In this article, the new Hermite–Hadamard type inequalities are studied via generalized s-convexity on fractal sets. These inequalities derived on fractal sets are shown to be the generalized s-convexity on fractal sets. We proved that the absolute values of the first and second derivatives for the new inequalities are the generalization of s-convexity on fractal sets.

Individuals with low health literacy (HL) are known to have poorer health outcomes and to have higher mortality rates compared to individuals with higher HL: hence, the improvement of HL is a key outcome in modern healthcare systems. Healthcare providers are therefore asked to support patients’ literacy skills by encouraging the implementation of autonomy-supportive patient centered communication (PCC), which in turn requires the enhancement of patient engagement. Our main hypothesis is that the well-known relationship between autonomy-supportive PCC and HL is mediated by patient engagement which is known to play a role in HL promotion and that is related to PCC as well. The purpose of this study was to formulate a hypothetical structural equation model (SEM) linking PCC to patient engagement and HL. A cross-sectional survey design was employed involving 1007 Italian chronic patients. The hypothetical model was tested using SEM to verify the hypothesized mediation of patient engagement between PCC and HL. Results show that the theoretical model has a good fit indexes and that patient engagement fully mediates the relationship between PCC and HL. This finding suggests healthcare systems to implement a new paradigm where patients are supported to play an autonomous role in their own healthcare.

Most Acinetobacter baumannii strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of H-NS in the regulation of expression of genes related to natural competency and the ability to uptake foreign DNA. The expression levels of the natural transformation-related genes pilA, pilT, pilQ, comEA, comEC, comF, and drpA were significantly increased in a Δhns derivative of Acinetobacter baumannii A118. Complementation of the mutant with a recombinant plasmid harboring hns restored expression levels of six of these genes (pilT remained expressed at high levels) to those of the wild-type strain. The transformation frequency of the A. baumannii A118 Δhns strain was significantly higher than that of the wild-type. Similar, albeit not identical, effects occurred when hns was deleted from the hypervirulent A. baumannii AB5075 strain. Reduction of gene expression in a few cases was not as pronounced as to reach wild-type levels, and expression of comEA was enhanced further. In conclusion, the expression of all seven transformation-related genes was enhanced after deleting hns in A. baumannii A118 and AB5075, and these modifications are accompanied by an increase in the cells’ transformability. The results demonstrate a role of H-NS in A. baumannii’s natural competence.

Drought events are predicted to become more prevalent in the future. Evaluating the performance of herbicide-resistant and susceptible weed ecotypes to progressive drought can provide insights into whether resistance trait(s) increased or reduced the fitness of a resistant population. Two experiments were conducted in the greenhouse between January and May 2021 to evaluate drought tolerance differences between Palmer amaranth accessions resistant to S-metolachlor or glyphosate and their susceptible counterparts. The accessions used were: S-metolachlor-resistant (17TUN-A), a susceptible standard (09CRW-A), and glyphosate-resistant (22 to 165 EPSPS copies) and glyphosate-susceptible (3 to 10 EPSPS copies) plants from accession 16CRW-D. Daily transpiration of each plant was measured. The daily transpiration rate was converted to normalized transpiration ratio (NTR) using a double-normalization procedure. The daily soil water content was expressed as a fraction of transpirable soil water (FTSW). The threshold FTSW (FTSWcr), after which NTR decreases linearly, was estimated using a two-segment linear regression analysis. The data showed differences between S-metolachlor- resistant and -susceptible accessions (P ≤ 0.05). The FTSW remaining in the soil at the breakpoint for the S-metolachlor-susceptible accession (09CRW-A) was 0.17±0.007. The FTSW remaining in the soil at the breakpoint for the S-metolachlor-resistant accession (17TUN-A) was 0.23±0.004. Although the mechanism endowing resistance to S-metolachlor might have contributed to increased drought tolerance, follow-up experiments are needed to verify this finding. Increased EPSPS copy number did not improve drought tolerance of Palmer amaranth.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

This study was designed to assess the reliability of geographic information using satellite image information in ungauged basins. For this, this study constructed geographic information using actual gauged data and satellite information data and conducted runoff analysis through S-RAT, a rainfall–runoff model, and performed the comparison and analysis of geographic information and runoff data. For actual gauged data, the gauged geographic information of the Water Resources Management Information System (WAMIS) was collected, and for satellite information, the image information of moderate-resolution imaging spectroradiometer (MODIS) observation sensor loaded on Terra Satellite was collected. As analysis areas, three basins where mountains occupy more than 80% and another three basins where urban areas occupy more than 7% in the Han River basin were selected. According to the analysis result, the gauged information and satellite image information showed great difference in runoff, maximum 50% in peak flood and maximum 17% in total flood, in the rivers with many urban areas, while the runoff difference in the rivers with many mountains showed maximum 13% in peak flood and 4% in total flood. What showed the greatest difference in image information was land use, and it turned out that the MODIS satellite recognized the urban rivers as cities for more than maximum 60% compared to WAMIS-gauged data. Meanwhile, in the forest area, the MODIS satellite image showed error of less than 5% of the WAMIS-gauged data, which indicates that it has higher applicability in Mountain Rivers.

Lead, known as a metal with high neurotoxicity to children, cadmium, which is a carcinogenic and bioaccumulative contaminant, and arsenic, a class 1 carcinogenic according to the International Agency for Research on Cancer, are toxic elements (TEs) whose relevant route of exposure may be diet. We determined the bio-accessible fraction of lead, cadmium, and arsenic from the diet of preschool children from two day care centers (DCC). A cross-sectional study was conducted with 64 one–four-year-old children from two DCCs where the 24-h duplicate diet samples were collected. The diet samples were analyzed by ICP-MS for lead, cadmium, and arsenic total concentrations (n = 64) and their bio-accessibility were analyzed for a subsample (n = 10). The dietary intake (DI) mean for lead, cadmium, and arsenic were 0.18 ± 0.11 µg kg⁻¹ bw, 0.08 ± 0.04 µg kg⁻¹ bw, and 0.61 ± 0.41 µg kg⁻¹ bw, respectively. All DI calculated for TEs, considering total intake, were found lower than the tolerable limits (TL) (European Union, or World Health Organization, WHO, when applicable) except for one child’s Pb intake. Bio-accessibilities ranged between 0% to 93%, 0% to 103%, and 0% to 69%, for lead, cadmium, and arsenic, respectively. Although DI for TEs has been found lower than TL, these reference values have been recently decreased or withdrawn since it was for lead and arsenic whose TL were withdrawn by WHO.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

Adaptive Sliceable-Bandwidth Variable Transceivers (S-BVTs) are key enabler for future optical networks. In particular, those based on Discrete MultiTone (DMT) modulation and Direct Detection (DD) can be considered a flexible solution suitable to address the cost efficiency requirement of optical metro networks. In this paper, we propose to use this cost-effective S-BVT option/implementation in optical metro networks adopting switching nodes based on Semiconductor Optical Amplifier (SOA) technology. Bit loading (BL) and power loading (PL) algorithms are applied to the Digital Signal Processing (DSP) modules, to maximize the performance and/or the capacity as well as enhance the flexibility and adaptability of the system. Our analysis considers switching nodes based on SOAs with and without filtering elements and fiber spans of 25 km. We present the results up to 100 km, with and without SOA-based nodes. Firstly, we analyze the adaptive BVT transmission using the Margin Adaptive (MA) BL/PL algorithm at a fixed bit rate of 28 Gb/s. The possibility of controlling the SOAs current is a key factor to face the transmission impairments due to the fiber and the filtering elements. We also analyze the system considering Rate Adaptive (RA) transmission at a fixed target BER of 3.8·10⁻³, showing that a maximum capacity above 34 Gb/s can be achieved for a single span of 25 km. Although the cascading of filtering elements still constitutes a limiting factor, we show that an improvement of the net bit rate performance can be obtained thanks to the combined use of S-BVT and SOA technology at the switching nodes, resulting in a promising approach for designing future optical metro networks.

