A series of novel substituted isoxazolidine derivatives was synthesized through 1,3-dipolar cycloaddition reactions of α-aryl-N-methyl nitrones with various ethylene moieties, resulting in the formation of isoxazolidine derivatives. The structures of the synthesized compounds were characterized using spectroscopic methods. The [3+2] cycloaddition (32CA) reactions of α-aryl-N-methyl nitrones with diverse ethylene substituents were computed employing Density Functional Theory (DFT) at the B3LYP/6–31G(d) level, upgrading bond parameters. An investigation of the electron localization function (ELF) unveiled the zwitterionic nature of α-aryl-N-methyl nitrones, devoid of pseudoradical or carbenoid centers. Utilization of CDFT indices enabled the prediction of global electronic flux from the strongly nucleophilic α-aryl-N-methyl nitrones to the varied electrophilic ethylene functionalities. Molecular docking and molecular dynamics simulations were conducted on the isoxazolidine derivatives against the EGFR receptor (PDB: 4ZAU). In silico assessment of the synthesized isoxazolidines involved molecular docking, wherein the compound with the highest docking score was subjected to molecular dynamics simulations. Compound 11a, out of the thirty isoxazolidine derivatives, displayed the most substantial binding energy, yielding a g score of -6.57 kcal/mol. These observations highlighted the functional role of amide NH2 and NO2 in the binding process with the target protein, influencing its activity. Furthermore, prediction of ADME drug-likeness properties was performed to identify a suitable candidate.

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

The description of the microscopic world in quantum mechanics is very different from that in classical physics, and there are some points of view that are contrary to intuition and logic. The first is the loss of reality, the behavior of micro particles shows randomness and hopping. The second is the loss of certainty, the conjugate physical variables of a system cannot be determined synchronously, they satisfy the Heisenberg uncertainty principle. The third is the non-local correlation. The measurement of one particle in the quantum entanglement pair will change the state of the other entangled particle simultaneously. In this paper, some concepts related to quantum entanglement, such as EPR correlation, quantum entanglement correlation function, Bell's inequality and so on, are analyzed in detail. Analysis shows that the mystery and confusion in quantum theory may be caused by the logical problems in its basic framework. Bell's inequality is only a mathematical theorem, but its physical meaning is actually unclear. The Bell state of quantum entangled pair may not satisfy the dynamic equation of quantum theory, so it cannot describe the true state of microscopic particles. In this paper, the correct correlation functions of spin entanglement pair and photonic entanglement pair are strictly derived according to normal logic. Quantum theory is a more fundamental theory than classical mechanics, and they are not parallel relation in logic. However, there are still some unreasonable contents in the framework of quantum theory, which need to be improved. In order to disclose the real relationship between quantum theory and classical mechanics, we propose some experiments which show the wave-particle duality simultaneously and provide intuitionistic teaching materials for the new interpretation of quantum theory.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

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

The aim of this study is to obtain the Bayes estimators and the maximum likelihood estimators (MLEs) for the unknown parameters of the Rayleigh Weibull (RW) distribution based on progres-sive type-II censored samples. The approximate Bayes estimators are calculated using the idea of Lindley and Tierney-Kadane's approximation method under the squared-error loss function when the Bayes estimators are not handed in explicit forms. In this study, the approximate Bayes esti-mates are compared with the maximum likelihood estimates in the aspect of the estimated risks (ERs) using Monte Carlo simulation. In addition, the coverage probabilities of the parametric bootstrap estimates are calculated. Real lifetime data sets belonging to the cancer types as bladder cancer, head and neck cancer, and leukemia are used to illustrate the emprical results belonging to the approximate Bayes estimates, the maximum likelihood estimates, and the parametric bootstrap intervals.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

