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The structure of exotic nuclei is one of the main interests in current nuclear physics. Exotic nuclei present unusual properties, such as a low breakup energy, a short lifetime and/or a halo structure. Because of their short lifetimes, they can not be studied by usual spectroscopic techniques. Indeed, targets of such nuclei are impossible to build. But since the availability of radioactive beams, nuclear reactions have provided possibilities of exploring nuclei far from stability.<p><p>The investigation of exotic nuclei has been recently reactivated by the development of intense radioactive nuclear beams. As firstly observed for the deuteron, and then for other exotic projectiles such as $^6$He and $^{11}$Be, the internal structures of the interacting nuclei can have a significant effect on the elastic cross sections. Due to their low binding energy, the projectile dissociation process, leaving the target in its ground state, highly affects elastic cross sections but also other measurements such as transfer and fusion reactions. Accurate reaction theories are therefore needed. The coupled discretized-continuum channel (CDCC) method is one of those theories and assumes a projectile made of N clusters (usually N=2 or 3) impinging on a target which is structureless. The N+1-body Schrödinger equation is approximately solved by expanding the total wave function over the bound and continuum states of the projectile. These latter take into account the dissociation events and are approximately described by a truncated set of square-integrable wave functions. There are two available methods for discretizing the continuum, the pseudostate method where the projectile Hamiltonian is diagonalized within a finite basis of square-integrable functions, or the bin method where exact scattering wave functions of the projectile are averaged over bins in a finite region of space. In both cases, the N+1-body Schrödinger equation is replaced by a set of coupled-channel differential equations, which provides the physical quantities such as the collision matrix. In principle, the CDCC method can be very close to the exact N+1-body wave function and is adapted to low as well as to high energy reactions. However, its main interest consists in the low-energy domain.<p><p>In the present work, we propose a new approach to solve the CDCC equations. This method is based on the R-matrix theory associated with a Lagrange mesh basis. We will show that the combination of both approaches provides a fast and accurate technique to solve the CDCC equations, even for large systems, where traditional methods meet convergence problems. Before investigating collisions with exotic projectiles, we restrict ourselves to the simplest nucleus, the deuteron. Then we make a step towards a more complicated system, the $^6$Li which is a well known stable nucleus. We apply the CDCC method to the d + $^{58}$Ni and $^6$Li + $^{40}$Ca elastic scattering and breakup. These systems are considered in the literature as test cases. They have been investigated by several authors who showed the importance of the breakup channels in the elastic cross sections.<p><p>After having validated the present version of the CDCC method, we focus on $^{11}$Be, a typical example of a halo nucleus, with low binding energy and large quadrupole moment. Elastic, inelastic and breakup cross sections are computed in the CDCC formalism, at energies near the Coulomb barrier, where continuum effects in the scattering of exotic nuclei, and more specifically on the $^{11}$Be + $^{64}$Zn scattering, are observed. We show that converged cross sections need high angular momenta as well as large excitation energies in the wave functions of the projectile.<p><p>A Borromean nucleus is made of three constituents which are weakly linked together, but where each pair of those three constituents does not form a bound system. The name "Borromean" comes from the Borromean rings where, if any one of three rings is removed, the remaining two become unbound. Collisions with $^6$He and $^9$Be Borromean projectiles are studied in the present work. Again we compare our method with the $^6$He + $^{208}$Pb and $^6$He + $^{12}$C benchmark calculations. Afterwards, the convergence against the parameters of the description of the $^9$Be projectile is tested for the elastic cross section. The sensitivity to the technique employed to remove the forbidden states and also the sensitivity to the collision energy are investigated. / Doctorat en Sciences de l'ingénieur / info:eu-repo/semantics/nonPublished

