This paper reports a new control strategy to improve sharing of unbalanced currents in islanded LV microgrids. This technique provides fast and effective sharing of positive-, negative- and zero-sequence currents, and is the first example of zero-sequence current sharing in the literature. The controllers are designed in the stationary frame. The control structure consists of four loops; 1)~the current controller; 2)~the voltage controller; 3)~the droop controller and the 4)~negative and zero sequence current controllers. The output current is considered unknown for the controller and is added to the control system as a disturbance. The proposed controller features a high gain in fundamental and harmonic frequencies, hence a good voltage quality is obtained in the presence of unbalanced and nonlinear loads. To this aim, a proportional-resonant (PR) controller is adopted as the current controller. By using a multi-resonant controller as current controller, a unified control structure is obtained which is suitable for both grid-connected and islanded modes. The voltage controller is designed using a resonant controller so that the voltage can have low VUF and THD in the presence of unbalanced and nonlinear loads. Furthermore, in this paper droop method is applied to the control structure to share real and reactive powers. Simulation studies show that the conventional droop method cannot share the oscillatory part of the output power that is due to the presence of unbalanced loads in the microgrid. This paper relies on using zero and negative sequence virtual impedance controller to share the oscillatory part of output power. By using zero-sequence virtual impedance controller (ZSVIC) and negative-sequence virtual impedance controller (NSVIC), the zero and negative sequence currents in the microgrid are controlled and shared effectively. By compensating zero- and negative-sequence currents locally, the flow of these currents in the microgrid is minimized, and the overall power quality of the islanded LV microgrid is improved.

This study aims to categorize the morphological changes during cabbage (B. oleracea ssp. capitata) development: seedling, rosette, folding, and heading and to elucidate the cellular mechanisms of leaf curvature, essential for the formation of the leafy head. We followed the growth of two cabbage morphotypes with distinct head shapes (round and pointed); we phenotyped the size and volume of the whole-plant as well as the size, shape, and curvature of the leaves during growth. By integrating these phenotypic data, we determined the four vegetative stages for both cabbages. Cytological phenotypes of microtome sections from five distinct leaf positions of the rosette, folding, and heading leaves at two timepoints during leaf growth were quantified and revealed variations in cellular parameters among leaf types, between leaf positions, and between the adaxial and abaxial sides. We identified two synergistic cellular mechanisms contributing to the curvature of heading leaves: differential growth across the leaf blade, with increased growth at the leaf's centre relative to the margins; and increased expansion of the spongy parenchyma layer compared to the palisade parenchyma layer, resulting in the direction of the curvature, which is inwards. These two processes together contribute to the typical leafy heads of cabbages.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

Transportation authorities aim to boost road safety by identifying risky locations and applying suitable safety measures. The Highway Safety Manual (HSM) is a vital resource for US transportation professionals, aiding in the creation of Safety Performance Functions (SPFs), which are predictive models for crashes. These models rely on Negative Binomial distribution-based regression and misinterpreting them due to unmet statistical assumptions can lead to erroneous conclusions, including inaccurately assessing crash rates or missing high-risk sites. The Florida Department of Transportation (FDOT) has introduced context classifications to HSM SPFs, complicating assumption violation identification. This study, part of an FDOT-sponsored project, investigates established statistical diagnostic tests to identify model violations and proposes a novel approach to determine optimal spatial regions for Empirical Bayes adjustment. This adjustment aligns HSM-SPFs with regression assumptions. The study employs a case study involving Florida roads. Results indicate that a 20-mile radius offers an optimal spatial sample size for modeling crashes of all injury levels, ensuring accurate assumptions. For severe injury crashes, which are less frequent and harder to predict, a 60-mile radius is suggested to fulfill statistical modeling assumptions. This methodology guides FDOT practitioners in assessing the conformity of HSM-SPFs with intended assumptions and determining appropriate region sizes.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. As of February 21, total 75,773 confirmed cases worldwide have spread to more than two dozen countries. Transmission of COVID-19 can occur early in the course of infection since SARS-CoV-2 viral loads in asymptomatic patients are similar to that in the symptomatic patients. Therefore, more sensitive diagnostic methods are needed to detect early phase of the infection to prevent secondary or tertiary spreads. Here, we compare the RT-PCR confirmatory test results using two different SARS-CoV-2 viral RNAs from two Korean COVID-19 confirmed cases.RT-PCR method targeting the RdRP gene, which was recommended by WHO guideline, was less sensitive than targeting N genes (as per CDC guideline). Because many countries follow the WHO guideline, our findings may contribute to the early diagnosis of COVID-19.

To implement renewable energy resources, microgrid systems have been adopted and developed into the technology of choice to assure mass electrification in the next decade. Microgrid systems have a number of advantages over the conventional utility grid systems, however, it faces severe instability issues due to continually increasing constant power loads. To improve the stability of the entire system, load side compensation technique is chosen because of its robustness and cost effectiveness. In this particular occasion, a sliding mode controller is developed for microgrid system in the presence of CPL to assure certain control objective of keeping the output voltage constant at 480V. After that, the robustness analysis of the sliding mode controller against parametric uncertainties is presented. The sliding mode controller robustness against parametric uncertainties, frequency variations, and additive white Gaussian noise (AWGN) are illustrated in this paper. Later, the performance of the PID and sliding Mode controller is compared in case of nonlinearity, parameter uncertainties, and noise rejection to justify the selection of Sliding Mode controller over PID controller. All the necessary calculations are reckoned mathematically and results are verified in the virtual platform such as MATLAB/Simulink with the appreciable outcome.

