bluuebunny/crossref_metadata_2025 huggingface dataset:
Marginal Density Expansions for Diffusions and Stochastic Volatility I: Theoretical Foundations
Authors: Deuschel J. D. , Friz P. K. , Jacquier A. , Violante S.
Published: August 2013

Density expansions for hypoelliptic diffusions (X1,…,Xd) are revisited. We are particularly interested in density expansions of the projection at time T > 0 with l ≤ d. Global conditions are found that replace the well‐known “not‐in‐cut‐locus” condition known from heat kernel asymptotics. Our small‐noise expansion allows for a “second order” exponential factor. As an application, new light is shed on the Takanobu‐Watanabe expansion of Brownian motion and Lévy's stochastic area. Further applications include tail and implied volatility asymptotics in some stochastic volatility models, discussed in the companion paper .© 2013 Wiley Periodicals, Inc.
Single‐Dose Pharmacokinetics of the CCR9 Receptor Antagonist Vercirnon in Healthy US and Japanese Subjects
Authors: Haberer Lynda J. , Hacquoil Kimberley , Ino Hiroko , Sakamoto Takashi , Kanemoto Noriaki , McSherry Iain , Hirama Toshiyasu
Published: August 2013

Two randomized, single‐dose, crossover studies were carried out to assess different formulations and doses of the CCR9 receptor antagonist vercirnon in healthy subjects. US study (n = 24): a five‐period crossover study in healthy US subjects to assess the bioavailability of four new GlaxoSmithKline formulations compared with a “reference” formulation. Each subject received a single 500 mg dose of each of the five vercirnon formulations in a fed state. Primary pharmacokinetic (PK) endpoints were maximum plasma concentration, (Cmax), and exposure as assessed by area under the curve (AUC). There was no significant difference in PK parameters and bioavailability between the formulations tested. Japanese study (n = 30): a four‐period crossover study in healthy Japanese male subjects to assess PK and dose proportionality following single, ascending, oral doses of 250, 500, and 1,000 mg vercirnon under fasted and fed conditions. Vercirnon Cmax and AUC parameters in the fasted state increased in a less than dose proportional manner and were on average 20% higher in fed subjects compared with fasted subjects. Overall, these results support the premise that vercirnon has similar PK/safety profiles within US and Japanese populations. There was no evidence to preclude the use of the new vercirnon formulation in future studies.
Solvation Dynamics of a Radical Ion Pair in Micro‐Heterogeneous Binary Solvents: A Semi‐Quantitative Study Utilizing MARY Line‐Broadening Experiments
Authors: Pal Kunal , Grampp Günter , Kattnig Daniel R.
Published: August 2013

This work aims at elucidating the mechanism of solvation of a radical ion pair (RIP) in a micro‐heterogeneous binary solvent mixture using magnetically affected reaction yield (MARY) spectroscopy. For the exciplex‐forming 9,10‐dimethylanthracene/N,N‐dimethylaniline system a comparative, composition‐dependent MARY line‐broadening study is undertaken in a heterogeneous (toluene/dimethylsulfoxide) and a quasi‐homogenous (propyl acetate/butyronitrile) solvent mixture. The half‐saturation field extrapolated to zero‐quencher concentration, B1/2, and the self‐exchange rate constants are analyzed in the light of solvent dynamical properties of the mixtures and a dielectric continuum solvation model. The dependence of B1/2 on the solvent composition is explained by cluster formation giving rise to shortened RIP lifetimes. The results are in qualitative agreement with the continuum solvation model suggesting that it could serve as a theoretical basis for quantitative modeling.
Valorization of Humin‐Based Byproducts from Biomass Processing—A Route to Sustainable Hydrogen
Authors: Hoang Thi Minh Chau , Lefferts Leon , Seshan K.
Published: August 2013

The synthesis of biomass‐based top value‐added chemical platforms, for example, 5‐hydroxymethyl furfural, furfural, or levulinic acid from the acid‐catalyzed dehydration of sugars results in high yields of insoluble by‐products, referred to as humin. Valorization of humin by steam reforming for H2 is discussed. Both thermal and catalytic steam gasification were investigated systematically. Humin undergoes drastic changes under thermal pre‐treatment to the gasification temperature. Alkali‐metal‐based catalysts were screened for the reactions. Na2CO3 showed the highest activity and was selected for further study. The presence of Na2CO3 enhances the gasification rate drastically, and gas‐product analysis shows that the selectivity to CO and CO2 is 75 % and 25 %, respectively, which is a H2/CO ratio of 2 (corresponding to 81.3 % H2 as compared to the thermodynamic equilibrium). A possible process for the complete, efficient conversion of humin is outlined.
Efficient, specific, developmentally appropriate cre‐mediated recombination in anterior pituitary gonadotropes and thyrotropes
Authors: Pérez‐Millán María Inés , Zeidler Michael G. , Saunders Thomas L. , Camper Sally A. , Davis Shannon W.
Published: August 2013

Tissue‐specific expression of cre recombinase is a well‐established genetic tool to analyze gene function, and it is limited only by the efficiency and specificity of available cre mouse strains. Here, we report the generation of a transgenic line containing a cre cassette with codon usage optimized for mammalian cells (iCre) under the control of a mouse glycoprotein hormone α‐subunit (αGSU) regulatory sequences in a bacterial artificial chromosome genomic clone. Initial analysis of this transgenic line, Tg(αGSU‐iCre), with cre reporter strains reveals onset of cre activity in the differentiating cells of the developing anterior pituitary gland at embryonic day 12.5, with a pattern characteristic of endogenous αGSU. In adult mice, αGSU‐iCre was active in the anterior lobe of the pituitary gland and in the cells that produce αGSU (gonadotropes and thyrotropes) with high penetrance. Little or no activity was observed in other tissues, including skeletal and cardiac muscle, brain, kidney, lungs, testis, ovary, and liver. This αGSU‐iCre line is suitable for efficient, specific, and developmentally regulated deletion of floxed alleles in anterior pituitary gonadotropes and thyrotropes. genesis 51:785–792. © 2013 Wiley Periodicals, Inc.
Method for the Preparation of Nonracemic Bis‐Cyclometalated Iridium(III) Complexes
Authors: Helms Melanie , Lin Zhijie , Gong Lei , Harms Klaus , Meggers Eric
Published: August 2013

