Researchers use sediment hysteresis in watershed sedimentation studies, however underlying processes controlling sediment hysteresis observations remain an open topic of investigation. We investigate the hypothesis that baseflow water and sediment can control sediment hysteresis in some cases by: (i) modelling water- -sediment mixing permutations that considers baseflow and runoff with their own sediment concentration distributions; (ii) analyzing sediment hysteresis for a karst basin with high baseflow contributions in Kentucky, USA by decoupling baseflow and runoff hysteresis via sensor data, a mixing model, and sediment transport modelling; and (iii) analyzing the alternative hypothesis of sediment origin controlling hysteresis for this system using modelling and tracing of sediment origin with stable isotopes. Results from mixing model permutations show that changes to the timing and magnitude of baseflow water and its sediment concentration can shift hysteresis looping from clockwise (HI > 0.1) to counterclockwise (HI <-0.1). Varying the baseflow contribution can reproduce most of the sediment hysteresis results reported in the literature, such as single loops, double loops, figure eights and complex loops. Results from the Kentucky basin where baseflow contributions are high show the dominance of a new taxonomy of sediment hysteresis loops called a 'J-loop'. 71 % of the loops observed were J-loops while the remaining 29 % were complex loops. The J-loop occurs when baseflow dominates over runoff for a hydrologic event and the baseflow to runoff volume ratio falls between 1.5 and 3. Analyses of the alternative hypothesis show that looping patterns do not depend on sediment origin for the events studied. Sediment origin varied by dominance of the distal sediment source (26 % of events), proximal source (55 %), and nearly equal mixture of the two sources (18 %). J-loops and complex loop occurrence was not consistent with any sediment origin dominance. We analyzed 43 sediment hysteresis studies reported in hydrology journals and found many studies show hysteresis that resembles J-loops. These occur during events with low antecedent moisture, low-intensity rain, and low amounts of runoff-all of which point towards baseflow dominance. The results herein suggest the importance of the J-loops in systems with high baseflow contributions as well as the overall influence of baseflow to impact loop interpretations. This result is relevant because recent findings show that the majority of hydrologic events in many regions are dominated by baseflow. In such systems, the baseflow contribution and it's control on sediment hysteresis looping challenges the common interpretation that hysteresis loops reflect proximal and distal sediment sources.

ABSTRACTWhile tracing the sources of fluvial sediment using carbon and nitrogen stable isotopic ratios (δ13C and δ15N) has progressed significantly over the last two decades, the conservativeness of these tracers remains questionable. Recent work indicates that δ13C and δ15N alterations in streambed deposition zones likely represent the largest source of uncertainty impacting usefulness of the isotopic ratios as tracers. Here we report a 14‐year dataset of δ13C and δ15N of fluvial sediment from a streambed‐dominated basin in Kentucky, USA, and employ empirical model decomposition (EMD) to identify dominant temporal trends that may impact conservativeness. Results from EMD show significant seasonality of δ13C and δ15N for sediment as well as underlying multi‐year variation. The seasonal and multi‐year variance account for 72% and 50% of the total data variation for δ13C and δ15N, respectively. The prominent seasonality for δ13C and δ15N show a mean intra‐annual change of 0.6‰ and 1.1‰, respectively, and the seasonal change is attributed to algal accrual and organic matter turnover in the streambed sediment deposits. Mixing model simulations show that the mean streambed isotopic ratios should be separated from other sediment sources by 3.0‰ and 3.6‰ for δ13C and δ15N, respectively, to achieve 90% accuracy in source apportionment when the isotopic ratios are used independently; and the mean streambed value of both isotopic ratios should be separated from other sediment sources by 3.0‰ when δ13C and δ15N are used in combination. Our results lead to the recommendation that isotope ratios of sources be separated by at least 3‰ when the streambed is expected to be a prominent sediment source, which far exceeds the prior recommendation of 1‰ mean separation of sources.

This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. In vitro imaging confirms the microneedle patch penetrates the pig's ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, in vitro drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, in vivo studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.

