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Soil microbes vigorously produce and consume gases that reflect active soil biogeochemical processes. Soil gas measurements are therefore a powerful tool to monitor microbial activity. Yet, the majority of soil gases lack non-disruptive subsurface measurement methods at spatiotemporal scales relevant to microbial processes and soil structure. To address this need, we developed a soil gas sampling system that uses novel diffusive soil probes and sample transfer approaches for high-resolution sampling from discrete subsurface regions. Probe sampling requires transferring soil gas samples to above-ground gas analyzers where concentrations and isotopologues are measured. Obtaining representative soil gas samples has historically required balancing disruption to soil gas composition with measurement frequency and analyzer volume demand. These considerations have limited attempts to quantify trace gas spatial concentration gradients and heterogeneity at scales relevant to the soil microbiome. Here, we describe our new flexible diffusive probe sampling system integrated with a modified, reduced volume trace gas analyzer and demonstrate its application for subsurface monitoring of biogeochemical cycling of nitrous oxide (N2O) and its site-specific isotopologues, methane, carbon dioxide, and nitric oxide in controlled soil columns. The sampling system observed reproducible responses of soil gas concentrations to manipulations of soil nutrients and redox state, providing a new window into the microbial response to these key environmental forcings. Using site-specific N2O isotopologues as indicators of microbial processes, we constrain the dynamics of in situ microbial activity. Unlocking trace gas messengers of microbial activity will complement -omics approaches, challenge subsurface models, and improve understanding of soil heterogeneity to disentangle interactive processes in the subsurface biome.

