Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Endophytic fungi colonize the inner tissues of plants and provide direct and indirect benefits to the plant. Although Mongolia is rich in medicinal plants, due to climatic and anthropogenic reasons the resources are being depleted and many species are under the threat of gradual extinction, while the endophytic fungi of Mongolian plants are largely unknown. Understanding the diversity and metabolic potential of endophytic fungi is of great significance in terms of the utilization of beneficial fungal strains in plant propagation and the discovery of bioactive compounds. In this study, a total of 24 culturable endophytic fungal strains were isolated from Cynomorium songaricum (Rupr.), a medicinal and vulnerable plant species of Mongolia. Based on the morphological characteristics and the sequences of the rDNA internal transcribed spacer (ITS) region, the isolates were identified to 6 genera: Fusarium (8), Clonostachys (7), Penicillium (6), Alternaria (1), Aspergillus (1), and Madurella (1). The antimicrobial activity was assessed by agar-diffusion method, revealing that 15 strains were able to inhibit the growth of at least one of the test organisms. Among them, 1 strain showed inhibitory activity against Escherichia coli, 12 against Bacillus subtilis, 13 against Staphylococcus aureus, 8 against Aspergillus niger, respectively. All fungal strains were screened for their ability to solubilize complex phosphorus and zinc minerals and for their production of indole-3-acetic acid (IAA). The strains were preserved in the national culture collection for further sustainable exploitation of their biotechnological potential.

Lucky bamboo (Dracaena sanderiana hort. ex Mast. = Dracaena braunii) is a domestic species widely cultivated for ornamental purposes in China. In March 2022, a severe occurrence of anthracnose disease was observed on the stems of lucky bamboo plants in a greenery retail store located in Nanjing, Jiangsu Province, China. The morphological characteristics of isolates obtained from diseased stem tissues were identical with those described for Colletotrichum species. Based on multilocus phylogenetic analysis with the internal transcribed spacer (ITS), actin (ACT) gene, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, the pathogen was identified as Colleto-trichum gloeosporioides (Penz.) Penz. & Sacc. Pathogenicity was verified by mycelial plug-inoculating stem cuttings of one-year-old lucky bamboo plants and spray-inoculating whole one-year-old lucky bamboo plants, respectively. Koch’s postulates were fulfilled by the re-isolation of C. gloeosporioides from symptomatic tissues. To the best of our knowledge, this report describes the first time that C. gloeosporioides was observed to cause anthracnose on lucky bamboo in China.

Endophytic microbes are a ubiquitous group of plant-associated communities that colonize the intercellular or intracellular host tissues while giving numerous beneficial effects to the plants. All the plant species are thought to be associated with endophytes, majorly constituted with bacteria and fungi. During the last two decades, there has been a considerable movement toward the study of endophytes associated with coffee plants. In this review, the main consideration is given to address the coffee-associated endophytic bacteria and fungi, particularly their action on plant growth promotion and the biocontrol of pests. In addition, we sought to identify and analyze the gaps in available research. Additionally, the potential of endophytes to improve the quality of coffee seeds is briefly discussed. Even though there are limited studies on the subject, it has been well recognized the potentiality of coffee endophytes in plant growth promotion through enhancing nitrogen fixation, availability of minerals, nutrient absorption, secretion of phytohormones, and other bioactive metabolites. Further, the antagonistic effect against various coffee pathogenic bacteria, fungi, nematodes, and also insect pests lead to the protection of the crop. Furthermore, it is recognized that endophytes enhance the sensory characteristics of coffee as a new field of study.

In Nitrate Vulnerable Zones (NVZ) site-specific techniques are needed to match N availability with durum wheat (Triticum turgidum subsp. durum Desf.) requirements. Enhanced-efficiency fertilizers (EEF) can improve efficient N supply and reduce leaching, thus contributing to sustainable agriculture. To study the effects of rates, sources and timings of nitrogen application, two-year field experiments were carried out at two Mediterranean NVZs of Central Italy (Pisa and Arezzo). The trial compared: i) two N rates: one based on the crop N requirements (NO), the other on the Action Programmes’ prescriptions of the two NVZ (NAP); ii) three N sources (urea, methylene urea (MU), and nitrification inhibitor (NI) 3,4-Dimethylpyrazole phosphate (DMPP); and two top-dressing timings (1st tiller visible and 1st node detectable). Grain yield and yield components were determined, together with N uptake. Results showed that: i) grain and biomass production were reduced with NAP at both locations; ii) urea performed better than slow-release fertilizers; iii) the best application time varied depending on N source and location: at Pisa enhanced-efficiency fertilizers achieved higher yields when applied earliest, while for urea the contrary was true; at Arezzo different N fertilizers showed similar performances between the two application timings. Different behaviors of top-dressing fertilizers at the two localities could be related to the diverse patterns of temperatures and rainfall. Therefore, optimal fertilization strategies vary according to environmental conditions.

Accurate climate data at fine spatial resolution are essential for scientific research and the development and planning of crucial social systems, such as energy and agriculture. Among them, sea surface temperature plays a critical role as the associated El Niño-Southern Oscillation (ENSO) is considered a significant signal of global interannual climate system. In this paper, we propose an implicit neural representation-based interpolation method with temporal information (T_INRI) to reconstruct climate data of high spatial resolution, with sea surface temperature as the research object. Traditional deep learning models for generating high-resolution climate data are only applicable to fixed resolution enhancement scales. In contrast, the proposed T_INRI method is not limited to the enhancement scale provided during the training process and its results indicate that it can enhance low-resolution input by arbitrary scale. Additionally, we discuss the impact of temporal information on the generation of high-resolution climate data, specifically, which month the low-resolution sea surface temperature data is from. Our experimental results indicate that T_INRI is advantageous over traditional interpolation methods under different enhancement scales, and the temporal information can improve T_INRI performance for a different calendar month. We also examined the potential capability of T_INRI in recovering missing grid value. These results demonstrate that the proposed T_INRI is a promising method for generating high-resolution climate data and has significant implications for climate research and related applications.

Super duplex stainless steel (SDSS) is used for manufacturing large valves and pipes in offshore plants because of its excellent strength and corrosion resistance. Large valves and pipes are manufactured by forging after casting, and the outside and inside microstructures are different owing to the difference in the cooling rate caused by the thermal conductivity. This microstructural variation causes cracks during solution annealing, which breaks the materials. To study toe corrosion resistance of the SDSS forged material, the microstructure was conducted based on the difference in the cooling rate between the inside and outside of the cast SDSS. To analyze the effects of the secondary phase fraction before solution annealing on the solution and corrosion resistance, the corrosion resistance with and without solution annealing was measured using the potentiodynamic polarization test and critical temperature test after the precipitation of the secondary phase. In the potentiodynamic polarization test, the secondary phase decreased the activation polarization and increased the corrosion rate. The critical pitting temperature exhibited the effect of the secondary phase.