We obtain some generalised Minkowski-type integral formulas for compact Riemannian (resp. spacelike) hypersurfaces in Riemannian (resp. Lorentzian) manifolds admitting an arbitrary vector field that we assume to be timelike in the case where the ambient space is Lorentzian. Some of these formulas generalize existing formulas in the case of conformal and Killing vector fields. We apply these integral formulas to obtain interesting results concerning the characterization of such hypersurfaces in some particular cases such as when the ambient space is Einstein admitting an arbitrary (in particular, conformal or Killing) vector field, and when the hypersurface has constant mean curvature.

The cytoplasmic membrane is the fundamental component of all living cells, which participates in various physiological processes, such as material exchange, stress response, cell recognition, signal transduction, cellular immunity, apoptosis, pathogenicity, etc. The normal function of a cytoplasmic membrane requires stable organization of transmembrane protein-lipid microdomains, transmembrane protein-cell wall microdomains, and cytoskeleton-transmembrane protein microdomains. Here, we review the mechanisms and functions of various membrane lipid components, fatty acid content and saturation, membrane curvature, and cell wall and cytoskeleton in plasma membrane homeostasis affecting the pathogenicity of pathogenic fungi. Pathogenic fungi maintains plasma membrane homeostasis and contributes to fungal virulence by maintaining plasma membrane assembly, structural and functional integrity of pathogenic fungi at various stages of cell development through interactions among lipid components of cytoplasmic membranes, transmembrane proteins, cytoskeleton and cell wall components, etc.

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.

Terms related to gradients of scalar fields are introduced as scalar products into the formulation of entropy. A Lagrange density is then formulated by adding constraints based on known conservation laws. Applying the Lagrange formalism to the resulting Lagrange density leads to the Poisson equation of gravitation and also includes terms being related to curvature of space. The formalism further leads to terms possibly explaining nonlinear extensions known from modified Newtonian dynamics approaches. The article concludes with a short discussion of the presented methodology and provides an outlook on other phenomena, which might be tackled using this new approach.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

In our study we used the data set on morphimetric traits in beetles species. It has been constantly replenishing for 20 years by the samples, received from different regions of Russia and abroad. In this case we have selected data on nine species for which the left and right sides had been measured and fluctuating asymmetry (FA) could be estimated. The samples were from 6 provinces of Russia and Belarus, which ranged in 3 degrees in latitude and 57 degrees in longitude and included more than 150 plots in different types of biotopes. FA was assessed according to the standard method in 5265 specimen in one dimensional trait and one - meristic. ANOVA showed that biotope, species and their interaction affected FA in both traits, that is different species reacted differently to biotope type. In uncommon biotopes (according to accepted in carabidology classification) FA was increased. In forest species the negative relationship between FA in dimensional and meristic traits in the range in biotopes was revealed. In those species only FA values were higher in males than in females. In generalist species FA varieв similarly in both sexes and in both traits being the highest in open biotopes. In eudomonant of arable lands biotopes – Poecilus cupreus – the highest values of FA were recorded in the meadows, being about equal in all types of crops.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

The author’s opinion is that the negative energy solutions of the Dirac equation mean that a particle can be of negative kinetic energy (NKE) besides positive kinetic energy (PKE). We think that NKE particles are dark ones and NKE matter is dark matter. In our previous works, the dark matter theory of the NKE version and the dark energy theory that matched dark matter theory were put forth. In this work, we investigate the topics related to the metamorphosis of objects between PKE and NKE. We first evaluate the collosions between a PKE and a NKE particles. A scenario of accelerating PKE particles is raised. We put forth the cosmic dark radiation background and gravity potential background. In the universe, negative energy is predominating. In the observable universe, substances constitute stable PKE systems. The total energy of every such system is negative. We propose a mechanism that NKE substances combine into stable PKE systems. Macroscopically, NKE objects can constitute stable PKE astrophysical systems by means of gravity between them. Microscopically, NKE particles can combine into stable PKE systems by means of attractive interactions between them, say, Coulomb attraction. Currently, people think that there are four ingrediants in the universe: photons \Omega_R0, matter \Omega_M0, dark matter \Omega_DM, and dark energy \Omega_\lambda0. We analyze the order of the appearance of the four ingredients and conclude that qualitatively, their proportions should be \Omega_\lambda0 > \Omega_DM > \Omega_M0 > \Omega_R0.

Traditional dry fermented meat products are obtained artisanally in many countries, where they represent a gastronomic heritage well distinguished from industrial counterparts. This food category is most often obtained from red meat, a food commodity that is under attack because of evidences of increased risk of cancer and degenerative diseases with high consumption. However, traditional fermented meat products are intended for moderate consumption and gastronomic experience and, as such, their production must be continued also to safeguard culture and economy of the geographical areas of origin. In this review, the main risks attributed to these products are considered and how these risks are minimized by following precise production norms, respectful of the ancient manufacturing processes is described. Moreover, results obtained in studies reporting use of autochthonous microbial cultures of lactic acid bacteria (LAB), coagulase negative staphylococci (CNS), Debaryomyces hansenii and Penicillium nalgiovense to improve safety and quality of traditional fermented meats are summarized. The role of these products as a source of microorganisms that can be beneficial to the host are also considered. From the results of the studies reviewed here it appears that the development of autochthonous cultures for these foods ensure safety and stabilize sensory characteristics with possibility to be extended to the large variety of traditional productions.

