Effect of angle-of-attacks on deterministic lateral displacement (DLD) with symmetric airfoil pillars.

Deterministic lateral displacement (DLD) is a microfluidic technique for size fractionation of particles/cells in continuous flow with a great potential for biological and clinical applications. Growing interest of DLD devices in enabling high-throughput operation for practical applications, such as circulating tumor cell (CTC) separation, necessitates employing higher flow rates, leading to operation at moderate to high Reynolds number (Re) regimes. Recently, it has been shown that symmetric airfoil shaped pillars with neutral angle-of-attack (AoA) can be used for high-throughput design of DLD devices due to their mitigation of vortex effects and preservation of flow symmetry under high Re conditions. While high-Re operation with symmetric airfoil shaped pillars has been established, the effect of AoAs on the DLD performance has not been investigated. In this paper, we have characterized the airfoil DLD device with various AoAs. The transport behavior of microparticles has been observed and analyzed with various AoAs in realistic high-Re. Furthermore, we have modeled the flow fields and anisotropy in a representative airfoil pillar array, for both positive and negative AoA configurations. Unlike the conventional DLD device, lateral displacement has been suppressed with +5° and + 15° AoA configurations regardless of particle sizes. On the other hand, stronger lateral displacement has been seen with -5° and - 15° AoAs. This can be attributed to growing flow anisotropy as Re climbs, and significant expansion or compression of streamlines between airfoils with AoAs. The findings in this study can be utilized for the design and optimization of airfoil DLD microfluidic devices with various AoAs.

Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over-diagnosis and over-treatment. Further, current strategies for clinical intervention do not distinguish clinically aggressive prostate cancer from indolent disease. This mini-review takes advantage of a large number of functionally characterized microRNAs (miRNA), epigenetic regulators of prostate cancer, that define prostate cancer cell activity, tumor stage, and circulate as biomarkers to monitor disease progression. Nanoparticles provide an effective platform for targeted delivery of miRNA inhibitors or mimics specifically to prostate tumor cells to inhibit cancer progression. Several prostate-specific transmembrane proteins expressed at elevated levels in prostate tumors are under investigation for targeting therapeutic agents to prostate cancer cells. Given that prostate cancer progresses slowly, circulating miRNAs can be monitored to identify tumor progression in indolent disease, allowing identification of miRNAs for nanoparticle intervention before the crucial point of transition to aggressive disease. Here, we describe clinically significant and non-invasive intervention nanoparticle strategies being used in clinical trials for drug and nucleic acid delivery. The advantages of mesoporous silica-based nanoparticles and a number of candidate miRNAs for inhibition of prostate cancer are discussed.

Ethanol and Other Short-Chain Alcohols Inhibit NLRP3 Inflammasome Activation through Protein Tyrosine Phosphatase Stimulation.

Immunosuppression is a major complication of alcoholism that contributes to increased rates of opportunistic infections and sepsis in alcoholics. The NLRP3 inflammasome, a multiprotein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the proinflammatory cytokines IL-1ß and IL-18, can be inhibited by ethanol, and we sought to better understand the mechanism through which this occurs and whether chemically similar molecules exert comparable effects. We show that ethanol can specifically inhibit activation of the NLRP3 inflammasome, resulting in attenuated IL-1ß and caspase-1 cleavage and secretion, as well as diminished apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, without affecting potassium efflux, in a mouse macrophage cell line (J774), mouse bone marrow-derived dendritic cells, mouse neutrophils, and human PBMCs. The inhibitory effects on the Nlrp3 inflammasome were independent of γ-aminobutyric acid A receptor activation or N-methyl-d-asparate receptor inhibition but were associated with decreased oxidant production. Ethanol treatment markedly decreased cellular tyrosine phosphorylation, whereas administration of the tyrosine phosphatase inhibitor sodium orthovanadate prior to ethanol restored tyrosine phosphorylation and IL-1ß secretion subsequent to ATP stimulation. Furthermore, sodium orthovanadate-induced phosphorylation of ASC Y144, necessary and sufficient for Nlrp3 inflammasome activation, and secretion of phosphorylated ASC were inhibited by ethanol. Finally, multiple alcohol-containing organic compounds exerted inhibitory effects on the Nlrp3 inflammasome, whereas 2-methylbutane (isopentane), the analogous alkane of the potent inhibitor isoamyl alcohol (isopentanol), did not. Our results demonstrate that ethanol antagonizes the NLRP3 inflammasome at an apical event in its activation through the stimulation of protein tyrosine phosphatases, an effect shared by other short-chain alcohols.

