@article{cosgriff-hernandez_aguado_akpa_fleming_moore_porras_boyle_chan_chesler_christman_et al._2022, title={A roadmap towards equitable hiring to diversify biomedical engineering faculty}, volume={6}, url={https://doi.org/10.35542/osf.io/8hcw5}, DOI={10.35542/osf.io/8hcw5}, abstractNote={Hiring practices in academia have critically limited the entry of individuals from historically excluded groups into our biomedical engineering faculty. Excluding diverse individuals has hindered our profession’s research impact and ability to equitably educate our students. With many departments committed to “do better,” we now need to embrace a new mindset and gain the skills necessary to rectify injustices in our faculty hiring processes. Here, we offer a faculty hiring roadmap that departments can leverage to eliminate many barriers of entry to members of historically excluded groups as faculty in biomedical engineering. We call on our colleagues to recognize the failings of our current hiring practices and adopt the guidelines provided here to diversify biomedical engineering departments so that we might collectively accelerate the impact, innovation, and power of our profession.}, publisher={Center for Open Science}, author={Cosgriff-Hernandez, Elizabeth and Aguado, Brian A. and Akpa, Belinda Sena and Fleming, Gabriella Coloyan and Moore, Erika and Porras, Ana Maria and Boyle, Patrick M. and Chan, Deva D. and Chesler, Naomi and Christman, Karen L. and et al.}, year={2022}, month={Jun} }
 @article{barbera_granados_vanoye_abramova_kulbak_ahn_george_akpa_levitan_2022, title={Cholesterol-induced suppression of Kir2 channels is mediated by decoupling at the inter-subunit interfaces}, volume={25}, ISSN={["2589-0042"]}, url={http://dx.doi.org/10.1016/j.isci.2022.104329}, DOI={10.1016/j.isci.2022.104329}, abstractNote={Cholesterol is a major regulator of multiple types of ion channels. Although there is increasing information about cholesterol binding sites, the molecular mechanisms through which cholesterol binding alters channel function are virtually unknown. In this study, we used a combination of Martini coarse-grained simulations, a network theory-based analysis, and electrophysiology to determine the effect of cholesterol on the dynamic structure of the Kir2.2 channel. We found that increasing membrane cholesterol reduced the likelihood of contact between specific regions of the cytoplasmic and transmembrane domains of the channel, most prominently at the subunit-subunit interfaces of the cytosolic domains. This decrease in contact was mediated by pairwise interactions of specific residues and correlated to the stoichiometry of cholesterol binding events. The predictions of the model were tested by site-directed mutagenesis of two identified residues—V265 and H222—and high throughput electrophysiology.}, number={5}, journal={ISCIENCE}, publisher={Elsevier BV}, author={Barbera, Nicolas and Granados, Sara T. and Vanoye, Carlos Guillermo and Abramova, Tatiana V. and Kulbak, Danielle and Ahn, Sang Joon and George, Alfred L., Jr. and Akpa, Belinda S. and Levitan, Irena}, year={2022}, month={May} }
 @article{mcdaniel_flores_akpa_2021, title={Predicting Inter-individual Variability During Lipid Resuscitation of Bupivacaine Cardiotoxicity in Rats: A Virtual Population Modeling Study}, volume={7}, ISSN={["1179-6901"]}, url={https://doi.org/10.1007/s40268-021-00353-4}, DOI={10.1007/s40268-021-00353-4}, abstractNote={Intravenous lipid emulsions (ILE) have been credited for successful resuscitation in drug intoxication cases where other cardiac life-support methods have failed. However, inter-individual variability can function as a confounder that challenges our ability to define the scope of efficacy for lipid interventions, particularly as relevant data are scarce. To address this challenge, we developed a quantitative systems pharmacology model to predict outcome variability and shed light on causal mechanisms in a virtual population of rats subjected to bupivacaine toxicity and ILE intervention.We combined a physiologically based pharmacokinetic-pharmacodynamic model with data from a small study in Sprague-Dawley rats to characterize individual-specific cardiac responses to lipid infusion. We used the resulting individual parameter estimates to posit a population distribution of responses to lipid infusion. On that basis, we constructed a large virtual population of rats (N = 10,000) undergoing lipid therapy following bupivacaine cardiotoxicity.Using unsupervised clustering to assign resuscitation endpoints, our simulations predicted that treatment with a 30% lipid emulsion increases bupivacaine median lethal dose (LD50) by 46% when compared with a simulated control fluid. Prior experimental findings indicated an LD50 increase of 48%. Causal analysis of the population data suggested that muscle accumulation rather than liver accumulation of bupivacaine drives survival outcomes.Our results represent a successful prediction of complex, dynamic physiological outcomes over a virtual population. Despite being informed by very limited data, our mechanistic model predicted a plausible range of treatment outcomes that accurately predicts changes in LD50 when extrapolated to putatively toxic doses of bupivacaine. Furthermore, causal analysis of the predicted survival outcomes indicated a critical synergy between scavenging and direct cardiotonic mechanisms of ILE action.}, journal={DRUGS IN R&D}, publisher={Springer Science and Business Media LLC}, author={McDaniel, Matthew and Flores, Kevin B. and Akpa, Belinda S.}, year={2021}, month={Jul} }
 @misc{hodgens_akpa_long_2021, title={Solving the puzzle of Fe homeostasis by integrating molecular, mathematical, and societal models}, volume={64}, ISSN={["1879-0356"]}, url={https://doi.org/10.1016/j.pbi.2021.102149}, DOI={10.1016/j.pbi.2021.102149}, abstractNote={To ensure optimal utilization and bioavailability, iron uptake, transport, subcellular localization, and assimilation are tightly regulated in plants. Herein, we examine recent advances in our understanding of cellular responses to Fe deficiency. We then use intracellular mechanisms of Fe homeostasis to discuss how formalizing cell biology knowledge via a mathematical model can advance discovery even when quantitative data is limited. Using simulation-based inference to identify plausible systems mechanisms that conform to known emergent phenotypes can yield novel, testable hypotheses to guide targeted experiments. However, this approach relies on the accurate encoding of domain-expert knowledge in exploratory mathematical models. We argue that this would be facilitated by fostering more "systems thinking" life scientists and that diversifying your research team may be a practical path to achieve that goal.}, journal={CURRENT OPINION IN PLANT BIOLOGY}, publisher={Elsevier BV}, author={Hodgens, Charles and Akpa, Belinda S. and Long, Terri A.}, year={2021}, month={Dec} }
 @inbook{utility of stable isotope ratios of tap water and human hair in determining region of origin in central and southern mexico_2020, url={http://dx.doi.org/10.1002/9781119482062.ch23}, DOI={10.1002/9781119482062.ch23}, abstractNote={This chapter explores the relationships between tap water, bottled water, and hair samples of known Mexican origin from Central and Southern Mexico. It quantifies the relationship between Mexican hair and tap water values and investigates whether the semi-mechanistic model modified by Bowen was an appropriate choice for Mexican populations, given the established challenges. The chapter outlines how the populations in different Mexican regions are impacted by water stress, and how these nuanced experiences impact drinking water choices and water isotope mapping. It also investigates differences in the sources of agricultural water and drinking water in Mexico, and the impact these differences have on modeling assumptions. Practically, the mathematical models proposed for provenance analysis based on hair and drinking water presume a near-linear relationship between hair isotopes and drinking water. Parameter estimation for model fitting was performed in Matlab using the approach of approximate Bayesian computation.}, booktitle={Forensic Science and Humanitarian Action}, year={2020}, month={Feb} }