Freshwater benthic algae form complex mat matrices that can confer ecosystem benefits but also produce harmful cyanotoxins and nuisance taste-and-odor (T&O) compounds. Despite intensive study of the response of pelagic systems to anthropogenic change, the environmental factors controlling toxin presence in benthic mats remain uncertain. Here, we present a unique dataset from a rapidly urbanizing community (Kansas City, USA) that spans environmental, toxicological, taxonomic, and genomic indicators to identify the prevalence of three cyanotoxins (microcystin, anatoxin-a, and saxitoxin) and two T&O compounds (geosmin and 2-methylisoborneol). Thereafter, we construct a random forest model informed by game theory to assess underlying drivers. Microcystin (11.9 ± 11.6 µg/m2), a liver toxin linked to animal fatalities, and geosmin (0.67 ± 0.67 µg/m2), a costly-to-treat malodorous compound, were the most abundant compounds and were present in 100 % of samples, irrespective of land use or environmental conditions. Anatoxin-a (8.1 ± 11.6 µg/m2) and saxitoxin (0.18 ± 0.39 µg/m2), while not always detected, showed a systematic tradeoff in their relative importance with season, an observation not previously reported in the literature. Our model indicates that microcystin concentrations were greatest where microcystin-producing genes were present, whereas geosmin concentrations were high in the absence of geosmin-producing genes. Together, these results suggest that benthic mats produce microcystin in situ but that geosmin production may occur ex situ with its presence in mats attributable to adsorption by organic matter. Our study broadens the awareness of benthic cyanobacteria as a source of harmful and nuisance metabolites and highlights the importance of benthic monitoring for sustaining water quality standards in rivers.

The Ohio River Basin (ORB) is responsible for 35% of total nitrate loading to the Gulf of Mexico yet controls on nitrate timing require investigation. We used a set of submersible ultraviolet nitrate analyzers located at 13 stations across the ORB to examine nitrate loading and seasonality. Observed nitrate concentrations ranged from 0.3 to 2.8 mg L−1 N in the Ohio River's mainstem. The Ohio River experiences a greater than fivefold increase in annual nitrate load from the upper basin to the river's junction with the Mississippi River (74–415 Gg year−1). The nitrate load increase corresponds with the greater drainage area, a 50% increase in average annual nitrate concentration, and a shift in land cover across the drainage area from 5% cropland in the upper basin to 19% cropland at the Ohio River's junction with the Mississippi River. Time‐series decomposition of nitrate concentration and nitrate load showed peaks centered in January and June for 85% of subbasin‐year combinations and nitrate lows in summer and fall. Seasonal patterns of the terrestrial system, including winter dormancy, spring planting, and summer and fall growing‐harvest seasons, are suggested to control nitrate timing in the Ohio River as opposed to controls by river discharge and internal cycling. The dormant season from December to March carries 51% of the ORB's nitrate load, and nitrate delivery is high across all subbasins analyzed, regardless of land cover. This season is characterized by soil nitrate leaching likely from mineralization of soil organic matter and release of legacy nitrogen. Nitrate experiences fast transit to the river owing to the ORB's mature karst geology in the south and tile drainage in the northwest. The planting season from April to June carries 26% of the ORB's nitrate and is a period of fertilizer delivery from upland corn and soybean agriculture to streams. The harvest season from July to November carries 22% of the ORB's nitrate and is a time of nitrate retention on the landscape. We discuss nutrient management in the ORB including fertilizer efficiency, cover crops, and nitrate retention using constructed measures.

Knowledge is lacking for sediment organic matter degradation and its influence on water quality for low gradient agriculturally impacted streams despite their importance for freshwater biogeochemical cycles and ecological restoration. We hypothesized degradation rates vary across sediment type and are a function of the connectivity regimes for low gradient systems. We carried out aerobic incubation experiments to assess oxidation and mineralization-nitrification rates and changes in stable isotopic ratios for sediment and dissolved organic matter and nitrate. Sediment originated from erosion across the watershed's surface shows higher carbon oxidation rates (k = 3.9 x 10-3 d-1) and lower nitrogen mineralization-nitrification rates (k = 7.9 x 10-4 d-1) compared to sediment originated from the creek's streambed that integrates algae and other autotrophic matter (k = 1.6 x 10-3 d-1 and k = 3.4 x 10-3 d-1). Differences are attributed to sediment transport of humified and plant matter during storms of high watershed connectivity and sediment transport of autochthonous sediment for low con-nectivity. Results support our hypothesis and suggest that the sediment connectivity regime of the watershed exhibits control on biogeochemical cycling of the stream network. Cumulatively, sediment degradation rates were one to two orders magnitude higher than previously assumed. Sediment rates reflect aerobic waters and place the organic matter as active and comparable to reported turnover of algae and fine sized leaf litter. Stable isotopic ratios of sediment change marginally for the two sediment types for carbon (epsilon = 0.4 %o and 1.3 %o) and nitrogen (epsilon = 3.5 %o and 1.5 %o). Dissolved organic nitrogen of stream water degraded similarly across all ex-periments (k = 1.8 x 10-2 d-1), and turnover rates were an order of magnitude higher than recent rates reported for lake water. Nitrate concentration in the solute increased by an average 35 % during experiments and the nitrogen stable isotopic ratio of nitrate decreased by over 1 %o showing the potential of sediment and dissolved organic matter degradation to influence nitrate flux and its isotopic signal.

