Individual Mobility and Uncertain Geographic Context: Real-time Versus Neighborhood Approximated Exposure to Retail Tobacco Outlets Across the US.

There is growing interest in the way exposure to neighborhood risk and protective factors affects the health of residents. Although multiple approaches have been reported, empirical methods for contrasting the spatial uncertainty of exposure estimates are not well established. The objective of this paper was to contrast real-time versus neighborhood approximated exposure to the landscape of tobacco outlets across the contiguous US. A nationwide density surface of tobacco retail outlet locations was generated using kernel density estimation (KDE). This surface was linked to participants' (N p = 363) inferred residential location, as well as to their real-time geographic locations, recorded every 10 min over 180 days. Real-time exposure was estimated as the hourly product of radius of gyration and average tobacco outlet density (N hour = 304, 164 h). Ordinal logit modeling was used to assess the distribution of real-time exposure estimates as a function of each participant's residential exposure. Overall, 61.3% of real-time, hourly exposures were of relatively low intensity, and after controlling for temporal and seasonal variation, 72.8% of the variance among these low-level exposures was accounted for by residence in one of the two lowest residential exposure quintiles. Most moderate to high intensity exposures (38.7% of all real-time, hourly exposures) were no more likely to have been contributed by subjects from any single residential exposure cluster than another. Altogether, 55.2% of the variance in real-time exposures was not explained by participants' residential exposure cluster. Calculating hourly exposure estimates made it possible to directly contrast real-time observations with static residential exposure estimates. Results document the substantial degree that real-time exposures can be misclassified by residential approximations, especially in residential areas characterized by moderate to high retail density levels.

Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra.

Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records.

Isotopic and Geochemical Tracers for U(VI) Reduction and U Mobility at an in Situ Recovery U Mine.

In situ recovery (ISR) uranium (U) mining mobilizes U in its oxidized hexavalent form (U(VI)) by oxidative dissolution of U from the roll-front U deposits. Postmining natural attenuation of residual U(VI) at ISR mines is a potential remediation strategy. Detection and monitoring of naturally occurring reducing subsurface environments are important for successful implementation of this remediation scheme. We used the isotopic tracers (238)U/(235)U (δ(238)U), (234)U/(238)U activity ratio, and (34)S/(32)S (δ(34)S), and geochemical measurements of U ore and groundwater collected from 32 wells located within, upgradient, and downgradient of a roll-front U deposit to detect U(VI) reduction and U mobility at an ISR mining site at Rosita, TX, USA. The δ(238)U in Rosita groundwater varies from +0.61‰ to -2.49‰, with a trend toward lower δ(238)U in downgradient wells. The concurrent decrease in U(VI) concentration and δ(238)U with an ε of 0.48‰ ± 0.08‰ is indicative of naturally occurring reducing environments conducive to U(VI) reduction. Additionally, characteristic (234)U/(238)U activity ratio and δ(34)S values may also be used to trace the mobility of the ore zone groundwater after mining has ended. These results support the use of U isotope-based detection of natural attenuation of U(VI) at Rosita and other similar ISR mining sites.

Fibroblast Growth Factor 2 Mediates Isoproterenol-induced Cardiac Hypertrophy through Activation of the Extracellular Regulated Kinase.

Fibroblast growth factor 2 (basic FGF or FGF2) has been shown to affect growth and differentiation in some tissues and to be required for cardiac hypertrophy in vivo. FGF2 has been shown in vitro to signal through the mitogen-activated protein kinase (MAPK) to affect cell survival and growth. To ascertain the role of FGF2 in cardiac hypertrophy, wildtype, Fgf2 knockout, non-transgenic, and FGF2 transgenic mice were treated with isoproterenol or saline via subcutaneous mini-osmotic pump implants to induce a hypertrophic response to ß-adrenergic stimulation. Fgf2 knockout hearts are protected from isoproterenol-induced cardiac hypertrophy; whereas, FGF2 transgenic hearts show exacerbated cardiac hypertrophy as assessed by heart weight-to-body weight ratios and myocyte cross-sectional area. Echocardiography reveals significantly decreased fractional shortening in isoproterenol-treated FGF2 transgenic mice but not in Fgf2 knockout mice suggesting that FGF2 mediates the maladaptive cardiac dysfunction seen in cardiac hypertrophy induced by isoproterenol. Western blot analysis also reveals alterations in MAPK signaling in Fgf2 knockout and FGF2 transgenic hearts subjected to isoproterenol treatment, suggesting that this cascade mediates FGF2's pro-hypertrophic effect. Pharmacologic inhibition of extracellular signal-regulated kinase (ERK) signaling results in an attenuated hypertrophic response in isoproterenol-treated FGF2 transgenic mice, but this response is not seen with p38 mitogen-activated protein kinase (p38) pathway inhibition, suggesting that FGF2 activation of ERK but not p38 is necessary for FGF2's role in the mediation of cardiac hypertrophy.