In our recently published papers, considering Planck mass based light speed growing black hole universe and scaled Hawking’s black hole temperature formula, we have developed a simple procedure for estimating the current Hubble parameter and current cosmic mass. In addition to that, without considering galactic dark matter, starting from 10 km/sec to 500 km/sec, we have tried to fit the observed galactic flat rotation speeds with a concept of super gravity of galactic baryonic mass. To estimate the equivalent mass of currently hypothecated galactic dark matter, we have introduced a timely increasing cosmological reference mass unit. Its current magnitude seems to be around 200 million solar masses. In this paper, considering 200 million solar masses as a characteristic representation of cosmic weak interaction mass unit, we have developed a simple formula for its estimation. We would like to appeal that, weak interaction boosts the gravity of galaxies in proportion with their virtual dark mass as (galactic baryonic mass)^3/2 / (200 million solar masses)^1/2. With further study- dark matter existence and physical properties can be understood in a theoretical approach.

Green innovation has become an important combination of high-quality economic growth and sustainable development of ecological environment. In this paper, the super-efficiency network SBM model is used to measure the two-stage green innovation efficiency of industrial science and technology R&D and achievement transformation in 30 provinces and cities from 2009 to 2019, and exploratory Data Analysis (ESDA) and spatial econometric model are used to investigate the spatial-temporal evolution characteristics and influencing factors of green innovation efficiency. The results show that: firstly, the overall efficiency of industrial green innovation is low, and the efficiency of scientific research and development and achievement transformation has experienced three stages of "upward-declining-revitalized period". The low efficiency of achievement transformation is an important factor hiding the improvement of the efficiency of industrial green innovation. Secondly, The industrial green innovation efficiency gradually increases from northwest to southeast, forming a centralized "line" and "block" distribution. The high efficiency area is still concentrated in the eastern coastal region, and the balanced development trend is obvious in the central and western regions. Finally, openness has a positive impact on the two-stage green innovation efficiency; Industrial structure and government investment in science and technology have a positive impact on the efficiency of science and technology research and development, but have no significant effect on the efficiency of achievement transformation. Enterprise size has a positive effect on achievement transformation efficiency, but has no significant effect on R&D efficiency. Environmental regulation has a positive impact on R&D efficiency and a negative impact on achievement transformation efficiency.

The holy grail of Artificial Intelligence (AI) has been to mimic human intelligence using computing machines. Autopoiesis which refers to a system with well-defined identity and is capable of re-producing and maintaining itself and cognition which is the ability to process information, apply knowledge, and change the circumstance are associated with resilience and intelligence. While classical computer science (CCS) with symbolic and sub-symbolic computing has given us tools to decipher the mysteries of physical, chemical and biological systems in nature and allowed us to model, analyze various observations and use information to optimize our interactions with each other and with our environment, it falls short in reproducing even the basic behaviors of living organisms. We present the foundational shortcomings of CCS and discuss the science of infor-mation processing structures (SIPS) that allows us to fill the gaps. SIPS allows us to model su-per-symbolic computations and infuse autopoietic and cognitive behaviors into digital machines. They use common knowledge representation from the information gained using both symbolic and sub-symbolic computations in the form of system-wide knowledge networks consisting of knowledge nodes and information sharing channels with other knowledge nodes. The knowledge nodes wired together fire together to exhibit autopoietic and cognitive behaviors.

This paper combines the Good Regulator Theorem with the Law of Requisite Variety and seven other requisites that are necessary and sufficient for a cybernetic regulator to be effective and ethical. The resulting Ethical Regulator Theorem provides a basis for systematically evaluating and improving the adequacy of existing or proposed designs for systems that make decisions that can have ethical consequences; regardless of whether the regulators are human, machines, cyberanthropic hybrids, organizations, corporations, or government institutions. The theorem is then used to define an ethical design process that has potentially far-reaching implications for society. A six-level framework is proposed for classifying cybernetic and superintelligent systems, which highlights the existence of a possibility-space bifurcation in our future time-line. The implementation of “super-ethical” systems is identified as an urgent imperative for humanity to avoid the danger that superintelligent machines might lead to a technological dystopia. Third-order cybernetics is defined as the cybernetics of ethical systems. Concrete actions, a grand challenge, and a vision of a super-ethical society are proposed to help steer the future of the human race and our wonderful planet towards a realistically achievable minimum viable cyberanthropic utopia.

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.

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.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared by freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at −180 °C with subsequent immersion in liquid nitrogen at −196 °C. These materials were then dried under reduced pressure in a freeze-dryer after which they were sintered by heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of up to 1.24 µm and macroscopic, interconnected pores up to 25.8 µm in size. The effects of non-ionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of the study is to evaluate the clinical findings of glucose 6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency, to prevent further examinations for prolonged jaundice, and to contribute by regulating its treatment. At the same time, it is to determine whether systemic-immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can be used in addition to conventional complete blood count (CBC) parameters in the diagnosis of neonatal prolonged jaundice. Methods: In full term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 5 mg/dL, whose jaundice persisted after the 10th day, were included in the study. Results: 63.5% of the patients were male and the mean age was 31±6 days. G6PD was negatively perfectly correlated with NLR (r: -1; p

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Microbial production is a promising method that can overcome major limitations in conventional methods of lycopene production, such as low yields and variations in product quality. Significant efforts have been made to improve lycopene production by engineering either the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway or mevalonate (MVA) pathway in microorganisms. To further improve lycopene production, it is critical to utilize metabolic enzymes with high specific activities. Two enzymes, 1-deoxy-D-xylulose-5-phosphate synthase (Dxs) and farnesyl diphosphate synthase (IspA), are required in lycopene production using MEP pathway. Here, we evaluated the activities of Dxs and IspA of Vibrio sp. dhg, a newly isolated and fast-growing microorganism. Considering that the MEP pathway is closely related to the cell membrane and electron transport chain, the activities of the two enzymes of Vibrio sp. dhg were expected to be higher than the enzymes of E. coli. We found that Dxs and IspA in Vibrio sp. dhg exhibited 1.08-fold and 1.38-fold higher catalytic efficiencies, respectively. Consequently, the heterologous overexpression improved the specific lycopene production by 1.88-fold. Our findings could be widely utilized to enhance production of lycopene and other carotenoids.

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performed transcriptome-wide profiling of differential gene expression for human retinal endothelial cells (HRECs) treated with PlGF antibody. The effect of antibody treatment on the samples was validated using trans-endothelial electric resistance (TEER), and western blot. A total of 3760 genes (1750 upregulated and 2010 downregulated) were found to be differentially expressed between the control and PlGF antibody treatment group. These differentially expressed genes (DEGs) were used for gene ontology and enrichment analysis to identify gene function, signal pathway, and interaction networks. The gene ontology results revealed that catalytic activity (GO:0003824) of molecular function, cell (GO:0005623) of the cellular component, and cellular process (GO:0009987) were among the most enriched biological processes. Pathways such as TGF-β, VEGF-VEGFR2, p53, apoptosis, pentose phosphate pathway, and ubiquitin-proteasome pathway, were among the most enriched, and TGF-β1 was identified as a primary upstream regulator. These data provide new insights into the underlying molecular mechanisms of PlGF in mediating biological functions, in relation to DR.