A radical, albeit pragmatic protocol for experimental access to putative String/M-theoretic, Einstein Unified Field Mechanical (UFM) additional dimensionality (XD) of the brane-bouquet bulk is presented. If successful, results demonstrate the existence dimensionality beyond the metric of observed physical reality provided by the Standard Model (SM) of particle physics and Cosmology. Quantum Mechanics (QM), as well-known is incomplete and further, should no longer be considered the basement of reality; meaning, Locality and Unitarity – the fundaments of quantum theory are an insufficient basis for extending the representation of reality. A seminal model of Tight Bound States (TBS) below the lowest Bohr orbit in the hydrogen atom, proposed by Vigier, is extended to a Kaluza-Klein-like (KK) cyclical tier of XD hyperspherical cavities defined within a manifold of uncertainty (MOU) of finite radius up to the semi-quantum limit, predicting, within its domain, new spectral lines in Hydrogen. The proposed protocol for this process, with phase modifications, provides efficacy of large-scale additional dimensionality (LSXD) of the brane bulk; XD-LSXD incursion duality accesses nonlocal Einsteinian UFM phenomena, leading to myriad new classes of technological innovation.

In this paper we obtain some inequalities of Hermite-Hadamard type for composite convex functions. Applications for AG, AH-h-convex functions, GA, GG, GH-h-convex functions and HA, HG, HH-h-convex function are given.

Invasive weeds cause significant crop yield and economic losses in agriculture. The highest in-direct impact may be attributed to the role of invasive weeds as virus reservoirs especially within the commercial growing areas. The new tobamovirus tomato brown rugose fruit virus (ToBRFV), recently identified in the Middle-East, overcomes the Tm-22 resistance allele in the cultivated tomato varieties grown in greenhouses. In this study, we determined the role of invasive weed species as potential hosts for ToBRFV and pepino mosaic virus (PepMV). Out of all tested weed species, the invasive species So-lanum elaeagnifolium and S. rostratum, mechanically inoculated with ToBRFV, were positive for To-BRFV in both enzyme linked immunosorbent assay (ELISA) and RT-PCR tests. S. rostratum was also positive for PepMV. No conspicuous phenotype was observed on ToBRFV infected S. elaeagnifolium plants suggesting a hostplant associated defense response. S. rostratum plants inoculated with either ToBRFV alone or a mixture of ToBRFV and PepMV-IL, contained high ToBRFV levels. In addition, when inoculated with ToBRFV or PepMV-IL disease symptom manifestations were observed in S. rostratum plants and the symptoms were exacerbated upon mixed infections with both viruses. The distribution and abundance of both Solanaceae species increase the risks of virus transmission between species.

Phenotyping is the task of measuring plant attributes for analyzing the current state of the plant. In agriculture, phenotyping can be used to make decisions concerning the management of crops, such as the watering policy, or whether to spray for a certain pest. Currently, large scale phenotyping in fields is typically done using manual labor, which is a costly, low throughput process. Researchers often advocate the use of automated systems for phenotyping, relying on the use of sensors for making measurements. The recent rise of low cost, yet reasonably accurate, RGB-D sensors has opened the way for using these sensors in field phenotyping applications. In this paper, we investigate the applicability of 4 different RGB-D sensors for this task. We conduct an outdoor experiment, measuring plant attribute in various distances and light conditions. Our results show that modern RGB-D sensors, in particular, the Intel D435 sensor, provides a viable tool for close range phenotyping tasks in fields.

Detection of PLA2R and THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring and prognosis. Anti-PLA2R can be detected in 70-90% of primary MGN patients while anti-THSD7A in 2-3% of anti-PLA2R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive respectively and can detect the presence of anti-PLA2R and anti-THSD7A with higher sensitivity and specificity, significant in patients’ monitoring and prognosis better than exposing patients to frequent biopsy which is an invasive procedure. Different techniques of detection of PLA2R and THSD7A in patients’ urine and sera were reviewed with the aim of providing newer and alternative techniques. We proposed the use of biomarkers (PLA2R and THSD7A) in making the diagnosis, treatment decision and follow up of patients with primary MGN. We also reviewed other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin in order to detect progression of renal damage for early intervention.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

Let R be a commutative graded ring with unity, S be a multiplicative subset of homogeneous elements of R and P be a graded ideal of R such that P\bigcap S=\emptyset In this article, we introduce several results concerning graded S-prime ideals. Then we introduce the concept of graded weakly S-prime ideals which is a generalization of graded weakly prime ideals. We say that P is a graded weakly S-prime ideal of R if there exists s\in S such that for all x, y\in h(R), if 0\neq xy\in P, then sx\in P or sy\in P. We show that graded weakly S-prime ideals have many acquaintance properties to these of graded weakly prime ideals.

In the article, by applied the concept of strongly convex function and one known identity, we establish several Ostrowski type inequalities involving conformable fractional integrals. As applications, some new error estimations for the midpoint formula are provided as well.

The variation of the cationic composition in I2-II-IV-VI4 semiconductor compounds is an effective tool for altering their properties in a controlled manner. In particular, a partial substitution of Cu for Ag in kesterite Cu2ZnSnS4 was proposed to suppress Cu-Zn antisite defects and the improve photovoltaic performance. However, the efficiency of this approach may substantially depend on the fabrication route. Here, we report on the synthesis of (Cu,Ag)-Zn-Sn-S (CAZTS) and Ag-Zn-Sn-S (AZTS) nanocrystals (NCs) by means of "green" chemistry in aqueous solution and their detailed characterization by Raman spectroscopy and by several complementary techniques. Through a systematic variation of the nominal composition and quantification of the constituent elements in CAZTS and AZTS NCs by XPS, we identified the vibrational Raman and IR fingerprints of both the main AZTS phase and secondary phases of Ag-Zn-S and Ag-Sn-S compounds (for the first time). The formation of the secondary phases of Ag-S and Ag-Zn-S cannot be avoided entirely for this type of synthesis. The Ag-Zn-S phase, having its bandgap in near infrared range, is the reason of the non-monotonous dependence of the absorption edge of CAZTS NCs on the Ag content, with a trend to redshift even below the bandgaps of bulk AZTS and CZTS.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.

