The One Health approach often reaches classrooms through Environmental Education (EE), which aims to guide society's response to current crises (environmental, health, economic, values). However, traditional EE teaching has focused on isolated ecological concepts and standardized solutions, ignoring the multidimensional nature of EE and failing to integrate the interdependence between environmental, animal, and human health. Moreover, teacher training often neglects didactic content knowledge, preventing students from acquiring the systemic vision needed to address eco-social problems and create sustainable solutions aligned with the Sustainable Development Goals (SDGs). This limits teachers’ ability to influence students' concerns and behaviours. In this context, this study aims to reflect on the current state of the issue and propose strategies informed by Science Education research to improve EE teaching, enabling the integration of One Health dimensions through effective didactics to achieve Transformative Environmental Education (TEE). For this purpose, we begin by addressing the limitations identified in recent systematic reviews, shifting the paradigm towards a symbiosis of EE and Science Education through scientific practices. We then present practical examples showcasing successful EE initiatives that foster a deeper understanding of socio-environmental issues, encourage innovative solutions, and nurture engaged citizens from early education onwards. These proposals can support classroom practice and ongoing teacher self-development. Pedagogical strategies include tackling issues that require systemic and critical thinking by developing scientific and epistemic practices while raising awareness of environmental justice. Thus, this study advocates for a new vision of EE, integrating the One Health approach, which could be applied to develop new educational programs, including teacher training. This would lead to a new learning evaluation model and help identify key determinants that trigger pro-environmental behaviours.

In recent years, the economies of many countries of the world are in a situation of intense shock processes. The current situation urgently needs to change the economic paradigm in the near future, which objectively requires the development of new conceptual models. The purpose of the paper is to develop the basic theoretical provisions of a new macroeconomics based on impulse and jump processes. Research problems are the following: 1) to describe the main types of impulse and jump functions with examples from economic theory and practice; 2) to perform an analytical representation of impulse and jump functions; 3) to select macroeconomic characteristics for the analysis of rapidly changing processes in the economy; 4) to create models and mechanisms for predicting impulsive and abrupt changes in macroeconomics. The approaches to the development of macroeconomic theory and its methods proposed in the article are not associated with the use of evolutionary continuous functions, for example, power functions, which is typical for many canonical macroeconomic models. These approaches do not include management decisions to achieve optimal values of given target functions, which is typical for recursive macroeconomic models of dynamic programming. This article is about formulating the foundations of macroeconomic theory and its methods, which, with some degree of accuracy, could give a forecast about the impending possibility of abrupt changes (impulse, shock, jump, stepwise and others) in the macroeconomic situation. The research methodology is statistical analysis, special methods for studying impulse and jump processes developed by the author. As a result of the study, the main provisions of the macroeconomic theory based on rapid impulse and spasmodic changes were formulated, approaches were outlined for constructing the tools of this theory, problems and tasks for further research were identified.

While various studies have explored the integration of sustainability in the construction sector of Tanzania, particularly in areas like energy efficiency and green building practices, there remains a significant gap in understanding the specific barriers to the selection of sustainable building materials (SBMs) in residential projects. This research intends to bridge this gap by identifying and analyzing the critical barriers that hinder the effective selection of SBMs in Tanzania's residential building projects. By employing qualitative interviews with experts from regulatory bodies, public developers, and academic researchers, the study provides a comprehensive overview of the barriers. To ensure the collection of relevant and insightful data, the study involved the selection of participants based on specific criteria tailored to each category of experts. To be able to analyze qualitatively the data collected, this study employed Atlas.ti and MS Excel software. The findings revealed six categories of critical barriers affecting the selection of SBMs for residential building projects in Tanzania were identified and analyzed: (1) Regulatory and Policy Barriers (2) Financial Barriers (3) Knowledge and Awareness Barriers (4) Technical Barriers (5) Market and Supply Chain Issues (6) Cultural and Social Barriers. Moreover, the lack of awareness and limited knowledge issue were as equally importantly voiced as regulatory and policy barriers to affect the effective selection of sustainable materials in Tanzania. This study underscores the need for targeted policy interventions that address the lack of awareness, financial difficulties, and the absence of comprehensive regulatory frameworks to promote the selection of sustainable materials.

The basis of the discrete-impulse energy supply (DIES) concept is the efficient use of supplied energy. The references describe in detail the general principles of DIES, examine the energy and thermodynamic aspects and the main mechanisms of intensification that can be initiated on the basis of this principle. DIES mechanisms conveniently can be divided into hard and soft ones. The former should be used to stimulate hydromechanical processes, and the latter to accelerate the processes of phase heat and mass transfer, or for the purpose of intensive mixing of multicomponent media. The authors have studied the possibility of using DIES to intensify the hydromechanical processes, in particular emulsification of milk fat (homogenization of milk, preparation of spreads), processing of cream cheese masses. Objects of research were whole non-homogenized milk, fat emulsions, cream cheese mass. In order to evaluate the efficiency of milk homogenization the homogenization coefficient change was studied, which was determined by centrifugation method as the most affordable and accurate one. Emulsions were evaluated according to the degree of destabilization, resistance and dispersion of the fat phase. The rheological characteristics of cheese masses were evaluated by the effective viscosity change.

Resonance inductive coupling is widely used for wireless power transfer (WPT) in medical applications. In this paper, we analyze the LCL-compensated WPT structure and propose a novel constant voltage transmission system based on gain estimation, without any extra feedback from the receiver. The system is capable for implant neural stimulation where the load impedance and the coupling coefficient are both variable. Compared to existing methods for constant voltage transmission, our approach offers advantages in compact size and the compatibility with the industrial, scientific and medical (ISM) band. We validate the load-independent resonant characteristic and the feasibility of constant voltage transmission using an experimental prototype working at 6.78MHz. Finally, we discuss the structure of the implant stimulator and methods of applying the proposed WPT system.

Protons are gaining increasing attention as neurotransmitters due to their extraordinary abilities to rapidly transfer electrical charge, mobilize cellular calcium and modulate ion channels. How all this is possible is currently the subject of in-depth studies and discussions concerning not only neurophysiology, but also biological materials for artificial intelligence. In this short review, some biochemical mechanisms are described by which protons, in combination with calcium, can initiate firing in sensory neurons and transmit impulse across synapses. Furthermore, mechanisms are put forward concerning how three neurotransmitters, glutamate, gamma-aminobutyric acid and acetylcholine, are able to generate protons. The results of the numerous experimental works taken into consideration indicate that protons can play a fundamental role both in the generation and in the transmission of the nerve impulse.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

The dielectric constant (ε) reflects the ability of a material to align and orient electrical dipoles within its structure in response to an externally applied electric field; the greater the polarizability of molecules, the greater the value of dielectric constant. In this study a data set of 86 polymers was investigated to develop a structure-property quantitative relations (QSPR) model to predict the dielectric constant in polymers. An initial set of 1273 descriptors was used to select a best set of descriptors and to construct two machine learning models with Gradient Boosting Regressor (GB_A and GB_B). The best performing model (GB_A) with 8 descriptors, exhibited a performance of (R2train) = 0.938 and (R2test) = 0.802. The models were internally validated by 5 folds cross-validation, demonstrating robustness. Additionally, using the Accumulative Local Effect (ALE) technique, we analyzed the relationship between the 8 descriptors involved and the impact of these descriptors to dielectric constant of polymers.

Camera malfunctions or loss of storage elements in imaging devices may lead to loss of important image information or random impulse noise interference. Low rank is one of the important prior information in image optimization processing. This paper uses different low-rank constraint models of the image matrices to recover the impulse interference satellite images. Firstly, an overview of image inpainting models based on nuclear norm, truncated nuclear norm, weighted nuclear norm, and matrix-factorization-based F-norm is presented, and corresponding optimiza-tion iterative algorithms are provided. Then, we conducted experiments under three types of pulse interference and provided visual and numerical results. Finally, it is concluded that the WSVT_ADMM method based on the weighted nuclear norm can obtain the best image inpainting results; The UV_ADMM method based on F norm of matrix factorization has the least computa-tion time and can be used for large-scale low-rank matrix computation; The WSVT_ADMM method based on weighted nuclear norm and the TSVT_ ADMM method based on truncated nuclear norms can significantly improve the repair effect compared to the nuclear norm-based methods such as SVT, SVP, and n_ADMM.