<p>Користећи NAXSUN технику развијену уЈРЦ-Геел,мерени су ефикасни пресеци зареакције изазване неутронима187Re(n, p) 187W и 185Ре (n, 3n) 183Rе мерене у енергетском распону између 13,08 MeV и 19,5 МеV. Ови подаци су прве експериментално добијене вредности за нуклеарне реакције у овом енергетском опсегу неутрона. Добијени резултати упоређени су са постојећим процењеним прорачунимаТАЛИС 1.9 и ЕМПИРЕ 3.2.3 користећи различите доступне моделе. Упоређени су теоријски прорачуни са експерименталним резултатима. У раду је, на основу три снимљена гама спектра калифорнијумовог извора, закључено о утицају акумулације фисионих продуката на укупну специфичну гама константу извора.</p> / <p>Koristeći NAXSUN tehniku razvijenu uJRC-Geel,mereni su efikasni preseci zareakcije izazvane neutronima187Re(n, p) 187W i 185Re (n, 3n) 183Re merene u energetskom rasponu između 13,08 MeV i 19,5 MeV. Ovi podaci su prve eksperimentalno dobijene vrednosti za nuklearne reakcije u ovom energetskom opsegu neutrona. Dobijeni rezultati upoređeni su sa postojećim procenjenim proračunimaTALIS 1.9 i EMPIRE 3.2.3 koristeći različite dostupne modele. Upoređeni su teorijski proračuni sa eksperimentalnim rezultatima. U radu je, na osnovu tri snimljena gama spektra kalifornijumovog izvora, zaključeno o uticaju akumulacije fisionih produkata na ukupnu specifičnu gama konstantu izvora.</p> / <p>Using the NAXSUN technique developed at the JRC-Geel, the cross section functions for the neutron induced reactions 187Re(n,p)187W and 185Re(n,3n)183Re have been measured in the energy range between 13.08 MeV and 19.5 MeV. These data are the first experimentally obtained values for those nuclear reactions in this neutron energy range. Obtained results have been compared withexisting evaluated The TALYS 1.9 and EMPIRE 3.2.3 calculations were performed using different available. A comparison between theoretical model calculations and experimental results was made. Based on three recorded gamma ray spectra of a Californiumsource, conclusion is made if there are influences of fission product accumulation on the total specific gamma ray constant of the source.</p>

<p>      </p> <p>Full exploitation of shale resources requires new catalytic techniques to efficiently convert the methane, ethane, and propane found in shale gas to value-added fuels and chemicals. A promising process of converting ethane and propane involves catalytic light alkane dehydrogenation and the subsequent oligomerization of light alkenes. The first part of this work focuses on the examination of the mechanistic details of propane dehydrogenation on Pt-based alloy catalysts, where first principles-based free energy, microkinetic, and degrees of rate control analyses are performed to understand and rationalize the selective propane dehydrogenation using a Pt3Mn alloy. We show that only the under-coordinated, Mn-decorated Pt sites, represented by a Pt3Mn(211) surface, are selective to propylene formation, which can be attributed to several key mechanistic details: (1) facile propylene desorption and (2) hindered pathways that are inherently non-selective to propylene and lead to the formation of isomers. These kinetic details can, in turn, be interpreted using the free energy landscapes of propane dehydrogenation on the Pt3Mn(211) surface, which features a reasonably stronger binding of propylene than those of its isomers. From this study, we extract two selectivity descriptors for propane dehydrogenation: The energetics of propylene desorption versus deep-dehydrogenation, as well as the energetics of the formation of propylene versus its isomers. The properties can be used for designing further improved light alkane dehydrogenation catalysts.</p>

