Abstract: The emergence and persistence of life pose a profound paradox: abiogenesis appears statistically almost impossible under standard physical chemistry, yet once present, living systems exhibit remarkable long-term stability against entropic decay. Here we propose that both phenomena can be explained by the action of a hitherto unobserved informational reservoir that subtly “leaks” into biological systems, biasing microstate probabilities in real time. While quantum coherence and nonlocality currently represent the most plausible physical substrates, the hypothesis deliberately remains agnostic about the ultimate origin of this reservoir. Crucially, the transfer need not be intentional; it may constitute an unintended “crosstalk” across an ontological boundary—analogous to sound leaking through a wall between apartments. This framework offers a strictly naturalistic alternative to intelligent design theories while generating falsifiable predictions distinguishable from both pure chance and directed panspermia.

Abstract: The Electron-Ion Interaction Potential (EIIP) is an empirically derived descriptor introduced through pseudopotential theory, representing the effective interaction between conduction electrons and atomic cores. Remarkably, EIIP depends solely on the atomic number Z, positioning it as a direct function of the periodic system. This paper revisits the theoretical foundation of EIIP and demonstrates its proportionality to the fine-structure constant α≈1/137, revealing a universal relationship that bridges quantum electrodynamics and the periodic architecture of matter. We show that EIIP can be expressed as EIIP=f(Z)⋅α, where f(Z) is a periodic function empirically determined from spectroscopic data. This insight establishes EIIP as a structural descriptor with broad applicability across physics, chemistry, and biology. Extending this framework, we introduce the concept of an effective biological fine-structure constant αbio, which quantifies the degree of electromagnetic coherence in living systems. Life is viewed as a resonant electromagnetic phenomenon, where molecular recognition and energy flow depend on synchronized electron and photon exchange. We define αbio in terms of dielectric and charge-transfer properties of biological media, and propose its deviation from α as a marker of aging and decoherence. By unifying EIIP and αbio, we establish a theoretical foundation for Electronic Biology, linking atomic periodicity with biological vitality through a shared electromagnetic language.

Abstract: Biological systems maintain coherent organization across spatial and temporal scales that cannot be fully explained by classical biochemical or electrophysiological models. Building on the dissipative quantum field theoretical framework introduced by Vitiello and collaborators, this work develops an organism-wide model in which coherence emerges from multiple quantum substrates undergoing spontaneous symmetry breaking (SSB). Each substrate—coherent water domains, microtubular dipole fields, mitochondrial excitons, chromatin vibrational dipoles, ionic phase waves, and large-scale electromagnetic modes—defines a distinct coherent sector represented by macroscopic fields Θ₁–Θ₁₂. These fields are characterized by condensation amplitudes θₖ(t) derived from the vacuum structure.Using operator doubling, Bogoliubov transformations, and projection of the doubled Liouville equation, we obtain macroscopic evolution equations for θₖ(t) and show that their dynamics form a gradient flow on a multi-field free-energy landscape with a global attractor Θ_ref. The Biological Coherence Index (BCI), based on vacuum overlap, provides an experimentally accessible measure of whole-organism coherence.This framework offers a unified quantitative approach to long-range biological coherence, cross-scale coupling, and integrative regulation in living systems.

Abstract: We propose a generalization of the dissipative quantum field theory (DQFT) as developed by Celeghini, Rasetti, and Vitiello to describe the dynamic informational feedback underlying biological coherence. The new framework, termed the Quantum Blueprint Formalism (QBF), builds on the fact that in DQFT the conjugate field ψ̃ is an active dynamical partner of ψ, representing the time-reversed degrees of freedom that co-generate dissipation, irreversibility, and the selection of inequivalent vacuum states. Rather than functioning as a mere repository of past interactions, ψ̃ participates continuously in the system’s coherent evolution through SU(1,1) Bogoliubov mixing.QBF extends this structure by allowing the ψ–ψ̃ coupling to become explicitly state-dependent, thereby endowing the conjugate field with an informational role that reflects and influences the system’s ongoing coherence pattern. Correlation parameters Θ = {θₖ} quantify the instantaneous coherence relations between the two sectors and evolve in time according to a nonlinear stochastic differential equation derived from the dissipative field dynamics.This extended formalism provides quantitative links between informational coherence and physiological observables such as heart rate variability (HRV), EEG phase synchronization, water-domain ordering, and ultraweak photon emission. It thereby establishes a bridge between dissipative quantum physics, information theory, and experimental biophysics, offering a consistent mathematical and empirical basis for understanding life as an informationally guided, self-organizing process in which ψ and ψ̃ jointly sustain and regenerate coherence.