Single Image Super Resolution (SSIR) is a problem in computer vision where the goal is 1 to create high-resolution images from low-resolution ones. It has important applications in fields 2 such as medical imaging and security surveillance. While traditional methods such as interpolation 3 and reconstruction-based models have been used in the past, deep learning techniques have recently 4 gained attention due to their superior performance and computational efficiency. This article proposes 5 an Autoencoder based Deep Learning Model for SSIR, in particular, a light model that uses fewer 6 parameters without compromising performance. The down-sampling part of the Autoencoder 7 mainly uses 3 by 3 convolution and has no subsampling layers. The up-sampling part uses transpose 8 convolution and residual connections from the down sampling part. The model is trained using a 9 subset of the VILRC ImageNet database. The model is evaluated using quantitative metrics PSNR, 10 SSIM as well as qualitative measures such as perceptual quality. PSNR and SSIM figures as high as 11 76.06 and 0.93 are reported.

With 500+ papers and 20+ books spanning many scientific disciplines, Mark Burgin has left an indelible mark and legacy for future explorers of human thought and information technology professionals. In this paper, I discuss his contribution to the evolution of machine intelligence using his general theory of information (GTI) based on my discussions with him and various papers I co-authored during the past eight years. His construction of a new class of digital automata to overcome the barrier posed by the Church-Turing Thesis, and his contribution to Super-Symbolic Computing with Knowledge Structures, Cognizing Oracles, and Structural Machines are leading to practical applications changing the future landscape of information systems. GTI provides a model for the operational knowledge of biological systems to build, operate, and manage life processes using 30+ trillion cells capable of replication and metabolism. The schema, and associated operations derived from GTI are also used to model a digital genome specifying the operational knowledge of algorithms executing the software life processes with specific purposes using replication and metabolism. The result is a digital software system with a super-symbolic computing structure exhibiting autopoietic and cognitive behaviors that biological systems also exhibit. We discuss here one of these applications.

The eco-efficiency of cultivated land use (ECLU) is an important indicator for the construction of ecological civilization in China. Exploring the spatiotemporal dynamic evolution of the ECLU is helpful for sustainable use of arable land, ensuring food security and ecological security. However, previous studies have mostly focused on the use of a slacks-based measure (SBM) model for ECLU measurement, ignoring the more accurate epsilon-based measure (EBM) model. Therefore, in this study, firstly, we explored the conceptual framework of ECLU, and then, based on the panel data of the counties in the region around Beijing and Tianjin from 2005 to 2020, we investigated the spatial and temporal evolution of ECLU by using the Super-EBM model, kernel density estimation method, and spatial Markov chain model. Results displayed: (1) From 2005 to 2020, the ECLU in the region around Beijing and Tianjin displayed an increasing state, but the average value was only 0.55. (2) The time evolution of the ECLU has gradually polarized, the internal gap has widened, but it tends to stabilize. (3) The ECLU in the region around Beijing-Tianjin was more inclined to keep it the same and there was a "club convergence" phenomenon, which was meaningfully affected by the background of neighboring areas. In the light of local conditions, the government should reasonably formulate the path to optimize the ECLU, strengthen the linkage with the surrounding cities, and bring into play the positive spillover effect.

This paper presents results of the magnetic dynamics study (the microwave power absorptions at the fixed frequencies, during magnetic field sweeping) in samples of Y3Fe5O12 single crystals in the form of plates and spheres of various sizes, at frequencies exceeding 30 GHz, in magnetic fields up to 18 kOe, at room temperature and T=77 K. It was found, that in this case, the inhomogeneity’s of the magnetic state manifested itself in the Y3Fe5O12 samples in as 2D local phase separation regions. These 2D phase separation regions formed inside domain walls representing superlattices with size’s 700 – 900 Å. Landau diamagnetism or de Haas van Alphen oscillations observed in the 2D phase separation regions at room temperature and T=77 K, depending on the shape and size of the studied plates and spheres.

We introduce a new class of Vertex Operator Algebras Y+ and their duals, which generalize the standard W-algebras WN of type sl(N). These algebras can be defined in terms of junctions of boundary conditions and interfaces in the GL-twisted N = 4 Super Yang Mills gauge theory. The aim of these technical calculations is to find the relation of these ortho-symplectic Y-algebras to truncations of even W\infinity.

Deep Learning is a recent and important addition to the computational toolbox available for image reconstruction in fluorescence microscopy. We review state-of-the-art applications such as image restoration, super-resolution, and light-field imaging, and discuss how the latest Deep Learning research can be applied to other image reconstruction tasks such as structured illumination, spectral deconvolution, and sample stabilisation. Despite its successes, Deep Learning also poses significant challenges, has often misunderstood capabilities, and overlooked limits. We will address key questions, such as: What are the challenges in obtaining training data? Can we discover structures not present in the training data? And, what is the danger of inferring unsubstantiated image details?

The development of saltiness enhancement peptides is important in reducing salt intake and promoting dietary health. Our study aimed to analyze and identify straw mushroom enzymatic peptides with salty taste enhancing effects. The taste-related peptides within the straw mush-room extract were isolated via ultrafiltration and identified using UPLC-Q-TOF-MS/MS. Sub-sequent, E-tongue and sensory analyses unveiled that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides exhibited a saltiness enhancement effect. The UPLC-Q-TOF-MS/MS analysis identified 220 peptides within the ultrafiltration fractions (500-2000 Da), which were then assessed for their interaction with the T1R1/T1R3 receptor. The investigation underscored the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in the binding of peptides from triple enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Notably, 3.2 mmol of VPGGQEIKDR enhanced a 0.05% NaCl solution to the saltiness level of a 0.15% NaCl solution. Also, 0.8 mmol of YNEDNGIVK elevated a 0.05% NaCl solution to the saltiness of a 0.1% NaCl solution.

The main objective of the paper is to provide a thorough analysis of currently used modulation control schemes for single phase bidirectional dual active bridge DC/DC converter. In this article, it will be shown that single phase shift, extended phase shift and Dual phase shift modulation schemes are special cases of triple phase shift (TPS) modulation scheme. The article aims to highlight six TPS switching modes and their complements with the operational constraints. Unlike previous studies that regarded TPS as a complex scheme, this paper simplifies the analysis of each mode and aims to standardize the understanding of TPS modulation in DAB converters. Power equations, range of power transferred and zero voltage switching (ZVS) are derived for all the modes under TPS without assuming fundamental component analysis. Additionally, a generic optimization algorithm is developed to show the advantages of TPS modulation and thus, detailed analysis presented in this paper provides valuable insights for single phase DAB converter designers in identifying a wide range of optimization algorithms to achieve higher efficiency under TPS modulation. This analysis contributes to the advancement of bidirectional DAB converter technology and facilitates its application in various power electronic systems.