<p dir="ltr">Metal speciation and structure can be influenced by the deposition method used during synthesis, interactions with the support, and by post-deposition treatments and reaction conditions experienced during its lifetime of carrying out a catalytic reaction. Supported metal particles of different size contain different surface structures and coordination environments, which may not only influence reaction rates but also the interconversion between agglomerated metallic domains and dispersed metal atom or ion sites. Here, we address the influence of post-deposition treatments and support properties on the structural interconversion of Pd and Cu on aluminosilicate chabazite (CHA) zeolites, Pt on gamma-alumina (γ-Al2O3), and Pd on amorphous oxides (γ-Al2O3, La-doped Al2O3, ΘΔ-Al2O3). The fundamental insights from these studies can be used to design catalysts used widely in automotive exhaust aftertreatment systems, including Pd-exchanged zeolites for passive NOx (x = 1,2) adsorbers (PNA), Cu-exchanged zeolites for NOx (x = 1,2) selective catalytic reduction (SCR), Pt/Al2O3 for NH3 oxidation, and Pd/oxides for three-way catalysts (TWC). Incipient wetness impregnation (IWI) and colloidal methods were used to prepare Pd nanoparticles deposited on CHA zeolites with distinct Pd nanoparticle sizes and distributions. These Pd-CHA samples were used to investigate the effects of Pd particle size distribution on structural interconversion between ion-exchanged Pd and agglomerated Pd domains under realistic operating conditions. Smaller Pd nanoparticles had larger fractions of agglomerated Pd that converted to ion-exchanged Pd2+ sites at fixed air treatment temperatures (598–973 K) and H2O pressures (2–6 kPa H2O), consistent with thermodynamic predictions from DFT calculations. Furthermore, the addition of H2O during air treatment of different Pd nanoparticles (2–14 nm) inhibited the formation of ion-exchanged Pd2+ (thermodynamics), but not the rate of redispersion (kinetics). This demonstrates that, regardless of Pd nanoparticle size, water vapor in automotive exhaust streams facilitate metal sintering in PNA applications. Aqueous-phase exchange of Cu on CHA zeolites with varying support properties (i.e., number of paired Al sites in the 6 membered ring) were used to prepare materials with distinct types and numbers of extraframework Cu species (Cu2+, CuOH+). These Cu-CHA materials were used to analyze Cu structural changes before and after exposure to hydrothermal aging conditions. In the absence of H2O, some Cu2+ sites condense to form binuclear Ox-bridged Cu species that can be reduced with H2 to form Cu-hydride sites and reject H2O, leading to a sub-stoichiometric H2 consumption (H2/Cu < 0.5). In the presence of H2O, all nominally isolated Cu2+ species convert to [CuOH]+ structures, which can subsequently be reduced by H2 to form a Cu-hydride and reject H2O, leading to stoichiometric H2 consumption (H2/Cu ~ 0.5). Furthermore, the presence of H2O led to reduction features in H2 temperature programmed reduction (TPR) profiles that were similar among Cu-CHA materials, regardless of the initial Cu2+ speciation, further supporting the proposal that all nominally isolated Cu2+ sites convert to a similar [CuOH]+ motif. This demonstrates how water influences Cu speciation on CHA materials of varying origin or treatment history, aiding in quantifying SCR-active isolated Cu ions and SCR-inactive Cu species (e.g., CuO, CuAl2O4). Pt supported on γ-Al2O3 were prepared with different average Pt particle sizes (2–13 nm) by increasing the temperature of post-deposition air treatment (523–873 K). This suite of materials was interrogated to isolate the effects of Pt particle size on NH3 oxidation rates and selectivities during conditions relevant to NH3 slip applications in diesel exhaust aftertreatment. For all Pt particle sizes, NH3 oxidation rates displayed a hysteresis with temperature, with high rates measured during temperature decreases than during temperature increases. Smaller Pt particles (2 nm) had lower rates (per surface Pt, quantified by CO chemisorption) than larger Pt particles (13 nm), signifying that NH3 oxidation is a structure-sensitive reaction. Furthermore, surfaces of Pt particles restructure under NH3 oxidation reaction conditions, influencing effective Pt oxidation states, surface structures (numbers and types of exposed Pt sites), and surface coverages of intermediates leading to the observed hysteresis in rate. These findings demonstrate that Pt particles undergo dynamic structural changes during reaction, influencing their ability to convert NH3 to environmentally benign products in NH3 slip applications. The influence of treatment conditions, support properties, and initial Pd particle size and distribution on the kinetics of nanoparticle sintering were investigated to identify which material properties allow maintaining high dispersion to maximize metal utilization for three way catalysts (TWC) during the conversion of regulated pollutants (CO, hydrocarbons, NOx). Pd was deposited