Abstract: Biological tissue analyses rely on morphological descriptors like shape, layering and cellular composition. We introduce Architectural Dynamics, a framework that employs more than one hundred quantifiable parameters to define architectural and dynamical properties of a cellular microenvironment, including structural, mechanical, geometrical, physical, network-theoretic, cellular and biochemical features. Biological tissues are portrayed as weighted networks whose nodes and edges carry measurable physical quantities like diffusion conductance, mechanical impedance, curvature and material anisotropy. Standard network metrics like global efficiency, modularity, diameter and centrality acquire physiological meaning as indicators of accessibility, compartmentalization and exposure to mechanical or biochemical cues. In parallel, physical fields such as diffusion, mechanics, curvature and topography generate patterns of transport, signaling, force propagation and communication that link microscale architecture to mesoscale dynamical behavior. Using combined descriptions, we show that behaviors like migration patterns, polarization, domain formation, compartmentalization, metabolic coupling, signal propagation and stability of functional domains emerge from agent dynamics shaped by weighted topology, structural heterogeneity, mechanical anisotropy and geometric confinement. Our perspective shifts the emphasis from cellular identity to quantitative analysis of local physical cues and global topological organization within a high-dimensional architectural space, enabling prediction of cellular behaviors directly from tissue architecture. Changes in development, health or disease correspond to movements along well-defined architectural directions rather than to simple morphological or biochemical alterations. Our framework applies to engineered scaffolds, organoids and regenerative medicine as well as extracellular matrices, cortical microcircuits and pathological architectures like tumors, where the modulation of architectural regimes becomes central to interpreting tissue organization.

Abstract: Amniotic membrane used as a scaffold in the creation of a tissue-engineered complex for the restoration of the anterior layers of the cornea, and as a therapeutic coating is extremely attractive in that the biological substrate made from it is transparent and bioresorbable, which allows monitoring the state of the pathological focus. At the same time, the biomaterial used for therapeutic effects in corneal pathology should specifically react with tissues, since the cornea is an avascular tissue. Consequently, as a result of the therapeutic effect of the biopolymer, there should be no newly formed vessels either on the surface or in the thickness of the cornea, but at the same time proliferation should be activated and a specific epithelial cover should be formed. On the contrary, in the process of skin and bone regeneration, stimulation of angiogenesis is important. Native amniotic membrane has a set of biologically active substances that are preserved to some extent during preservation. However, native biomaterial is not currently used due to the risk of infecting recipients. Biomaterial stored with preservation of the viability of cellular structures and with a violation of vitality is used. The most common cryopreservation technique undoubtedly allows preserving both the cellular structures and the anatomical integrity of the amniotic membrane, thus retaining biologically active substances. According to researchers, cryopreserved amniotic membrane prevents the formation of new vessels in the implantation zone. However, some researchers who prefer to use lyophilized decellularized biomaterials express their doubt regarding the preservation of biologically active properties even in the amniotic membrane without viable cellular structures and consider it necessary to carry out further studies. Taking into account the experience of the Samara Tissue Bank in developing methods for lyophilization of biological tissues and the widespread use of decellularized matrices and implying the use of physical methods of decellularization and a special mode of sublimation drying, we have developed a method for processing and lyophilization of amniotic membrane. The aim of the given research was to study the preservation of biologically active substances and morphological assessment of efficiency in decellularized lyophilized amniotic membrane.

Abstract:

Over the past 50 years, scientific interest in electromagnetic field-biology interactions has flourished. Important experimental observations and mathematical hypotheses remain central to academic debate. Adey [1, 2] and Blackman [3, 4] found that specific electromagnetic frequencies affect calcium transport in cells. To explain this phenomenon, Liboff introduced ion cyclotron resonance-like (ICR-like) theory [5, 8-10, 32], proposing a specific mechanism for ion modulation. Preparata and Del Giudice introduced quantum electrodynamics (QED) [26-28], offering controversial quantum-level explanations that complement classical models. Lucia and NASA contributed further with thermomagnetic resonance [69-74] and experimental observations [76]. Together, these hypotheses have partially clarified how weak electromagnetic fields interact with cells and suggest possible parallel endogenous mechanisms. The aim of this narrative review is to provide a clear and logical framework for understanding biological events, both those that arise naturally within biology and those that can be initiated externally through the application of electromagnetic fields. Since electromagnetism is one of the 4 fundamental forces, this peculiarity deserves careful scientific attention.