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 main functions of the automated systems rely on the advanced sensors for detection and perception of the environment around the vehicle. Radars and cameras are commonly utilized to detect the potential obstacles and vehicles ahead on the road. Nevertheless, cameras can generate spurious detections in the extreme weather conditions such as fog, rain, dust, snow, dark, and heavy sunlight in the sky. Due to limitations in vertical field view of the radars, single radars are not reliable to detect the height of the targets precisely. In this paper, a triple radar arrangement (long-range, medium-range, and short-range radars) based on sensor fusion technique is proposed to detect objects with different size in level 2 Advanced Driver-Assistance (ADAS) system. The typical objects including truck, pedestrians, and animals are detected in different scenarios. The developed model considered ISO 26262 and ISO/PAS 21448 to reasonably address insufficient robustness and inability of the sensors. The models of sensor and level 2 ADAS systems are developed using MATLAB toolbox and Simulink. Sensor detection performance is determined by running simulations with triple radar setup. Obtained results demonstrate that the proposed approach generates accurate detections of targets in all tested scenarios.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients, compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and this is associated with cancer metastasis to the bone and poor prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression that may be linked to the pathogenic behavior of fibroblast-like synoviocytes, cartilage destruction, and bone erosion.

Integrating triple bottom line (TBL) goals into supply chains (SCs) is a challenging task which necessitates the careful coordination of numerous stakeholders’ individual interests. Recent technological advancements can impact TBL sustainability by changing the design, structure and management of modern SCs. Blockchain technology enables immutable data records and facilitates a shared data view along the supply chain. The Physical Internet (PI) is an overarching framework that can be applied to create a layered and comprehensive view of the SC. In this conceptual paper I define and combine these technologies and derive several high-level research areas and research questions to investigate adoption, management as well as structural SC issues. I suggest a theory-based research agenda for the years to come that exploits the strengths of rigorous academic research, while remaining relevant for the industry. Furthermore, I suggest various well-established theories to tackle the respective research questions and provide specific directions for future research.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

A system of simultaneous multi-variable nonlinear equations can be solved by the Newton’s method with local q-quadratic convergence if the Jacobian is analytically available. If this is not the case, then quasi-Newton methods with local q-superlinear convergence give solutions by approximating the Jacobian in some way. Unfortunately, the quasi-Newton condition (secant equation) doesn’t completely specify the Jacobian approximate in multi-dimensional case, so its full-rank update is not possible with classic variants of methods. The suggested new iteration strategy (“T-Secant”) allows full-rank update of the Jacobian approximate in each iteration by determining two independent approximates for the solution. They are used to generate a set of new independent trial approximates, then the Jacobian approximate can fully be updated. It is shown, that the T-Secant approximate is in the vicinity of the classic quasi-Newton approximate, providing that the solution is evenly surrounded by the new trial approximates. The suggested procedure increases the super-linear convergence of the secant method (φS = 1.618...) to super-quadratic (φT = φS + 1 = 2.618...) and the quadratic convergence of the Newton-method (φN = 2) to cubic (φT = φN + 1 = 3) in one dimensional case. The Broyden-type efficiency (mean convergence rate) of the suggested method in multi-dimensional case is an order higher than the efficiency of other classic low-rank update quasi-Newton methods as shown by numerical examples on a Rosenbrock-type test-function with up to 1000 variables. The geometrical representation (hyperbolic approximation) in single variable case helps explaining the basic operations and a vector-space description is also given in multi-variable case.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

The cellular cytoskeleton provides the cell with a mechanical rigidity which allows mechanical interaction between cells and the extracellular environment. The actin structure plays a key role in mechanical events like motility, or establishment of cell polarity. From the earliest stages of development, as represented by ex vivo expansion of naïve embryonic stem cells (ESCs), the critical mechanical role of the actin structure is becoming recognized as a vital cue for correct segregation and lineage control of cells and as a regulatory structure that controls several transcription factors. Naïve ESCs have a characteristic morphology and the ultrastructure that underlies this condition remains to be further investigated. Here, we investigate the 3D actin cytoskeleton of naïve mouse ESCs using super resolution optical reconstruction microscopy (STORM). We investigate the morphological, cytoskeletal and mechanical changes in cells cultured in 2i or Serum/LIF media reflecting a homogenous preimplantation cell state and a state that is closer to embarking on differentiation. STORM imaging showed that the peripheral actin structure undergoes a dramatic change between the two media conditions. We also detected micro-rheological differences in the cell periphery between the cells cultured in these two media correlating well with the observed nano-architecture of the ESCs in the two different culture conditions. These results pave the way for linking physical properties and cytoskeletal architecture to cell morphology during early development.

To understand the mystery of final unification, in our earlier publications, we proposed that, 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions; and 2) There exists a strong interaction elementary charge (e_s) in such a way that, it's squared ratio with normal elementary charge is close to inverse of the strong coupling constant. In this context, starting from lepton rest masses to stellar masses, we have developed many interesting and workable relations. We noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 585 GeV. It can be considered as the zygote of all elementary particles and galactic dark matter. Proceeding further, with a characteristic fermion-boson mass ratio of 2.27, quarks can be classified into quark fermions and quark bosons. Considering strong charge conservation and electromagnetic charge conservation, fractional charge quark fermions and quark bosons can be understood. Quark fermions that generate observable massive baryons can be called as Fluons. Quark bosons that generate observable mesons can be called as Bluons. By considering a new hadronic fermion of rest energy 103.4 GeV, rest masses of fluons and bluons can be estimated and there by baryon masses and meson masses can be estimated.

A cursory look at Indian prime time news tells us much about the tone and tenor of the people associated with it. Exaggerations, hyperbole, and tempers run wild and news anchors flail in theatrical rage. News channels and news editors display their ideological affiliations subliminally. These affiliations — a factor of personal political stance, funding bodies, and investors — lead to partisan bias in the framing of news and, in some cases, can easily translate into racial prejudice. In this paper, I examine news coverage related to Muslims in India. I study the coverage of two issues specifically– love jihad and triple talaq –in prime time English news of two channels – Times Now and Republic TV. My analysis of the content, tone, and tenor of their coverage shows that these channels propagate associations between Islam and backwardness, ignorance and violence through consistent employment of the following tropes – ‘Muslim women need to be saved from Muslim men’, ‘Hindu women need to be saved from Muslim men’, and ‘Muslims are not fully Indian – they are anti-national’. I place this study of news media within the current political climate in India and briefly touch on the conversations it guides and provokes. This is also a call for further analysis on this subject to examine and evaluate how discourse manipulates public conversations and policy decisions.

