Since the electro-hydraulic servo shaking table exists many nonlinear elements, such as, dead zone, friction and blacklash, its acceleration response has higher harmonics which result in acceleration harmonic distortion, when the electro-hydraulic system is excited by sinusoidal signal. For suppressing the harmonic distortion and precisely identify harmonics, a combination of the adaptive linear neural network and least mean M-estimate (ADALINE-LMM), is proposed to identify the amplitude and phase of each harmonic component. Namely, the Hampel’s three-part M-estimator is applied to provide thresholds for detecting and suppressing the error signal. Harmonic generators are used by this harmonic identification scheme to create input vectors and the value of the identified acceleration signal is subtracted from the true value of the system acceleration response to construct the criterion function. The weight vector of the ADALINE is updated iteratively by the LMM algorithm, and the amplitude and phase of each harmonic, even the results of harmonic components, can be computed directly online. The simulation and experiment are performed to validate the performance of the proposed algorithm. According to the experiment result, the above method of harmonic identification possesses great real-time performance and it has not only good convergence performance but also high identification precision.

Peptidergic GPCR systems are broadly distributed in the human body and regulate numerous physiological processes by activating complex networks of intracellular biochemical events responsible for cell regulation and survival. Their failure due to overaction, ill-function, or blockade gives rise to cell disturbances, eventually causing disease if compensatory mechanisms do not suffice. Revision of updated experimental research provided an evident relationship associating peptidergic GPCR malfunction with tumor formation and maintenance resulting from uncontrolled cell proliferation and migration, colonization, inhibition of apoptosis or altered metabolism, and increased angiogenesis in tumoral tissues. Determination of the implication of GPCR peptide signaling in specific neoplasia is crucial to designing tailored pharmacological treatments to counteract or dismantle the origin of the signaling circuitry causing cellular disruption. In some cases, particular ligands for these receptors may serve as concomitant treatments to aid other pharmacological or physical approaches to eradicate neoplasias.

As with all new fields of discovery, work on the biological role of G-quadruplexes (GQ) has produced a number of results that at first glance are quite baffling, sometimes because they do not fit well together, but mostly because they are different from commonly held expectations. Like other classes of flipons, those that form G-quadruplexes have a repeat sequence motif that enables the fold. The canonical DNA motif (G3N1-7)3G3, where N is any nucleotide and G is guanine, a feature that is under active selection in avian and mammalian genomes. The involvement of G-flipons in genome maintenance traces back to the invertebrate Caenorhabditis elegans and to ancient DNA repair pathways. A role for GQ in transcription is supported by the observation that yeast Rap1 protein binds both B-DNA, in a sequence-specific manner, and GQ, in a structure-specific manner, through the same helix. Other sequence-specific transcription factors (TF) also engage both conformations to actuate cellular transactions. Noncoding RNAs can also modulate GQ formation in a sequence-specific manner and engage the same cellular machinery as localized by TF, linking the ancient RNA world with the modern protein world. The coevolution of noncoding RNAs and sequence-specific proteins is supported by studies of early embryonic development, where the transient formation of G-quadruplexes coordinates the epigenetic specification of cell fate.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

From a differential geometric perspective, information geometry (IG) aims to characterise the structure of statistical geodesic models. The research done for this paper offers a novel method for modelling the information geometry of a queuing system. From the perspective of IG, the manifold of the transient M/M/infinity queue is described in this context. The Fisher Information matrix (FIM) as well as the inverse of (FIM), (IFIM) of transient M/M/infinity QM are devised. In addition to that, new results that uncovered the significant impact of stability of QM on the existence of (IFIM) are obtained. Moreover, the Geodesic equations of motion of the coordinates of the underlying transient are obtained. Also, it is revealed that stable QM is developable (i.e., has a zero Gaussian curvature) and has a non-zero Ricci Curvature Tensor (RCT). Novel stability dynamics of transient M/M/iInfinity queue manifold is revealed by discovering the mutual dual impact between the behaviour of (RCT) and the stability(instability) phases of M/M/Infinity QM. Furthermore, a new discovery that presents the significant impact of stability of queue manifold and the continuity of the unique representation between M/G/1 queue manifold and Ricci Curvature Tensor (RCT). The information matrix exponential (IME) is devised. Also, it is shown that stability of the devised (IME) enforces the instability of M/M/ Infinity QM. More interestingly, novel relativistic info-geometric queueing theoretic links are revealed .

Cucurbitacin phytonematicides consistently suppress population densities of plant nematodes, but have no effect against bacteria, fungi and insects. This study investigates the mechanism through which cucurbitacin phytonematicides consistently exert nematicidal properties on nematodes. Post 72-h exposure of second-stage juveniles (J2) of Meloidogyne enterolobii to geometric concentration of Nemafric-BL phytonematicide, J2 total proteins were measured using TruspecCHNS Macro. Total proteins versus phytonematicide exhibited a negative quadratic relation (R² = 0.97), with the minimum total proteins achieved at x = 4.9% phytonematicide. Beyond the minimum, total proteins increased gradually, depicting the existence of both isoprenylation (breakdown) and farnesylation (biosynthesis) of total proteins. In conclusion, cucurbitacins and nematode cuticles are both chemically structured, which provides the mechanism through which the test chemicals consistently decrease population densities of plant nematodes.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.

Systematic results of lattice dynamical calculation are reported for the novel (SiC)m/(GeC)n superlattices (SLs) by exploiting a modified-linear chain model (M-LCM) and a realistic rigid-ion- model (RIM). By employing the bond polarizability method in the framework of M-LCM, we have simulated Raman intensities for the graded (SiC)10-D/(Si0.5Ge0.5C)D/(GeC)10-D/(Si0.5Ge0.5C)D SLs by carefully integrating interfacial layer thickness D (≡ 0, 1, 2, 3 monolayers (MLs)). The variation of D has initiated considerable up (down) shifts of GeC-, (SiC)-like Raman peaks in the middle of the optical phonon frequency region. With D = 3 MLs, the maximum energy shift (by ~ 47 cm-1) of SiC-like modes has caused substantial changes in the Raman intensity profiles linked to the localization of atomic displacements at the interfacial transition regions. This effect can be considered as a vital tool for authenticating the interfacial structures in technologically important SLs. By using a RIM, we have reported SL phonon dispersions along the growth [001] as well as in the plane [100], [110] perpendicular to the growth. Our simulations of phonons in the acoustic mode region have not only confirmed the formation of minigaps at the zone center and zone edges but also provided evidence of anti-crossing and phonon confinement. Besides examining angular dependence of zone-center optical modes, we have also discussed phonon folding, confinement and anisotropic behavior in (SiC)m/(GeC)n SLs.