The Sulfur Dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental Sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using Density Functional Theory calculation of the relative transition state barriers for the 2-step Dehydro-sulfurization oxidation-reduction reaction. Additionally, doubly-charged nanoscale platelet Molybdenum Disulfide (MoS2), Armchair (6,6) Carbon Nanotube, 28-atom Graphene nanoflake (GR-28), and Fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the 2-step oxidation-reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious Lynchpin TM drones.

Zingiber cassumunar Roxb. is a powerful medicinal plant that has been used as traditional medicine to cure respiratory problems, pain, and inflammation in China, Indonesia, Thailand and other Asian countries by using the crude extracts. The objective of this research is to identify phytochemical composition of Z. cassumunar Roxb. and to analyze antibacterial activity of crude extract, purified compounds, and their microencapsulated products of Rhizome Z. cassumunar Roxb. Identification of phytochemical composition in crude extract of rhizome Z. cassumunar Roxb. was achieved by chromatography-mass spectrophotometer. The major phytochemical composition in crude extract of Z. cassumunar Roxb. is essential oils, including terpinen4-ol (37.7%), β-pinene (20.8%), and (E)-1-(3,4-dimethoxyphenyl)but-1-ene (13.3%). Crude extract of Z. cassumunar Roxb. was purified with silica gel flash column chromatography, resulting two purified compounds. The antibacterial activity of crude extract, purified compounds, and their microencapsulated products of Rhizome Z. cassumunar Roxb. were evaluated against agricultural and foodborne pathogens by using disc agar diffusion and broth microdilution techniques. All of the samples studied (crude extracts, purified compounds, and microencapsulated of Z. cassumunar Roxb.) were effective against all the bacteria. Based on the results of the disc-diffusion assay suggested that amongst the samples studied, purified compounds (compound 1 and 2) and microencapsulated purified compounds (compound 1 and 2) exhibited more effective against all the bacteria compared to the crude extracts. Antibacterial activity of the rhizome of Z. cassumunar Roxb. was contributed mainly by the essential oils components as the active compounds. Gram-negative bacteria (X. oryzae, X. translucens, Pseudomonas spp, E. coli, and S. typhimurium) appeared to the most resistant to the crude extracts, purified compounds, and microencapsulated of Z. cassumunar Roxb. compared to the gram-positive bacteria (S. aureus, B. cereus, and L. monocytogenes). Microencapsulated of the tested samples (crude extract, purified compound 1, and purified compound 2) of the rhizome Z. cassumunar Roxb. exhibited high antibacterial activity with no significantly different with the tested samples without microencapsulation. These results suggest potential antibacterial properties of Z. cassumunar Roxb., which useful for agricultural plant health, food preservation, natural therapies, and pharmaceuticals.

The Sulfur Dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental Sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using Density Functional Theory calculation of the relative transition state barriers for the 2-step Dehydro-sulfurization oxidation-reduction reaction. Additionally, doubly-charged nanoscale platelet Molybdenum Disulfide (MoS2), Armchair (6,6) Carbon Nanotube, 28-atom Graphene nanoflake (GR-28), and Fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the 2-step oxidation-reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious Lynchpin TM drones.

Direct electron transfer (DET)-type bioelectrocatalysis, which couples electrode reactions and catalytic functions of redox enzymes without any redox mediator, is one of the most intriguing subjects studied over the past decades in the field of bioelectrochemistry. In order to realize the DET-type bioelectrocatalysis and to improve the performance, nanostructures of the electrode surface have to be carefully tuned for each enzyme. In addition, enzymes can also be tuned by protein engineering approach for the DET-type reaction. This review summarizes the resent progresses in this field of the research, while taking into consideration of the importance of nanostructure of electrodes as well as redox enzymes. Described are basic concepts and theoretical aspects of DET-type bioelectrocatalysis, significance of nanostructures as scaffolds for DET-type reactions, protein engineering approached for DET-type reactions, and concepts and facts of bidirectional DET-type reactions, from a cross-disciplinary viewpoint.

Compressive residual stresses in thin films can inhibit crack propagation under normal or sliding contact loading, with associated enhancement of the coating apparent toughness, load bearing capacity and wear resistance. This study investigates the influence of residual stress distributions on the thin film/substrate adhesion using a nanoindenter coupled with scanning electron microscope (SEM) investigations of indentation induced failure modes. Reactive and un-reactive magnetron sputtering with ion plating was used to coat a (100) silicon substrate with aluminum nitride (AlN) with and without an aluminum (Al) adhesion layer. The presence of an Al bond layer gives additional interfacial tensile stress because of the difference in thermal expansion coefficient. Additionally, a different magnitude of residual stresses in the AlN coating was achieved by changing the applied bias voltage onto the substrate. Wafer curvature method and incremental focused ion beam (FIB) milling, combined with high-resolution in situ scanning electron microscopy (SEM) imaging and full field strain analysis by digital image correlation (DIC), were used to measure the average and in-depth stress residual stress distribution in the produced coatings. The adhesion energy was then quantified by using a nanoindentation based model. Results demonstrate that the additional tensile residual stress in the aluminum adhesion layer decrease significantly the coating adhesion, even in presence of a higher compressive stress state in the AlN top-layer. Therefore, the coatings without Al-layer showed better adhesion because of a more homogeneous compressive residual stress in comparison with the coating having Al layer, even though both groups of coatings are produced under same bias voltage. Results are discussed, and some general suggestions are made on the correlation between coating/substrate property combination and the adhesion energy of multilayer stacks. The results suggested that Al bond-layer and inhomogeneous residual stresses affected the adhesion of AlN negatively to a substrate like silicon.