 @article{barbera_ayee_akpa_levitan_2019, title={Molecular Dynamics Simulations of Kir2.2 and Cholesterol Reveal State- and Concentration-Dependent Binding Sites}, volume={116}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/J.BPJ.2018.11.266}, DOI={10.1016/J.BPJ.2018.11.266}, abstractNote={Cholesterol is a major component of cell membranes and is an important regulator of multiple types of ion channels. However, the dynamics of its interactions and the specific mechanisms through which it mediates ion channel function are not well understood. One family of ion channels, inwardly rectifying potassium (Kir) channels, was shown to be sensitive to cholesterol through direct interactions with "cholesterol-sensitive" regions on the channel protein. It is unclear though whether these regions correspond to a well-localized binding site or are representative of a broad and shallow thermodynamic landscape. To investigate the interactions between cholesterol and Kir channels, we developed Martini coarse-grained simulations of Kir2.2 embedded in a POPC model membrane bilayer with varying concentrations of cholesterol. This approach allowed us to simulate the unbiased diffusion of cholesterol from the bilayer environment to both the surface and recessed pockets of the channel. We found that, unlike small drug-like molecules, which tightly bind to a single site, cholesterol interacts with the channel on a range of different time scales, with multiple cholesterol molecules in contact with the channel simultaneously. Following this, we utilized principles from network theory to identify four discrete cholesterol binding sites on the channel, which exist depending on the conformational state of the channel. Furthermore, we found that a twofold decrease in the bilayer concentration of cholesterol, which was shown previously to increase Kir2 channel activity, leads to a decrease in occupancy in only a subset of identified binding sites. These results allow us to discriminate between functionally relevant and functionally non-relevant cholesterol interaction sites, and hypothesize a mechanism of cholesterol regulation.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Barbera, Nicolas and Ayee, Manuela A. and Akpa, Belinda S. and Levitan, Irena}, year={2019}, month={Feb}, pages={41a} }
 @article{barbera_ayee_akpa_levitan_2018, title={Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of Cholesterol Molecules}, volume={115}, ISSN={["1542-0086"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85052990007&partnerID=MN8TOARS}, DOI={10.1016/j.bpj.2018.07.041}, abstractNote={Cholesterol is a major regulator of multiple types of ion channels, but the specific mechanisms and the dynamics of its interactions with the channels are not well understood. Kir2 channels were shown to be sensitive to cholesterol through direct interactions with "cholesterol-sensitive" regions on the channel protein. In this work, we used Martini coarse-grained simulations to analyze the long (μs) timescale dynamics of cholesterol with Kir2.2 channels embedded into a model membrane containing POPC phospholipid with 30 mol% cholesterol. This approach allows us to simulate the dynamic, unbiased migration of cholesterol molecules from the lipid membrane environment to the protein surface of Kir2.2 and explore the favorability of cholesterol interactions at both surface sites and recessed pockets of the channel. We found that the cholesterol environment surrounding Kir channels forms a complex milieu of different short- and long-term interactions, with multiple cholesterol molecules concurrently interacting with the channel. Furthermore, utilizing principles from network theory, we identified four discrete cholesterol-binding sites within the previously identified cholesterol-sensitive region that exist depending on the conformational state of the channel-open or closed. We also discovered that a twofold decrease in the cholesterol level of the membrane, which we found earlier to increase Kir2 activity, results in a site-specific decrease of cholesterol occupancy at these sites in both the open and closed states: cholesterol molecules at the deepest of these discrete sites shows no change in occupancy at different cholesterol levels, whereas the remaining sites showed a marked decrease in occupancy.}, number={7}, journal={BIOPHYSICAL JOURNAL}, author={Barbera, Nicolas and Ayee, Manuela A. A. and Akpa, Belinda S. and Levitan, Irena}, year={2018}, month={Oct}, pages={1264–1280} }
 @article{juarez_ramey_flaherty_akpa_2019, title={Oxygen and hydrogen isotopes in human hair and tap water: Modeling relationships in a modern Mexican population}, volume={90}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85073499730&partnerID=MN8TOARS}, DOI={10.13110/humanbiology.90.3.04}, abstractNote={abstract This study investigated the relationship between 18O and 2H isotopes in samples of Mexican hair and drinking water. The purpose of this study was twofold: to quantify the relationship between isotopes in Mexican hair and tap water, in order to understand the impact of water stress and differing socioeconomic status on accurate predictions of drinking water; and to determine whether currently existing semimechanistic models can accurately represent the relationship between hair and tap water. This study used a subset of paired samples of human hair (n = 62) and tap water (n = 76). Isotope values in tap water ranged from –11.4‰ to –4.3‰ and –79.1‰ to –22.5‰, and in hair from +9.5‰ to +16.1‰ and –90.8‰ to –53.7‰, for δ18O and δ2H, respectively. The most depleted δ18O and δ2H hair values came from individuals in the state of Morelos. For modern Mexican populations, positive correlations between isotopes in hair and water were not significant, with correlation coefficients r = 0.61 (p = 0.05) and r = 0.60 (p = 0.06) for 18O and 2H, respectively. Error-in-variables regression yielded linear fits that were somewhat better for 2H relative to 18O: δ18Oh = 0.183 [±0.132] δ18Otw + 15.7 [±0.9]‰ (r2 = 0.23); δ2Hh = 0.181 [±0.076] δ2Htw – 64.0 [±3.0]‰ (r2 = 0.34). In short, data from this Mexican population did not exhibit the strong relationships between isotope values of 18O and 2H in tap water and hair that have been characteristic of other populations studied to date. Given the economic stratification of this region and the poor correlation between hair and water samples, the authors considered the possibility that l, the fraction of the diet derived from local sources, and fs, the fraction of nonexchangeable H in keratin that was fixed in vivo, are local rather than global parameters for this population. The authors estimated different values of l and fs for each location. Given the anticipated importance of the nonlocal dietary contribution, they treated the isotopic content of nonlocal food and the offset parameters for predicting isotopes in locally derived food as tuning parameters and compared the results with parameters based on the American supermarket diet. They found that, although O and H isotopes in water and hair maintained similar geographic distributions, O and H isotopes in tap water explained only a small part of the variation observed in hair samples. Compared to the standard American supermarket diet, the Mexican estimates for nonlocal diet and local diet offsets predicted regional distributions of l and fs that cleanly segregated urban areas from rural towns.}, number={3}, journal={Human Biology}, author={Juarez, C.A. and Ramey, R. and Flaherty, D.T. and Akpa, B.S.}, year={2019}, pages={197–211} }