Spatial Mapping of Protein Adsorption on Mesoporous Silica Nanoparticles by Stochastic Optical Reconstruction Microscopy.

Exposure to biological fluid envelops a nanoparticle in layers of proteins and biomolecules, which has a profound impact on the nanoparticle's biological fate. Although the identities and amounts of the proteins in this "corona" have been thoroughly examined, the spatial arrangement of the proteins is unclear, a problem that is compounded on porous nanoparticles due to penetration of proteins within the porous network. To address this problem, we have developed a procedure based on information derived from stochastic optical reconstruction microscopy. We employed a mathematical model to reveal the penetration depth of several proteins within porous nanoparticles. Understanding protein penetration depth provides an explanation for the composition of the protein corona, aiding in the development of safe and effective particle-based therapies.

Adsorption and release of siRNA from porous silica.

Porous silica particles are potential transfection agents for nucleic acid-based therapies because of their large specific surface areas and pore volumes and the ease with which they can be chemically modified to maximize the loading of cargo and to effect targeting in vivo. Here, we present a systematic study of the effects of pore size and pore modification on the adsorption and release of short, interfering RNA (siRNA) from a mesoporous silica particle developed in our laboratory. Using adsorption isotherms and release experiments, we found that the short polyamine diethylenetriamine was the best chemical modification for achieving both the adsorption and release of large amounts of siRNA. The degree of functionalization with diethylenetriamine caused drastic changes in the loading capacity and binding strength of siRNA to silica with relatively large pores (8 nm and larger), but the degree of functionalization had a weaker effect in narrow pores (4 nm). Multilayer adsorption could occur in materials with large pores (15 nm). Release experiments showed that intermediate pore sizes and intermediate degrees of functionalization resulted in the best compromise between maximizing loading (from strong adsorption) and maximizing release. Capillary electrophoresis and quantitative, real-time PCR demonstrated that siRNA was released intact and that these particles functioned as a transfection agent of mammalian cells in vitro.

Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts.

BACKGROUND: Malignant mesotheliomas (MMs) are chemoresistant tumors related to exposure to asbestos fibers. The long latency period of MM (30-40 yrs) and heterogeneity of tumor presentation make MM difficult to diagnose and treat at early stages. Currently approved second-line treatments following surgical resection of MMs include a combination of cisplatin or carboplatin (delivered systemically) and pemetrexed, a folate inhibitor, with or without subsequent radiation. The systemic toxicities of these treatments emphasize the need for more effective, localized treatment regimens. METHODS: Acid-prepared mesoporous silica (APMS) microparticles were loaded with doxorubicin (DOX) and modified externally with a mesothelin (MB) specific antibody before repeated intraperitoneal (IP) injections into a mouse xenograft model of human peritoneal MM. The health/weight of mice, tumor volume/weight, tumor necrosis and cell proliferation were evaluated in tumor-bearing mice receiving saline, DOX high (0.2 mg/kg), DOX low (0.05 mg/kg), APMS-MB, or APMS-MB-DOX (0.05 mg/kg) in saline. RESULTS: Targeted therapy (APMS-MB-DOX at 0.05 mg/kg) was more effective than DOX low (0.05 mg/kg) and less toxic than treatment with DOX high (0.2 mg/kg). It also resulted in the reduction of tumor volume without loss of animal health and weight, and significantly decreased tumor cell proliferation. High pressure liquid chromatography (HPLC) of tumor tissue confirmed that APMS-MB-DOX particles delivered DOX to target tissue. CONCLUSIONS: Data suggest that targeted therapy results in greater chemotherapeutic efficacy with fewer adverse side effects than administration of DOX alone. Targeted microparticles are an attractive option for localized drug delivery.

Response of Colorado River runoff to dust radiative forcing in snow.