The storage of biochemical information, which is a prerequisite for the development of the first cell, is an unsolved problem affecting all concepts of the origin of life. However, if the protected environment in the continental crust is taken into account, completely new possibilities emerge for identifying processes that may have been crucial for the formation of the first cell. Under this background, we can hypothesize that cellular life began, with a self-sustaining cycle of molecular reaction steps and information storage of peptide sequences in RNA in a crustal depth of approximately 1000 m. This cycle was made possible in an open system bound to gas-permeable tectonic fracture zones with a high proportion of CO₂ and/or N₂. It can be assumed that a large number of RNA-like molecular strands formed in the crustal environment, from which a special RNA was selected by flotation processes, which formed the basis of a proto-tRNA. The formation of peptides and vesicles in supercritical CO₂ and the chemical evolution of peptides have already been proven at conditions of the upper continental crust. The behavior of individual amino acids in connection with vesicle formation deserves special interest. Hydrophobic amino acids accumulate in the vesicle membrane, with their position in the membrane depending on the degree of hydrophobicity. Selection of a proto-tRNA with an acceptor arm ending with the bases CCA resulted in a distinctive property. The position of adenine at the tip of the acceptor arm permitted it to penetrate the membrane, allowing it to be linked to an amino acid at the 3'-OH position of the terminal ribose. The penetration depth was controlled by the hydrophobicity of the opposite anti-codon, with adenine always occupying the middle position for the hydrothermally formed hydrophobic amino acids. When the vesicle membrane was closely occupied by proto-tRNAs, the anti-codons acted as templates and stored the sequence of the peptides that form. In the cases of hydrophilic anti-codons, the acceptor arm does not reach far enough into the membrane. This allowed hydrophilic amino acids to be linked to 2´-OH.

KLHL genes and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in normal cell function and in disease (KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies that examined epigenetic factors affecting transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in a super-enhancer. The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence that gene neighbors (HHATL and FBXO32) of KLHL40 and KLHL38 harbor enhancer chromatin that likely upregulates the adjacent KLHL gene. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5’ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3’ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5’ ends of genes in studies of normal and abnormal gene regulation.

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 study presents a mathematical modeling for supporting the premise that our body is composed of blockchain systems. A cell population is considered a space with peer-to-peer communication networks for applying blockchain protocol. Transaction is defined as gene expression that constantly occurs for protein synthesis in each cell. The transaction process proceeds according to the blockchain protocol with sharing and recording the data on the blockchain ledger. The premise comes from the clues of the previous research such that the cell population is a complex structured network system having cell-to-cell connections. Although individual cells exhibit stochastic nonlinear dynamic behavior, cell population shows consensus behavior that reaches to ensemble through interaction among cells. It is inferred that gene expression is not regulated by the corresponding cell only nor determined by external intelligence such as the brain. This is achieved through a consensus through stochastic interactions between cells over the whole cell population. These findings imply that mathematical blockchain modeling is a suitable for gene expression process. The original contribution of the study is a methodology for applying mathematically the blockchain protocol to the real biological gene expression process. In other words, the DNA sequence is converted into a numeral bit sequence that makes it possible to implement the blockchain protocol. A new DNA sequence scheme is proposed with adding methylated cytosine and adenine as the 5th and 6th bases for including epigenetic information which has profound effect on gene expression and regulation. The methodology was applied to the real biological synthesis process of protein samples. The protein is composed of amino acids that are encoded by triplet codons of 216 kinds with 6 base RNA sequence. The gene expression information is traced backward from a synthesized protein sample, amino acids of codons, RNA transcript up to DNA sequence. One of the results is a numeric value in the form of a bit sequence with which mathematical blockchain modeling is applicable. The cryptographic authentication and the consensus process are mathematically proven to work properly by the blockchain protocol. It implies that the same protein is synthesized, but with different epigenetic data, then protein's latent material properties will certainly be different. Although the result has not been justified by the biologic experiment yet, it is sure that the biological hidden algorithm inside DNA sequence will be revealed by the binary bit-logic with physical on/off states which is mathematically proven. The research will greatly contribute to disease treatment and medicine development as well as epigenetics in the future.

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.

An off-grid solar energy storage system (ESS) in National Pingtung University of Science and Technology (NPUST) was built and officially operated on Jun. 16th 2022. The system is installed in a 40' general container with PV panels of solar power 8250 W_p on top of the container. The ESS is made by repurposed lithium iron phosphate (LFP) batteries of 20 kWh capacity, where a battery management system (BMS) is adopted to ensured the safety of the battery system. An energy management system (EMS) is built to receive, process, analyse, store, and output the energy information. In this manuscript, a brief engineering report about the system is given.

In the present study, the efficiency of a biomimetic approach by coating demineralized bone matrix (DBM) amorphous calcium phosphate (DBM+CaP), including its combination with serum albumin (DBM+CaP+BSA), was investigated. The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into DPCD with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/ml in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM+CaP and DBM+CaP+BSA, but more pronounced effects for DBM+CaP+BSA. In addition, for the DBM+CaP+BSA samples, a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite have been achieved.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

The Mediator is composed of multiple subunits conserved from yeast to humans and plays a central role in transcription. The tail components are not required for basal transcription but are required for response to different stresses. While some stresses are familiar such as heat, desiccation, and starvation, others are exotic, yet yeast can elicit a successful stress response. MCHM is a hydrotrope that induces growth arrest in yeast. We found that a naturally occurring variation in the Med15 allele, a component of the Mediator tail, altered the stress response to many chemicals in addition to MCHM. Med15 contains two polyglutamine repeats (polyQ) of variable lengths that change the gene expression of diverse pathways. Med15 protein existed in multiple isoforms and its stability was dependent on Ydj1, a protein chaperone. The protein level of the Med15 with longer polyQ tracts was lower and turned over faster than the allele with shorter polyQ repeats. MCHM sensitivity via variation of Med15 was regulated by Snf1 in a Myc tag dependent manner. Tagging Med15 with Myc altered its function in response to stress. Genetic variation in transcriptional regulators magnifies genetic differences in response to environmental changes. These polymorphic control genes are master variators.

Based on four major cosmological and astrophysical coincidences, it seems possible to develop a new model of Hubble-Hawking Universe having light speed expansion. Considering the analysis of 740 super novae data, it is possible to consider a constant rate of cosmic expansion. As there is no physical reasoning for the observed speed of light and all the cosmological observations are completely based on speed of light-by considering ‘light speed expansion’ as a characteristic nature of the universe, big bang, inflation, dark energy, quintessence and lambda term like ideal and unidentified concepts can be reviewed and relinquished at fundamental level and a practical model of expanding universe can be developed with ease and clarity. In this context, we would like to emphasize the point that, traditional definition of cosmic red shift is absolutely wrong. In terms of energy of photon, true cosmic red shift must be defined as - ratio of loss of energy in photon to the energy of photon at galaxy. We encourage the reader to see Figure 1 and Table 1 pertaining to light travel distances prepared with $\left(\frac{z}{1+z}\right)\left(\frac{c}{H_0}\right)\cong z_{new}\left(\frac{c}{H_0}\right)$. For data comparison, readers are encouraged to visit https://cosmocalc.icrar.org/ and http://www.atlasoftheuniverse.com/cosmodis.c. It may be noted that, considering 200 million solar masses as a cut off for ordinary gravity, dark matter can be considered as an effect of power law based super gravity of galactic baryonic mass. It is well believed that, Hawking’s findings about black holes are the most important contributions to physics in recent decades. Hence, we appeal the science community to recommend our Hubble-Hawking model for further research and study.