 @article{barbera_ayee_akpa_levitan_2017, title={Differential Effects of Sterols on Ion Channels: Stereospecific Binding vs Stereospecific Response}, volume={80}, ISSN={["1063-5823"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85024131558&partnerID=MN8TOARS}, DOI={10.1016/bs.ctm.2017.06.001}, abstractNote={Numerous ion channels have been shown to be regulated by the level of membrane cholesterol, but the mechanisms responsible for these effects are still not well understood. The key question in the field is how to discriminate between the contributions of the two central mechanisms that might be responsible for the sensitivity of ion channels to cholesterol: specific sterol-protein interactions or regulation of channels by the bilayer physical properties. Comparative analysis of cholesterol and its isomers on the function of an ion channel is a powerful tool to achieve this goal. An increasing number of studies show that cholesterol regulates several types of ion channels in a stereospecific manner, suggesting an involvement of specific sterol-protein interactions. However in this chapter, we present evidence that the stereospecificity of cholesterol-ion channel interactions may be mediated, not by a lack of binding, as has been generally assumed, but by the specificity of the interaction, which results in a functional effect, in the case of native cholesterol, and a lack of functional effect, in the case of a cholesterol isomer. In other words, accumulating evidence suggests that the structural requirements of ion channel cholesterol-binding sites are lax, allowing chiral isomers of cholesterol to bind to the same site in a nonstereospecific way, but the ability of a sterol to confer a functional effect on the channel activity can still be stereospecific. This is an important distinction both conceptually and methodologically. Indeed, our analysis shows that the orientations of cholesterol and its chiral isomer ent-cholesterol within a hydrophobic binding pocket of Kir2.2 are significantly different, and we propose that this difference may underlie distinct functional outcomes.}, journal={STEROL REGULATION OF ION CHANNELS}, author={Barbera, Nicolas and Ayee, Manuela A. A. and Akpa, Belinda S. and Levitan, Irena}, year={2017}, pages={25–50} }
 @article{ayee_lemaster_shentu_singh_barbera_soni_tiruppathi_subbaiah_berdyshev_bronova_et al._2017, title={Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids}, volume={112}, ISSN={["1542-0086"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85010443448&partnerID=MN8TOARS}, DOI={10.1016/j.bpj.2016.12.002}, abstractNote={The influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics was investigated computationally and experimentally. The truncated tail phospholipids, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), are two major oxidation products of the unsaturated phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine. A combination of coarse-grained molecular dynamics simulations, Laurdan multiphoton imaging, and atomic force microscopy microindentation experiments was used to determine the impact of POVPC and PGPC on the structure of a multicomponent phospholipid bilayer and to assess the consequences of their incorporation on membrane packing and endothelial cell stiffness. Molecular simulations predicted differential bilayer perturbation effects of the two oxidized phospholipids based on the chemical identities of their truncated tails, including decreased bilayer packing, decreased bilayer bending modulus, and increased water penetration. Disruption of lipid order was consistent with Laurdan imaging results indicating that POVPC and PGPC decrease the lipid packing of both ordered and disordered membrane domains. Computational predictions of a larger membrane perturbation effect by PGPC correspond to greater stiffness of PGPC-treated endothelial cells observed by measuring cellular elastic moduli using atomic force microscopy. Our results suggest that disruptions in membrane structure by oxidized phospholipids play a role in the regulation of overall endothelial cell stiffness.}, number={2}, journal={BIOPHYSICAL JOURNAL}, author={Ayee, Manuela A. A. and LeMaster, Elizabeth and Shentu, Tzu Pin and Singh, Dev K. and Barbera, Nicolas and Soni, Dheeraj and Tiruppathi, Chinnaswamy and Subbaiah, Papasani V. and Berdyshev, Evgeny and Bronova, Irina and et al.}, year={2017}, month={Jan}, pages={325–338} }
 @article{liang_chen_akpa_neuberger_webb_magin_2017, title={Using spectral and cumulative spectral entropy to classify anomalous diffusion in Sephadex (TM) gels}, volume={73}, ISSN={["1873-7668"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85010202543&partnerID=MN8TOARS}, DOI={10.1016/j.camwa.2016.12.028}, abstractNote={Sephadex™ gel beads are commonly used to separate mixtures of similar molecules based on trapping and size exclusion from internal submicron diameter cavities. Water, as it freely moves through the porous gel and enclosed chambers of Sephadex™ beads, exhibits both normal (Gaussian) and anomalous (non-Gaussian) water diffusion. The apparent diffusion coefficient (ADC) of water in Sephadex™ gels can be measured using magnetic resonance imaging (MRI) by applying diffusion-weighted pulse sequences. This study investigates the relationship between the ADC of water and the complexity (i.e., size and number of cavities) of a series of Sephadex™ beads. We first classified the stochastic movement of water by using the solution to the space and time fractional diffusion equation to extract the ADC and the fractional time and space parameters ( α , β ), which are essentially the order of the respective fractional derivatives in Fick’s second law. From the perspective of the continuous time random walk (CTRW) model of anomalous diffusion, these parameters reflect waiting times (trapping) and jump increments (nano-flow) of the water in the gels. The observed MRI diffusion signal decay represents the Fourier transform of the diffusion propagator (i.e., the characteristic function of the stochastic process). In two series of Sephadex™ gel beads, we observed a strong inverse correlation between bead porosity (which is also responsible for molecular size exclusion) and the fractional order parameters; as the gels become more heterogeneous, the ADC decreases, both α and β are reduced and the diffusion exhibits anomalous (sub-diffusion) behavior. In addition, as a new measure for the structural complexity in Sephadex™ gel beads, we propose using the spectral and the cumulative spectral entropy that are derived from the observed characteristic function. We find that both measures of entropy increase with the porosity and tortuosity of the gel in a manner consistent with fractional order diffusional dynamics.}, number={5}, journal={COMPUTERS & MATHEMATICS WITH APPLICATIONS}, author={Liang, Yingjie and Chen, Wen and Akpa, Belinda S. and Neuberger, Thomas and Webb, Andrew G. and Magin, Richard L.}, year={2017}, month={Mar}, pages={765–774} }