Computational Fluid Dynamics (CFD) simulations, based on Reynolds Averaged Navier Stokes (RANS) models, are a useful tool for a wide range of coastal and offshore applications, providing a high fidelity representation of the underlying hydrodynamic processes. Generating input waves in the CFD simulation is performed by a numerical wavemaker (NWM), with a variety of different NWM methods existing for this task. While NWMs, based on impulse source methods, have been widely applied for wave generation in depth averaged, shallow water models, they have not seen the same level of adoption in the more general RANS based CFD simulations, due to difficulties in relating the required impulse source function to the resulting free surface elevation for non-shallow water cases. This paper presents an implementation of an impulse source wavemaker, which is able to self-calibrate the impulse source function to produce a desired wave series in deep or shallow water at a specific point in time and space. Example applications are presented, for a numerical wave tank (NWT), based on the opensource CFD software OpenFOAM, for wave packets in deep and shallow water, highlighting the correct calibration of phase and amplitude. Also, the suitability for cases requiring very low reflection from NWT boundaries is demonstrated. Possible issues in the use of the method are discussed and guidance for good application is given.

Induction heating is a fast, reproducible, and efficient heating method used in various manufacturing processes. However, there is no established additive manufacturing (AM) process based on induction heating using wire as feedstock. This study investigates a novel approach to AM based on inductive heating, where a steel wire is melted and droplets are detached periodically using a two-winding induction coil. The process parameters and energy input into the droplets are characterized. The induction generator exhibits sluggish response to the excitation voltage, resulting in a lag in the coil current. The process is captured using a high-speed camera, revealing regular droplet formation and uniform size and shape when operated within an appropriate process window. Larger drops and increased spatter formation occur outside this window. The proposed method allows for the production of droplets with almost spherical shapes. Further analysis and characterization of droplet formation and energy input provide insights into process optimization and overall efficiency.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

In this paper, by using the variational method, a sufficient condition for the unique existence of the stationary solution of the reaction-diffusion ecosystem is obtained, which directly leads to the global asymptotic stability of the unique equilibrium point. Moreover, delayed feedback ecosystem with reaction-diffusion item is considered, and utilizing impulse control results in the globally exponential stability criterion of the delayed ecosystem. It is worth mentioning that the Neumann zero-boundary value that the infected and the susceptible people or animals should be controlled in the epidemic prevention area and not allowed to cross the border, which is a good simulation of the actual situation of epidemic prevention. And numerical examples illuminate the effectiveness of impulse control, which has a certain enlightening effect on the actual epidemic prevention work . That is, in the face of the epidemic situation, taking a certain frequency of positive and effective epidemic prevention measures is conducive to the stability and control of the epidemic situation. Particularly, the newly-obtained theorems quantifies this feasible step. Besides, utilizing Laplacian semigroup derives the $p$th moment stability criterion for the impulsive ecosystem.

Time recordings of impulse-type oscillation responses are short and highly transient. These characteristics may complicate the usage of classical spectral signal processing techniques for a) describing the dynamics and b) deriving discriminative features from the data. However, common model identification and validation techniques mostly rely on steady-state recordings, characteristic spectral properties and non-transient behavior. In this work, a recent method, which allows reconstructing differential equations from time series data, is extended for higher degrees of automation. With special focus on short and strongly damped oscillations, an optimization procedure is proposed that fine-tunes the reconstructed dynamical models with respect to model simplicity and error reduction. This framework is analyzed with particular focus on the amount of information available to the reconstruction, noise contamination and non-linearities contained in the time series input. Using the example of a mechanical oscillator, we illustrate how the optimized reconstruction method can be used to identify a suitable model and to extract features from uni-variate and multivariate time series recordings in an engineering-compliant environment. Moreover, the determined minimal models allow for identifying the qualitative nature of the underlying dynamical systems as well as testing for the degree and strength of non-linearity. The reconstructed differential equations would then be potentially available for classical numerical studies, such as bifurcation analysis. These results represent a physically interpretable enhancement of data-driven modeling approaches in structural dynamics.

Two-dimensional periodic Stokes flow of viscous incompressible fluid in a rectangular cavity with constant velocities applied to the top and bottom walls is considered. The study of chaotic advection regimes is reduced to the sequential solving of two problems. To solve the first problem, the analytical method of superposition, that allows to obtain any desired accuracy of the velocity field, is used. To solve the second problem, which is associated with obtaining the trajectories of individual fluid particles, numerical calculations of the Cauchy problem were performed. An analysis of the boundary conditions accuracy was performed based on the control of local integration. The advection of the selected volume of fluid in the rectangular cavity under the periodic motion of walls for a finite period time based on piecewise spline cubic interpolation is modelled. The obtained numerical results agree with well-known experimental data.

Planck's constant plays an important role in quantum mechanics but has little physical meaning apart from its contribution to the formulas. Evaluating each of the constant's unit dimensions gives a more granular account of the physical phenomena described by the equations. These formulas show how classical and quantum mechanical equations are related, and they give consistent descriptions of phenomena like momentum and energy in classical and quantum systems.

Background and objectives: sickle cell disease is the most common hemoglobinopathy in the world. It is considered to be a real public health problem. Sickle cell patients are subjected to several factors causing inflammation such as iron metabolism. The study aimed to look for inflammation in children with sickle cell disease in Cameroon, identify the factors associated with inflammation, and raise the consequences for the patient including the iron profile and the profile of the hemogram. Materials and methods: We conducted an analytical cross-sectional study for 03 months. The sickle cell disease patients coming and/or followed at the Hematology Department of the Regional Hospital of Bafoussam and the Central Hospital of Yaoundé have been recruited. The exploration of inflammation was made by determining CRP, IL6, and ferritin concentrations. The hematological parameters and iron profile were evaluated using standard methods. Statistical analysis of the data was performed; Univariate and multivariate logistic regression analyses allowed to identification of factors associated with inflammation in patients, using the statistical tool R version 4.1.1.. The proportions were compared with the chi-square test when the expected numbers were greater than 5 and the Fisher test when not. Results: The frequency of inflammation in the population was 42.3%. Hyperferritinemia was significantly greater (p<0.001) in patients with inflammation compared to the non-inflammatory patients (96.8% and 76.7% respectively). Patients with inflammation showed a significant elevation of iron parameters (p<0.05). In addition, ferritin and IL6 elevation were associated with inflammation during sickle cell disease respectively (Or = 4.96; 95% CI [1.15-36.42]; p=0.056) and (Or =6.23; 95% CI [1.43-45.96]; p=0.030). Conclusions: The elevated iron in plasma is an effect of inflammation in sickle cell patients. Hence the need of controlling inflammation and iron in the latter is necessary.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

This paper presents a control algorithm for soft-switching series LC converters. The conventional voltage-to-voltage controller is split into a master and a slave controller. The master controller implements constant-current-constant-voltage (CCCV) control, required for demanding applications, i.e. lithium battery charging or laboratory power supplies. It defines the set-current for the open-loop current slave controller, which generates the PWM parameters. The power supply achieves fast large-signal responses, e.g. from 5 V to 24 V, where 95% of the target value is reached in less than 400 µs. The design is evaluated extensively in simulation and on a prototype. A consensus between simulation and measurement is achieved.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGen database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined by Mendelian randomization. 253 genes that exerted trans-regulatory impacts on 1,439 genes were identified. Majority of the identified gene-pairs aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. Genes with higher gene expression heritabilities displayed broader regulatory impact in the network. The network displayed the scale-free topology, this provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and higher expression of HHEX is associated with lower triglycerides and risk of type 2 diabetes. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The identified network displayed scale-free topology indicating the hub genes of a tissue-specific network could be targeted to prevent disease outcomes.

