Cyclodextrin mediation offers a unique mechanism with the potential for interesting control of reaction parameters. Cyclodextrin mediation of hydrophobic monomers may offer desirable kinetics over conventional free radical polymerizations, and it has been shown in this work that cyclodextrin mediation facilitates polymerization of hydrophobic monomers in aqueous solution and in ethylene glycol. It also may be a facile method for controlling relative reactivity of comonomer mixtures. In addition, complexation of cyclodextrin with guest molecules has been utilized in selective synthesis where the host cyclodextrin has been utilized to sterically hinder the attack of certain reactive sites contained within the host cavity. This aspect of inclusion complexation could also be utilized in free radical polymerizations of monomers with multiple reactive double bonds to preferentially reduce the reactivity of the hindered reactive sites. This thesis involves the use of methylated(1.8)-beta-cyclodextrin (MeCD) as a mediator for polymerizations in solvents that would not facilitate polymerization of the pure monomer in the absence of cyclodextrin. This study focuses on the carbohydrate mediation of a series of methacrylic monomers. t-Butyl methacrylate, n-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate were complexed with methylated(1.8)-beta-cyclodextrin and subsequently dissolved in either water or ethylene glycol. The complexes were studied by 1H and 13C NMR spectroscopy, thin layer chromatography, CPK modeling, and thermogravimetric analysis, and were found to have molar ratios of cyclodextrin to monomer as high as 1.0 to 0.72. These complexes were then free radically polymerized in either water or ethylene glycol and resulted in high molecular weight polymers that precipitated out of solution, allowing for facile polymer isolation through filtration. Isolated yields were found to be as high as 86 %. The majority of the cyclodextrin remained in solution after polymerization. It was also recovered and found to be recyclable. Heterogeneous polymerizations were also performed with 2-ethylhexyl methacrylate in which linear dextrin and methylated (1.8)-beta-cyclodextrin were used in emulsifier quantities. It was found that linear dextrin, at concentrations of 3.0 wt% produced a stable latex product with high molecular weight and an isolated yield of >90%. MeCD on the other hand failed to produce a stable emulsion at concentrations between 0.9-3.0 wt%, but remarkably MeCD at 3.0 wt% gave high molecular weight coagulated polymer with a yield of >90%. It is proposed that a heterogeneous mechanism inconsistent with the four major types discussed by Arshady is taking place. Unlike typical suspension or emulsion polymerizations, the cyclodextrin mediated polymerizations are completely homogeneous at the onset, making them more like a dispersion or precipitation polymerization. However, in dispersion and precipitation polymerizations the pure monomer is soluble in the reaction media. In the absence of cyclodextrin, the monomers utilized in this study possessed no appreciable solubility in the reaction media. Therefore, it is proposed that cyclodextrin acts as a phase transfer agent, effectively solublizing the hydrophobic monomer and allowing for the aqueous dispersion or precipitation type polymerization to occur, depending on the relative solubility of the components. Bulk polymerizations of t-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate and their subsequent use in the preparation of carbohydrate/poly(alkyl methacrylate) blends was also performed in this project. Bulk polymers were utilized as references for physical properties for the polymers produced through polymerization of the MeCD/monomer complexes in either aqueous solution or in ethylene glycol. 