In 1969, Jean-Marie Souriau introduced a “Lie Groups Thermodynamics” in Statistical Mechanics in the framework of Geometric Mechanics. This Souriau’s model considers the statistical mechanics of dynamic systems in their "space of evolution" associated to a homogeneous symplectic manifold by a Lagrange 2-form, and defines in case of non null cohomology (non equivariance of the coadjoint action on the moment map with appearance of an additional cocyle) a Gibbs density (of maximum entropy) that is covariant under the action of dynamic groups of physics (eg, Galileo's group in classical physics). Souriau Lie Group Thermodynamics was also addressed 30 years after Souriau by R. F. Streater in the framework of Quantum Physics by Information Geometry for some Lie algebras, but only in the case of null cohomology. Souriau method could then be applied on Lie Groups to define a covariant maximum entropy density by Kirillov representation theory. We will illustrate this method for homogeneous Siegel domains and more especially for Poincaré unit disk by considering SU(1,1) group coadjoint orbit and by using its Souriau’s moment map. For this case, the coadjoint action on moment map is equivariant. For non-null cohomology, we give the case of Lie group SE(2). Finally, we will propose a new geometric definition of Entropy that could be built as a generalized Casimir invariant function in coadjoint representation, and Massieu characteristic function, dual of Entropy by Legendre transform, as a generalized Casimir invariant function in adjoint representation, where Souriau cocycle is a measure of the lack of equivariance of the moment mapping.

In this paper, we derive multifarious relationships among the two types of higher order q-Daehee polynomials and p-adic gamma function via Mahler theorem. Also, we compute some weighted p-adic q-integrals of the derivative of p-adic gamma function related to the Stirling numbers of the both kinds and the q-Bernoulli polynomials of order k.

Recent advancements of computer and electronic systems have motivated the extensive use of intelligent systems for automation of agricultural industries. In this study, the temperature variation of the mushroom growing room is modeled through using a multi-layered perceptron (MLP) and radial basis function networks. Modeling has been done based on the independent parameters including ambient temperature, water temperature, fresh air and circulation air dampers, and water tap. According to the obtained results from the networks, the best network for MLP is found to be the second repetition with 12 neurons in the hidden layer and 20 neurons in the hidden layer for radial basis function networks. The obtained results from comparative parameters for two networks showed the highest correlation coefficient (0.966), the lowest root mean square error (RMSE) (0.787) and the lowest mean absolute error (MAE) (0.02746) for radial basis function. Therefore, the neural networks with radial basis function was selected as the optimal predictor for the behavior of the system.

Most astrophysicists today believe that the present universe was produced in a big bang. This article explores the big cycle of matter and energy in the universe, with the big bang as an important part of the cycle.The authors approve of the idea that the universe is gravitationally closed. That is, its average density is higher than the critical value. All the matter and radiation cannot fly out the closed universe.The 3k background radiation is a vast heat ocean in the closed universe, stable and eternal. It is not the afterglow of the thermal radiation of the decoupled fire ball, 380,000 years after the big bang, as many people believed so far. The big bang and the following big expansion drove the matter of more than 2×10¹² galaxies to the remote space. Their potential energies become higher and higher, while their huge kinetic energies that they derived from the big bang become smaller and smaller until drop down to zero. The galaxies will then return back one after another, passing the central region of the universe with tremendously great kinetic energies. They of course cannot all return back directly to their start point of the big bang and restore to the state of the original cosmic core. They will rush to pass the central region and fly to the other sides of the universe, and shuttle around the central part ceaselessly. From the big bang to the following expansion, to the numerous galaxies, to the more than 2×10²³ stars, and to the stars releasing huge nuclear energy due to their internal nuclear fusion each for about 10¹⁰ years, all these enormous processes are irreversible, resulting in enormous increase in entropy. These processes produce large amount of light and other radiations and pour them into the extremely vast heat ocean. These light and other radiations will also be shuttling ceaselessly in the vast heat ocean until, by their interaction with the rare dusts in the galaxies, they mingle into the 3K thermal radiation of the heat ocean. In all the galaxies, there are various black holes. Every black hole, since its birth, ceaselessly extracts the matter and radiation that approach it, and gets larger. In the above mentioned shuttling of all the galaxies, numerous stars and black holes in these galaxies have many chances to approach even meet each other. A black hole can annex other celestial bodies that it meets, including annex other black holes. All these processes carry on and on ceaselessly, resulting in the matter of these celestial bodies to concentrate again and again. The number of all the celestial bodies including the black holes reduces ceaselessly, and the mass of the survived black holes become larger, and their shuttling amplitudes become shorter. The larger black holes and the shorter amplitudes result in the rate of concentration of mass to be faster. Eventually, all the matter in the universe will be concentrated to form a tremendously large central black hole. The central black hole has an astonishingly large Schwarzschild sphere, absorbing the thermal radiation from the vast heat ocean very rapidly and ceaselessly until some threshold value of its internal energy is exceeded, and a new big bang breaks out. The black holes provide a way in the Universe to re-concentrate matter and energy again. Black holes are Maxwell’s demons in the Nature.