Abstract: Curcumin, a natural polyphenol derived from Curcuma longa, is widely recognized for its therapeutic properties. However, its clinical utility is limited because of poor solubility, rapid degradation and hence low bioavailability. To overcome these issues, nanoformulation approaches, especially PEGylated liposomes, have been explored as advanced delivery systems. PEGylation, which involves attaching polyethylene glycol (PEG) to the liposomal surface, enhances circulation time by creating a steric shield that reduces protein interactions and clearance by the mononuclear phagocyte system (MPS). However, PEG can alter lipid membrane properties, which may in turn affect curcumin’s solubility and distribution within the liposomal bilayer, ultimately reducing its loading efficiency. To ensure that PEG-modified liposomes can be effectively loaded with curcumin, we investigated curcumin–membrane interactions in saturated (DMPC) and unsaturated (POPC) liposomes, both in the presence and absence of PEG. Based on dissociation constants (Kd) obtained from fluorescence spectroscopy measurements, we found that PEGylated DMPC liposomes exhibit the strongest binding affinity for curcumin. Fluorescence quenching experiments showed that curcumin adopts a transbilayer orientation in all membranes examined. Curcumin’s location within PEGylated and non-PEGylated liposomal membranes was further confirmed by examining its effects on membrane properties, including fluidity, polarity, and oxygen transport. These effects were investigated using electron paramagnetic resonance (EPR) spectroscopy with spin labels. The results indicate that PEG does not impose major changes on membrane properties. Curcumin, however, was found to reinforce the liposomal membranes, increase their polarity, and reduce oxygen availability. Overall, the findings suggest that liposomes, particularly those composed of PEGylated DMPC, are effective vehicles for curcumin delivery.

Abstract: In Greek philosophy, symmetry was closely tied to the concepts of harmony, beauty, and unity of Nature. Modern physics reveals that the integrity of the Universe is intimately linked to concepts of symmetry and relativity. In philosophy, the idea that a single set of laws and principles governs all forms of existence is called monism. In physics, this conjecture was first articulated by Galileo as the relativity principle (RP). Thus, it is fair to say that Galileo is the father of relativity. The historical perspective unveils that the most generalized manifestation of RP is the unity of the Universe. All subsequent evolutions of RP were unfolding of this foundational idea. The evolution of the RP was closely tied to the refinement of the mathematical formulation of space-time geometry and symmetry. Euclidean geometry was gradually displaced from the status of absolute to the role of an initial approximation of physical space determinants. At present, it becomes evident that perceptual indistinguishability of uniform motion, articulated by Galileo, is a consequence of fundamental determinants of existence - space-time symmetry and relativity (STSR). Remarkable, but the nature of elementary (smallest) constituents, the evolution of the largest scales of the Universe, and human behavior follow the same fundamental physical principles. The review is written in a language comprehensible to physicists, mathematicians, biologists, and philosophers (students and teachers). Prerequisite: The biologists should be familiar with the fundamental aspects of geometry, and physicist with the origin and evolution of life.

Abstract: We propose a Dual Anaplerotic Model (DAM) of beta cell insulin secretion, integrating two anaplerotic pathways: the classical glucose-driven route via pyruvate carboxylase (PC) and the GABA shunt–mediated pathway. PC plays a crucial role in the PEP cycle, enabling localized ATP production in microdomains near KATP channels. The GABA shunt provides fresh carbon to the TCA cycle, thereby amplifying the mitochondrial oxidative (MitoOx) phase. Replenishment of the GABA pool is linked to the cataplerosis of α-ketoglutarate during the mitochondrial cataplerotic (MitoCat) phase, a process critically supported by simultaneous PC-derived anaplerotic flux. For the first time, these pathways are recognized as integral, interdependent, and temporally coordinated routes of anaplerosis in beta cells. DAM thus synthesizes recent advances: the PC anaplerotic pathway with the PEP cycle, and the anaplerotic role of the GABA shunt, within the coordinating framework of the MitoCat–MitoOx model. This synergistic minimal model captures key experimental findings and predicts the interplay of major metabolite pools—the glycolytic, TCA, and GABA pools, together with the signaling role of Ca²⁺—highlighting the central role of the TCA–GABA–Ca²⁺ module in determining slow oscillatory periods in beta cells.

