Pore Regions Research Articles

Four new Amynthas and Metaphire earthworm species from nine provinces in southern China.

Four new species belonging to genera Amyntha and Metaphire were discovered from an extensive area in southern China, covering the provinces Sichuan, Yunnan, Guizhou, Guangdong, Guangxi, Fujian, Hunan, Jiangxi and Anhui. The species are named Amynthas dispersus Sun Qiu, sp. nov., Amynthas shanghangensis Sun Qiu, sp. nov., Amynthas dentiformis Sun Jiang, sp. nov. and Metaphire sanmingensis Sun Jiang, sp. nov. The first two new species have four pairs of intersegmental spermathecal pores in 5/6-8/9. A. dispersus has elliptical and glandular male pore porophores raised on a low pad-like area surrounded by two to three shallow skin folds, the genital papillae are variable in the spermathecal pore and male pore regions, and prostate glands are vestigial or rudimentary. Amynthas shanghangensis has male porophores surrounded by three papillae, each prostate gland accompanied by an accessory gland, and the distal ½-⅓ of the spermathecal diverticulum dilated into a rod-shaped seminal chamber. Amynthas dentiformis has two pairs of spermathecal pores in 7/8-8/9, male pores always surrounded by two papillae, and small sacs on the dorsal and ventral margins of the intestinal caecae; the prostate gland occasionally has stalked accessory glands. M. sanmingensis is in the Metaphire houlleti-group, and has secondary male pores opening to copulatory pouches, rod-shaped spermathecal seminal chamber, as well as variable genital papillae in spermathecal and male pores regions. The GenBank accession numbers of DNA barcode data are attached under the description of each species.

Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor

Store-operated Ca2+ entry signals are mediated by plasma membrane Orai channels activated through intermembrane coupling with Ca2+-sensing STIM proteins in the endoplasmic reticulum (ER). The nature of this elaborate Orai-gating mechanism has remained enigmatic. Based on the Drosophila Orai structure, mammalian Orai1 channels are hexamers comprising three dimeric subunit pairs. We utilized concatenated Orai1 dimers to probe the function of key domains within the channel pore and gating regions. The Orai1-E106Q selectivity-filter mutant, widely considered a dominant pore blocker, was surprisingly nondominant within concatenated heterodimers with Orai1-WT. The Orai1-E106Q/WT heterodimer formed STIM1-activated nonselective cation channels with significantly enlarged apparent pore diameter. Other Glu-106 substitutions entirely blocked the function of heterodimers with Orai1-WT. The hydrophobic pore-lining mutation V102C, which constitutively opens channels, was suppressed by Orai1-WT in the heterodimer. In contrast, the naturally occurring R91W pore-lining mutation associated with human immunodeficiency was completely dominant-negative over Orai-WT in heterodimers. Heterodimers containing the inhibitory K85E mutation extending outward from the pore helix gave an interesting partial effect on both channel activation and STIM1 binding, indicating an important allosteric link between the cytosolic Orai1 domains. The Orai1 C-terminal STIM1-binding domain mutation L273D powerfully blocked STIM1-induced channel activation. The Orai1-L273D/WT heterodimer had drastically impaired STIM1-induced channel gating but, unexpectedly, retained full STIM1 binding. This reveals the critical role of Leu-273 in transducing the STIM1-binding signal into the allosteric conformational change that initiates channel gating. Overall, our results provide important new insights into the role of key functional domains that mediate STIM1-induced gating of the Orai1 channel.

Propofol inhibits prokaryotic voltage-gated Na+ channels by promoting activation-coupled inactivation.

Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na+ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations (2-10 µM). In both Navs, propofol induced a hyperpolarizing shift of the pre-pulse inactivation curve without any significant effects on recovery from inactivation at strongly hyperpolarized voltages, demonstrating that propofol does not stabilize the inactivated state. Moreover, there was no evidence of fast or slow pore block by propofol in a non-inactivating NaChBac mutant (T220A). Propofol also induced hyperpolarizing shifts of the conductance-voltage relationships with negligible effects on the time constants of deactivation at hyperpolarized voltages, indicating that propofol does not stabilize the open state. Instead, propofol decreases the time constants of macroscopic activation and inactivation. Adopting a kinetic scheme of Nav gating that assumes preferential closed-state recovery from inactivation, a 1.7-fold acceleration of the rate constant of activation and a 1.4-fold acceleration of the rate constant of inactivation were sufficient to reproduce experimental observations with computer simulations. In addition, molecular dynamics simulations and molecular docking suggest that propofol binding involves interactions with gating machinery in the S4-S5 linker and external pore regions. Our findings show that propofol is primarily a positive gating modulator of prokaryotic Navs, which ultimately inhibits the channels by promoting activation-coupled inactivation.