The core motivation for this study emanates from Voronin S.'s seminal work on the universality of the zeta function. This universality positions the zeta function as a pivotal element in the conceptual framework of global artificial intelligence, suggesting its potential as a foundational component. A critical barrier to harnessing this promising universality has been the absence of efficient algorithms capable of actualizing this concept.

New insights into the causes and mechanisms of congenital heart disease (CHD) have been gained through the use of next-generation sequencing. Examination of the whole exome sequence detects detrimental gene variations modifying single or contiguous nucleotides, that are characterised as pathogenicity based on statistical assessments of families. and correlates with congenital heart disease, elevated expression during heart development, and reduction of harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities enriched for gene classes meeting these criteria. CHDs and extracardiac defects, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data reveal the expression of genes associated with CHD in specific cell lineages, and emerging evidence suggests that genetic variants disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole genome sequence studies.

In the paper, by the Faά di Bruno formula, several identities for the Bell polynomials of the second kind, and an inversion theorem, the authors simplify coefficients of two families of nonlinear ordinary differential equations for the generating function of the Catalan numbers and discover inverses of fifteen closely related lower triangular integer matrices.

In the paper, the authors present unified generalizations for the Bell numbers and polynomials, establish explicit formulas and inversion formulas for these generalizations in terms of the Stirling numbers of the first and second kinds with the help of the Faà di Bruno formula, properties of the Bell polynomials of the second kind, and the inversion theorem connected with the Stirling numbers of the first and second kinds, construct determinantal and product inequalities for these generalizations with aid of properties of the completely monotonic functions, and derive the logarithmic convexity for the sequence of these generalizations.

Abstract: The S1 subunit of SARS-CoV-2 Spike has been found in the blood of covid patients and vaccinated individuals. From BioGRID, we selected 146 significant human proteins experimentally interacting with S1. Then, we derived an interactome model that facilitated the study of functional activities. Through a reverse engineering approach, we identified 27 specific one-to-one interac-tions of S1 with the human proteome. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, carry multiple attacks on single human proteins out, showing a different functional engagement. Through Cytoscape we showed functional implications and its tropism to human organs/tissues, such as nervous system, liver, blood, and lungs. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 GO biological processes, much more than the 1430 terms controlled when operating in a group. A Data-Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single bio-logical process of 26.19. However, many human proteins get entangled in over 100 biological different activities each. Clustering analysis showed statistically significant activations of many molecular mechanisms, like those related to hepatitis-B infections. This suggests potential in-volvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.

We define computable functions $g,h:$ $\mathbb N$ $\setminus \{0\} \to$ $\mathbb N$ $\setminus \{0\}$. For an integer $n \geqslant 3$, let $\Psi_n$ denote the following statement: if a system ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: (i,k \in \{1,\ldots,n\}) \wedge (i \neq k)\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers $x_1,\ldots,x_n$, then each such solution $(x_1,\ldots,x_n)$ satisfies $x_1,\ldots,x_n \leqslant g(n)$. For a positive integer $n$, let $\Gamma_n$ denote the following statement: if a system $S \subseteq \Bigl\{x_i \cdot x_j=x_k:~i,j,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{2^{\textstyle 2^{\textstyle x_i}}=x_k:~i,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers $x_1,\ldots,x_n$, then each such solution $(x_1,\ldots,x_n)$ satisfies $x_1,\ldots,x_n \leqslant h(n)$. We prove: (1) if the equation $x!+1=y^2$ has only finitely many solutions in positive integers, then the statement $\Psi_6$ guarantees that each such solution $(x,y)$ belongs to the set $\{(4,5),(5,11),(7,71)\}$, (2) the statement $\Psi_9$ proves the following implication: if there exists a positive integer $x$ such that $x^2+1$ is prime and $x^2+1>g(7)$, then there are infinitely many primes of the form $n^2+1$, (3) the statement $\Psi_9$ proves the following implication: if there exists an integer $x \geqslant g(6)$ such that $x!+1$ is prime, then there are infinitely many primes of the form $n!+1$, (4) the statement $\Psi_{16}$ proves the following implication: if there exists a twin prime greater than $g(14)$, then there are infinitely many twin primes, {\bf (5)}~the statement $\Gamma_{13}$ proves the following implication: if $n \in$ $\mathbb N$ $\setminus \{0\}$ and $2^{\textstyle 2^{\textstyle n}}+1$ is composite and greater than $h(12)$, then $2^{\textstyle 2^{\textstyle n}}+1$ is composite for infinitely many positive integers $n$.