Ante-mortem bovine tuberculosis (bTB) tests for buffaloes include the single comparative intradermal tuberculin test (SCITT), interferon-gamma (IFN-γ) release assay (IGRA) and IFN-γ-inducible protein 10 release assay (IPRA). Although parallel test interpretation increases detection of Mycobacterium bovis-infected buffaloes, these algorithms may not be suitable for screening buffaloes in historically bTB-free herds. In this study, the specificities of three assays were determined using M. bovis unexposed herds, and a high specificity diagnostic algorithm developed. Serial test interpretation using the IGRA and IPRA showed significantly greater specificity (98.3%) than individual tests or parallel testing (73%). When the SCITT was added, the algorithm had a 100% specificity. Since the cytokine assays had imperfect specificity, potential cross-reactivity with nontuberculous mycobacteria (NTM) was investigated. No association was found between NTM presence (in oronasal swab cultures) and positive cytokine assay results. As a proof-of-principle, serial testing was applied to high-value buffaloes (n=153) in a historically bTB-free herd. Buffaloes positive on a single test (n=28) were regarded as test negative. Four buffaloes were positive on IGRA and IPRA, and M. bovis infection was confirmed following culling. These results demonstrate the value of using IGRA and IPRA in series to screen buffalo herds with no previous history of M. bovis infection.

We find solutions of a magnetically charged non-singular black hole in some modified theory of gravity coupled with nonlinear electrodynamics. The metric of a magnetized black hole is obtained which has one (an extreme horizon), two horizons, or no horizons (naked singularity). Corrections to the Reissner-Nordstrom solution are found as the radius approaches to infinity. The asymptotic of the Ricci and Kretschmann scalars are calculated showing the absence of singularities. We study the thermodynamics of black holes by calculating the Hawking temperature and the heat capacity. It is demonstrated that phase transitions take place and we show that black holes are thermodynamically stable at some range of parameters.

Background The use of antimicrobials to treat food animals leaves antimicrobial residues in foodstuffs. The World Health Organization (WHO) defines the acceptable daily intakes (ADIs) of these residues as the dose of these antimicrobials that is safe for an average human to consume on a daily basis. We hypothesized that the low dose of ciprofloxacin classified as safe by the WHO could select for ciprofloxacin resistant strains of Klebsiella pneumoniae in a Galleria mellonella model. Objectives We aimed to evaluate if the consumption of peri-ADI doses of ciprofloxacin could select for ciprofloxacin-resistant (Ser464Phe, GyrB, ciprofloxacin MIC of 4 µg/mL) compared to -susceptible (isogenic, ciprofloxacin MIC of 0,047 µg/mL) strains of K. pneumoniae in a Galleria mellonella model. Methods A model of K. pneumoniae infection in G. mellonella larvae was used for the experiment. The larvae were inoculated with K. pneumoniae followed by 10x ADI, 1x ADI, 1/10^th ADI, 1/100^th ADI, 1/1000^th ADI doses of ciprofloxacin. Isolation of K. pneumoniae colonies was then performed on selective agar plates with and without ciprofloxacin (1 µg/mL) plates. The proportion of colonies with ciprofloxacin resistance was then calculated for each group at 24 and 48 hours. Results A significant increase was seen in the proportion of resistance for the 1x ADI and 1/10^th ADI concentration on day 2 compared to the positive control. Conclusion We found that at 48 hours, there was an enrichment of K. pneumoniae colonies with ciprofloxacin resistance in the larvae receiving 1x ADI and 1/10^th ADI concentrations of ciprofloxacin. These results suggest that the ciprofloxacin MSC_select for K. pneumoniae in this model is 1/10^th of the acceptable daily concentration (ADI) dose of ciprofloxacin, which is equivalent to 0.239 ng/µl.

Neutropenia is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with esti-mated glomerular filtration rate (eGFR) 60–89 ml/min/1.73m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophy-laxis of FN. The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of cre-atinine assessment enabled the use of the newly recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR<60ml/min/1.73m2, while 15 (62.5%) eGFR< 90ml/min/1.73m2. The relative risk of neutro-penia in patients with impaired eGFR was over six times higher than in patients with eGFR>90 ml/min/1.73m2 (RR=6.08; 95%CI:1.45–27.29; p< 0.01). Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

Modified structure along latent tracks and track formation process have been investigated in poly(allyl diglycol carbonate), PADC, which is well recognized as a sensitive etched track detector. This knowledge is essential to develop novel detectors with improved track registration property. The track structures of protons and heavy ions (He, C, Ne, Ar, Fe, Kr and Xe) have been examined by means of FT-IR spectrometry, covering the stopping power region between 1.2 to 12,000 eV/nm. Through a set of experiments on low-LET radiations – such as gamma ray -, multi-step damage process by electron hits was confirmed in the radiation-sensitive parts of the PADC repeat-unit. From this result, we unveiled for the first-time the layered structure in tracks, in relation with the number of secondary electrons. We also proved that etch pit was formed when at least two repeat-units were destroyed along the track radial direction. To evaluate the number of secondary electrons around tracks, a series of numerical simulations were performed with Geant4-DNA. Therefore, we are proposing new physical criterions to describe the detection thresholds. Futhermore, we propose a present issue of the definition of detection threshold for semi-relativistic C ions. And as a possible chemical criterion, formation density of hydroxyl group is suggested to express the response of PADC.