With the economic recession and the deterioration of the ecological environment becoming more and more prominent in the world, the sustainable operation of enterprises is facing the most difficult choice in history. For each responsible enterprise, it is crucial to choose the market power expansive strategy that can improve the realistic viability or the technological innovation strategy that can improve the future development potential. This is of great significance to reduce the negative external effects of the corporate social environment and ensure their sustainable development. In this paper, we select the data of 18 large listed petrochemical companies from 2003 to 2018 as samples and construct a linear regression model for empirical analysis. Meanwhile, we put forward more practical business management strategies for the sustainable development of petrochemical enterprises in developing countries in further research.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Most of the research in data mining concentrated on finding the positive associations that exist in frequent patterns. Frequent patterns have no bearing on the time duration and, therefore, lose interestingness. The Regularity of an itemset is related to the time at which the transaction occurred and the time distance between the transactions. Frequent Regular item sets can be generated considering the Frequency and the Regularity of the occurrence of the Item Sets. The frequent and regular Item sets will be so huge that they cannot be handled in real time. The count of Frequent and regular item sets gets reduced drastically when the properties “closed” and “Maximality” are applied. Finding negative associations among such patterns are important in the field of medicine. Many drugs administered to cure some diseases have counter reactions leading to many other diseases. Negative associations among the mined patterns are important as they reveal significant contradictions frequently among medical drugs administered by medical practitioners to cure some diseases. This paper proposes a method that mines medical databases to find regular, frequent patterns applied with closed and maximal properties and find negative associations among those patterns. The proposed algorithm is accurate to 98% and performs 9% more efficiently than the other algorithms presented in the literature.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

The negative energy solutions of the Klein-Gordon and Dirac equations have been used to define the antiparticle with the positive energy from the Feynman - Stueckelberg interpretation in the standard model based on the 4-D Minkowski space with the relative time. The negative energy solutions of the Klein-Gordon and Dirac equations are used to define the antiparticles with the negative energy in the present 3-D quantized space model. Note that all the present results are based on the 4-D Euclidean space with the absolute time (t) and relative time (t_l). Then the particle with the positive energy and antiparticle with the negative energy have the 4-D P₄ = TCP = T_cP symmetry. The continuity equations are derived from the Klein-Gordon, Dirac and Schrodinger equations. The Klein-Gordon and Schrodinger equations with the potential barriers are solved. The Klein paradox is explained by using the pair production of the electron with the positive energy and positron with the negative energy under the P₄ = _TcP symmetry, The effective velocity ( c_eff=√2 " c " ) and effective energy ("Etl =" √2 E ) along the relative time axis (ctl) give the relative time momentum of "p_tl"=E_tl/c_eff =(√2 E)/(√2 c)=E/c=p_t=p_x. This indicates that the photons with the energy of E have the constant photon velocity of c and the constant photon momentum of "ptl"=E_tl/c_eff =(√2 E)/(√2 c)=E/c=p_t=p_x. For the negative energy particles, the space momentum directions are opposite to the particle velocity directions because the energy is negative. And the matter collapse to the photons at the very high particle velocity is discussed from the length expansion. It is, for the first time, proposed that the gamma ray burst is originated from the matter collapse to the photons near the black hole. Also, the wave function collapse is explained from the length expansion. The wave function collapse takes place when the measurement makes the particle velocity to be zero. It is concluded that the negative energy solutions of the Klein-Gordon and Dirac equations support the existence of the partner antimatter universe with the negative energy and negative time direction. Our matter universe has the positive energy and the positive time direction.

The modulation instability of surface capillary-gravity water waves is analysed in a shear flow model with a tangential discontinuity of velocity. It is assumed that air blows along the surface of the water with a uniform profile in the vertical direction. Such a model, despite its simplicity, plays an important role in hydrodynamics as the reference model for investigating basic physical phenomena of wave-current interactions and acquiring insights into a series of complex phenomena. In certain cases where the wavelength of interfacial perturbations is much bigger than the width of the shear fow profile, the model with the tangential discontinuity in the velocity is adequate for describing physical phenomena at least within limited spatial and temporal frameworks. A detailed analysis of the air-flow conditions under which modulation instability sets in is presented. It is also shown that the interfacial waves are subject to dissipative or radiative instability when negativeenergy waves appear at the interface.

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

The move to a low carbon economy is very important for enhancing international competitiveness. The eco-innovation is the critical factor of the green paradigm. This study is designed to investigate deeply the determinants of eco-innovation of manufacturing firms in Korea by suggesting anticipated regulations, self-regulations, and industry-specific characteristics as external factors and open information sources as internal factors. The data used in the analysis is 1946 sample firms from Korean Innovation Survey 2010 based on the Oslo Manual. Using the multi-variate probit analysis and the zero-inflated negative binomial (ZINB) regression analysis, we have found out that the anticipated regulations and self-regulations have significant influences both on eco-process innovation and eco-product innovation, while industrial characteristics have no effects. The empirical results also show that the breadth of information sources has a positive effect on businesses in implementing eco-innovations. Our findings show that the Korean government should provide a good platform where firms can better understand the future trends of environmental policies, particularly policies on anticipated and self-regulations. At the same time, Korean firms should establish a voluntary system to control environmental activities so that they can improve eco-innovations through integrating external information.

