools is provided to support the analyses. The method is validated using examples with known solutions, and a further example demonstrates the possible forms of shells that the proposed method permits. Additionally, a guideline to configure a proper set of boundary conditions is presented through the lens of asymptotic lines of the stress functions.

An active power dispatch method for a microgrid (MG) with multi-type loads, renewable energy sources (RESs) and distributed energy storage devices (DESDs) is the focus of this paper. The MG operates in a grid-connected model, and distributed power sources contribute to the service for load demands. The outputs of multiple DESDs are controlled to optimize the active power dispatch. Our goal with optimization is to reduce the economic cost under time-of-use (TOU) price, and to adjust the excessively high or low load rate of distributed transformers (DTs) caused by the peak-valley demand and load uncertainties. To simulate a practical environment, the stochastic characteristics of multi-type loads are formulated. The transition matrix of system state is provided. Then, a finite-horizon Markov decision process (FHMDP) model is established to describe the dispatch optimization problem. A learning-based technique is adopted to search the optimal joint control policy of multiple DESDs. Finally, simulation experiments are performed to validate the effectiveness of the proposed method, and the fuzzification analysis of the method is presented.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Recent discovery of triangular boron Nanotubes makes it a competitor of carbon in many respects. Closed forms of M-polynomial of nanotubes produce closed forms of many degree-based topological indices which are numerical parameters of the structure and, in combination, determine properties of the concerned nanotubes. In this report, we give M-polynomials of triangular boron nanotubes and recover many important topological degree-based indices of these nanotubes. We also plot surfaces associated to these nanotubes.

One of the rare diseases throughout the world is Glycogen Storage Disease, which appears due to problems in glycogen metabolism. Among various subtypes of GSD, GSD Type 1a is the most abundant one of GSD Type 1, seen in approximately 80% and caused by different kinds of mutations in the Glucose-6-Phosphatase Catalytic Subunit (G6PC) gene in human chromosome 17q21. G6PC gene encodes for glucose-6-phosphatase (G6Pase) protein, which cleaves glucose-6-phosphate into glucose and inorganic phosphate (Pi), and GSD Type 1a patients fail to breakdown glucose-6-phosphate due to several mutations in the G6PC gene. In our study, we aim to create new therapeutic approaches for GSD 1a. We collected mutation data of 57 GSD Type 1a patients from Turkey. According to the data, 16 types of mutations were observed in the G6PC gene. Allele frequencies of these mutations are calculated as 59% for R83C/H, 11% for W160*, 7% for G270V, and 28% for others which have less frequency. Up to now, the tertiary protein structure of G6Pase has not been structured yet. To understand the possible impacts of these mutations, we statistically obtained possible tertiary structure predictions of G6Pase by running 5 different tools. At the end of the study, we suggest two effective and promising gene therapy methods for GSD Type 1a, Prime Editing for R83C/H mutations, and mRNA delivery for other mutations, in addition to a promising, commercially available drug suggestion for patients with W160*, W86*, and S15* mutations, although the drug belongs to another disease.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Abstract Background: Diabetes mellitus is dramatically increasing in the wide world. The managing of diabetes care emphasized the self-management education and support into patients’ care and family care. Objective: to review and synthesizes the effectiveness of DSME strategies involving family as a key person to provide social support for diabetes mellitus self-management of glycemic uncontrolled patients Method: Three databases through PubMed, CINAHL, and Scopus were reviewed to assess the relevant articles. The following search terms: “type 2 diabetes,” “self-management,” “family support,” and “glycemic uncontrolled.” We summarized details of family support on self-management among glycemic uncontrolled patients for 14 existing studies. Results: A total of 22 intervention studies were identified. Those studies have a heterogeneous of the education strategies, support perceived, follow-ups strategies and outcomes among type 2 DM. Family integration on diabetes self-management education (DSME) has a positive impact on several outcomes including, self-care behaviors, psychological outcomes, self-efficacy and clinical outcomes Conclusions: This systematic review found robust data related to the integration of family support on diabetes self-management among glycemic uncontrolled patients. Consequently, the improvement in outcomes was identified. Implications: The findings suggest model of family engagement is better and needed for sustaining the diabetes care in the long-term care

Lectins are carbohydrate-interacting proteins playing a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through the carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensor for capturing and identification of bacterial species. In this work, we have characterized the bacterial agglutination properties of three C-type lectins from the Lepidoptera Spodoptera exigua. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as biosensor or other biotechnological applications involving bacterial capturing.

M-polynomial of different molecular structures helps to calculate many topological indices. A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR) quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular topological indices such as the Zagreb indices, Randic index, Symmetric division index, Harmonic index, Inverse sum index, Augmented Zagreb index, multiple Zagreb indices etc. are correlated. In this report, we compute closed forms of M-polynomial, first Zagreb polynomial and second Zagreb polynomial of Octagonal network. From the M-polynomial we recover some degree-based topological indices for Octagonal network. Moreover, we give a graphical representation of our results.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

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.

This article develops duality principles and related convex dual formulations suitable for the local optimization of non-convex primal formulations for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a Ginzburg-Landau type equation.

Splines and quasi-interpolation operators are important both in approximation theory and applications. In this paper, we construct a family of quasi-interpolation operators for the bivariate quintic spline spaces S₅³ (∆_mn⁽²⁾). Moreover, the properties of the proposed quasi-interpolation operators are studied, as well as its applications for solving two-dimensional Burgers’ equation and image reconstruction. Some numerical examples show that these methods, which are easy to implement, provide accurate results.

Societies around the world face serious energy problems related to the consumption of fossil fuels and the emission of dangerous radiation. To solve these problems, a new superconductor exhibiting a critical temperature higher than room temperature has been pursued but not achieved. This paper proposes a new energy generation system based on a circuit approach. Secondary to this process, a new type of superconductivity without refrigeration is demonstrated. In our previous paper [1], this system was proposed, but it did not describe the underlying theory in detail and did not mention an actual method to generate energy from the system. The present paper describes the theory of the existence of divergent current density and new superconductivity with no refrigeration. Moreover, the present paper proposes a method for extracting energy from the system by employing a voltage-controlled current source (i.e., a voltage–current converting method).The principle of the system is based on a circuit of two loops and independent current sources. First, the two electric loops are prepared, each with 4 diodes, where the diodes are oriented in the same direction within each loop, but their direction is opposite from loop to loop; four independent current sources connect the loops. In this circuit system, current is added iteratively as it flows along the loop according to Kirchhoff’s circuit law. As a result, a large current and electric potential are present along the loop. To confirm that this system works properly, it is necessary to demonstrate the presence of divergent currents in the transient state, and to do this, the present paper employs the Dirac equation and Lorentz conservation. Electric circuit software is employed to demonstrate that the presented method generates energy actually from our system.Our results confirm the presence of divergent current at a connected point of an independent current source in the transient state. Moreover, in the steady state, the theory demonstrates the Meissner effect (i.e., a London equation) and a new type of macroscopic wave function and condensation. For an initial small input current of 0.1 μA, the simulation reveals a large generating current of 7 kA and electric power of 10¹¹ W, which is much larger than unit of power from an average thermal power station; moreover, the system presents with superconducting electrical transport conditions.The present study is significant because it demonstrates theoretically the existence of divergent current density and a new type of superconductivity requiring no refrigeration. Secondly, the simulations show the generation of a large energy density that can be obtained in a small laboratory room with minimal cost.