(1) Background: Malaria remains a global public health problem. Unfortunately, the resistance of malaria vectors to insecticides commonly used threatens disease control and elimination efforts. Molecular mechanisms helping some malaria vectors to now survive to greater doses of insecticides remains poorly understood. Here, we elucidated the pattern of resistance escalation in the main malaria vector Anopheles gambiae in a pesticide-driven agricultural hotspot in Cameroon and its impact on vector control tools; (2) Methods: Larval stages and indoor blood-fed females (F0) were collected in Mangoum in May and November and forced to lay eggs; the emerging mosquitoes were used for WHO tube, synergist and cone tests. Molecular identification was done using SINE PCR whereas TaqMan-based PCR was used for genotyping of L1014F/S and N1575Y kdr and the G119S-ACE1 resistance markers. Transcription profile of candidate resistance genes was performed using qRT-PCR methods. Characterization of the breeding water and soil from Mangoum was also performed using HPLC technique; (3) Results: An. gambiae s.s. was the only species in Mangoum with 4.10 % infection with Plasmodium. These mosquitoes were resistant to all the four classes of insecticides with mortality rates &lt;7% for pyrethroids and DDT and &lt;54% for carbamates and organophophates. This population also exhibited high resistance intensity to pyrethroids (permethrin, alpha-cypermethrin and deltamethrin) after exposure to 5X and 10X discriminating doses and Synergist assays with PBO revealed only a partial recovery of susceptibility to permethrin, alpha-cypermethrin and deltamethrin. Only PBO-based nets (Olyset plus and permaNet 3.0) and Royal Guard showed an optimal efficacy. A high amount of alpha-cypermethrin was detected in breeding sites (5.16 fold LOD) suggesting ongoing selection from agricultural pesticides. The 1014F-kdr allele was fixed (100%) whereas the 1575Y-kdr (37.5%) and the 119S Ace-1R (51.1%) are moderately present. Elevated expression of P450s respectively in permethrin and deltamethrin resistant mosquitoes [CYP6M2 (10 and 34-fold), CYP6Z1(17 and 29-fold), CYP6Z2 (13 and 65-fold), CYP9K1 (13 and 87-fold)] supports their role in the observed resistance besides other mechanisms including chemosensory genes as SAP1 (28 and 13-fold), SAP2 (5 and 5-fold),SAP3 (24 and 8-fold) and cuticular genes as CYP4G16 (6 and 8-fold) and CYP4G17 (5 and 27-fold). However, these candidate genes were not associated with resistance escalation as expression level did not differ significantly between 1x, 5x and 10x surviving mosquitoes. (4) Conclusions: Intensive and multiple resistance is being selected in malaria vectors from pesticide-based agricultural hotspot of Cameroon leading to loss of efficacy of pyrethroid-only nets. Further studies are needed to decipher the molecular basis underlying such resistance escalation to better assess its impact on control interventions.

In modern physics, it is assumed that the Planck length is a derived constant from Newton's gravitational constant, the Planck constant and the speed of light, $l_p=\sqrt{\frac{G\hbar}{c^3}}$. This was first discovered by Max Planck in 1899. We suggest a way to find the Planck length independent of any knowledge of Newton's gravitational constant or the Planck constant, but still dependent on the speed of light (directly or indirectly).

The main purpose of the study was to study the effects of a specific rowing ergometer training program on the athletic performance of young adolescents (n=56; 11.73 ± 1.4 years old) com-pared to a workout based on general strength training. Eight-week training program was im-plemented, with four sessions per week and two-hours per session. Sample was divided in two groups: a control group (CG) that performed circuit training with exercises aimed at building general strength and an experimental group (EG) who focused on specifically training on a rowing ergometer (rowing machine). The data obtained in a rowing meter test over the compe-tition distance were analyzed to obtain the average power attained (W) at the beginning of the training, at the middle (4 weeks), at the end of the training (8 weeks) and one year after the ex-perimentation. The results show that, although both forms of training improve the average W obtained in both categories, the EG subjects (+29.94W) obtained better averages in all phases of the study compared to the CG (+5.88W). Furthermore, this increase was greater in male rowers (+ 34.06W) than in female rowers (+24.54W). These results reveal that a specific rower rowing ergometer training program has a significant effect than a general strength program and these effects can even be observed a year after the intervention.

Despite saltmarshes being considered as nature-based solutions (NbS) towards climate change mitigation, India’s saltmarsh ecosystems are least studied. This study quantifies the seasonal variation in carbon stocks mono-specific saltmarsh species (Porteresia coarctata) and its potential to play an important role in India’s climate change mitigation plans. Seasonal (pre-and post-monsoon) sampling of P. coarctata surface water, biomass and 30 cm sediment core was collected across four locations on the east coast of India to quantify sediment dry bulk density (DBD), organic matter (OM%), organic carbon (Corg%), Corg stocks of sediment and biomass, total carbon (C%) and nitrogen (N%) and stable isotopes of δ13C and δ15N. In general, the sediment DBD, OM and Corg of P. coarctata meadows was higher in post-monsoon and was influenced by salinity and pH changes. Isotope (δ¹³C) modelling of various sediment C sources suggested, particulate organic matter (POM) contribution was highest (0.04-0.79%) followed by P. coarctata (0.01–052%) and other macrophytes across our study locations. The seasonal variation of δ¹³C showed increased contribution of marine derived particulate and dissolved organic matter into P. coarctata meadows in post-monsoon season. Heavier δ¹⁵N values were observed in post-monsoon season suggesting anthropogenic input, that was utilized by P. coarctata to increase its above and below-ground biomass and shoot density. The combined ecosystem (30 cm sediment + biomass) Corg stocks of P. coarctata was 1.7-fold higher in post-monsoon (4021.20± 917 Mg C) compared to pre-monsoon (2297.36 ±647 Mg C) season among the four locations with a sediment Corg contribution >70%. Based on the International Panel for Climate Change Tier II assessment the P. coarctata meadows (443 ha) can help in avoiding the pre and post-monsoon emissions of 8431.34 and 14757.84 Mg CO₂ respectively. The combined price of the total CO₂ equivalent stored in P. coarctata meadows in pre- and post-monsoon is US$ 14.50 and US$ 25.38 million respectively. Further studies quantifying the NbS potential of P. coarctata mono-specific and mixed meadows of India’s coast is needed along with integration of saltmarsh ecosystems into India’s National Action Plan on Climate Change.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

The global increase in population has placed significant pressure on food security, leading to the emergence of aquaculture as a vital source of aquatic foods. However, rising costs and the limited availability of fishmeal in aquafeeds have spurred the search for alternative protein sources. While plant-based ingredients have been integrated into commercial aquafeeds, they come with challenges, including low protein content, palatability issues, and the presence of antinutritional factors. In this context, fish silage, derived from fish waste and discarded fish, stands out as a promising alternative technology due to its cost-effectiveness and sustainability attributes. The production of fish silage involves the addition of organic/inorganic acids or lactic acid bacteria to homogenized fish waste. This process yields a valuable mixture rich in peptides, free amino acids, and partially hydrolyzed proteins, offering significant nutritional benefits for animal diets. Beyond its nutritional advantages, fish silage contributes to environmental sustainability by reducing the impact of waste disposal and enhancing the value of fish waste. The objective of this review is to promote sustainable practices in the aquaculture industry in response to the increasing demand for high-quality feed nutrients. To achieve this, it includes an analysis of research results related to silage technology, an appraisal of the advantages and disadvantages of using fish silage as a feed additive, and a focus on emerging trends in this field.

Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is believed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. After reviewing the available data on epidemiology and evolution of respiratory viruses, this study examines the effect of varying vaccination rates across different age groups during the 2019/2020 influenza season in Saudi Arabia. Utilizing an age-structured SEIR (Susceptible–Exposed–Infectious–Recovered) model, it develops customized vaccination policies by considering age-specific incidence rates. This pioneering research segments the population into five age groups—infants and school-aged children, junior and older youth, young adults and adults, middle-aged, and seniors—across five regional areas in Saudi Arabis: Eastern, Central, Northern, Western, and Southern. A contact matrix, compiled from multiple sources, is used to delineate the dynamics of influenza transmission. The study undertakes a thorough comparison of three distinct vaccination scenarios: no vaccination, national vaccination, and optimized vaccine allocation policy, under various potential pandemic situations. It examines their impact on vaccination campaigns in terms of the total number of infections, mortality, and morbidity rates. The results emphasize the crucial impact of population demographics on disease transmission and vaccine distribution. According to the findings, the optimized vaccination scenario proved to be the most effective strategy in all scenarios.

With reference to our earlier published views on large nuclear gravitational constant , nuclear elementary charge and strong coupling constant , in this paper, we present simple relations for nuclear stability range, binding energy of isotopes and magic proton numbers.

We generalize the idea of quantum clock time to quantum spacetime reference frame via physical realization of a reference system by quantum rulers and clocks. Omitting the internal degrees of freedom (such as spins) of the physical rulers and clocks, only considering their metric properties, the spacetime reference frame is described by a bosonic non-linear sigma model (NLSM). We study the quantum behavior of the system under approximations, and obtain (1) a cosmological constant valued (2/π)ρ_c0 (ρ_c0 the critical density at near current epoch) which is very close to the observations; (2) an effective Einstein-Hilbert term; (3) the ratio of variance to mean-squared of spacetime interval tends to a universal constant 2/π in the infrared region. This effect is testable by observing a linear dependence between the inherent quantum variance and mean-squared of the redshifts from cosmic distant spectral lines. The proportionality is expected to be the observed percentage of the dark energy. The equivalence principle is also generalized to the quantum level.