Crash prediction of the sharp horizontal curve segment (SHCS) of a freeway is an important tool in analyzing safety of SHCSs and in building a crash prediction model (CPM). The design and crash report data of 88 SHCSs from different institutions were surveyed and three negative binomial (NB) regression models and three generalized negative binomial (GNB) regression models were built to prove that the interactive influence of explanatory variables plays an important role in fitting goodness. The study demonstrates the effective use of the GNB model in analyzing the interactive influence of explanatory variables and in predicting freeway basic segments. Traffic volume, highway horizontal radius, and curve length have been formulated as explanatory variables. Subsequently, we performed statistical analysis to determine the model parameters and conducted sensitivity analysis. Among the six models, the result of model 6, which considered interactive influence, is much better than those of the other models by fitting rules. We also compared the actual results from crashes of 88 SHCSs with those predicted by models 1, 3, and 6. Results demonstrate that model 6 is much more reasonable than models 1 and 3.

This study presents an exact solution to the free vibration analysis of a uniform Timoshenko beam, with a harmonic vibration being assumed. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. In this paper, a moment-shear force-circular frequency-curvature relationship was presented. The complete study was based on this relationship and closed-form expressions of efforts and deformations were derived. The free vibration response of single-span systems and spring-mass systems was analyzed; closed-form formulations of matrices expressing the boundary conditions were presented and the natural frequencies were determined by solving the eigenvalue problem. Systems with intermediate mass, spring, or spring-mass system were also analyzed. Furthermore, first-order dynamic stiffness matrices in local coordinates were derived. Finally, a second-order analysis of beams resting on an elastic Winkler foundation was conducted. The results obtained in this paper were in good agreement with those of other studies.

In the paper, by convolution theorem for the Laplace transforms and analytic techniques, the author finds necessary and sufficient conditions for complete monotonicity, monotonicity, and inequalities of several functions involving polygamma functions. By these results, the author derives a lower bound of a function related to the sectional curvature of the manifold of the beta distributions. Finally, the author poses several guesses and open problems related to monotonicity, complete monotonicity, and inequalities of several functions involving polygamma functions.

Sepsis is a life-threatening complication of an infectious process that results from excessive and uncontrolled activation of the host's pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of the Gram-negative bacteria outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs), that inhibit LPS toxic effects, and are of interest as potential drugs for the sepsis treatment. The structure, physicochemical properties, antimicrobial and LPS-binding/neutralizing activity of these proteins and their synthetic analogues are considered in details. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n=83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p=0.04) and staphylococcal (p=0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p=0.001) abundance and S. hominis (p=0.01) relative staphylococcal abundance. In nares, significant reductions occurred for S. hominis (p=0.02), S. haemolyticus (p=0.02), and S. pasteuri (p=0.003) relative to other staphylococci. S. aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. S. epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.

Tuberculosis cause of death worldwide and the leading cause from a single infectious agent, ranking above Human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). The aim of this study is to ascertain the trend of tuberculosis prevalence and the effect of HIV prevalence onl Tuberculosis case in some West African countries from 2000 to 2016 using count panel data regression models. The data used annual HIV and Tuberculosis cases spanning from 2000 to 2016 extracted from online publication of World health Organization (WHO). Panel Poisson regression model and Negative binomial regression model for fixed and random effects were used to analyzed the count data, the result revealed a positive trend in TB cases while increased in HIV cases leads to increase in TB cases in West African countries. Among the competing models used in this study, Panel Negative Binomial Regression Model with fixed effect emerged the best model with log likelihood value of -1336.554. This study recommended that Government and NGOs need more strategies to fight against HIV menace in West Africa as this will in turn reduced TB cases in West Africa.

In Sub-Saharan African Countries such as Nigeria with high prevalence rate, Child HIV/AIDs acquired through Mother-to-Child transmission (MTCT) can be largely prevented by using a well-established prevention programme and scheme. This study examined factors that can enhanced Prevention of Mother-to-Child transmission (PMTCT) in Nasarawa State. To achieve this, structured questionnaire were used to collect data from one hundred and sixteen (116) women attending two (2) primary facilities and two (2) secondary facilities in the State. This study utilized methods of Poisson Regression, Negative Binomial Regression and Logistic Regression Analyses. Results revealed that women with at least a secondary school education, women with husband in military and women with perceived confidentiality of their HIV status significantly enhanced PMTCT of HIV in Nasarawa State while significant proportion of the women attest to the fact that drugs are available in the facilities (p-value=0.0000<0.05) . Other factors include mother income level, willingness to continue with PMTCT programme and women in support group can also enhanced PMTCT though they are not significant. This study recommends that the factors identified should be explored by NGOs, Ministry of Health and, Support groups and other relevant agencies since they have the capacity to enhanced PMTCT of HIV in Nasarawa State, Nigeria.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

In this study, Silicon Carbide (SiC) nano-particle based serigraphic printing inks were formulated to fabricate highly sensitive and wide temperature range SiC printed thermistors. Initially, commercial silver ink was screen printed to fabricate inter-digitated electrodes (IDE’s) onto flexible Kapton® substrate via screen printing. Thermistor inks with different weight ratios of SiC nano- particles dispersed in polyimide resin matrix were fabricated. The SiC-polyimide temperature sensing inks were screen printed atop the IDE structures to form fully printed thermistors and encapsulated with a adhesive backed polyimide film for humidity inhibition. The high temperature tolerance of the Kapton® allowed the the sensors to be tested over a wide temperature range form 25◦C to 170◦C. The printed SiC thermistors exhibit excellent repeatability and stability over 15 hours of continuous operation. Optimal device performance was achieved with 30 wt.% SiC-polyimide ink. We report highly sensitive devices with a temperature coefficient of Resistance (TCR) of -0.556 %/◦C, a thermal coefficient of 502 K (β-index) and an activation energy of 0.08 eV which are comparable with printed thermistors previous reported. Further, the thermistor demonstrates an accuracy of ±1.35◦C which is well within the range offered by commercially available high sensitivity thermistors. SiC thermistors exhibit a small 6.5% drift due to changes in relative humidity between 10-90 %RH and a 4.2 % drift in baseline resistance after 100 cycles of aggressive bend testing at a 40°angle. The use of commercially available low cost materials, simplicity of design and fabrication techniques coupled with the chemical inertness of the Kapton® substrate and SiC nanoparticles paves the way to use all-printed SiC thermistors towards a wide range of applications where temperature monitoring is vital for optimal system performance.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

