Thrombosis is characterized by the pathological formation of fibrin clots within a blood vessel, leading to the obstruction of blood flow. Fibrinolytic enzymes from microorganisms have exhibited promising effects to dissolve clots in a more efficient and safe way. Then, the aim of this study was to evaluate the biomass and fibrinolytic enzyme production of Tetradesmus obliquus under autotrophic and mixotrophic conditions using different concentration of corn steep liquor (CSL). Different extraction and precipitating methods were tested, and the enzyme was purified by ion exchange chromatography. More advantageous culture condition was mixotrophic using 0.25% CSL, showing the highest values of biomass productivity (Px = 169.3 ± 44.36 mg∙L-1day-1) and specific growth rate (µmax = 0.17 ± 0.00 day-1), and significant fibrinolytic production (391.34 ± 40.03 U∙mg-1). Moreover, fibrinolytic activity was higher when extracted by homogenization and precipitated using acetone, which exhibited clear zone of fibrin degradation in the fibrinolytic plate assay. Additionally, the purified enzyme showed specific activity of 1176.90 ± 140.37 U∙mg-1 and molecular weight around 97 kDa. Finally, the enzyme has higher enzymatic activity than various fibrinolytic enzymes, and the obtained enzyme has potential to be developed as a therapeutic agent in thrombosis treatment. Additional studies are need to investigate the biochemical properties and biological profile of this enzyme.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

Taking into consideration the arising resistance towards the currently available antimycobacterial, there is still an unmet need for the development of new chemotherapeutic agents to combat the infectious agent. This study presents the X-ray single-crystal analysis to verify the structure of leading sulfonyl hydrazone 3b, which have proven their potent antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC value of 0.0716 μM, respectively, low cytotoxicity and very high selectivity indexes (SI=2216) and fully characterized by NMR and HRMS methods. Furthermore, this study assessed the ex vivo antioxidant activity, acute and subacute toxicity, and in vitro inhibition capacity against enoyl-ACP reductase of hydrazones 3a and 3b, as 3a was identified as the second leading compound in our previous research. Compared to isoniazid, compounds 3a and 3b demonstrated lower acute toxicity for intraperitoneal administration, with LD50 values of 866 and 1224.7 mg/kg, respectively. Subacute toxicity tests, involving the repeated administration of a single dose of the test samples per day, revealed no significant deviations in hematological and biochemical parameters or pathomorphological tissues. The compounds exhibited potent antioxidant capabilities, reducing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH). Enzyme inhibition assays of the sulfonyl hydrazones 3a and 3b with IC50 values of 18.2 µM and 10.7 µM, respectively and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. In conclusion, the investigated sulfonyl hydrazones display promising antitubercular drug-like properties and warrant further investigation.

In this paper, new types of M-fractional wave solutions of mathematical physics model named as truncated M-fractional (1+1)-dimensional non-linear simplified Modified Camassa-Holm model are achieved by applying the modified simplest equation (MSE), Sardar sub-equation and generalized Kudryashov techniques. The gained solutions containing dark, bright, periodic and mixed wave solitons. Effect of fractional order derivative is also discussed. Achieved wave solitons are verified by Mathematica tool. Few of the gained wave solitons are also described through 2-dimensional, 3-dimensional and contour graphs through Mathematica tool. The gained solutions are helpful for the further development of concerned model. Finally, these techniques are simple, fruitful and effective to deal with non-linear FPDEs.

In light of the current situation where no testing equipment is available for measuring thermal deformation of objects, this paper proposes a novel method for accurate and precise measurement. The method overcomes the limitations of previous approaches that relied on pitch angle. By utilizing the principle of biplane multiple reflections, a bivariate laser spot displacement analysis algorithm is devised to attain highly precise measurements of bivariate angles. Additionally, a temperature gradient comparison algorithm is introduced to calculate the indicator test results under specific temperature conditions. To validate the effectiveness and reliability of this method, a testing system is constructed and utilized. The results demonstrate that the thermal deformation angle change test achieves an impressive accuracy of 0.015″ and a rate of thermal deformation angle change of 0.3247″/°C. These values are in close agreement with the previously simulated analysis result of 0.359″/°C, with only a relative error of 9.55%. Therefore, the test results confirm the efficacy and reliability of this testing method along with the feasibility of the algorithm processing.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body's immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using Receiver Operating Characteristic (ROC) curve and AUC (Area Under the Curve) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT with a value of r=0.933 and p <0.001. The value ≥37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, positive, and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of corona-virus disease 19 (COVID-19) and employs angiotensin-converting enzyme 2 (ACE2) as the recep-tor. Although the expression of ACE2 is crucial for cellular entry, we found that the interaction of ACE2 with the Spike (S) protein in the same cells led to its downregulation through degradation in the lysosomal compartment via the endocytic pathway. Interestingly, the ability of the S protein from previous variants of concern (VOCs) to downregulate ACE2 was variant-dependent and correlated with disease severity. The S protein from the Omicron variant, associated with milder disease, exhibited a lower capacity to downregulate ACE2 than that of the Delta variant, which is linked to a higher risk of hospitalization. Chimeric studies between the S proteins from the Delta and Omicron variants revealed that both the receptor-binding domain (RBD) and S2 subunit played crucial roles in the reduced ACE2 downregulation activity observed in the Omicron var-iant. In contrast, three mutations (L452R/P681R/D950N) located in the RBD, S1/S2 cleavage site, and HR1 domain were identified as essential for the higher ACE2 downregulation activity ob-served in the Delta variant than that in the other VOCs. Our results suggested that dysregulation of the renin-angiotensin system due to the ACE2 downregulation activity of the S protein of SARS-CoV-2 may play a key role in the pathogenesis of COVID-19.

The humoral response of the COVID-19 vaccine varies from person to person. It largely depends on prior SARS-CoV-2 infection, obtaining an adequate immune response, and leaving a trace of changing antibody concentration over time. We retrospectively analyzed five clinical cases from selected patients and employees of the oncology hospital. All mild COVID-19 convalescents received the BNT162b2-Comirnaty mRNA vaccine three or four times. The levels of SARS-CoV-2 IgM- and IgG-specific antibodies, as well as S-RBD antibodies, were analyzed for two years. The concentration of antibodies was assessed in the laboratory using the chemiluminescent immunoassay CLIA, MAGLUMI. Results: (1) Active autoimmune disease stabilized the level of IgG-specific antibodies after systemic mRNA vaccination for at least six months. (2) Post-vaccination IgG and S-RBD levels decreased when vaccination was performed within three months of onset. (3) The booster dose administered only increased the S-RBD antibody levels. Declining IgG-specific antibodies were observed. (4) The S-RBD IgG levels were not correlated with the SARS-CoV-2 IgG levels in the vaccinated convalescents. (5) Subsequent reinfection with SARS-CoV-2 after vaccination three times released a more significant specific antibody response. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive but not equivalent to a specific humoral response for SARS-CoV-2 IgG. We suggested that administering at least three doses of the mRNA vaccine should serve as the basis for immunization. The three-month interval may be the best alternative to an immunization schedule for non-immunocompromised people.