Invited for the cover of this issue is the team of Prof. Meggers. The cover image shows the Λ and Δ enantiomers of a bis‐cyclometalated iridium(III) complex and their corresponding mirror‐imaged CD spectra.
One‐Pot Two‐Step Synthesis of 1‐(Ethoxycarbonyl)indolizines via Pyridinium Ylides
Authors: Allgäuer Dominik S. , Mayr Herbert
Published: August 2013

Pyridinium salts Py+‐CH2‐EWG (EWG = CO2Et, CONEt2, CN, COMe, COPh) reacted with Michael acceptors Ar‐CH=C(CO2Et)(Acc) (Acc = CO2Et, COMe, SO2Me, CONH2) at ambient temperature in the presence of base to give [3 + 2]‐cycloadducts by stepwise [3 + 2]‐cycloaddition of the intermediate pyridinium ylides. Treatment of the crude reaction mixtures with 1 equiv. of chloranil and atmospheric oxygen in the presence of sodium hydroxide gave 1‐(ethoxycarbonyl)indolizines by dehydrogenation and elimination of the acceptor group (Acc). A good yield of indolizine was also obtained from Py+‐CH2CN and iPr‐CH=C(CO2Et)2, which indicates that this method is not restricted to aromatic Michael acceptors. Structurally related isoquinolinium salts react with Michael acceptors analogously to give pyrrolo[2,1‐a]isoquinolines.
Effects of temperature and copper pollution on soil community—extreme temperature events can lead to community extinction
Authors: Menezes-Oliveira Vanessa B. , Scott-Fordsmand Janeck J. , Soares Amadeu M.V.M. , Amorim Monica J.B.
Published: August 2013

Global warming affects ecosystems and species' diversity. The physiology of individual species is highly influenced by changes in temperature. The effects on species communities are less studied; they are virtually unknown when combining effects of pollution and temperature. To assess the effects of temperature and pollution in the soil community, a 2-factorial soil mesocosms multispecies experiment was performed. Three exposure periods (28 d, 61 d, and 84 d) and 4 temperatures (19 °C, 23 °C, 26 °C, and 29 °C) were tested, resembling the mean annual values for southern Europe countries and extreme events. The soil used was from a field site, clean, or spiked with Cu (100 mg Cu/kg). Results showed clear differences between 29 °C treatment and all other temperature treatments, with a decrease in overall abundance of organisms, further potentiated by the increase in exposure time. Folsomia candida was the most abundant species and Enchytraeus crypticus was the most sensitive to Cu toxicity. Differences in species optimum temperatures were adequately covered: 19 °C for Hypoaspis aculeifer or 26 °C for E. crypticus. The temperature effects were more pronounced the longer the exposure time. Feeding activity decreased with higher temperature and exposure time, following the decrease in invertebrate abundance, whereas for the same conditions the organic matter turnover increased. Hence, negative impacts on ecosystem services because of temperature increase can be expected by changes on soil function and as consequence of biodiversity loss. Environ Toxicol Chem 2013;32:2678–2685. © 2013 SETAC
Distribution of pyrethroid insecticides in secondary wastewater effluent
Authors: Parry Emily , Young Thomas M.
Published: August 2013

Although the freely dissolved form of hydrophobic organic chemicals may best predict aquatic toxicity, differentiating between dissolved and particle-bound forms is challenging at environmentally relevant concentrations for compounds with low toxicity thresholds such as pyrethroid insecticides. The authors investigated the distribution of pyrethroids among 3 forms: freely dissolved, complexed with dissolved organic carbon, and sorbed to suspended particulate matter, during a yearlong study at a secondary wastewater treatment plant. Effluent was fractionated by laboratory centrifugation to determine whether sorption was driven by particle size. Linear distribution coefficients were estimated for pyrethroid sorption to suspended particulate matter (Kid) and dissolved organic carbon (Kidoc) at environmentally relevant pyrethroid concentrations. Resulting Kid values were higher than those reported for other environmental solids, and variation between sampling events correlated well with available particle surface area. Fractionation results suggest that no more than 40% of the pyrethroid remaining in secondary effluent could be removed by extending settling periods. Less than 6% of the total pyrethroid load in wastewater effluent was present in the dissolved form across all sampling events and chemicals. Environ Toxicol Chem 2013;32:2686–2694. © 2013 SETAC
Dietary bioavailability of cadmium presented to the gastropod Peringia ulvae as quantum dots and in ionic form
Authors: Khan Farhan R. , Schmuecking Katarina , Krishnadasan Siva H. , Berhanu Deborah , Smith Brian D. , deMello John C. , Rainbow Philip S. , Luoma Samuel N. , Valsami-Jones Eugenia
Published: August 2013