High temperature (HT) geothermal wells can provide green power 24h a day 7 days a week. Harsh environmental and operational conditions, long-term durability requirements of such wells require special cementitious composites for well construction. This paper reports a comprehensive assessment of geothermal cement composites in cyclic pressure function laboratory tests, field exposures in an HT geothermal well (300-350oC) as well as a numerical model to complement the experimental results. Performances of calcium-aluminate-cement (CAC)-based composites and calcium free cement were compared against reference Ordinary Portland Cement (OPC)/silica blend. The stability and degradation of the tested materials was characterized by crystalline composition, thermo-gravimetric, and elemental analyses, morphological studies, water-fillable porosity, and mechanical properties measurements. All CAC-based formulations outperformed the reference blend both in the function and exposure tests. The reference OPC/silica lost its mechanical properties during the 9-month well exposure through extensive HT carbonation, while properties of the CAC-based blends improved over that period. The Modified Cam-Clay (MCC) plasticity parameters of several HT cement formulations were extracted from triaxial and Brazilian tests and verified against the experimental results of function cyclic tests. These parameters can be used in well integrity models to predict field-scale behavior of the cement sheath under geothermal well conditions.

Deterministic-stochastic empirical mode decomposition (EMD) is used to obtain low-frequency (non-diffusive, i.e., background velocity) and high-frequency (diffusive, i.e., eddies) components from a Lagrangian drifter‘s trajectory. Eddy characteristics are determined from the time series of eddy trajectories from individual Lagrangian drifter such as the eddy radial scale, eddy velocity scale, eddy Rossby number, and eddy-background kinetic energy ratio. A long-term dataset of the SOund Fixing And Ranging float time series obtained near the California coast by the Naval Postgraduate School from 1992 to 2004 at depth between 150 and 600 m (http://www.oc.nps.edu/npsRAFOS/) is used as an example to demonstrate the capability of the deterministic-stochastic EMD.

The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, is preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MCs has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors enabling its activation by a vast variety of potentially harmful exogenous and endogenous molecules, and by reproductive hormones in the female sex organs. Activated MCs release a unique composition of pre-formed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects—spanning generations—in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell

Low Power Wide Area Networks (LPWAN) enable a growing number of Internet-of-Things (IoT) applications with large geographical coverage, low bit-rate, and long lifetime requirements. LoRa (Long Range) is a well-known LPWAN technology that uses a proprietary Chirp Spread Spectrum (CSS) physical layer, while the upper layers are defined by an open standard - LoRaWAN. In this paper, we propose a simple yet effective method to improve the Quality-of-Service (QoS) of LoRa networks by fine-tuning specific radio parameters. Through a Mixed Integer Linear Programming (MILP) problem formulation, we find optimal settings for the Spreading Factor (SF) and Carrier Frequency (CF) radio parameters, considering the network traffic specifications as a whole, to improve the Data Extraction Rate (DER) and to reduce the packet collision rate and the energy consumption in LoRa networks. The effectiveness of the optimization procedure is demonstrated by simulations, using LoRaSim for different network scales. In relation to the traditional LoRa radio parameter assignment policies, our solution leads to an average increase of 6% in DER, and a number of collisions 13 times smaller. In comparison to networks with dynamic radio parameter assignment policies, there is an increase of 5%, 2.8%, and 2% of DER, and a number of collisions 11, 7.8 and 2.5 times smaller than equal-distribution, Tiurlikova's (SoTa), and random distribution, respectively. Regarding the network energy consumption metric, the proposed optimization obtained an average consumption similar to Tiurlikova's, and 2.8 times lower than the equal-distribution and random dynamic allocation policies. Furthermore, we approach the practical aspects of how to implement and integrate the optimization mechanism proposed in LoRa, guaranteeing backward compatibility with the standard protocol.