The diets and environments that individuals experience can vary greatly within and among wildlife populations. These individual experiences can be compared using the chemical signatures of animal tissues, which can differentiate animals into groups, including those raised in the wild versus those held in captive facilities. In this study, we compared different combinations of four stable isotope ratios and 15 trace elements derived from the claw tips of captive wood turtles throughout the eastern U.S. and wild wood turtles (Glyptemys insculpta) from Maine to develop predictive models used to determine their origins. The purpose of this work is to develop an objective statistical tool that law enforcement can use to help prosecute poachers. We found that the chemical signatures of 14 (12 trace elements and 2 stable isotope ratios) of the 19 markers we explored were different between wild and captive wood turtles, thus reflecting the differences in their diets and environments. We found that our stable isotope ratio model had nearly perfect predictive accuracy in classifying wild wood turtles as wild and captive wood turtles as captive, whereas our trace element and combined model were 100% accurate, thus validating this statistical approach for determining the origins of confiscated wood turtles from Maine.

Carbon and nitrogen stable isotopic ratios are increasingly used in sediment fingerprinting studies. However, questions remain regarding tracer conservativeness during sediment transport and other error considerations. We investigate conservativeness processes, including carbon oxidation and nitrogen mineralization, using experiments. We also test how other considerations impact the isotopic ratios including algae accrual into temporary sediment deposits in the river, the physical loss of organic matter via disaggregation, concentration dependent mixing, and time-varying isotopic ratios of sediment sources. Results show all processes and considerations can change isotope abundance, however, significance varied. Carbon oxidation, nitrogen mineralization and upland seasonality of sediment sources did not significantly change isotopic ratios. Algae accrual, concentration dependency mixing, physical loss of organic matter during transport, and seasonality of the in-stream sediment source significantly changed the isotopic ratios for the conditions tested. Fertilization significantly impacted the stable carbon isotopic ratio in one case considered. Results from sediment fingerprinting simulations and testing how well the virtual mixture fits the mass balance equation agreed with significance results for tracer changes, and some uncertainty considerations changed fractional contribution of sources by as much as 50%. A noteworthy recommendation is the mean isotopic ratios of sediment sources should be separated by at least 1‰ to lessen tracer conservativeness concerns in fingerprinting simulation. We recommend concentration dependent mixing becomes the accepted practice when using isotopic ratios, however, we warn against using particle size corrections. We recommend the loss of organic matter during disaggregation be accounted for in fingerprinting estimates. We recommend algae accrual in in-stream sediment deposits should either be accounted for or in-stream sediment should be treated as a time-varying source in sediment fingerprinting simulations. Finally, we recommend both the carbon and nitrogen isotopic ratio should be tested as potential tracers because the two tracers performed similarly when testing how well the virtual mixture fits the mass balance equations.

Wildlife traffickers often claim that confiscated animals were captive-bred rather than wild-caught to launder wild animals and escape prosecution. We used stable isotopes (δ13C and δ15N) derived from the claw tips of wild wood turtles from Maine and captive wood turtles throughout the eastern U.S. to develop a predictive model used to classify confiscated wood turtles as wild or captive. We found that the claw tips of wild and captive wood turtles (Glyptemys insculpta) were isotopically distinct. Captive turtles had significantly higher δ13C and δ15N values than wild turtles. Our model correctly classified all wild turtles as wild (100%) and nearly all captive turtles as captive (94%). All but two of the 71 turtles tested were successfully predicted as wild or captive (97.2% accuracy), yielding a misclassification rate of 2.8%. In addition to our model being useful to law enforcement in Maine, we aim to develop a multi-species model to assist conservation law enforcement efforts to curb illegal turtle trafficking from locations across the eastern United States and Canada.