 @article{ayee_lemaster_akpa_levitan_2016, title={Endothelial Membrane Modulation by OxLDL: Molecular-Scale Effects of Oxidation Products on Model Membranes}, volume={110}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/J.BPJ.2015.11.498}, DOI={10.1016/J.BPJ.2015.11.498}, abstractNote={Oxidatively modified low-density lipoprotein (OxLDL) has been implicated in a range of disorders, including certain cardiovascular, metabolic, and immunological diseases. The bioactive oxidation products of this lipoprotein include a vast array of oxidized lipids, sterols, and triglycerides. Some of these species may play a significant role in the pathophysiological effects observed at elevated OxLDL concentrations. However, the particular biological effects of specific OxLDL components, as well as the mechanisms by which they elicit these responses, are poorly understood. To elucidate some of the effects of OxLDL, we undertake a molecular-scale investigation of changes induced in endothelial membranes in the presence of various oxidation products. Specifically, in order to disaggregate the individual effects of particular oxidized species, we utilize coarse-grained molecular dynamics simulations. With this technique, we probe alterations to the biomechanical properties (structure and dynamics) of multi-component model membranes by compounds that have been previously shown, through experimental means, to induce endothelial stiffening. This study may begin to clarify some of the molecular mechanisms underlying endothelial cell dysfunction resulting from exposure to OxLDL.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Ayee, Manuela A. and LeMaster, Elizabeth and Akpa, Belinda S. and Levitan, Irena}, year={2016}, month={Feb}, pages={81a} }
 @article{barbera_ayee_akpa_levitan_2016, title={Molecular Dynamics Simulations of Kir2.2-Cholesterol Interactions}, volume={110}, ISSN={0006-3495}, url={http://dx.doi.org/10.1016/J.BPJ.2015.11.1038}, DOI={10.1016/J.BPJ.2015.11.1038}, abstractNote={Inwardly rectifying potassium (Kir) channels form a major family of potassium channels and have been shown to play a critical role in setting resting membrane potential, regulating potassium homeostasis, and modulating membrane excitability. Cholesterol, which forms a major component of mammalian cell membranes, has been shown in the past to suppress Kir family channel function in high concentrations and is linked to a number of pathological conditions. Recently, it has been proposed that cholesterol binds to specific non-annular sites between the transmembrane domains of the Kir protein, and that this bonding helps to stabilize a closed conformation for the channel. In order to better understand this interaction, we have taken a computational approach which utilizes coarse-grained molecular dynamics simulations - employing the MARTINI force field - to further investigate the spatial and temporal mechanics of cholesterol binding. In addition to the mechanics of binding, this approach has allowed us to more closely examine the physiological effects of cholesterol binding on Kir channel function in a more physiologically relevant membrane environment. Through this we have been able to examine a greater range of binding effects, such as binding time, binding instances, changes in channel conformation, and ion flux through the channel.}, number={3}, journal={Biophysical Journal}, publisher={Elsevier BV}, author={Barbera, Nicolas and Ayee, Manuela A. and Akpa, Belinda S. and Levitan, Irena}, year={2016}, month={Feb}, pages={186a} }
 @article{ayee_roth_akpa_2016, title={Structural perturbation of a dipalmitoylphosphatidylcholine (DPPC) bilayer by warfarin and its bolaamphiphilic analogue: A molecular dynamics study}, volume={468}, ISSN={["1095-7103"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84956856058&partnerID=MN8TOARS}, DOI={10.1016/j.jcis.2016.01.056}, abstractNote={Compounds with nominally similar biological activity may exhibit differential toxicity due to differences in their interactions with cell membranes. Many pharmaceutical compounds are amphiphilic and can be taken up by phospholipid bilayers, interacting strongly with the lipid–aqueous interface whether or not subsequent permeation through the bilayer is possible. Bolaamphiphilic compounds, which possess two hydrophilic ends and a hydrophobic linker, can likewise undergo spontaneous uptake by bilayers. While membrane-spanning bolaamphiphiles can stabilize membranes, small molecules with this characteristic have the potential to create membrane defects via disruption of bilayer structure and dynamics. When compared to the amphiphilic therapeutic anticoagulant, warfarin, the bolaamphiphilic analogue, brodifacoum, exhibits heightened toxicity that goes beyond superior inhibition of the pharmacological target enzyme. We explore, herein, the consequences of anticoagulant accumulation in a dipalmitoylphosphatidylcholine (DPPC) bilayer. Coarse-grained molecular dynamics simulations reveal that permeation of phospholipid bilayers by brodifacoum causes a disruption of membrane barrier function that is driven by the bolaamphiphilic nature and size of this molecule. We find that brodifacoum partitioning into bilayers causes membrane thinning and permeabilization and promotes lipid flip-flop – phenomena that are suspected to play a role in triggering cell death. These phenomena are either absent or less pronounced in the case of the less toxic, amphiphilic compound, warfarin.}, journal={JOURNAL OF COLLOID AND INTERFACE SCIENCE}, author={Ayee, Manuela Aseye Ayele and Roth, Charles William and Akpa, Belinda Sena}, year={2016}, month={Apr}, pages={227–237} }
 @article{feinstein_akpa_ayee_boullerne_braun_brodsky_gidalevitz_hauck_kalinin_kowal_et al._2016, title={The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures}, volume={1374}, ISSN={["0077-8923"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84983483095&partnerID=MN8TOARS}, DOI={10.1111/nyas.13085}, abstractNote={Superwarfarins were developed following the emergence of warfarin resistance in rodents. Compared to warfarin, superwarfarins have much longer half‐lives and stronger affinity to vitamin K epoxide reductase and therefore can cause death in warfarin‐resistant rodents. By the mid‐1970s, the superwarfarins brodifacoum and difenacoum were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raise the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1–2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K–dependent and –independent effects, which are not mitigated by vitamin K therapy. In this review, we summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches.}, number={1}, journal={COUNTERMEASURES AGAINST CHEMICAL THREATS}, author={Feinstein, Douglas L. and Akpa, Belinda S. and Ayee, Manuela A. and Boullerne, Anne I. and Braun, David and Brodsky, Sergey V. and Gidalevitz, David and Hauck, Zane and Kalinin, Sergey and Kowal, Kathy and et al.}, year={2016}, pages={111–122} }