Recently, the properties of bouncing oil droplets, also known as `walkers', have attracted much attention because they are thought to offer a gateway to a better understanding of quantum behaviour. They indeed constitute a macroscopic realization of wave-particle duality, in the sense that their trajectories are guided by a self-generated surrounding wave. The aim of this paper is to try to describe walker phenomenology in terms of de Broglie-Bohm dynamics and of a stochastic version thereof. In particular, we first study how a stochastic modification of the de Broglie pilot-wave theory, à la Nelson, affects the process of relaxation to quantum equilibrium, and we prove an H-theorem for the relaxation to quantum equilibrium under Nelson-type dynamics. We then compare the onset of equilibrium in the stochastic and the de Broglie-Bohm approaches and we propose some simple experiments by which one can test the applicability of our theory to the context of bouncing oil droplets. Finally, we compare our theory to actual observations of walker behavior in a 2D harmonic potential well.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution and their effects on HIF-dependent signalling are discussed in this review.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and <100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p<0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p<0.01); vs LT=2.74±0.84; (p<0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p<0.001), and LAVi (r=0.70; p<0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

In the paper we consider conformal mappings of Riemannian spaces onto Ricci-2-symmetric Riemannian spaces and geodesic mappings of spaces with affine connections onto Ricci-2-symmetric spaces. The main equations for the mappings are obtained as a closed system of differential equations of Cauchy-type in covariant derivatives. We have found the number of essential parameters which the solution of the system depends on. Similar approach was applied for the case of conformal mappings of Riemannian spaces onto Ricci-m-symmetric Riemannian spaces and geodesic mappings of spaces with affine connections onto Ricci-m-symmetric spaces.

A variant of the von Neumann-Wigner Interpretation is proposed. It does not make use of the familiar language of wave functionsand observers. Instead it pictures the state of the physical world as a vector in a Fock space and, therefore not, literally, a functionof any spacetime coordinates. And, rather than segregating consciousness into individual points of view (each carrying with it asense of its proper time), this model proposes only unitary states of consciousness, Q(t), where t represents a fiducial time withrespect to which both the state of the physical world and the state of consciousness evolve. States in our world's Fock space areclassified as either 'admissible' (meaning they correspond to definite states of consciousness) or 'inadmissible' (meaning they donot). The evolution of the state vector of the world is such as to always keep it restricted to 'admissible' states. Consciousness istreated very much like what Chalmers calls an "M-Property." But we try to show that problems with the quantum Zeno effect do not arise from this model.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

Ethylene is a plant hormone controlling physiological and developmental processes such fruit maturation, hairy root formation and leaf abscission. Its effect on regeneration systems, such as organogenesis and somatic embryogenesis (SE), has been studied and progresses in molecular biology techniques have contributed to unveil mechanisms behind its effects. This compound affects regeneration differently, depending on the species, genotype and explant. In some species, ethylene seems to revert recalcitrance in genotypes with low regeneration capacity. However, its effect is not addictive, since in genotypes with high regeneration capacity this ability decreases in the presence of ethylene precursors, suggesting that regeneration is modulated by ethylene. Several lines of evidence have shown that the role of ethylene on regeneration is markedly connected to biotic and abiotic stresses as well as to hormonal-crosstalk, in particular with key regeneration hormones and growth regulators of the auxin and cytokinin families. Transcriptional factors of the ethylene response factor (ERF) family are regulated by ethylene and strongly connected to SE induction. Thus, an evident connection between ethylene, stress responses and regeneration capacity is markedly established. In this review the effect of ethylene and the way it interacts with other players during organogenesis and somatic embryogenesis is discussed.

Abstract The present work was designed to investigate antiviral potential of novel mono and oligomeric Chitosan derivatives through in-silico approaches to find potent broad-spectrum anti-viral and promising drug candidates against SARS-CoV-2 and augmentation of their mode of action. Chitosan biopolymer and its derivatives were screened virtually against spike glycoprotein and human ACE2 receptor of nCoV-19. HTCC a polymeric Chitosan has been reported to interact with the corona viral Spike (S) protein and blocks its interaction with ACE2 receptor. Better biocompatibility, structural correlations, variation in degree of decetylation and molecular weight of modified Chitosan derivatives are the key attributes for enhancement of anti-viral activity. The Chitosan derivatives constructively interact with viral S protein. N-Carboxy methyl Chitosan (NCMC) among the Chitosan derivatives displayed efficient binding affinity. NCMC, when compared to mHTCC, a monomeric Chitosan for its interaction with the S protein, RBD site and ACE2 receptor, displayed efficient binding affinity with binding energy of -7.9, -6.3 and -7.4; -6.2, -4.8 and -5.5 Kcal/mol respectively. The interaction of S protein with ACE2 and ligand mHTCC-S protein complex and NCMC-S protein complex with ACE2 was calculated through flexible docking resulted in efficient reduction of binding energy from -901.2kJ/mol to -765.06kJ/mol and-814.72kJ/mol respectively, elucidated that the binding affinity of the viral S protein for its receptor ACE2 decreases in the presence of NCMC/mHTCC. The computational study envisages the antiviral efficiency of NCMC, mHTCC and biocompatible Chitosan derivatives for the first time,as preventive intervention against Covid-19.

The extended finite element method (XFEM) is now widely used in crack simulations and the direction of propagation of the XFEM crack in SS-304 has been quite interesting. This paper discusses the direction,θ(+ve in anti-clockwise direction), of the XFEM crack (under mode-I) propagation based on the von Mises stress-field around the crack-tip for static loading under the light water reactors (LWRs) conditions. The Mises core region from the crack-tip is chosen for β=〖90〗^o, the angle between the load and the initial crack. Experimental data for LWRs’environment is obtained and the simulations have been carried out applying three different static loads and results for the direction of the crack are calculated by measuring the stress-field around the crack-tip. It has been found that the direction of the XFEM varies inversely as the stress-field around the crack tip is increased. The computational results have been compared with the numerical results based on the minimum strain energy density criterion[S-criterion].

Macromolecules with well-defined structures in terms of molar mass and monomer sequence became interesting building blocks for modern materials. The precision of the macromolecular structure makes fine-tuning of the properties of resulting materials possible. Conjugated macromolecules exhibit excellent optoelectronic properties that make them exceptional candidates for sensors construction. The importance of chain length and monomer sequence is particularly important in conjugated systems. The sequence lengths, monomer sequence and structural modification often influence the energy bang gap between HOMO and LUMO orbitals of the molecules that reflect in their properties. Moreover, the supramolecular aggregation that is often observed in oligo-conjugated systems is usually strongly affected by even minor structural changes that are used for sensor designs. This review summarizes the examples of well-defined conjugated macromolecules based on oligo(arylene ethynylene)s skeleton used for sensor applications. The sensing mechanisms and importance of uniformity of structure are discussed.

Protein oligomerzation is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads abnormal protein oligomerization resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson’s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants: H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near physiological conditions. All three variants are found to adopt well folded and highly rigid structures in solution, although the elements of secondary structure are somewhat shorter than those observed in cystallography studies. R121C alters the environment of nearby residues only. By constrast, the mutation H13A affects local residues as well as nearby active site residues residues K41 and H119. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of most duplex structure and little or no G-quadruplex formation.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

A convenient and fast multiresidue method for the efficient identification and quantification of 72 pesticides belonging to different chemical classes in red and white grape wines have been developed. The analysis was based on gas chromatography tandem quadrupole mass spectrometric determination (GC–MS/MS). An optimization strategy involved the selection of MWCNTs amount and cleanup procedure cycle times for m-PFC was performed to achieve ideal recoveries and reduce sample matrix compounds in the final extracts. The optimized procedure obtained consistent recoveries between 70.2 and 108.8% (70.2% and 108.8% for white wine, 72.3% and 106.0% for red wine) , with relative standard deviations (RSDs) generally lower than 8.3% at three spiking levels of 0.01, 0.05 and 0.2 mg/kg. Linearity was studied in the range between 0.005 and 0.2 mg/kg using pesticide standards prepared both in pure solvent and in the presence of matrix, showing coefficients of determination (R²) higher than 0.985 for all the pesticides. To improve accuracy, matrix matched calibration curves were used for calculating the quantification results. Finally, the method was used successfully in detecting pesticide residues in commercial gape wines.