Microstructural evolution and densification behavior of porous kaolin-based mullite ceramic added with MoO3

Microstructural evolution and densification behavior of porous kaolin-based mullite ceramic added with MoO3 were investigated. The results indicated that MoO3 addition not only lowered the secondary mullitization temperature to below 950 °C, but also facilitated effectively the anisotropic growth of mullite grains. Fine mullite whiskers grew and interlocked with one another in the pre-existing pore regions, in-situ forming a stiff 3D skeleton structure of mullite whiskers, which arrested further densification of the sample. On the other hand, due to the great capillary attraction of small pores, the liquid phase tended to spread over small grains, which favored the growth from small mullite grains into whiskers at the expense of the liquid phase. Consequently, competitive mechanisms of sintering and crystal growth of mullite functioned, which further limited the sample densification. As a result, the total linear shrinkage of the sample added with MoO3 after firing at 1400 °C was only − 2.75%, and its porosity was retained at as high as 67%.

An in Vitro Assay of hERG K + Channel Potency for a New EGFR Inhibitor FHND004.

FHND004 is a newly synthesized epidermal growth factor receptor (EGFR) inhibitor for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the impacts of FHND004 on human ether-à-go-go-related gene (hERG) K+ channels and the molecular mechanisms underlying of its action. Whole-cell patch clamp recording was performed on wild type (WT), mutant hERG channels heterologously expressed in human embryonic kidney (HEK) 293 cells or IKr endogenously expressed in HL-1 cells, respectively. FHND004 inhibited hERG K+ currents in a concentration-dependent manner with IC50 values of 8.46 ± 0.33 μM in HEK293 cells and 7.52 ± 1.27 μM in HL-1 cells, respectively. However, the inhibitory potency of FHND004 on hERG channels was significantly less than its precursor AZD9291. FHND004-induced inhibition was state-dependent with a preference within open state, but did not alter other kinetics including activation, inactivation, and recovery from inactivation or deactivation. In addition, FHND004 exhibited more potent inhibitory effects on WT/A422T and WT/H562P-hERG, two known long QT syndrome (LQTS) associated KCNH2 mutations, than WT alone. Mutations of the residues at pore regions (F656C, Y652A, S624A, and F557L) in hERG channels attenuated block effects of FHND004. Taken together, our results demonstrate the evidence that FHND004 is a less potent hERG blocker than its precursor AZD9291. There is, however, a need for caution in the potential use of FHND004 for treating NSCLC patients, especially in those with other concurrent triggering factors.

Pharmacological characterization of potent and selective NaV1.7 inhibitors engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V.

Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area of vigorous pursuit. In an effort to identify more potent leads compared to our previously reported GpTx-1 peptide series, electrophysiology screening of fractionated tarantula venom discovered the NaV1.7 inhibitory peptide JzTx-V from the Chinese earth tiger tarantula Chilobrachys jingzhao. The parent peptide displayed nominal selectivity over the skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging identified a key Ile28Glu mutation that improved NaV1.4 selectivity over 100-fold, and further optimization yielded the potent and selective peptide leads AM-8145 and AM-0422. NMR analyses revealed that the Ile28Glu substitution changed peptide conformation, pointing to a structural rationale for the selectivity gains. AM-8145 and AM-0422 as well as GpTx-1 and HwTx-IV competed for ProTx-II binding in HEK293 cells expressing human NaV1.7, suggesting that these NaV1.7 inhibitory peptides interact with a similar binding site. AM-8145 potently blocked native tetrodotoxin-sensitive (TTX-S) channels in mouse dorsal root ganglia (DRG) neurons, exhibited 30- to 120-fold selectivity over other human TTX-S channels and exhibited over 1,000-fold selectivity over other human tetrodotoxin-resistant (TTX-R) channels. Leveraging NaV1.7-NaV1.5 chimeras containing various voltage-sensor and pore regions, AM-8145 mapped to the second voltage-sensor domain of NaV1.7. AM-0422, but not the inactive peptide analog AM-8374, dose-dependently blocked capsaicin-induced DRG neuron action potential firing using a multi-electrode array readout and mechanically-induced C-fiber spiking in a saphenous skin-nerve preparation. Collectively, AM-8145 and AM-0422 represent potent, new engineered NaV1.7 inhibitory peptides derived from the JzTx-V scaffold with improved NaV selectivity and biological activity in blocking action potential firing in both DRG neurons and C-fibers.