 @article{fettiplace_akpa_rubinstein_weinberg_2015, title={Confusion About Infusion: Rational Volume Limits for Intravenous Lipid Emulsion During Treatment of Oral Overdoses.}, volume={66}, url={https://doi.org/10.1016/j.annemergmed.2015.01.020}, DOI={10.1016/j.annemergmed.2015.01.020}, abstractNote={After the initial report of treatment of bupropion and lamotrigine overdose by intravenous lipid emulsion, 1 Sirianni A.J. Osterhoudt K.C. Calello D.P. et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med. 2008; 51: 412-415 Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar additional case reports have asserted the usefulness of lipid emulsion for enteral poisonings. 2 Cave G. Harvey M. Intravenous lipid emulsion as antidote: beyond local anesthetic toxicity: a systematic review. Acad Emerg Med. 2009; 16: 815-824 Crossref PubMed Scopus (159) Google Scholar , 3 Weinberg G. Lipid emulsion infusion resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012; 117: 180-187 Crossref PubMed Scopus (169) Google Scholar In accordance with these and other reports, the American College of Medical Toxicology offered interim guidelines on lipid resuscitation therapy 4 American College of Medical ToxicologyACMT position statement: interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011; 7: 81-82 Crossref PubMed Scopus (72) Google Scholar ; they recommended a bolus of 1.5 mL/kg, followed by an infusion of 0.25 mL/kg/min of intravenous lipid emulsion if toxicity persists. This recommendation was based on guidelines for treatment of local anesthetic toxicity, 5 Harrop-Griffiths W, Harbey M, Meek T, et al. AAGBI safety guideline: management of severse local anaesthetic toxicity. Association of Anaesthetists of Great Britain and Ireland. 2010. Google Scholar , 6 Neal J.M. Bernards C.M. Butterworth J.F. et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010; 35: 152-161 Crossref PubMed Scopus (413) Google Scholar in which absorption is quick and toxicity short lived. In contrast to local anesthetic toxicity, prolonged absorption during enteral overdose can result in extended toxicity, with a need for continuing medical support, including a protracted infusion of lipid emulsion. Guidelines for lipid resuscitation therapy in local anesthetic toxicity set an upper limit of 10 to 12 mL/kg during the first half hour, but because of the aforementioned nature of oral overdoses, the American College of Medical Toxicology did not provide a limit on total lipid infusion volume or duration of infusion. In the absence of limits, an increasing number of cases have reported the use of large volumes of lipid to treat oral overdose. However, until definitive studies can be conducted, there is a need for rational volume limits to prevent undisciplined use of intravenous lipid emulsion. Is a 1% Plasma Lipid Concentration Helpful to Treat the Intoxicated Patient?Annals of Emergency MedicineVol. 67Issue 3PreviewWe read with interest the article by Fettiplace et al.1 The authors propose a lipid emulsion infusion regimen to induce a 1% plasma triglyceride concentration to treat a prolonged absorption after oral overdose resulting in a lengthened increased plasma concentration. Full-Text PDF}, number={2}, journal={Annals of emergency medicine}, author={Fettiplace, M.R. and Akpa, B.S. and Rubinstein, I. and Weinberg, G.}, year={2015}, month={Feb}, pages={185–188} }
 @article{fettiplace_lis_ripper_kowal_pichurko_vitello_rubinstein_schwartz_akpa_weinberg_2015, title={Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion}, volume={198}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84949117634&partnerID=MN8TOARS}, DOI={10.1016/j.jconrel.2014.11.018}, abstractNote={Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose.}, journal={Journal of Controlled Release}, author={Fettiplace, M.R. and Lis, K. and Ripper, R. and Kowal, K. and Pichurko, A. and Vitello, D. and Rubinstein, I. and Schwartz, D. and Akpa, B.S. and Weinberg, G.}, year={2015}, pages={62–70} }
 @article{fettiplace_akpa_ripper_zider_lang_rubinstein_weinberg_2014, title={Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect.}, volume={120}, url={http://europepmc.org/articles/PMC4077021}, DOI={10.1097/ALN.0000000000000142}, abstractNote={Abstract
               
                  Background:
                  Recent publications have questioned the validity of the “lipid sink” theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms such as hemodilution. To address these issues, the authors tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, the authors modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration, and inotropy to this response with the use of an in silico model.
               
               
                  Methods:
                  Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. After catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of the four treatments: 30% intravenous lipid emulsion, 20% intravenous lipid emulsion, intravenous saline, or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared with the predictions of a pharmacokinetic–pharmacodynamic model parameterized using previously published laboratory data.
               
               
                  Results:
                  Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no treatment. An increase in arterial blood pressure underlay the recovery in both lipid emulsion–treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery, and the model that combined volume, sequestration, and inotropy predicted in vivo results most accurately.
               
               
                  Conclusion:
                  Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, which is driven by a cardiotonic response that complements the previously reported sequestration effect.
               }, number={4}, journal={Anesthesiology}, author={Fettiplace, M.R. and Akpa, B.S. and Ripper, R. and Zider, B. and Lang, J. and Rubinstein, I. and Weinberg, G.}, year={2014}, month={Apr}, pages={915–925} }
 @inproceedings{akpa_2013, title={Positive inotropy - A likely mechanism for lipid reversal of local anesthetic toxicity}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911417408&partnerID=MN8TOARS}, booktitle={Food, Pharmaceutical and Bioengineering Division 2013 - Core Programming Area at the 2013 AIChE Annual Meeting: Global Challenges for Engineering a Sustainable Future}, author={Akpa, B.S.}, year={2013}, pages={535} }
 @inproceedings{ayee_akpa_2013, title={Sequestering of toxins for the reversal of drug toxicity: A coarse grained molecular dynamics study}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911478625&partnerID=MN8TOARS}, booktitle={Computational Molecular Science and Engineering Forum 2013 - Core Programming Area at the 2013 AIChE Annual Meeting: Global Challenges for Engineering a Sustainable Future}, author={Ayee, M.A.A. and Akpa, B.S.}, year={2013}, pages={248} }
 @article{kuo_akpa_2013, title={Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic toxicity: a physiologically based pharmacokinetic model study.}, volume={118}, url={https://doi.org/10.1097/ALN.0b013e31828ce74d}, DOI={10.1097/aln.0b013e31828ce74d}, abstractNote={Abstract
               
                  Background:
                  In vitro observations support the lipid sink theory of therapeutic action by confirming the capacity of lipid emulsions to successfully uptake bupivacaine from aqueous media. However, competing hypotheses and some in/ex vivo small animal studies suggest that a metabolic or positive inotropic effect underlies the dramatic effects of lipid therapy. Controlled clinical tests to establish causality and mechanism of action are an impossibility. In an effort to quantitatively probe the merits of a “sink” mechanism, a physiologically based pharmacokinetic model has been developed that considers the binding action of plasma lipid.
               
               
                  Methods:
                  The model includes no fitting parameters and accounts for concentration dependence of plasma protein and lipid:anesthetic binding as well as the metabolism of the lipid scavenger. Predicted pharmacokinetics were validated by comparison with data from healthy volunteers administered a nontoxic dose of bupivacaine. The model was augmented to simulate lipid therapy and extended to the case of accidental IV infusion of bupivacaine at levels known to cause systemic toxicity.