For quantum dots (QDs) synthesized in solvents that are immiscible in water, dietary, rather than aqueous, exposure is expected to be the primary route of uptake. The estuarine snail Peringia ulvae was presented with mats of simulated detritus spiked with oleic acid capped cadmium sulfide (CdS; 3.1 ± 0.4 nm) or cadmium selenide (CdSe; 4.2 ± 0.8 nm) nanoparticles, synthesized using a microfluidics method, or Cd2+ (added as Cd[NO3]2) as a control. A biodynamic modeling approach was used to quantify parameters that describe the dietary accumulation of the Cd forms. Ingestion rates decreased across treatments at higher exposure concentrations, indicating a metal-induced stress response related to Cd dose rather than form. Although Cd was bioavailable from both CdS and CdSe QDs, uptake rate constants from diet were significantly lower than that of Cd2+ (p < 0.05). After 72 h depuration, however, no loss of Cd was observed from snails that had accumulated Cd from either type of QD. In comparison, snails ingesting Cd2+-spiked detritus eliminated 39% of their accumulated body burden per day. The almost identical uptake and efflux rates for Cd in both QDs suggest no effect of the chalcogenide conjugates (S or Se). The findings of the present study indicate that the availability of Cd in the form of nanoparticles and its apparent in vivo persistence will lead to bioaccumulation. The implications of this are discussed. Environ Toxicol Chem 2013;32:2621–2629. ©2013 SETAC
Maternal transfer of inorganic mercury and methylmercury in aquatic and terrestrial arthropods
Authors: Saxton Heidi J. , Goodman James R. , Collins Jeffrey N. , Black Frank J.
Published: August 2013

The transfer of mercury from females to their offspring plays an important role in mercury accumulation and toxicity during early development. To quantify the transfer of inorganic mercury and methylmercury from female arthropods to their eggs, the authors collected and analyzed brine shrimp (Artemia franciscana), wolf spiders (Alopecosa spp.), and their attached eggs from aquatic and terrestrial ecosystems at the Great Salt Lake, Utah, USA. Essentially all of the mercury in both the female brine shrimp and their eggs was methylmercury (94 ± 17% and 90 ± 21%, respectively). The brine shrimp eggs had methylmercury concentrations that were 84 ± 2% lower than in the females, reflecting the fact that females transferred 45 ± 4% of their total body mass but only 11 ± 3% of their methylmercury burden to their eggs. As a result of this sequestration, the concentration of methylmercury in the female brine shrimp increased by 62 ± 8% during egg formation. The percentage of the total mercury that was methylmercury in female wolf spiders (77 ± 21%) was similar to that in their egg masses (81 ± 19%), indicating similar maternal transfer efficiencies for inorganic mercury and methylmercury in these invertebrates. The concentration of inorganic mercury and methylmercury in the female spiders was the same as in their eggs. These arachnids transferred 48 ± 9% of their total body mass, 55 ± 13% of their inorganic mercury, and 50 ± 9% of their methylmercury to their egg masses. Thus, female wolf spiders do not have the ability to reduce the transfer of methylmercury to their eggs, nor does this process represent an important pathway for the depuration of mercury. The present study demonstrates that although some arthropods have mechanisms to minimize the transfer of methylmercury to their eggs and reduce the potential for mercury toxicity during early development, other arthropods do not. Environ Toxicol Chem 2013;32:2630–2636. © 2013 SETAC
Landslide velocity, thickness, and rheology from remote sensing: La Clapière landslide, France
Authors: Booth Adam M. , Lamb Michael P. , Avouac Jean‐Philippe , Delacourt Christophe
Published: August 2013

Quantifying the velocity, volume, and rheology of deep, slow‐moving landslides is essential for hazard prediction and understanding landscape evolution, but existing field‐based methods are difficult or impossible to implement at remote sites. Here we present a novel and widely applicable method for constraining landslide 3‐D deformation and thickness by inverting surface change data from repeat stereo imagery. Our analysis of La Clapière, an ~1 km2 bedrock landslide, reveals a concave‐up failure surface with considerable roughness over length scales of tens of meters. Calibrating the thickness model with independent, local thickness measurements, we find a maximum thickness of 163 m and a rheology consistent with distributed deformation of the highly fractured landslide material, rather than sliding of an intact, rigid block. The technique is generally applicable to any mass movements that can be monitored by active or historic remote sensing.
Flexural versus dynamic processes of subsidence in the North American Cordillera foreland basin
Authors: Painter Clayton S. , Carrapa Barbara
Published: August 2013

Dynamic subsidence related to subduction is an important process in retroarc foreland basin systems. Dynamic subsidence in the North American retroarc foreland has been proposed as dominant in the Late Cretaceous; however, questions remain about the nature of the subcrustal load and the basin response to such processes. We present new isopach data using 130 data points covering a large portion of the U.S. and a revised flexural analysis of the Sevier foreland. Higher rigidity associated with the Wyoming craton can best model flexural subsidence directly prior to ~81 Ma. We constrain the transition from flexural to nonflexural subsidence to ~81 Ma and correlate this with large Late Cretaceous progradation. The locus of subsidence and the location of the subducted Shatsky oceanic plateau suggest that dynamic loading from viscous flow above the subducting plate is the mechanism driving dynamic subsidence in the retroarc foreland basin of the North American Cordillera.
Bias in estimates of lithosphere viscosity from interseismic deformation
Authors: Hines T. T. , Hetland E. A.
Published: August 2013

The estimation of uniform viscosities representing the lower crust and uppermost mantle from postseismic or interseismic deformation (i.e., apparent viscosities) is inherently biased with respect to a depth dependence of the viscosities within each layer. Estimates are biased toward a more viscous lower crust or a less viscous lithospheric mantle, depending on the relative geometric mean viscosities of the two layers. When there is a low‐viscosity shear zone beneath the fault, apparent viscosities are close to that of the shear zone immediately after the earthquake, although the apparent viscosities increase significantly during the later interseismic period. Inferences made from interseismic deformation that the lower crust is more viscous than the upper mantle may be entirely consistent with depth‐dependent viscosity profiles that have a significant increase in viscosity from the lowermost crust to the uppermost mantle.
Organic Stereochemistry. Part 8
Authors: Testa Bernard
Published: August 2013