Abstract: Intrinsically disordered regions enable transcription factors (TFs) to undergo structural changes upon ligand binding, facilitating the transduction of environmental signals into gene expression. In this study, we combined molecular modeling methods to explore the hypothesis that unstructured inter-domain and subdomain linkers in bacterial TFs can function as sensors for carbohydrate signaling molecules. We combined molecular dy-namics simulations and carbohydrate docking to analyze six repressors with GntR-type DNA-binding domains, including UxuR, GntR and FarR from Escherichia coli, as well as AraR, NagR and YydK from Bacillus subtilis. Protein models obtained from different time points of the dynamic simulations were subjected to the sequential carbohydrates dock-ing. We found that the inter-domain linker of the UxuR monomer binds D-fructuronate, D-galacturonate, D-glucose, and D-glucuronate with affinities lower that its structured FadR-type effector-binding domain. However, in the monomer, these ligands formed mul-timolecular clusters, a feature absent in the dimer, suggesting that protein dimerization may depend on linker occupancy by cellular carbohydrates. Interacting with linkers con-necting subdomains of the LacI/GalR-type E-domains in GntR and AraR, D-glucose was able to form hydrogen bonds connecting distant structural modules of the proteins, while in NagR, FarR and YydK it bridged the inter-domain linkers and a β-sheet within the HutC-type E-domains. Our results establish flexible linkers as pivotal metabolic sensors that directly integrate nutritional cues to alter gene expression in bacteria.

Abstract: The design of selective kinase inhibitors remains a formidable challenge due to the high structural conservation of the ATP-binding site across the kinome, and the topological complexity of pharmacophores required for potent inhibition. While modern generative AI has enabled rapid exploration of chemical space, many advanced models operate as black boxes, obscuring the chemical rationale behind design choices and limiting interpretability for medicinal chemists. Here, we present a modular, chemistry-first generative framework for de novo design of SRC kinase inhibitors, integrating ChemVAE-based latent space modeling, a chemically interpretable Kinase Inhibition Likelihood scoring function, Bayesian optimization, and cluster-guided local neighborhood sampling. Our generative pipeline employs a hybrid AI framework that integrates deep variational autoencoding, interpretable machine learning–based scoring, and probabilistic optimization to enable targeted exploration of kinase inhibitor chemical space. Our analysis reveals three pivotal findings. We demonstrate that kinase inhibitors—spanning ten families—spontaneously organize into a coherent, low-dimensional manifold in latent space, with SRC acting as a structural “hub” that enables rational scaffold transformation. Our local neighborhood sampling-based approach successfully converts inhibitors from other kinase families (notably LCK) into novel SRC-like chemotypes, with LCK-derived molecules accounting for ~40% of high-similarity outputs. However, both generative strategies reveal a critical limitation: SMILES-based representations systematically fail to recover multi-ring aromatic systems—a hallmark of clinical kinase inhibitors—despite aromatic ring count being a top feature in Kinase Inhibition Likelihood scoring function. This “representation gap” underscores that no amount of scoring refinement can compensate for a generative engine that cannot access topologically complex regions. By diagnosing these constraints within a transparent, interpretable pipeline, our work provides a foundational benchmark for current AI and a blueprint for hybrid systems that blend algorithmic innovation with medicinal chemistry principles.

Abstract: Big Bang theories are connected to gravity by force of attraction. Forced lengthening, like eccentric contractions instigate proprioception as a result of working against gravity. Piezo2, as the principle mechanosensory ion channel responsible for proprioception, may fine modulates these anti-gravitational contractions in order to provide system-wide ultrafast postural control. This mechanism instantaneously emits blast energy by Piezo2 in order to offset gravity and it is suggested to be propagated by quantum tunneling of protons (and electrons). However, wormholes should be considered as part of this ultrafast long-distance non-synaptic neurotransmission despite quantum gravity concept is short of being unequivocally proven to be unified with quantum theory. The impairment of this signaling is the equivalent of the Big Bang within a given compartment, or acquired Piezo2 channelopathy, leading to the principle gateway to pathophysiology.