AbstractUnderstanding the effects of long‐term traditional and alternative agricultural management practice effects on carbon (C) and nitrogen (N) cycling and storage within particulate organic matter (POM) and light fractions (LF) within various soil aggregate‐size classes can be illuminated by isotopic 13C/12C (δ13C) and 15N/14N (δ15N) differences. The objective of this study was to evaluate the effects of residue level, residue burning, tillage, and irrigation on δ13C and δ15N values of the bulk‐soil, macro‐ (>250 μm) and micro‐aggregate‐(53–250 μm), coarse‐ (>250 μm), and fine‐ (53–250 μm) POM, and coarse‐ and fine‐LF in the top 10 cm following 13 yr of consistent management in a wheat (Triticum aestivum L.)–soybean [Glycine max (L.) Merr.] double‐crop system on a silt‐loam soil in eastern Arkansas. Various treatment combinations affected (p < .05) δ13C values within the bulk‐soil and fine‐POM, as well as δ15N values within the bulk‐soil, macro‐aggregate, coarse‐LF, and fine‐LF fractions. Averaged across all other field treatments, macro‐aggregate δ15N was greater (p < .01) in the no‐tillage (NT)‐low‐ (3.23%) compared with NT–high‐residue (3.05%) and CT‐high‐ and low‐residue combination, which did not differ and averaged 3.11%, indicating that more labile residue can be achieved in the NT–high‐residue treatment combination. Results showed significant variations in aggregate‐associated δ13C and δ15N, as affected by long‐term residue and water management practices that would otherwise not have been evident from simple, bulk‐soil analysis or a short‐term field study.

Nitrogen removal rates can vary with time, space, and external environmental drivers, but are underreported for karst environments. We carried out a multi‐year study of a karst conduit where we: (a) measured inputs and outputs of sediment nitrogen (SN and δ15NSed) and nitrate (NO3− and δ15NNO3); (b) developed, calibrated, and applied a numerical model of nitrogen physics and biogeochemistry; and (c) forecasted the impacts of climate and land use changes on nitrate removal and export. Data results from conduit inputs (SN = 0.43% ± 0.07%, δ15NSed = 5.07‰ ± 1.01‰) and outputs (SN = 0.36% ± 0.09%, δ15NSed = 6.45‰ ± 0.71‰) indicate net‐mineralization of SN and increase of δ15NSed (p < 10−2). However, δ15NSed increase cannot be explained by SN mineralization alone and is instead accompanied by immobilization of isotopically heavier mineral nitrogen (δ15NNO3 = 11.25‰ ± 6.96‰). Modeled SN and δ15NSed sub‐routines provided a boundary condition for DIN simulation and improved NO3− model performance (from NSE = 0.06 to NSE = 0.68). Modeled spatial zones of removal occur in close proximity to conduit entrances, where deposition of labile organic matter promotes a three‐fold increase in denitrification (∼60 mg N m−2 d−1). Modeled temporal periods of removal occur during the dry‐season where longer residence times cause up to 90% removal of NO3− inputs. Projected effects of environmental drivers suggest an increase in denitrification (+14.1%); however, this removal is largely offset by greater nitrate soil leaching (+28.1%) from wetter regional climate. Results suggest that conduits underlying mature karst terrain experience spatiotemporal removal gradients, which are modulated by solute and sediment delivery.

Microbial fermentation is a common form of metabolism that has been exploited by humans to great benefit. Industrial fermentation currently produces a myriad of products ranging from biofuels to pharmaceuticals. About one-third of the world's food is fermented, and the brewing of fermented beverages in particular has an ancient and storied history. Because fermentation is so intertwined with our daily lives, the topic is easily relatable to students interested in real-world applications for microbiology. Here, we describe the curriculum for a guided inquiry-based laboratory course that combines yeast molecular ecology and brewing. The rationale for the course is to compare commercial Saccharomyces cerevisiae yeast strains, which have been domesticated through thousands of generations of selection, with wild yeast, where there is growing interest in their potentially unique brewing characteristics. Because wild yeasts are so easy to isolate, identify, and characterize, this is a great opportunity to present key concepts in molecular ecology and genetics in a way that is relevant and accessible to students. We organized the course around three main modules: isolation and identification of wild yeast, phenotypic characterization of wild and commercial ale yeast strains, and scientific design of a brewing recipe and head-to-head comparison of the performance of a commercial and wild yeast strain in the brewing process. Pre-and postassessment showed that students made significant gains in the learning objectives for the course, and students enjoyed connecting microbiology to a real-world application.