The waters of the Colorado River serve 27 million people in seven states and two countries but are overallocated by more than 10% of the river's historical mean. Climate models project runoff losses of 7-20% from the basin in this century due to human-induced climate change. Recent work has shown however that by the late 1800s, decades prior to allocation of the river's runoff in the 1920s, a fivefold increase in dust loading from anthropogenically disturbed soils in the southwest United States was already decreasing snow albedo and shortening the duration of snow cover by several weeks. The degree to which this increase in radiative forcing by dust in snow has affected timing and magnitude of runoff from the Upper Colorado River Basin (UCRB) is unknown. Here we use the Variable Infiltration Capacity model with postdisturbance and predisturbance impacts of dust on albedo to estimate the impact on runoff from the UCRB across 1916-2003. We find that peak runoff at Lees Ferry, Arizona has occurred on average 3 wk earlier under heavier dust loading and that increases in evapotranspiration from earlier exposure of vegetation and soils decreases annual runoff by more than 1.0 billion cubic meters or ∼5% of the annual average. The potential to reduce dust loading through surface stabilization in the deserts and restore more persistent snow cover, slow runoff, and increase water resources in the UCRB may represent an important mitigation opportunity to reduce system management tensions and regional impacts of climate change.

Identifying the dominant transport mechanism in single nanoscale pores and 3D nanoporous media.

Gas transport mechanisms can be categorized into viscous flow and mass diffusion, both of which may coexist in a porous media with multiscale pore sizes. To determine the dominant transport mechanism and its contribution to gas transport capacity, the gas viscous flow and mass diffusion processes are analyzed in single nanoscale pores via a theoretical method, and are simulated in 3D nanoporous media via pore-scale lattice Boltzmann methods. The apparent permeability from the viscous flow and apparent diffusivity from the mass diffusion are estimated. A dimensionless parameter, i.e., the diffusion-flow ratio, is proposed to evaluate the dominant transport mechanism, which is a function of the apparent permeability, apparent diffusivity, bulk dynamic viscosity, and working pressure. The results show that the apparent permeability increases by approximately two orders of magnitude when the average Knudsen number (Kn avg) of the nanoporous media or Knudsen number (Kn) of single nanoscale pores increases from 0.1 to 10. Under the same conditions, the increment in the apparent diffusivity is only approximately one order of magnitude. When Kn < 0.01, the apparent permeability has a lower bound (i.e., absolute permeability). When Kn > 10, the apparent diffusivity has an upper bound (i.e., Knudsen diffusivity). The dominant transport mechanism in single nanoscale pores is the viscous flow for 0.01 < Kn < 100, where the maximum diffusion-flow ratio is less than one. In nanoporous media, the dominant transport relies heavily on Kn avg and the structural parameters. For nanoporous media with the pore throat diameter of 3 nm, Kn avg = 0.2 is the critical point, above which the mass diffusion is dominant; otherwise, the viscous flow is dominant. As Kn avg increases to 3.4, the mass diffusion is overwhelming, with the maximum diffusion-flow ratio reaching ∼4.

Light-activated controlled release of camptothecin by engineering porous materials: the ship in a bottle concept in drug delivery.

Many systems for controlled drug release have been developed using different types of nanoparticles modified with azobenzene moieties. In these systems, drug release is often triggered by UV irradiation (either direct or using a near-infrared photosensitizer). These drug delivery systems often face challenges to their use, such as their lack of stability in physiological environments and concerns about their toxicity and bioavailability, that have hindered their translation from pre-clinical studies to clinical trials. Here, we propose a conceptual change by shifting photoswitching activity from the vehicle (nanoparticle) to the load (drug). In this "ship in a bottle" concept, the molecule to be delivered is trapped within a porous nanoparticle and its release is accomplished through a photoisomerization process. Using molecular dynamics, we designed and synthesized a photoswitchable prodrug of the antitumor drug camptothecin that contains an azobenzene functionality, and we have prepared porous silica nanoparticles with pore diameters designed to limit its release when in the trans form. Molecular modelling was used to show that the cis isomer was smaller and better able to pass through the pores than the trans isomer, which was confirmed by stochastic optical reconstruction microscopy (STORM). Thus, prodrug-loaded nanoparticles were prepared by loading the cis prodrug and then using UV irradiation to convert cis to trans isomers, trapping them, within the pores. Release of the prodrug was then accomplished by using a different UV wavelength to convert trans isomers back to cis. In this way, prodrug encapsulation and release could be achieved "on demand" through controlled cis-trans photoisomerization, which allowed the prodrug to be delivered safely and its release to be triggered precisely at the region of interest. Finally, the intracellular release and cytotoxic activity of this novel drug delivery system has been validated in several human cell lines, confirming the ability of this system to accurately control the release of the camptothecin prodrug.