The paper presents data from a monthly campaign for the elemental composition of PM10 in a specific receptor Kotórz Mały (Opole Voivodeship) located in the vicinity of a moderately inhabited rural area, measured in one-hour samples with the use of the PX-375 analyzer by the Horiba company. The hourly variability of SO2, NO, NO2, CO, O3 concentrations as well as the variability of meteorological parameters were also determined. On average, during the entire measurement period, the elements related to PM10 can be arranged in the following order: As<V<Ni<Pb<Cr<Mn<Cu<Ti<Zn<K<Fe<Ca<Al<Si<S. Trace elements, including toxic elements, such as As, V, Ni, Pb, Cr, Mn, were present in low concentrations, not exceeding 10 ng/m3 (average daily value). These elements had fairly even concentrations, daily and hourly. The concentrations of the main elements in the PM10 in the receptor are subject to strong hourly changes related not only to changes in the structure of the sources identified in the statistical analysis but mainly to wind speed and direction changes (soil and sand particles pick-up and inflow of pollutants from coal combustion). It has been shown that the transport emission in the receptor can have an intense effect on PM10 in the afternoon.

The construction of carbon-carbon bonds by direct involvement of two unactivated carbon-hydrogen bonds, without any directing group, ensures an high atom economy of the entire process. Here it is described a simple protocol for the Pd(II)/Cu(II)-promoted intermolecular cross-dehydrogenative coupling (CDC) of 5-arylimidazoles, benzimidazoles, benzoxazole and 4,5-diphenylimidazole at their C-2 position with functionalized styrenes. This specific CDC, known as Fujiwara-Moritani reaction or oxidative Heck coupling, allowed also the C-4 alkenylation of the imidazole nucleus when both 2 and 5 positions are occupied.

In this paper, we proposed a novel saddle type FinFET (S-FinFET) to effectively solve problems occurring under the capacitor node of dynamic random-access memory (DRAM) cell and showed how its structure was superior to conventional S-FinFETs in terms of short channel effect (SCE), subthreshold slope (SS), and gate-induced drain leakage (GIDL). The proposed FinFET exhibited 4 times lower Ioff than modified S-FinFET called RFinFET with more improved DIBL characteristics while minimizing Ion reduction compared to RFinFET. Our results also confirmed that the proposed device showed improved DIBL and Ioff characteristics as gate channel length decreased.

In this paper, some mixed type bounds on the spectral radius $\rho(A\circ B)$ for the Hadamard product of two nonnegative matrices ($A$ and $B$) and the minimum eigenvalue $\tau(C\star D)$ of the Fan product of two $M$-matrices ($C$ and $D$) are researched. These bounds complement some corresponding results on the simple type bounds. In addition, a new lower bound on the minimum eigenvalue of the Fan product of several $M$-matrices is also presented: $$ \tau(A_{1}\star A_{2}\cdots\star A_{m})\geq \min_{1\leq i\leq n}\{\prod^{m}_{k=1}A_{k}(i,i)-\prod^{m}_{k=1}[A_{k}(i,i)^{P_{k}}-\tau(A_{k}^{(P_{k})})]^\frac{1}{P_{k}}\}, $$ where $A_{1},\ldots, A_{k}$ are $n\times n$ $M$-matrices and $P_{1},\ldots, P_{k}>0$ satisfy $\sum^{m}_{k=1}\frac{1}{P_{k}}\geq 1$. Some special cases of the above result and numerical examples show that this new bound improves some existing results.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

The search for novel brewing strains from non-brewing environments represents an emerging trend to increase genetic and phenotypic diversities in brewing yeast culture collections. Another valuable tool is hybridization, where beneficial traits of individual strains are combined in a single organism. This has been used successfully to create de novo hybrids from parental brewing strains by mimicking natural Saccharomyces cerevisiae ale x Saccharomyces eubayanus lager yeast hybrids. Here, we integrated both these approaches to create synthetic hybrids for lager fermentation using parental strains from niches other than beer. Using a phenotype-centered strategy, S. cerevisiae sourdough strains and the S. eubayanus x Saccharomyces uvarum strain NBRC1948 (also referred to as Saccharomyces bayanus) were chosen for their brewing aptitudes. We demonstrated that, in contrast to S. cerevisiae x S. uvarum crosses, hybridization yield was positively affected by time of exposure to starvation, but not by staggered mating. In laboratory-scale fermentation trials at 20°C, one triple S. cerevisiae x S. eubayanus x S. uvarum hybrid showed a heterotic phenotype compared with the parents. In 2L wort fermentation trials at 12°C, this hybrid inherited the ability to consume efficiently maltotriose from NBRC1948 and, like the sourdough S. cerevisiae parent, produced appreciable levels of the positive aroma compounds 3-methylbutyl acetate (banana/pear), ethyl acetate (general fruit aroma) and ethyl hexanoate (green apple, aniseed, and cherry aroma). Based on these evidences, the phenotype-centered approach appears promising for design of de novo lager beer hybrids and may help to diversify aroma profiles in lager beers.

Global financial investments in energy production and consumption are significant since all aspects of a country's economic activity, and development require energy resources. In this paper, we assess the investment trends in the global energy sector during, before and after financial crises of 2008 using two data sources: (1) Dealogic database providing cross‐border mergers and acquisitions (M&As), and (2) fDi Intelligence fDi Markets database providing greenfield (GF) foreign direct investments (FDIs). We highlight the changing role of China and compare its M&A and GF FDI activities to those of the United States, Germany, UK, Japan and others during this period. We analyze the investments along each segment of the energy supply chain of these countries to highlight the geographical origin and destination, sectoral distribution, and cross‐border M&As and GF FDI activities. Our paper shows that while energy accounts for nearly 25% of all GF FDI, it only accounts for 4.82% of total M&A FDI activity in the period 1996-2016. China's outbound FDI in the energy sector started its ascent around the time of the global recession and had accelerated in the post-recession phase. In the energy sector, the development of China's outbound cross‐border M&As is similar to USA or UK, located mostly in the developed countries in the west, while their outbound GF investments are spread across many countries around the world. Also, China's outbound energy M&As are concentrated in certain segments (extraction, and electricity generation) while their GF covers all segments of the energy supply chain.

The war to technology and economic power have been the driver for industrialization in most developed countries. The first industrial revolution (industry 1.0) earned millions for textile mill owners while the second industrial revolution (industry 2.0) opened the way for tycoons and captains of industry like John D. Rockefeller, J.P. Morgan and Henry Ford. The third industrial revolution (industry 3.0) engendered technology giants like Apple and Microsoft, and made magnates of men like Steve Jobs and Bill Gates. Now, the race for the fourth industrial revolution (industry 4.0) is on and there is no option, every country whether developed or developing must participate. Many countries have positively responded to industry 4.0 by developing strategic initiatives to strengthen industry 4.0 implementation. Unlocking the country’s potential to industry 4.0 has been of interest to researchers in the recent past. However, the extent to which industry 4.0 initiatives being launched globally has never been revealed. Therefore, the present study aimed at exploring industry 4.0 initiatives through comprehensive electronic survey of literature to estimate the extend of its launching in different regions. Inferences were drawn from industry 4.0 initiatives in developed nations to be used as the recommendations for East Africa Community. Results of the survey revealed that 117 industry 4.0 initiatives have been launched in 56 countries worldwide consisting of five regions. The country’s percent of industry 4.0 initiatives as per region were: Latin America and the Caribbean (15%), North America (40%), Europe (53%), Asia and Oceania (25%), Middle East and Africa (11%). While the worldwide percent was estimated as 25%. This revealed that the big gap is existing between countries towards the race for industry 4.0.