For bounded unit interval, we propose a new Kumaraswamy generalized (G) family of distributions from a new generator which could be an alternate to the Kumaraswamy-G family proposed earlier by Cordeiro and de-Castro in 2011. This new generator can also be used to develop alternate G-classes such as beta-G, McDonald-G, Topp-Leone-G, Marshall-Olkin-G and Transmuted-G for bounded unit interval. Some mathematical properties of this new family are obtained and maximum likelihood method is used for estimating the family parameters. We investigate the properties of one special model called a new Kumaraswamy-Weibull (NKwW) distribution. Parameter estimation is dealt and maximum likelihood estimators are assessed through simulation study. Two real life data sets are analyzed to illustrate the importance and flexibility of this distribution. In fact, this model outperforms some generalized Weibull models such as the Kumaraswamy-Weibull, McDonald-Weibull, beta-Weibull, exponentiated-generalized Weibull, gamma-Weibull, odd log-logistic-Weibull, Marshall-Olkin-Weibull, transmuted-Weibull, exponentiated-Weibull and Weibull distributions when applied to these data sets. The bivariate extension of the family is proposed and the estimation of parameters is given. The usefulness of the bivariate NKwW model is illustrated empirically by means of a real-life data set.

Taste signaling is a complex process that is linked to obesity and its associated metabolic syndromes. The sweet taste is mediated through a heterodimeric G protein coupled receptor (GPRC) in a species-specific manner and at multi-tissue specific levels. The sweet receptor recognizes a large number of ligands with structural and functional diversities to modulate different amplitudes of downstream signaling pathway(s). The human sweet-taste receptor has been extremely difficult to study by biophysical methods due to inadequate methods for producing large homogeneous quantities of the taste-receptor protein and a lack of reliable in vitro assays to precisely measure productive ligand binding modes leading to activity upon their interactions with the receptor protein. We report a multimodal high throughput assays to monitor ligand binding, receptor stability and conformational changes to model the molecular interactions between ligand-receptor. We applied saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR) complemented by differential scanning calorimetry (DSC), circular dichroism (CD) spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize binding interactions. Our method using complementary NMR and biophysical analysis is advantageous to study the mechanism of ligand binding and signaling processes in other GPCRs.

In this study, a diverse collection of images of myxozoans from the genera Henneguya and Myxobolus was created, providing a practical dataset for application in computer vision. Four versions of the YOLOv5 network were tested, achieving an average precision of 97.9%, a recall of 96.7%, and an F1 score of 97%, demonstrating the effectiveness of MLens in the automatic detection of these parasites. These results indicate that machine learning has the potential to make micro-parasite detection more efficient and less reliant on manual work in parasitology. The beta version of the MLens shows strong performance, and future improvements may include fine-tuning the WebApp hyperparameters, expanding to other myxosporean genera, and refining the model to handle more complex optical microscopy scenarios. This work represents a significant ad-vancement, opening new possibilities for the application of machine learning in parasitology and substantially accelerating parasite detection.

Understanding the structural intricacies of RNA molecules is essential for deciphering numerous biological processes. Traditionally, scientists have relied on experimental methods to gain insights and draw conclusions. However, the recent advent of advanced computational techniques has significantly accelerated and refined the accuracy of research results in several areas. A particularly challenging aspect of RNA analysis is the prediction of its secondary structure, which is crucial for elucidating its functional role in biological systems. This paper deals with the prediction of pseudoknots in RNA, focusing on two types of pseudoknots: K-type and M-type pseudoknots. Pseudoknots are complex RNA formations in which nucleotides in a loop form base pairs with nucleotides outside the loop and thus contribute to essential biological functions. Accurate prediction of these structures is crucial for understanding RNA dynamics and interactions. Building on our previous work in which we developed a framework for the recognition of H- and L-type pseudoknots, an extended grammar-based framework tailored to the prediction of K- and M-type pseudoknots is proposed. This approach uses syntactic pattern recognition techniques and provides a systematic method to identify and characterize these complex RNA structures. Our framework uses context-free grammars (CFGs) to model RNA sequences and predict the occurrence of pseudoknots. By formulating specific grammatical rules for type K and type M pseudoknots, we enable efficient parsing of RNA sequences to recognize potential pseudoknot configurations. This method ensures an exhaustive exploration of possible pseudoknot structures within a reasonable time frame. In addition, the proposed method incorporates essential concepts of biology, such as base pairing optimization and free energy reduction, to improve the accuracy of pseudoknot prediction. These principles are crucial to ensure that the predicted structures are biologically plausible. By embedding these principles into our grammar-based framework, we aim to predict RNA conformations that are both theoretically sound and biologically relevant.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

A new method for the synthesis of azido-propargyloxy derivatives of 1,3,5-triazine has been developed. The antibacterial activity against E. coli bacteria of propargyloxy substituted 1,3,5-triazines - 2,4,6-trispropargyloxy-1,3,5-triazine, 2-azido-4,6-bispropargyloxy-1,3,5-triazine and 2,4-diazido-6-propargyloxy-1,3,5-triazine and their hyperbranched polymers. It has been shown that the presence of an azide group in the compound directly affects the antibacterial activity. The cytotoxicity of these compounds against the M-HeLa, FetMSC and Vero cell lines was studied. The IC50 value was determined for low molecular weight compounds. It has been shown that hyperbranched polymers without azide groups don’t exhibit pronounced cytotoxicity and can be used in biomedical applications.