Rifampicin is one of the most important chemotherapeutic agents used in the treatment of tuberculosis. M. tuberculosis clinical strains resistant to rifampicin harbor mainly mutation in an 81-base pair region of rpoB. These mutations mainly consist of single amino acid substitutions. However insertions also can be related with rifampicin resistance strains. Herein, we described an insertion of 12 nucleotides in clinical isolates of M. tuberculosis resistant to rifampicin, all obtained from inmates. To evaluate the importance this insertion in surviving and drug resistance, it were carried out fitness experimental assays as well as in silico studies of 3D structural models, molecular docking simulations and virtual screening. The medical records of the seven patients showed all were previously treated to tuberculosis. Growth curves shown that the insertion determines a biological cost when compared to wild type rpoB and katG; or the double mutated rpoB S531L and katG S315T. From docking and molecular dynamics simulations it can be inferred that the insertion does not affect the process of synthesis of RNA transcripts. On the other hand, in the mutant RNAP-RIF complex rifampicin confirmed a low affinity interaction for the mutant form. Interesting, virtual screening for potential inhibitors for wtRNAP and mRNAP using a library of 1446 compounds approved by the FDA showed that the best ligands were mainly compounds with antibiotic activity, although the targets involved in the pharmacological action are other than RNAP. In conclusion, seven strains of M. tuberculosis RIF resistant that present an insertion of four amino acids in RNA polymerase showed by growth curve assays, a biological cost. Further, bioinformatics tools had characterized the putative drug resistance dynamic as well as the maintenance of RNA polymerase activity.

To solve large scale linear equations involved in the Fast Multipole Boundary Element Method (FM-BEM) efficiently, an iterative method named the generalized minimal residual method (GMRES)(m)algorithm with Variable Restart Parameter (VRP-GMRES(m) algorithm) is proposed. By properly changing a variable restart parameter for the GMRES(m) algorithm, the iteration stagnation problem resulting from improper selection of the parameter is resolved efficiently. Based on the framework of the VRP-GMRES(m) algorithm and the relevant properties of generalized inverse matrix, the projection of the error vector r_m+1 on r_m is deduced. The result proves that the proposed algorithm is not only rapidly convergent but also highly accurate. Numerical experiments further show that the new algorithm can significantly improve the computational efficiency and accuracy. Its superiorities will be much more remarkable when it is used to solve larger scale problems. Therefore, it has extensive prospects in the FM-BEM field and other scientific and engineering computing.

Here we mathematically model black holes and the early universe following dynamics similar to RLC electrical models, focusing on their similarities at the singularity. We use this mathematically modelling to hypothesize the evolution of an expanding universe as the result of a black hole collapse followed by its evaporation. Or model consists of several steps defined by: (1) the formation of a black hole following general relativity equations; (2) growth of the black hole modelled as a resistance-capacitance-like electrical circuit; (3) expansion of space-time following the disintegration of the black hole, modelled by RLC-like dynamics. In updating this article, version 2, we will expand by presenting three additional examples related to the theory of the generalization Boltzmann's constant in curved space-time and the theory of general and especial relativity. We will calculate the critical mass to produce a black hole in the LHC, the existence of a high temperature Bose-Einstein condensate and finally we will demonstrate the existence of a tangential force to the repulsion force in the disintegration of subatomic particles. In the update of this article, version 3, we will expand to develop two examples. First, we will present the relationship between M-theory, extra dimensions with the theory of the generalization of Boltzmann's constant in curved space-time. Secondly, we will propose the idea of ​​updating the Lambda-CDM model, considering the primordial gravitational waves to correctly describe the evolution of the universe.

A construction for the systems of natural and real numbers is presented in Zermelo-Fraenkel Set Thoery, that allows for simple proofs of the properties of these systems, and practical and mathematical applications. A practical application is discussed, in the form of a Simple and Linear Fast Adder (Patent Pending). Applications to finite group theory and analysis are also presented. A method is illustrated for finding the automorphisms of any finite group $G$, which consists of defining a canonical block form for finite groups. Examples are given, to illustrate the procedure for finding all groups of $n$ elements along with their automorphisms. The canonical block form of the symmetry group $\Delta_4$ is provided along with its automorphisms. The construction of natural numbers is naturally generalized to provide a simple and sound construction of the continuum with order and addition properties, and where a real number is an infinite set of natural numbers. A basic outline of analysis is proposed with a fast derivative algorithm. Under this representation, a countable sequence of real numbers is represented by a single real number. Furthermore, an infinite $\infty\times\infty$ real-valued matrix is represented with a single real number. A real function is represented by a set of real numbers, and a countable sequence of real functions is also represented by a set of real numbers. In general, mathematical objects can be represented using the smallest possible data type and these representations are calculable. In the last section, mathematical objects of all types are well assigned to tree structures in a proposed type hierarchy.

The Late Bronze Age on the territory of Southern Transurals is represented by two major archeological cultures: Srubnaya and Andronovskaya (Alakul culture and Fyodorovskaya – type). Their interaction of constitutes a special mix of material cultures which preserves common features of two independent, Srubnaya and Andronovskaya cultures, but also creates novel local material features. These cultural groups are also known to have brought to the region the technology of bronze production. This is evidenced, amongst others, by the proximity of the largest copper mining in the region, Kargaly mines Chernykh (2002). New methods to produce ceramics and to work bones were also developed, combining two traditions, coming from Srubnaya and Andronovskaya cultures respectively. Importantly, the features of these cultures are commonly encountered together in a single cultural horizon across the distribution ares. These diffusion processes took place in a vast area (more than 120,000 km²) andwere reflected in archeological micro-district of the Urshak river basin. We present here the most recent results of the scientific examination of the Late Bronze Age settlements in southern Transurals and attempt to address a peculiar cultural co-habitation of two distinct cultural groups in this region. We also discuss their synchronism based on absolute dates and elaborate on this cultural syncretism in the entire territory of the Volga-Ural region.

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.

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

Here we will electrically-quantum model the neutron and proton as a three-phase alternating current electric generator, for this, we will use the theory of three-phase electric generators and vector or phasor diagrams. We will use this model to hypothesize how the quarks that form neutrons and protons with a combined mass of 10 MeV/c², can generate, through quarks-antiquarks-gluon interactions, a mass of 939.56 MeV/c² for the neutron and a mass of 938.27 MeV/c² for the proton. Using quantum mechanics and the theory of the generalization of the Boltzmann constant in curved space-time we will calculate the number of quarks-antiquarks-gluons and gravitons inside a neutron. We will also analyse βˉ decay using vector diagrams, we will calculate the tension of the string T₀ and the length of the string ℓs between quarks-antiquark and finally, we will model a black hole using a neutron equivalent model. In version 2 of this article, we will update the vector diagrams of the βˉ decay and theoretically calculate the energy of the W⁻ boson, the Z⁰ boson, and the Θ angle, Θ = arc cos (W⁻/Z⁰). We will demonstrate, through vector diagrams, that quarks-antiquarks-gluon interactions are the cause of the origin of the W⁻ boson and the Z⁰ boson. We will also demonstrate how the fine structure constant α originates. It is important to make clear, in future updates, we will describe the relationship that exists between the theory described in this paper and the Isospin theory, flavour and colour theory