Silica microparticles as a solid support for gadolinium phosphonate magnetic resonance imaging contrast agents.

Particle-based magnetic resonance imaging (MRI) contrast agents have been the focus of recent studies, primarily due to the possibility of preparing multimodal particles capable of simultaneously targeting, imaging, and treating specific biological tissues in vivo. In addition, particle-based MRI contrast agents often have greater sensitivity than commercially available, soluble agents due to decreased molecular tumbling rates following surface immobilization, leading to increased relaxivities. Mesoporous silica particles are particularly attractive substrates due to their large internal surface areas. In this study, we immobilized a unique phosphonate-containing ligand onto mesoporous silica particles with a range of pore diameters, pore volumes, and surface areas, and Gd(III) ions were then chelated to the particles. Per-Gd(III) ionic relaxivities ranged from ∼2 to 10 mM(-1) s(-1) (37 °C, 60 MHz), compared to 3.0-3.5 mM(-1) s(-1) for commercial agents. The large surface areas allowed many Gd(III) ions to be chelated, leading to per-particle relaxivities of 3.3 × 10(7) mM(-1) s(-1), which is the largest value measured for a biologically suitable particle.

Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells.

BACKGROUND: Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 106µm2/cm2). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression. RESULTS: Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 × 106µm2/cm2) amounts, respectively (p < 0.05/cut off ≥ 2.0-fold change). Exposure to amorphous silica micro-particles at high amounts (150 × 106µm2/cm2) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p < 0.05) induced by crystalline silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (FOS, ATF3, IL6 and IL8) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 106µm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 106µm2/cm2) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. CONCLUSIONS: Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and/or metabolic activity is insufficient to predict their pathogenicity. Moreover, they show that acute responses of the lung epithelium, including up-regulation of genes linked to inflammation, oxidative stress, and proliferation, as well as secretion of inflammatory and proliferative mediators, can be indicative of pathologic potential using either immortalized lines (BEAS 2B) or primary cells (NHBE). Assessment of the degree and magnitude of these responses in vitro are suggested as predictive in determining the pathogenicity of potentially harmful particulates.

Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy.

New and effective treatment strategies are desperately needed for malignant mesothelioma (MM), an aggressive cancer with a poor prognosis. We have shown previously that acid-prepared mesoporous microspheres (APMS) are nontoxic after intrapleural or intraperitoneal (IP) administration to rodents. The purpose here was to evaluate the utility of APMS in delivering chemotherapeutic drugs to human MM cells in vitro and in two mouse xenograft models of MM. Uptake and release of doxorubicin (DOX) alone or loaded in APMS (APMS-DOX) were evaluated in MM cells. MM cell death and gene expression linked to DNA damage/repair were also measured in vitro. In two severe combined immunodeficient mouse xenograft models, mice received saline, APMS, DOX or APMS-DOX injected directly into subcutaneous (SC) MM tumors or injected IP after development of human MMs peritoneally. Other mice received DOX intravenously (IV) via tail vein injections. In comparison to DOX alone, APMS-DOX enhanced intracellular uptake of DOX, MM death and expression of GADD34 and TP73. In the SC MM model, 3× weekly SC injections of APMS-DOX or DOX alone significantly inhibited tumor volumes, and systemic DOX administration was lethal. In mice developing IP MMs, significant (p < 0.05) inhibition of mesenteric tumor numbers, weight and volume was achieved using IP administration of APMS-DOX at one-third the DOX concentration required after IP injections of DOX alone. These results suggest APMS are efficacious for the localized delivery of lower effective DOX concentrations in MM and represent a novel means of treating intracavitary tumors.

Isolation and Quantification of miRNA from the Biomolecular Corona on Mesoporous Silica Nanoparticles.

To understand the factors that control the formation of the biomolecular corona, a systematic study of the adsorption of several miRNAs shown to be important in prostate cancer on amine-functionalized mesoporous silica nanoparticles (MSN-NH2) has been performed. Process parameters including miRNA type, nanoparticle concentration, incubation temperature and incubation time were investigated, as well as the potential competition for adsorption between different miRNA molecules. The influence of proteins and particle PEGylation on miRNA adsorption were also explored. We found that low particle concentrations and physiological temperature both led to increased miRNA adsorption. Adsorption of miRNA was also higher when proteins were present in the same solution; reducing or preventing protein adsorption by PEGylating the MSNs hindered adsorption. Finally, the amount of miRNA adsorbed from human serum by MSN-NH2 was compared to a commercial miRNA purification kit (TaqMan®, Life Technologies, Carlsbad, CA, USA). MSN-NH2 adsorbed six times as much miRNA as the commercial kit, demonstrating higher sensitivity to subtle up- and downregulation of circulating miRNA in the blood of patients.