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.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

This paper contains a comparative review of existing Zitterbewegung models. It attempts to synthesize them by offering a toy model containing an extra hypothesis of electromagnetic self-oscillation at the Fermi scale (10−15m). Inspired by Bell violation experiments, Zitterbewegung models and hydrodynamic walker studies, we revisit standing waves in quantum mechanics, echoing de Broglie-Bohm pilot wave theories. Starting with the electromagnetic self-oscillation hypothesis at the Fermi scale we propose an emergent and deductive hierarchical electron structure across multiple scales. The model spans Fermi, Compton (10−13m), Bohr (10−11m) and finally de Broglie (>10−10m). At the Fermi scale, the hypothesis is one of "source-free chiral light", known as the "zilch", emerging as a self-oscillating electromagnetic field at the Schwinger limit. This self-interaction of retarded potentials due to real relativistic delays is a generic self-oscillation of Liénard-Wiechert potentials. This primary Fermi oscillation accounts for charge and mass at the Fermi scale. It generates secondary stable "auto-orbits" dynamics at the Compton scale, manifesting as observable spin and other quantum properties of the usual Dirac zitterbewegung models. These zitter models account for known electron characteristics, including mass, charge, spin and g/2 anomalous factors up to 9 digits precision. We explain the de Broglie wavelength through Doppler-shifted Compton-scale standing waves, in the tradition of de Broglie. The framework extends to electron-positron pair production at the Schwinger limit, described as a result of natural light focusing in non-homogeneous media, utilizing René Thom’s catastrophe theory. This offers a new perspective on baryogenesis and matter emergence from electromagnetic fields. We dub this toy model the "sub-standard" model of the electron.

The sub-economic dynamics studies the relationship between people's economic impulses and market behavior. Using Bourbaki structuralism as a philosophical consideration and quantum chromodynamics as a conceptual and modeling method, sub-economic dynamics theory is constructed. In this theory, we discuss the deep structure of the free market and analyze the errors in Mises' anthropological arguments. Sub-economic dynamics is the psychological basis of market dynamics. Guided by the preface, this paper is divided into six sections: (1) The Free Market and Impulse Flavor Charge, including topics such as the fate of the free market, the food chain and psychology, and the flavor charge of economic impulses; (2) The Nature of Economic Impulses, including topics such as the flavor and generation of impulses and counter-impulses, and the bound state of impulses and fractional market charges; (3) Freud's Color Charge Space and Spin, including topics such as the Pauli exclusion rule and color charge, and Freud's personality theory; (4) Consciousness and Gluons; (5) Gauge Transformations and SU(3) Symmetry Group; and (6) General Discussion.

It is widely believed that the dramatic transformation of the spherical outflows of AGB stars into the extreme aspherical geometries seen during the planetary nebula (PN) phase is linked to binarity and driven by the associated production of fast jets and central disks/torii. The key to understanding the engines that produce these jets and the jet-shaping mechanisms lies in the study of objects in transition between the AGB and PN phases. I discuss the results of our recent studies with high-angular-resolution (with ALMA & HST) and at high-energies (with GALEX, XMM-Newton & Chandra) of several such objects, which reveal new details of close binary interactions and high-speed outflows. These include two PPNe (the Boomerang Nebula and IRAS16342-3814), and the late carbon star, V Hya. The Boomerang is notable for a massive, high-speed outflow that has cooled below the microwave background temperature, making it the coldest object in the Universe. IRAS16342 is the prime example of the class of water-fountain PPNe (very young PPNe with high-velocity H₂O masers) and shows the signature of a precessing jet. V Hya ejects high-speed bullets every 8.5 years associated with the periastron passage of a companion in an eccentric orbit. I discuss our work on AGB stars with strongly-variable high-energy (FUV, X-ray) emission, suggesting that these objects are in the early stages of binary interactions that result in the formation of accretion disks and jets.

In recent years, an interest in multimedia services has grown expeditiously where the main part is comprised of video. Firms as well as subscribers require higher resolutions, framerates and sampling precision which results to higher amount of data need for processing, storing and transmitting. Therefore, a big challenge arises for researchers to develop new compression standards which should reduce the huge amount of data and keep quality at the same level. This paper examines compression performance of the latest and currently most used video codecs, namely H.266/VVC, AV1, H265/HEVC and H.264/AVC. The test set consists of seven sequences with various content at 8K, Ultra HD and Full HD resolution and encoded to bitrates from 1 to 15 Mbps for Full HD and Ultra HD resolutions and from 5 to 50 Mbps for 8K resolution, respectively. Codec performance was measured using PSNR, SSIM and VMAF objective quality metrics. In terms of the Bjøntegaard-Delta (BD) model, the results showed that H.266/VVC outperforms all other codecs, namely H.264/AVC,H.265/HEVC and AV1, respectively. Averaged bitrate savings were approximately 78\% for H.266/VVC, 63\% for AV1 and 53\% for H.265/HEVC relative to H.264/AVC, 59\% for H.266/VVC, 22\% for AV1 compared to H.264/AVC and 46\% for H.266/VVC relative to AV1, all for 8K resolution. The results also showed that the performance varies depending on resolution – with higher resolution, the efficiency of newly developed codecs such as H.266/VVC and AV1 is greater, which confirmed the fact that the H.266/VVC and AV1 codecs have been primarily developed for videos at high resolutions as 8K and/or UHD.

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.

The article obtains large deviation asymptotic for sub-critical communication networks modelled as signal-interference-noise-ratio(SINR) random networks. To achieve this, we define the empirical power measure and the empirical connectivity measure, as well as prove joint large deviation principles(LDPs) for the two empirical measures on two different scales. Using the joint LDPs, we prove an Asymptotic equipartition property(AEP) for wireless telecommunication Networks modelled as the subcritical SINR random networks. Further, we prove a Local Large deviation principle(LLDP) for the sub-critical SINR random network. From the LLDPs, we prove the large deviation principle, and a classical McMillan Theorem for the stochastic SINR model processes. Note that, the LDPs for the empirical measures of this stochastic SINR random network model were derived on spaces of measures equipped with the $\tau-$ topology, and the LLDPs were deduced in the space of SINR model process without any topological limitations. We motivate the study by describing a possible anomaly detection test for SINR random networks.

Hippophae is a tree species with ecological, economic and social benefits. In this study, we assembled and annotated chloroplast genomes of sympatric Hippophae gyantsensis and H. rhamnoides subsp. yunnanensis. Their full-length are 155260 and 156415 bp, respectively. Each of them has 131 genes, comprising 85 protein-coding genes, 8 ribosomal RNA genes and 38 transfer RNA genes. After comparing the chloroplast genomes, we found 1302 base difference loci, and 63.29% are located in the intergenic region or intron sequences and 36.71% are located in the coding sequences. The SSC region has the highest mutation rate, followed by the LSC region; the IR regions have the lowest mutation rate. Among the protein-coding genes, three had a ratio of nonsynonymous to synonymous substitutions (Ka/Ks) >1 (but P values were non-significant) and 66 had Ka/Ks <1 (46 were significant). In general, the chloroplast protein-coding genes may be subject to purification selection. Among H. gyantsensis and H. rhamnoides subsp. yunnanensis chloroplast protein-coding genes, there are 20 and 16 optimal codons, respectively. Most of the optimal codons were ending with A or U, which indicates significant AT preference. It is an important reference for studies on the general characteristics and evolution of the Hippophae chloroplast genome.

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause are presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD, with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years. Neuroimaging, laboratory study, genetic testing. In addition, a systematic review of the PSEN2-AD were performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related with myelin disruption induced by amyloid accumulation.