Nanoscale zero-valent iron (NZVI) has been proven effective at degrading environmental ‎contaminants of concern, yet field performance as an in situ remedy is lacking due to short ‎reactive lifetimes and poor transport through porous media. The main ‎objective of this study was to investigate and compare the performance of different carbon ‎powders with different properties (surface ‎area, pore-volume, conductivity, functional groups) on trichloroethylene (TCE) removal and transport ‎properties. Carbon ‎powders were used as the support for bimetallic FeNi nanoparticles, the composites were stabilized by poly(vinyl pyrrolidone), and the performance of ‎the modified novel FeNi-carbon composites was compared. It was confirmed that several properties of the carbon were found to not affect TCE degradation by the FeNi-C composites while ‎surface area, pore size, and functional groups are responsible for TCE adsorption by carbon ‎powders. Carbon particle size was found to inversely affect the transport of the composite ‎through porous media, with smaller carbon supports such as carbon black correlating to a wider ‎radius of influence, as compared to larger biochar carbon particulates. Significantly, FeNi-C ‎shows improved TCE degradation over Fe or FeNi nanoparticles alone, indicating the utility of ‎using carbon supports to promote dehalogenation reactions and increase NZVI longevity‎.

Improved understanding of mechanisms for carbon (C) and nitrogen (N) stabilization is needed to develop new management systems that enhance agricultural sustainability for the intensively cultivated loessial and alluvial soils in the Lower Mississippi River Valley. The distribution of C and N among particulate organic matter (POM) fractions may be key to improving the long-term sustainability of agricultural soils with extensive cultivation histories. The objective of this field study was to evaluate the effects of alternative and conventional agricultural management practices on C and N associated with various POM fractions. In the top 10 cm, following 14 years of consistent management in a wheat (Triticum aestivum L.)-soybean (Glycine max [L.] Merr.), double-crop (WSDC) system on a loessial soil (Glossaquic Fraglossudalf) in eastern Arkansas, averaged across tillage and burn treatments, the coarse-light-fraction C content of the soil was 20.3% greater (P < 0.02) in the irrigated-low- (107.3 g m(-2)) than the irrigated-high-residue (89.2 g m(-2)) and 65.4% greater than in the non-irrigated treatment combinations, which did not differ and averaged 64.8 g m(-2). Averaged across tillage, burn, and residue-level, coarse-intra-aggregate POM C content of the soil was 46% greater (P < 0.01) in the irrigated (424 g m(-2)) than in the non-irrigated treatments (290 g m(-2)). Increasing POM C and N fractions using a combination of conventional and alternative soil and water management practices has the potential for increasing soil C and N storage and maintaining long-term sustainability in intensively cultivated soils. (C) 2019 Elsevier B.V. All rights reserved.

Excessive nitrate threatens a wide range of water resources, aquatic habitats, and sensitive infrastructure. Despite this problem, tracing a nutrient from its eventual fate back to its origin remains an elusive challenge due to heterogeneity in how nutrient sources and hydrologic pathways are connected. Typically, this problem is underdetermined (i.e., too many unknowns, not enough equations) and cannot be solved with existing methodologies. The theory of optimal transport allows for the solution of underdetermined systems, and here we construct a novel formulation for its use in water quality modeling. Our objective was to develop an optimal transport modeling framework—coupled to Bayesian source unmixing, loadograph pathway separation, and geospatial connectivity analysis—to apportion nitrate loading from three sources (soil, fertilizer, and manure) across three pathways (quick, intermediate, and slow), resulting in nine possible source‐pathway couplings (soil‐quick, soil‐intermediate, …, manure‐slow). We apply this model to a 30 month elemental (NO3−) and isotopic (δ15N and δ18O) nitrate data set from a karst watershed in Kentucky, USA. Modeling results indicate that—of the nine possible source‐pathway couplings—nearly 60% of nitrate export is facilitated by just three: fertilizer‐quick (16.4%), manure‐intermediate (15.4%), and soil‐slow (27.2%). Further, we reinforce the need to explicitly consider heterogeneity in source‐pathway connectivity as homogeneous assumptions lead to erroneous inferences. The applicability of the model, its input requirements, and transferability to other sites is discussed. Lastly, we simulated two land management scenarios (field buffers and septic repair) and demonstrate how optimal transport can be used to test nutrient reduction strategies.