The migration from MATLAB to Python (M-to-PY) has gained significant traction in recent computational research. While MATLAB has long served as a linchpin in myriad scientific endeavors, there's an emerging trend to rejuvenate these projects using Python's extensive AI tools and libraries. This study presents a semi-automated process for M-to-PY conversion, using a detailed case study of an image skeletonization project comprising fifteen MATLAB files and a 1404-image dataset. Skeletonization is foundational for ongoing 3D motion detection research using AI transformers, predominantly developed in Python. The utilization of ChatGPT-4, acting as an AI co-programmer, is pivotal in this conversion. By leveraging the public OpenAI API, we developed an M-to-PY converter prototype, evaluated its efficacy using test cases from the Bard bot, and subsequently employed the converted code in an AI application. The dual contributions encompass a well-tested M-to-PY converter and a Skeleton App capable of sketching and skeletonizing any given image, enriching the AI toolset. This study accentuates how AI resources, like ChatGPT-4, can simplify code transitions, opening doors for innovative AI implementations using primarily MATLAB-coded scientific research.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Acute and chronic bone infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), remains a major complication and therapeutic challenge. It is documented that local administration of vancomycin offers better results than the usual routes of administration (e.g. intravenous) when ischemic areas are present. In this work, we evaluate the antimicrobial efficacy against S. aureus and S. epidermidis and analyzed the potential cytotoxic effect of a novel hybrid 3D-printed scaffold based on poly(caprolactone) and chitosan loaded with different vancomycin concentrations (1, 5, 10 and 20%). For this purpose, vancomycin release was measured by means of HPLC, and the biological response of ah-BM-MSCs in the presence of the scaffolds was evaluated in terms of cytotoxicity (LDH activity), proliferation (AlamarBlueⓇ) and osteogenic differentiation (ALP activity, Alizarin Red staining). In addition, two cold plasma treatments were evaluated to improve the adhesion of hydrophobic polymers to hydrogels. The hybrid PCL/CS/Van scaffolds tested were found to be biocompatible, bioactive, and bactericide, as demonstrated by no cytotoxicity or functional alteration and by bacterial inhibition. Our results suggest that the scaffolds developed would be excellent candidates to be used in a wide range of biomedical fields such as drug delivery systems or tissue engineering applications.

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

Categorical data analysis of 2 x 2 contingency tables is extremely common, not least because they provide odds and risk ratio statistics in medical research. The χ2 test is most often used, although some researchers use the likelihood ratio test (LRT). Does it matter which test is used? This paper argues that the LRT rather than the χ2 test should be used when we are interested in testing whether two variables are independent, as is typically the case. In contrast, the χ2 test should be reserved for where the data appear to match too closely a particular hypothesis (e.g. the null hypothesis), as may occur in the investigation of data integrity. Finally, it is argued that the evidential approach provides a consistent and coherent way in which tests can be made for each of these situations.

In photolithography process, nanometer level precise, wavefront aberration models enable the machine to be able to meet the overlay (OVL) drift and critical dimension (CD) specifications. Software control algorithms take as input these models and correct any expected wavefront imperfections before reaching the wafer. In such way a near optimal image is exposed on the wafer surface. Optimizing the parameters of these models though, involves several time costly sensor measurements which reduce the throughput performance, in terms of exposed wafers per hour, of the machine. In that case, photolithography machines come across the trade-off between throughput and quality. Therefore one of the most common Optimal Experimental Design (OED) problems in photolithography machines (and not only) is how to choose the minimum amount of sensor measurements that will provide the maximum amount of information. Additionally, each sensor measurement corresponds to a point on the wafer surface and therefore we must measure uniformly around the wafer surface as well. In order to solve this problem, we propose a Sensor Marks Selection Algorithm which exploits Genetic Algorithms. The proposed solution first selects a pool of points that qualify as candidates to be selected in order to meet the uniformity constraint. Then, the point that provides the maximum amount of information, quantified by the Fisher based criteria of G, D and A-Optimality, is selected and added to the measurement scheme. This process though is considered "greedy", and for this reason Genetic Algorithms (GA) are exploited to further improve the solution. By repeating in parallel the "greedy" part several times we get an initial population that will be the input to our GA. This meta-heuristic approach outperforms the "greedy" approach significantly. The proposed solution is applied in a real life semiconductors industry use case and achieves interesting industry and academical results as well.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

By generalizing the notion of pointwise 1-type Gauss map, the generalized 1-type Gauss map has been recently introduced. Without any assumption, we classified all possible ruled surfaces with generalized 1-type Gauss map in a 3-dimensional Minkowski space. In particular, null scrolls do not have the proper generalized 1-type Gauss map. In fact, it is harmonic.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.

The rare abscopal effect during radiotherapy is thought to be caused by the release of immune-stimulated damage-associated molecular patterns, such as high mobility group box-1 protein (HMGB1), from cancer cells. Although external irradiation of cancer cells increases HMGB1 release, it is not clear if HMGB1 is released from cells after administering 131I-labeled m-iodobenzylguanidine (131I-MIBG) as an internal targeted radiotherapeutic agent. This study aimed to determine if HMGB1 is released from human-derived cancer and normal cells after administering 131I-MIBG. Methods: Extracellular lactate dehydrogenase (LDH) and HMGB1 released from H441 (human-derived lung adenocarcinoma cell line) and HaCaT (human keratinocyte cell line) 1 day after 2- and 10-Gy X-ray irradiation were measured. Accumulations of 131I-MIBG in SH-SY5Y (human-derived neuroblastoma cell line) and HaCaT were measured 60 min after administering 131I-MIBG (0.37, 1.85, 3.7 MBq/well). Extracellular LDH and HMGB1 released from SH-SY5Y and HaCaT 1 day after administering 131I-MIBG were also measured. Results: The extracellular LDH and HMGB1 released from H441 after 10-Gy X-ray irradiation were significantly increased. However, the extracellular LDH and HMGB1 released from HaCaT after 2-Gy and 10-Gy X-ray irradiation were not increased. After administering 1.85 MBq and 3.7 MBq 131I-MIBG, the extracellular LDH and HMGB1 released from SH-SY5Y were both significantly increased, but only the extracellular LDH released from HaCaT was significantly increased. Conclusions: HMGB1 was released from neuroblastomas but not from normal cells after 131I-MIBG administration, suggesting that a combination of 131I-MIBG and immunotherapy may be feasible.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

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

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In search for therapeutic alternatives to treat the cancer disease, a se-ries of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a-h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in EtOH, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evalu-ated for their binding interactions with two well-known anticancer targets, namely the epider-mal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. CD experi-ments suggested 5a as a stabilizer agent of the G-quadruplex from the KRAS oncogene promot-er. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hy-drazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.