A host-rotaxane derivatized with carboxylic acids efficiently delivers a highly cationic fluoresceinated peptide.

A cleft-[2]rotaxane (CR2+2-) was derivatized with carboxylic acids to enhance the intracellular delivery of a highly cationic or anionic pentapeptide. CR2+2- delivers the fluorescein (Fl) tagged peptide Fl-KKALR to a greater amount than Fl-QEAVD, and at a higher concentration, a greater amount than Fl-AVWAL. The level of delivery is largely temperature and ATP independent, suggesting that the Fl-peptide.CR2+2- complexes pass through the cellular membrane without requiring active cell-mediated processes. This study shows that selective delivery of peptides is possible by using a suitably derivatized host-rotaxane as the transporter.

Host-[2]rotaxanes as cellular transport agents.

Host-[2]rotaxanes, containing a diarginine-derivatized dibenzo-24-crown-8 (DB24C8) ether as the ring and a cyclophane pocket or an aromatic cleft as one blocking group, are cell transport agents. These hosts strongly associate with a variety of amino acids, dipeptides, and fluorophores in water (1 mM phosphate buffer, pH 7.0), DMSO, and a 75/25 (v/v) buffer to DMSO solution. All peptidic guests in all solvent systems have association constants (K(A)'s) in the range of 1 x 10(4) to 5 x 10(4) M(-)(1), whereas the K(A) range for the fluorophores is 1 x 10(4) to 9 x 10(5) M(-)(1). Association constants for the cyclophane itself, cyclophane 3, are smaller. These values are in the 1 x 10(3) to 5 x 10(3) M(-)(1) range, which shows that the rotaxane architecture is advantageous for guest binding. Cyclophane-[2]rotaxane 1 efficiently transports fluorescein and a fluorescein-protein kinase C (PKC) inhibitor into eukaryotic COS-7 cells, including the nucleus. Interestingly, cleft-[2]rotaxane 2 does not transport fluorescein as efficiently, even though the results from the fluorescence assays show that both [2]rotaxanes bind fluorescein with the same ability.

Host-[2]rotaxane: advantage of converging functional groups for guest recognition.

A host-[2]rotaxane was constructed by converting a diaminophenylcalix[4]arene into a [2]rotaxane using the DCC-rotaxane method (Zehnder, D.; Smithrud, D. B. Org. Lett. 2001, 16, 2485-2486). N-Ac-Arg groups were attached to the dibenzo-24-crown-8 ring of the rotaxane to provide a convergent functional group. To demonstrate the advantage provided by the rotaxane architecture for recognition of guests that contain a variety of functional groups, association constants (K(A)) for N-Ac-Trp, indole, N-Ac-Gly, fluorescein, 1-(dimethylamino)-5-naphthalenesulfonate, and pyrene bound to the [2]rotaxane were determined by performing (1)H NMR and fluorescence spectroscopic experiments. The host-[2]rotaxane had the highest affinity for fluorescein with a K(A) = 4.6 x 10(6) M(-)(1) in a 98/2 buffer (1 mM phosphate, pH 7)/DMSO solution. A comparison of K(A) values demonstrates that both the aromatic pocket and ring of the host-[2]rotaxane contribute binding free energy for complexation. Association constants were also derived for the same guests bound to the diaminophenylcalix[4]arene and to a diphenylcalix[4]arene that contained arginine residues displayed in a nonconvergent fashion. The host-[2]rotaxane provides higher affinity and specificity for most guests than the host with divergent N-Ac-Arg groups of the one that only has an aromatic pocket. For example, the K(A) for the complex of the host-[2]rotaxane and fluorescein in the DMSO/water mixture is more than 2 orders of magnitude greater than association constants derived for the other hosts.