Stabilized un-doped Zinc Telluride (ZnTe) thin films were grown on glass substrates under vacuum using closed space sublimation (CSS) technique. A dilute copper nitrate solution (0.1/100 ml) was prepared for copper doping known as ion exchange process in the matrix of ZnTe thin film. The reproducible polycrystalline cubic structure of undoped and Cu doped ZnTe thin films with preferred orientation (111) was confirmed by X-rays diffraction (XRD) technique. Lattice parameter analyses verified the expansion of unit cell volume after incorporation of Cu species into ZnTe thin films samples. The micrographs of scanning electron microscopy (SEM) were used to measure the variation in crystal sizes of samples. The energy dispersive X-rays was used to validate the elemental composition of undoped and Cu-doped ZnTe thin films. The bandgap energy 2.24 eV of ZnTe thin film decreased after doping Cu to 2.20 eV may be due to the introduction of acceptors states near to valance band. Optical studies showed that refractive index was measured from 2.18 to 3.24 whereas thicknesses varied between 220 nm to 320 nm for un-doped and Cu doped ZnTe thin film respectively using Swanepoel model. The oxidation states of Zn⁺², Te⁺² and Cu⁺¹ through high resolution X-ray photoelectron spectroscopy (XPS) analyses was observed. The resistivity of thin films changed from ~10⁷ Ω-cm for undoped ZnTe to ~1 Ω-cm for Cu-doped ZnTe thin film, whereas p-type carrier concentration increased from to respectively. These results predicted that Cu-doped ZnTe thin film can be used as an ideal, efficient and stable intermediate layer between metallic and absorber back contact for the heterojunction thin film solar cell technology.

Introduction: Type 2 diabetes (T2D) is a major driver of health care costs, thus treatments enabling T2D reversal may reduce expenditures. We examined the impact of a T2D continuous care intervention (CCI) on health care utilization. Previous research documented that CCI, including individualized nutrition supported by remote care, simultaneously reduced hemoglobin A1c and medication use and improved cardiovascular status after two years; however, the impact on utilization is unknown. Methods: This study used four years of data (two years pre-intervention, two years post-intervention) from the Indiana Network for Patient Care (INPC) health record. Two methods estimated the impact of CCI on utilization. First, an interrupted time series (ITS) including only CCI participants (n=193) compared post-intervention utilization to expected utilization had the pre-intervention trend persisted. Deviation from the trend was estimated non-parametrically for each 6-month interval after the implementation of CCI . Second, a 1:3 matched comparator group (n=579) was constructed and used for a difference-in-differences (DiD) analysis. The primary outcome was annualized outpatient encounters. Secondary outcomes included emergency encounters and hospitalizations. Results: In two years prior to intervention, CCI participants had a mean of 5.77 annualized encounters (5.62 outpatient, 0.04 hospitalizations, 0.11 emergency). The CCI group showed a reduction in outpatient utilization after intervention. In ITS analysis, 1.6 to 1.9 fewer annualized outpatient encounters occurred in each 6-month interval post-intervention relative to expected utilization based on pre-intervention trends (p<0.01 each 6-month period; 28-33% reduction). The DiD analysis suggested a larger reduction; 5 fewer annualized outpatient encounters in the quarter after intervention, diminishing to 2.5 fewer after 2 years (p<0.01 each quarter). The study was underpowered to draw conclusions about hospitalization and emergency encounters due to the limited number of CCI patients and the rarity of encounters. Conclusions: Outpatient encounters were significantly reduced for a T2D patient population up to 2 years after receiving an individualized intervention supporting nutrition and behavior change through remote care.

This study presents a vibration control using actively tunable vibration absorbers (ATVA) to suppress vibration of a thin plate. The ATVA’s is made of a sandwich hollow structure embedded with the electrorheological fluid (ERF). ERF is considered to be one of the most important smart fluids and it is suitable to be embedded in a smart structure due to its controllable viscosity property. ERF’s apparent viscosity can be controlled in response to the electric field and the change is reversible in 10 microseconds. Therefore, the physical properties of the ERF-embedded smart structure, such as the stiffness and damping coefficients, can be changed in response to the applied electric field. A mathematical model is difficult to be obtained to describe the exact characteristics of the ERF embedded ATVA because of the nonlinearity of ERF’s viscosity. Therefore, a fuzzy modeling and experimental validations of ERF-based ATVA from stationary random vibrations of thin plates are presented in this study. Because Type-2 fuzzy sets generalize Type-1 fuzzy sets so that more modelling uncertainties can be handled, a semi-active vibration controller is proposed based on Type-2 fuzzy sets. To investigate the different performances by using different types of fuzzy controllers, the experimental measurements employing type-1 fuzzy and interval type-2 fuzzy controllers are implemented by the Compact RIO embedded system. The fuzzy modeling framework and solution methods presented in this work can be used for design, performance analysis, and optimization of ATVA from stationary random vibration of thin plates.

The main aim of this paper is to establish two generalized integral formulas involving the extended Mittag–Leffler function based on the well known Lavoie and Trottier integral formula and the obtain results are express in term of extended Wright-type function. Also, we establish certain special cases of our main result.

Current commercially available instruments for monitoring mitochondrial respiration are incapable of single cell measurements. Therefore, we developed a three-electrode, Clark-type biosensor suitable for mitochondrial respirometry in single oocytes and embryos. The biosensor was embedded in a PMMA (polymethyl methacrylate) micro-chamber to allow investigation of single oocytes/embryos immersed in up to 100 µL of respiration buffer. The micro-chamber was completely sealed to avoid oxygen exchange between the inside of the chamber and the atmosphere, while being maintained at a temperature of 38.5 ˚C to preserve cell viability. Using amperometry, the oxygen consumption of cells inside the micro-chamber was measured as a change in output current and converted to femto-mol (fmol) oxygen consumed per second based on calibrations with known buffer oxygen concentrations. The sensor measured basal cell respiration supported by endogenous substrates, respiration associated with proton leak induced by inhibition of the adenosine triphosphate (ATP) synthase (complex V) with oligomycin, and the maximal non-coupled respiratory capacity revealed by Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) titration. Some potential applications of this oxygen sensor system include evaluating effects of metabolic therapies on oocyte bioenergetics, and monitoring mitochondrial function throughout oocyte maturation and blastocyst development to predict embryo viability to compliment assisted reproductive technologies

Researches on flexible thermoelectric (TE) materials usually focus on conducting polymers (CPs) and CP-based composites; however, it is a great challenge to obtain high TE properties comparable to inorganic counterparts. Here, we report an n-type Ag₂Se film on flexible nylon membrane with an ultrahigh power factor ~987.4 ± 104.1 μWm⁻¹K⁻² at 300 K and an excellent flexibility (93% of the original electrical conductivity retention after 1000 bending cycles around a 8-mm diameter rod). The flexibility is attributed to a synergetic effect of the nylon membrane and the Ag₂Se film intertwined with numerous high-aspect-ratio Ag₂Se grains. A TE prototype composed of 4-leg of the hybrid film generates a voltage and a maximum power of 19 mV and 460 nW, respectively, at a temperature difference of 30 K. This work opens opportunities of searching for high performance TE film for flexible TE devices.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with significant mortality rate of up to 40% in the endemic areas, with evidence for geographical expansion. Lacking effective therapeutics and control measures, the development of protective CCHFV vaccine remains a crucial public health task. This manuscript describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4) based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity and protection potential in BALB/c and IFNAR^-/- mice models in comparison with Adenovirus type 5 (Ad5-N) and pCDNA3.1 myc/His A (pCD-N1), two widely used vaccine platforms. All constructs expressing viral nucleocapsid (N) protein successfully elicited cytokine and total/specific antibody responses in BALB/c mice. BoHV4-∆TK-CCHFV-N and Ad5-N constructs further produced 100% protection in IFNAR^-/- mice during CCHFV Ank-2 strain lethal challenge. Despite elevated specific antibody responses in both animal models, the produced antibodies were unable to neutralize the virus in vitro. A comparison of delivery platforms was not possible, due to similar protection rates in IFNAR^-/- mice. In conclusion, vector-based CCHFV N protein expression proved to constitute an effective approach for the vaccine development pipeline and BoHV-4 emerged as a strong alternative to previously-used virus vectors.