Background: In the heart, aldosterone (Aldo) binds the mineralocorticoid receptor (MR) to exert damaging, adverse remodeling-promoting effects. We recently showed that G protein-coupled receptor (GPCR)-kinase (GRK)-5 blocks the cardiac MR by directly phosphorylating it, thereby repressing its transcriptional activity. MR antagonist (MRA) drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure. Non-steroidal MRAs, such as finerenone, may provide better cardio-protection against Aldo than classic, steroidal MRAs, like spironolactone and eplerenone. Herein, we sought to investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade. Methods: We used the cardiomyocyte cell line H9c2 and neonatal rat ventricular myocytes (NRVMs). Results: GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone. Unlike eplerenone, finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity, thus displaying inverse agonism. GRK5 is necessary for finerenone`s inverse agonism, since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity. Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels. Finally in NRVMs, GRK5 is necessary for the anti-apoptotic and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis and fibrosis. Conclusions: Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart. GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

Advanced composite materials have drawn significant interest in the last years as an alternative to traditional materials due to their higher performance. However, industry struggle to provide low-cost, higher occupational safety, lower footprint with composites, making them suitable for holistic analyses. Therefore, the material design becomes an essential element that can impact the competitiveness, particularly in terms of productivity, circularity, safety, sustainability, and quality of the value chain. The Material Design-for-eXcellence is a state-of-art methodology for material performance multi-dimensional assessment along its life cycle phases, either useful to support ma-terial selection for new products or also to new material design support optimizing resource effi-ciency. In this methodology, the material behaviour and its multiple characteristics assessment, and the manufacturing processes efficiency are evaluated. The framework considers the analogy of product design holistic approaches, as Lean Design-for-X, to organize and assess the mul-ti-dimensional performance for each “X” Material Property. In this work, it was possible to observe that the bio-based composites solutions could be a good sustainable alternative for several sectors. Every day researchers are creating more new materials, having a diversity of properties at different scales, Material Design-for-eXcellence must also in the near future consider other factors. Hence, additional studies are thus foreseen to explore and develop this new tool.

In present paper, spatial Minkowski Pythagorean Hodograph (MPH) curves are characterized with Rational Rotation Minimizing Frames (RRMFs). We define Euler-Rodrigues Frame (ERF) for MPH curves and by means of this concept, we reach the definition of MPH curves of type (n, m). Expressing the conditions provided by these curves in the form of Minkowski-Hopf map that we define, it is aimed to establish a connection with the Lorentz force which occurs during the process of Computer Numerical Control (CNC) type sinker Electronic Discharge Machines (EDMs). This approach is reinforced by split quaternion polynomials. Finally, we give conditons satisfied by MPH curves of low degree to be type (n, m) and construct illustrative examples.

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

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

Maternal and child nutrition has been a critical component of health, sustainable development, and progress in low- and middle-income countries (LMIC). While a decrement in maternal mortality is an important indicator, simply surviving pregnancy and childbirth does not imply better maternal health. One of the fundamental obligations of nations under international human rights law is to enable mothers and teenage girls to endure pregnancy and delivery as an aspect of their enjoyment of reproductive and sexual health and rights and live a dignified life. The aim of this study was to discover the correlation between the Maternal Observation and Motivation (MOM) program and m-Health support for maternal and newborn health. A Comparative study was done among 109 pregnant mothers (study group-94; control group-102 mothers) with not less than 20 weeks of gestation. Maternal outcomes such as Hb, weight gain and newborn results like birth weight and crown- heel length was obtained on the baseline, 28 and 36 weeks of gestation. Other secondary data collected were abortion, stillbirth, low birth weight, major congenital malformations, twin or triplet pregnancies, physical activity and maternal wellbeing. The MOM intervention included initial face to face education, three in-person visits and eight virtual health coaching by WhatsApp. The baseline data on Hb of the mothers show that 31(32.98%) vs 27(28.72%) of the study and control group had anaemia, which improved to 27.66% and 14.98% among study group mothers at 28 and 36 weeks of gestation (p<0.001). The weight gain (p< 0.001), level of physical activity (p< 0.001), and maternal wellbeing (p< 0.01) also had significant differences after the Intervention. Even after controlling for potentially confounding variables, the maternal food practices regression model revealed that birth weight was directly correlated with consumption of milk (p 0.001), fruits (p 0.01), and green vegetables (p 0.05).As per the physical activity and maternal wellbeing regression model, the birth weight and crown heel length were strongly related with the physical activity and maternal wellbeing of mothers at 36 weeks of gestation (p <0.05). Combining the MOM intervention with standard antenatal care is a safe and effective way to improve maternal welfare while upholding pregnant mothers' human rights.

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

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

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

G-protein-coupled receptors (GPCR) belong to a large family of molecules eliciting different responses to a variety of signaling molecules. These receptors participate in various physiologic pathways such as metabolism, growth, immune responses, inflammation, vision, taste, olfaction, neurotransmission and even and pathologic responses including chronic inflammatory and vascular diseases. Receptors contributing to the biological responses of renin-angiotensin system (RAS) are members of GPCR family. COVID-19-induced inflammatory cascade has been attributed to acute ACE2 downregulation and imbalance of proinflammatory ACE/AngII/AT1R and anti-inflammatory ACE2/angiotensin (1-7)/Mas axes in favor of the former. Some of the receptors contributing to activities of proteins in RAS including AT1R, AT2R and Mas receptors are members of GPCR family. It is notable that these receptors induce their effects both through G protein and β-arrestin pathway; the former exerts temporary and the latter more sustained effects. In addition to the imbalance of GPCR responses contributing to RAS activities, it has been suggested that SARS-CoV2 pathogenesis might be attributed to the activation of GPCRs or modulating G-proteins involved in adenosine-CFTR regulation system and epithelial Na channel function.This article includes a minireview about the physiological functions of GPCRs and their contribution to COVID-19.

Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host cell, the availability of host cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (Adenovirus and Adeno-associated vi-rus) and enveloped viruses (Retro/Lentivirus, Rabies, Vesicular stomatitis virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches such as rational design, directed evo-lution, in silico and machine learning-based methods for generating novel AAV variants with desired tropism, and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements, and discuss the challenges and future directions in engineering viral tropism.

The spin magnetic moments and spin g factors (g_s = -2) of electron, muon and tau are explained based on the electric charges (EC) and lepton charges (LC) in terms of the three-dimensional quantized space model. The spin g factors of electron, muon and tau are g_s = -2 which is the sum of the EC g factor (g_EC = -1) and the LC g factor (g_LC = -1). The spin g factor (g_s = -2) of the electron is predicted by the Dirac’s equation. The orbit g factors of electron, muon and tau are g_L = g_EC = -1 from the EC g factor (g_EC = -1) without the contribution of the LC g factor (g_LC = -1). The spin g factors of the elementary fermions are calculated from the equation of g_s = g_EC + g_LC + g_CC where g_EC = EC/|EC|, g_LC = LC/|LC| and g_CC = CC/|CC|. For example, the spin g factors of the neutrinos and dark matters are g_s = -1. The spin g factors of the u and d quarks are g_s = 0 and g_s = -2, respectively. The g factor problem of neutrinos with the non-zero LC charges are solved by the LC Coulomb force of F_c(LC) ≈0. It is, for the first time, proposed that the binary motion (fluctuations) of the m_EC and m_LC masses for the electron, muon and tau leptons make the anomalous g factor. This binary motion could be originated from the virtual particle processes including the photons. Also, the weak force (beta) decay is closely related to the binary motion of the m_EC and m_LC for the electron, muon and tau leptons.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, liver damage can be found and the imperative of employing natural antioxidants becomes apparent. In this study, we first showed that 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed group compared to controls (p&lt;0.05). Interestingly, P.lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces P.lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Furthermore, our investigations unveil P.lentiscus’s anti-proliferative efficacy against different human breast cancer cell lines. Thus, our findings underscore P.lentiscus‘s robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene induced mammary cancer initiation. We posit that P.lentiscus may serve as a prophylactic agent against breast cancer and liver oxidative damage instigated by this carcinogen.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

This investigation introduces an efficient method for assessing the reliability of semi-rigid steel frame connections in existing buildings, explicitly targeting the Top Angle and Seat Pad (TA-SP) semi-rigid connection commonly used in Australian cities' high-rise buildings. The moment capacity of these connections was examined through parameter power model testing, meticulously considering the bending, shear, and prying forces actions to determine the weakest elements in the connection system. A plastic hinge model was applied to ensure computational efficiency and accuracy in assessing the connections' ultimate strength. Comparatively, the finite element (F.E) method M−θ curves were introduced to scrutinise the nonlinear behaviour of the connection, providing validation for the predicted analytical approach. Further emphasis was placed on identifying the reliability of the weakest elements in the connection system, employing the First-Order and Second-Order Reliability Methods models to estimate their reliability index. The correlation between the model's failure probability and a percentile error was also explored, utilising Monte Carlo simulation reference for refined validation. Novel formulas and methodologies were introduced to compute the locked-chain-series system reliability, which accounts for the inherent material and geometric variability. The findings highlight the critical significance of the weakest element in determining the overall reliability of the existing TA-SP connection.

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

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

Antifungal properties are found in essential oil extracts of oregano (Origanum vulgare), rosemary (Salvia rosmarinus), clove (Syzygium aromaticum), thyme (Thymus), cinnamon (Cinnamomum verum), basil (Ocimum basilicum), therefore, the ability to prevent or inhibit the growth of Cladosporium spp., Lasiodiplodia spp., Colletotrichum spp., Fusarium spp., and Aspergillus spp. was studied. Cladosporium spp., Lasiodiplodia spp. Colletotrichum spp. Fusarium spp. y Aspergillus spp. fungi that were isolated and purified from the rot found on the banana peels (Musa paradisiaca). To perform a visual (macro-scopic) analysis of the Petri dish containing the pure fungus and a more detailed (microscopic) analysis of the fungal spores to classify it by genus, then, dilutions are prepared to inoculate onto amended PDA medium with chloramphenicol. Weekly re-inoculations are performed until iso-lated and purified fungi are obtained, which are then evaluated for in vitro inhibition and in vivo growth, according to the results of the in vivo analysis, the fungi were classified from higher to lower severity in: Colletotrichum spp., Lasiodiplodia spp., Aspergillus spp., Fusarium spp. and Cladosporium spp and based on fungal growth observations, it was found that basil and rosemary do not inhibit growth at the maximum concentration. Cinnamon inhibits at 400 ppm, rosemary halts fungal growth at 600 ppm, clove at 1000 ppm, and oregano at 800 ppm.

In this paper, the new optical wave solutions of truncated M-fractional perturbed Kundu-Eckhaus model with full non-linearity are obtained by utilizing the expa function technique and modified extended tanh expansion function technique. The solutions are in the form of dark soliton, bright soliton, singular solitons and other form of solutions. The gained solutions are helpful for the further development of concerned model. The obtained results have also been presented graphically in both two-dimensional and three-dimensional formats to discuss the dynamical features as well as the parametric dependence of the constructed solutions. The study offers a highly spectacular and acceptable techniques to combine various intriguing wave demonstrations for more sophisticated models of the modern day.