1H NMR analysis of the polymers from both the cyclodextrin mediation and bulk polymerizations indicated that the tacticity of the polymers produced in both cases were identical. The bulk polymers were also used in the preparation of carbohydrate/methacrylic blends with potential applications in the areas of selective barriers, biodegradable films. Inclusion of drug molecules or antioxidants into these cyclodextrin containing films also may have potential in drug delivery, or food packaging applications. In addition, the side chain liquid crystalline monomer, 6-(4-hexyloxy-biphenyl-4-yloxy)hexyl methacrylate was synthesized in high purity via a three-step procedure and confirmed by a combination of mass spectrometry, thin layer chromatography, and 1H and 13C NMR. This hydrophobic liquid crystalline monomer was subsequently complexed with 1.0-3.0 equivalents of methylated(1.8)-beta-cyclodextrin in an attempt to alter the water solubility of the monomer. Complexes of this side-chain liquid crystalline monomer have not been studied previously and it is proposed that complexation with cyclodextrin will lead not only to novel polymerizations routes for this monomer, but also to novel smectic phases for this thermotropic liquid crystalline polymer. / Master of Science

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23199号 / 工博第4843号 / 新制||工||1756(附属図書館) / 京都大学大学院工学研究科材料工学専攻 / (主査)教授 邑瀬 邦明, 教授 宇田 哲也, 教授 作花 哲夫 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

<p><strong>Apstrakt je obrađen tehnologijama za optičko prepoznavanje teksta (OCR).</strong></p><p>U radu je ispitana raspodela pektinaza u vodenim dvofaznim sistemima sastavljenim od polietilen glikola 4000 i jednog od dva dekstrana, sirovog i dekstrana 40000. Koncepcija rada je podrazumevala definisanje sistema u kojima su vr&scaron;eni eksperimenti raspodele, ispitivanje parametara raspodele pektinaza komercijalnog enzimskog preparata u model sistemima i, konačno, kultivaciju Polyporus squamosus u dvofaznim sistemima.<br />Ispitivanje uticaja masenih udela polietilen glikola na raspodelu pektinaza u model sistemu, pri konstantnom udelu sirovog dekstrana od 7.5% (w/w), pokazalo je negativan uticaj na parametre raspodele, te su najveće vrednosti koeficijenta raspodele (K) dobijene pri najmanjem ispitivanom udelu polietilen glikola, 5% (w/w), i iznosili su za endo-pektinazu (endo-p) 1.76, odnosno za egzo- pektinazu (egzo-p) 1.22. Istu zavisnost je pokazalo i ispitivanje u model sistemu sa dekstranom 40000, ali je vrednost K_endo bila mnogo niža (0.22). Povećanje udela sirovog dekstrana, pri stalnom udelu, 5% (w/w), polietilen glikola, negativno je uticalo na vrednosti parametara raspodele egzo-p, te su maksimalne vrednosti dobijene pri najmanjem udelu, 3% (w/w), dekstrana (K_egzo 0.79, prinos u gornjoj fazi (Y) 62.04%, stepen preči&scaron;ćenosti u gornjoj fazi (st.preč.) 5.5).<br />Sa povećanjem dužine veznih linija u model sistemu sa sirovim dekstranom opadale su vrednosti parametara raspodele pektinaza. Najbolji rezultati (K_endo 1.66, Y_endo 60.85%, K_egzo 0.95, Y_egzo 47.07%) dobijeni su najkraćoj veznoj liniji, dužine 7.44%. Povećanje odnosa zapremina u istom sistemu smanjilo je koeficijente raspodele endo- i egzo-p, kao i njihove stepene preči&scaron;ćenosti u gornjoj fazi, a u isto vreme povećalo prinose u toj fazi.<br />Dodatak amonijum sulfata i natrijum sulfata u model sistem polietilen glikol/sirovi dekstran u koncentraciji od po 15 mmoI/l povećao je K_endo 1-25, odnosno 1.2 puta, dok je K_egzo u prisustvu 15 mmol/l amonijum sulfata ili 5 mmol/l natrijum sulfata bio za 60% veći. Povećanje rN vrednosti KH₂PO₄-Na₂HPO₄ pufera povećalo je koeficijente raspodele oba tipa pektinaza, te je K_endo, na rN 7.5, bio 0.9, a K_egzo 0.76, na rN 7.0. Najbolja raspodela endo-p u gornju fazu model sistema ostvarena je pri 0.4 mol/l fosfatnog pufera (K 4.21, Y 85.78%, st.preč. 10). Vrednosti iznad 0.1 mol/l fosfatnog pufera nisu imale značajnijeg uticaja na raspodelu egzo-p.