SCN5A mutation type and topology are associated with the risk of ventricular arrhythmia by sodium channel blockers

BackgroundVentricular fibrillation in patients with Brugada syndrome (BrS) is often initiated by premature ventricular contractions (PVCs). Presence of SCN5A mutation increases the risk of PVCs upon exposure to sodium channel blockers (SCB) in patients with baseline type-1 ECG. In patients without baseline type-1 ECG, however, the effect of SCN5A mutation on the risk of SCB-induced arrhythmia is unknown. We aimed to establish whether presence/absence, type, and topology of SCN5A mutation correlates with PVC occurrence during ajmaline infusion. Methods and resultsWe investigated 416 patients without baseline type-1 ECG who underwent ajmaline testing and SCN5A mutation analysis. A SCN5A mutation was identified in 88 patients (S+). Ajmaline-induced PVCs occurred more often in patients with non-missense mutations (Snon-missense) or missense mutations in transmembrane or pore regions of SCN5A-encoded channel protein (Smissense-TP) than patients with missense mutations in intra-/extracellular channel regions (Smissense-IE) and patients without SCN5A mutation (S−) (29%, 24%, 9%, and 3%, respectively; P<0.001). The proportion of patients with ajmaline-induced BrS was similar in different mutation groups but lower in S− (71% Snon-missense, 63% Smissense-TP, 70% Smissense-IE, and 34% S−; P<0.001). Logistic regression indicated Snon-missense and Smissense-TP as predictors of ajmaline-induced PVCs. ConclusionsSCN5A mutation is associated with an increased risk of drug-induced ventricular arrhythmia in patients without baseline type-1 ECG. In particular, Snon-missense and Smissense-TP are at high risk.

Activation Mechanisms Underlying Influx-Operated Calcium Entry of TRPP Channels

TRPP channels are permeable to Ca2+, and are also regulated by Ca2+. For instance, PKD2L1 (also known as TRPP3) channel can respond to the rapid increase of extracellular calcium, resulting in an influx-operated Ca2+ entry (ICE) (Hu et al. 2015 Cell Reports). However, the molecular mechanism of ICE activation has not been elucidated. In this study, we show that both Ca2+ and the outer pore play dual roles: Ca2+ can act as both charge carrier and activation ligand for channels; meanwhile, the channel pore regions can act as both the selective filter and also the activation gate. The affinity of Ca2+ in the outer pore region is highly correlated with the activation of ICE. The negatively charged residues prefer Ca2+ over Na+ assuring channel activation. Thus, less charged residues or more extracellular Na+ downregulate ICE. Moreover, the actual ion-binding affinity (irrelevant of selectivity here) is highly regulated by other sites within the outer pore. Such active mechanism of Ca2+ and outer pore in activation may also underlie other ion channels.

A dual porosity model of high-pressure gas flow for geoenergy applications

This paper presents the development of a dual porosity numerical model of multiphase, multicomponent chemical–gas transport using a coupled thermal, hydraulic, chemical, and mechanical formulation. Appropriate relationships are used to describe the transport properties of nonideal, reactive gas mixtures at high pressure, enabling the study of geoenergy applications such as geological carbon sequestration. Theoretical descriptions of the key transport processes are based on a dual porosity approach considering the fracture network and porous matrix as distinct continua over the domain. Flow between the pore regions is handled using mass exchange terms and the model includes equilibrium and kinetically controlled chemical reactions. A numerical solution is obtained with a finite element and finite difference approach and verification of the model is pursued to build confidence in the accuracy of the implementation of the dual porosity governing equations. In the course of these tests, the time-splitting approach used to couple the transport, mass exchange, and chemical reaction modules is shown to have been successfully applied. It is claimed that the modelling platform developed provides an advanced tool for the study of high-pressure gas transport, storage, and displacement for geoenergy applications involving multiphase, multicomponent chemical–gas transport in dual porosity media, such as geological carbon sequestration.