This review terminates our general presentation of the principles of stereochemistry with special reference to the biomedicinal sciences. Here, we discuss and illustrate the principles of prostereoisomerism, and apply these to product and substrateproduct stereoselectivity in drug metabolism. The review begins with an overview of the concept of prostereoisomerism, discussing such aspects as homotopic, enantiotopic, and diastereotopic groups and faces. The main part of this review is dedicated to drug and xenobiotic metabolism. Here, the concept of prostereoisomerism proves particularly helpful to avoid confusing metabolic reactions in which an existing stereogenic element (e.g., a stereogenic center) influences the course of the reaction (substrate stereoselectivity), with metabolic reactions which create a stereogenic element (almost always a stereogenic center; product stereoselectivity). Specifically, examples of product stereoselectivity will be taken from functionalization reactions (so‐called phase‐I reactions) and conjugation (so‐called phase‐II reactions). Cases where stereoisomeric substrates show distinct product stereoselectivities (substrateproduct stereoselectivity) will also be presented.
Triterpene Saponins from Entada phaseoloides
Authors: Xiong Hui , Mei Zhinan , Yang Guangzhong , Mo Shasha , Yang Xinzhou , Zhang Peng , Wu Jizhou
Published: August 2013

Four oleanane‐type triterpene saponins, phaseoloideside A–D (1–4), were isolated from the seed kernels of Entada phaseoloides, along with rheediinoside B. The structures of the four new compounds were established by 2D‐NMR spectroscopic methods, HR‐ESI‐MS analysis, and chemical degradation. Phaseoloideside D (4) showed cytotoxic activity against the Eca‐109 cell line with an IC50 value of 28.0 μM.
Microwave‐Assisted Convenient Synthesis of α,β‐Unsaturated Esters and Ketones via Aldol‐Adduct Elimination
Authors: Suman Pathi , Nageswara Rao Rayala , China Raju Bhimapaka
Published: August 2013

Various fluorinated 3‐oxo ester/1,3‐diketones were reacted with carbonyl compounds, in presence of piperidine and under microwave irradiation, to afford (E)‐α,β‐unsaturated esters and ketones in good yields. The systematic study reveals that the reaction proceeded through the formation of aldol adduct. The method provides a new and simple way for C,C bond formations.
Superacid‐Promoted Cyclodehydration Leading to the Imidazo[2,1‐a]isoquinoline Ring System
Authors: Kethe Anila , Naredla Rajasekhar Reddy , Klumpp Douglas A.
Published: August 2013

A series of heterocycle‐substituted acetophenones were prepared and reacted with the Brønsted superacid CF3SO3H (triflic acid=trifluoromethanesulfonic acid). Cyclodehydration provided aryl‐substituted imidazo[2,1‐a]isoquinolines and related products (28–85%, seven examples). A mechanism is proposed involving dicationic intermediates.
Stereoselective Synthesis of (−)‐(1R,1′R,5′R,7′R)‐1‐Hydroxy‐exo‐brevicomin and (+)‐exo‐Brevicomin from 3,4,6‐Tri‐O‐acetyl‐D‐glucal
Authors: Sabitha Gowravaram , Maheswara Reddy Arekuti , Siva Sankara Reddy Singam , Singh Yadav Jhillu
Published: August 2013

Stereoselective syntheses of (−)‐(1R,1′R,5′R,7′R)‐1‐hydroxy‐exo‐brevicomin (1) and (+)‐exo‐brevicomin (2) were accomplished from 3,4,6‐tri‐O‐acetyl‐D‐glucal (5; Schemes 2 and 3). Chemoselective reduction, Grignard reaction, BartonMcCombie deoxygenation, and ketalization were used as key steps.
Influence of a coarse interlayer on seawater intrusion and contaminant migration in coastal aquifers
Authors: Liu Yi , Mao Xiaomin , Chen Jian , Barry D. A.
Published: August 2013

Vertical 2D slice laboratory experiments were carried out in homogenous and layered sand tanks to elucidate the effects of a highly permeable (coarse‐grained sand) interlayer on seawater intrusion and transport of contaminants to a coastal sea. Tidal fluctuations produced oscillations in the seawater–freshwater transition zone, fluctuations of the contaminant infiltration rate and a zigzag contaminant plume outline. The seawater wedge became discontinuous at the (vertical) edges of the interlayer because of increased lateral movement of the seawater–freshwater interface within the interlayer. The contaminant plume formed a tail within the interlayer depending on the tidal stage, and similar to the wedge, its movement was accentuated. A simple analytical model that neglected vertical flow reliably predicted steady‐state seawater intrusion into the coastal aquifer. Numerical modeling was used to gain insight into the groundwater hydrodynamics and contaminant migration. The numerical results confirmed the experimental findings, i.e. that a highly permeable interlayer can provide a rapid transit path for contaminants to reach the seaward boundary and that the interlayer amplifies the effects of tidal fluctuations, resulting in wider transition zones for the seawater wedge and contaminant plume. Numerical simulations further showed that, with increasing interlayer hydraulic conductivity, the maximum seawater intrusion distance inside the interlayer increases approximately linearly. For the fixed‐head contaminant injection condition used, the model showed that contaminant infiltration increases approximately logarithmically with increasing interlayer hydraulic conductivity (other factors held fixed). Copyright © 2013 John Wiley & Sons, Ltd.
Factors affecting the measurement of the vertical hydraulic conductivity of a streambed sediment using standpipe tests
Authors: Huang Yong , Zhou Zhifang , Guo Qiaona , Tang Yuzhou , Lu Wenlong
Published: August 2013