<br />Kultivacija Polyporus squamosus je bila moguća u dvofaznom sistemu polietilen glikol/sirovi dekstran, sa pektinom. kao inducerom, pri čemu je ostvareno odvajanje biomase od pektinaza njihovom raspodelom u suprotne faze. U sistemu sastava 5% (w/w) polietilen glikol/4% (w/w) sirovi dekstran, količina produkovane biomase je bila 4.5 puta veća od one u homogenom medijumu, ukupne egzo-p aktivnosti 1.82 puta veća, a endo-p aktivnosti jednaka onoj u homogenom medijumu. Drugog dana kultivacije ostvarene su najveće vrednosti parametara raspodele (K_endo 2.45, Y_endo 80.22%, st.preč._endo 7; K_egzo 0.6, Yegzo 49.83%, st.preč._egzo 5.19). Povećanje koncentracije amonijum sulfata za 15 mmol/l u podlozi za kultivaciju u dvofaznom sistemu sastava 5% (w/w) polietilen glikol/4% (w/w) sirovi dekstran, povećalo je koeficijent raspodele endo-p za 81%, vrednost ove aktivnost u grnjoj fazi za 37%, a da nije uticalo na raspodelu biomase P. squamosus.<br />Prisustvo različitih koncentracija fosfata nije uticalo na raspodelu biomase P. squamosus u dvofaznom sistemu. Pri 0.2 mol/l KH2PO4 postignuto je idealno odvajanje biomase od endo-p, uz K_egzo 112. Najveća vrednost ukupnih produkovanih aktivnosti oba tipa ostvarena je pri 0,1 mol/l fosfata, uz koeficijente raspodele za endo-p i egzo-p 3.9 i 0.95 i visoke stepene njihove preči&scaron;ćenosti u gornjoj fazi (5.89 i 14.36, redom).<br />Kultivacija P. squamosus je ostvarena i u dvofaznom sistemu koji je sadržao suve izlužene repine rezance, sa raspodelom biomase u donju fazu. Koeficijenti raspodele su iznosili 4.70, odnosno 2.78, za endo-p, odnosno egzo-p. Prinosi oba enzima u gornjoj fazi su bili 90.71% za endo-p i 85.24% za egzo-p, uz najveće stepene njihove preči&scaron;ćenosti, 4.26 i 7.98, redom.</p> / <p><br /><strong>Abstract was processed by technology for Optical character recognition (OCR).</strong></p><p>Partition of pectinases in aqueous two-phase systems composed of polyethylene glycol 4,000 and crude dextran or dextran 40,000 was studied in this work. As the first step, phase diagrams were constructed, than partition of commercial pectinases was studied in model systems and finally, cultivation of Polyporus squamosus in aqueous two-phase systems was conducted.<br />Increasing of the concentration of polyethylene glycol in model system at fixed 7.5% (w/w) crude dextran decreased partition parameters. Maximal values for partition coefficient (К) of endo-pectinase (endo-p), 1.76, and exo-pectinase (ехо-р), 1.22, were obtained at 5% (w/w) polyethylene glycol. The same was revealed in investigations in model system with dextran 40,000, but Kendo was lower (0.22). Increasing of concentration of crude dextran at fixed 5% (w/w) polyethylene glycol decreased partition parameters of ехо-р, so their maximal values (Кexo 0.79, top phase yield (Y) 62.04% and purification factor in top phase 5.5) were obtained at 3% (w/w) crude dextran.<br />Increasing of the tie-line length caused decreasing of partition parameters and maximal results were achieved at the shortest tie-line 7.44% (Kendo 1-66, Yendo 60.85%, Кехо 0.95, Yexo 47.07%) in model system with crude dextran. With increasing of the volume ratio, partition coefficients of endo-p and ехо-р were decreased, as well as their purification factor in top phase, while top phase yield for both enzymes had higher values.<br />The addition of 15 mmol ammonium sulphate/l and 15 mmol sodium sulphate/l in model system, composed of polyethylene glycol and crude dextran, increascd Kendo 1.25 and 1.2 times, respectively, while Кехо in the presence of 15 mmol ammonium sulphate/l or 5 mmol sodium sulphate/l was 60% higher. Increasing of рН of KH2PO4- Na2HPO4 buffer favoured partition of both endo-p and ехо- p in top phase, so Kendo was 0.9 at рН 7.5 and Кехо was 0.76 at рН 7.0. The favourable partition of endo-p in top phase was achieved in the presence of 0.4 mol phosphate buffer/l (К 4.21, Y 85.78% and purification factor in top phase 10). Concentrations of phosphate buffer above 0.1 mol/l didn&rsquo;t have significant influence on partition of ехо-р.