The oral treatment of feline hyperthyroidism with antithyroid drugs often results in gastrointestinal side effects (10-20%). To date only oral formulations are approved although the oral application is not tolerated by all cats. Transdermal therapy can be an alternative. Nanocarriers could be used to ensure adequate transport of active agents through the skin. The present pilot study investigated the efficacy and safety of a novel dermal formulation of thiamazole for the treatment of feline hyperthyroidism. For the first time, amphiphilic dendritic core-multishell-nanocarriers were used. Cats with T4 values ≥ 4.0 µg/dl or a T4 value from 3.0-4.0 µg/dl and defined clinical findings were recruited. The euthyroid range for the T4 value was defined from ≥ 0.8 and ≤ 4.0 µg/dl. A total of 24 hyperthyroid cats were included and treated with thiamazole ointment for three weeks (24 cats) up to eight weeks (12 cats). The treatment success was 50% after three weeks and 41,7% after eight weeks. Cats that were within the euthyroid range required after three weeks a mean total dose of 1,09 mg/kg/d (0,68-1,7 mg/kg/d, 12/24) and after eight weeks 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). No side effects were observed during the three resp. eight-week study period. Variations of the T4 value in companion cats in the same household were comparable to those of an independent control group. Thiamazole ointment based on nanocarriers is suitable for the treatment of feline hyperthyroidism.Bei der oralen medikamentösen Behandlung der felinen Hyperthyreose mit Thyreostatika kommt es bei 10–20% der Katzen zu gastrointestinalen Nebenwirkungen. Aktuell sind ausschließlich orale Formulierungen zugelassen, wobei nicht alle Katzen eine orale Medikamentengabe tolerieren. Eine Alternative kann die transdermale Therapie sein, bei der ein Wirkstofftransport über die Haut durch Nanocarrier gewährleistet wird. In der vorliegenden Pilotstudie wurde die Wirksamkeit und Sicherheit einer neuartigen dermalen Formulierung von Thiamazol zur Behandlung der felinen Hyperthyreose untersucht. Zum Einsatz kamen erstmals amphiphile dendritische Kern-Multischalen-Nanocarrier. Eingeschlossen wurden Katzen mit einem Serum- T4-Wert ≥ 4,0 µg/dl oder einem T4-Wert zwischen 3,0–4,0 µg/dl und festgelegten klinischen Befunden. Der euthyreote Bereich wurde mit einem T4-Wert zwischen ≥ 0,8 und ≤ 4,0 µg/dl definiert. Insgesamt wurden 24 hyperthyreote Katzen eingeschlossen und drei (24 Katzen) bis acht Wochen (12 Katzen) mit Thiamazolsalbe behandelt. Der Behandlungserfolg lag nach drei Wochen bei 50%, nach acht Wochen bei 41,7%. Die Katzen, die den euthyreoten Bereich erreichten, erhielten nach drei Wochen eine mittlere Dosis von 1,09 mg/kg/d (0,68–1,7 mg/kg/d, 12/24) bzw. nach acht Wochen 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). Während des drei bzw. achtwöchigen Studienzeitraumes konnten keine Nebenwirkungen beobachtet werden. Die Schwankungen der T4-Werte von im selben Haushalt lebenden Partnerkatzen waren mit denen einer unabhängigen Kontrollgruppe vergleichbar. Die auf Nanocarriern basierende Thiamazolsalbe ist zur Behandlung der felinen Hyperthyreose geeignet.Le traitement oral de l’hyperthyroïdie féline avec des médicaments antithyroïdiens entraîne souvent des effets secondaires gastro-intestinaux (10 à 20% des cas). À ce jour, seules les formulations orales sont approuvées, bien que l’application orale ne soit pas tolérée par tous les chats. La thérapie transdermique peut être une alternative. Des nanoporteurs pourraient être utilisés pour assurer un transport adéquat des agents actifs à travers la peau. La présente étude pilote a examiné l’efficacité et l’innocuité d’une nouvelle formulation cutanée de thiamazole pour le traitement de l’hyperthyroïdie féline. Pour la première fois, des nanoporteurs à noyau multicellulaire dendritiques amphiphiles ont été utilisées. Des chats avec des valeurs T4 ≥ 4,0 µg/dl ou une valeur T4 de 3,0–4,0 µg/dl et un tableau clinique définis ont été recrutés. La gamme euthyroïdienne pour la valeur T4 a été définie entre ≥ 0,8 et ≤ 4,0 µg/dl. Un total de 24 chats hyperthyroïdiens ont été inclus et traités avec une pommade au thiamazole pendant une période allant de trois semaines (24 chats) jusqu’à huit semaines (12 chats). Le succès du traitement était de 50% après trois semaines et de 41,7% après huit semaines. Les chats qui se trouvaient dans la gamme euthyroïdienne avaient besoin après trois semaines d’une dose totale moyenne de 1,09 mg/kg/j (0,68–1,7 mg/kg/j, 12/24) et après huit semaines 1,65 mg/kg/j (1,49-2,04 mg/kg/j, 5/12). Aucun effet secondaire n’a été observé pendant les trois respectivement les huit semaines de l’étude. Les variations de la valeur T4 chez les chats vivant dans le même ménage étaient comparables à celles d’un groupe témoin indépendant. La pommade au thiamazole à base de nanoporteurs convient au traitement de l’hyperthyroïdie féline.Il trattamento orale dell’ipertiroidismo felino con farmaci tirostatici causa nel 10-20% dei gatti degli effetti collaterali gastrointestinali. Attualmente sono approvate solo delle formulazioni orali anche se non tutti i gatti tollerano un medicamento per via orale. Un’alternativa sarebbe una terapia transdermica che garantisce via dei nanovettori il trasporto del principio attivo attraversa la pelle. In questo studio pilota è stata studiata l’efficacia e la sicurezza di una nuova formulazione dermica con tiomazolo per il trattamento dell’iperdiroidismo nei felini. Per la prima volta si sono utilizzati nanovettori anfifilici dendritici con nucleo a più gusci. Sono stati presi in considerazione solo gatti con risultati clinici accertati e con un valore sierico T4 ≥ 4,0 µg/dl oppure con un valore T4 tra 3,0–4,0 µg/dl. La zona eutiroidea è stata definita con un valore T4 compreso tra ≥ 0,8 e ≤ 4,0 µg/dl. Sono stati inclusi un totale di 24 gatti ipertiroidei e sono stati trattati con un unguento al tiomazolo durante 3 (24 gatti) a otto settimane (12 gatti). Il successo del trattamento dopo tre settimane era del 50% e dopo otto settimane del 41.7%. I gatti che hanno raggiunto la zona eutiroidea avevano ricevuto dopo tre settimane una dose media di 1,09 mg/kg/d (0,68–1,7 mg/kg/d, 12/24) e dopo otto settimane 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). Non sono stati rilevati effetti collaterali durante il periodo dello studio di tre a otto settimane. Le variazioni dei valori T4 tra gatti partner che vivevano nella stessa famiglia erano paragonabili a quelle di un gruppo di controllo indipendente. L’unguento a base di tiomazolo con nanovettori è adatto al trattamento dell’ipertiroidismo felino.