As humans age, aberrancies in several signaling pathways occur. In the aging population, some patients display abnormal bone morphogenetic protein (BMP) signaling. This can lead to osteoporosis (OP), a debilitating bone disorder caused by an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery as it is crucial for bone formation. However, complications have been reported with rhBMP-2 and primary osteoblasts isolated from OP patients are unresponsive to BMP-2. While patient samples are available, previous medical history may alter results. Therefore, C57BL/6 mice, an aging model that displays aberrant BMP-signaling, can be utilized to investigate OP and aging. We show that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month mice similar to previous data. We show that a conjugation between BMP-2 and Quantum Dots (QDot®s) effectively binds to BMPRIa and can investigate BMP-2 activity. After incubating BMSCs with methyl-β-cyclodextrin (MβCD), BMP-signaling is restored in 15-month mice as shown by western blotting and the von Kossa assay. MβCD may be used to rescue BMPRIa and the BMP-signaling pathway can be utilized by future therapeutics to treat OP.

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

In this paper, modelling designing and simulation of a simple voltage amplidyne system is done using robust control theory. In order to increase the performance of the voltage amplidyne system with H ∞ optimal control synthesis and H ∞ optimal control synthesis via ∞-iteration controllers are used. The open loop response of the voltage amplidyne system shows that the system can amplify the input 7 times. Comparison of the voltage amplidyne system with H ∞ optimal control synthesis and H ∞ optimal control synthesis via ∞-iteration controllers to track a desired step input have been done. Finally, the comparative simulation results prove the effectiveness of the proposed voltage amplidyne system with H ∞ optimal control synthesis controller in improving the percentage overshoot and the settling time.

Let R be a commutative ring with identity and S be a multiplicatively closed subset of R. The purpose of this paper is to introduce the concept of weakly S-primary ideals as a new generalization of weakly primary ideals. An ideal I of R disjoint with S is called a weakly S-primary ideal if there exists s∈S such that whenever 0≠ab∈I for a,b∈R, then sa∈√I or sb∈I. The relationships among S-prime, S-primary, weakly S-primary and S-n-ideals are investigated. For an element r in any general ZPI-ring, the (weakly) S_{r}-primary ideals are charctarized where S={1,r,r²,⋯}. Several properties, characterizations and examples concerning weakly S-primary ideals are presented. The stability of this new concept with respect to various ring-theoretic constructions such as the trivial ring extension and the amalgamation of rings along an ideal are studied. Furthermore, weakly S-decomposable ideals and S-weakly Laskerian rings which are generalizations of S-decomposable ideals and S-Laskerian rings are introduced.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

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.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

The regulation of intracellular pH in yeast (Saccharomyces cerevisiae) cells is critical for cell function and viability. In yeast, protons (H+) can be excreted from cell by the plasma membrane ATPase Pma1 and pumped into vacuoles by the vacuolar H+-ATPase. Because Pma1 is critical to the survival of yeast cells, it is unknown whether other compensatory components are involved in the pH homeostasis in the absence of Pma1. To elucidate how intracellular pH is regulated independently of Pma1, we employed a screening approach by exposing the yeast haploid deletion mutant library (ver 4.0) to the selective plant plasma membrane H+-ATPase inhibitor PS-1, which we previously reported. After repeated screenings and verification, we identified two proteins, ALY1 and ALY2, that play a role in the regulation of intracellular pH when Pma1 is deficient. Our research uncovers a new perspective on the regulation of intracellular pH related to Pma1 and also preliminarily reveals a role for ALY1 and ALY2 in the regulation of intracellular pH.

Satellite altimetry is successfully developing during the past three decades for the sea level, ocean dynamics, coastal oceanography, planetary waves, ocean tides, wind and wave, ice cover, Earth’s gravity field, and climatology research. We propose a new essential add-on of satellite altimetry related to the peculiarities of the orbits of the Topex/Poseidon and Jasons’ satellite missions which were not mentioned before in the scientific publications. Derived subsets of “self-crossover” and “inter-crossover” points in sub-polar latitudes are discussed in detail in the context of water exchange, and wind-wave dynamics, and potential challenges to be solved. The relatively short time lags between measurements at these crossovers provide additional information on anomalies of magnitudes and directions of ocean currents, and characteristics of wind-driven waves. Resulting data snapshots with constant space and time intervals can be regarded as time series of virtual buoys, an analog of continuous buoy measurements of the sea level, wind speed, and wave height. Areas of the World Ocean where these specific crossovers occur are described in the context of water exchange, wind wave studies, and potential challenges to be solved. The value of these special crossovers for studies and monitoring of the sub-polar seas is illustrated by a case study.

In this work, we introduce the class of h-MN-convex functions by generalizing the concept of MN-convexity and combining it with h-convexity. Namely, let M : [0, 1] → [a, b] be a Mean function given by M (t) = M (t; a, b); where by M (t; a, b) we mean one of the following functions: A_t (a, b) := (1 − t) a + tb, G_t (a, b) = a^1−tb^t and H_t (a, b) := $\frac{ab}{ta+\left(1-t\right)b}=\frac{1}{A_t\left(\frac{1}{a},\frac{1}{b}\right)}$ with the property that M (0; a, b) = a and M (1; a, b) = b. Let I, J be two intervals subset of (0, ∞) such that (0, 1) ⊆ J and [a, b] ⊆ I. Consider a non-negative function h : J → (0, ∞), a function f : I → (0, ∞) is said to be h-MN-convex (concave) if the inequality f (M (t; x, y)) ≤ (≥) N (h(t); f (x), f (y)), holds for all x, y ∈ I and t ∈ [0, 1]. In this way, nine classes of h-MN-convex functions are established, and therefore some analytic properties for each class of functions are explored and investigated. Characterizations of each type are given. Various Jensen’s type inequalities and their converses are proved.

In this work, several inequalities of Popoviciu type for h-MN-convex functions are proved, where M and N are denote to Arithmetic, Geometric and Harmonic means and h is a non-negative superadditive or subadditive function.

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.

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.

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

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.

Topological indices have been used to modeling biological and chemical properties of molecules in quantitive structure property relationship studies and quantitive structure activity studies. All the degree based topological indices have been defined via classical degree concept. In this paper we define a novel degree concept for a vertex of a simple connected graph: S degree. And also we define S indices of a simple connected graph by using the S degree concept. We compute the S indices for well-known simple connected graphs such as paths, stars, complete graphs and cycles.

A wave is an energy that can propagate with a medium, the propagation of a wave moves with respect to time by carrying energy that moves with velocity per unit of time. Sea waves are one of the propagating wave problems that are broken down to produce wave propagation with a relatively inhomogeneous minimum amplitude and speed of sea waves which have their own difficulties in solving them numerically. This study aims to analyze the stability of wave propagation of submerged breakwaters using the Boundary Element Method. This research will approximate the boundary discretization of the breakwater domain and then combine it with the Finite Element Method in determining the moving elements of the velocity of fluid flow through a porous submerged breakwater. This study varies the magnitude of the incoming propagation velocity and the influence of the breakwater distance. The results of this study indicate that the resulting minimal wave assuming v = 1 m/s and the breakwater distance of s = 20 m gives a wave reflection with a minimum wave speed and amplitude of 0.12515 m

In this paper, a horizontally moving suspended mass pendulum base is designed and controlled using robust control theory. H infinity optimal loop shaping with first and second order desired loop shaping function controllers are used to improve the performance of the system using Matlab/Simulink Toolbox. Comparison of the H infinity optimal loop shaping with first and second order desired loop shaping function controllers for the proposed system have been done to track the desired angular position of the pendulum using step and sine wave input signals and a promising result has been obtained succesfully.