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

Work-related thoughts in off-job time have been studied extensively in occupational health psychology and related fields. We provide a focused review of research on overcommitment – a component within the effort-reward imbalance model – and aim to connect this line of research to the most commonly studied aspects of work-related rumination. Drawing on this integrative review, we analyze survey data on ten facets of work-related rumination, namely (1) overcommitment, (2) psychological detachment, (3) affective rumination, (4) problem-solving pondering, (5) positive work reflection, (6) negative work reflection, (7) distraction, (8) cognitive irritation, (9) emotional irritation, and (10) inability to recover. First, we leverage exploratory factor analysis to self-report survey data from 357 employees to calibrate overcommitment items and to position overcommitment within the nomological net of work-related rumination constructs. Second, we leverage confirmatory factor analysis to self-report survey data from 388 employees to provide a more specific test of uniqueness vs. overlap among these constructs. Third, we apply relative weight analysis to quantify the unique criterion-related validity of each work-related rumination facet regarding (1) physical fatigue, (2) cognitive fatigue, (3) emotional fatigue, (4) burnout, (5) psychosomatic complaints, and (6) satisfaction with life. Our results suggest that several measures of work-related rumination (e.g., overcommitment and cognitive irritation) can be used interchangeably. Emotional irritation and affective rumination emerge as the strongest unique predictors of fatigue, burnout, psychosomatic complaints, and satisfaction with life. Our study assists researchers in making informed decisions on selecting scales for their research and paves the way for integrating research on effort-reward imbalance and work-related rumination.

Complex modeling has received significant attention in recent years and is increasingly used to explain the statistical phenomenon with increasing and decreasing fluctuations such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which ends up a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID database, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains of Wuhan, Beijing, New York, German, and UK variant B.1.1.7) were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2 for which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolvement of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS>SARS-CoV-1>SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

This study explores the perception of a “sense of place” among tourists visiting Hegra, an archaeological site in northern Saudi Arabia, through reviews on TripAdvisor. The 267 reviews reviewed on TripAdvisor between 2020 and 2023 were analyzed with the VADER sentiment po-larity analysis tool and object modeling using the NMF machine learning algorithm. The results highlight positive factors linked to the history and uniqueness of the place while showing some critical issues related to isolation, cost, privatization, and competitiveness. The originality of the research lies in the type of case study chosen, an archaeological site of a country that has recently opened its doors to tourism, and in the pragmatic nature of the investigation, oriented towards the search for possible solutions to be adopted in terms of heritage management based on the feedback received for the development of the tourist destination.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.

It has been theorized that black holes are surrounded by firewalls, although there is not universal agreement concerning this. We first review basic concepts pertaining to Schwarzschild black holes and Hawking radiation. Then we discuss the anticipation of Hawking radiation—albeit from non-black holes—initially by R. C. Tolman and shortly thereafter with P. Ehrenfest. We compare evaporation into a vacuum at absolute zero (0 K) of black holes with that of non-black holes, and show that not only black holes but also non-black holes evaporate within a finite time. The times required for evaporation of black holes and non-black holes are compared. Next, we show that (i) if firewalls exist, they can originate via Hawking radiation at the minimum possible ruler distance (the Planck length) beyond the Schwarzschild horizon, where it has not suffered any gravitational redshift, or, alternatively, suffered maximal gravitational blueshift and (ii) the firewall temperature is on the order of the Planck temperature, independently of the mass and hence also of the Schwarzschild radius of a Schwarzschild black hole. We then explain the exponential nature of the gravitational frequency shift as a function of the gravitational potential. Next, we consider the firewall-mass problem, and provide an at least prima facie tentative resolution thereto based on: (i) the mass of a firewall being canceled by the negative gravitational mass = (negative gravitational energy)/c² accompanying its formation, (ii) the unchanged observations of a distant observer upon formation of a firewall, and (iii) Birkhoff's Theorem (actually first discovered by Jørg Tofte Jebsen). We then consider one aspect of thermodynamics in gravitational fields, showing that equilibrium relativistic gravitational temperature gradients cannot be exploited to violate the Second Law of Thermodynamics.

The structure and phenomena arising from charge transfer in cold field emission modus in a single closed carbon nanotube under cold field emission conditions were studied. By studying microphotographs in various microscopes - AFM, SEM, TEM it was found inhomogeneities in the form of two types of superlattices. The conductivity of the emitter section of a nanodiode circuit with an emitter made of an individual closed carbon nanotube (CNT) and arrays of closed CNTs was studied. High values of cold field emission were observed, as well as nonlinearity and anomalies of the current-voltage characteristic (I-V characteristics), which manifested themselves in the form of peaks at low and high current values. Peaks in the CVC have distinct areas of negative differential conductivity. It is argued, that the anomalously high currents in the I–V characteristics of cold field emission of electrons from a nanoemitter made of closed CNTs can be associated with a sharp increase in the density of electron states at energies near the van Hove singularity.