As neck and/or shoulder pain (NSP) frequently occur together with tension-type headache (TTH) and migraine, we explored how concomitant NSP affects perceived treatment responses to an analgesic. An anonymous survey was performed among 895 TTH and migraine sufferers who used the analgesic 400 mg ibuprofen/100 mg caffeine. NSP was relatively abundant among patients (42.4% for TTH; 39.2% for migraine), and associated with &gt;1 additional day with headache per month. Reported pain reduction was independent from NSP for TTH and migraine. More patients became pain-free at 2 h in migraine with NSP (42.9%) compared to migraine without NSP (32.2%), which is different from TTH with NSP (60.6%) and TTH without NSP (71.4%). For both, migraine and TTH, a recurrence of headache on the same day was more prevalent in those with concomitant NSP leading to a greater likelihood of taking a second dose of the analgesic. NSP frequently occurs together with TTH and migraine patients. In migraine, NSP seems to be associated with a better treatment response at 2 h. The more frequent recurrence of pain in those with concomitant NSP indicates that NSP makes both headache types worse. Further studies are needed to substantiate these effects.

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

The wind industry is looking for ways to accurately predict the reliability and availability of newly installed wind turbines. Failure modes, effects and criticality analysis (FMECA) is a technique utilized for determining the critical subsystems of wind turbines. There are several studies which applied FMECA for wind turbines in the literature, but no studies so far have considered different weather conditions or climatic regions. Furthermore, various design types of wind turbines have been analyzed applying FMECA but no study so far has applied FMECA to compare the reliability of geared and direct-drive wind turbines. We propose to fill these gaps by using Koppen-Geiger climatic regions and two different turbine models of direct-drive and geared-drive concepts. A case study is applied on German wind farms utilizing the WMEP database which contains wind turbine failure data from 1989 to 2008. This proposed methodology increases the accuracy of reliability and availability predictions and compares different wind turbine design types and eliminates underestimation of impacts of different weather conditions.

Place attachment is an emotion that people experience in connection to a specific place and it is needed to maintain sustainable neighborhood community. The emotion is affected by various factors, such as experience, function, environment, and satisfaction. This study focuses on commercial structures, which are one feature that characterize the physical environments of neighborhoods. The aim of this study is to determine the effects of commercial activities in different commercial environments on social bonding and place attachment in residents. Two sites were selected for analysis due to their different commercial environments, and path analysis was used to examine the relationships among factors. The results indicate that the type of commercial environment had effects on commercial activities, including shopping frequency, and that commercial activities affected social bonding and place attachment in residents. Also, commercial activities had indirect effects on place attachment through social bonding between residents. These results suggest that the commercial environment is an important element affecting the community and place attachment of residents in neighborhoods.

This paper proposes a method of extracting energy from zero-point energy and evaluates the amount of energy gained. In addition, this electric circuit-based approach exhibits the Meissner effect, suggesting a new type of superconductivity that does not require refrigeration. The proposed method can provide extremely large amounts of energy, which is more than a conventional power station, without consuming fossil fuels or emitting radiation. Thus, it has the potential to solve the global energy problem. It involves preparing two electric loops containing diodes and connecting the loops together with current sources. The diodes are oriented in the same direction within each loop but in opposite directions in different loops. With this setup, the currents from the current sources build iteratively within the loops, resulting in large output currents. Our numerical analysis indicates that extremely large electric potentials are produced, which in turn yield large output currents. In addition, we confirm numerically that the voltage is zero around a loop and show analytically that the Meissner effect is present, proving the existence of a new type of superconductivity. Furthermore, when we introduce induction coils to not break the loop’s symmetry, they store extremely large amounts of energy and we can thus obtain energy from them via discharge currents.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

Visible Light Communication (VLC) uses an intensity-modulation and direct-detection (IM/DD) scheme to transmit data. The light source utilized in VLC structures is constantly switched on and off rapidly, resulting in flickering. Furthermore, most of illumination systems exclude dimming support to permit customers to dim the light source to the desired stage. Therefore, the modulation scheme for information transmission in VLC should consist of flicker mitigation and dimming manage abilities. Double inverse pulse position modulation (DIPPM), sub-carrier pulse position modulation (SC-L-PPM), and M-ary variable pulse position modulation (M-VPPM) are recommended for minimizing the flicker issues and supporting an excessive degree of dimming for VLC systems. In this paper, a comparison is introduced between DIPPM, SC-L-PPM, and M-VPPM according to error performance and bit rate. In addition, a simulation is carried out to measure the optical power distribution for a LED lamp in an indoor room topology for each modulation technique. The obtained results indicated that SC-L-PPM is the best choice regarding the bit error rate (BER) and optical power distribution compared to the other two schemes. A 10^-6 BER is achieved with a very low power requirement at L=8, while a remarkable power distribution of 1.5 to 6.5 dBm is observed from 3×5×5 m³ room corners to the center, respectively. According to the bit rate, it is noticed that, M-VPPM is the most efficient one compared to the two other schemes. It achieves 2.3×10⁷ bps at signal to noise ratio (SNR) of 22 dB and M=8.

Not only does this paper present a novel type-2 fuzzy system for identification and behavior prognostication of an experimental solar cell set and a wind turbine, but also it brings forward an exquisite technique to acquire an optimal number of membership functions and the corresponding rules. It proposes a seven-layered NCPRT2FS. For fuzzification in the first two layers, Gaussian type-2 fuzzy membership functions with uncertainty in the mean, are exploited. The third layer comprises rule definition and the forth one embeds fulfillment of type reduction. The three last remained layers are the ones in which resultant left–right firing points, two end-points and output all get assessed correspondingly. It should not be neglected off the nutshell that recurrent feedback at the fifth layer exerts delayed outputs ameliorating efficiency of the suggested NCPRT2FS. Later in the paper, a modern structural learning, established on type-2 fuzzy clustering, is held forth. An adaptively rated learning back-propagation algorithm is extended to adjust the parameters ensuring the convergence as well. Eventually, solar cell photo-voltaic and wind turbine are deemed as case studies. The experimental data are exploited and the consequent yields emerge so persuasive.

This article aims to identify the generating function of modi…ed Apostol type q-Bernoulli polynomials. With the aid of this generating function, some properties of modi…ed Apostol type q-Bernoulli polynomials are given. It is shown that aforementioned polynomials are q-Appell. Hence, we make use of these polynomials to have applications on q-Umbral calculus. From those applications, we derive some theorems in order to get Apostol type modi…ed q-Bernoulli polynomials as a linear combination of some known polynomials which we stated in the paper.

Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. EF-hands are among the largest Ca2+-binding motif in proteins. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle and is able to form amyloids under acidic conditions. Since nucleating Ca2+ protein have a propensity to form extended β-strand structures, we wondered whether amyloid assemblies of a protein containing refolded EF-hand motifs were able to influence the in vitro calcium carbonate crystallization. Here we have used the Gad m 1 chain as model to generate monomeric and amyloid assemblies and analyze their effect on in vitro calcite formation. We found that only amyloid assemblies alter calcite morphology.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

In this paper a robust version of the Wald test statistic for composite likelihood is considered by using the composite minimum density power divergence estimator instead of the composite maximum likelihood estimator. This new family of test statistics will be called Wald-type test statistics. The problem of testing a simple and a composite null hypothesis is considered and the robustness is studied on the basis of a simulation study. Previously, the composite minimum density power divergence estimator is introduced and its asymptotic properties are studied.