<br />Cultivation of Роlуроrus squamosus in polyethylene glycol/crude dextran aqueous two-phase system was accomplished with pectin as inducer and biomass was separated from pectinases by their partition into opposite phases. In system composed of 5% (w/w) polyethylene glycol and 4% (w/w) crude dextran, amounts of produced biomass and ехо-р activity were 4.5 and 1.82 times higher, respectively, and endo-p activity equal to those obtained in homogeneous cultivation. At the second day of cultivation the highest values of partition parameters were obtained (Kendo 2.45, Yendo 80.22%, purification factor for endo-p 7; Кeхо 0.6, Yexo 49.83%, purification factor for ехо-р 5.19). Increasing of concentration of ammonium sulphate in two-phase medium for 15 mmol/l increased Kendo for 81% and endo-p activity in top phase for 37%, but didn&rsquo;t influence partition of biomass.<br />Presence of phosphate at various concentrations didn&rsquo;t affect partition of biomass in two-phase system. At 0.2 mol KH2PO4/I tlie onesided partition of endo-p was accomplished while Кeхо was 1.12. The highest amounts of produced activities of endo-p and ехо-р were obtained at 0.1 mol phosphate/l and partition coefficients were 3.9 and 0.95, respectively, followed by high values of purification factors in top phase (5.89 and 14.36, rcspectively).<br />Cultivation of P. squamosus was accomplished in two-phase system containing dry sugar beet extraction waste and fungal growth was restrected to bottom phase. Partition coefficients were 4.70 and 2.78 for endo-p and ехо-р, respectively. Тор phase yields amounted 90.71% for endo-p and 85.24% for ехо-р followed by the highest obtained purification factors in top phase (4.26 and 7.98, respectively).</p>

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness worldwide. The only modifiable risk factor for POAG is elevated intraocular pressure, resulting from increased aqueous humor production or decreased drainage. Resistance to drainage in the aqueous outflow pathway is believed to reside in the juxtacanalicular connective tissue (JCT) and to be modulated by the inner wall (IW) endothelium of Schlemm’s canal (SC); however, the mechanisms that increase resistance in POAG remain unclear. To cross the IW, aqueous humor passes through I-pores on giant vacuoles (GVs) or B-pores between adjacent endothelial cells. Additionally, outflow around the circumference of the eye is segmental, or non-uniform, and fluorescent tracers can be used to label areas of high-flow and non-flow. The morphological differences in the endothelial cells of SC and their GVs in high- vs. non-flow areas have not been fully elucidated. In this project, we investigated the role of GVs and pores in the IW endothelial cells of SC in regulating segmental outflow in human eyes. We used serial block-face scanning electron microscopy to generate thousands of serial images and visualize these structures in 3D at the ultrastructural level. First, we 3D-reconstructed 45 individual IW cells and their GVs and quantified the number of connections each cell makes with the underlying JCT matrix/cells. We found that cells in high-flow areas made significantly fewer connections to JCT matrix/cells compared to cells in non-flow areas. Secondly, we analyzed 3,302 GVs for I-pores and basal openings and found a significantly greater percentage of GVs with both basal openings and I-pores in high-flow area compared to non-flow area, suggesting this type of GVs form a channel through which aqueous humor passes from JCT to SC. We also found that GVs with I-pores were significantly larger than those without I-pores. Our results suggest that decreasing number of cellular connections and increasing number of GVs with pores may be potential strategies to increase the amount of high-flow area and aqueous outflow for glaucoma treatment. Together, these studies add to our understanding of the role of GVs and pores in regulating segmental flow around the eye.