Classical models of gene expression were built using genetics and biochemistry. Although these approaches are powerful, they have very limited consideration of the spatial and temporal organization of gene expression. Although the spatial organization and dynamics of RNA polymerase II (RNAPII) transcription machinery has fundamental functional consequences for gene expression, its detailed studies have been for long time abrogated by the limits of classical light microscopy. The advent of super-resolution microscopy (SRM) techniques allowed for the visualization of the RNAPII transcription machinery with nanometer resolution and millisecond precision. In this review, we summarize the recent methodological advances in SRM, focus on its application for studies of the nanoscale organization in space and time of RNAPII transcription, and discuss its consequences for the mechanistic understanding of gene expression.

Due to its spatio-temporal variability, the mismatch between the weather and demand patterns challenges the design of highly renewable energy systems. A principal component analysis is applied to a simplified networked European electricity system with a high share of wind and solar power generation. It reveals a small number of important mismatch patterns, which explain most of the system's required backup and transmission infrastructure. Whereas the first principal component is already able to reproduce most of the temporal mismatch variability for a solar dominated system, a few more principal components are needed for a wind dominated system. Due to its monopole structure the first principal component causes most of the system's backup infrastructure. The next few principal components have a dipole structure and dominate the transmission infrastructure of the renewable electricity network.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

In this work, the author employs the quantum hydrodynamic formalism to achieve the geometrization of spacetime for describing the gravitational interaction within the framework of quantum theory. This approach allows for the development of an equation of gravity that is mathematically connected to the fermion and boson fields. This achievement is accomplished by incorporating two fundamental principles: covariance of the quantum field equations and the principle of least action. By considering these principles, a theory is established that enables the calculation of gravitational corrections to Quantum Electrodynamics, and potentially, to the standard model of particle physics as well. The theory also provides an explanation for two phenomena: the existence of a cosmological pressure density similar to quintessence, that is compatible with the small value of the observed cosmological constant, and the breaking of matter-antimatter symmetry at high energies offering insights into why there is an imbalance between the two in the early universe. In the cosmological modeling of the theory, there exists a proposal to account for the formation of supermassive black holes that are accompanied by their own surrounding galaxies, without relying on the process of mass accretion. The model, in accordance with recent observations conducted by the James Webb Space Telescope, supports the notion that galactic configurations were established relatively early in the history of the universe, shortly after the occurrence of the Big Bang.

It is extremely fascinating and astonishing that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3).Therefore, it is the author’s first intuitional imagining that this field could directly convert into mass. In so strong a gravitational field, electron and proton could be produced directly from graviton–photon collision. The gravitational field exists in everywhere in our universe. No vacuum that the region of a space is “empty” does exist. A particle is clearly always being acted on by the gravitational field. The quantum vacuum fluctuation and vacuum polarization need be re-understood with the interaction between photon and gravitational field. Therefore, the gravitational field is naturally one of the foundations of modern physics.

With an estimated 3 to 5 million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society [1] and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are shedding new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.

Descriptive geometry has indispensable applications in many engineering activities, some of which are presented in the first chapter of this paper in order to place the development presented here among them. As a result of the continuous variability of the technological environment according to various optimization aspects, the engineering activities must also be continuously adapted to the changes, which an appropriate approach and formulation are required from the practitioners of descriptive geometry, and can even lead to improvement in the field of descriptive geometry. The imaging procedures are always based on the methods and theorems of descriptive geometry. Resolving contradictions in spatial geometry reconstruction research is a constant challenge, to which a possible answer in many cases is the search for the right projection direction. A special method of enumerating the possible infinite viewpoints for the representation of the surface edge curves is presented in another part of the paper. The procedure for determining the correct directions in a mathematically exact way is also presented through examples. The analysis and some of the results of the Monge mapping, which is suitable for the solution of a mechanical engineering task to be solved in a specific technical environment, are also presented.

This study investigates the efficiency of a biogas-powered cooling system through the utilization of energy and exergy calculations. Biogas, which can be generated and stored in small-scale plants as needed, serves as a viable fuel source for absorption cooling systems. The present research focuses on the biogas consumption of a triple-effect absorption cooling system, specifically designed to supply a fixed cooling load of 100 kW under varying operational conditions. The study highlights the COP (Coefficient of Performance) and ECOP (Exergetic Coefficient of Performance) values of the system, along with the exergy destruction rates of its individual components, at the optimal temperatures of operation. Furthermore, to determine the necessary biogas consumption, the study explores the establishment of dedicated farms for various animal species, ensuring an adequate number of animals for biogas production. The findings reveal a COP of 1.78 and an ECOP of 35.4% at the optimized operating temperatures. The minimum mass flow rate of biogas is determined to be 0.0034 kg/s, facilitating the operation of the boiler with a methane content of 65%. The study concludes that a total of 290 head of cattle is required to generate the annual biogas consumption necessary for the cooling system. Also, number of the cattle is enough to establish 284 biogas plants in Bursa province in Türkiye.

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.

The structure of existing activated models is inherently deficient in reflecting the major role of the membrane filtration. This study developed and proposed a novel model, MASM, for the membrane activated process. The effective filtration size imposed by the membrane module, entrapping larger size particles was adopted as the basis of the proposed model. The model defined a modified COD fractionation, accounting for the captured COD fractions as additional model components and utilizing related mass balance relationships. It was implemented for testing the fate of soluble hydrolysable COD and system performance of super-fast membrane activated sludge based on real data for the characterization and process kinetics of domestic sewage and denim processing effluents. Model evaluation was carried for parallel systems with gravity settling and membrane filtration operated at a sludge age range of 0.5-2.0 d. Results reflected significantly better performance of super-fast membrane activated sludge system for both wastewaters, underlining that it was crucially important to account for the captured COD fractions to provide an accurate evaluation of system behavior and effluent quality. This should also be identified as the major shortcoming of the ASM models for evaluating and predicting system performance of activated sludge configurations with membrane separation.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (mass), charges and absolute time are newly defined based on the 4-D Euclidean space. The photons and gravitons are understood as the 2-D space fluctuations along the space axes and 1-D time fluctuations along the time axis, respectively. This indicates that the electromagnetic (EM) and gravitational (G) waves can be unified into the so called gravityelectromagnetic (GEM) wave which has both space and time fluctuations. The photon with zero force fields is the 2EM wave because an EM wave corresponds to a charged fermion. The dark matter bosons, weak force bosons, strong force bosons are the 1-D time fluctuations which can be expressed by the G waves. This indicates that all five forces are unified by the GEM wave. It is called as the super unification theory in the present work. And the force carrying bosons and mesons are, for the first time, proposed as the possible candidates of the magnetic monopoles like the fermions and baryons are the electric monopoles. The signs of the magnetic charges quantized as q_m=cq are newly defined. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry.