We have proposed a simple algorithm to retrieve the total ozone column and snow properties (spectral albedo and effective light absorption path) using the high spatial resolution single – view MSI/S-2 measurements over Antarctica.

This paper compares the finite sample performance of three non-parametric threshold estimators via Monte Carlo method. Our results show that the finite sample performance of the three estimators is not robust to the relative position of the threshold level along the distribution of threshold variable, especially when a structural change occurs at the tail part of the distribution.

The -blocker (S)-practolol ((S)-N-(4-(2-hydroxy (isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the -blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)- 3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol was also produced in 53% yield, with 99% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. The yield of all four chlorohydrins increased by use of catalytic amounts of base. The reason for this was found to be less formation of the dimeric by-products compared to use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previous reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB) from SyncoZymes Co, Shanghai, China. Optical rotations confirmed the absolute configuration of the enantiopure drugs.

The compound, C27H23N3 (1), crystallizes in the triclinic system of the P-1 space group. The unit cell comprises a dimer of 1, in which the monomers are linked by two complementary hydrogen bonds between N1 and H1-C1 of another molecule. The dimers form chains along the a-axis through intermolecular interactions between the N2 acceptor atoms and C17 donors from molecules in the nearest neighbouring dimer. These interactions form extended sheets of the dimers of 1, along the ab plane. The quinolinylmeth-2-yl groups of 1 lie in almost orthogonal planes and their N1/2(q) donor atoms being away from the apical amino N3 atom.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25-colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review about what is currently known on this new family of antibacterial enzymes as well as on their potential use of food preservatives or therapeutic agents.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

This paper proposes a multifractal model, with the aim of providing a possible explanation for the locality phenomenon that appears in the estimation of the Hurst exponent in stationary second order temporal series representing self-similar traffic flows in current high-speed computer networks. It is shown analytically that this phenomenon occurs if the network flow consists of several components with different Hurst exponents.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

The World Health Organization(WHO) in 2016 considered mHealth as: “the use of mobile wireless technologies including smart devices such as smartphones and smartwatches for public health” as an important resource for health services delivery and public health given their ease of use, broad reach and acceptance. WHO emphasizes the potential of this technology to increase access to health information, services and skills as well as promoting positive changes in health behaviors and management of diseases. In this regard, the capability of smartphones and smartwatches for m-health monitoring as well as verification of the patient the signal has become an important component of mHealth system. Most of the smartwatches could extract more than one bioelectrical signal therefore, therefore they provide suitable platform for extracting health data for e-monitoring. The existing approaches have not considered the integrity of data obtained from these smart devices. Therefore, it is important that the integrity of the collected data be verified continuously through user authentication. This could be done using any of the bioelectrical signals extracted and transmitted for e-monitoring. In this article, a smartwatch is used for extracting bioelectrical signal before decomposing the signal into sub-bands of Detail and Approximation Coefficient for user authentication. To select suitable features using biorthogonal wavelet decomposition of signal from a non-intrusive extraction, a detailed experiment is conducted extracting suitable statistical features from the bioelectrical signal from 30 subjects using different biorthogonal wavelet family. Ten features are extracted using Biorthogonal wavelet to decompose the signal into three levels of sub-band Detail and Approximation Coefficient and features extracted from each level the decomposed Detail and Approximation Coefficients. Comparison analysis is done after the classification of the extracted features based on the Equal Error Rate (EER). Using Neural Network (NN) classifier, Biorthogonal Wavelet Detail Coefficient Sub-band level 3 of bior1.1 achieved the best result of EER 13.80% with the fusion of the best sub-band three levels of bior1.1 achieving a better result of 12.42% EER.

Helicobacter pylori is a common human pathogen that causes gastroduodenal diseases. H. pylori genome consists of numerous restriction-modification (R-M) genes. It is established that N6-adenine methylation plays a crucial role in bacterial gene regulation and virulence, but not much is known about the role of C5-cytosine methylation. In this study, we examined the influence of an orphan cytosine methyltransferase, hpyAVIBM on gastric infection in mice and cultured cells. Histopathological staining showed that the deletion of hpyAVIBM in H. pylori strain SS1 had increased damaging hemorrhagic effects on the mice stomach. The gelatin-zymography result demonstrated that the mice infected with mutant SS1ΔhpyAVIBM had significantly up-regulated pro-MMP-9 than those infected with SS1. Additionally, ELISA results of pro-inflammatory cytokines proved that mutant strain caused significantly more inflammatory effect on mice stomach than its wild-type counterpart. The immunohistochemistry data showed that mutant strain caused attenuated epithelial cell damage. Co-culture studies of H. pylori with AGS (Human Gastric Adenocarcinoma cell line) cells revealed that SS1ΔhpyAVIBM instigated significantly more apoptotic death in the AGS cells compared to the wild-type strain. Our results indicated that DNA methylation by hpyAVIBM plays a crucial role in modulating virulence factors in bacterial cells and their interaction with the host cells.

Specifically this work is based on the concept of ‘dark energy’ as a phenomenal effect of expansion through which a theoretical value of Hubble’s constant has been introduced. It is a constant that is based on a postulate that the square root of ratio of the Siva’s constant ‘K’ and Hubble’s constant ‘H’ is exactly equal to the diameter of the neutral hydrogen atom. That is the, exact theoretical value of Hubble’s constant. This is always constant .However, space-time conversions and the changes in the velocity of light will affect the distance and velocity in Hubble’s equation. Deviation factors in velocity, distance and the Hubble’s constant have been calculated separately which are affected by change of velocity of light with expansion of space time. The observations are related to red shift. So the change factor in terms of Hubble’s constant has been calculated with respect to red shift. Thus a factor which affects the theoretical Hubble’s constant has been calculated to find the exact value of Hubble’s constant that satisfies the experimental results. The present theoretical value of Hubble’s constant has been calculated. The experimental results by plank, ACT (Atacama Cosmology Telescope), WMAP (Wilkinson Microwave Anisotropy Probe) etc. experiments are at par with the theoretical result. Thus the ontology of space time introduced in this theoretical work supposed to be correct and leads to a new theory of origin of universe for which a brief description has been provided.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p &lt; 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

A Zn(II) perchlorate complex has been prepared and characterized by single X-ray crystallography, nuclear magnetic resonance spectroscopy, thermogravimetric analysis, infrared spectroscopy, elemental analysis, and UV-vis spectroscopy. The complex crystallizes in the monoclinic space group P21/c (Z = 4) with a pentacoordinated zinc center. Interestingly, the Zn complex was found be to a potential fluorophore that could sense acetone and other ketones with high selectivity and sensitivity.

The prim objective of commenced article is to determine q-sumudu transforms of a product of unified family of q-polynomials with basic (or q-) analogue of fox’s H-function and q-analog of I-functions. Specialized cases of the leading outcome are further evaluated as q-sumudu transform of general class of q-polynomials and q-sumudu transforms of the basic analogues of Fox’s H-function and I-functions.