The vertical hydraulic conductivity (Kv) of a stream or lake sediment is often determined in the field using standpipe tests. Calculation of Kv is based on the assumption that the hydraulic head in the pipe is equal to that of the stream or lake stage. In this work, a modified equation for Kv is developed for the standpipe test which is applicable when this assumption is not valid. The equation involves not only the hydraulic head at different times but also the difference in the hydraulic head (a) between the groundwater level and river stage. The effects of certain factors on Kv, such as the ratio of the hydraulic head at different times (h1/h2), the difference a, and the initial water table height (h0), are also discussed. The results show that when h1/h2 is constant, the relative error (Er) in Kv increases with the ratio a/h2. Furthermore, if a/h2  <  0.05, then for any value of h1/h2, Er is less than 5% using the modified equation. Also, if a/h2 is large, hydraulic head readings with larger h1/h2 ratios must be used to avoid large Er values. The results of a field test also indicate that the error in Kv decreases as the value of h0 increases. Copyright © 2013 John Wiley & Sons, Ltd.
Spatial, seasonal, and source variability in the stable oxygen and hydrogen isotopic composition of tap waters throughout the USA
Authors: Landwehr Jurate M. , Coplen Tyler B. , Stewart David W.
Published: August 2013

To assess spatial, seasonal, and source variability in stable isotopic composition of human drinking waters throughout the entire USA, we have constructed a database of δ18O and δ2H of US tap waters. An additional purpose was to create a publicly available dataset useful for evaluating the forensic applicability of these isotopes for human tissue source geolocation. Samples were obtained at 349 sites, from diverse population centres, grouped by surface hydrologic units for regional comparisons. Samples were taken concurrently during two contrasting seasons, summer and winter. Source supply (surface, groundwater, mixed, and cistern) and system (public and private) types were noted. The isotopic composition of tap waters exhibits large spatial and regional variation within each season as well as significant at‐site differences between seasons at many locations, consistent with patterns found in environmental (river and precipitation) waters deriving from hydrologic processes influenced by geographic factors. However, anthropogenic factors, such as the population of a tap's surrounding community and local availability from diverse sources, also influence the isotopic composition of tap waters. Even within a locale as small as a single metropolitan area, tap waters with greatly differing isotopic compositions can be found, so that tap water within a region may not exhibit the spatial or temporal coherence predicted for environmental water. Such heterogeneities can be confounding factors when attempting forensic inference of source water location, and they underscore the necessity of measurements, not just predictions, with which to characterize the isotopic composition of regional tap waters. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Comparing hydraulic properties of different forest floors
Authors: Rasoulzadeh Ali , Homapoor Ghoorabjiri Majid
Published: August 2013

The forest floor plays an important role in runoff rate, soil erosion and soil infiltration capacity by protecting mineral soils from the direct impact of falling raindrops. Forest floor consists of different kinds of litter with different hydraulic properties. In this study, the inverse method was used to estimate the hydraulic properties of three kinds of forest floor (broad‐leaved, needle‐leaved and mixed‐stand) at three replications in a completely random design. Forest floor samples were collected from the Gilan Province, Iran. The samples were piled up to make long columns 40.88 cm high with an inner diameter of 18.1 cm. Artificial rainfall experiments were conducted on top of the columns, and free drainage from the bottom of the columns was measured in the laboratory. Saturated hydraulic conductivity (Ks), saturated water content and water retention curve parameters (van Genuchten equation) were estimated by the inverse method. The results showed that the Ks of needle‐leaved samples differed significantly (p < 0.05) from those of broad‐leaved and mixed‐stand samples, whereas the latter two did not differ in this regard. No significant differences emerged in the water retention function parameters of van Genuchten (θr, β and α) in the three forest floor samples. The saturated water content of mixed‐stand samples was significantly different (p < 0.05) from that of broad‐leaved and needle‐leaved treatments with the latter two samples showing no significant difference. The good agreement between simulated and observed free drainage for all forest floor samples in the validation period indicates that the estimated hydraulic properties efficiently characterize the unsaturated water flow in the forest floor. Copyright © 2013 John Wiley & Sons, Ltd.
Assessing effects of PCB exposure on American mink (Mustela vison) Abundance in Portland Harbor
Authors: Luxon Matt , Toll John , Hanson Craig
Published: August 2013