Background To understand the presence and impact of social and cultural factors on health vulnerability it is important for improving diabetes care and management. In fact, through the social dimension, it is possible to identify the priorities and attitudes towards diabetes and diabetes care among those living with the condition. Methods The study was carried out as part of the global Cities Changing Diabetes programme, involved a sample of individuals living with diabetes in the Rome metropolitan area and employed mixed-method and qualitative approaches to data collection and analysis (survey, sorting procedure and focus group). Results Four specific sub-groups of participants have been identified, each with distinct but shared priorities and attitudes towards diabetes: Health conscious thanks to the context; Medicalized elderly people; Fatalistic citizens; Worried but undisciplined young people. The connection between the place where you live and the possibility to adopt a healthier lifestyle was confirmed. For these patients, the disease is mainly characterized by its relationship with food and its connections with psychological aspects are also relevant. Conclusions An important issue concerns information and the different understandings of diabetes. A clear need emerged for further elaboration of the various aspects of a disease that tends to be underestimated also by those who have it. Another aspect concerns the importance of the living environment and consequently of the actions on its urban planning, mobility, but also in everyday life organization, as factors that can make a difference in properly managing the disease. These results are very important to promote a joint action, that have to involve public and private stakeholders, in order to improve treatment opportunities and quality of life of people facing diabetes every day in the Rome metropolitan area. Key messages An important issue concerns information. A clear need emerged for further elaboration of the various aspects of a disease that tends to be underestimated also by those who have it. The living environment in important too and the actions on its urban planning, mobility, in everyday life organization, as factors that can make a difference in properly managing the disease.

Understanding magnetic phases in quantum mechanical systems is one of the essential goals in condensed matter physics, and the advent of prototype quantum simulation hardware has provided new tools for experimentally probing such systems. We report on the experimental realization of a quantum simulation of interacting Ising spins on three-dimensional cubic lattices up to dimensions 8 × 8 × 8 on a D-Wave processor (D-Wave Systems, Burnaby, Canada). The ability to control and read out the state of individual spins provides direct access to several order parameters, which we used to determine the lattice's magnetic phases as well as critical disorder and one of its universal exponents. By tuning the degree of disorder and effective transverse magnetic field, we observed phase transitions between a paramagnetic, an antiferromagnetic, and a spin-glass phase.

Hillslopes turn precipitation into runoff and thus exert important controls on various Earth system processes. It remains difficult to collect reliable data necessary for understanding and modeling these Earth system processes in real catchments. To overcome this problem, controlled experiments are being conducted at the Landscape Evolution Observatory at Biosphere 2, The University of Arizona. Previous experiments have revealed differences in hydrological response between 2 landscapes within Landscape Evolution Observatory, even though both landscapes were designed to be identical. In an attempt to discover where the observed differences stem from, we use a fully 3-dimensional hydrological model (CATchment HYdrology) to show the effect of soil water retention characteristics and saturated hydraulic conductivity on the hydrological response of these 2 hillslopes. We also show that soil water retention characteristics can be derived at hillslope scale from experimental observations of soil moisture and matric potential. It is found that differences in soil packing between the 2 landscapes may be responsible for the observed differences in hydrological response. This modeling study also suggests that soil water retention characteristics and saturated hydraulic conductivity have a profound effect on rainfall–runoff processes at hillslope scale and that parametrization of a single hillslope may be a promising step in modeling rainfall–runoff response in real catchments.

National Science Foundation [EAR-1344552, EAR-1344664]; Philecology Foundation; CUAHSI Pathfinder Fellowship; Science Without Borders Program; CAPES Foundation, Brazil

Stable water isotopes are widely used in ecohydrology to trace the transport, storage, and mixing of water on its journey through landscapes and ecosystems. Evaporation leaves a characteristic signature on the isotopic composition of the water that is left behind, such that in dual-isotope space, evaporated waters plot below the local meteoric water line (LMWL) that characterizes precipitation. Soil and xylem water samples can often plot below the LMWL as well, suggesting that they have also been influenced by evaporation. These soil and xylem water samples frequently plot along linear trends in dual-isotope space. These trend lines are often termed "evaporation lines" and their intersection with the LMWL is often interpreted as the isotopic composition of the precipitation source water. Here we use numerical experiments based on established isotope fractionation theory to show that these trend lines are often by-products of the seasonality in evaporative fractionation and in the isotopic composition of precipitation. Thus, they are often not true evaporation lines, and, if interpreted as such, can yield highly biased estimates of the isotopic composition of the source water., Hydrology and Earth System Sciences, 22 (5), ISSN:1027-5606, ISSN:1607-7938