Because imbalanced power will cause the loss of the propulsion motor of the railway vehicle, and the increase in temperature will shorten the service life of the electric vehicle. Not only this, but also increase the cost of electricity and maintenance. In the past, the industry only focused on methods to improve power quality such as load capacity, relay setting, and harmonic resolution. Now, the consider of three-phase unbalance rate (TPUR) must be applied. I propose special transformers wiring (STW) to improve the three unbalance rates and provide different transformer wiring methods. According to the IEEE Committee, in the future, power companies will need to install balanced relay stations to improve three-phase unbalance rate. the internal regulations of Taipower must be less than 4.5% (voltage unbalance rate (NPSUR)of 2.5% and motor temperature rise of 12.5%). the derivation of the transformer "three-phase unbalance rate" model is the focus of the railway system. This research is based on the model derivation of different wiring methods to improve the hot problem caused by the three-phase imbalance and improve the service life of the train. And pointed out that Scott, Le-Blanc, Modified-Woodbridge three wiring methods can be applied to future railway system routes to improve the three-phase unbalance rate, in line with the IEEE standard of less than 2%.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

Chen, et al., compared two modified polyurethane-based wound dressings (PUE and PUESi), both intended for use in chronic wounds, with a negative control (gauze) and a positive control (PolyMem) via a series of preliminary in vitro and rodent model tests. Future studies may find that one or both of these two new dressings are beneficial. However, the results of this first study cannot be relied upon. Although they exhibited in-depth knowledge of manufacturing techniques, the study designers seem far less familiar with the science of wound healing and with PolyMem wound dressings. This helps explain the flaws in the methods that lead to many of their tests not being translatable to real-world settings. In addition, the interpretation of some of the test results is questionable.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

AI is extraordinarily useful technology but it is becoming increasingly powerful with rapidly growing capabilities to disrupt and harm human society. We call on international and national organizations and individuals to join forces in banning the development of superintelligent AI and introducing regulations to prevent and mitigate AI-caused harm.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

In general, a superconductor has zero resistance, although it requires significant refrigeration or high pressures with high manufacturing costs, which prevents it into practical applications. In other words, solving these issues implies main superconducting researches. To solve these problems, this paper describes a new type of superconductivity, which is independent for temperatures and which operates without pressures. The principles of the presented system are as follows:First a voltage source, a current source and a load are connected in series. Then, the voltage of the voltage source is adjusted to balance the voltage of the load. Under this condition, the balance of the two voltages provides a zero voltage between the taps of the current source and the generated current from the voltage source becomes zero because of the internal infinite resistance of the current source. As a result, the electric powers generated by the two sources are zero, and therefore, the load cannot generate Joule heating because of energy conservation. However, the current from the current source (not the voltage source) is not zero; therefore, we can predict that the resistance of the load must be zero. As a theory, we derived a new electric field and transient attractive force, which result in a very short coherence of an electron pair because there is not the Coulomb repulsive force due to the existence of the above transient attractive force. Note that both the forces are derived by the Poisson equation, which implies that they cannot be compatible. Therefore, the pair combination energy from spins becomes extremely strong, which is not destroyed by the normal heat energy. Moreover, every center-of-mass motion of electron pair results in the Bose-Einstein condensation and the macroscopic wave function, which produces the London equation (i.e., the Meissner effect). Moreover, by introducing the equivalent circuit, this paper conducted numerical calculations. As a result, we could derive numerically zero resistance and responses for additional static magnetic fields as a discharged current, which implies the Meissner effect. Note that this paper has prepared Appendix section, which provides a guide to reproduce actual experiments and preliminary experimental results. These results in the Appendix indicate the zero resistances and Meissner effects.

Abstract: Discussed is an expansion of SRT to fourth-order of space-time including any velocities and possible negative kinetic energies by real rest mass in analogy of the model amplitude of enforced damped oscillation. This paper serves an introduction to developed SRT including superluminar translating velocities without tachyons or imaginary restmass. Focused is on those parts, which develop the elaborated lorentz-transformations. Discussed are the problems of this theory.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. Results: HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p&lt;0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

Forest recreation can be successfully conducted for the purpose of psychological relaxation, as has been proven in previous scientific studies. During the winter in many countries, when snow cover occurs frequently, forest recreation (walking, relaxation, photography, etc.) is common. Nevertheless, whether forest therapy conducted in a forest environment with a snow cover will also have a positive effect on psychological indicators remains unknown. Furthermore, male subjects frequently participate in forest therapy experiments, whereas females are rarely involved. Thus, in this study, the effectuality of forest recreation during winter and with snow cover was tested on 32 young females. For these reasons, the experiment involved 15-minute periods of relaxation in a forest environment or in an urban environment, in addition to a pre-test under indoor conditions. Four psychological questionnaires (POMS, PANAS, ROS, SVS) were administered to participants before and after interventions. Results showed that participants’ levels of negative mood, as measured by different aspects of the POMS questionnaire (tension-anxiety, anger-hostility, depression-dejection, confusion, fatigue), decreased after exposure to the forest environment. In contrast, both tension-anxiety and anger-hostility increased in the urban environment. The indicator of negative affect from the PANAS questionnaire also increased after exposure to the urban environment, whereas the indicator of positive affect based on PANAS was higher in the forest environment than in the urban environment. Restorativeness and subjective vitality exhibited higher values after exposure to the forest environment in comparison to those from the control and pre-test. The changes in these indicators demonstrates that forest recreation in the snow during winter can significantly increase psychological relaxation in young females, as well as showing that recreation can be successfully conducted under these winter conditions.