Chasing a Protein’s Tail: Detection of Polypeptide Translocation through Nanopores

Chasing a Protein’s Tail: Detection of Polypeptide Translocation through Nanopores

Modeling Solute Mass Exchange between Pore Regions in Slurry‐Injected Soil Columns during Intermittent Irrigation

Core Ideas Water flow and solute transport models described solute leaching during slurry injection. Intermittent flow increased leaching of injected slurry compounds compared with steady flow. Mass exchange of slurry compounds during interruptions occurred from im‐ to mobile pore regions. Mass exchange between pore regions should be included in larger scale model predictions. Animal slurry application to agricultural land can be a threat to the quality of groundwater and nearby surface water bodies by percolation of solutes from slurry sources. We hypothesized that local‐scale processes, such as mass exchange between preferential flow paths and matrix pore regions, can play a substantial role in relation to slurry application and nutrient leaching. To improve understanding of these mass exchange mechanisms, soil column leaching data of nonreactive slurry components after injection of dairy slurry were analyzed under different initial and boundary conditions with single‐ and double‐porosity model approaches. The data set was from nine intact soil columns (20‐cm i.d., 20‐cm height) of the plow layer of arable loamy topsoil that were percolated under unsaturated steady‐flow conditions with a suction of 5 cm applied at the bottom. Both single‐ and double‐porosity water flow and mobile–immobile solute transport models could describe these experimental breakthrough curves. Rainfall interruptions mimicking more natural conditions and variably saturated intermittent flow led to higher leaching of injected slurry compounds than steady‐flow conditions. These observations could be explained by an increased mass exchange of dissolved injected slurry components from the immobile to the mobile pore water regions during interruptions. The results suggest that column tests under steady‐flow conditions could lead to false predictions of solute leaching after slurry injection in structured soils. Furthermore, local‐scale processes, such as mass exchange between pore regions, should be included in larger scale model predictions of nutrient losses from agricultural fields.

Ionic liquid structure, dynamics, and electrosorption in carbon electrodes with bimodal pores and heterogeneous surfaces

We investigate the aggregation, diffusion, and resulting electrochemical behavior of ionic liquids inside carbon electrodes with complex pore architectures and surface chemistries. Carbide-derived carbons (CDCs) with bimodal porosities and defunctionalized or oxidized electrode surfaces served as model electrode materials. Our goal was to obtain a fundamental understanding of room-temperature ionic liquid ion orientation, mobility, and electrosorption behavior. Neat 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide confined in CDCs was studied using an integrated experimental and modeling approach, consisting of quasielastic neutron scattering, small-angle neutron scattering, X-ray pair distribution function analysis, and electrochemical measurements, which were combined with molecular dynamics simulations. Our analysis shows that surface oxygen groups increase the diffusion of confined electrolytes. Consequently, the ions become more than twice as mobile in oxygen-rich pores. Although greater self-diffusion of ions translates into higher electrochemical mobilities in oxidized pores, bulk-like behavior of ions dominates in the larger mesopores and increases the overall capacitance in defunctionalized pores. Experimental results highlight strong confinement and surface effects of carbon electrodes on electrolyte behavior, and molecular dynamics simulations yield insight into diffusion and capacitance differences in specific pore regions. We demonstrate the significance of surface defects on electrosorption dynamics of complex electrolytes in hierarchical pore architectures of supercapacitor electrodes.

Position-Dependent Dynamics Explain Pore-Averaged Diffusion in Strongly Attractive Adsorptive Systems.

Using molecular simulations, we investigate the relationship between the pore-averaged and position-dependent self-diffusivity of a fluid adsorbed in a strongly attractive pore as a function of loading. Previous work (Krekelberg, W. P.; Siderius, D. W.; Shen, V. K.; Truskett, T. M.; Errington, J. R. Connection between thermodynamics and dynamics of simple fluids in highly attractive pores. Langmuir 2013, 29, 14527-14535, doi: 10.1021/la4037327) established that pore-averaged self-diffusivity in the multilayer adsorption regime, where the fluid exhibits a dense film at the pore surface and a lower density interior pore region, is nearly constant as a function of loading. Here we show that this puzzling behavior can be understood in terms of how loading affects the fraction of particles that reside in the film and interior pore regions as well as their distinct dynamics. Specifically, the insensitivity of pore-averaged diffusivity to loading arises from the approximate cancellation of two factors: an increase in the fraction of particles in the higher diffusivity interior pore region with loading and a corresponding decrease in the particle diffusivity in that region. We also find that the position-dependent self-diffusivities scale with the position-dependent density. We present a model for predicting the pore-average self-diffusivity based on the position-dependent self-diffusivity, which captures the unusual characteristics of pore-averaged self-diffusivity in strongly attractive pores over several orders of magnitude.