In 2018, Iran witnessed approximately 21,000 fatalities resulting from road accidents, ranking it as the fifth leading cause of death across all age groups. These incidents carry substantial economic and social burden for the nation, claiming more than 5% of its GDP. Human behavior emerges as a significant contributing factor to high-risk driving offenses. It has been proposed that by influencing general deterrence, a rigorous defense can be established against such violations. Various theories posit that by reinforcing or diminishing influential factors, general deterrence perception can be molded, presenting a potential avenue for an effective deterrent against traffic infractions. This study examines deterrence perceptions prevailing among the public in Iran regarding the enforcement of traffic laws. Employing Structural Equation Modeling (SEM), we delve into the intricate relationships between variables, allowing for a comprehensive exploration of the factors influencing general deterrence. The study draws on the data derived from a survey comprising 548 questionnaires for modeling purposes. An innovative concept, private sector enforcement, is introduced and incorporated into the questioning and modeling process. The findings reveal that socioeconomic status (p-value&lt;0.01), police enforcement (p-value&lt;0.05), private sector enforcement (p-value&lt;0.05), specific deterrence (p-value&lt;0.01), and the use of technology (p-value&lt;0.01) have direct and indirect impacts on the general deterrence perception of drivers.

Recent observations of the dark energy density have demonstrated the fine-tuning problem, and the challenges faced by theoretical modeling. In this study, we apply the self-similar symmetry (SSS) model, describing the hierarchical structure of the universe based on the Dirac large numbers hypothesis, to Einstein's cosmological term. We introduce a new similarity dimension, D_B, in the SSS model. Using the D_B SSS model, the cosmological constant Λ is simply expressed as a function of the cosmic microwave background (CMB) temperature. The result shows that both the gravitational constant G and Λ are coupled with the CMB temperature, which simplifies the solution of Einstein's field equations for the variable Λ-G model.

The stage of a super-early scale-invariant Universe is considered on the basis of the Poincaré–Weyl gauge theory of gravity in a Cartan–Weyl space-time. An approximate solution has been found that demonstrates an inflationary behavior of the scale factor and, at the same time, a sharp exponential decrease in the effective cosmological constant from a huge value at the beginning of the Big Bang to an extremely small (but not zero) value in the modern era, which solves the well-known “cosmological constant problem”.

CO2 emission activity of xylotrophic fungi response to an increase in temperature in the range of 10-30 °C on the example of pure dikaryotic cultures of Fomes fomentarius s. str., F. inzengae, Fomitopsis betulina, F. pinicola, Phellinus igniarius was analyzed. Emission activity was assessed by the difference in CO2 concentration in 0.5-liter exposure chambers with Petri dishes with mycelium growing on agar at the beginning of exposure and an hour later using a Gasmet DX-4030 FTIR spectrometer (Gasmet Technologies Oy, Finland), error measurements ±50 ppm. Specific (μg CO2/cm2/h) and total (μg CO2/h) emission activity and its relationship with temperature and size (area) of the mycelium were assessed. It has been shown that in the range of 10-30 °C, the specific and total CO2 emission activity of the mycelium is closely and positively related to temperature. Specific emission, which is an indicator of the respiratory activity of the mycelium, does not depend on its size; its only driver is temperature, the relationship with which is linear: an increase in temperature by 10 °C causes an increase in the specific emission activity of the mycelium by 1.7 times. The total CO2 emission activity, which is an indicator of the total amount of CO2 emitted, is directly proportional to the specific emission activity and the size of the mycelium. In the range of 10-30 °C, an increase in temperature causes an almost equal increase in both the specific emission activity of the mycelium (Q10 1.7) and its growth (Q10 1.5) and causes an exponential increase in the total emission of CO2. This must be taken into account when predicting CO2 emissions from woody debris under climate change, as it could potentially contribute to accelerating climate change.

Steel damper columns (SDCs) are energy-dissipating members that are suitable for reinforced concrete (RC) buildings and are often used for multistory housing. The evaluation of the peak deformation and hysteretic dissipated energy of such building structures is essential for the rational seismic design of RC buildings with SDCs. In a previous study, the authors proposed an energy-based prediction procedure for the peak and cumulative response of an RC frame building with SDCs. In this procedure, the accuracy of the equivalent velocity of the maximum momentary input energy (V_ΔE1^*)–peak equivalent displacement (D₁^*_max) relationship is essential for high quality predictions. In this article, the V_ΔE1^*–D₁^*_max relationships of RC moment-resisting frames with and without SDCs are invested using a critical pseudo-double impulse (PDI) analysis based on a study by Takewaki and coauthors. The results show that the V_ΔE1^*–D₁^*_max relationship obtained from the critical PDI analysis agrees well with that calculated from the equations proposed in the previous study.

Here we will model the curvature and contraction of space-time using as a basis the equation of state of an ideal gas and the Hawking´s equation for the temperature of a black hole. We will use this mathematical model to hypothesize that the Boltzmann´s constant depends on the state of matter, that is, there is a known Boltzmann´s constant for flat space-time and an effective Boltzmann´s constant for curved space-time. This model will allow us to quantify the structure of space-time and will serve as a basis to determine the origin of gravity and the origin of elementary particles. Using the Shannon-Boltzmann-Gibbs entropy relation, we will demonstrate that information is not lost and depends on the state of matter, the information is encoded and depends on the effective Boltzmann´s constant.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

We propose a promising model of discrete spacetime based on nonassociative geometry and complex networks. Our approach treats space as a simplicial 3-complex (or complex network), built from "atoms" of spacetime and entangled states forming n-dimensional simplices (n=1,2,3). At large scales, a highly connected network is a coarse, discrete representation of a smooth spacetime. We show that for high temperatures, the network describes disconnected discrete space. At the Planck temperature, the system experiences the phase transition, and for low temperatures, the space becomes a triangulated discrete space. We show that the cosmological constant depends on the universe’s topology. The "foamy" structure, analogous to Wheeler’s "spacetime foam," significantly contributes to the effective cosmological constant, which is determined by the Euler characteristic of the universe.

Although the presence of dark energy is well established from various observations, its true nature is still not well understood. The cosmological constant term seems to be the preferred candidate. In earlier work we had a constant cosmological constant term to limit the sizes of large-scale structures at lower redshifts. In this work, we extend this to large scale structures at higher redshifts. Here we invoke a time varying cosmological constant to set constraints on sizes of galaxies at high redshifts and see that they are consistent with their observed sizes. The time-varying cosmological constant also provides a possible solution to the puzzle of structure formation of large disk galaxies (like the Wolfe disk) observed at very early stages of the Universe. Future observations of galaxies at even higher redshifts could support our approach.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

The cosmological constant problem is examined by taking an Einstein--scalar with a Higgs-type potential and scrutinizing the infrared structure induced by finite temperature effects. A variant optimal perturbation theory is implemented in the recently proposed quantum-gravitational framework. The optimized renormalized mass, i.e., the renormalized mass determined by the variant optimal perturbation theory, of the scalar field turns out to be on the order of the temperature. This shifts the cosmological constant problem to compatibility of the consequent perturbative analysis. The compatibility is guaranteed essentially by renormalization group invariance of physical quantities. We point out the resummation behind the invariance.

Iterations of continuous maps are the simplest models of generic dynamical systems. In particular, circle maps display several key properties of complex dynamics, such as phase-locking and the quasi-periodicity route to chaos. Our work points out that Planck’s constant may be derived from the scaling behavior of circle maps in the asymptotic limit.

To account for the very low mass density associated with Dark Energy and the Cosmological Constant, a new approach to the ground state of empty space is presented. The resulting model for the vacuum state associated with empty space proposes a crystalline-like texture for the chromatic structure of empty space. This vacuum state has the appropriate mass density and predicts acceleration for the Universe expansion. Furthermore, the model predicts that this texture is anisotropic and may lead to measurable changes in the production of electron and positron pairs by gamma rays incident on a solid crystal of low mass density such as graphite.