Supplier selection is one of the most important multi criteria decision making (MCDM) problems for decision makers in competitive market. Organizations of today’s world are seeking new ways to reduce negative effects of their organizations to the environment and to reach a greener system. At this point, green supplier selection concept has gained great importance with its ability on incorporating environmental or green criteria into the classical supplier selection practices. Therefore, in this study, it is aimed at proposing a multi-phase MCDM model based on Best-Worst Method (BWM) and interval type-2 fuzzy technique for order preference by similarity to ideal solution (TOPSIS). A case study in a plastic injection molding facility in Turkey is performed to show the applicability of the proposed integrated methodology. The paper ensures insights into the decision making, methodology, and managerial implications. Results of the case study are examined and suggestions for future research are provided.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

We report diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a rare, hereditary neurodegenerative disease of childhood, in a four and a half year old girl, the first child of non-consanguineous parents with no family history. Despite extensive efforts by the parents, her clinical condition remained undiagnosed and without management, until recently. Our published “Bottom-up Approach”, based on comprehensive and multidisciplinary clinical, pathological, radiographical and genetic evaluations, played key role in diagnosis of the disease. Detailed analyses involving Next Generation Sequencing confirmed a missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene. In silico analyses predicted it to be highly pathogenic. Further family screening (including her both unaffected parents and asymptomatic, one year old younger sister) of the identified variation through Sanger Sequencing, revealed a perfect autosomal recessive segregation in the family. This study is the first case report on classic CLN2 from Jammu and Kashmir-India. This study is also indicating the effectiveness of our “Bottom-up Approach” in understanding rare disorders in low resource regions and the importance of timely diagnosis. Like in the proband, had diagnosis been established a bit early, the family might have benefitted at least with reference to their second child through counselling programmes.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

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

1) Background: A survey of biogenic amines profile in opened wine bottles has been established. Opened bottles of red and white wine were submitted to different temperature as well as different kind of stopper (screw cap, cork stopper) and use of vacuum devices. A total of six wine made from different variety of grapes were obtained from Polish vineyard places in different region of Poland; 2) Results: DLLME-GC-MS procedure for biogenic amines determination was validated and applied for wine samples analysis. The total content of BAs in white wines ranged from 442 µg/L to 929 µg/L, while in red wines ranged from 669 µg/L to 2244 µg/L the set of just opened wine samples. The most abundant biogenic amines in the six analysed wines were histamine and putrescine; 3) Conclusion: Considering the commercial availability of the analysed wines, there was no relationship between the presence of biogenic amines in a given wine and their availability on the market. However, it was observed that the different storage conditions employed in this experiment affect not only the biogenic amines profile, but also the pH. The results were confirmed by chemometric analysis.

This article develops dual variational formulations for a large class of models in variational optimization. The results are established through basic tools of functional analysis, convex analysis and duality theory. The main duality principle is developed as an application to a Ginzburg-Landau type system in superconductivity in the absence of a magnetic field. In the first sections, we develop new general dual convex variational formulations, more specifically, dual formulations with a large region of convexity around the critical points which are suitable for the non-convex optimization for a large class of models in physics and engineering. Finally, in the last section we present some numerical results concerning the generalized method of lines applied to a Ginzburg-Landau type equation.

After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21^st Century Biology.

The “Crisis of Reproducibility” has received considerable attention both within the scientific community and without. While factors associated with scientific culture and practical practice are most often invoked, I propose that the Crisis of Reproducibility is ultimately a failure of generalization with a fundamental scientific basis in the methods used for biomedical research. The Denominator Problem describes how limitations intrinsic to the two primary approaches of biomedical research, clinical studies and pre-clinical experimental biology, lead to an inability to effectively characterize the full extent of biological heterogeneity, which compromises the task of generalizing acquired knowledge. Drawing on the example of the unifying role of theory in the physical sciences, I propose that multi-scale mathematical and dynamic computational models, when mapped to the modular structure of biological systems, can serve a unifying role as formal representations of what is conserved and similar from one biological context to another. This ability to explicitly describe the generation of heterogeneity from similarity addresses the Denominator Problem and provides a scientific response to the Crisis of Reproducibility.

Relationship between the results of penile duplex doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data of 148 patients with ED were analysed retrospectively. Patients who did not respond to therapy were classified as Group I (n = 32), those responded partially were classified as Group II (n = 40) and complete responders were classified as Group III (n = 76). Age, comorbid diseases, vascular and penile pathology were compared among the three groups. While diabetes mellitus (DM) and dyslipedimia positivity adversely affect the response to treatment, the presence of hypertension (HT), peyronie's disease and priapism increase the therapeutic response to the treatment (p < 0.05). Arterial insufficiency was present in 20(30.3%), 25(37,9%) and 21(31.8%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Venous insufficiency was observed in 3(14.3%) patients in Group I and in 8(85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen in 9(30%), 14(46.7%) and 7(23.3%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Response rate to treatment was highest in normal patients according to PDDU, followed by patients with venous insuffiency. Besides, it was found that DM decreased the response to treatment, whereas response was increased in cases with HT, priapism and Peyronie’s disease.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

This paper focuses on evaluating airline service quality from the perspective of passengers view. Until now a lot of researches has performed in airline service quality evaluation in the world but a little research has been conducted in Iran, yet. In this research a framework for measuring airline service quality in Iran is proposed. After reviewing airline service quality criteria, SSQAI model was selected because of its comprehensiveness in covering airline service quality dimensions. SSQAI questionnaire items were redesigned to adopt with Iranian airlines requirements and environmental circumstances in the Iran's economic and cultural context. This study includes fuzzy decision-making theory, considering the possible fuzzy subjective judgment of the evaluators during airline service quality evaluation. Fuzzy TOPSIS have been applied for ranking airlines service quality performances. Three major Iranian airlines which have the most passenger transfer volumes in domestic and foreign flights, were chosen for evaluation in this research. Results demonstrated Mahan airline has got the best service quality performance rank in gaining passengers' satisfaction with delivery of high quality services to its passengers, among the three major Iranian airlines. IranAir and Aseman airlines placed in the second and third rank, respectively, according to passenger's evaluation.Statistical analysis have been used in analyzing passenger responses. Due to abnormality of data, Non-parametric tests were applied. To demonstrate airline ranks in every criterion separately, Friedman test was performed. Variance analysis and Tukey test were applied to study the influence of increasing in age and educational level of passengers' on degree of their satisfaction from airline's service quality. Results showed that age has not significant relation with passenger satisfaction of airlines, however increasing in educational level demonstrated a negative impact on passengers' satisfaction from airline's service quality.

In this paper, we study the well-posedness and asymptotic behaviour of solutions to a laminated beam in thermoelasticity of type III. We first give the well-posedness of the system by using the semigroup method. Then, we show that the system is exponentially stable under the assumption of equal wave speeds. Furthermore, it is proved that the system is lack of exponential stability for case of nonequal wave speeds. In this regard, a polynomial stability result is proved.