This article presents an integrated analysis using a Monte Carlo exposure model, dose–response effects model and habitat, and population dynamics models, all of which allow us to quantitatively estimate the effects of polychlorinated biphenyl (PCB) exposure on American mink (Mustela vison) abundance at the Portland Harbor Superfund Site (Site), and the associated uncertainties. The Site extends from river mile 1.9 of the Lower Willamette River, near its confluence with the Columbia River, to river mile 11.8, just downstream of downtown Portland, Oregon. The potential effects of PCBs on the American mink population were evaluated in the Baseline Ecological Risk Assessment (BERA) due to the historical presence of mink in the area and because mink are known to be highly sensitive to the effects of PCBs. Hazard quotients (HQs) calculated in the BERA indicated that PCB concentrations measured in Portland Harbor fish were above levels known to cause reproductive effects in mink. Further analysis was needed to evaluate the potential magnitude of effects on the Site mink population. The integrated analysis presented herein demonstrates that if an effect of PCB exposure is a less than 30% reduction in kit production, then PCB remediation is not expected to have any effect on mink abundance. This is a Site-specific conclusion that depends on the quality, abundance, and distribution of mink habitat in Portland Harbor. The PCB dose associated with a 30% reduction in kit production was calculated as 101 μg/kg bw/d (90% CI = 69–146 μg/kg bw/d). The mink PCB dose estimates from the Portland Harbor BERA indicate that if mink are present, their baseline exposure levels probably exceed 101 μg/kg bw/d. Therefore, some level of reduction in PCB exposure could be beneficial to the species if the study area provides sufficient habitat to support a mink population. This analysis demonstrates that risk analysis for population-level assessment endpoints benefits from analyses beyond those that calculate exposure and predict organism-level effects. Evaluation of population-level impacts provides risk managers with a richer perspective within which to evaluate the environmental protectiveness and cost-effectiveness of feasibility study alternatives across a range of potential remediation goals. Integr Environ Assess Manag 2013;X:000–000. © 2013 SETAC Integr Environ Assess Manag 2013;9999:XX–XX. © 2013 SETAC Integr Environ Assess Manag 2014;10:60–68. © 2013 SETAC
The proinflammatory peptide substance P promotes blood–brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions
Authors: Rodriguez Pedro L. , Jiang Shuxian , Fu Yigong , Avraham Shalom , Avraham Hava Karsenty
Published: August 2013

Neuropeptide substance P (SP) has been implicated in inflammation, pain, depression and breast cancer cell (BCC) growth. Here, we examined the role of SP in trafficking of BCCs (human MDA‐MB‐231 and MDA‐MB‐231BrM2 cells) across the blood–brain barrier (BBB) and brain microvascular endothelial cells (BMECs) using in vitro and in vivo models. SP was secreted from BCCs and mediated adhesion and transmigration of BCCs across human BMECs (HBMECs) in vitro. SP induced activation of HBMECs, leading to secretion of Tumor Necrosis Factor alpha (TNF‐α) and angiopoietin‐2 (Ang‐2) from HBMECs, resulting in changes in localization and distribution of tight junction (TJ) ZO‐1 (tight junction protein zonula occludins‐1) and claudin‐5 structures as well as increased permeability of HBMECs. Using spontaneous breast cancer metastasis mouse model (syngeneic) of GFP‐4T1‐BrM5 mammary tumor cells administered into mammary fat pads of Balb/c mice, SP inhibitor spantide III inhibited in vivo changes in permeability of the BBB and BMEC‐TJs ZO‐1 and claudin‐5 structures as well as decreased tumor cell colonization in brain. Thus, SP secreted from BCCs induces transmigration of BCCs across the BBB, leading to activation of BMECs and secretion of TNF‐α and Ang‐2, resulting in BBB impairment and colonization of tumor cells in brain. Therefore, therapies based on SP inhibition in combination with other therapies may prevent breaching of the BBB by BCCs and their colonization in brain.
Bcr‐Abl activates AURKA and AURKB in chronic myeloid leukemia cells via AKT signaling
Authors: Yang Jing , Ikezoe Takayuki , Nishioka Chie , Udaka Keiko , Yokoyama Akihito
Published: August 2013

This study explored molecular mechanisms by which Bcr‐Abl induced expression of Aurora kinase A and B (AURKA and AURKB) in chronic myeloid leukemia cells. Lentiviral transduction of Bcr‐Abl into either Ba/F3 or CD34+ hematopoietic stem/progenitor cells potently increased levels of AURKA and AURKB in association with phosphorylation of AKT and stimulated their proliferation. Bcr‐Abl‐mediated expression of AURKA and AURKB were decreased in CD34+ HSPCs when AKT was inactivated by an shRNA against AKT, suggesting that Bcr‐Abl induced expression of AURKA and AURKB via AKT signaling. MLN8237, an inhibitor of AURKA, significantly inhibited the proliferation of freshly isolated CD34+ CML cells in a dose‐dependent manner as measured by colony forming assay. Importantly, inhibition of AURKA in CD34+ leukemia cells freshly isolated from individuals with blast crisis of CML with Bcr‐Abl T315I mutant (n = 2) by MLN8237 significantly impaired the engraftment of these cells in severely immunocompromised mice and decreased the weight of spleens. Taken together, Bcr‐Abl induces expression of AURKA and AURKB at least in part via AKT. Inhibition of AURKA could be useful to overcome imatinib‐resistance mediated by Bcr‐Abl mutants.
Oroxylin A has therapeutic potential in acute myelogenous leukemia by dual effects targeting PPARγ and RXRα
Authors: Hui Hui , Chen Yan , Yang Hao , Zhao Kai , Wang Qian , Zhao Li , Wang Xiaotang , Li Zhiyu , Lu Na , Guo Qinglong
Published: August 2013