by IWI methods to generate polydiserse particle size distributions, and using colloidal Pd nanoparticle solutions to generate monodisperse size distributions, onto various supports (γ-Al2O3, La-doped Al2O3, ΘΔ-Al2O3) and subjected to aging under oxidative and reductive conditions relevant for TWC operation. The average Pd particle size for all materials increased with treatment time under both reductive and oxidative environments. For samples prepared with IWI (i.e., log normal distribution of Pd particle sizes), reductive aging treatments led to higher sintering rates than oxidative treatments. In contrast, for samples prepared using colloidal Pd solutions (i.e., normal distribution of Pd particle sizes), oxidative aging treatments led to higher sintering rates than reduction treatments. Furthermore, after the same treatment condition and time, samples prepared with IWI resulted in higher average Pd particle sizes. These results indicate that more monodisperse initial Pd particle size distributions lead to lower sintering rates, providing guidance to design of supported metal TWCs with improved metal utilization during their lifetimes. Here, the combination of synthesis approaches to prepare a suite of model (e.g., powder) supported metal catalysts of varying structure and composition, interrogated using site and structural characterizations and steady-state and transient kinetic measurements, along with predictions from theoretical calculations, enabled unraveling the influence of material properties and gas environments that affect metal speciation, structure, and oxidation state in real-world aftertreatment systems that use more complex catalytic architectures (e.g., layered washcoats) and reactor designs (e.g., monoliths). This approach provides insights into the fundamental thermodynamic and kinetic factors influencing metal restructuring and interconversion under realistic conditions encountered in automotive exhaust aftertreatment applications, and the kinetic and mechanistic factors that underlie complex phenomena (e.g., reaction rate hysteresis) from data measured in the absence of hydrodynamic artifacts. The overall approach used in this work enabled development of synthesis-structure-function relationships on various metal supported catalysts for automotive exhaust aftertreatment applications, which can provide guidance for material design and treatment strategies to form and retain desired metal structures throughout the material lifetime, including synthesis, reaction, and regeneration treatments.</p>

<p dir="ltr">Zeolites are microporous crystalline aluminosilicates that are widely used as catalysts for upgrading hydrocarbons and oxygenates to higher value chemicals and fuels. The substitution of tetrahedral Si⁴⁺ with Al³⁺ in a charge-neutral silica framework ([SiO_4/2]) generates anionic centers ([AlO_4/2]^-), which charge-compensate Brønsted acid protons (H⁺) that serve as active sites for catalysis. Brønsted acid sites in aluminosilicates of diverse topologies have similar acid strength, but can be located within varying intracrystalline (or internal) microporous environments (0.4‒2 nm diameter) or at extracrystalline (or external) surfaces and mesoporous environments (>2 nm diameter); yet, catalytic diversity exists, <i>even</i> for a fixed zeolite framework topology, because micropores impose constraints on molecular access to and from intracrystalline active sites and provide van der Waals contacts that influence the stabilities of reactive intermediates and transition states. Tailoring the material properties of a given zeolite framework for targeted catalytic applications requires strategies to design both the bulk crystallite properties (e.g., morphology, active site density) that influence intracrystalline diffusion and the secondary environments that surround active sites and influence intrinsic kinetics, and further necessitates molecular-level insights to elucidate the influences of bulk and active site properties on catalysis. In this work, we provide synthetic and post-synthetic strategies to respectively tune active site environments within varying micropore voids and at external surfaces of zeolites, and develop gas-phase toluene methylation and liquid-phase mesitylene benzylation as probe reactions to quantify the catalytic consequences of active site environments on aromatic alkylation catalysis.