               
               
                  Results:
                  The model yielded quantitative agreement with available pharmacokinetic data. Simulated lipid infusion following an IV overdose was predicted to yield (1) an increase in total plasma concentration, (2) a decrease in unbound concentration, and (3) a decrease in tissue content of bupivacaine.
               
               
                  Conclusions:
                  Results suggest that the timescale on which tissue content is reduced varies from organ to organ, with the concentration in the heart falling by 11% within 3 min. This initial study suggests that, in isolation, the lipid sink is insufficient to guarantee a reversal of systemic toxicity.
               }, number={6}, journal={Anesthesiology}, author={Kuo, I. and Akpa, B.S.}, year={2013}, month={Jun}, pages={1350–1361} }
 @article{akpa_d’agostino_gladden_hindle_manyar_mcgregor_li_neurock_sinha_stitt_et al._2012, title={Solvent effects in the hydrogenation of 2-butanone}, volume={289}, ISSN={0021-9517}, url={http://dx.doi.org/10.1016/j.jcat.2012.01.011}, DOI={10.1016/j.jcat.2012.01.011}, abstractNote={In liquid-phase reaction systems, the role of the solvent is often limited to the simple requirement of dissolving and/or diluting substrates. However, the correct choice, either pure or mixed, can significantly influence both reaction rate and selectivity. For multi-phase heterogeneously catalysed reactions observed variations may be due to changes in mass transfer rates, reaction mechanism, reaction kinetics, adsorption properties and combinations thereof. The liquid-phase hydrogenation of 2-butanone to 2-butanol over a Ru/SiO2 catalyst, for example, shows such complex rate behaviour when varying water/isopropyl alcohol (IPA) solvent ratios. In this paper, we outline a strategy which combines measured rate data with physical property measurements and molecular simulation in order to gain a more fundamental understanding of mixed solvent effects for this heterogeneously catalysed reaction. By combining these techniques, the observed complex behaviour of rate against water fraction is shown to be a combination of both mass transfer and chemical effects.}, journal={Journal of Catalysis}, publisher={Elsevier BV}, author={Akpa, B.S. and D’Agostino, C. and Gladden, L.F. and Hindle, K. and Manyar, H. and McGregor, J. and Li, R. and Neurock, M. and Sinha, N. and Stitt, E.H. and et al.}, year={2012}, month={May}, pages={30–41} }
 @article{magin_akpa_neuberger_webb_2011, title={Fractional Order Analysis of Sephadex Gel Structures: NMR Measurements Reflecting Anomalous Diffusion.}, volume={16}, url={http://europepmc.org/articles/PMC3144506}, DOI={10.1016/j.cnsns.2011.04.002}, abstractNote={We report the appearance of anomalous water diffusion in hydrophilic Sephadex gels observed using pulse field gradient (PFG) nuclear magnetic resonance (NMR). The NMR diffusion data was collected using a Varian 14.1 Tesla imaging system with a home-built RF saddle coil. A fractional order analysis of the data was used to characterize heterogeneity in the gels for the dynamics of water diffusion in this restricted environment. Several recent studies of anomalous diffusion have used the stretched exponential function to model the decay of the NMR signal, i.e., exp[−(bD)α], where D is the apparent diffusion constant, b is determined the experimental conditions (gradient pulse separation, durations and strength), and α is a measure of structural complexity. In this work, we consider a different case where the spatial Laplacian in the Bloch–Torrey equation is generalized to a fractional order model of diffusivity via a complexity parameter, β, a space constant, μ, and a diffusion coefficient, D. This treatment reverts to the classical result for the integer order case. The fractional order decay model was fit to the diffusion-weighted signal attenuation for a range of b-values (0 < b < 4000 s mm−2). Throughout this range of b values, the parameters β, μ and D, were found to correlate with the porosity and tortuosity of the gel structure.}, number={12}, journal={Communications in nonlinear science & numerical simulation}, author={Magin, R.L. and Akpa, B.S. and Neuberger, T. and Webb, A.G.}, year={2011}, month={Dec}, pages={4581–4587} }
 @article{bern_akpa_kuo_weinberg_2011, title={Lipid resuscitation: a life-saving antidote for local anesthetic toxicity.}, volume={12}, url={https://doi.org/10.2174/138920111794295800}, DOI={10.2174/138920111794295800}, abstractNote={Local anesthetic toxicity is a rare, but potentially lethal, complication of regional anesthesia that cannot be prevented by any single measure. It is associated with CNS excitation and can lead to refractory cardiac dysfunction and collapse. The development of lipid emulsion for the treatment of anesthetic-induced toxicity resulted from a set of observations during a study on the potent, lipophilic drug bupivacaine and its associated clinical risk of intransigent cardiac toxicity in otherwise healthy individuals. Subsequent laboratory studies and clinical reports have shown that infusion of lipid can reliably reverse toxicity from potent local anesthetics as well as other drugs. The underlying mechanisms of lipid resuscitation may be a combination of a 'lipid sink' and metabolic effect. Lipid rescue has led to a reduction in fatalities associated with severe systemic toxicity, but continued research is necessary for a better mechanistic understanding. Increased physician awareness and education, as well as optimized treatment protocols, will significantly reduce the rate of morbidity and mortality from local anesthetic toxicity.}, number={2}, journal={Current pharmaceutical biotechnology}, author={Bern, S. and Akpa, B.S. and Kuo, I. and Weinberg, G.}, year={2011}, month={Feb}, pages={313–319} }
 @inproceedings{magin_akpa_gao_zhou_neuberger_webb_2009, title={Fractional order NMR reflects anomalous diffusion}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77949893097&partnerID=MN8TOARS}, DOI={10.1109/ETFA.2009.5347158}, abstractNote={Recently, we proposed a new diffusion model in nuclear magnetic resonance (NMR) by solving the Bloch-Torrey equation using fractional order calculus with respect to time and space (Magin, RL, et al, J Magn Reson 2008; 190:255–270). This model yields a new set of parameters to describe anomalous diffusion: diffusion coefficient D, fractional order derivative in space ß, and a spatial variable μ (in units of µm). In this study, we demonstrate that fractional calculus (FC) can be successfully applied to analyze diffusion images of sephadex gels and brain tissues from healthy humans in vivo. Although the biophysical basis of ß and μ remains to be understood, the perspectives of using these parameters to characterize the environment for molecular diffusion may lead to a new way to investigate tissue structural changes in disease.}, booktitle={ETFA 2009 - 2009 IEEE Conference on Emerging Technologies and Factory Automation}, author={Magin, R.L. and Akpa, B. and Gao, Q. and Zhou, X.J. and Neuberger, T. and Webb, A.}, year={2009} }