In this article it is shown how Milgrom’s acceleration constant is related with the Ω_Λ, Ω_m and Ω_B values of the matter distribution within observable universe as defined in the Standard Model of Cosmology, established by the Planck Collaboration Group. The result is a two-parameter model for the observable universe. The two parameters are the age of the universe and Milgrom’s acceleration constant. It is shown that these are sufficient to calculate the amounts of matter and dark energy in the universe, as well as the contributions of dark matter and baryonic matter in the matter part. The numerical results are in agreement with those of the Lamda-CDM model.

Sick leave is influenced by various modifiable lifestyle factors and sex differences. This study examines the impact of body mass index, fruit and vegetable consumption, physical activity, smoking, and alcohol consumption on sick leave among Serbia's working population, focusing on sex differences. Data from the 2019 National Health Survey of Serbia were analyzed, focusing on a representative sample of 4,652 individuals aged 18-65. Chi-square tests and logistic regression models assessed the relationships between lifestyle factors and sick leave, adjusting for sociodemographic, work-related, and health-related variables. Among respondents, 15.8% reported sick leave in the past 12 months, with higher rates among women in both, short-term (13.9% vs. 10.6%) and long-term sick leave (3.4% vs. 2.2%). For men, obesity (OR = 2.6), poor dietary habits (fruit OR = 2.1; vegetables OR = 2.8), smoking (OR = 1.9), and risky alcohol consumption (OR = 4.1) significantly increase the likelihood of sick leave. In women, smoking (OR = 1.8) and risky alcohol consumption (OR = 3.1) are major predictors, while BMI and physical activity show less impact. Fruit and vegetable consumption and physical activity have inconsistent effects on sick leave, indicating the need for further research. This study identifies obesity, poor dietary habits, smoking, and alcohol consumption as key predictors of sick leave in men. In women, smoking and risky alcohol consumption are major predictors. Smoking is a risk factor for both sexes, while risky alcohol consumption emerges as a prominent predictor and is a significant predictor overall. These findings highlight the need for targeted public health interventions to address these lifestyle factors and reduce sick leave rates. Further research is needed to clarify the roles of dietary habits and physical activity in influencing sick leave.

The study aimed to analyze thoracic and lumbar erector spinae muscle activations during 3D elongation exercises in individuals with adolescent idiopathic scoliosis (AIS). Participants included 24 adolescents, meeting specific criteria such as a Cobb angle between 10° and 20°, and not having undergone surgical or brace treatments. EMG data were collected to evaluate muscle activations. The study found no significant interaction between exercise type and the side of the curve, but a significant main effect of exercise type on muscle activation, irrespective of Cobb angle. Different exercise types significantly affected muscle activity, with the highest activations in the TheraBand exercise, followed by manual and without equipment conditions. This suggests that exercise type significantly impacts muscle engagement in AIS patients, providing valuable insights for targeted exercise program design. The study, however, focused on short-term muscle activation, not long-term Cobb angle progression, pointing to the need for further research in this area.

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

The thermodynamics of black holes is discussed for the case, when the Newton constant G is not a constant, but is the thermodynamic variable. This gives for the first law of the Schwarzschild black hole thermodynamics: d S BH = − A d K + d M T BH , where the gravitational coupling K = 1 / 4 G , M is the black hole mass, A is the area of horizon, and T BH is Hawking temperature. From this first law it follows that the dimensionless quantity M 2 / K is the adiabatic invariant, which in principle can be quantized if to follow the Bekenstein conjecture. From the Euclidean action for the black hole it follows that K and A serve as dynamically conjugate variables. This allows us to calculate the quantum tunneling from the black hole to the white hole, and determine the temperature and entropy of the white hole.

In this paper we show that the Schwarzschild radius can be extracted easily from any gravitationally-linked phenomena without having knowledge of the Newton gravitational constant or the mass size of the gravitational object. Further, the Schwarzschild radius can be used to predict any gravity phenomena accurately, again without knowledge of the Newton gravitational constant and also without knowledge of the size of the mass, although this may seem surprising at first. Hidden within the Schwarzschild radius are the mass of the gravitational object, the Planck mass (their relative mass), and the Planck length. We do not claim to have all the answers, but this seems to indicate that gravity is quantized, even at a cosmological scale, and this quantization is directly linked to the Planck units. This also supports our view that the Newton gravitational constant is a universal composite constant of the form $G=\frac{l_p^2{c}^3}{\hslash }$ , rather than relying on the Planck units as a function of G. This does not mean that Newton’s gravitational constant is not a universal constant, but that it is instead a composite universal constant that depends on the Planck length, the speed of light, and the Planck constant. Further, $\frac{G\times 1\hspace{0.17em}\mathrm{weight}\hspace{0.17em}\mathrm{unit}}{c^2}=\frac{G}{c^2}$ is the Schwarzschild radius off one weight unit. So G is only needed when we want to use gravity to find the weight of an object, such as weighing the Earth. This is, to our knowledge, the first paper that shows how a long series of major gravity predictions and measurements can be completed without any knowledge of the mass size of the object, or Newton’s gravitational constant. As a minimum we think it provides an interesting new angle for evaluating existing gravity theories, and it may even give us a small hint on how to combine quantum gravity with Newton and Einstein gravity.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

We evaluated the potential of using fish species and functional traits as indicators of land use impacts to fish assemblages. We used environmental data collected at multiple spatial scales (local, reach, and upstream catchment) for 19 tributary and main stem sites in the Nolichucky River watershed in Tennessee. Canonical correspondence analyses showed that temperature, elevation, specific conductivity, sediment yield, impervious surfaces, and row crop cover at the catchment scale were strongly associated with fish assemblage structure, as well as forest cover from all three spatial scales. Blocked indicator species analysis, with stream size as the block, showed that significantly strong indicators of the least-impacted riparian land use condition (≥60% forest cover) were Saffron Shiner (Notropis rubricroceus), Rainbow Trout (Oncorhyncus mykiss), Longnose Dace (Rhynichthys cataractae), Creek Chub (Semotilus atromaculatus), and Mottled Sculpin (Cottus bairdi). Traits indicative of the least-impacted sites were the herbivorous trophic guild, mean female age-at-maturity, longevity, rock-gravel spawners, montane geology and pelagic swimmers. Specific conductivity was strongly related to multiple catchment-scale land use variables, and was a strong local-scale influence on fish assemblage structure. Our results show promise for using a relatively common but endemic southern Appalachian fish species, the Saffron Shiner, as an indicator for land-use related impacts to these streams.

Uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which are directly associated to their functions. Considering this, application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. Decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed ECM composition and structure by optical and scanning electronic microscopy, FTIR and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting significative reduction of cellular content. Structural and spectroscopy analyses revealed that produced scaffolds remained well structured and with ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing cell survival and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

We study the divisibility properties of the constant terms of certain meromorphic modular forms for Hecke groups. We relate those properties to those of some sequences that have already appeared in the literature. For possible use in later drafts, we show how to invert the map taking a Laurent series $f(x) = 1/x + \sum_{n=0}^{\infty}a_{n+1} x^n$ to the sequence of constant terms of its positive powers. At the end of the article, we construct from elementary arithmetic functions some meromorphic but not necessarily modular functions and study their constant terms.

Many strategies have been developed for the synthesis of silicon carbide (SiC) thin films on silicon (Si) substrates by plasma-based deposition techniques, especially plasma enhanced chemical vapor deposition (PECVD) and magnetron sputtering, due to importance of these materials for microelectronics and related fields. A drawback is the large lattice mismatch between SiC and Si. The insertion of a thin aluminum nitride (AlN) buffer layer between them has been shown useful to overcome this problem. Herein, the high-power impulse magnetron sputtering (HiPIMS) technique was used to grow SiC thin films on AlN/Si substrates. Furthermore, the SiC films were also grown on Si substrates. Comparisons of the structural and chemical properties of SiC thin films grown on the two types of substrates allowed us to evaluate the influence of AlN buffer layer on such properties. The chemical composition and stoichiometry of the samples were investigated by Rutherford backscattering spectrometry (RBS) and Raman spectroscopy, while the crystallinity was characterized by grazing incidence X-ray diffraction (GIXRD). Our set of results evidenced the versatility of HiPIMS technique to produce polycrystalline SiC thin films at near room temperature only varying the discharge power. In addition, this study opens up a feasible route for the deposition of crystalline SiC films with a good structural quality using AlN buffer layer.