Abstract: Experiments have shown that non-double strand break (DSB) clustered damage consisting of two or more base damages (BDs) or BD with single strand breaks (SSBs) occur with higher frequency than DSBs after ionizing radiation exposure. However experiments that measure tandem non-DSB clusters has not been developed. I develop a probability model of clustered damage that is combined with energy imparted spectra to predict the relative contributions of tandem and bistranded non-DSB clustered damage. The model considers probabilities for direct damage to sugar-phosphate moieties leading to SSBs, direct damage to DNA bases leading to abasic or oxidized sites, and indirect damage leading to radical formation with subsequent SSB and BD formation. Additional probabilities account for relative location of SSB and BD to model damage clusters. The model predicts for electrons and ions the relative contribution of tandem or bistranded lesions, the larger occurrence of clustered non-DSBs compared to DSBs, and the predominance of mixtures of damage types. Predictions of ratios of non-DSB clusters to DSB of 4-to-6 are found for electrons and high energy ions. The model provides an accurate method to predict DSB and non-DSB damage clusters as a function of radiation modality and to model resulting damage processing.

Abstract: The development of neuroanatomy and neurophysiology has revealed many new details about neurons’ electrical operation over the past few decades, requiring modifications to their theoretical models. The development of computing technology enables us to consider the fine details the new model requires, but it necessitates a different approach. As it was long ago suspected, the faithful simulation of biological processes requires accurately mapping biological time to technical computing time(s). Therefore, the paper focuses on time handling in biology-targeting computations. However, the operation of biology and the physical/mathematical processes in living matter are also unusual from the point of view of algorithmic description. Furthermore, the way technical computing works prevents achieving the needed accuracy in reproducing biological operations using computer programs. We also touch on the question of simulating the operation of their network, contrasted with that of spiking artificial neural networks. On the one side, we use an updated theoretical model that considers neuronal current as charged ions (and so considers thermodynamic effects) and opens the way for explaining mechanical, optical, etc., consequence phenomena of the electric operation. On the other hand, we use a new technology, a tool designed to achieve extreme accuracy in simulating high-speed electronic circuits. The algorithm that applies this model, along with the unusual programming method, provides new insights into both neuronal operation and its computing implementation.

Abstract: Words matter in science, particularly when they define technologies with distinct biological mechanisms. High-Intensity Laser Therapy (HILT) is often conflated with High-Power Laser Therapy or High-Level Laser Therapy (HPLT/HLLT), despite these terms referring to laser systems with very different capabilities. Whereas many therapeutic lasers can elicit photochemical and photothermal effects, only devices delivering high-peak, short-duration pulses at very low duty cycles are able to generate acoustic pressure waves and thus qualify as true HILT systems. These photoacoustic effects uniquely activate mechanotransduction pathways involved in cellular differentiation, extracellular matrix remodeling, and long-term tissue regeneration. This review highlights the widespread misclassification in the laser therapy literature, where devices lacking genuine photoacoustic capability are nonetheless described as HILT. Such semantic ambiguity undermines biological specificity, inflates clinical claims, and delays technological progress. Within the laser science community, it is well recognized that average power alone is insufficient to characterize a therapeutic mechanism and provides no indication of the ability to induce pressure waves. We therefore propose a mechanism-based classification that clearly separates photochemical, photothermal, and photoacoustic effects, and call for greater rigor in reporting technical parameters such as peak power, pulse duration, and duty cycle. Correct terminology will advance scientific rigor and enable meaningful comparisons across regenerative medicine studies.

Abstract: Protein and nucleic acid play central roles in biology and pharmaceuticals. Both share a similar architecture made of a backbone and side chains. Protein has a peptide backbone and various side chains, whereas nucleic acid has a phosphate backbone and aromatic side chains. However, they are significantly different in the chemical properties of the backbone and side chains. The protein backbone is uncharged, while nucleic acid backbone is negatively charged. The protein side chains comprise widely different chemical properties, while the nucleic acid side chains comprise a uniform chemical property of aromatic bases. Such differences lead to fundamentally different folding and molecular interactions and co-solvent interactions, which are the focus of this review. In regular protein secondary structures, the peptide groups form polar hydrogen bonds, making the interior hydrophilic, while the side chains of different chemical properties are exposed on the outside and participate in molecular interactions and co-solvent interactions. On the contrary, hydrophobic/aromatic nucleobase side chains locate inside the typical double helix or quadruplex structures and charged phosphate groups of the nucleic acid backbone locate outside participating in molecular interactions. The nucleobases are also involved in molecular interactions, when exposed in breaks, hairpins, kinks and loops. These structural differences between protein and nucleic acid confer different interactions with commonly used co-solvents, such as denaturants, organic solvents and polymers.