In this paper, the design and analysis of coupled tank water level control system is done using robust control theory. The main aim of this work is to improve level controlling mechanisms in industries and household areas. In this paper, H ∞ and μ –synthesis controllers are designed to improve the level control system. The coupled tank water level control system is designed using the proposed controller’s comparison and tested for tracking a reference level signals (step, sine wave and random) and simulation results have been analyzed successfully. Finally the comparative simulation results prove the effectiveness of the proposed coupled tank water level control system with H ∞ controller for improving the tracking mechanism performance of the system.

Vehicle windshield wiper system increases the driving safety by contributing a clear shot viewing to the driver. In this paper, modelling, designing and simulation of a vehicle windshield wiper system with robust control theory is done successfully. H∞ loop shaping and robust pole placement controllers are used to improve the wiping speed by tracking a reference speed signals. The reference speed signals used in this paper are step and sine wave signals. Comparison of the H∞ loop shaping and robust pole placement controllers based on the two reference signals is done and convincing results have been obtained. Finally the comparative results prove the effectiveness of the proposed H∞ Loop Shaping controller to improve the wiping mechanism for the given two reference signals.

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.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

In this paper, modelling designing and simulation of a Ward Leonard layout system is done using robust control theory. In order to increase the performance of the Ward Leonard layout system with H infinity optimal control synthesis and H infinity optimal control synthesis via gamma-iteration controllers are used. The open loop response of the Ward Leonard layout system shows that the system needs to be improved. Comparison of the Ward Leonard layout system with H∞ optimal control synthesis and H infinity optimal control synthesis via gamma-iteration controllers to track a desired step speed input have been done. Finally, the comparative simulation results prove the effectiveness of the proposed Ward Leonard layout system with H infinity optimal control synthesis controller in improving the percentage overshoot and the settling time.

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.

In this article, we first defined a stronger form of (r,s)-generalized fuzzy semi-closed sets (briefly, (r,s)-gfsc sets) called (r,s)-g*fsc sets and investigated some of its features. Moreover, we showed that (r,s)-fsc set → (r,s)-g*fsc set → (r,s)-gfsc set, but the converse may not be true. In addition, we explored novel types of fuzzy generalized mappings between double fuzzy topological spaces (U, τ, τ*) and (V, η, η*), and the relationships between these classes of mappings were examined with the help of some illustrative examples. Thereafter, we introduced novel types of higher separation axioms called (r,s)-GFS-regular and (r,s)-GFS-normal spaces with the help of (r,s)-gfsc sets and discussed some topological properties of them. Finally, some novel types of compactness via (r,s)-gfso sets were defined and the relationships between them were introduced.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

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.

There were designed and synthesized two new sulfone 2-aminobenzimidazole derivatives. Coordination compounds were obtained with nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) and these novel ligands. There were fully characterized by spectroscopic and analytical techniques. Single crystal X-ray structural analysis was performed on order to study the relevant intra and inter non-covalent interactions, mainly H...π, lone pair·...π, π...π, highlighting the difference between the ethyl and phenyl groups in such interactions. Dimeric and trimeric supramolecular syntons were found for some of these compounds. Their biological activity was investigated, being the copper(II) compounds with the sulfone phenyl derivative the most active.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

Low-sodium salt substitute (LSSS) has the potential in regulating sodium and potassium intake and has been available in China market for years. However, its real-world use and impact to sodium\potassium intake is unclear. Baseline data of 4000 adult participants who participated in three similar-designed randomized controlled trails were pooled together for this study. Self-reported awareness and use of LSSS were collected using the uniform questionnaire, and the 24-h urinary sodium and potassium excretion was used to estimate their dietary intake. Mixed-effects models were developed to assess the relationship between LSSS and 24-h urinary sodium and potassium excretion. 32.0% of the participants reported awareness of LSSS and 11.7% reported its current use. After adjusting location, sex, age, and education, compared with the group of participants unaware of LSSS, participants who were aware but not using LSSS and those who were using LSSS had a lower 24-h urinary sodium excretion by –356.1(95% CI: –503.9, –205.9) mg/d and –490.6(95% CI: –679.2, –293.7), respectively (p&lt;0.001). No significant difference was found for 24-h urinary potassium excretion and sodium-to-potassium ratio among the three groups (p&gt;0.05). In conclusion, although associated with lower sodium intake, the awareness and real-world use of LSSS are still very low in China.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like te-mozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glio-blastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. 3D glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NR). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n=9) and 77% (n=20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp be-ing REGO-NR. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO com-pared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal ex-ploration of the molecular changes induced by treatment, unveiling promising biomarkers in-dicative of drug response.

Aim: To compare the effectiveness of conventional and rotary NiTi files for Gutta-Percha (GP) removal in straight roots during retreatment root canal treatment (RCT), using manual Hedstrom files and ProTaper Universal System, respectively. Methods: It was an in-vitro experimental study using non-probability consecutive sampling. Sixty extracted single rooted maxillary and mandibular permanent teeth with straight canals were selected for this study. Following preparation, the root canals were filled with GP along with a sealer and kept for two weeks in a moist environment at room temperature. Thirty teeth were randomly allocated to the study and control groups each. GP removal was accomplished with Hedstrom files and Pro Taper retreatment files in group 1 and group 2, respectively. Digital radiographs were obtained using Kodak RVG digital radiography system software version VER.6.10.8.3-A and analyzed for the difference of opacities indicating residual GP. AutoCAD 2006 software was used to outline the root canal and the residual root filling. Independent sample t test was used to compare the total residual GP in both groups. Results: No significant difference in the residual root filling was observed following removal with conventional Hedstrom files versus ProTaper universal retreatment files. In both groups, the residual GP was confined to the apical third of the roots. Conclusion: ProTaper Universal Retreatment files and manual Hedstrom files are equally effective in the removal of GP in straight canals.

In this paper, we focus on the influence of Riemann space-time curvature on the laws of electromagnetism, such as Gauss’s law, Maxwell-Amp´ere’s law, and Faraday’s law. Furthermore, we also introduce the work done on the unification of the gravitation and electromagnetic fields.

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

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.

Streptococcus mutans is a key bacterium in dental caries- one of the most prevalent chronic infectious diseases. Conventional treatment both fails to specifically target the pathogenic bacteria and at-tempts to eradicate commensal bacteria as well. Thus, caries remains one of most common and challenging diseases. The use of bacterial viruses as anti-bacterial agents, is gaining interest worldwide. Hardly any phages were described against S. mutans. The objective of this study was to isolate anti-S. mutans phages and to characterize their antimi-crobial properties. Human saliva samples were filtered and screened for potential phages. Standard double-layered agar method was used for isolation. Whole genome sequence analysis and morphology visualization by TEM, were used for anti-S. mutans phage identification. Antibacterial properties were evaluated using clinical strains and ATCC strains of S. mutans in various states. Antibacterial effect was also tested on human cariogenic dentin. One phage against S. mutans was isolated and termed SMHBZ8. This phage showed effective lytic activity in vitro against both planktonic and biofilm S. mutans cultures. Moreover, the phage showed antibacterial effect when used on cariogenic dentin. The isolation and characterization of SMHBZ8 may be the first step in developing a potential phage therapy for dental caries.