Fractal behavior and long-range dependence are widely observed in measurements and characterization of traffic flow in high-speed computer networks of different technologies and coverage levels. This paper presents the results obtained when applying fractal analysis techniques on a time series obtained from traffic captures coming from an application server connected to the Internet through a high-speed link. The results obtained show that traffic flow in the dedicated high-speed network link have fractal behavior when the Hurst exponent is in the range of 0.5, 1, the fractal dimension between 1, 1.5, and the correlation coefficient between –0.5, 0. Based on these results, it is ideal to characterize both the singularities of the traffic and its impulsiveness during a fractal analysis of temporal scales. Finally, based on the results of the time series analyses, the fact that the traffic flows of current computer networks exhibit fractal behavior with a long-range dependency is reaffirmed.

A two-fold integrated research study was conducted; firstly, to understand effects of copper (Cu) and zinc (Zn) on the growth and oxidative stress in Nile tilapia, Oreochromis niloticus; secondly, to study the beneficial effects of the duckweed Lemna minor L. as a heavy metal remover from wastewater. Experiments were conducted in mesocosms with and without duckweed. Tilapia fingerlings were exposed to Cu (0.004 and 0.02 mg/L) and Zn (0.5 and 1.5 mg/L) and fish fed for four weeks. We evaluated the fish growth performance, the hepatic DNA structure using comet assay, the expression of antioxidative genes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx and glutathione-S-transferase, GST) and GPx and GST enzymatic activity. The results showed that Zn exhibited more pronounced toxic effects than Cu. Low dose of Cu did not influence the growth whereas higher doses of Cu and Zn significantly reduced the growth rate of tilapia compared to control, but addition of duckweed prevented weight loss. Further, in the presence of a high dose of Cu and Zn, DNA damage decreased, antioxidant gene expressions and enzymatic activities increased. In conclusion, results suggest that duckweed and Nile tilapia can be suitable candidates in metal remediation wastewater assessment programs.

Work from the last years indicate that the extracellular matrix (ECM) plays a direct role in vari-ous cellular processes including proliferation, migration and differentiation. Besides homeostat-ic processes, its regulatory function in inflammation becomes more and more evident. In in-flammation like inflammatory bowel disease, the ECM composition is constantly remodeled which can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we will provide an over-view of relevant diagnostic methods focusing on ECM changes.

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies were carried out, glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine, core- and/or an-tennary fucosylation. In the higher mass region these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as to understand pathogens molecular recognition.

An extension of the models used to generate fractal traffic flows is presented by means of the formulation of a model that considers the use of one-dimensional chaotic maps. Based on the disaggregation of the temporal series generated by the model, a valid explanation of behavior of the values of Hurst exponent is proposed and the feasibility of their control from the parameters of the proposed model is shown.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

The global pandemic caused by the new coronavirus has largely changed established business practices. The aim of the study is to present the results of eighteen-month intensive research into the effects of the pandemic on e-consumer behavior. In one of the most active e-commerce markets in Europe, the Czech Republic, we analyzed a sample of more than one and a half million Facebook users in terms of their C2B interactions on the B2C activities of the five major e-commerce market players. The measurements were carried out in three periods, which corresponded to the onset of the first wave, peak, and fading of the second wave of the pandemic. This enabled us to monitor the effect of seasonality and the stabilization of patterns of consumer behavior during the coronavirus crisis. The results suggest that a specific panic pattern of e-consumer behavior was developed at the time of the onset of the pandemic. However, as the pandemic progressed, the market has adapted to a new normal, which, as evidenced by the change in trends, appears to be a combination of the pre-pandemic and pandemic behavioral patterns. Using a statistical analysis, it was possible to identify delta of changes within the patterns of consumer behavior, thus fulfilling the final condition for creating an empirical model of the COVID-19 pandemic impacts on e-consumer behavior presented in this study.

The effects of acidic electrolyzed water (AEW) on the microbiological and physicochemical properties of fresh-cut red cabbages were studied. The fresh-cut red cabbages and artificially inoculated red cabbages with Salmonella Typhimurium DT104 were washed with distilled water (DW) and different available chlorine concentration (ACC) of AEW for different times. AEW treatments significantly reduced the populations of native aerobic bacteria, molds and yeasts, and artificially inoculated S. Typhimurium DT104 compared to the DW treated and untreated red cabbage samples. The effectiveness of AEW treatments was greatly enhanced with increasing ACC and treatment times. S. Typhimurium DT104 were not detected in the washing water after the red cabbages treated by AEW. The surface color, pH, and total phenolic contents were did not significantly change when the red cabbages were washed with DW and 100 ppm AEW for 3 min. The anthocyanin contents and antioxidant activities of red cabbage were significantly reduced by 18.5% for cyanidin, 22.1% for pelargonidin, and 11.2% for DPPH radical scavenging activity, the impacts on the nutritional benefits of red cabbage were considered as limited and acceptable. The optimal process condition of AEW for washing red cabbage was 100 ppm for 3 min. In these conditions, most of the native microflora were inactivated, and artificial inoculated S. Typhimurium DT104 on the red cabbage were reduced by 40.2% (3.67 log CFU/g) and with minimal losses of nutrients and antioxidant activity, as well as no requirement of discontinuation treatment on the washing water.

Infections contribute to carcinogenesis through inflammation-related mechanisms. It is well established that H. pylori infection is an etiological factor in gastric carcinogenesis. However, the mechanism through which H. pylori infection contributes to the development of gastric cancer has not been fully elucidated. H. pylori-associated chronic inflammation is linked to genomic instability via reactive oxygen and nitrogen species (RONS). In this article, we summarize the current knowledge of H. pylori-induced double strand breaks (DSBs). Further, we will provide mechanistic insight into how processing of oxidative DNA damage via base excision repair (BER) leads to double strand breaks (DSBs). We review the recent progress how H. pylori infection triggers NF-kB /iNOS versus NF-kB/nucleotide excision repair (NER) axis mediated DSBs to drive genomic instability. Taken together, this review discusses current findings related to DSBs and their implications for the mechanisms of DSB repair.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

Epilepsy is characterized by repeated spontaneous reactions caused by hyper-excitability and neurons firing in high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients and nearly 30% of individuals are refractory to treatment of antiepileptic drugs. Therefore, there is an urgent need to develop new medicines to manage and control the refractory epilepsy. Cannabinoid ligands including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands may serve as the novel candidates for this need. Cannabinoid systems appear to regulating seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including a rat pilocarpine model of acquired epilepsy, in vitro hippocampal neuronal culture models of acquired epilepsy and status epilepticus, a pentylenetetrazole model of myoclonic seizures in mice and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. For this reason, we summarize the relationship between brain CB2 receptors and seizures, and emphasize the potential mechanisms of their therapeutic effects involving affecting neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.

The most widely distributed bla_CTX-M gene on a global scale is bla_CTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. This study aimed to review and describe the genetic environments of bla_CTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was done through PubMed, and Google Scholars electronic databases, 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of bla_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected associated with the genetic environment of bla_CTX-M-15 in Africa. Seven different genetic patterns were seen in bla_CTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the bla_CTX-M-15 gene while insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of bla_CTX-M-15 by insertion sequences IS26 and IS3. Class 1 integron (Intl1) was most reported to be associated with bla_CTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transfer bla_CTX-M-15 gene. Aminoglycoside modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with bla_CTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1and IncF plasmid in the mobilization and continental dissemination of the bla_CTX-M-15 gene in Africa.