Abstract: This paper presents a interdisciplinary inquiry into the possibility of non-carnal human procreation, informed by spiritual symbolism, cultural mythology, and metaphysical philosophy.[5]. Drawing upon Indian traditions, the work examines folkloric accounts such as the peacock’s tear-based mating ritual and links them to spiritual figures like Lord Krishna.[1]. It further proposes biological pathways by which sperm may enter the bloodstream or atmosphere, travel via respiratory or ocular channels, potentially reaching other tissues or being exhaled or absorbed by another body. The discussion includes analogies to botanical pollination, theological parallels to divine births in Christianity and classical antiquity, and speculative models of sperm motility across physiological and environmental media. Emphasis is placed on emotional resonance— such as the gaze of “loveful eyes”—as a potential channel for metaphysical conception. While unorthodox and not corroborated by conventional science, these hypotheses are framed as metaphoric and symbolic provocations intended to inspire novel reflections on the limits of reproductive science and the possibilities of spiritual embodiment. The work concludes with experimental suggestions for exploring the plausibility of these ideas under controlled and ethically guided conditions, advocating for a dialogue between the measurable domain of empirical science and the contemplative depth of spiritual insight.

Abstract: Nearly two centuries after Charles Darwin formulated the theory of evolution by natural selection, resistance to evolutionary science persists among influential strands of Christian thought, particularly within creationist and Intelligent Design (ID) movements. This study examines recent publications by Olen R. Brown and David A. Hullender, whose peer-reviewed papers exemplify how this ideological conflict can manifest within scientific discourse. Although written in technically calibrated language, their arguments reproduce the rhetorical structure of Christian apologetics—characterized by moralizing tone, faith-based framing, and metaphysical vocabulary disguised as empirical reasoning. Using GPT-5 for linguistic and semantic analysis, combined with manual verification, this study identifies recurring patterns consistent with apologetic framing embedded in ostensibly scientific texts. The results demonstrate how theological rhetoric can infiltrate peer-reviewed literature through the idioms of biomathematics, complex systems theory and artificial intelligence, often invoking complexity or emergence to confer scientific legitimacy. These findings underscore the importance of epistemic vigilance in interdisciplinary research. Detecting and contextualizing such rhetorical patterns is essential to safeguarding scientific integrity and preventing the instrumentalization of academic publishing for theological or ideological ends.

Abstract: We previously established that Multifrequency Electromagnetic Pulse (MEMP) treatment selectively eradicates tumorigenic cells in vitro. While this treatment proved safe in mice and prevented tumor formation by pre-treated cells, its efficacy against established tumors remained unknown. Here we evaluate the therapeutic effect of two different systemic MEMP treatment regimens (30 Hz, >2 T) on syngeneic MC38 colon adenocarcinoma es-tablished subcutaneously in C57BL/6 mice. The impact of MEMP on anti-tumor immune infiltration (CD4, CD8, CD68) responses, as well as oxidative stress (HO-1, MDA), and DNA damage (γH2AX), cell biology markers, were analyzed by immunohistochemistry. The MEMP regimes significantly reduced the growth of the xenografted tumors leading to an apparent regression in a small subset of animals, and extended survival without af-fecting animal welfare. Of note, mice that achieved complete tumor regression mounted a protective immune response, demonstrating robust resistance to a subsequent tumor re-challenge, indicative of immunological memory. Importantly, the quantitative penetra-tion of immune effectors CD68+ cells into tumors suggests the involvement of a strong, macrophage-mediated anti-tumor response, although the ultimate mechanisms driving the MEMP effects in vivo deserve further research. These findings place MEMP as a prom-ising anti-cancer treatment and a strong candidate procedure for combination with other systemic immunotherapies.