Steel damper columns (SDCs) are energy-dissipating members that are suitable for reinforced concrete (RC) moment-resisting frames (MRFs) and those often used for multistory housing. In a previous study, an energy-based prediction procedure for the peak and cumulative response of an RC frame building with SDCs was proposed. In this procedure, the accuracy of the equivalent velocity of the maximum momentary input energy (V_ΔE1^*)–peak equivalent displacement (D₁^*_max) relationship is essential for improved prediction. In this article, the seismic capacity curve (V_ΔE1^*–D₁^*_max relationship) of RC MRFs with and without SDCs is evaluated using incremental critical pseudo-multi impulse analysis (ICPMIA). In the ICPMIA, which is based on a study by Takewaki and coauthors, the structure is subjected to various intensities of critical pseudo-multi impulsive lateral force. An ICPMIA of four 8- and 16-story RC MRFs with and without SDCs is performed to obtain their structural behaviors under various intensities of pulsive input. Then, the seismic capacity curve obtained from the ICMPIA results are compared with the predicted results based on the simplified equations. The main findings of this article are as follows. (i) The seismic capacity curve of RC MRFs without SDCs strongly depends on the number of impulsive lateral forces (N_p). As N_p increases, the seismic capacity decreases. The predicted seismic capacity curve severely underestimates that obtained from the ICMPIA in the case of large N_p. This trend is notable when the level of pinching behavior in the RC members is severe. (ii) In the case of an RC MRF with SDCs, however, the influence of N_p on its seismic capacity curve is small. The predicted seismic capacity curve agrees very well with that obtained from the ICMPIA. The influence of the level of pinching behavior in RC members on the seismic capacity curve is small.

The paper explores the features of numerical simulation to analyze the dynamic behavior of drives controlled by pulse-width modulators. Modern motor control systems widely use pulse width modulation. Effective numerical modeling of such systems has specific features because the models employed are continuous-event and have hybrid behavior due to the presence of nonlinear links with discontinuities of the first kind. Therefore, it is essential to have special integration methods with variable steps, which should be factored in when developing the model. The paper shows how these problems are solved when modeling an electric drive with a DC motor in the SimInTech software.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

In the realm of artificial intelligence, knowledge graphs have become a fascinating area of research. Relationships between entities are depicted through a structural framework in knowledge graphs. In this paper, we propose to build a domain-specific medicine dictionary (DSMD) based on the principles of knowledge graphs. Our dictionary is composed of structured triples, where each entity is defined as a concept, and these concepts are interconnected through relationships. This comprehensive dictionary boasts more than 348,000 triples, encompassing over 20,000 medicine brands and 1,500 generic medicines. It offers a groundbreaking approach to storing and accessing medical data. Our dictionary facilitates various functionalities, including medicine brand information extraction, brand-specific queries, as well as queries involving two words or question answering. We anticipate that our dictionary will serve a broad spectrum of users, catering to both human users, such as diverse range of healthcare professionals as well as AI applications.

The length of stay (LOS) in the hospital emergency department (ED) is a crucial key performance indicator that is used to track and manage the performance of the ED as a whole. Our study had two objectives. Firstly, we aimed to evaluate the association between LOS and the most common primary ICD-10 diagnoses. To achieve this, we examined LOS in groups with specific (internal, surgical, neurological, and traumatic diseases) and non-specific diagnoses in adult ED visits at a tertiary referral hospital between 2017 and 2019 (134,675 visits in total). Our secondary objective was to measure LOS by age, day of the week, time of day, and season. The mean LOS was 254 minutes and was the shortest in the traumatic group (160 minutes), while in other groups it was significantly longer: neurological by 185 minutes, internal medicine by 158 minutes, surgical by 36 minutes, and non-specific by 24 minutes. In conclusion, non-specific diagnoses accounted for 21% of all ICD-10 primary diagnoses. In this group of patients, the percentage of hospitalizations was the highest. Other significant determinants of LOS were the patients’ age, the day of the week, the time of arrival, and repeated visits.

Resonance inductive coupling is widely used for wireless power transfer (WPT) in medical applications. In this paper, we analyze the LCL-compensated WPT structure and propose a novel constant voltage transmission system based on gain estimation, without any extra feedback from the receiver. The system is capable for amplitude-modulated implant neural stimulation where the load impedance and the coupling coefficient are both variable. Compared to existing methods for constant voltage transmission, our approach offers advantages in compact size and the compatibility with the industrial, scientific and medical (ISM) band. We validate the load-independent resonant characteristic and the feasibility of constant voltage transmission using an experimental prototype working at 6.78MHz. Finally, we discuss the structure of the implant stimulator and methods of applying the proposed WPT system.

To understand the mystery of final unification, in our earlier publications, we proposed that there exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. During cosmic evolution, if one is willing to give equal importance to Higgs boson and Planck mass in understanding the massive origin of elementary particles, then it seems quite logical to expect a common relation in between Planck scale and Electroweak scale. Based on these two points, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 585 GeV. It can be considered as the zygote of all elementary particles and galactic dark matter. H-bar seems to be a characteristic outcome of unified electroweak gravity. Electron rest mass seems to be a characteristic outcome of electroweak and strong gravity. Proton rest mass seems to be a characteristic outcome of electroweak, strong and electromagnetic gravity. Recently observed 3.5 keV photon seems to be an outcome of annihilation of charged baby lepton of rest energy 1.75 keV. Interesting point to be noted is that, Schwarzschild radius of electron is 0.48 nanometer and it needs further investigation with respect to emerging nano-science and technology. Proceeding further, by considering electromagnetic and weak gravitational constants, neutron life time can be understood.

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often closely related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called “superinfection exclusion”, whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISF) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimize vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control.

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated by bioinformatics tools the protein structure and the possible effects of the known variations reported in public databases. Following a procedure already established, we created a 3D model of the whole protein and modelled the structure of 105 protein variants due to known point mutations. The effects of the amino acid substitution at the level of impact on protein structure, stability, and possibly function, were detected by the bioinformatics procedure and described in detail. A web application was implemented to browse the results of the analysis and visualize the 3D models, with the opportunity of downloading the models and analyze by the own software. Among 105 amino acid substitutions investigated, the study evidenced in 44 cases at least one change in any of the investigated structural parameters. Other 6 variations are also relevant, although a structural effect is not detected by our analysis, because they substituted amino acids highly conserved, which suggests a possible function role. All these variations should be the object of particular attention, as they may induce loss of functionality in the protein.

The detection of early biomarkers and molecular mechanisms in Parkinson’s disease (PD) remains a challenge. Recent research has pointed to potential roles for peptidylarginine deiminases (PADs), a family of calcium activated enzymes, and associated post-translational protein citrul-lination/deimination in early stages of the disease, with a focus on hippocampal and cortex re-gions of the brain. Further analysis of brain region specific changes in PAD isozymes and identi-fication of brain-region specific citrullinomes, therefore remain to be studied. This study assessed brain-region specific PAD isozyme expression (PADs 1-4; PAD6) and associated citrullinated protein targets in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb were compared between con-trols/shams and the PD model. In cortex, a significant increase of PAD2 and PAD3 was observed in the PD model. In hippocampus, PAD3, PAD4 and PAD6 showed strongest levels, but with no significant changes observed between PD and controls. In striatum, a significant reduction in all PAD isozymes was observed in the PD model. In the olfactory bulb, PAD3 was significantly el-evated in PD. In midbrain, PAD2, PAD4 and PAD6 showed strongest signal but with no signifi-cant changes between PD and controls. In cerebellum, a significant increase was seen in PAD3, PAD4 and PAD6 in the PD model. Citrullinated protein hits were most abundant in cortex and hippocampus, while for the PD model an increase in citrullinated hits was particularly observed in cortex and cerebellum, compared to controls. For all brain regions there was a considerable difference in citrullinated protein IDs between the PD model and the controls. Citrullinome as-sociated KEGG pathways differed in the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. KEGG pathways identified in PD brains onlywere: “Axon guidance”; “Spinocerebellar ataxia”; “Hippo signalling pathway”; “NOD-like receptor signalling pathway”; “Phosphatidyl-inositol signalling system”; “Rap1 signalling pathway”; “Platelet activation”; “Yersinia infection”; “Fc gamma R-mediated phagocytosis”; “Human cytomegalovirus infection”; “Inositol phosphate metabolism”; “Thyroid hormone signalling pathway”; “Progesterone-mediated oocyte matura-tion”; “Oocyte meiosis”; and “Choline metabolism in cancer”. Our findings highlight differences in PAD isozymes, citrullinated proteins and associated KEGG pathways between brain regions, in pre-motor PD.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Measured values of the electron mass and Compton wavelength produce a value of Planck's constant with a relative standard uncertainty of 3 x 10^-10. This is only slightly larger than the 1.3 x 10^-10 relative standard uncertainty in measurements performed using the Kibble balance. Compton scattering represents an alternative pathway to improving the value of Planck's constant in the future. Natural units of length, mass, and time offer new pathways to improving the values of physical constants. While extensive values of the Planck units lie beyond the reach of present-day instrumentation, certain product and quotient pairs of Planck units such as the speed of light can be measured with relatively high precision. Better measurements of certain unit pairs will improve the value of the gravitational constant.