In this paper, the design and control of a hydraulic system based tire changer machine have been analyzed and simulated using Matlab/Simulink Toolbox successfully. The machine have a displacement input which is a leg pedal displacement in order to push the piston of the pump to fed the motor with a pressured hydraulic fluid to rotate the tire with an angular speed to mount and dismount it. Augmentation based H_∞ and H₂ optimal synthesis controllers have been used to improve the performance of the machine. Comparison of the proposed controllers for tracking a reference input speed have been done using two reference inputs (step and random) signals. Finally the comparative simulation results proved the effectiveness of the proposed tire changer with H synthesis controller in improving the settling time and percentage overshoot.

A novel type of phosphazene containing additive that act both as catalyst and as flame retardant for benzoxazine binders is presented in this study. The synthesis of a derivative of hexachlorocyclotriphosphazene (HCP) and meta-toluidine was carried out in the medium of the latter, which made it possible to achieve complete substitution of chlorine atoms in the initial HCP. Thermal and flammability characteristics of modified compositions are revealed. The modifier catalyzes the process of curing and shifts the beginning of reaction from 222.0 C for pure benzoxazine to 205.9 C for composition with 10 phr of modifier. The additive decreases the glass transition temperature of compositions. Achievement of the highest category of flame resistance (V-0 in accordance with UL-94) is ensured both by increasing the content of phenyl residues in the composition and by the synergistic effect of phosphorus and nitrogen. Brief research of the curing kinetics disclosed the complex nature of the reaction. An accurate two-step model is obtained using extended Prout-Tompkins equation for both steps.

This study uses a recently developed theory and technique to examine post-acquisition evidence as to the motives for mergers and acquisitions(M&As), and decomposed the M/B ratio into three components: firm-specific error, time-series sector error, and long-run value-to-book. We make a multidimensional grouping according to the frequency of M&As , payment method, proportion of shares acquired, M/B ratio before the merger and total assets of the acquirers before the merge. The results confirm that M&As involve multiple motives, such as market timing, industry and economic shocks, agency and hubris. Using a sample of 2,035 M&As in China, we find that 59% are related to market timing, 68% are related to agency and hubris, 21% are related to industry and economic shocks, 51% are related to multiple motives. Our empirical research finds that the main motives for M&As of listed companies in China are value-decreasing, which have negative impact on the acquirers‘ sustainable development.

Background: Insecticide resistance in Anopheles gambiae s.l. is a major challenge for malaria vector control in Nigeria. Both target-site insensitivity and metabolic resistance have been im-plicated in resistance process, with the latter receiving little attention in Nigeria. Therefore, we investigated metabolic enzyme activities in Anopheles gambiae s.l populations resistant to Del-tamethrin and Diethyldichlorotriethylethane (DDT) in South-West Nigeria. Methods: Anopheles larvae were collected from Ibadan, Oyo and Badagry, Lagos. Adults were exposed to Deltamethrin and DDT using WHO method. Cohorts of populations were further exposed to Pyperonil Butoxide (PBO) and Deltamethrin. Insecticide-exposed and unexposed co-horts were examined for metabolic enzyme activities. Results were compared between exposed and unexposed samples ANOVA (P<0.05). Results: Mosquitoes were identified as An. gambiae (89%, Ibadan; 0%, Badagry) and An. coluzzii (11%, Ibadan; 100%, Badagry). The populations showed varied level of resistance to Deltamethrin (26%, Ibadan; 71%, Badagry) and DDT (2%, Ibadan; 44%, Badagry). Mortality to Deltamethrin in-creased from 26% to 64% (Ibadan) and 71% to 84% (Badagry) when populations were pre-exposed to PBO. Biochemical analysis revealed significant high levels (P<0.05) of cytochrome P450 and GST in exposed samples. Conclusions: Cytochrome P450 and GST are involved in Deltamethrin and DDT resistance in Anopheles gambiae s.l populations in South-West Nigeria.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

This article will briefly review the progress of h-BN based solid-state metal semiconductor metal (MSM) neutron detectors. In the last decade, several groups have been working on hexagonal boron nitride (h-BN) based solid-state neutron detectors. Recently, the detection efficiency of 59% has been reported. Efficient, low-cost neutron detectors made from readily available materials are essential for various applications. Neutron detectors are widely used to detect fissile materials and nuclear power plants for security applications. The most common and widely used neutron detectors are 3He based, which are sometimes bulky, difficult to transport, have high absorption length, need relatively high bias voltage (>1000 V), and have low Q-value (0.764 MeV). Also, 3He is not readily available material. Thus, there is a strong need to find an alternative detection material. 10B isotope has a high neutron absorption cross-section, and it has been tested as a coating on the semiconducting materials. Due to the two-step process, neutron capture through 10B, and then electron-hole pair generation in a typical semiconducting material, the efficiency of these devices is not up to the mark. The progress in h-BN based detectors requires a review to envision the further improvement in this technology.

Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected. In the 90s cases related to CFS, com-plaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis. As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a differ-ence in treatment and recovery. Low grade inflammatory conditions are related to Th2 predom-inance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests. In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.

Staphylococcus aureus is a major food-borne pathogen. The ability of S. aureus to produce biofilm is a significant virulence factor triggering its persistence in hostile environments. In this study, we screened a total of 420 different food samples and human hand swabs to detect S. aureus and to determine their biofilm formation ability. Samples analyzed were meat, milk, egg, fish, fast foods, and hand swabs. S. aureus were detected by culturing, staining, biochemical, and PCR. Biofilm formation ability was determined by Congo Red Agar (CRA) plate and Crystal Violet Microtiter Plate (CVMP) tests. The icaA, icaB, icaC, icaD, and bap genes involved in the synthesis of bio-film-forming intracellular adhesion compounds were detected by PCR. About 23.81% (100/420; 95% CI: 14.17-29.98%) samples harbored S. aureus as revealed by detection of the nuc gene. CRA plate revealed 20% of S. aureus isolates as strong biofilm producers, while 69% and 11% as in-termediate and non-biofilm producers, respectively. By the CVMP staining method, 20%, 77%, and 3% of the isolates were found strong, intermediate, and non-biofilm producers. Furthermore, 21% of S. aureus isolates carried at least one biofilm-forming gene, where icaA, icaB, icaC, icaD, and bap genes were detected in 15%, 20%, 7%, 20%, and 10% of the S. aureus isolates, respectively. Bivariate analysis showed high significant correlations (p<0.001) between any of the two adhesion genes of S. aureus isolates. To the best of our knowledge, this is the first study in Bangladesh describing the detection of biofilm-forming S. aureus from foods and hand swabs with molecular-based evidence. Our findings suggest that food samples should be deemed a potential reservoir of biofilm-forming S. aureus that indicates a potential public health significance.

Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (MTB) and M. africanum (MAF) remains a major global health threat. The varying response of different host to contact with the TB bacteria, indicates the importance of host genetics in susceptibility to TB disease. We explored the association among selected human/host genomic variants and disease caused by the two causative pathogens in Ghana through a case control study. MTBC isolates (323) recovered from pulmonary TB patients recruited between 2016 and 2018 were genotyped using spoligotyping. A selection of 29 SNPs from MTB-related genes with high frequency among African populations were genotyped using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Associations between MTBC lineages and host variables were assessed using univariate and multivariate logistic regression. The prevalence of MTB and Maf among the participants were 79% and 21% respectively. Association analysis between the controls and MAF showed that rs2695342 variant on the SIC11A1 gene have the propensity to confer susceptibility to MAF infections (P = 0.093, OR = 8.35, 95% CI = 0.70 – 99.24) whilst the rs17048476 (P = 0.088, OR = 1.57, 95% CI = 0.93 – 2.63) and rs1482868 (P = 0.095, OR = 0.60, 95% CI = 0.33 – 1.09) were observed to be only suggestive. Our findings implicate SLC11A1 as a potential susceptibility gene of substantial interest for TB caused by MAF which is an important pathogen in West Africa and highlight the need for in-depth host pathogen studies in West Africa.