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

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

Several stochastic H∞ filters for estimating the attitude of a rigid body from line-of-sight measurements and rate gyro readings are developed. The measurements are corrupted by white noise with unknown variances. Our approach consists of estimating the quaternion while attenuating the transmission gain from the unknown variances and initial errors to the current estimation error. The time-varying H∞ gains are computed through differential and algebraic linear matrix inequalities whose parameters are independent of the state. The case of a gyro drift is addressed, too. Extensive Monte Carlo simulations show that the proposed stochastic H∞ quaternion filters perform well for a wide range of noise variances. The actual attenuation, which improves with the noise level and is worst in the noise-free case, is better than the guaranteed attenuation by one order of magnitude. The proposed stochastic H∞ filter produces smaller biases than a standard quaternion Kalman filter and similar standard deviations at large noise levels. An essential advantage of this H∞ filter is that the gains are independent of the quaternion, which makes it insensitive to modeling errors. This desired feature is illustrated by comparing its performances against those of unmatched Kalman filters. When provided with too high or too low noise variances the Kalman filter is outperformed by the $H_\infty$ filter, which essentially delivers identical error magnitudes.

Academic engagement provides opportunities and resources for students to engage in socio-educational interactions and academic learning. Our study provides an overview of high-impact research in academic engagement and the potential causes of its high valuation in the scientific community based on a bibliometric analysis of 4667 articles indexed in Web of Science, processed mainly by VOSviewer software. In terms of results, the publication of selected articles grows exponentially year by year, presenting concentration levels of 1% in authorship, 49% in a single country, and 5% of the journals. As well as 6% in highly cited articles, which in this case is associated with authors with high levels of publication. The most cited current topics are those relating academic engagement with motivation and emotional aspects.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values &lt; 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

Licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata. CRC treatment has always been challenged by the development of resistance. We investigated the antiproliferative activity of LCH in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including phospho (p)-EGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation, as verified by N-acetyl-L-cysteine (NAC) treatment, and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP and increased. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of subG1 cells and arrested the cell cycle at the G1 phase. LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

A fundamental tool in mathematical physics is the logarithmic Sobolev inequality. A quantitative version proven by Carlen with a remainder involving the Fourier-Wiener transform is equivalent to an entropic uncertainty principle more general than the Heisenberg uncertainty principle. In the stability, the remainder is in terms of an entropy, not a metric. Recently, a stability result for H¹ was obtained by Dolbeault, Esteban, Figalli, Frank, and Loss in terms of an L^p norm. Afterwards, Brigati, Dolbeault, and Simonov discussed the stability problem involving a stronger norm. A full characterization with a necessary and sufficient condition to have H¹ convergence is identified in this paper. Moreover, an explicit H¹ bound via a moment assumption is shown. Also, the L^p stability of Dolbeault, Esteban, Figalli, Frank, and Loss is proven to be sharp.

The ability of 2D hybrid structures formed by boron, nitrogen and carbon atoms (h-BNCs) as potential substrates for surface enhanced Raman spectroscopy (SERS) detection of dioxin-like pollutants is theoretically analyzed. The strong confinement and high tunability of the electromagnetic response of the carbon nanostructures embedded within the h-BNC sheets point out that these hybrid structures could be promising for applications in optical spectroscopies, such as SERS. In this work, two model dioxin-like pollutants, TCDD and TCDF, and a model h-BNC surface composed by a carbon nanodisk of ninety-six atoms surrounded by a string of borazine rings, BNC96, are employed for the simulation of the adsorption complexes and the static and pre-resonance Raman spectra of the adsorbed molecules. A large affinity of BNC96 by these pollutants is reflected on the large interaction energies obtained for the most stable stacking complexes, with dispersion being the most important contribution to their stability. The large vibrational coupling of some active modes of TCDF and, specially, of TCDD makes the Raman static spectra display a ‘pure’ chemical enhancement of one order of magnitude. On the other hand, due to the strong electromagnetic response of BNC96, confined within the carbon nanodisk, pre-resonance Raman spectra obtained for TCDD and TCDF display large enhancement factors of 108 and 107, respectively. Promisingly, laser excitation wavelengths frequently used in SERS experiments also provoke significant Raman enhancements, around 104, for the TCDD and TCDF signals. Both the strong confinement of the electromagnetic response within the carbon domains and the high modulation of the resonance wavelengths within the visible and/or UV ranges in h-BNCs should lead to a higher sensitivity than graphene and white graphene parent structures, solving one of the main disadvantages of using 2D substrates for SERS applications.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

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.

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.

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.

The past two decades has seen a growing demand for high-power, high-voltage utility scale inverters mostly fueled by the integration of large solar PV and wind farms. Multilevel inverters have emerged as the industry choice for these megawatt range inverters because their reduced voltage stress, capable of generating an almost sinusoidal voltage, in-built redundancy, among others. This paper present a new Switched-Source Multilevel Inverter (SS MLI) architecture. The new inverter show superior over existing topologies. It has reduced voltage stress on the semiconductor, uses less number of switches –reduced size/weight/cost and increased efficiency. The new SSMLI is comprised of two voltage sources (V₁, V₂) and 6 switches. It is capable of generating 5-level output voltage in symmetric modes (i.e., V₁ = V₂), and 7-level output voltage in asymmetric modes (i.e., V₁ ≠ V₂). To demonstrate the validity of the proposed inverter, simulations results using MATLAB^® /Simulink^® for 5- and 7-level output voltages are presented . The simulations are also verified experimentally using a laboratory prototype.

The biofilm is a conglomerate of cells surrounded by an extracellular matrix, which contributes to the persistence of infections. The difficulty in removing the biofilm drives the research for new therapeutic options. In this work, the effect of terpenes (-)-trans-Caryophyllene, (S)-cis-Verbenol, (S)-(-)-Limonene, (R)-(+)-Limonene, and linalool was evaluated, individually and in combinations on bacterial growth, by assay with resazurin; the formation of biofilm, by assay with violet crystal; and the expression of associated genes, by real-time PCR, in two clinical isolates of S. aureus, ST30-t019 and ST5-t311, responsible for more than 90% of pediatric infections by this pathogen in Paraguay. All combinations of terpenes can inhibit biofilm formation in more than 50% without affecting bacterial growth. The most effective combination was (-)-trans-Caryophyllene and linalool at a 500 μg/mL concentration for each, with an inhibition percentage of 88%. This combination decreased the expression levels of the sdrD, spa, agr, and hld genes associated with the initial cell adhesion stage and quorum sensing. At the same time, it increased the expression levels of the cap5B and cap5C genes related to the production of capsular polysaccharides. The combinations of compounds tested are promising alternatives to inhibit biofilm formation in S. aureus.