Indiana University-Purdue University Indianapolis (IUPUI) / Glaucoma is a multi-factorial ocular disease associated with death of retinal ganglion cells and irreversible vision loss. Many risk factors contribute to glaucomatous damage, including elevated intraocular pressure (IOP), age, genetics, and other diseases such as diabetes and systemic hypertension. Interestingly, alterations in retinal hemodynamics have also been associated with glaucoma. A better understanding of the factors that contribute to these hemodynamic alterations could lead to improved and more appropriate clinical approaches to manage and hopefully treat glaucoma patients. In this thesis, we develop several mathematical models aimed at describing ocular hemodynamics and oxygenation in health and disease. Precisely we describe: (i) a time-dependent mathematical model for the retinal circulation that includes macrocirculation, microcirculation, phenomenological vascular regulation, and the mechanical effect of IOP on the retinal vasculature; (ii) a steady-state mathematical model for the retinal circulation that includes macrocirculation, microcirculation, mechanistic vascular regulation, the effect of IOP on the central retinal artery and central retinal vein, and the transport of oxygen in the retinal tissue using a Krogh cylinder type model; (iii) a steady-state mathematical model for the transport of oxygen in the retinal microcirculation and tissue based on a realistic retinal anatomy; and (iv) a steady-state mathematical model for the production and drainage of aqueous humor (AH). The main objective of this work is to study the relationship between IOP, systemic blood pressure, and the functionality of vascular autoregulation; the transport and exchange of oxygen in the retinal vasculature and tissue; and the production and drainage of AH, that contributes to the level of IOP. The models developed in this thesis predict that (i) the autoregulation plateau occurs for different values of IOP in hypertensive and normotensive patients. Thus, the level of blood pressure and functionality of autoregulation affect the changes in retinal hemodynamics caused by IOP and might explain the inconsistent outcomes of clinical studies; (ii) the metabolic and carbon dioxide mechanisms play a major role in the vascular regulation of the retina. Thus, the impairment of either of these mechanisms could cause ischemic damage to the retinal tissue; (iii) the multi-layer description of transport of oxygen in the retinal tissue accounts for the effect of the inner and outer retina, thereby improving the predictive ability of the model; (iv) a greater reduction in IOP is obtained if topical medications target AH production rather that AH drainage and if IOP-lowering medications are administrated to patients that exhibit a high initial level of IOP. Thus, the effectiveness of IOP-lowering medications depend on a patient’s value of IOP. In conclusion, the results of this thesis demonstrate that the insight provided by mathematical modeling alongside clinical studies can improve the understanding of diseases and potentially contribute to the clinical development of new treatments.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第18221号 / 薬科博第25号 / 新制||薬科||4(附属図書館) / 31079 / 京都大学大学院薬学研究科医薬創成情報科学専攻 / (主査)教授 掛谷 秀昭, 教授 高須 清誠, 准教授 大野 浩章 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(地球環境学) / 甲第18487号 / 地環博第121号 / 新制||地環||25(附属図書館) / 31365 / 京都大学大学院地球環境学舎環境マネジメント専攻 / (主査)教授 勝見 武, 准教授 田中 周平, 准教授 乾 徹 / 学位規則第4条第1項該当 / Doctor of Global Environmental Studies / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第19958号 / 理博第4225号 / 新制||理||1607(附属図書館) / 33054 / 京都大学大学院理学研究科化学専攻 / (主査)教授 杉山 弘, 教授 三木 邦夫, 教授 秋山 芳展 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21787号 / 工博第4604号 / 新制||工||1717(附属図書館) / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 安部 武志, 教授 作花 哲夫, 教授 阿部 竜 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Predicting the dissolution rates of immiscible contaminants in groundwater is crucial for developing environmental remediation strategies, but quantitative modeling efforts are inherently subject to multiple uncertainties. These include unknown residual amounts of non-aqueous phase liquids (NAPL) and source zone dimensions, inconsistent historical monitoring of contaminant mass discharge, and the mathematical simulation of field-scale mass transfer processes. Effective methods for simulating NAPL dissolution must therefore be able to assimilate a variety of data through physical and scalable mass transfer parameters to quantify and reduce site-specific uncertainties. This investigation coupled upscaled and numerical mass transfer modeling with uncertainty analyses to understand and develop data-assimilation and parameter-scaling methods for characterizing NAPL source zones and predicting depletion timeframes. Parameters of key interest regulating kinetic NAPL persistence and contaminant fluxes are residual mass and saturation, but neither can be measured directly at field sites. However, monitoring and characterization measurements can constrain source zone dimensions, where NAPL mass is distributed. This work evaluated the worth of source zone delineation and dissolution monitoring for estimating NAPL mass and mass transfer coefficients at multiple