Challenges and opportunities in modelling of proton exchange membrane fuel cells (PEMFC)

Challenges and opportunities in modelling of proton exchange membrane fuel cells (PEMFC)

1D Atmosphere Models from Inversion of Fe i 630 nm Observations with an Application to Solar Irradiance Studies

Abstract Present-day semi-empirical models of solar irradiance (SI) variations reconstruct SI changes measured on timescales greater than a day by using spectra computed in one dimensional atmosphere models (1D models), which are representative of various solar surface features. Various recent studies have pointed out, however, that the spectra synthesized in 1D models do not reflect the radiative emission of the inhomogenous atmosphere revealed by high-resolution solar observations. We aimed to derive observation-based atmospheres from such observations and test their accuracy for SI estimates. We analyzed spectropolarimetric data of the Fe i 630 nm line pair in photospheric regions that are representative of the granular quiet-Sun pattern (QS) and of small- and large-scale magnetic features, both bright and dark with respect to the QS. The data were taken on 2011 August 6, with the CRisp Imaging Spectropolarimeter at the Swedish Solar Telescope, under excellent seeing conditions. We derived atmosphere models of the observed regions from data inversion with the SIR code. We studied the sensitivity of results to spatial resolution and temporal evolution, and discuss the obtained atmospheres with respect to several 1D models. The atmospheres derived from our study agree well with most of the 1D models we compare our results with, both qualitatively and quantitatively (within 10%), except for pore regions. Spectral synthesis computations of the atmosphere obtained from the QS observations return an SI between 400 and 2400 nm that agrees, on average, within 2.2% with standard reference measurements, and within −0.14% with the SI computed on the QS atmosphere employed by the most advanced semi-empirical model of SI variations.

Investigating the Wear Behavior of Fe-Based Amorphous Coatings under Nanoscratch Tests

The wear behavior of two coatings (Fe49.7Cr18Mn1.9Mo7.4W1.6B15.2C3.8Si2.4 and Fe40Cr23Mo14C15B6Y2) sprayed by high-velocity air fuel technology was investigated through nanoscratch tests under ramping loads. Compared with the substrate, the Fe-based amorphous coatings exhibit lower penetration depth, higher elastic recovery, and lower wear volume, indicating the excellent wear resistance of the coatings. This behavior is related to the high hardness and high hardness/elastic modulus ratio (H/E) of the Fe-based amorphous coatings. From the scanning electron microscopy images of the scratch grooves, it is found out that ploughing governs the wear behavior of the coatings and substrate. In addition, spalling wear easily occurs in the pore regions of the coatings.

Olfactory Ionotropic Receptors in Mosquito Aedes albopictus (Diptera: Culicidae).

Ionotropic glutamate receptors (iGluRs) are a conserved family of ligand-gated ion channels that primarily function to mediate neuronal communication at synapses. A variant subfamily of iGluRs, the ionotropic receptors (IRs), was recently identified in insects and proved with the function in odorant recognition. Ionotropic receptors participate in a distinct olfactory signaling pathway that is independent of olfactory receptors activity. In the present study, we identify 102 putative IR genes, dubbed as AalbIr genes, in mosquito Aedes albopictus (Skuse) by in silico comparative sequence analysis. Among AalbIr genes, 19 show expression in the female antenna by RT-PCR. These putative olfactory AalbIRs share four conservative hydrophobic domains of amino acids, similar to the transmembrane and ion channel pore regions found in conventional iGluRs. To determine the potential function of these olfactory AalbIRs in host-seeking, we compared their transcript expression levels in the antennae of blood-fed females with that of non-blood-fed females by quantitative real-time RT-PCR. Three AalbIr genes showed downregulation when the mosquito finished a bloodmeal. These results may help to improve our understanding of the IR-mediated olfactory signaling in mosquitoes.