Background/Objectives: This study aimed to evaluate compliance and accuracy in comparison with traditional PD diaries for tracking motor symptoms using a new smartphone application (My Parkinson’s) and paper diary strategies. Parkinson's disease (PD) is a neurodegenerative disorder with progressive motor symptoms. Treatment becomes more challenging as PD progresses, motor complications in the form of wearing-off phenomenon and levodopa-induced dyskinesia develop. Traditional paper diaries and clinical scales used to evaluate patients may be inadequate in assessing whether the patient is “on” or “off,” resulting in less-than-ideal treatment changes. Methods: A randomized crossover design was utilized to examine 22 advanced PD patients who underwent symptomatic assessment with both diaries during two separate 24-hour periods seven days apart. The compliance and accuracy of data were assessed by comparing diary entries with the clinical examination notes and WhatsApp queries. Latterly, patients' diary preferences were also evaluated.; Results: The digital diary had significantly better compliance and accuracy than the paper diaries, with substantial/almost perfect levels of agreement (κ = 0·615 to 0·818) between logged symptoms and clinical examination notes. 65% of patients preferred the digital diary for follow-ups, and there was no significant difference in ease of use compared to paper diaries. Conclusions: Digital diaries are helpful in the clinical management of PD patients as they minimize recall bias and reduce data errors in appropriately selected patients. Our study suggests a broader adoption of digital health technologies in PD management. Still, additional research is necessary to improve the tools and assess long-term patient outcomes.

Staphylococcus aureus, found in the oral cavity as an opportunistic bacterium, has been reported as a cause of infective endocarditis and pneumonia. Salt is an essential mineral component for maintaining human body cells and has attracted attention as a promoter of S. aureus biofilms. This study was conducted to clarify how salt affects biofilm formation by S. aureus and S. mutans, which is a pathogen implicated in the dental caries. Bacteria were cultivated with various concentration of sodium chloride (NaCl) in Toryptic Soy Broth with 0.25% sucrose and 0.25% glucose (TSBs and TSBg) for 16 hours. Contribution of GTF on the membrane vesicles (MVs) from S. mutans and extracellular DNA (eDNA) was also analyzed in the biofilm formation. S. aureus biofilms were induced by the addition of 0.004–0.25 M NaCl but decreased by NaCl concentrations greater than 0.25 M, in TSBs. The biofilm formation of mixed bacteria (S. aureus and S. mutans) gradually increased in a NaCl concentration-dependent manner in TSBs and TSBg. Moreover, the biofilm was dependent on glucan formation by GTF in MVs at high salinity. The mixed-species biofilm of S. aureus and S. mutans was upregulated by the collaboration of eDNA and MVs. Therefore, eDNA and MVs are developmental factors for S. aureus biofilm formation under harsh conditions. The intake of sucrose and glucose may be a risk factor for infection by opportunistic pathogens such as S. aureus in persons who consume high concentrations of salt in foods and drinks in custom-type foods.

We report on the role of synergistic polarization of Ba0.9Sr0.1TiO3 (BST) nanoparticles in sulfur cathodes to enhance the redox kinetics of polysulfides for high-capacity Li-S batteries. Ferroelectric nanoparticles are known to significantly improve the electrochemical performance of Li-S batteries due to their inherent self-polarization and high adsorption capacity towards polysulfides. X-ray diffraction spectra confirmed the tetragonal symmetry (c/a=1.0073), while Raman spectroscopic analysis validated the presence of tetragonal orientation Raman modes in BST-modified composites. Scanning electron microscope (SEM) images showed a homogeneous distribution of BST in the sulfur cathode system, with grain sizes ranging from 1 to 1.5 μm. Notably, the BST-coupled S50BST30CB10PVDF10 composite cathode achieved a capacity of approximately 820 mAh/g at 100 mA/g, maintaining stability over 100 cycles, demonstrating improved electrochemical performance. Two distinct plateaus between 2.3 V to 2.0 V and 2.0 V to 1.5 V further underscore the superior performance of BST ferroelectric nanoparticles in enhancing the redox kinetics of Li-S batteries. By leveraging the favourable affinity of polar substances towards polysulfides, we aimed to create a more stable reactive environment within the cathodic site, effectively trapping polysulfide intermediates through the synergistic polarization of BST nanoparticles. The synergistic polarization induced by the asymmetric crystal structure of ferroelectrics is anticipated to generate internal electric fields, enhancing chemisorption with heteropolar reactive. The observed high cyclic stability further validates the efficacy of these composite cathodes in mitigating the polysulfide shuttle effect, offering promising prospects for advancing Li-S battery technology.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

This article takes the representative uncultivated riverfront internet-famous sites (the uncultivated RIFSs) in Changsha city, China as an example, to explore the internal mechanism of its formation, and finds out that they are closely related to "urban subculture" and "informality of urban public space". In terms of methodology, through questionnaire surveys and in-depth interviews, this study investigates the behavioral characteristics of on-site visitors, overall perceptions and satisfaction of public spaces, and perceptions of spatial and humanistic elements of visitors. It also compares the online-offline differences of the spatial perceptions on the uncultivated RIFSs between this study and previous research, that is, instead of focus on the urban physical spaces, the online social media users pay more attention to their self-presentation. Meanwhile, the visitors place greater emphasis on the functionality, practicality, and experiential activities of the urban physical spaces. Finally, this article proposes the optimization strategies for the uncultivated RIFSs from two aspects: planning and governance, and public space design. Firstly, it is necessary to protect this special type of spaces, avoiding the binary opposition between "formal spaces" and "informal spaces”, achieving a gradual integration of "subculture spaces" and "mainstream culture spaces", and highlighting the city's inclusiveness. Secondly, human-centric space design should be demonstrated, that is, paying practical attention to people's diverse lifestyles and value needs, strengthening the composite utilization of riverside spaces to enhance diverse vitality.

Diagnostics is believed to drive about 70% of medical interventions, but this may not be true for all demographics. With more than 30% of the African population living in extreme poverty ($1.9 per day - 2022); and healthcare costs competing unfavorably against unbridled access to antibiotics and herbal concoctions, especially in Sub-Saharan Africa, how do you convince such a people to choose diagnostics first? More importantly, how do you design a medical device targeted at meeting the diagnostic needs of this demographic? In developing diagnostic devices for such a market, what is worth sacrificing? How dire is the need for advanced technologies in devices developed for such a demographic? These are questions that remain unaddressed by the technological breakthroughs and current research in medical device development, especially for infectious disease diagnostics. The objective of this paper is to underscore critical concerns which must be considered in the bid to successfully design medical diagnostic devices for Africa and perhaps, other limited-resource settings. It is also written as a suggestive guidance document for researchers whose interest is in the development of infectious disease diagnostic platforms for rural Africa and similar limited-resource environments.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

These counterexamples have shown the relationships between the power of a Pythagorean equation and Pythagorean’s triples. There are three positive integers that satisfy Fermat’s equation when the power n is equal to 2 in the case of the Pythagorean theorem and it’s applicable relationships in right triangles. On the other hand, as the power varies from positive to negative integers or any integers other than 2, such as in the case of Fermat’s last theorem, the hypotenuse z of a right triangle tends to be equal to one of the sides x or y of the triangle and the other side tends to be equal to zero. And the application of this idea describes the behavior of a mass object in motion. Since the total energy of the object is the sum of its energy in motion and its rest energy, at a particular power n, the total energy of the object tends to be equal to either the rest energy or the photon energy.