The Subtropical Front (STF) plays a key role in the ecology of Chilean jack mackerel Trachurus murphyi. Nonetheless, there are few remote sensing studies of the STF in the open Southeast Pacific Ocean, and almost all of them have been conducted by satellite oceanographers in Russia and Ukraine to support respective large-scale fisheries of jack mackerel in this region. We reviewed these studies that documented long-term seasonal and interannual variability of the STF from sea surface temperature (SST) and sea surface height (SSH) data. We also mapped the STF from satellite sea surface salinity (SSS) data of the SMOS mission (2012-2019). The Subtropical Front consists of two fronts -- North and South STF about 500 km apart -- that border the Subtropical Frontal Zone (STFZ) in-between. The STF is density-compensated, with spatially divergent manifestations in temperature and salinity. In the temperature field, the STF extends in the WNW to ESE direction in the Southeast Pacific. In the salinity field, the STFZ appears as a broad frontal zone, extending zonally between 30-35°S across the entire South Pacific. Three major types of satellite data – SST, SSH, and SSS – can be used to locate the STF. The SSH data is most advantageous with regard to the jack mackerel fisheries owing to the all-weather capability of satellite altimetry and the radical improvement of the spatial resolution of SSH data in the near future. Despite the dearth of dedicated in situ studies of the South Pacific STFZ, there is a broad consensus regarding the STFZ being the principal spawning and nursing ground of T. murphyi as well as a major migration corridor between Chile and New Zealand.

This research article provides an unconditional proof of an inequality proposed by \textit{Srinivasa Ramanujan} involving the Prime Counting Function $\pi(x)$, \begin{align*} (\pi(x))^{2}<\frac{ex}{\log x}\pi\left(\frac{x}{e}\right) \end{align*} for every real $x\geq \exp(547)$, using specific order estimates of the \textit{Mertens Function}, $M(x)$. The proof primarily hinges upon investigating the underlying relation between $M(x)$ and the \textit{Second Chebyshev Function}, $\psi(x)$, in addition to applying the meromorphic properties of the \textit{Riemann Zeta Function}, $\zeta(s)$ with an intention of deriving an improved approximation for $\pi(x)$.

We propose that quarks and gluon flux tubes emerge from networks of standing vacuum waves. Each unbound nucleon, in its ground state, may be electromagnetically modeled as massless quantized charge on two pairs of orbiting arcs. Each charge arc is associated with a superposition of radially-oriented vacuum fundamental harmonics. These quantum superpositions of radial waves are coupled to nucleon mass-energy. The charge arcs orbit on the two surfaces of a spindle torus with polar charge-exclusion zones. These ground-state models of unbound nucleons may be interpreted as pairs of virtual Möbius bands. The optimal triangular Möbius band may explain proton uniqueness. These unbound proton and neutron models are shown to be precisely connected via a parameter dependent on neutron mass and the sum of the up and down bare quark masses. Due to this precise connection, and the relatively high experimental precision of proton magnetic moment, neutron magnetic moment is calculated about two orders of magnitude more precisely than the most accurate experiments to date. This quantum network-based approach to modeling unbound low-energy nucleons calculates several other measurable parameters.

This study investigates the preparation of KNN-ZnO composites through optimized sintering conditions under both inert and oxygen atmospheres. Initial experiments employing inert hot pressing were hindered by the necessity for annealing, which resulted in cracks due to the differing thermal expansion coefficients of KNN and ZnO, rendering this method unsuitable for composite fabrication. Consequently, sintering under an oxygen atmosphere was adopted, yielding a uniform distribution of ZnO particles within the KNN matrix. The resultant microstructure demonstrated significant densification, enhanced homogeneity, and minimal porosity. Electrical performance evaluations revealed that while the incorporation of ZnO led to a slight reduction in the ferroelectric properties (d₃₃ and polarization) of the KNN matrix, it concurrently improved the electromechanical quality factor (Q_m) by 40%. However, the overall enhancements were less pronounced when compared to analogous BNT-BT systems, underscoring the necessity for further optimization of processing conditions to boost electromechanical efficiency and piezoelectric response in KNN-based ceramics.

It has been more than a century since Erlang published his paper in 1909. The classical queueing system for the M/D/c queue has been investigated by many authors. The key is to find the roots of an equation using explicit or numerical methods. We present an alternate form of explicit solution(s) of this/these root(s) using the Lambert-W function in this paper. In addition, the unsaturated probabilities of the number of customers in the system is derived explicitly in terms of this/these root(s). Finally, the mean number of customers in the system and the mean queueing delay are obtained from these probabilities. The exact queueing delay formula for the M/D/c queue is expressed in closed-form in terms of the root(s). Numerical results show that they are in excellent agreement with the numerical results published by Seelen, Tijms and Van Hoorn.

We investigate the shear quasinormal modes (QNMs) in the context of electron stars, focusing on the Lifshitz geometry and exploring the behavior in the small star limit. The study begins by analyzing the shear sector modes in the infrared (IR) Lifshitz limit, where the geometry approaches that of a pure Lifshitz space. We derive and solve the differential equations governing the shear modes, revealing the asymptotic behavior in terms of the Lifshitz exponent. In the special case of integer values of the exponent, we obtain analytic corrections to the solutions to extract hydrodynamical QNMs. We then explore the cases with a Lifshitz exponent equal to or greater than three, providing analytical corrections to the Lifshitz IR solutions. A special case with an exponent of two is also considered, leading to modified solutions. The study extends to finding hydrodynamical QNMs, emphasizing the role of the Lifshitz geometry. Further investigations involve the flux with real and complex frequencies, considering the off-shell Lagrangian and deriving conserved flux expressions. Our analysis focuses on the exterior of the star, modeled by the Reissner-Nordström-AdS geometry. The small star limit is examined, revealing interesting features in the behavior of fermionic excitations. In summary, we provide a detailed exploration of shear quasinormal modes in electron stars, shedding light on their behavior in Lifshitz geometry, small star limits, and the interplay between real and complex frequencies. Our findings contribute to our understanding of the dynamics of electron stars and their gravitational properties.

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

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

We investigate some information properties of consecutive k-out-of-n:G systems in light of fractional generalized cumulative residual entropy. We firstly derive a formula to compute fractional generalized cumulative residual entropy related to the system's lifetime and explore its preservation properties in terms of established stochastic orders. Additionally, we obtain useful bounds. To aid practical applications, we propose two non parametric estimators for the fractional generalized cumulative residual entropy in these systems. The efficiency and performance of these estimators are illustrated using simulated and real datasets.

Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.

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 (&gt;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.

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

Using assembly theory, we investigate the assembly pathways of fixed-length binary strings formed by joining the individual bits present in the assembly pool and the strings that entered the pool as a result of previous joining operations. We show that the string assembly index is bounded from below and above, and we conjecture about the form of the upper bound. We show that a string having the smallest assembly index can be assembled by an elegant trivial program of length equal to this index, if the length of the string is expressible as a product of Fibonacci numbers. We conjecture that there is no binary program that has a length shorter than the length of the string having the largest assembly index that could assemble this string. We conjecture that a black hole surface is defined by a balanced distinct string that satisfies the upper bound of a distinct string assembly index. The results confirm that four Planck areas provide a minimum information capacity that provides a minimum thermodynamic (Bekenstein-Hawking) entropy. Knowing that the problem of determining the assembly index is at least NP-complete, we conjecture that the problem of determining the assembly index of a given binary string is NP-complete, while the problem of creating the string so that it would have a predetermined maximum assembly index is NP-hard. Therefore, once the new information is assembled by a dissipative structure or by a human, increasing the information entropy according to the second law of infodynamics, it is subject to the second law of thermodynamics, and nature seeks to optimize its assembly pathway.

Immobilized metal affinity chromatography (IMAC) is a popular and valuable method for the affinity purification of polyhistidine-tagged recombinant proteins. However, it often shows practical limitations, which might require cumbersome optimizations, additional polishing, and enrichment steps. Here, we present functionalized corundum particles for the efficient, economical, and fast purification of recombinant proteins in a column-free format. The corundum surface is first derivatized with the amino silane APTES, then EDTA dianhydride, and subsequently loaded with nickel ions. The Kaiser test, well-known in solid-phase peptide synthesis, was used to monitor amino silanization and the reaction with EDTA dianhydride. In addition, ICP-MS was performed to quantify the metal-binding capacity. His-tagged protein A/G (PAG), mixed with bovine serum albumin (BSA), was used as a test system. The PAG binding capacity was around 3 mg protein per gram of corundum. Cytoplasm obtained from different E. coli strains was examined as an example of a complex matrix. The imidazole concentration was varied in the loading and washing buffers. As expected, higher imidazole concentrations during loading are usually beneficial when higher purities are desired. Even when higher sample volumes, such as one liter, were used, recombinant protein down to a concentration of 1 µg/mL could be isolated selectively. Comparing the corundum material with standard Ni-NTA agarose beads indicated higher purities of proteins isolated using corundum. His6-MBP-mSA2, a fusion protein consisting of monomeric streptavidin and maltose-binding protein in the cytoplasm of E. coli, was purified successfully. To show that this method is also suitable for mammalian cell culture supernatants, purification of the SARS-CoV-2-S-RBD His8 expressed in human Expi293F cells was performed. The material cost of the nickel-loaded corundum material (without regeneration) is estimated to be less than 30 cents for 1 gram of functionalized support or 10 cents per milligram of isolated protein. Another advantage of the novel system is the corundum particles' extremely high physical and chemical stability. The new material should be applicable in small laboratories and large-scale industrial applications. In summary, we could show that this new material is an efficient, robust, and cost-effective purification platform for the purification of His-tagged proteins, even in challenging, complex matrices and large sample volumes of low product concentration.

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

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

Here, using the theory of electrical modelling of the neutron and proton as a three-phase alternating current electrical generator, we will begin the path to demonstrate that the interactions of electromagnetic forces, weak force and strong force that are part of the standard model, can be described by a single electromagnetic force interaction, in other words: SU(3) x SU(2) --> U(1). We will also hypothesize two particles that would give rise to gravitons. It is the interactions of the quarks (U, Û, D, ^D) that dominate the dynamics; They are responsible for the origin of bosons (photons, gluons, W⁺, W⁻, Z⁰, gravitons and Higgs boson).

We are going to demonstrate the origin of dark energy, using a Hardwire similarity, a test that is carried out in terrestrial seismic with vibroseis in the search for gas and oil. In the first instance, we are going to analyse the mathematical function of Dirac's delta and compare it with the detonation of an explosive that is carried out in the search for gas and oil. Let's understand that in both cases a frequency spectrum is produced. We will also explain the meaning of a non-causal, zero-phase system; a causal system, of minimum phase, in order to determine the mathematical behaviour that corresponds to the Big Bang. Next, following the line of seismic, we will analyse a Hardwire Similarity to demonstrate that a vibroseis source, which generates a sweep, produces, in addition to the ideal sweep of fundamental frequencies, spurious harmonic frequencies and additional noise. We will show that this additional energy generated by the spurious harmonic frequencies and additional noise adds to the energy of the fundamental frequency sweep in analogy as dark energy does.

Here, using the theory of electrical-quantum modelling of the neutron and proton as a three-phase alternating current electrical generator, we will analyse the proton decay and the inverse neutron decay and determine the following subatomic particles, Dproton, Protoniu, Dneutron and Neutroniumd.

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

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

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

Here we will explain the correlation between the Kerr-Newman diagram and the theory: RLC electrical modelling of a black hole and the early universe. We will develop a black hole model that describes and explains both theories. In the development of our analysis, we will emphasize the following conditions: M² > Q² + a², M² = Q² + a² and M² < Q² + a² and we will also analyse the condition in which the mass of a black hole reaches its critical mass M = Mc. We will demonstrate that the interpretation of the Kerr-Newman diagram is equivalent to the interpretation of the theory: RLC electrical modelling of a black hole and the early universe. Finally, we will generalize the proposed model for a black hole and propose a black hole model formed by negative particles, neutroniumd, which after reaching critical conditions of mass, pressure, volume, temperature, density, etc.; decays into a positively charged black hole, protoniu. Let us remember that both models are formed by charged particles of matter (they do not contain antimatter), but their vector configuration means that the net charges of both proposed black holes are zero.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.