Investigation of the luminescence, mechanical, and thermal properties of ZnO-entrapped poly(N-isopropyl acrylamide) gels

ZnO nanoparticles were synthesized in the pores that are formed inside the PNIPAm (poly(N-isopropyl acrylamide)) gels during polymerization. Different pore regions were obtained with changing the cross-linker concentrations of gels. We concluded from the SEM results that when the cross-linker concentration of the gels is increased, the average size of the pores becomes narrower. Thus, depending on the internal porosity of the gel, the size and distribution of ZnO nanoparticles were changed and accordingly it ranged in the fluorescence spectra. It is observed that fluorescence spectra of ZnO nanoparticles released from PNIPAm gel with low cross-linker concentration have only UV emission, while the nanoparticles released from PNIPAm gel with high cross-linker concentration have both the UV and the green emissions of ZnO. The size distributions of these nanoparticles were measured by Stabino-Nanoflex analyzer and it clearly indicates that the width of the size distribution decreases with increasing cross-linker concentration. To see the effect of ZnO nanoparticles on the properties of the gel, we investigated the luminescence, mechanical, and thermal properties of these ZnO/PNIPAm composites and plain gels of which the internal morphology was set by changing the cross-linker concentration. The nature of interactions between the nanoparticles and polymer strands affects both mechanical and thermal behaviors. Compared to plain gels, entrapping ZnO nanoparticles into the gels cause an increased compressive elastic modulus and strength. We proved that ZnO nanoparticles improve considerably the mechanical properties of PNIPAm gels.

Borehole image-based evaluation of coral reef porosity distribution characteristics

ABSTRACTIn this study, we used digital borehole image camera to obtain images of porosity distribution in coral reefs in South China Sea, and developed an effective evaluation system for such distributions. First, the original images are preprocessed, allowing the pore regions to be automatically detected. The depth and sectional functions are established to measure five parameters: pore count, pore radius, radius concentration rate, total pore area ratio, and fractal dimension count. These are used to calculate the characteristic values of porosity distributions, and their fuzzy relationships are used to build the evaluation model, determine the Hamming distances between distributions, and establish the relationships between the characteristics and coral rock classifications. Test results from applying the method on a deep borehole image segment show the results to be consistent with other methods, and the following conclusions can be reached: (1) the porosity evaluation model is a viable way to analyze porosity distribution characteristics; (2) the resulting classification method is viable; and (3) porosity distribution analysis on coral reefs has important implications.

Evaluation of accessible mineral surface areas for improved prediction of mineral reaction rates in porous media

The rates of mineral dissolution reactions in porous media are difficult to predict, in part because of a lack of understanding of mineral reactive surface area in natural porous media. Common estimates of mineral reactive surface area used in reactive transport models for porous media are typically ad hoc and often based on average grain size, increased to account for surface roughness or decreased by several orders of magnitude to account for reduced surface reactivity of field as opposed to laboratory samples. In this study, accessible mineral surface areas are determined for a sample from the reservoir formation at the Nagaoka pilot CO2 injection site (Japan) using a multi-scale image analysis based on synchrotron X-ray microCT, SEM QEMSCAN, XRD, SANS, and FIB-SEM. This analysis not only accounts for accessibility of mineral surfaces to macro-pores, but also accessibility through connected micro-pores in smectite, the most abundant clay mineral in this sample. While the imaging analysis reveals that most of the micro- and macro-pores are well connected, some pore regions are unconnected and thus inaccessible to fluid flow and diffusion. To evaluate whether mineral accessible surface area accurately reflects reactive surface area a flow-through core experiment is performed and modeled at the continuum scale. The core experiment is performed under conditions replicating the pilot site and the evolution of effluent solutes in the aqueous phase is tracked. Various reactive surface area models are evaluated for their ability to capture the observed effluent chemistry, beginning with parameter values determined as a best fit to a disaggregated sediment experiment (Beckingham et al., 2016) described previously. Simulations that assume that all mineral surfaces are accessible (as in the disaggregated sediment experiment) over-predict the observed mineral reaction rates, suggesting that a reduction of RSA by a factor of 10–20 is required to match the core flood experimental data. While the fit of the effluent chemistry (and inferred mineral dissolution rates) greatly improve when the pore-accessible mineral surface areas are used, it was also necessary to include highly reactive glass phases to match the experimental observations, in agreement with conclusions from the disaggregated sediment experiment. It is hypothesized here that the 10–20 reduction in reactive surface areas based on the limited pore accessibility of reactive phases in core flood experiment may be reasonable for poorly sorted and cemented sediments like those at the Nagaoka site, although this reflects pore rather than larger scale heterogeneity.