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. The activating cleavage of VEGF-C is mediated by at least five different proteases: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by different proteases. During embryonic development, ADAMTS3 activates VEGF-C. In contrast, thrombin and plasmin likely activate VEGF-C/-D during tissue injury-induced lymphangiogenesis, and PSA and cathepsin D perhaps during tumor-associated pathological lymphangio­genesis. Additionally, cathepsin D from saliva might activate latent VEGF-C/-D upon wound licking, thereby accelerating healing. Similar to tyrosine kinase receptors and VEGFs themselves, these activating proteases could be targeted to modulate angiogenesis and lymphangiogenesis in relevant diseases.

Transition between the unfolded and native states of the ordered globular proteins is accompanied by accumulation of several intermediates, such as pre-molten globule, wet molten globule, and dry molten globule. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under the conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

The trafficking of illegal drugs by criminal networks at borders, harbors, or airports is an increasing issue in public health as these routes ensure the main supply of illegal drugs. The prevention of drug smuggling, including the installation of scanners and other analytical devices to detect ultra-small traces of drugs within a reasonable time frame, remains a challenge. The presented immunosensor is based on a monolithic affinity column with a large excess of immobilized hapten, which traps fluorescently labeled antibodies as long as the analyte cocaine is absent. In the presence of the drug, some binding sites of the antibody will be blocked, which leads to an immediate breakthrough of the labeled protein, detectable by highly sensitive laser-induced fluorescence with the help of a Peltier-cooled complementary metal-oxide-semiconductor (CMOS) camera. Liquid handling is performed with high-precision syringe pumps and microfluidic chip-based mixing devices and flow cells. The biosensor achieved limits of detection of 23 pM (7 ppt) of cocaine with a response time of 90 seconds and a total assay time below 3 minutes. With surface wipe sampling, the biosensor was able to detect 300 pg of cocaine. This immunosensor belongs to the most sensitive and fastest detectors for cocaine and offers near-continuous analyte measurement.

We propose a novel framework for understanding quantum phenomena through the lens of a modified electromagnetic spacetime governed by Einstein field equations. By assuming the existence of an electromagnetic spacetime that adheres to these modified geodesic and Einstein field equations, provided the field equations satisfy the Coulomb force law in weak-field approximations, we explore the derivation of Maxwell’s equations and highlight the necessity of incorporating spin to validate these equations. We derive the wave equation for the normalized transverse metric and establish its equivalence with the de Broglie wave proposition, suggesting a relationship between this metric and the particle's wavefunction. This approach offers a classical explanation for several quantum phenomena, including the double-slit experiment, entanglement, tunneling, non-locality, and wavefunction collapse. Additionally, it posits a method to visualize atomic orbital structures in line with quantum mechanical predictions. These findings suggest that the foundational principles of quantum mechanics can be interpreted as linearized approximations of general relativity applied to electromagnetic spacetime. While this theory does not yet extend to the correlations between general relativity, quantum electrodynamics (QED), and quantum chromodynamics (QCD), it provides a valuable visualization tool for physicists and advances our understanding of the unresolved challenges linking quantum mechanics with general relativity.

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

Monitoring seaweed growth rates and biomass is crucial for optimizing harvest strategies in aquaculture systems. While such a task can be performed manually on a small farm, such as the Integrated Multi-Trophic Aquaculture (IMTA) system at Harbor Branch Oceanographic Institute at Florida Atlantic University (HBOI), a commercial farm will have to rely on the automated sensor to perform such a task. This study introduces an advanced LSTM-based approach for forecasting seaweed growth and biomass. Utilizing a combination of real and synthetic data, LSTM models are trained and evaluated for their predictive performance. Synthetic sensor data was generated using mathematical equations that simulate realistic aquaculture conditions, with added noise to reflect sensor variability. Building on the foundation of the Pseudorandom Encoded Light for Evaluating Biomass (PEEB) sensor deployed at the seaweed tank in the HBOI IMTA system, we refine the process of biomass estimation by introducing non-linear regression models for predicting seaweed growth and biomass. The results showed that the LSTM model trained with a loss function under physics constraint, combining MSE and physical laws, outperformed models trained with MSE alone, achieving a significantly lower error in predicting seaweed growth. The variation trend of the predicted biomass from the network matched well with the sensor measurement after moving average preprocessing, demonstrating the robustness of the proposed technique in handling noisy sensor data. This study highlights the potential of integrating machine learning with physical models to optimize seaweed cultivation and support sustainable aquaculture practices.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