Oroxylin A (OA) is a flavonoid derived from a Chinese herb that has previously been reported to inhibit the proliferation of several cancer cell lines. It is found that OA significantly inhibited the growth of myeloid leukemia cell lines and as xenografts in immunodeficient mice and primary blasts from acute myelogenous leukemia (AML) patients. Furthermore, OA‐induced cell cycle arrest and differentiation were observed in OA‐treated AML cell lines. OA‐induced increase of CD11b/CD14 expression was reversed by GW9662, a specific PPARγ inhibitor, or transient transfection with PPARγ siRNA. Docking study showed OA bound to ligand‐binding domain of PPARγ via forming hydrogen bonds with Arg288 and Leu340 sites. Results of fluorescence polarization‐based ligand assay verified PPARγ‐binding activity of OA, and in OA‐treated cells, intranuclear accumulation and increased binding activity of PPARγ to PPRE were detected. We also found that GW9662 attenuated OA‐induced upregulation of C/EBPβ, an important regulator of leukemic differentiation, and p21, which is a potent inhibitor of CDKs that can inhibit phosphorylation of Rb by cyclin D1‐CDK4 complexes. Moreover, our results showed that OA displayed synergistic effects with all‐trans retinoic acid and VD3 in part related to reduction of intranuclear phosphorylated RXRα that has been reported to block nuclear receptor/RXRα heterodimer transcriptional activity. This reduction of phosphorylated RXRα was associated with inhibition of the specific upstream MAP kinase ERK1/2. We suggest that OA may provide a novel complement to AML treatment by its dual effects of augmenting PPARγ activity and sensitizing nuclear receptors to specific ligands.
Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma
Authors: Bidard François‐Clément , Madic Jordan , Mariani Pascale , Piperno‐Neumann Sophie , Rampanou Aurore , Servois Vincent , Cassoux Nathalie , Desjardins Laurence , Milder Maud , Vaucher Isabelle , Pierga Jean‐Yves , Lebofsky Ronald , Stern Marc‐Henri , Lantz Olivier
Published: August 2013

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been recently investigated in several cancer types, but their respective clinical significance remains to be determined. In our prospective study, we compared the detection rate and the prognostic value of these two circulating biomarkers in patients with metastatic uveal melanoma. GNAQ/GNA11 mutations were characterized in archived tumor tissue. Using a highly sensitive and mutation‐specific bidirectional pyrophosphorolysis‐activated polymerization (bi‐PAP) technique, GNAQ c.626A>T, GNAQ c.626A>C and GNA11 c.626A>T copy numbers were quantified in plasma from 12 mL of blood. CTCs were detected at the same time in 7.5 mL of blood by the CellSearch® technique. Patient characteristics and outcome were prospectively collected. CTCs (≥1) were detected in 12 of the 40 included patients (30%, range 1–20). Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4–11,421 copies/mL). CTC count and ctDNA levels were associated with the presence of miliary hepatic metastasis (p = 0.004 and 0.03, respectively), with metastasis volume (p = 0.005 and 0.004) and with each other (p < 0.0001). CTC count and ctDNA levels were both strongly associated with progression‐free survival (p = 0.003 and 0.001) and overall survival (p = 0.0009 and <0.0001). In multivariate analyses, ctDNA appeared to be a better prognostic marker than CTC. In conclusion, ctDNA and CTC are correlated and both have poor prognostic significance. CTC detection can be performed in every patient but, in patients with detectable mutations, ctDNA was more frequently detected than CTC and has possibly more prognostic value.
UNRAVELLING THE SPATIO‐TEMPORAL PATTERN OF IRRIGATION DEVELOPMENT AND ITS IMPACT ON INDIAN AGRICULTURE
Authors: Srivastava Shivendra K. , Ghosh Souvik , Kumar Ashwani , Brahmanand Pothula S.
Published: August 2013

Irrigation, the dominant use of water resources, has always remained a decisive factor in agricultural growth and development. The present study provides a critical analysis of inter‐regional variations in water resources and irrigation development over successive plan periods (1950–2007) and ascertains the long‐term impact of irrigation development on Indian agriculture using tabular, growth and econometric analysis. With impressive irrigation development over successive five‐year plans, India possesses the largest irrigated area in the world. However, the positive impact of irrigation development could not be achieved equally across different geographical regions, and unsustainable water resource development in one part coexists with its underutilization in other parts of the country. The Northern region of India showed better performance both in irrigation and agriculture while the Eastern region was found to be poorest in spite of a rich water resource base. Panel data analysis revealed a positive correlation between irrigation and crop yield though with varying degree. The findings of the present study provides a platform for institutional restructuring, policy reframing and technological interventions to improve water use efficiency and develop water resources in a equitable, holistic and sustainable manner. Copyright © 2013 John Wiley & Sons, Ltd.
Efficient lookup table using a linear function of inverse distance squared
Authors: Jung Jaewoon , Mori Takaharu , Sugita Yuji
Published: August 2013

The major bottleneck in molecular dynamics (MD) simulations of biomolecules exist in the calculation of pairwise nonbonded interactions like Lennard‐Jones and long‐range electrostatic interactions. Particle‐mesh Ewald (PME) method is able to evaluate long‐range electrostatic interactions accurately and quickly during MD simulation. However, the evaluation of energy and gradient includes time‐consuming inverse square roots and complementary error functions. To avoid such time‐consuming operations while keeping accuracy, we propose a new lookup table for short‐range interaction in PME by defining energy and gradient as a linear function of inverse distance squared. In our lookup table approach, densities of table points are inversely proportional to squared pair distances, enabling accurate evaluation of energy and gradient at small pair distances. Regardless of the inverse operation here, the new lookup table scheme allows fast pairwise nonbonded calculations owing to efficient usage of cache memory. © 2013 Wiley Periodicals, Inc.
Multiple‐dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA‐IgG1), a novel erythropoietic agent, in healthy postmenopausal women
Authors: Sherman Matthew L. , Borgstein Niels G. , Mook Louisa , Wilson Dawn , Yang Yijun , Chen Nianhang , Kumar Ravindra , Kim Kenneth , Laadem Abderrahmane
Published: August 2013