scales of spatial resolution. Mass transfer processes in controlled laboratory and field experiments were analyzed by simulating monitored dissolved-phase concentrations through the parameterization of explicit and lumped system properties in volume-averaged (VA) and numerical models of NAPL dissolution, respectively. Both methods were coupled with uncertainty analysis tools to investigate the relationship between data availability and model design for accurately constraining system parameters and predictions. The modeling approaches were also combined for reproducing experimental bulk effluent rates in discretized domains, explicitly parameterizing mass transfer coefficients at multiple grid scales. Research findings linked dissolved-phase monitoring signatures to model estimates of NAPL persistence, supported by source zone delineation data. The accurate characterization of source zone properties and kinetic dissolution rates, governing NAPL longevity, was achieved by adjusting model parameterization complexity to data availability. While multistage effluent rates accurately constrained explicit-process parameters in VA models, spatially-varying lumped-process parameters estimated from late dissolution stages also constrained unbiased predictions of NAPL depletion. Advantages of the numerical method included the simultaneous assimilation of bulk and high-resolution monitoring data for characterizing the distribution of residual NAPL mass and dissolution rates, whereas the VA method predicted source dissipation timeframes from delineation data alone. Additionally, comparative modeling analyses resulted in a methodology for scaling VA mass transfer coefficients to simulate NAPL dissolution and longevity at multiple grid resolutions. This research suggests feasibility in empirical constraining of lumped-process parameters by applying VA concepts to numerical mass transfer and transport models, enabling the assimilation of monitoring and source delineation data to reduce site-specific uncertainties. / Doctor of Philosophy / Predicting the dissolution rates of immiscible contaminants in groundwater is crucial for developing environmental restoration strategies, but quantitative modeling efforts are inherently subject to multiple uncertainties. These include unknown mass and dimensions of contaminant source zones, inconsistent groundwater monitoring, and the mathematical simulation of physical processes controlling dissolution rates at field scales. Effective simulation methods must therefore be able to leverage a variety of data through rate-limiting parameters suitable for quantifying and reducing uncertainties at contaminated sites. This investigation integrated mathematical modeling with uncertainty analyses to understand and develop data-driven approaches for characterizing contaminant source zones and predicting dissolution rates at multiple measurement scales. Parameters of key interest regulating the lifespan of source zones are the distribution and amount of residual contaminant mass, which cannot be measured directly at field sites. However, monitoring and site characterization measurements can constrain source zone dimensions, where contaminant mass is distributed. This work evaluated the worth of source zone delineation and groundwater monitoring for estimating contaminant mass and dissolution rates at multiple measurement scales. Rate-limiting processes in controlled laboratory and field experiments were analyzed by simulating monitored groundwater concentrations through the explicit and lumped representation of system properties in volume-averaged (VA) and numerical models of contaminant dissolution, respectively. Both methods were coupled with uncertainty analysis tools to investigate the relationship between data availability and model design for accurately constraining system parameters and predictions. The approaches were also combined for predicting average contaminant concentrations at multiple scales of spatial resolution. Research findings linked groundwater monitoring profiles to model estimates of contaminant persistence, supported by source zone delineation data. The accurate characterization of source zone properties and contaminant dissolution rates was achieved by adjusting model complexity to data availability. While monitoring profiles indicating multi-rate contaminant dissolution accurately constrained explicit-process parameters in VA models, spatially-varying lumped parameters estimated from late dissolution stages also constrained unbiased predictions of source mass depletion. Advantages of the numerical method included the simultaneous utilization of average and spatially-detailed monitoring data for characterizing the distribution of contaminant mass and dissolution rates, whereas the VA method predicted source longevity timeframes from delineation data alone. Additionally, comparative modeling analyses resulted in a methodology for scaling estimable VA parameters to predict contaminant dissolution rates at multiple scales of spatial resolution. This research suggests feasibility in empirical constraining of lumped parameters by applying VA concepts to numerical models, enabling a comprehensive data-driven methodology to quantify environmental risk and support groundwater cleanup designs.