The detection performance of small objects in remote sensing images has not been satisfactory compared to large objects, especially in low-resolution and noisy images. A generative adversarial network (GAN)-based model called enhanced super-resolution GAN (ESRGAN) showed remarkable image enhancement performance, but reconstructed images usually miss high-frequency edge information. Therefore, object detection performance showed degradation for small objects on recovered noisy and low-resolution remote sensing images. Inspired by the success of edge enhanced GAN (EEGAN) and ESRGAN, we applied a new edge-enhanced super-resolution GAN (EESRGAN) to improve the quality of remote sensing images and used different detector networks in an end-to-end manner where detector loss was backpropagated into the EESRGAN to improve the detection performance. We proposed an architecture with three components: ESRGAN, EEN, and Detection network. We used residual-in-residual dense blocks (RRDB) for both the ESRGAN and EEN, and for the detector network, we used a faster region-based convolutional network (FRCNN) (two-stage detector) and a single-shot multibox detector (SSD) (one stage detector). Extensive experiments on a public (car overhead with context) dataset and another self-assembled (oil and gas storage tank) satellite dataset showed superior performance of our method compared to the standalone state-of-the-art object detectors.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p<0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p<0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p<0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. Biopsies were processed for immunohistochemical analysis of resin embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area and particle area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 month later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller particle area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the Hyac hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting.

Spinal Cord (SC) Anatomy is often assimilated to a morphologically encapsulated neural entity, but its functional anatomy remains only partially understood. We hypothesized that it could be possible to reexplore SC neural networks by performing live electrostimulation mapping, based on “super-selective” Spinal Cord Stimulation (SCS), originally designed as a therapeutical tool to address chronic refractory pain. As a starting point, we initiated a systematic SCS lead programming approach using live electrostimulation mapping on a chronic refractory perineal pain patient, previously implanted with multicolumn SCS at the level of the conus medullaris (T12-L1). It appeared possible to (re)explore the classical anatomy of the conus medullaris using statistical correlations of paresthesia coverage mappings, resulting from 165 different electrical configurations tested. We highlighted that sacral dermatomes were not only located more medially but also deeper than lumbar dermatomes at the level of the conus medullaris, in contrast with classical anatomical descriptions of SC somatotopical organization. As we were finally able to find a morpho-functional description of ‘Philippe-Gombault’s triangle’, in 19th century historical textbooks of neuroanatomy, matching remarkably with these conclusions, the concept of “Neuro-Fiber-Mapping” was introduced.

The rising severity and frequency of wildfires in recent years in the United States have raised numerous concerns regarding the improvement in wildfire emergency response management and decision-making systems, which require operational high temporal and spatial resolution monitoring capabilities. Satellites are one of the tools that can be used for wildfire monitoring. However, none of the currently available satellite systems provide both high temporal and spatial resolution. For example, GOES-17 geostationary satellite fire products have high temporal (1-5 min) but low spatial resolution (2 km), and VIIRS polar orbiter satellite fire products have low temporal (~12 h) but high spatial resolution (375 m). This work aims to leverage currently available satellite data sources, such as GOES and VIIRS, along with Deep Learning (DL) advances to achieve an operational high-resolution, both spatially and temporarily, wildfire monitoring tool. Specifically, this study considers the problem of increasing the spatial resolution of high temporal but low spatial resolution GOES-17 data products using low temporal but high spatial resolution VIIRS data products. The main idea is using an Autoencoder DL model to learn how to map GOES-17 geostationary low spatial resolution satellite images to VIIRS polar orbiter high spatial resolution satellite images. In this context, several loss functions and DL architectures are implemented and tested to predict both the fire area and the corresponding brightness temperature. These models are trained and tested on wildfire sites from 2019 to 2021 in the western U.S. The results indicate that DL models can improve the spatial resolution of GOES-17 images, leading to images that mimic the spatial resolution of VIIRS images. Combined with GOES-17 higher temporal resolution, the DL model can provide high-resolution near-real-time wildfire monitoring capability as well as semi-continuous wildfire progression maps.

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.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P<0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P<0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (E=cDtDV), charges (|q|= cDt) and absolute time (ct) are newly defined based on the 4-D Euclidean space. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry. Our universe is the matter universe with the negative charges of electric charge (EC), lepton charge (LC) and color charge (CC). This first universe is made of three dark matter -, lepton -, and quark - primary black holes with the huge negative charges which cause the Coulomb repulsive forces much bigger than the gravitational forces. The huge Coulomb forces induce the inflation of the primary black holes, that decay to the super-massive black holes. The dark matter super-massive black holes surrounded by the normal matters and dark matters make the galaxies and galaxy clusters. The spiral arms of galaxies are closely related to the decay of the 3-D charged normal matter black holes to the 1-D charged normal matter black holes. The elementary leptons and quarks are created by the decay of the normal matter charged black holes, that is caused by the Coulomb forces much stronger than the gravitational forces. The Coulomb forces are very weak with the very small Coulomb constants (k₁(EC) = k_dd(EC) ) for the dark matters and very strong with the very big Coulomb constants (k₂(EC) = k_nn(EC)) for the normal matters because of the non-communication of the photons between the dark matters and normal matters. The photons are charge dependent and mass independent. But the dark matters and normal matters have the similar and very weak gravitational forces because of the communication of the gravitons between the dark matters and normal matters. The gravitons are charge independent and mass dependent. Note that the three kinds of charges (EC, LC and CC) and one kind of mass (m) exist in our matter universe. The dark matters, leptons and quarks have the charge configurations of (EC), (EC,LC) and (EC,LC,CC), respectively. Partial masses of elementary fermions are calculated, and the proton spin crisis is explained. The charged black holes are not the singularities.

Technological advancements and innovations have profoundly changed the lives of people giving rise to smart environments, cities, and societies. As homes are the building block of cities and societies, smart homes are critical to establishing smart living and are expected to play a key role in enabling smart cities and societies. The current academic literature and commercial advancements on smart homes have mainly focused on developing and providing smart functions for homes to provide security management and facilitate the residents in their various activities such as ambiance management. Homes are much more than physical structures, buildings, appliances, operational machines, and systems. Homes are composed of families and are inherently complex phenomena underlined by humans and their relationships with each other, subject to individual, intragroup, intergroup, and intercommunity goals. There is a clear need to understand, define, consolidate existing research, and actualize the overarching roles of smart homes, the roles of smart homes that would serve the needs of future smart cities and societies. This paper introduces our data-driven parameter discovery methodology and uses it to provide, for the first time, an extensive, rather fairly comprehensive, analysis of the families and homes landscape seen through the eyes of academics and the public using over a hundred thousand research papers and nearly a million tweets. We develop a methodology using deep learning, natural language processing (NLP), and big data analytics methods and apply it to automatically discover parameters that capture a comprehensive knowledge and design space of smart families and homes comprising social, political, economic, environmental, and other dimensions. The 66 discovered parameters and the knowledge space comprising 100s of dimensions are explained by reviewing and referencing over 300 articles from the academic literature and tweets. The knowledge and parameters discovered in this paper can be used to develop a holistic understanding of matters related to families and homes facilitating the development of better, community-specific, policies, technologies, solutions, and industries for families and homes, leading to strengthening families and homes, and in turn, empowering sustainable societies across the globe.