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.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

This paper presents a novel adaptive fault-tolerant neural-based control design for wind turbines with unknown dynamic and unknown wind speed. By utilizing the barrier Lyapunov function in the analysis of the Lyapunov direct method, the constrained behavior of the system is provided in which the rotor speed, its variation and generated power remain in the desired bounds. In addition, input saturation is also considered in terms of smooth pitch actuator bounding. Furthermore, by utilizing a Nussbaum-type function in designing the control algorithm, the unpredictable wind speed variation is captured without requiring accurate wind speed measurement, observation or estimation. Moreover, with the proposed adaptive analytic algorithms, together with the use of radial basis function neural networks, a robust adaptive and fault-tolerant control scheme is developed without the need for precise information about the wind turbine model nor the pitch actuator faults. Additionally, the computational cost of the resultant control law is reduced by utilizing a dynamic surface control technique. The effectiveness of the developed design is verified using theoretical analysis tools and illustrated by numerical simulations on a high-fidelity wind turbine benchmark model with different fault scenarios. Comparison of the achieved results to the ones that can be obtained via an available industrial controller shows the advantages of the proposed scheme.

Our previous in vitro reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of chelesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of chelesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.

An analysis of workplace accidents in the mining sector has been done using the database from the Spanish administration between the period 2005-2015 and applying data mining techniques. Data has been processed by means of the software Weka. Two scenarios were chosen regarding the accidents database, surface and underground mining. The most important variables involved in occupation accidents and their association rules have been determined. These rules are formed by several predictor variables that cause an accident, defining its characteristics and context. This study exposes the 20 most important association rules of the sector, either surface or underground mining, based on statistical confidence levels of each rule obtained by Weka. The outcomes display the most typical immediate causes with the percentage of accident basis of each association rule. The most typical immediate cause is body movement with physical effort or overexertion and type of accident is physical effort or overexertion. On the other hand, the second most important immediate cause and type of accident change in both scenarios. Data mining techniques have been proved as a very powerful tool to find out the root of the accidents, apply corrective measures and verify their effectiveness, either for public or private companies.

Shear connectors are used in steel beam–concrete slabs of composite frame and bridge structures to transfer shear force according to design loads. The existing Y-type perfobond rib shear connectors are designed for girder slabs of composite bridges. Therefore, the rib and transverse rebars of the conventional Y-type perfobond rib shear connectors are extremely large for the composite frames of building structures. We performed push-out tests of stubby Y-type perfobond rib shear connectors for composite frames. These shear connectors have relatively small ribs than conventional Y-type perfobond rib shear connectors. To confirm the shear resistance of these stubby shear connectors, we performed an experiment by using transverse rebars D13 and D16. The results indicate that these shear connectors have suitable shear strength and ductility for application in composite frame structures. The shear strengths obtained using D13 and D16 were not significantly different. However, the ductility of the shear connectors with D16 was 45.1% higher than that of the shear connectors with D13.

Let g be a strictly increasing function on $\left(a,b\right),$ having a continuous derivative g′ on $\left(a,b\right).$ For the Lebesgue integrable function $f:\left(a,b\right)\to \mathbb{C}$ , we define the k-g-left-sided fractional integral of f by $S_{k,g,a+}f\left(x\right)={\int }_a^{x}k\left(g\left(x\right)-g\left(t\right)\right)g^{\prime }\left(t\right)f\left(t\right)dt,x\in \left(a,b\right]$ and the k-g-right-sided fractional integral of f by $S_{k,g,b-}f\left(x\right)={\int }_x^{b}k\left(g\left(t\right)-g\left(x\right)\right)g^{\prime }\left(t\right)f\left(t\right)dt,x\in [a,b),$ where the kernel k is defined either on $\left(0,\infty \right)$ or on $\left[0,\infty \right)$ with complex values and integrable on any finite subinterval. In this paper we establish some Ostrowski and trapezoid type inequalities for the k-g-fractional integrals of functions of bounded variation. Applications for mid-point and trapezoid inequalities are provided as well. Some examples for a general exponential fractional integral are also given.

Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.

This research aimed to figure out the applications of HbA1c protein and HbA1 gene as the prognostic biomarkers for assessing the risks of different cancers among male T2D patients in Bangladesh considering their serological and oncoinformatic parameters. Depending on the concentrations of HbA1c (%) of the T2D patients (n=300), their individual FBS (mmol/L); THABF (mmol/L); creatinine (mg/dl); SC (mg/dl); STGs (mg/dl); HDLC (mg/dl); and LDLC (mg/dl) were estimated. The values of the patients were compared with the control (n=60) group as the serological analysis. Besides, HbA1 gene (encoding hBA1c protein) overexpression and promotor methylation responsible for BLCA, BRCA, CHOL, COAD, LUAD, LUSC, PAAD, and PRAD cancers in the male T2D patients were profiled as the oncoinformatic parameters based on the sample types; caner stages; racial footprints; gender; age; nodal metastasis; p53 methylations; pancreatitis; diabetes status; smoking behaviors; and overall/disease-free survivability. Finally, the ‘HbA1 gene strings’ responsible for genetic coexpression; endophytic vesicle regulation; antioxidant regulation; oxygen species metabolic regulation; and gene-mediated response to the reactive oxygen molecules were studied comprehensively. A strong correlation between BMI and FBS was observed in both the patients and the control (P<0.0001). Similarly, the values of FBS, THABF, and creatinine resulted in equal significance (P<0.0001) as compared to the HbA1c concentrations of all the T2D and control individuals. The SC, STGs, HDLC, and LDLC concentrations regulated ardently in both the control (P<0.0001), and patients group (P<0.0001), while HbA1c ranged from 3.8-5.8%, and 5.11-15.8% respectively. HbA1 gene is found downregulating with cancer progressed in most of the oncoinformatic parameters. According to the DA, CS, EI, CE, PC, NC, GF, H, and AT profiles; the HbA1 gene interacts with 8 other genes responsible for creating a protein cluster comprising- AHSP, HBA1, HBA2, HBB, HBD, HBE1, HBG2, RPS12, and RPS19 proteins for cancer formation. To recapitulate, HbA1c protein and HbA1 gene can be used as the prognostic serological and molecular biomarkers respectively for determining the risks of cancers among male chronic T2D patients.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

In this paper Brinkman type fluid over an infinite plate between side walls is being investigated. The flow is generated by oscillating shear stress of the bottom plate and the solutions are obtained by using Fourier integral transformation. The obtained results are presented in steady and transient states for both sin and cos shear stresses. The general solutions are reduced to some special cases corresponding, namely to the Brinkman type fluid over an infinite plate and flow of a Newtonian viscous fluid. Graphical illustrations are carried out to have in depth analysis of the involved physical parameters

The aim of this article is to establish a new class of unified integrals associated with the generalized Lommel-Wright functions, which are expressed in terms of Wright Hypergeometric function.Some integrals involving trigonometric,generalized Bessel function and Struve functions are also indicated as special cases of our main results.further, with the help of our main results and their special cases, we obtain two reduction formulas for the Wright hypergeometric function.

Sea anemones are a remarkable source of active principles due to a decentralized venom system. Blood vessel formation or angiogenesis is a very promising target against cancer, but the few available anti-angiogenic compounds have a limited efficacy. In this study, a protein fraction was purified from tentacles of Anemonia viridis able to limit endothelial cells proliferation and vessel network formation or angiogenesis at low concentration (14 nM). The sequences in this protein fraction were determined with Edman degradation and Mass Spectrometry In Source Decay and revealed homologies with BDS sea anemones. The presence of a two turn alpha helix observed with Circular Dichroism and a trypsin activity inhibition suggested that the active principle could be a Kunitz-type inhibitor, which may interact with an integrin due to a RGD motif well exposed to the solvent as revealed by Molecular Modeling. This active principle could improve antiangiogenic therapy from existing antiangiogenic compounds binding on the VEGF.