The closed forms of the non-resonant thermonuclear function in the Maxwell-Boltzmann and Tsallis case with depleted tail are obtained in generalized special functions. The results are written in terms of H-function of two variables. The importance of the results in this paper lies in the fact that the reaction rate probability integrals in Maxwell-Boltzmann and Tsallis cases are not obtained by the conventional method of approximation or by means of a single variable transform technique but by means of a two variable transform method. The Behaviour of the depleted non-resonant thermonuclear functions are examined using graphs. The results in the paper are of much interest to astrophysicists and statisticians in their further work in this area.

This article introduces ten similarity measures that utilize cosine and cotangent functions to compare (m,n)-rung orthopair fuzzy sets, this a super class of q-rung orthopair fuzzy sets. Further, we applied our established weighted similarity measures to medical diagnosis, pattern recognition,and building material problems and also presented the comparison between established measures with the existing cosine and cotangent measures of q-rung orthopair, pythagorean and intuitionistic fuzzy sets. Lastly, we considered a numerical example that demonstrates the effective and scientific application of these similarity measures in plant leaf disease classification. Furthermore, we present graphical interpretations to demonstrate the effectiveness of our established measures.

The increase in the number of firms manipulating financial reports has misled shareholders' investment decisions and resulted in an indelible blot on foreign investors’ trust. Due to earnings management (EM) practice, managers' inefficiency, and lack of transparency in Iraq companies. This study tested the influence of the corporate governance mechanisms (CG), (board independence, audit committee, meeting frequency) on EM based on agency theory, as well, to link between EM and firm's performance (FP) in Iraqi listed companies and the impact of moderating role of corporate social responsibility (CSR) based on the Stakeholder Theory. The study's sample consists of 65 companies for the 2013-2018 financial years. Data were collected mainly from the annual reports (secondary data) of the Iraqi listed firms. This study uses the M-score model to detect EM practices as practical techniques in detecting earnings manipulation practices. The panel static model estimators. Hence, this paper adds to the CG literature from the perspective of stakeholder theory using Iraq's unique industrial environment. Based on the research results, policy-makers might use the study‘s findings to recognize the essential roles of several CG mechanisms in alleviating the opportunistic practices in Iraq. Further, companies should also be encouraged to enhance the CSR disclosure quality.

Abstract: Due to their rapid evolution and their impact on health care, be-ta-lactamases, protein degrading beta-lactam antibiotics, are used as generic model of protein evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases TEM-1 and CTX-M-15. Interestingly we found a site with a complex pattern of genetic interactions. Mutation G251W in TEM-1 is in-activating the protein’s function just as the reciprocal mutation W251G in CTXM-15. Phylogenetic analysis revealed that mutation G has been entrenched in TEM-1 background: while rarely observed throughout the phylogeny it is es-sential in TEM-1. Using a rescue experiment in TEM-1 G251W mutant, we could identify sites that alleviates the deviation from G to W. While few of these muta-tions could potentially involve local interactions, most of them were found on distant residues in the 3D structure. Many well-known mutations having an impact on protein stability, such as M182T, were recovered. Our results there-fore suggest that entrenchment of an amino acid may rely on diffuse interactions among multiple sites with a major impact on protein stability.

Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions

Studies have previously described the occurrence of multidrug-resistant (MDR) Escherichia coli in human and veterinary medical settings, livestock, and, to a lesser extent, in the environment and food. While they mostly analyzed foodborne E. coli regarding phenotypic and sometimes genotypic antibiotic resistance and basic phylogenetic classification, we have limited understanding of the in vitro and in vivo virulence characteristics and global phylogenetic contexts of these bacteria. Here, we investigated an E. coli strain (PBIO3502) isolated from a pork sausage in Germany in 2021 in-depth. Whole-genome sequence analysis revealed sequence type (ST)58, which is an emerging international high-risk clonal lineage. In addition to its MDR phenotype that mostly matched the genotype, PBIO3502 demonstrated pronounced virulence features, including in vitro biofilm formation, siderophore secretion, serum resilience, and in vivo mortality in Galleria mellonella larvae. Along with the genomic analysis indicating close phylogenetic relatedness of our strain with publicly available, clinically relevant representatives of the same ST, these results suggest the zoonotic and pathogenic character of PBIO3502 with the potential to cause infection in humans and animals. Also, our study highlights the necessity of the One Health approach while integrating human, animal, and environmental health, as well as the role of meat products and food chains in the putative transmission of MDR pathogens.

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH towards different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g. sulfenylation, S-thiolation, nitrosylation and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

In 2007, the excavation of the M-30 ring road located in Madrid and the creation of a green corridor either side of the Manzanares river brought significant change to the metropolitan area. The corridor and linear park which it provided were designed to contribute to the regeneration of the fluvial ecosystem, establish links among residents on each side of the river and promote cultural and leisure activities. This paper provides a sustainability analysis of the excavation of the M-30 (involving the socio-economic and environmental impact) 14 years after its construction. In order to show such an impact, an analysis of the area both prior to the project and after completion, as well as a hypothetical solution that uses improved materials, has been performed. This entails use of the multi-criteria decision-making model named MIVES (initials in Spanish, modelo integrado de valor para una evaluación sostenible). The MIVES method is based on the application of value functions of sustainability indicators selected by socio-economic and environmental criteria, chosen by experts. Results from analysis showed that the excavation of the M-30 considerably improved the sustainability of the area (sustainable index 3.43 and 6.26 both before and after the excavation works). However, use of improved materials in contrast with the application of conventional materials slightly improved the sustainability of the work (Sustainability Index 6.26 and 6.74, respectively, of the conventional materials).

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

Chronic fatigue syndrome (CFS) is a disease in which fatigue that interferes with daily life persists for six months or longer. The number of patients with CFS is increasing, as CFS-like symptoms have been reported to occur in the sequelae of both COVID-19 infection and the SARS-CoV-2 vaccine, both of which have become significant issues in recent years. While the pathogenesis mechanism is not yet fully understood, research suggests that oxidative stress (OS) may play a role in the development of CFS. In this paper, we discuss the antioxidant potential of the antioxidant formulation Twendee M® (TwM) and the results of a questionnaire that monitored changes in symptoms before and after TwM in a total of 23 men and women diagnosed with CFS. TwM is a supplement containing 15 different ingredients, and has a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. The results of the questionnaire showed that TwM significantly improved all of the major symptoms of CFS, including fatigue, muscle pain, joint pain, sleep disturbance, decreased memory and concentration, and headache. TwM was shown to alleviate various symptoms of CFS and improve quality of life.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Considering the fault "N-1" checksum and the power flow, the single-phase power flow model is further transformed into a three-phase power flow model, and the asymmetry of the three-phase power flow is measured by the three-phase unbalance factor. The calculation model is linearized by the second-order cone relaxation and the Big-M method. At the same time, the load response and distribution network reconstruction are used to improve the reliability of the power supply network to cope with the power failure. The relationship between power supply capability and power flow constraints, main transformer capacity and distributed power parameters is analyzed by IEEE 33-node three-phase power distribution system. The feasibility of the proposed model and the accuracy of the second-order cone relaxation are verified by numerical examples, which provides a technical reference for distribution network planning.