Nitrate (NO3-) fate estimates in turbulent karst pathways are lacking due, in part, to the difficulty of accessing remote subsurface environments. To address this knowledge and methodological gap, we collected NO3-, (delta N-15(NO3), and delta O-18(NO3) data for 65 consecutive days, during a low-flow period, from within a phreatic conduit and its terminal end-point, a spring used for drinking water. To simulate nitrogen (N) fate within the karst conduit, the authors developed a numerical model of NO3- isotope dynamics. During low-flow, data show an increase in NO3- (from 1.78 to 1.87 mg N L-1; p < 10(-4)) coincident with a decrease in delta N-15(NO3)(from 7.7 to 6.8 parts per thousand; p < 10(-3)) as material flows from within the conduit to the spring. Modeling results indicate that the nitrification of isotopically-lighter ammonium (delta N-15(NH4)) acts as a mechanism for an increase in NO3- that coincides with a decrease in delta N-15(NO3). Further, numerical modeling assists with quantifying isotopic overprinting of nitrification on denitrification (i.e., coincident NO3- production during removal) by constraining the rates of the two processes. Modeled denitrification fluxes within the karst conduit (67.0 +/- 19.0 mg N m(-2) d (-1)) are an order-of-magnitude greater than laminar ground water pathways (1-10 mg N m(-2) d(-1)) and an order-of-magnitude less than surface water systems (100-1000 mg N m(-2) d(-1)). In this way, karst conduits are a unique interface of the processes and gradients that control both surface and ground water end-points. This study shows the efficacy of ambient N stable isotope data to reflect N transformations in subsurface karst and highlights the usefulness of stable isotopes to assist with water quality numerical modeling in karst. Lastly, we provide a rare, if not unique, estimate of N fate in subsurface conduits and provide a counterpoint to the paradigm that karst conduits are conservative source-to-sink conveyors. (C) 2019 Elsevier Ltd. All rights reserved.

A major challenge in photothermal treatment is generating sufficient heat to eradicate diseased tissue while sparing normal tissue. Au nanomaterials have shown promise as a means to achieve highly localized photothermal treatment. Toward that end, the synthetic peptide anginex was conjugated to Au nanocages. Anginex binds to galectin-1, which is highly expressed in dividing endothelial cells found primarily in the tumor vasculature. The skin surface temperature during a 10 min laser exposure of subcutaneous murine breast tumors did not exceed 43°C and no normal tissue damage was observed, yet a significant anti-tumor effect was observed when laser was applied 24 h post-injection of targeted nanocages. Untargeted particles showed little effect in immunocompetent, tumor-bearing mice under these conditions. Photoacoustic, photothermal, and ICP-MS mapping of harvested tissue showed distribution of particles near the vasculature throughout the tumor. This uptake pattern within the tumor combined with a minimal overall temperature rise were nonetheless sufficient to induce marked photothermal efficacy and evidence of tumor control. Importantly, this evidence suggests that bulk tumor temperature during treatment does not correlate with treatment outcome, which implies that targeted nanomedicine can be highly effective when closely bound/distributed in and around the tumor endothelium and extensive amounts of direct tumor cell binding may not be a prerequisite of effective photothermal approaches.

Atmospheric rivers and tropical cyclones originate in the tropics and can transport high rainfall amounts to inland temperate regions. The purpose of this study was to investigate the response of nitrate (NO3−) pathways, concentration peaks, and stable isotope (δ15NNO3, δ18ONO3, δ2HH2O, δ18OH2O, and δ13CDIC) measurements to these extreme events. A tropical cyclone and atmospheric river produced the number one and four ranked events in 2017, respectively, at a Kentucky USA watershed characterized by mature karst topography. Hydrologic responses from the two events were different due to rainfall characteristics with the tropical cyclone producing a steeper rising limb of the spring hydrograph and greater runoff generation to the surface stream compared to the atmospheric river. Local minima and maxima of specific conductance, δ2HH2O, δ18OH2O, and δ13CDIC coincided with hydrograph peaks for both events. Minima and maxima of NO3−, δ15NNO3, δ18ONO3, and temperature lagged behind the hydrograph peak for both events, and the values continued to be impacted by diffuse recharge during hydrograph recession. Quick-flow pathways accounted for less than 20% of the total NO3− yield, while intermediate (30%) and slow-flow (50%) pathways composed the remaining load. However, hydrograph separation into quick-, intermediate-, and slow-flow pathways was not able to predict the timing of NO3− concentration peaks. Rather, the intermediate-flow pathway is conceptualized to experience a shift in porosity, associated with a change from epikarst macropores and fissures to soil micropores, with the arrival of water from the latter component likely causing peak NO3− concentration at the spring. Our results suggest that a more discretized conceptual model of pathways may be needed to predict peak nutrient concentration in rivers draining karst topography.