Three-dimensional quantized space model is newly introduced. Quantum mechanics and relativity theory are explained in terms of the warped three-dimensional quantized spaces with the quantum time width (Dt=t_q). The energy is newly defined as the 4-dimensional space-time volume of E = cDtDV in the present work. It is shown that the wave function of the quantum mechanics is closely related to the warped quantized space shape with the space time-volume. The quantum entanglement and quantum wave function collapse are explained additionally. The special relativity theory is separated into the energy transition associated with the space-time shape transition of the matter and the momentum transition associated with the space-time location transition. Then, the quantum mechanics and the general relativity theory are about the 4-dimensional space-time volume and the 4-dimensional space-time distance, respectively.

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

In this article, the research team has systematically developed a method to model the kinematics and dynamics of a 3-wheeled robot subjected to external disturbances and sideways wheel sliding. These models will be used to design control laws that compensate for wheel slippage, model uncertainties, and external disturbances. These are control algorithms developed based on Dynamic Surface Control (DSC). Adaptive trajectory tracking DSC algorithm using fuzzy logic system (AFDSC) and radial neural network (RBFNN) with fuzzy logic system to overcome the disadvantages of DSC and expand the application domain for wheeled Mobile Robots (WMR). However, this Adaptive Fuzzy Neural Network Dynamic Surface Control (AFNNDSC) adaptive controller ensures the closed system is stable and follows the preset trajectory in the presence of wheel slippage model uncertainty and is affected by significant amplitude disturbances. The stability and convergence of the closed-loop system are guaranteed based on the Lyapunov analysis. The AFNNDSC adaptive controller is evaluated by simulation on MATLAB/Simulink software and in a steady state. The maximum position error on the right wheel and left wheel is 0.000572 (m) and 0.000523 (m), and the angular velocity tracking error in the right and left wheels of the control method is 0.000394 (rad/s). The experimental results show the correctness of the theoretical analysis, the effectiveness of the proposed controller, and the possibility of practical application.

In the paper, the author introduces the notions "multi-order logarithmic numbers" and "multi-order logarithmic polynomials", establishes an explicit formula, an identity, and two recurrence relations by virtue of the Faa di Bruno formula and two identities of the Bell polynomials of the second kind in terms of the Stirling numbers of the first and second kinds, and constructs some determinantal inequalities, product inequalities, logarithmic convexity for multi-order logarithmic numbers and polynomials by virtue of some properties of completely monotonic functions.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

For evaluating probabilities of arbitrary random events with respect to a given multivariate probability distribution, specific techniques are of great interest. An important two-dimensional high risk limit law is the Gauss-exponential distribution whose probabilities can be dealt with based upon the Gauss-Laplace law. The latter will be considered here as an element of the newly introduced family of (p,q)-spherical distributions. Based upon a suitably defined non-Euclidean arc-length measure on (p,q)-circles we prove geometric and stochastic representations of these distributions and correspondingly distributed random vectors, respectively. These representations allow dealing with the new probability measures similarly like with elliptically contoured distributions and more general homogeneous star-shaped ones. This is demonstrated at hand of a generalization of the Box-Muller simulation method. En passant, we prove an extension of the sector and circle number functions.

In the present study. At first, some properties of r-fuzzy soft β-closed sets are introduced on fuzzy soft topological spaces based on the paper Aygunoglu et al. (Hacet. J. Math. Stat. 2014, 43, 193-208). Also, we define the closure and interior operators with respect to the classes of r-fuzzy soft β-closed and r-fuzzy soft β-open sets, and investigate some of their properties. In addition, the concept of r-fuzzy soft β-connected sets is introduced and characterized with help of fuzzy soft β-closure operators. Thereafter, some properties of a fuzzy soft β-continuity are studied. Furthermore, we introduce and study the concepts of fuzzy soft almost (weakly) β-continuous functions, which are weaker forms of a fuzzy soft β-continuity. Also, the relationships between these classes of functions are specified with the help of some illustrative examples. Finally, we explore new types of fuzzy soft functions called, fuzzy soft β-irresolute (strongly β-irresolute, β-irresolute open, β-irresolute closed and β-irresolute homeomorphism) functions, and discuss some properties of them. Also, we show that fuzzy soft strongly β-irresolute → fuzzy soft β-irresolute → fuzzy soft β-continuity, but the converse may not be true.