Ligands of the transforming growth factor‐beta superfamily and activin‐receptor signaling play an important role in erythropoiesis. Sotatercept, an activin receptor type IIA (ActRIIA) ligand trap, is a novel, recombinant, fusion protein comprising the extracellular domain of human ActRIIA linked to the Fc portion of human immunoglobulin G1. Sotatercept, originally developed to increase bone mineral density, was noted to have robust effects on erythropoiesis. Here, we evaluated the safety, pharmacokinetic properties, and pharmacodynamic effects of sotatercept in 31 healthy postmenopausal women. Sotatercept was administered at dose level 0.1, 0.3, or 1 mg/kg every 28 days subcutaneously for up to four doses. Sotatercept was generally safe and well tolerated, and elicited clinically significant, dose‐dependent increases in hemoglobin, hematocrit, and red blood cell counts that persisted for up to 4 months. The effect of sotatercept on hemoglobin was dose‐limiting. Sotatercept also increased bone mineral density and biomarkers of bone formation. The sotatercept serum exposure–dose relationship was linear, with a mean terminal half‐life of approximately 23 days. ActRIIA ligands are important regulators of erythrocyte production in healthy individuals. Clinical studies are ongoing to explore the potential of sotatercept to treat anemia and diseases of ineffective erythropoiesis as well as an agent to increase bone mineral density.
Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity
Authors: Stoll Felicitas , Burhenne Jürgen , Lausecker Berthold , Weiss Johanna , Thomsen Torben , Haefeli Walter Emil , Mikus Gerd
Published: August 2013

This study aimed to demonstrate that the dose of a CYP3A substrate (simvastatin) can be adapted individually on the basis of CYP3A activity as assessed by midazolam metabolic clearance. In 18 healthy participants individual CYP3A activity was quantified using midazolam metabolic clearance both alone and during CYP3A inhibition with 40 mg ritonavir. Thereafter, simvastatin acid exposure was determined after a simvastatin standard dose (40 mg) and doses adapted to individual CYP3A activity at baseline and during CYP3A inhibition. Interindividual variability of CYP3A activity and simvastatin acid AUC0–24 was large and both correlated (r2 = 0.745, P < .001). The adapted simvastatin doses ranged from 25 to 80 mg and their administration reduced simvastatin variability fivefold. Despite the low adapted simvastatin dose of 12 mg during CYP3A inhibition with ritonavir, exposure increased (point estimate of 4.2 [90% CI: 3.15–5.61]) probably caused by additional OATP1B1 inhibition. CYP3A activity‐based dose adaptation can be used to reduce interindividual variability in simvastatin exposure.
Application limits and data correction in number of molecules and brightness analysis
Authors: Trullo Antonio , Corti Valeria , Arza Elvira , Caiolfa Valeria R. , Zamai Moreno
Published: August 2013

Number of molecules and Brightness (N&B) has been proposed for measuring the molecular brightness and number of fluorophores in time‐sequence of images, in live cells. If the fluorescently tagged‐proteins are mobile in the illumination volume, the stoichiometry of their oligomers can be derived from the increase of the brightness of the fluorescent dyes due to clustering. We examine aspects concerning extra‐fluctuation effects induced by cell shifts and photobleaching, which yield large overestimates of the clusters size and sub‐unit counts. We develop an offline corrective approach consisting in frame re‐alignment and boxcar filtering for recovering precision of the analysis. Using simulations we derive general criteria for approaching this analysis, and assess the application limits of the corrective procedure. We tested the approach in extreme experimental conditions (few pixels, large extra‐variance perturbations), in which we analyzed the minimal increases of brightness as that expected between a monomeric and dimeric GPI‐mEGFP constructs. We show how most of the perturbing effects can be abolished, and obtain the correct the brightness of GPI‐mEGFP monomers and dimers. Microsc. Res. Tech. 76:1135–1146, 2013. © 2013 Wiley Periodicals, Inc.
A new 3‐D spherical hybrid model for solar wind interaction studies
Authors: Dyadechkin S. , Kallio E. , Jarvinen R.
Published: August 2013

A 3‐D spherical hybrid model has been developed to study how the solar wind interacts with various solar system bodies. The main advantages of the new spherical model, called the HYB‐s, compared with traditional Cartesian models are that the spherical model allows significantly reduced radial cell size and, consequently, a smaller total number of cells and particles in the simulation. The high radial resolution makes it possible to use the new model for 3‐D physical studies that have not been feasible before. Especially, the spherical model allows the inclusion of self‐consistent ionospheric photochemistry in global hybrid simulations of the solar wind interaction with terrestrial planets Venus and Mars. In this paper we describe the main aspects of the developed spherical hybrid model. We also study the solar wind interaction with Venus in a global hybrid simulation using the spherical hybrid model and our already published Cartesian hybrid model. The comparison between the two models suggests the high potential of the developed spherical hybrid model in studies of planetary plasma interactions.
Global features of Kelvin‐Helmholtz waves at the magnetopause for northward interplanetary magnetic field
Authors: Li Wenya , Wang Chi , Tang Binbin , Guo Xiaocheng , Lin Dong
Published: August 2013

We investigate the global features of Kelvin‐Helmholtz waves (KHW) at the low‐latitude magnetopause for constant northward interplanetary magnetic field conditions, using global magnetohydrodynamic simulations. The root‐integrated power (RIP) of X component of bulk velocity is employed to analyze the magnetopause mode of KHW along the boundary layer. The RIP distribution of the outer KHW is much broader than that of the inner one, and the maximum amplitude of global KHW occurs near the dawn/dusk terminator regions. In the dayside magnetopause, the phase of the waveform at middle latitudes leads to that at low latitudes, while the situation reversed in the nightside. The global evolution of KHW phases is a representation of an interesting feature that the axis of the Kelvin‐Helmholtz vortex aligns with the geomagnetic field lines. We suggest that the reported features may also exist in other KHW active regions with flow‐sheared plasma.