In South Western Indian ocean (IO), Extended-Spectrum β-Lactamase producing Enterobacteriaceae (ESBL) are a main public health issue. In livestock, ESBL burden was unknown. The aim of this study was estimating the prevalence of ESBL on commercial farms in Reunion, Mayotte and Madagascar and genes involved. Secondly, risk factors of ESBL occurrence in broiler, beef cattle and pig farms were explored. In 2016-2017, commercial farms were sampled using boot swabs and samples stored at 4°C before microbiological analysis for phenotypical ESBL and gene characterization. A semi-directive questionnaire was performed. Prevalences observed in all production types and territories were elevated, except for beef cattle in Reunion which differed significantly. The most common ESBL gene was the CTX-M-1 subtype. Generalized linear models explaining ESBL occurrence varied between livestock production sectors and allowed identifying main protective (e.g., water quality control and detergent use for cleaning) and risk factors (e.g., recent antibiotic use, other farmers visiting the exploitation, pet presence). This study is the first to explore tools for antibiotic resistance management in IO farms. It provides interesting hypothesis to explore about antibiotic use in IO and ESBL transmission between pig, beef cattle and humans in Madagascar.

Background: Obesity and diabetes are two metabolic disorders linked by an inflammatory process named insulin resistance (IR). Various research on the role of gut microbiota in developing obesity and its associated disorders has led to the growing interest in probiotic supplementation. Considering the life-threatening complications of diabesity this mini-review explored the effects of probiotic supplementation on IR in obesity-associated diabetes. Method: This review is based on recent articles from 2005-2020, studying the role of probiotic supplementation on glucose and insulin parameters in healthy and diabetic mouse models. Result: Probiotic supplementation altered the gut microbiota composition, increased short-chain fatty acid production, and decreased pro-inflammatory cytokines. Additionally, they decreased intestinal permeability, circulating lipopolysaccharide, and metabolic endotoxemia hence improved insulin sensitivity and reduced obesity. Although multi-strain probiotic supplementation showed greater benefits than single strain interventions, variations in the concentration of probiotics used and the duration of treatment also influenced the results. Conclusion: Probiotic supplementation could manipulate the gut microbiota by reducing intestinal permeability, inflammation and ameliorate IR and obesity-associated diabetes in animal models which requires further long-term clinical studies in humans.

Vitamin D and ω-3 fatty acids (ω-3) co-supplementation potentially improve type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation.This cohort study preliminary to a randomized control trial (RCT) is aimed to evaluate, in a series of T1D children assuming Mediterranean diet and taking cholecalciferol 1000U/day fromT1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS).Therefore, 22 new onsets of 2017 received ω-3 [eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60mg/kg/day], and were compared retrospectively vs. 37 previous onsets without ω-3 supplementation. HbA1c%, daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/dayx4 + HbA1c%) as surrogate of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As outcome, decreased insulin demand (p<0.01), particularly pre-meal boluses (p<0.01), and IDAA1c (p<0.05), were found in the ω-3 group while HbA1c% were not different in the two groups. Diet analysis, at T12 vs. T0, showed that the intake of arachidonic acid (AA) was decreased (p<0.01) in the ω-3 supplemented group while other nutrients were unchanged; at T0, the AA intake was inversely correlated with HbA1c% (p<0.05; r;.0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation and AA reduction in Mediterranean diet display benefits for T1D children and deserve further investigation.

Formation of Fe- and Mg-rich smectite and zeolite under alkaline conditions is concerned as secondary minerals after alkaline alteration of bentonite in a repository of radioactive wastes. It might be crucial for safety assessment whether smectite will be formed or not as secondary minerals after alkaline alteration of bentonite. In present paper, Fe- and Mg-rich smectite which are currently interacting with hyperalkaline groundwater was found at Narra in Palawan, Philippines. Mineralogical and geochemical investigation was conducted to understand formation process of smectite and factors determined secondary mineral species. Our study revealed a certain amount of smectite may have been produced under hyperalkaline conditions, altered from amorphous or poorly crystalline material such as M-S-H and F-S-H. Key factor which decides smectite or zeolite as secondary minerals after alkaline alteration of bentonite might be whether nuclei of M-S-H and/or F-S-H will be formed or not. This might be decided by the presence of dissolved Mg2+ and Fe2+ in the system. Our suggested formation process of smectite under alkaline conditions is analogue with generally-accepted model of smectite formation that might have been occurred on early Mars.

A highly crystallized monoclinic-scheelite type BiVO4 powders were successfully synthesized by solvothermal method. The as-synthesized BiVO4 powders were characterized by XRD, FE-SEM, Raman spectroscopy, UV-vis DRS spectroscopy and TA-PL. From the XRD data and Raman spectra, the monoclinic-scheelite phase BiVO4 sample can be obtained at higher solvothermal synthesis temperature more than 140 oC. The preparation conditions such as, the Bi/V molar ratio and synthesis temperature, have significantly effects on the morphologies of the BiVO4 samples. BVO2 sample shows the highest PL peak, which has the highest formation rate of OH radicals and the highest photocatalytic activity. This result suggests that the formation rate of OH radicals shows a good correlation with the photocatalytic activity.

Land Surface Temperature (LST) is a basic parameter in energy exchange between the land and atmosphere and is frequently used in many sciences such as climatology, hydrology, agriculture, ecology, etc. LST time series data have usually deficient, missing and unacceptable data caused by the presence of clouds in images, presence of dust in atmosphere and sensor failure. In this study, Singular Spectrum Analysis (SSA) algorithm was used to resolve the problem of missing and outlier data caused by cloud cover. The region studied in the present research included an image frame of MODIS with horizontal number 22 and vertical number 05 (h22v05). This image involved a large part of Iran and Turkmenistan and Caspian Sea. In this study, MODIS LST sensor (MOD11A1) was used during 2015 with 1×1 Km spatial resolution and day/night LST data (daily temporal resolution). The results of the data quality showed that cloud cover caused 36.37% of missing data in the studied time series with 730 day/night LST images. Further, the results of SSA algorithm in reconstruction of LST images indicated the Root Mean Square Error (RMSE) of 2.95 K between the original and reconstructed data in LST time series in the study region. In general, the findings showed that SSA algorithm using spatio-temporal interpolation in LST time series can be effectively used to resolve the problem of missing data caused by cloud cover.

The heavy demand of water resources from the Zarqa River Basin (ZRB) has resulted in a base-flow reduction of the River from 5m³/s to less than 1m³/s. This paper aims at predicting Curve Numbers (CN) as a baseline scenario and proposing restoration scenarios for ZRB. The method includes classifying the soil type and land use, predicting CNs, and proposing CN restoration scenarios. Prediction of existing CNs will be in parallel with the runoff prediction using the US Army Corps of Engineers HEC-1 Model, and Rainfall-Runoff Model (RRM). The models have been set up at the land use distribution of 0.3% water body, 9.3% forest and orchard, 71% mixture of grass, weeds, and desert shrubs, 7.0% crops, 4.0% urban areas, and 8.4% bare soil. The results show that CN under dry condition are 59, 78 under a normal condition and 89 under a wet condition. During vegetation period, CN are 52, 72 and 86 for the dry, normal and wet condition respectively. The restoration scenarios; CN decreases runoff, and increases soil moisture when using the contours, terraces and crop residues. Analyzing results of CN scenarios will be a fundamental tool to support end-users related to their targets to achieve watershed restoration.