 @inproceedings{akpa_nitsche_wedgewood_minshall_2008, title={A computational and experimental investigation of mechanisms for caveolae-mediated endocytosis}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952289953&partnerID=MN8TOARS}, booktitle={AIChE Annual Meeting, Conference Proceedings}, author={Akpa, B.S. and Nitsche, L.C. and Wedgewood, L.E. and Minshall, R.D.}, year={2008} }
 @article{graf von der schulenburg_akpa_gladden_johns_2008, title={Non-invasive mass transfer measurements in complex biofilm-coated structures.}, volume={101}, url={https://doi.org/10.1002/bit.21913}, DOI={10.1002/bit.21913}, abstractNote={AbstractWe demonstrate a novel application of 13C pulsed field gradient (PFG) NMR to monitor mass transfer, due to both flow and diffusion, in a 3D complex porous support structure modified by biofilm growth. This enables timescales an order of magnitude larger than previously possible to be accessed with respect to displacement probability distribution (propagator) measurements. The evolution in the propagator shape with observation time to the Gaussian asymptote (constant dispersion coefficient) is consequently well resolved. We also simulated the measured displacement propagators with good agreement between experiment and prediction. The methodology has significant potential for the selective characterization of the transport of nutrients, metabolic products, pollutants and biocides in such complex biofilm‐containing structures. Biotechnol. Bioeng. 2008;101: 602–608. © 2008 Wiley Periodicals, Inc.}, number={3}, journal={Biotechnology and bioengineering}, author={Graf Von Der Schulenburg, D.A.G. and Akpa, B.S. and Gladden, L.F. and Johns, M.L.}, year={2008}, month={Oct}, pages={602–608} }
 @inproceedings{akpa_2008, title={Quantitative, multinuclear magnetic resonance microscopy methods for the study of multiphase systems}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952300806&partnerID=MN8TOARS}, booktitle={AIChE Annual Meeting, Conference Proceedings}, author={Akpa, B.S.}, year={2008} }
 @inproceedings{akpa_matthews_sederman_yunus_fisher_johns_gladden_2008, title={Study of miscible and immiscible flows in a microchannel using magnetic resonance imaging}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952285034&partnerID=MN8TOARS}, booktitle={AIChE Annual Meeting, Conference Proceedings}, author={Akpa, B.S. and Matthews, S.M. and Sederman, A.J. and Yunus, K. and Fisher, A.C. and Johns, M.L. and Gladden, L.F.}, year={2008} }
 @article{parkar_akpa_nitsche_wedgewood_place_sverdlov_chaga_minshall_2009, title={Vesicle formation and endocytosis: function, machinery, mechanisms, and modeling.}, volume={11}, url={http://europepmc.org/articles/PMC2850289}, DOI={10.1089/ars.2008.2397}, abstractNote={Vesicle formation provides a means of cellular entry for extracellular substances and for recycling of membrane constituents. Mechanisms governing the two primary endocytic pathways (i.e., caveolae- and clathrin-mediated endocytosis, as well as newly emerging vesicular pathways) have become the focus of intense investigation to improve our understanding of nutrient, hormone, and drug delivery, as well as opportunistic invasion of pathogens. In this review of endocytosis, we broadly discuss the structural and signaling proteins that compose the molecular machinery governing endocytic vesicle formation (budding, invagination, and fission from the membrane), with some regard for the specificity observed in certain cell types and species. Important biochemical functions of endocytosis and diseases caused by their disruption also are discussed, along with the structures of key components of endocytic pathways and their known mechanistic contributions. The mechanisms by which principal components of the endocytic machinery are recruited to the plasma membrane, where they interact to induce vesicle formation, are discussed, together with computational approaches used to simulate simplified versions of endocytosis with the hope of clarifying aspects of vesicle formation that may be difficult to determine experimentally. Finally, we pose several unanswered questions intended to stimulate further research interest in the cell biology and modeling of endocytosis.}, number={6}, journal={Antioxidants & redox signaling}, author={Parkar, N.S. and Akpa, B.S. and Nitsche, L.C. and Wedgewood, L.E. and Place, A.T. and Sverdlov, M.S. and Chaga, O. and Minshall, R.D.}, year={2009}, month={Jun}, pages={1301–1312} }
 @inbook{gladden_akpa_anadon_dunckley_lim_mantle_sederman_2008, title={Chapter 26. Magnetic Resonance Imaging: A New Window on the Catalyst Operating in the Reactor Environment}, ISBN={9780854041145}, url={http://dx.doi.org/10.1039/9781847558183-00457}, DOI={10.1039/9781847558183-00457}, abstractNote={Magnetic resonance imaging (MRI) is an emerging measurement technique for the study of chemical reactions in situ within reactor environments,1 and a subject closely related to, and derived from, the work and vision of John Meurig Thomas. The real opportunities in developing MRI for application to t...}, booktitle={Turning Points in Solid-State, Materials and Surface Science}, publisher={Royal Society of Chemistry}, author={Gladden, L.F. and Akpa, B. S. and Anadon, L. D. and Dunckley, C. P. and Lim, M. H. M. and Mantle, M. D. and Sederman, A. J.}, year={2008}, month={Feb}, pages={457–478} }
 @article{akpa_holland_sederman_johns_gladden_2007, title={Enhanced (13)C PFG NMR for the study of hydrodynamic dispersion in porous media.}, volume={186}, url={https://doi.org/10.1016/j.jmr.2007.02.001}, DOI={10.1016/j.jmr.2007.02.001}, abstractNote={PFG NMR methods are frequently used as a means of probing both coherent and incoherent molecular motions of fluids contained within heterogeneous porous media. The time scale over which molecular displacements can be probed in a conventional PFG NMR experiment is limited by the relaxation characteristics of 1H—the nucleus that is typically observed. In multiphase systems, due to its sensitivity to susceptibility gradients and interactions with surfaces,1H signal is frequently characterized by rapid T1 and T2 relaxation. In this work, a heteronuclear approach to PFG NMR is demonstrated which allows the study of molecular displacement over extended time scales (and, consequently, length scales) by exploiting the longer relaxation time of 13C. The method presented employs the DEPT technique of polarization transfer in order to enhance both the sensitivity and efficiency of 13C detection. This hybrid coherence transfer PFG technique has been used to acquire displacement propagators for flow through a bead pack with an observation time of up to 35 s.}, number={1}, journal={Journal of magnetic resonance (San Diego, Calif. : 1997)}, author={Akpa, B.S. and Holland, D.J. and Sederman, A.J. and Johns, M.L. and Gladden, L.F.}, year={2007}, month={Feb}, pages={160–165} }