In the paper, the author (1) presents an explicit formula and its inversion formula for higher order derivatives of generating functions of the Bell polynomials, with the help of the Faà di Bruno formula, properties of the Bell polynomials of the second kind, and the inversion theorem for the Stirling numbers of the first and second kinds; (2) recovers an explicit formula and its inversion formula for the Bell polynomials in terms of the Stirling numbers of the first and second kinds, with the aid of the above explicit formula and its inversion formula for higher order derivatives of generating functions of the Bell polynomials; (3) constructs some determinantal and product inequalities and deduces the logarithmic convexity of the Bell polynomials, with the assistance of the complete monotonicity of generating functions of the Bell polynomials. These inequalities are main results of the paper.

The SARS-CoV-2-induced acute COVID-19 pandemic disorder seems to have begun all of the sudden in 2020, with very little data available regarding prior times in which people experienced mysterious flu-like illness symptoms characteristic of the pandemic disease. The scientific community seems to be divided into a few parts with regards to the belief of the kind of viral origins. A significant number of scientists believe that the virus solely has natural origins and that it underwent a thorough process of zoonosis, independent of laboratory research-based research that would only catalyse zoonosis due to helping the virus gain additional function of transmission and virulence. Many other scientists believe that the virus has wide origins characteristic of “gain-of-function” laboratory research, whilst many other scientists believe that most of the viral genome has natural origins, with the zoonotic process having been artificially catalysed only in its latter part of transmission to humans. Considerable extent of scientific evidence suggests that the virus underwent a restricted, but considerable extent of “gain-of-function” research, prior to having been accidentally leaked into the nearby environment, whilst its process of zoonotic spillover into humans was influenced by such events, given for example the multidimensional pathogenetic process displayed by the virus and its main antigen of action, the spike glycoprotein, causing all kinds of immune pathophysiology - including transient immunosuppression. Investigations into the origins of the novel coronavirus have been lasting for years, seemingly with no concrete end in sight, and the available molecular testing methods to detect SARS-CoV-2 infection displaying less than perfect results have not significantly helped the process. Evidence even started pointing toward the existence of artificial, laboratory research-based viral origins, exposing a probable accidentally-induced artificial process of “accelerated viral evolution”, which could be particularly dangerous because of the nature of the SARS-CoV-2 pathogenic agent. Likewise, it is possible that the prevention of distribution of scientific data regarding scenarios as such in fact constitutes censorship, rather than regulation of data that may be considered not to be significantly evidence based. Simultaneously, it is important not to regard all hypotheses and preliminary reports of scientific research as evidence-based, but to ensure that due diligence is performed in all cases. The integrity of scientific research and ultimately of the innovation process of medical solutions depends on the integrity of democracy and the rule of law, as well as on regulating partnerships with scientific companies from world nations where autocracy rules their society.

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

We assume that poetic devices have an implicit goal: producing an overall sound scheme that will induce the reader to associate intended and expressed meaning to the sound of the poem. Sounds may be organized into categories and assigned presumed meaning as suggested by traditional literary studies. In my work, I have extracted automatically the sound grids of all the sonnets by William Shakespeare and have combined them with the themes expressed by their contents. In a first experiment I have computed lexically and semantically based sentiment analysis obtaining an 80% of agreement. In a second experiment sentiment analysis has been substituted by Appraisal Theory thus obtaining a more fine-grained interpretation which in some cases contradicts the first one. The computation for the second poet - regarded by many critics the best of last century - includes both vowels and consonants. In addition, it combines automatic semantically and lexically based sentiment analysis with sound grids. The results produce visual maps that clearly separate poems into three clusters: negative harmony, positive harmony and disharmony where the latter instantiates the need by the poet to encompass the opposites in a desperate attempt to reconcile them.