</p><p dir="ltr">The MFI framework (orthorhombic phase) consists of 12 crystallographic distinct tetrahedral-sites and 26 unique framework oxygen atoms located around channels (~0.55 nm diameter) or channel intersections (~0.70 nm diameter). The synthesis of MFI zeolites using the conventional tetra-<i>n</i>-propylammonium (TPA⁺) organic structure directing agent (OSDA) is known to place framework Al and their attendant H⁺ sites within the larger intersection environments, because electrostatic interactions are favorable between such locations of [AlO_4/2]^- and the quaternary N⁺ center in TPA⁺ that becomes positioned rigidly within channel intersections during crystallization. The methylation of toluene by dimethyl ether (DME; 403 K) on MFI-TPA zeolites of fixed active site densities (~2 Al per unit cell) result in <i>ortho</i>-xylene (<i>o</i>-X; ~65%) as the major product over <i>para</i>-xylene (<i>p</i>-X; ~27%) and <i>meta</i>-xylene (<i>m</i>-X; ~8%). In contrast, toluene methylation on MFI zeolites (~2 Al per unit cell) synthesized using non-conventional OSDAs, such as ethylenediamine (EDA) or 1,4-diazabicyclo[2.2.2]octane (DABCO), predominantly forms <i>p</i>-X (~75%) over <i>o</i>-X (~23%) and <i>m</i>-X (~2%). Within the subsets of MFI-TPA and MFI-EDA/DABCO zeolites, measured xylene formation rates and isomer selectivities are independent of crystallite sizes (0.1‒13 µm), toluene conversions (0.02‒2.0%) and external H⁺ content (up to 9% external H⁺ per total Al), indicating negligible effects of diffusion-enhanced secondary xylene isomerization reactions at intracrystalline or extracrystalline domains. The invariance of xylene isomer selectivity with reactant pressures (0.2‒9 kPa toluene, 25‒66 kPa DME) or methylating agent (1‒4 kPa methanol) indicate that differences in reactivity of toluene to form each xylene isomer reflects differences in the stabilities of their respective kinetically relevant transition states that share the same reactive intermediate. Measured xylene isomer formation rate constants and rate constant ratios, obtained from mechanism-derived rate expressions and interpreted using transition state theory formalisms, are used alongside density functional theory (DFT) calculations to reveal that intersection void environments (~0.70 nm diameter) similarly stabilize all three xylene transition states over unconfined surfaces (>2 nm diameter) without altering the established aromatic substitution patterns, while channel void environments (~0.55 nm diameter) preferentially destabilize bulkier <i>o</i>-X and <i>m</i>-X transition states thereby resulting in high intrinsic <i>p</i>-X selectivity. DFT calculations reveal that the ability of protonated DABCO complexes to reorient within MFI intersections and participate in additional hydrogen-bonding interactions with anionic Al centers during synthesis, facilitates the placement of Al in smaller channel environments that are less favored by TPA⁺. These molecular-level details, enabled by combining synthesis, characterization, kinetics and DFT, establish a mechanistic link between OSDA structure, active site placement and transition state stability, and provide active site design strategies orthogonal to crystallite design approaches that rely on complex reaction-diffusion phenomena.</p><p dir="ltr">For various reactions including toluene methylation at higher reaction temperatures (573‒773 K) and toluene conversions (>10%), extracrystalline H⁺ sites in MFI zeolites are reported to influence reactivity, selectivity, and deactivation behavior during catalysis in undesired ways. Post-synthetic chemical treatments to passivate external H⁺ sites on MFI zeolites result in unintended (but not always undesirable) changes to bulk structural properties and Al and H⁺ contents. The number of extracrystalline H⁺ sites is difficult to quantify using conventional spectroscopic or titrimetric methods, especially when present in dilute amounts on samples whose surfaces have been passivated. The systematic treatment of MFI zeolites (2.4, 5.7 and 7.1 Al per unit cell) using ammonium hexafluorosilicate (AHFS) at varying treatment duration times, AHFS concentrations and number of successive treatments resulted in MFI zeolites that retain their bulk structural properties and total Al and H⁺ contents, except for one parent MFI sample containing a significant amount of non-framework Al species. The benzylation of mesitylene by dibenzyl ether (363 K) occurs exclusively at external H⁺ sites because the bulky 