It is challenging to apply the receiver function method to teleseisms recorded by ocean bottom seismographs (OBS) due to a specific working environment that differs from land stations. Tele-seismic incident waveforms reaching the vicinity beneath stations are contaminated by multiple reflections generated by seawater and sediments and noise resulting from currents. Furthermore, inadequate coupling between OBS and seabed reduces the signal-to-noise ratio (SNR) of seismograms, leading to poor quality of extracted receiver functions or even wrong deconvolution results. For instance, the poor results cause strong ambiguities regarding Moho depth. This study uses numerical modelling to analyze the influences of multiple reflections generated by seawater and sediments on H-kappa stacking and neighborhood algorithm. Numerical modellings show that seawater multiple reflections are mixed with coda waves of direct P-wave and slightly impact extracted receiver functions, thus can be ignored in subsequent inversion processing. However, synthetic seismograms have strong responses to the sediments. Compared to waveforms of horizontal and vertical components, sedimentary responses are too strong to identify the converted waves clearly. The extracted RFs correspond to the above influences, resulting in divergent results of H-kappa stacking (i.e., Moho depth and crustal average VP/VS ratio are unstable and have great uncertainties). Fortunately, waveform inversion approaches (e.g., neighborhood algorithm) is available and valid for obtaining S-wave velocity structure of the crust-upper mantle beneath the station with sediments varying in thickness and velocity.

The use of edible films has become a topic of great interest in the food and environmental sectors, due to their potential to prevent food deterioration and their biodegradability. In this context, this study aimed to develop and characterize edible films based on camu-camu residue, gelatin and glycerol, evaluating their solubility, thermal, degradability, antioxidant and water vapor permeability properties of the gelatin matrix. This is the first study incorporating camu-camu into a gelatin and glycerol matrix. The films produced with the incorporation of camu-camu residue proved to be manageable and soluble, with the presence of some non-soluble residues, providing a shine and a well-presented appearance. In the biodegradation results the samples 03 and 04 appeared to degrade the most, being two of the three most affected samples in the triplicate. The films showed degradation modifications from the third day of the experiment. In the germination and plant growth analysis, Sample 04 showed satisfactory development compared to other samples, making it the sample with the best overall result in the analyses. These results demonstrate that the produced materials have potential for food packaging applications.

The Shimensi super-large tungsten polymetallic deposit is located in Late Jurassic- Early Cretaceous Porphyry-Skarn tungsten ore belt in the south Yangtze metallogenic belt. There are 3 types of mineralization: veinlet-disseminated type, thick quartze vein type and hydrothermal crypto-explosive breccia type. Based on geological studies, this paper presents new petrographic, microthermometric, laser Raman spectroscopic and hydrogen and oxygen isotope research of the fluid inclusions from the deposit. The results show that there are five different types of fluid inclusions: liquid-rich inclusions, vapor-rich inclusions, pure liquid inclusions, pure vapor inclusions, and fluid inclusions containing a solid crystal. The homogenization temperatures of the fluid inclusion range from 140℃-270℃, the salinities are 3%-5% NaCleq and the densities of ore-forming fluid range from 0.64 g/cm3 to 0.99 g/cm3. For the analyses of Laser Raman spectroscopic, the ore-forming fluids can be approximated by a Ca2+-Na+-SO42--Cl- fluid system with small amount of CO2, CH4 and N2. Otherwise, the datas of the pressure, pH and Eh show a fluid metallogenic environment of low pressure, weak acid and weak reduction. The values of the homogenization temperature in 3 types of orebodies suggest that the mineralization is characterized by the decrease of the temperature under the condition of the fluid immiscibility. The H-O isotope values are interpreted to indicate that the ore-forming fluids are mainly composed of magmatic water, and also the meteoric water was added with the process of the magma rising.

Biodiesel is one of the most popular biofuels as it is a promising substitute of the conventional diesel fuel, but for now it cannot be used as a stand-alone fuel due to its low oxidative stability. For this reason, the last years there have been efforts for its upgrading through the partial hydrogenation of the fatty acid methyl esters (FAMEs) that biodiesel consists of. This procedure succeeds in resolving the problem of low oxidative stability, but in some cases a new problem arises as the non-selective hydrogenation is deteriorating the fuel’s cold flow properties, which are crucial for its operation without damaging the vehicle’s engine. More specifically, the problem of deteriorated cold flow properties is caused by the formation of trans-monounsaturated FAMEs and fully saturated FAMEs while the hydrogenation reaction is taking place. The hydrogenated biodiesels are preferred to contain more cis-monounsaturated FAMEs, because these are considered to have the best combination between high oxidative stability and good cold flow properties. As a result, various systems and methods have been tested in order to achieve a selective partial hydrogenation of biodiesel’s FAMEs. In this review article, the catalytic systems and methods that stood out in various researches are presented and the factors that lead to the best possible outcome are investigated and discussed.

Aim. To study the processes of lipid peroxidation and the activity of antioxidant defense enzymes depending on the chemiluminescent activity of neutrophilic granulocytes in patients with gastric cancer associated with H. pylori infection, depending on the stage. Materials and methods. 39 patients with stage I-II gastric cancer and 30 patients with stage III-IV gastric cancer were examined. The study of the chemiluminescent activity of neutrophilic granulocytes was carried out, the parameters of the lipid peroxidation system and antioxidant protection in plasma were determined using the spectrophotometric method. Statistical data processing was performed using the Statistica 7.0 software package (StatSoft, USA). Results. In patients with gastric cancer associated with H. pylori infection, regardless of stage, the proportion of neutrophilic granulocytes with normal activity does not exceed 1/3 of the total number of patients, the remaining 2/3 of patients have an altered chemiluminescent activity of neutrophilic granulocytes: in patients with gastric cancer by I -II stage of the disease, the majority revealed a reduced function of neutrophilic granulocytes, and in patients with gastric cancer stage III-IV of the disease, the majority showed increased chemiluminescent activity of neutrophilic granulocytes. In all patients with gastric cancer associated with H. pylori infection, regardless of the stage of the disease, an increase in lipid peroxidation processes with activation of antioxidant defense enzymes was detected. Conclusion. In all patients with gastric cancer associated with H. pylori infection, regardless of the stage of the disease, an increase in lipid peroxidation processes with activation of antioxidant defense enzymes was detected. At the same time, there are no statistically significant differences between the indicators of the system lipid peroxidation - antioxidant protection depending on the stage of gastric cancer and the chemiluminescent activity of neutrophilic granulocytes, which probably indicates that all reactive oxygen species produced by neutrophilic granulocytes in the respiratory burst are consumed locally, minimally affecting the development of oxidative stress in the blood plasma.

A simple undirected graph $\Gamma=(V_\Gamma,E_\Gamma)$ admits an $H$-covering if every edge in $E_\Gamma$ belongs to at least one subgraph of $\Gamma$ that isomorphic to a graph $H$. For any graph $\Gamma$ admitting $H$-covering, a total Labelling $\beta: V_\Gamma \cup E_\Gamma \longrightarrow \{1,2,\dots,p\}$ is called an $H$-irregular total $p$-labelling of $\Gamma$ if every two different subgraphs $H_1$ and $H_2$ of $\Gamma$ isomorphic to $H$ have distinct weights where the weight $w_\beta(K)$ of subgraph $K$ of $\Gamma$ is defined as $w_f(K):=\displaystyle \sum_{v\in V_K} f(v) + \sum_{e\in E_K} f(e)$. The smallest number $p$ for which a graph $\Gamma$ admits an $H$-irregular total $p$-labelling is called the total $H$-irregularity strength of $\Gamma$ and is denoted by $ths(\Gamma)$. In this paper, we determine the total $H$-irregularity strength of edge comb product of two graphs.

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.

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

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.

Noise reduction is the major issue in the loudspeaker for the application of the musical instruments and related areas. In this paper, a noise disturbance control of a loudspeaker with optimal and robust controllers has been done successfully. The noise of the loudspeaker has been analyzed by simply track a reference cone displacement with the actual cone displacement. Static output feedback and H infinity optimal loop shaping controllers have been used to compare the actual and reference cone displacements by using a sine wave and random cone displacement signals and a promising results have been analyzed.