The Hyper-Torus Universe Model (HTUM) proposes a novel framework to unify quantum mechanics, cosmology, and consciousness. This paper introduces HTUM's core concept: a higher-dimensional hyper-torus encompassing all possible states of existence. HTUM suggests that the universe functions as a quantum system where all outcomes are inherently connected, with consciousness playing a significant role in actualizing reality. The model introduces several key innovations, including the universe's 4-dimensional toroidal structure (4DTS), providing a new geometric interpretation of spacetime. HTUM presents dark matter and dark energy as nonlinear probabilistic phenomena within this toroidal framework, offering a unique perspective on their nature and interactions. The model proposes a mechanism for wave function collapse through universal self-observation, bridging quantum mechanics and gravity. It introduces a Topological Vacuum Energy Modulator (TVEM) function, offering a potential resolution to the cosmological constant problem. Furthermore, HTUM integrates consciousness as a fundamental aspect of the universe, influencing quantum state actualization and potentially resolving the hard problem of consciousness. The model explores the implications of a timeless singularity and the emergence of time as a product of causal relationships within the toroidal structure. This framework addresses critical challenges in modern physics, including the nature of quantum entanglement, the origin and fate of the universe, and the relationship between mind and matter. The paper discusses the mathematical formulation of HTUM, its implications for quantum mechanics and cosmology, and its potential to bridge the gap between science and philosophy. We present detailed predictions for the cosmic microwave background (CMB) power spectrum, gravitational wave signatures, and large-scale structure formation, demonstrating how HTUM differs from the standard ΛCDM model. Our analysis reveals distinctive oscillatory patterns in the relative difference between HTUM and ΛCDM predictions, with deviations reaching up to ±20% at certain scales. The paper also explores the unification of fundamental forces within the HTUM framework, proposing novel approaches to particle physics and quantum field theory. It introduces the concept of unified mathematical operations, suggesting a more holistic approach to mathematical thinking that aligns with the model's interconnected view of the universe. Additional testable predictions and proposed experimental approaches are discussed, including advanced space-based tests and laboratory experiments probing quantum gravity effects. These specific, quantifiable predictions offer multiple avenues for empirical validation, highlighting HTUM's potential to be distinguished from ΛCDM and other alternative cosmological models. HTUM represents a significant new perspective in our understanding of the universe, inviting further research and exploration into the nature of reality, consciousness, and the fundamental structure of the cosmos. By providing a comprehensive framework that unifies various aspects of physics, cosmology, and consciousness studies, HTUM offers a promising path toward a more complete understanding of our universe.

The article titled "Immunoglobulins and Its Applications" provides a comprehensive overview of the structure, function, and therapeutic significance of immunoglobulins, also known as antibodies. These vital proteins, produced by plasma cells in response to immunogens, are essential components of the immune system, playing a critical role in recognizing and neutralizing pathogens such as bacteria and viruses. The article elaborates on the five primary classes of immunoglobulins (IgA, IgD, IgE, IgG, and IgM), each distinguished by its unique structural and functional properties. It discusses the molecular composition of immunoglobulins, highlighting the significance of their variable and constant regions in antigen binding. The paper also explores the diverse immune functions mediated by these proteins, including precipitation, agglutination, and neutralization of antigens. Additionally, the article emphasizes the therapeutic applications of immunoglobulins, particularly in treating immune deficiencies and other diseases. Advances in monoclonal antibody technology have significantly expanded the utility of immunoglobulins in both research and medicine, leading to the development of innovative therapeutic approaches such as humanized monoclonal antibodies and bifunctional antibodies. This comprehensive analysis underscores the critical role of immunoglobulins in both natural immunity and therapeutic interventions.

This literature review investigates the morphological and behavioral significance of the horns of Carnotaurus sastrei, a theropod dinosaur from the Late Cretaceous period. Through a comprehensive analysis of fossil specimens, comparative anatomy, and biomechanical modeling, this review explores the evolutionary adaptations and potential functions of these distinctive cranial structures. The horns of Carnotaurus are hypothesized to serve multiple roles, including species recognition, thermoregulation, and intraspecific combat. Our findings suggest that its cranial horns likely served a primary role in species recognition, intimidating rivals and signaling mating readiness. It also could have been used occasionally in head-butting contests, potentially as a display of dominance, but likely did not play a role in thermoregulation. Additionally, we examine the ecological context in which Carnotaurus lived, assessing how environmental factors could have influenced the development of such features. The implications of this study extend to broader discussions on the functional morphology and adaptive strategies of theropod dinosaurs, highlighting the complex relationship between form and function in the evolutionary history of predatory dinosaurs like Carnotaurus sastrei.

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.