Non-Orthogonal Multiple Access (NOMA) is the key technology promised to be applied in next-generation networks in the near future. In this study, we propose a multi-points cooperative relaying (MPCR) NOMA model instead of just using a relay as the previous studies. Based on the channel state information (CSI), the base station (BS) selects a closest user equipment (UE) and sends a superposed signal to this UE as a first relay node. We have assumed that there are N UEs in the network and Nth UE, which is farthest from BS, has the poorest quality signal transmitted from the BS compared other UEs. Nth UE received the forwarded signal from N-1 relaying nodes that are UEs with better signal quality. At the ith relaying node, it detect its own symbol by using successive interference cancellation (SIC) and will forward the composite signal to the next closest user, namely i+1th UE, and include an excess power which will use for energy harvesting (EH) intention at the next UE. By these, the farthest UE in network can be significantly improved. In addition, closed-form expressions of outage probability for users over both the Rayleigh and Nakagami-m fading channels are also presented. Analysis and simulation results performed by Matlab software which are presented accurately and clearly show that the effectiveness of our proposed model and this model consistents with the multi-access wireless network in future.

This paper uses the $\exp(-\Phi(\xi))$-Expansion method to investigate solitons to the M-fractional nonlinear Schrödingers equation with cubic nonlinearity. The results obtained are dark solitons, trigonometric function solutions, hyperbolic solutions and rational solutions. Thus, the constraint relations between the model coefficients and the traveling wave frequency coefficient for the existence of solitons solutions are also derived.

A series of precise data consisting of zircon U–Pb ages, whole-rock geochemistry and Sr–Nd–Hf isotope compositions from the Huhetaoergai granitic pluton was collected in this study and combined with data from the western Huhetaoergai, Zhuxiaogubuhe and Yagan granitic plutons to constrain the petrogenesis and tectonic setting of granitic plutons in the northern Ya-Gan fault zone, North Alxa, China. The Huhetaoergai pluton is composed of hornblende diorite, medium- to coarse-grained biotite adamellite and coarse-grained biotite adamellite with K-feldspar megacrysts. The U–Pb zircon ages of biotite adamellite are 220.5 ± 1.9 Ma and 226.5 ± 2.4 Ma. These granitoids are I-type granites with highly radiogenic initial ⁸⁷Sr/⁸⁶Sr of 0.708085–0.735470, negative eNd(t) average values of −2.98–3.23 and high eHf(t) of 9–11.05. These features indicate the granitoids were formed from magmas generated from juvenile crust. We speculate that the granitoids of the Huhetaoergai pluton were emplaced during an episode of intense intraplate orogenic movement evolution in an extrusional setting after a period of extensional postcollisional intraplate evolution.

This research aims to estimate the micro-motion (m-m) of ships. The problem of motion and m-m detection of targets is usually solved using synthetic aperture radar (SAR) along-track interferometry (ATI) which is observed employing two radars spatially distanced by a baseline extended in the azimuth direction. This paper is proposing a new approach where the m-m estimation of ships, occupying thousands of pixels, is measured processing the information given by sub-pixel tracking generated during the coregistration process of several re-synthesized time-domain and overlapped sub-apertures. The SAR products are generated splitting the raw data, according to a small-temporal baseline strategy, observed by one single wide-band staring spotlight (ST) SAR image. The predominant vibrational modes of different ships are estimated and results are promising to extend this application in performing surveillance also of land-based industries activities. Experiments are performed processing one ST SAR image observed by the COSMO-SkyMed satellite system.

The Yangtze River is cross-linked with numerous lakes within its floodplain and is a worldwide biodiversity hotspot. There is no evidence indicating when this unique river-lake system developed. The endemic East Asian cyprinid clade has evolved diverse spawning adaptations to different flow conditions. Our ancestral egg-type reconstruction showed an ancestral state of adhesive eggs and later demersal eggs origination (both stream adaptations). Semi-buoyant eggs emerged ~18 Mya as a fast-flowing river adaptation, with increased hydration via three yolk protein degradation pathways, ion transport pathways and egg envelope permeability transition pores. Adhesive eggs evolved secondarily ~14 Mya with the egg envelope increasing to four layers and an adhesive layer, along with an increase in adhesiveness via microfilament/adhesive-related protein crosslinking and enhanced glycosaminoglycan biosynthesis, improving adherence to submerged lake plants, indicating that the cross-linked river-lake system formed in the mid-Miocene. This study provides a unique biological evidence for large-scale water system evolution.

Methods for high-quality DNA extraction and knowledge of sex expression and flowering time are essential for applying genomic-assisted breeding and improve the success with hybridization in Guinea yam. A dioecious or monoecious pattern of flowering and sometimes non-flowering is a common phenomenon within and between the Dioscorea species. The flowering in yam plants raised from botanical seeds often takes an extended period, mostly till the first clonal generation after propagation from the tubers. The prolonged process of testing required to identify plant sex and flowering intensity in yam breeding often poses a challenge to realize reduced breeding cycle and apply genomic selection. This study assessed sample preservation methods for DNA quality during extraction and potential of DNA marker to diagnose plant sex at the early seedling stage in white Guinea yam. The predicted sex at the seedling stage was further validated with the visual score for the sex phenotype at the flowering stage. DNA extracted from leaf samples preserved in liquid nitrogen, silica gel, dry ice, and oven drying methods was similar in quality with a high molecular weight than samples stored in ethanol solution. Yam plant sex diagnosis with the DNA marker (sp16) identified a higher proportion of ZW genotypes (female or monoecious phenotypes) than the ZZ genotypes (male phenotype) in the studied materials with 74% prediction accuracy. The results from this study provided valuable insights on suitable sample preservation methods for quality DNA extraction and the potential of DNA marker sp16 to predict sex in white Guinea yam.

Multicellularity evolved repeatedly in the history of life, but how it unfolded varies greatly between different lineages. Dictyostelid social amoebas offer a good system to study the evolution of multicellular complexity, with a well-resolved phylogeny and molecular genetic tools being available. We compare the life cycles of the Dictyostelids with closely related amoebozoans to show that complex life cycles were already present in the unicellular common ancestor of Dictyostelids. We propose frost resistance as an early driver of multicellular evolution in Dictyostelids and show that the cell signalling pathways for differentiating spore and stalk cells evolved from that for encystation. The stalk cell differentiation program was further modified, possibly through gene duplication, to evolve a new cell type, cup cells, in Group 4 Dictyostelids. Studies in various multicellular organisms including Dictyostelids, volvocine algae, and metazoans suggest as a common principle in the evolution of multicellular complexity that unicellular regulatory programs for adapting to environmental change serve as “proto-cell types” for subsequent evolution of multicellular organisms. Later, new cell types could further evolve by duplicating and diversifying the “proto-cell type” gene regulatory networks.

Graph theory plays a crucial role in modeling and designing of chemical structure or chemical network. Chemical Graph theory helps to understand the molecular structure of molecular graph. The molecular graph consists of atoms as vertices and bonds as edges. Topological indices capture symmetry of molecular structures and give it a mathematical language to predict properties such as boiling points, viscosity, the radius of gyrations etc. In this article, we study the chemical graph of carbon Crystal structure of graphite and cubic carbon and compute several degree-based topological indices. Firstly we compute M-Polynomials of these structures and then from these M-polynomials we recover nine degree-based topological indices.

During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10) were isolated from the extract of a bloom material of Microcystis sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey’s and advance Marfey’s methods and by comparison of ¹H and ¹³C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by N-methylation of Ahda amine group and extent of chlorination of Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease aminopeptidase M and exhibited low- to sub-nanomolar IC₅₀ values.