Morphogenesis remains a riddle, wrapped in a mystery, inside an enigma. It remains a formidable problem viewed from many different perspectives of morphology, genetics, and computational modelling. We propose a biochemical reductionist approach that shows how both internal and external physical forces contribute to plant morphogenesis via mechanical stress-strain transduction from the primary cell wall tethered to the plasma membrane by a specific arabinogalactan protein (AGP). The resulting stress vector with direction defined by Hechtian adhesion sites, has a magnitude of a few picoNewtons amplified by a hypothetical Hechtian growth oscillator. This paradigm shift involves stress activated plasma membrane Ca2+channels and auxin-activated H+-ATPase. The proton pump dissociates periplasmic AGP-glycomodules that bind Ca2+. Thus, as the immediate source of cytosolic Ca2+ an AGP-Ca2+ capacitor directs vectorial exocytosis of cell wall precursors and auxin efflux (PIN) proteins. In toto these components comprise the Hechtian Oscillator and also the gravisensor. Thus interdependent auxin and Ca2+ morphogen gradients account for the predominance of AGPs. The size and location of a cell surface AGP-Ca2+ capacitor is essential to differentiation and explains AGP correlation with all stages of morphogenetic patterning from embryogenesis to root and shoot. Finally, evolutionary origins of the Hechtian Oscillator in the unicellular Chlorophycean algae reflect the ubiquitous role of chemiosmotic proton pumps that preceded DNA at the dawn of life.

Around 1637, Pierre de Fermat famously wrote in the margin of a book that he had a proof for the equation $a^n + b^n = c^n$ having no positive integer solutions for exponents $n$ greater than 2. This statement, now known as Fermat's Last Theorem, remained unproven for centuries, despite the efforts of countless mathematicians. Andrew Wiles' work in 1994 finally provided a rigorous proof of Fermat's Last Theorem. However, Wiles' proof relied on advanced mathematical techniques that were far beyond the scope of Fermat's time, raising questions about whether Fermat could have truly possessed a proof using the methods available to him. Wiles's achievement was widely celebrated, and he was awarded the Abel Prize in 2016 in recognition of his groundbreaking work. The citation for the award described his proof as a "stunning advance" in mathematics. The present work offers a potential solution to Fermat's Last Theorem that may be more aligned with the original approach that Fermat claimed to have used.

HIGHLIGHTS Mach's principle is linked with inertia and the mass around. Nowadays, physicists believe its effect is infinitesimal, so Mach's principle is simply ignored. This paper looks at the consequence of applying Mach's principle. It could replace dark matter. ABSTRACT After seeing the history of Mach's principle, we will work out a new model of galaxies inspired by Mach’s principle, which is more satisfactory than current dark matter models. This new model is just maths and needs an explanation. One possible explanation is obviously that Mach's principle is at work in a galaxy.

Urban tourism has witnessed significant growth in recent years, driven by various factors that foster the transformation of urban areas into tourist hotspots. These factors include a rising interest in culture and heritage, ongoing urban redevelopment and conversion processes, and the introduction of new experiences and activities. Two particularly influential factors contributing to this growth are low-cost travel, which facilitates more accessible access to urban destinations, and the emergence of new types of accommodation, such as short-term rental (also known as local accommodation or Airbnb-type accommodation). This sudden and continuous growth of this type of tourist accommodation brings new challenges to cities and local communities. On the positive side, it contributes to job opportunities, the dynamism of the local economy, and urban revitalization. On the other hand, it also represents more difficulty in retaining the local population in city centers, as more and more buildings are converted into hostels and tourist apartments. In this context, it becomes essential to conduct studies evaluating the impacts of these dynamics in urban areas and how they influence residents' and visitors' perspectives. Therefore, this study aims to identify the main transformations resulting from short-term rental (STR) development, focusing on the impacts felt by tourists and residents in Porto. A questionnaire was distributed to tourists and residents in Porto's city center in June 2023. The results reveal differences in opinions between tourists and residents, particularly concerning historical heritage preservation, local population relocation, and reduced housing availability for residents. Nevertheless, there is a similarity in their opinions regarding the stimulus that local accommodation brings to the economy and the rehabilitation of buildings and urban areas. This study reinforces the need to pay more attention to the future development of tourist accommodation in city centers, especially regarding local policies and territorial planning, to balance better tourism development and local communities' quality of life.

Although the empirical Kepler’s laws can be proven by applying Newton’s laws to the dynamics of two particles attracted due to the gravitational interaction, there is no explicit formula for the motion as a function of time. In this paper, a quasi-analytical solution for this problem is proposed. It approximates the real behavior of celestial bodies with an acceptable degree of accuracy. All calculations involved require a low computational cost. This problem is closely related to Kepler’s equation, since, the solution for the equations of motion as a function of time gives us the solution to Kepler’s equation as well. The results are presented for each planet of the solar system (including Pluto), and the solution is compared against the real orbits.

The conformity assessment of products or a measured value with the given standards is carried out based on the global risk of producers and consumers calculation. A product may conform to specifications but be falsely rejected as non-conforming. This is about the producer's risk. If a product doesn't meet the requirements but is falsely accepted as conforming, that poses a risk to the consumer. The conventional approach to risk assessment, which yields only a single numerical value for the global risk of producers and consumers, is naturally extended, and utilized for assessing risk in measurement models with linear regression. The outcomes of the two-dimensional extension, along a moderate scale, are the parabolas with an opening upwards. Risk surfaces were obtained through three-dimensional extension over the area limited by the moderate scale and guard band axes. Four models with different ranges of tolerance intervals were used to test this innovative method of risk assessment in linear regression. The corresponding standard measurement uncertainties are determined by applying a simplified measurement model with the use of comprehensive data on the measurement performance and by determining measurement uncertainty derived from consideration of the functional relationship obtained by linear regression analysis. Models that utilize information from linear regression analysis to determine measurement uncertainty are biased towards risks at the edges of the moderate scale. Testing the model's performances with metrics related to the confusion matrix, such as the F1 score, further substantiated this assertion. The diagnostic odds ratio has been proven to be extremely effective in identifying the curve along the guard band axis, along which the global risks of producers and consumers are at their lowest.

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.

We discuss two queueing-inventory systems with catastrophes in the warehouse. Catastrophes occur according to Poisson process and upon arrival of a catastrophe all inventory in the system is instantly destroyed. But consumer customers in the system (in the server or in the buffer) continue still waiting for the replenishment of the stock. The arrivals of the consumer customers follow a Markovian Arrival Process (MAP) and they can be queued in an infinite buffer. Service time of a consumer customer follows a phase-type distribution. The system receives negative customers whose have Poisson flows to service facility and upon arrival of a negative customer one consumer customer is pushed out from the system, if any. One of two replenishment policies can be used in the system: either (s,S) or (s,Q). If upon arrival of the consumer customer, the inventory level is zero, then according to the Bernoulli scheme, this customer is either lost (lost sale scheme) or join the queue (backorder sale scheme). The system is formulated by a four-dimensional continuous-time Markov chain. Steady state distribution is obtained using the matrix-geometric method. A comprehensive numerical study is performed on the performance measures under various replenishment policies. Finally, an optimization study is presented.