We study a localization of gravity through the matching point between non-inertial frames and local inertial frames. This localization of gravity is done through defining relative gravitational red-shift. This lead to an emergence of a timeless state in a mathematically consistent way. In this timeless state of gravity, we find a geometric interpretation of the speed of light and mass. The experimental support of the timeless state is the quantum entanglement and internal symmetries that are independent of time. Therefore gravity would be responsible for measurements independent of time including quantum entanglement. Timeless state in that sense explain why do we have gravity/gauge correspondence. We conjecture that the universe emerged from a black hole with a global $SU(3)\times SU(2)\times U(1)$ symmetry on its event horizon that produces gauge fields Electromagnetism, weak and strong nuclear force through localization of this global symmetry. Through the localization in the gravity field, the timeless measurements such as spin will be correlated with the varying of timeless measurement which is relative gravitational red-shift. We present a gravitational or geometric interpretation of spin-0, spin-1, and spin-1/2 states. We present an interpretation of why do we measure matter rather than anti-matter. We found that the Higgs scalar field is represented by the gravitational red-shift at every point in the space around the black hole. We derive the numerical value of the cosmological constant that agrees with experimental observations.

In 1895, Korteweg and de Vries (KdV), derived their celebrated equation describing the motion of waves of long wavelength in shallow water. In doing so they made a number of quite reasonable assumptions, incompressibility of the water and irrotational fluid. The resulting equation, the celebrated KdV equation, has been shown to be a very reasonable description of real water waves. However there are other phenomena which have an impact on the shape of the wave, that of vorticity and viscosity. This paper examines how a constant vorticity affects the shape of waves in electrohydrodynamics. For constant vorticity, the vertical component of the velocity obeys a Laplace equation and also has the usual lower boundary condition. In making the vertical component of the velocity take central stage, the Burns condition can be thus bypassed.

By solving the weak field limit of Einstein’s Field Equation including the Cosmological Constant, under the constraint of spherical isotropy, it is shown that, at large cosmological distance, the gravitational force exceeds the one that is predicted by Newton’s gravity law, such that it corresponds with Milgrom’s MOND hypothesis. However, the resulting prediction that, at extremely large distances, gravity with some spatial periodicity turns on-and-off into antigravity marks a decisive difference.

By considering three virtual gravitational constants assumed to be associated with gravitational, electromagnetic and strong interactions, Fermi’s weak coupling constant can be shown to be a natural manifestation of microscopic quantum gravity. As our approach is heuristic and completely different from the current methods of estimating the Newtonian gravitational constant, with reference to the call of ‘Ideas lab 2016’ organized by NSF, we appeal for inclusion of this theoretical work as a project under unification scheme.

Dispersion of antibiotic in livestock farming represents a health concern worldwide, contributing to the spread of antimicrobial resistant bacteria through animals, the environment, and humans. Phenolic compounds could be alternatives to antibiotics, once drawbacks such as low water solubility, bioavailability, and reduced stability are overcome. Although nano- or microsized formulations could respond to these shortcomings they do not represent cost-effective options. Here, three phenolic compounds, obtained from wood processing manufacturers, were characterized, revealing suitable features such as antioxidant activity, size, and chemical and colloidal stability for in-field applications. The Minimum Inhibitory Concentration (MIC) of these colloidal suspensions was measured against six bacterial strains isolated from livestock. These particles showed different inhibition behaviors: Colloidal chestnut was effective against one of the most threatening antibiotic resistant pathogens such as S. aureus but was ineffective toward E. coli. On the other hand, colloidal pine showed a weak effect on S. aureus but specificity toward E. coli. The present proof-of-concept points at colloidal polyphenols as valuable alternatives for antimicrobial substitutes in the livestock context.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

This study presents a novel approach to understanding evolutionary dynamics through topological analysis of genotypic structures. We model the genome of a simple organism as a topological torus undergoing mutations at a constant rate of 1% per generation. Employing persistent homology and other topological data analysis techniques, we investigate how these mutations influence the overall topology of the genomic structure over time. Our simulations reveal that specific critical mutations lead to significant changes in the homotopic and homologic properties of the torus. We interpret these topological shifts as potential markers for the formation of new subspecies. By identifying the precise points of topological "breaks" within the toroidal genomic representation, our model provides a quantitative framework for observing the incremental transformations that underpin major evolutionary developments. The results offer new insights into the thresholds of speciation and adaptation, demonstrating how gradual genetic changes can accumulate to produce qualitative shifts in organismal traits. This approach bridges the gap between microscopic genetic mutations and macroscopic evolutionary outcomes, potentially revolutionizing our understanding of evolutionary processes. Our findings have implications for various fields, including theoretical biology, genetic engineering, and conservation biology. The model provides a novel perspective on genetic resilience and adaptability, offering a foundation for future research on the relationship between genomic topology and evolutionary trajectories. It also emphasizes the innovative nature of the research and its potential impact on multiple fields of study.

This paper discusses the theoretical and experimental correlations between fatigue and static strength statistical distributions. We use a two-parameter residual strength model that obeys the qualitative Strenght-Life Equal-Rank (SLERA) assumption for guidance. The modeling approach consists of recovering the model's parameters by best fitting the constant amplitude (CA) fatigue data at a given stress ratio, R, and the experimental Weibull parameters of the static strength distribution function. Once the model's parameters are fixed, its capabilities, potential, and limits are discussed by comparing its predictions with residual strength and fatigue data obtained at different stress ratios, R. Moreover, from a preliminary analysis, the theoretical extension of the model's capabilities to variable amplitude loadings is conceptualized. The application of Miner's rule is also discussed and compared with a new damage rule to analyze the fatigue responses under variable amplitude loadings.

In 1929, E. Hubble discovered a correlation between the distance of galaxies from Earth and the redshift in the spectra of the galaxies. This redshift astronomers interpreted it as evidence that galaxies are moving away from the Earth, and that the Universe is expanding. In 1998, researchers from two independent projects concluded that the universe is expanding with acceleration under the influence of "dark energy", the nature of which is completely incomprehensible. Another problem is related to the Hubble constant (H). To date there are two leading approaches to determining H. One of them is based on measurements of the cosmic microwave background, the other is based on measuring the redshift of distant galaxies and then determining the distances to them by luminosity of variables (Cepheids) and exploding (supernovae) stars. The problem is that these methods give different values of the Hubble constant: according to the first method H ≈ 67 (km/s)/Mpc, according to the other – H ≈ 73 (km/s)/Mpc. The difference is 7–8%. Accordingly, the calculated radii of the observable universe differ. The reason for this discrepancy is unclear and constitutes the essence of the so-called cosmological crisis. In the presented article, we show that the original Hubble formula needs to be corrected and give the corrected formula (corrected Hubble’s law), which is the key to solving these problems.

Henry’s constants for different existing compounds in water have great importance in transfer calculations. Measurement of these constants face different difficulties including high costs of experiment and low accuracy of measurement apparatus. Due to these facts, proposing a low cost and accurate approach becomes highlighted. To this end, adaptive neuro-fuzzy inference system (ANFIS) and least squares support vector machine (LSSVM) have been used as Henry’s constant predictor tools. The molecular structure of compounds has been used as inputs of models. After training the models, the visual and mathematical studies of outputs have been done. The coefficients of determination of LSSVM and ANFIS algorithms are 0.999 and 0.990 respectively. According to the comprehensiveness of databank and accurate prediction of algorithms, it can be concluded that LSSVM and ANFIS algorithms are accurate methods for prediction of Henry’s constant in wide range of chemical structure of compounds in water.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

Conceiving vacuum energy as gravitational particles subject to Heisenberg’s energy-time uncertainty, modelled as dipoles in a fluidal space at thermodynamic equilibrium, and interpreting the Bekenstein-Hawking entropy as the effective amount of spins of those dipoles enclosed within the event horizon of the universe, allows the calculation of Milgrom’s acceleration constant. The result is a quantum mechanical interpretation of gravity, and dark matter in particular.