Telemedicine at the Joint Readiness Training Center: Expanding Forward Medical Capability.

INTRODUCTION: The US Army's transition from counterinsurgency operations to preparation for large-scale combat operations is likely to bring unique access to care challenges on the battlefield. Ruggedized computer systems exist that allow forward medical personnel to establish telehealth connections with rear-based specialists. We describe our use of one such device during simulated force on force operations at the Joint Readiness Training Center (JRTC). METHODS: Our infantry brigade combat team brought a telehealth device to JRTC 20-02. The device comprised a mobile laptop and peripheral medical devices. We used the Warfighter Information Network-Tactical Increment 2 Tactical Communications Node (TCN) to establish communication between the device and external entities. We sought to establish connectivity in the Fort Polk, LA, cantonment area as part of reception, staging, onward movement, and integration operations. RESULTS: We successfully executed video calls from the field utilizing the telehealth device at the JRTC rear aid station and the local military treatment facility on Fort Polk, LA. We also executed calls to our home station military treatment facility on Fort Carson, CO. Each of these calls lasted approximately five minutes with sustained high-quality video and audio feeds. CONCLUSIONS: Our experience provides proof of concept that telehealth may enable rear-based medical personnel to expand the medical capabilities of medics based forward in the battlespace. Telehealth devices may prove feasible for use with strictly tactical communications architecture in the kinetic setting of large scale combat operations.

Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes.

BACKGROUND: Metabolic syndrome is associated with decreased physical activity and increased incidence of diabetes. Bone Mineral density (BMD) is positively associated with physical activity. Lower BMD is a risk factor for bone fractures. Whether subjects with metabolic syndrome alone show early signs of lower BMD and osteoporosis similar to those present in diabetic is not known. MATERIAL/METHODS: This cross-sectional study in male veterans examined the BMD in 3458 non-diabetic men and 735 men with type 2 diabetes. In addition, the BMD changes in non-diabetic men without any metabolic syndrome were compared with non-diabetic men with metabolic syndrome as established by the criteria of the Adult Treatment Panel III. RESULTS: BMD of hip was significantly lower and incidence of osteoporosis higher in diabetic subjects compared with age and body mass index (BMI) matched non-diabetic subjects. BMD of AP spine was significantly higher in diabetic subjects compared with non-diabetics but similar when subjects were matched for BMI. Men with metabolic syndrome alone had higher osteoporosis and lower BMD of hip compared with those without metabolic syndrome. CONCLUSIONS: The BMD of hip is lower in diabetics compared with age and BMI-matched non-diabetic men, and its level is similar in age and BMI-matched diabetics and non-diabetic men with metabolic syndrome. This suggests that both diabetes and metabolic syndrome are associated independently with higher osteoporosis and lower BMD of hip and are risk factors for increased incidence of hip fractures in men.

Protein Corona over Mesoporous Silica Nanoparticles: Influence of the Pore Diameter on Competitive Adsorption and Application to Prostate Cancer Diagnostics.

Diagnostic tests based on proteomics analysis can have significant advantages over more traditional biochemical tests. However, low molecular weight (MW) protein biomarkers are difficult to identify by standard mass spectrometric analysis, as they are usually present at low concentrations and are masked by more abundant resident proteins. We have previously shown that mesoporous silica nanoparticles are able to capture a predominantly low MW protein fraction from the serum, as compared to the protein corona (PC) adsorbed onto dense silica nanoparticles. In this study, we begin by further investigating this effect using liquid chromatography-mass spectrometry (LC-MS)/MS and thermogravimetric analysis (TGA) to compare the MW of the proteins in the coronas of mesoporous silica nanoparticles with the same particle size but different pore diameters. Next, we examine the process by which two proteins, one small and one large, adsorb onto these mesoporous silica nanoparticles to establish a theory of why the corona becomes enriched in low MW proteins. Finally, we use this information to develop a novel system for the diagnosis of prostate cancer. An elastic net statistical model was applied to LC-MS/MS protein coronas from the serum of 22 cancer patients, identifying proteins specific to each patient group. These studies help to explain why low MW proteins predominate in the coronas of mesoporous silica nanoparticles, and they illustrate the ability of this information to supplement more traditional diagnostic tests.