1,3,5-trimethyl-2-benzylbenzene product is sterically prevented from forming at intracrystalline H⁺ sites. The intrinsic zero-order rate constant (per external H⁺) for mesitylene benzylation is extracted from rate measurements (per total Al) on a suite of untreated MFI samples with known amounts of external H⁺ sites (1‒15% external H⁺ per total Al) quantified using bulky 2,6-di-<i>tert</i>-butylpyridine base titrants. Measured zero-order rate constants on AHFS-treated MFI zeolites are used to quantify the extent to which AHFS treatments passivate external H⁺ sites, revealing efficacies that depend on the specific treatment conditions and the parent sample used. The developed kinetic methods demonstrate the utility of catalytic probes, when compared to stoichiometric probes based on spectroscopic or titration methods, in amplifying and quantifying dilute concentrations of external H⁺ sites on zeolites. The methods enable comparisons of the efficacy of various post-synthetic passivation strategies and permit rigorous assessments of the influence of external H⁺ during acid catalysis.</p><p dir="ltr">Overall, this work provides (post-)synthetic strategies to tune active site environments within intracrystalline micropores or at extracrystalline surfaces and develops quantitative kinetic probes that enable a molecular-level understanding of catalytic consequences of active site environments on aromatic alkylation reactions. Taken together, the methodology and findings of this study have broader implications in zeolite catalyst design for selectively upgrading traditional fossil feedstocks (crude oil and shale gas) and emerging feedstocks (biomass and waste plastics).</p>

<p dir="ltr">Regulation of complex biological processes aims to achieve goals essential for an organism's survival or to exhibit specific phenotypes in response to stimuli. This regulation can occur at several levels, such as cellular metabolism, signaling pathways, gene transcription, mRNA translation into proteins, and post-translational modifications. Systems biology approaches can facilitate integrating mechanistic knowledge and high-throughput omics data to develop quantitative models that can help improve our understanding of regulations at various levels. However, computational modeling of biological processes is challenging due to the vast details of various processes with unknown mechanisms. The cybernetic modeling approach accounts for unknown control mechanisms by defining a biological goal that the system aims to optimize and subsequently mathematically formulates the cybernetic goal.</p><p dir="ltr">This thesis aims to develop a mathematical framework that integrates a cybernetic model with novel information-theoretic methods to study the inflammatory response in mammalian macrophage cells. The inflammatory response of the body is a protective mechanism that fights off infecting pathogens by inducing the production of immune signaling proteins called cytokines and chemokines, as well as specific lipids known as eicosanoids. However, excessive levels of cytokines and eicosanoids may result in chronic inflammatory diseases such as hyper-inflammation syndrome, COVID-19, and asthma. Only a few studies have focused on quantitative modeling of the role of lipid metabolism in inflammation. One key lipid is Arachidonic acid (AA), which during inflammation, gets converted into inflammatory lipids called eicosanoids. Previous models utilize Michaelis-Menten kinetics or assume the linear form and can, at best, include control at the gene expression level only. The distinguishing feature of a cybernetic model is that by defining a cybernetic objective, it can account for control at multiple levels, including transcriptional, translational, and post-translational modifications.</p><p dir="ltr">The following paragraphs address a specific research problem, outline the approaches to investigate it, and summarize the key findings.