Mereotopology is a concept rooted in analytical philosophy. The phase-field concept is based on mathematical physics and finds applications in materials engineering. The two concepts seem to be disjoint at a first glance. While mereotopology qualitatively describes static relations between things like x isConnected y (topology) or x isPartOf y (mereology) by first order logic and Boolean algebra, the phase-field concept describes the geometric shape of things and its dynamic evolution by drawing on a scalar field. The geometric shape of any thing is defined by its boundaries to one or more neighboring things. The notion and description of boundaries thus provides a bridge between mereotopology and the phase-field concept. The present article aims to relate phase-field expressions describing boundaries and especially triple junctions to their Boolean counterparts in mereotopology and contact algebra. An introductory overview on mereotopology is followed by an introduction to the phase-field concept already indicating first relations to mereo- topology. Mereotopological axioms and definitions are then discussed in detail from a phase-field perspective. A dedicated section introduces and discusses further notions of the isConnected relation emerging from the phase-field perspective like isSpatiallyConnected, isTemporallyConnected, isPhysicallyConnected, isPathConnected and wasConnected. Such relations introduce dynamics and thus physics into mereotopology as transitions from isDisconnected to isPartOf can be described.

With reference to electromagnetic interaction and Abdus Salam’s strong (nuclear) gravity, 1) Square root of ‘reciprocal’ of the strong coupling constant can be considered as the strength of nuclear elementary charge. 2) ‘Reciprocal’ of the strong coupling constant can be considered as the maximum strength of nuclear binding energy. 3) In deuteron, strength of nuclear binding energy is around unity and there exists no strong interaction in between neutron and proton. $G_s\cong 3.32688\times {10}^{28}{\mathrm{m}}^3{\mathrm{kg}}^{-1}{\sec }^{-2}$ being the nuclear gravitational constant, nuclear charge radius can be shown to be, $R_0\cong \frac{2G_s{m}_p}{c^2}\cong 1.24\mathrm{fm}.$ $e_s\cong \left(\frac{G_s{m}_p^2}{\hslash c}\right)e\cong 4.716785\times {10}^{-19}\mathrm{C}$ being the nuclear elementary charge, proton magnetic moment can be shown to be, ${\mu }_p\cong \frac{e_s\hslash }{2m_p}\cong \frac{e{G}_s{m}_p}{2c}\cong 1.48694\times {10}^{-26}\mathrm{J}{.\mathrm{T}}^{-1}.$ ${\alpha }_s\cong {\left(\frac{\hslash c}{G_s{m}_p^2}\right)}^2\cong 0.1153795$ being the strong coupling constant, strong interaction range can be shown to be proportional to $\exp \left(\frac{1}{{\alpha }_s^2}\right).$ Interesting points to be noted are: An increase in the value of ${\alpha }_s$ helps in decreasing the interaction range indicating a more strongly bound nuclear system. A decrease in the value of ${\alpha }_s$ helps in increasing the interaction range indicating a more weakly bound nuclear system. From $Z\cong 30$ onwards, close to stable mass numbers, nuclear binding energy can be addressed with, ${\left(B\right)}_{A_s}\cong Z\times \left\{\left(\frac{1}{{\alpha }_s}+1\right)+\sqrt{\sqrt{30\times 31}}\right\}\left(m_n-m_p\right)c^2\approx Z\times 19.66\mathrm{MeV}.$ With further study, magnitude of the Newtonian gravitational constant can be estimated with nuclear elementary physical constants. One sample relation is, $\left(\frac{G_N}{G_s}\right)\cong \frac{1}{2}{\left(\frac{m_e}{m_p}\right)}^{10}\left[\sqrt{\frac{G_F}{\hslash c}}/\left(\frac{\hslash }{m_{e}c}\right)\right]$ where $G_N$ represents the Newtonian gravitational constant and $G_F$ represents the Fermi’s weak coupling constant. Two interesting coincidences are, ${\left(m_p/m_e\right)}^{10}\cong \exp \left(1/{\alpha }_s^2\right)$ and $2G_s{m}_e/c^2\cong \sqrt{G_F/\hslash c}.$

Let  β= (((24!)!)!)!, and let {${\mathcal P}_{n^2+1}$} denote the set of all primes of the form {$n^2+1$}. Let ${\mathcal M}$ denote the set of all positive multiples of elements of the set {${\mathcal P}_{n^2+1} \cap (\beta,\infty)$}. The set {${\mathcal X}=\{0,\ldots,\beta\} \cup {\mathcal M}$} satisfies the following conditions: (1) ${\rm card}({\mathcal X})$ is greater than a huge positive integer and it is conjectured that ${\mathcal X}$ is infinite, (2)} we do not know any algorithm deciding the finiteness of ${\mathcal X}$, (3)~a~known and short algorithm for every {$n \in N$} decides whether or not {$n \in {\mathcal X}$}, (4) a known and short algorithm returns an integer~$n$ such that ${\mathcal X}$ is infinite if and only if ${\mathcal X}$ contains an element greater than $n$. The following problem is open: {\em simply define a set {${\mathcal X} \subseteq N$} such that ${\mathcal X}$ satisfies conditions (1)-(4), and \underline{we do not know any representation of~~${\mathcal X}$~~as a finite union of sets whose definitions are simpler than} \underline{the definition of ${\mathcal X}$}} {\tt (5)}. Let {$f(1)=2$}, {$f(2)=4$}, and let {$f(n+1)=f(n)!$} for every integer {$n \geqslant 2$}. For a positive integer $n$, let {$\Psi_n$} denote the following statement: {\em if a system of equations ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: i,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers \mbox{$x_1,\ldots,x_n$}, then each such solution \mbox{$(x_1,\ldots,x_n)$} satisfies {$x_1,\ldots,x_n \leqslant f(n)$}.} We prove that for every statement $\Psi_n$ the bound {$f(n)$} cannot be decreased. The author's guess is that the statements {$\Psi_1,\ldots,\Psi_9$} are true. We prove that the statement $\Psi_9$ implies that the set ${\mathcal X}$ of all {non-negative} integers $k$ whose number of digits belongs to {${\mathcal P}_{n^2+1}$} satisfies conditions {\tt (1)-(5)}.

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

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

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

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