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

Hidradenitis suppurativa and Langerhans cell histiocytosis are rare disorders that can reveal similar clinical manifestations, making differential diagnosis difficult. A definitive diagnosis requires biopsy and histological confirmation in suspicious cases. The complex pathophysiology of these diseases has still not been understood, therefore the treatment is still a challenge for physicians. It is seen with predilection in the intertriginous areas of the body, predominantly in the axillary region, rarely requiring a surgical procedure. However perineal, perianal, and gluteal HS usually necessitates some form of surgical treatment. Langerhans cell histiocytosis (histiocytosis X) is a very rare systemic disease manifested by clonal cell proliferation of histiocytic-dendritic nature, with pseudonodular manifestation that deeply infiltrates the hypodermis and ulcerates the epidermis on the surface. Langerhans cells are dendritic, antigen-presenting cells localized in the suprabasal regions of the squamous epithelium of the skin and mucous membranes, which help regulate the immune system. In this report, we present our experience with extensive gluteal, perineal, and perianal hidradenitis suppurativa and Langerhans cell histiocytosis cases, including our treatment methods and outcomes.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles

Matiyasevich's theorem states that there is no algorithm to decide whether or not a given Diophantine equation has a solution in non-negative integers. Smorynski's theorem states that the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable. We prove: (1) Smorynski's theorem easily follows from Matiyasevich's theorem, (2 ) Hilbert's Tenth Problem for Q has a negative solution if and only if the set of all Diophantine equations with a finite number of rational solutions is not recursively enumerable.

Assuming a two component, positive and negative mass, superfluid/supersolid for space (the Winterberg model), we model the Higgs field as a condensate made up of a positive and a negative mass, planckion pair. The connection is shown to be consistent (compatible) with the underlying field equations for each field, and the continuity equation is satisfied for both species of planckions, as well as for the Higgs field. An inherent length scale for space (the vacuum) emerges, which we estimate from previous work to be of the order of,

Gravitation is interpreted to be an “ontomathematical” force or interaction rather than an only physical one. That approach restores Newton’s original design of universal gravitation in the framework of “The Mathematical Principles of Natural Philosophy”, which allows for Einstein’s special and general relativity to be also reinterpreted ontomathematically. The entanglement theory of quantum gravitation is inherently involved also ontomathematically by virtue of the consideration of the qubit Hilbert space after entanglement as the Fourier counterpart of pseudo-Riemannian space. Gravitation can be also interpreted as purely mathematical or logical “force” or “interaction” as a corollary from its ontomathematical (rather than physical) realization. The ontomathematical approach to gravitation is implicit in general relativity equating it to operators in pseudo-Riemannian space obeying the Einstein field equation and also well-known by the “geometrization of physics”. Quantum mechanics shares the same by the separable complex Hilbert space and defining “physical quantity” by the Hermitian operators.

We present a new interpretation of the Higgs field as a composite particle made up of a positive, with, a negative mass Planck particle. According to the Winterberg hypothesis, space, i.e., the vacuum, consists of both positive and negative physical massive particles, which he called planckions, interacting through strong superfluid forces. In our composite model for the Higgs boson, there is an intrinsic length scale associated with the vacuum, different from the one introduced by Winterberg, where, when the vacuum is in a perfectly balanced state, the number density of positive Planck particles equals the number density of negative Planck particles. Due to the mass compensating effect, the vacuum thus appears massless, charge-less, without pressure, energy density, or entropy. However, a situation can arise where there is an effective mass density imbalance due to the two species of Planck particle not matching in terms of populations, within their respective excited energy states. This does not require the physical addition or removal of either positive or negative Planck particles, within a given region of space, as originally thought. Ordinary matter, dark matter, and dark energy can thus be given a new interpretation as residual vacuum energies within the context of a greater vacuum, where the populations of the positive and negative energy states exactly balance. In the present epoch, it is estimated that the dark energy number density imbalance amounts to, , per cubic meter, when cosmic distance scales in excess of, , are considered. Compared to a strictly balanced vacuum, where we estimate that the positive, and the negative Planck number density, is of the order, particles per cubic meter, the above is a very small perturbation. This slight imbalance, we argue, would dramatically alleviate, if not altogether eliminate, the long standing cosmological constant problem.

This study delves into the intricate interplay between cosmology and gravity in dilaton-based models, enhancing our understanding. Exploring boundary theories coupled to gravity, we derive a four-dimensional effective theory from the cosmological constant. Dilaton gravity is then scrutinized, revealing elegant solutions and insights into brane embedding. The analysis extends to probe scalar fields, employing the WKB approximation in both conformal and non-conformal cases. In summary, this work contributes to a nuanced understanding of the complex relationship between cosmology and gravity in dilaton-based frameworks.

We prove: (1) the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable, (2) the set of all Diophantine equations which have at most finitely many solutions in positive integers is not recursively enumerable, (3) the set of all Diophantine equations which have at most finitely many integer solutions is not recursively enumerable, (4) analogous theorems hold for Diophantine equations D(x₁, …, x_p) = 0, where p ∈ N\{0} and for every i ∈ {1, …, p} the polynomial D(x₁, …, x_p) involves a monomial M with a non-zero coefficient such that x_i divides M, (5) the set of all Diophantine equations which have at most k variables (where k ≥ 9) and at most finitely many solutions in non-negative integers is not recursively enumerable.

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

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.