 @article{akpa_matthews_sederman_yunus_fisher_johns_gladden_2007, title={Study of miscible and immiscible flows in a microchannel using magnetic resonance imaging.}, volume={79}, url={https://doi.org/10.1021/ac070364a}, DOI={10.1021/ac070364a}, abstractNote={Magnetic resonance imaging (MRI) is a noninvasive technique that can be used to visualize mixing processes in optically opaque systems in up to three dimensions. Here, MRI has been used for the first time to obtain both cross-sectional velocity and concentration maps of flow through an optically opaque Y-shaped microfluidic sensor. Images of 23 micromx23 microm resolution were obtained for a channel of rectangular cross section (250 micromx500 microm) fed by two square inlets (250 micromx250 microm). Both miscible and immiscible liquid systems have been studied. These include a system in which the coupling of flow and mass transfer has been observed, as the diffusion of the analyte perturbs local hydrodynamics. MRI has been shown to be a versatile tool for the study of mixing processes in a microfluidic system via the multidimensional spatial resolution of flow and mass transfer.}, number={16}, journal={Analytical chemistry}, author={Akpa, B.S. and Matthews, S.M. and Sederman, A.J. and Yunus, K. and Fisher, A.C. and Johns, M.L. and Gladden, L.F.}, year={2007}, month={Jul}, pages={6128–6134} }
 @article{lee_gundabala_akpa_johns_jeynes_routh_2006, title={Distribution of surfactants in latex films: a Rutherford Backscattering study.}, volume={22}, url={https://doi.org/10.1021/la0601760}, DOI={10.1021/la0601760}, abstractNote={Uneven distribution of surfactant in dried latex films can affect the final film properties such as its water-resistance, gloss, and adhesiveness. Therefore, it is important to understand the driving force for surfactant transport during drying. In this paper, the accumulation of surfactant on the surface of poly(styrene-co-butyl acrylate) latex is studied using Rutherford Backscattering (RBS) and compared with results from a model that is based on the diffusive transport of particles and surfactant. Experimentally, a 30-50 nm thick surface layer, rich in surfactant, is seen and the concentration in the bulk of the film, obtained from RBS, agrees, at least qualitatively, with the model predictions for two of the surfactants tested.}, number={12}, journal={Langmuir : the ACS journal of surfaces and colloids}, author={Lee, W.P. and Gundabala, V.R. and Akpa, B.S. and Johns, M.L. and Jeynes, C. and Routh, A.F.}, year={2006}, month={Jun}, pages={5314–5320} }
 @article{gladden_akpa_anadon_heras_holland_mantle_matthews_mueller_sains_sederman_et al._2006, title={Dynamic Mr Imaging of Single- and Two-Phase Flows}, volume={84}, ISSN={0263-8762}, url={http://dx.doi.org/10.1205/cherd06019}, DOI={10.1205/cherd06019}, abstractNote={Research in chemical engineering is inherently challenging because of the need to describe the unsteady-state behaviour of multi-phase, multi-component systems. Therefore there has been long-standing interest in developing tomographic techniques which can be applied to ‘look inside’ chemical engineering systems and characterise hydrodynamics and chemical composition. This paper summarizes the ‘state-of-the-art’ in ultra-fast magnetic resonance imaging applied to characterising hydrodynamics in single- and multi-phase flows. Typically ‘ultra-fast’ data acquisition implies acquisition of a 2-D data array of 128 × 128 pixels in less than 1 s. We report recent results showing the application of MR to characterize flows in such diverse systems as immiscible liquid flow in microchannels, gas–liquid pipe flow, granular dynamics in gas-fluidized beds and two-phase flow hydrodynamics in fixed-bed reactors.}, number={4}, journal={Chemical Engineering Research and Design}, publisher={Elsevier BV}, author={Gladden, L.F. and Akpa, B.S. and Anadon, L.D. and Heras, J.J. and Holland, D.J. and Mantle, M.D. and Matthews, S. and Mueller, C. and Sains, M.C. and Sederman, A.J. and et al.}, year={2006}, month={Apr}, pages={272–281} }
 @article{sullivan_akpa_matthews_fisher_gladden_johns_2007, title={Simulation of miscible diffusive mixing in microchannels}, volume={123}, ISSN={0925-4005}, url={http://dx.doi.org/10.1016/j.snb.2006.10.025}, DOI={10.1016/j.snb.2006.10.025}, abstractNote={The lattice Boltzmann (LB) method is used to simulate the flow field and subsequent analyte diffusion and convection of various analytes in a Y-shaped microchannel mixer, with a channel cross-section of 250 μm × 500 μm. This required a simulation code to be implemented that couples diffusive mass transfer with hydrodynamics, thus enabling a spatially varying viscosity that depends on a local analyte concentration. Where possible the simulation results were validated with 3D MRI experimental measurements of both the analyte concentration and the flow field in the microchannel; agreement is excellent. The simulation method is also able to quantify various expected physical observations, including the variation of diffusive dispersion due to the 3D velocity profile across the microchannel (butterfly effect), and the expected scaling laws for diffusive transport. The error resulting from employing a simplified 2D representation of the 3D microchannel for simulation purposes is also explored; typically this error is less than 3% of the maximum concentration.}, number={2}, journal={Sensors and Actuators B: Chemical}, publisher={Elsevier BV}, author={Sullivan, S.P. and Akpa, B.S. and Matthews, S.M. and Fisher, A.C. and Gladden, L.F. and Johns, M.L.}, year={2007}, month={May}, pages={1142–1152} }
 @article{akpa_mantle_sederman_gladden_2005, title={In situ 13C DEPT-MRI as a tool to spatially resolve chemical conversion and selectivity of a heterogeneous catalytic reaction occurring in a fixed-bed reactor.}, url={https://doi.org/10.1039/b501698c}, DOI={10.1039/b501698c}, abstractNote={The distortionless enhancement by polarisation transfer (DEPT) nuclear magnetic resonance (NMR) technique, combined with magnetic resonance imaging (MRI), has been used to provide the first in situ spatially-resolved and quantitative measurement of chemical conversion and selectivity within a fixed-bed reactor using natural abundance 13C NMR.}, number={21}, journal={Chemical communications (Cambridge, England)}, author={Akpa, B.S. and Mantle, M.D. and Sederman, A.J. and Gladden, L.F.}, year={2005}, month={Apr}, pages={2741–2743} }
 @inbook{gladden_akpa_mantle_sederman_2006, title={Reactors and Reactions: In Situ Reaction Imaging in Fixed-bed Reactors Using MRI}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84889459515&partnerID=MN8TOARS}, DOI={10.1002/3527607560.ch5e}, abstractNote={This chapter contains sections titled: In Situ Reaction Imaging in Fixed-bed Reactors Using MRI Introduction Spatial Mapping of Conversion: Esterification Case Study 13C DEPT Imaging of Conversion and Selectivity Future Directions}, booktitle={NMR Imaging in Chemical Engineering}, author={Gladden, L.F. and Akpa, B.S. and Mantle, M.D. and Sederman, A.J.}, year={2006}, pages={590–608} }