Oxidation of a mustard gas analogue using an aldehyde/O2 system catalyzed by V-doped mesoporous silica.

Vanadium-doped mesoporous silica was shown to be an effective heterogeneous catalyst for the oxidation of a mustard gas analogue, 2-chloroethyl ethyl sulfide (CEES), in the presence of an aldehyde and molecular oxygen. The oxidation was shown to involve a radical mechanism, which was indicated by the appearance of an induction period when the reaction occurred in the presence of a free radical scavenger. The reaction was initially selective for the oxidation of CEES to the sulfoxide, CEESO, although oxidation of the sulfoxide to the sulfone occurred once all the CEES had been oxidized. Chemical analysis indicated that V species did not leach from the silica support when the reaction was performed in the fluorinated solvent HFE-7100.

Surface complexation modeling of Cu(II) adsorption on mixtures of hydrous ferric oxide and kaolinite.

BACKGROUND: The application of surface complexation models (SCMs) to natural sediments and soils is hindered by a lack of consistent models and data for large suites of metals and minerals of interest. Furthermore, the surface complexation approach has mostly been developed and tested for single solid systems. Few studies have extended the SCM approach to systems containing multiple solids. RESULTS: Cu adsorption was measured on pure hydrous ferric oxide (HFO), pure kaolinite (from two sources) and in systems containing mixtures of HFO and kaolinite over a wide range of pH, ionic strength, sorbate/sorbent ratios and, for the mixed solid systems, using a range of kaolinite/HFO ratios. Cu adsorption data measured for the HFO and kaolinite systems was used to derive diffuse layer surface complexation models (DLMs) describing Cu adsorption. Cu adsorption on HFO is reasonably well described using a 1-site or 2-site DLM. Adsorption of Cu on kaolinite could be described using a simple 1-site DLM with formation of a monodentate Cu complex on a variable charge surface site. However, for consistency with models derived for weaker sorbing cations, a 2-site DLM with a variable charge and a permanent charge site was also developed. CONCLUSION: Component additivity predictions of speciation in mixed mineral systems based on DLM parameters derived for the pure mineral systems were in good agreement with measured data. Discrepancies between the model predictions and measured data were similar to those observed for the calibrated pure mineral systems. The results suggest that quantifying specific interactions between HFO and kaolinite in speciation models may not be necessary. However, before the component additivity approach can be applied to natural sediments and soils, the effects of aging must be further studied and methods must be developed to estimate reactive surface areas of solid constituents in natural samples.

Individuals with Borderline Personality Disorder show larger preferred social distance in live dyadic interactions.

Personal space regulation is a key component of effective social engagement. Personal space varies among individuals and with some mental health conditions. Simulated personal space intrusions in Borderline Personality Disorder (BPD) reveal larger preferred interpersonal distance in that setting. These findings led us to conduct the first test of live interpersonal distance preferences in symptoms in BPD. With direct observation of subjects' personal space behavior in the stop-distance paradigm, we found a 2-fold larger preferred interpersonal distance in BPD than control (n = 30, n = 23). We discuss this result in context of known biology and etiology of BPD. Future work is needed to identify neural circuits underlying personal space regulation in BPD, individual differences in preferred interpersonal distance in relation to specific symptoms and relationship to recovery status.

Differential Valuation and Learning From Social and Nonsocial Cues in Borderline Personality Disorder.

BACKGROUND: Volatile interpersonal relationships are a core feature of borderline personality disorder (BPD) and lead to devastating disruption of patients' personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus nonsocial information and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models. METHODS: Subjects (n = 20 BPD, n = 23 control subjects) played an extended reward learning task with a partner (confederate) that requires learning about nonsocial and social cue reward probability (the social valuation task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects' weighting of social and nonsocial cues was tested in mixed-effect regression models. Subjects' learning rates under stable and volatile conditions were modeled (Rescorla-Wagner approach) and group × condition interactions tested. RESULTS: Compared to control subjects, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily but had blunted learning responses to (nonsocial and social) volatility. CONCLUSIONS: This is the first report of patient behavior in the social valuation task. The results suggest that BPD subjects expect higher volatility than control subjects. These findings lay the groundwork for a neurocomputational dissection of social and nonsocial belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.