Rapid antigen detection tests (RAD) are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC) presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One-hundred and twenty samples were selected and tested with both RT-qPCR and five commercial RAD commonly sold in Belgian pharmacies. Of these, direct whole genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron. Sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) were comparable and ranged from 70.0% to 77.1% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct &gt; 25), poor performances were observed for the Delta strains (20.0 to 40.0%) and, even more so, for Omicron strains (0.0 to 23.1%). Two devices failed to detect all samples (n = 13) containing Omicron strains with a low viral load. The poor performance observed with low viral loads is an important limitation of RAD, which is not sufficiently highlighted in the instruction for use of these devices.

The flourishing landscape of agritourism in Albania has witnessed a steady increase in destinations over the years. Recognizing their pivotal role in driving economic development in rural areas, considerable attention is directed towards the promotion and expansion of these agricultural tourism spots. To enhance interactivity with visitors, these agritourism destinations actively leverage social networks and various digital platforms. However, the wealth of information pertaining to these destinations is currently scattered across different platforms, posing a challenge to accessibility. To address this issue, these points are strategically placed on Google Maps, along with essential details collected from users, such as websites, contact numbers, visitor ratings, and comments. Nevertheless, other valuable data remains dispersed on various social networks. In response to this fragmentation, this study proposes the development of algorithms and scripts to systematically collect and analyze this dispersed information. By doing so, the goal is to centralize and streamline the data, enabling a comprehensive understanding of the agritourism landscape in Albania. This approach not only facilitates efficient access to information for potential visitors but also provides valuable insights for stakeholders involved in the development and management of these agritourism destinations. The study aims to contribute to the sustainable growth of agritourism in Albania by harnessing the power of digital platforms to create a unified and organized database. Through this integration, the research seeks to unveil patterns, trends, and opportunities that can further guide policy-making, marketing strategies, and overall decision-making processes in the realm of agritourism development.

In the last two decades, our knowledge of synaptic proteomes and their relationship to normal brain function and neuropsychiatric disorders has been expanding rapidly through the use of more powerful neuroproteomic approaches. However, mass spectrometry (MS) based neuroproteomic studies of synapses still need cell-type, spatial, and temporal proteome information. With the advancement of sample preparation and MS techniques, we have just begun to identify and understand proteomes within a given cell type, subcellular compartment, and cell-type-specific synapse. Here, we review the progress and limitations of MS-based neuroproteomics of synapses in the mammalian CNS and highlight the recent applications of these approaches in studying neuropsychiatric disorders such as major depressive disorder and substance use disorders. Combining neuroproteomic findings with other omics studies can generate an in-depth, comprehensive map of synaptic proteomes and possibly identify new therapeutic targets and biomarkers of several central nervous system disorders.

The relativistic effects of the dynamical properties of light at angular incidence were analyzed from the perspectives of Bohr indeterminacy and Heisenberg uncertainties and statistical dispersion. It was found that these effects report minimal uncertainties that agree with one or the other according to the angular range of incidence and that decrease with increasing refringence of the medium, constituting a specific relativistic uncertainty at angular incidence. An anomaly is indicated for the uncertainty principle in the Quantum Theory (QT) setting for small angles of incidence, where the accuracy of the angular position does not imply an increase in the uncertainty of the linear momentum. The anomalies arise because TQ does not predict the alternation between the classical and relativistic regimes of photon inertia at angular incidence. Specific relativistic uncertainty particularizes the uncertainty principle in the transmission of light between media pairs at angular incidence for the relativistic scenario, considering an observer that registers the relativistic effects of measurements that interfere with the observed system, in another inertial referential.

In this paper we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the Free Energy Principle, we can emphasize the role of fostering resource renewal, harmonious system-entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability, both in an agent and in collectives. We start by connecting Active Inference with well-being, building on exsiting work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent, and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

NSD3 is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. NSD3 gene encodes three isoforms, the full length, a short (NSD3S) and WHISTLE isoforms. Importantly, NSD3S isoform corresponds to the N-terminal of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. Fusion proteins containing NSD3 have also been reported, such as leukemia NSD3-NUP98, and in NUT midline carcinoma (NMC), NSD3-NUT fusion. Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on stating the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. Altogether, there is evidence that both isoforms of NSD3 are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.

We present a first formal analysis of specific and complete local integration. Complete local integration was previously proposed as a criterion for detecting entities or wholes in distributed dynamical systems. Such entities in turn were conceived to form the basis of a theory of emergence of agents within dynamical systems. Here, we give a more thorough account of the underlying formal measures. The main contribution is the disintegration theorem which reveals a special role of completely locally integrated patterns (what we call ι-entities) within the trajectories they occur in. Apart from proving this theorem we introduce the disintegration hierarchy and its refinement-free version as a way to structure the patterns in a trajectory. Furthermore we construct the least upper bound and provide a candidate for the greatest lower bound of specific local integration. Finally, we calculate the i-entities in small example systems as a first sanity check and find that ι-entities largely fulfil simple expectations.

Superconductivity in highly-pressurized hydrides became primary direction for the exploration of fundamental upper limit for the superconducting transition temperature, Tc, after Drozdov et al (Nature 2015, 525, 73) discovered superconducting state with Tc=203 K in highly-compressed sulphur hydride. To date several dozens of high-temperature superconducting polyhydrides have been discovered. In addition, recently, it was reported that highly-compressed titanium and scandium exhibit record-high (up to 36 K), which is by manifold exceeded of niobium, which is the record high- ambient pressure metallic superconductor. Here we analysed experimental data on for recently discovered high-pressure superconductors (which exhibit high transition temperatures within their classes): elemental titanium (Zhang et al, Nature Communications 2022; Liu et al, Phys. Rev. B 2022), TaH3 (He et al, Chinese Phys. Lett. 2023), LaBeH8 (Song et al, Phys. Rev. Lett. 2023), and black (Li et al, Proc. Natl. Acad. Sci. 2018) and violet (Wu et al, arXiv 2023) phosphorous, to reveal the nonadiabaticity strength constant, TθTF (where Tθ is the Debye temperature, and TF the Fermi temperature) in these superconductors. The analysis showed that δ-phase of titanium and black phosphorous exhibit the Tθ/TF which are nearly identical to ones associated in A15 superconductors, while studied hydrides and violet phosphorous exhibit the constants in the same ballpark with H3S and LaH10.

In a particle swarm with a fixed kinetic energy, the constituent particles move randomly and their velocity magnitudes follow a Maxwell distribution characterized by specific parameters. Within a certain time frame, particles in a sub-swarm may exhibit a bias in their movement direction. Thus, the particles may exhibit a special characteristic (biased random motion), where the group velocity in a particular direction remains constant u. For this biased particle swarm, composed of randomly moving particles with a fixed average speed c, particles have a higher probability of moving in a specific direction. Conversely, their likelihood of moving in all other directions is equally reduced. This study starts from the perspective of biased random walks and using Mathematica software proves that the diffusion rate of particles (in the reference frame R_u observed from R₀) in all directions is slower than that of an unbiased particle swarm with the same average speed c. Specifically, the degree of reduction is determined by the Lorentz-like factor. Lastly, we present the Ito equation for this biased random motion and provide associated verification examples. This study aims to serve as a reference for comprehending the underlying principles of the special relativity effect.

This article analyzes in detail the influence of Jupiter on the measurement of the gravitational constant. Including a specific estimate of the change in the gravitational constant caused by the change of the earth's orbital position every half month. The influence of Jupiter's perihelion and aphelion on the gravitational constant is also estimated. On this basis, this article analyzes the data with specific time records such as BIPM-01, BIPM-14, JILA-10, UCI-14, HUST-09. The analysis results show that after considering the influence of Jupiter, the experimental results have been significantly improved.

In the paper we show that the general relativity in recent Einstein-Palatini formulation is equivalent to a gauge field. We begin with a bit of information of the Einstein-Palatini formulation and derive Einstein field equations from it. In the next section, we consider general relativity with a positive cosmological constant in terms of the corrected curvature. We show that in terms of the corrected curvature general relativity takes the form typical for a gauge field. Finally, we give a geometrical interpretation of the corrected curvature.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.