</p><p dir="ltr">First, we studied the cellular response to inflammatory stimuli that produce eicosanoids—prostanoids (PRs) and leukotrienes (LTs)—and signaling molecules—cytokines and chemokines—by macrophages. A few studies suggest that targeting eicosanoid metabolism could be a promising new approach to regulating cytokine storm in COVID-19 infection. We developed a cybernetic model combined with novel information-theoretic approaches to study the integrated system of eicosanoids and cytokines. Our cybernetic model formulates a cybernetic goal, which requires the causal relationship between the eicosanoid and cytokine secretion processes; however, this causal relationship is unknown due to insufficient mechanistic information. We developed novel information-theoretic approaches (discussed later in detail) to understand the causality between eicosanoids and cytokines. The causality result from information theory suggests that Arachidonic acid (AA) may be the cause for initiating the secretion of cytokine TNF. The model captured the data for all experimental conditions, including control, treatment with Adenosine triphosphate (ATP), (3-deoxy-d-manno-octulosonic acid) 2-lipid A (Kdo2-Lipid A, abbreviated as KLA), and a combined treatment of ATP and KLA in mouse bone marrow-derived macrophages (BMDM). The model explains the dynamics of metabolites for all experimental conditions, validating the hypothesis. It also enhanced our understanding of enzyme dynamics by predicting their profiles. The results indicated that the dominant metabolites are PGD2 (a PR) and LTB4 (an LT), aligning with their corresponding known prominent biological roles during inflammation. Based on the causality and cybernetic model result and using heuristic arguments, we also infer that AA overproduction can lead to increased secretion of cytokines/chemokines. Consequently, a potential clinical implication of this study is that modulating eicosanoid levels could lower TNFα expression, suggesting eicosanoids could be a viable strategy for managing hyperinflammation.</p><p dir="ltr">Second, we studied the dynamics of the anti-inflammatory lipid mediators from eicosapentaenoic acid (EPA) metabolism, which can be beneficial in reducing the severity of diseases such as cancer and cardiovascular effects and promoting visual and neurological development. This study employed a cybernetic model to study the enzyme competition between AA and EPA metabolism in murine macrophages. The cybernetic model adequately captured the experimental data for control non-supplemented and EPA-supplemented conditions in RAW 264.7 macrophages. The cybernetic variables provide insights into the competition between AA and EPA for the COX enzyme. Predictions from our model suggest that the system undergoes a switch from a predominantly pro-inflammatory state in control to an anti-inflammatory state with EPA supplementation. A potential application of this study is utilizing the model estimation of the ratio of concentrations required for the switch to occur as 2.2, which aligns with the experimental observations and falls within the recommended range of 1-5 needed to promote anti-inflammatory response.</p><p dir="ltr">Third, we focused on predicting novel causal connections between AA and cytokines using time series analysis as mechanistic information connecting AA and cytokines is unknown. In this work, we developed Time delay Renyi Symbolic Transfer Entropy (TDRSTE), a novel model-free information-theoretic metric. We computed it from high-throughput omics datasets for bivariate non-stationary time series to quantify causal time delays. The TDRSTE method adequately estimated time delay for the synthetic dataset, captured causality for the real-world biological dataset of the AA metabolic network with a prediction accuracy of 80.6%, where it correctly identified 25 out of 31 connections, and detected novel connections between non-stationary lipidomics and transcriptomics profiles for eicosanoids and cytokines, respectively. The results indicate that AA may initiate the secretion of cytokines like TNFα, IL1α, IL18, and IL10. Conversely, cytokines such as IL6 and IL1β may have an early causal impact on AA. These findings suggest a potential causal link between AA and cytokines, paving the way for further exploration with more extensive experimental data in future investigations.</p><p dir="ltr">This thesis develops a theoretical framework that integrates the cybernetic modeling technique with novel information-theoretic approaches to study the inflammatory response in mouse macrophages. As described in previous paragraphs, the success of the cybernetic framework in capturing the dynamic behavior of multiple processes serves to validate the idea that regulation is driven toward achieving cellular goals. The cybernetic framework can be applied to better understand the mechanisms underlying the normal and diseased states and to predict the behavior of the system given a perturbation.</p>