Transit times through hydrologic systems vary in time, but the nature of that variability is not well understood. Transit times variability was investigated in a 1 m3 sloping lysimeter, representing a simplified model of a hillslope receiving periodic rainfall events for 28 days. Tracer tests were conducted using an experimental protocol that allows time-variable transit time distributions (TTDs) to be calculated from data. Observed TTDs varied with the storage state of the system, and the history of inflows and outflows. We propose that the observed time variability of the TTDs can be decomposed into two parts: ‘internal' variability associated with changes in the arrangement of, and partitioning between, flow pathways; and ‘external' variability driven by fluctuations in the flow rate along all flow pathways. These concepts can be defined quantitatively in terms of rank StorAge Selection (rSAS) functions, which is a theory describing lumped transport dynamics. Internal variability is associated with temporal variability in the rSAS function, while external is not. The rSAS function variability was characterized by an ‘inverse storage effect', whereby younger water is released in greater proportion under wetter conditions than drier. We hypothesize that this effect is caused by the rapid mobilization of water in the unsaturated zone by the rising water table. Common approximations used to model transport dynamics that neglect internal variability were unable to reproduce the observed breakthrough curves accurately. This suggests that internal variability can play an important role in hydrologic transport dynamics, with implications for field data interpretation and modeling. This article is protected by copyright. All rights reserved.

Field studies analyzing the stable isotope composition of xylem water are providing important information on ecosystem water relations. However, the capacity of stable isotopes to characterize the functioning of plants in their environment has not been fully explored because of methodological constraints on the extent and resolution at which samples could be collected and analysed. Here, we introduce an in situ method offering the potential to continuously monitor the stable isotope composition of tree xylem water via its vapour phase using a commercial laser-based isotope analyser and compact microporous probes installed into the xylem. Our technique enables efficient high-frequency measurement with intervals of only a few minutes per sample while eliminating the need for costly and cumbersome destructive collection of plant material and laboratory-based processing. We present field observations of xylem water hydrogen and oxygen isotope compositions obtained over several days including a labelled irrigation event and compare them against results from concurrent destructive sampling with cryogenic distillation and mass spectrometric analysis. The data demonstrate that temporal changes as well as spatial patterns of integration in xylem water isotope composition can be resolved through direct measurement. The new technique can therefore present a valuable tool to study the hydraulic architecture and water utilization of trees.

Soil fluxes of CO2 (Fs) have long been considered unidirectional, reflecting the predominant roles of metabolic activity by microbes and roots in ecosystem carbon cycling. Nonetheless, there is a growing body of evidence that non-biological processes in soils can outcompete biological ones, pivoting soils from a net source to sink of CO2, as evident mainly in hot and cold deserts with alkaline soils. Widespread reporting of unidirectional fluxes may lead to misrepresentation of Fs in process-based models and lead to errors in estimates of local to global carbon balances. In this study, we investigate the variability and environmental controls of Fs in a large-scale, vegetation-free, and highly instrumented hillslope located within the Biosphere 2 facility, where the main carbon sink is driven by carbonate weathering. We found that the hillslope soils were persistent sinks of CO2 comparable to natural desert shrublands, with an average rate of −0.15 ± 0.06 µmol CO2 m2 s−1 and annual sink of −56.8 ± 22.7 g C m−2 y−1. Furthermore, higher uptake rates (more negative Fs) were observed at night, coinciding with strong soil–air temperature gradients and [CO2] inversions in the soil profile, consistent with carbonate weathering. Our results confirm previous studies that reported negative values of Fs in hot and cold deserts around the globe and suggest that negative Fs are more common than previously assumed. This is particularly important as negative Fs may occur widely in arid and semiarid ecosystems, which play a dominant role in the interannual variability of the terrestrial carbon cycle. This study contributes to the growing recognition of the prevalence of negative Fs as an important yet, often overlooked component of ecosystem C cycling.

We describe a novel procedure for estimating population-level vulnerability to type 2 diabetes and then demonstrate how differences in social and cultural factors among vulnerable sub-groups translate into design considerations for prevention-oriented community interventions. Our study adopted a mixed method approach combining a quantitative evaluation of population data with a qualitative vulnerability assessment that centered around in-depth interviews. Harris County, Texas serves as the setting. Four distinct sub-groups were identified within neighborhoods considered vulnerable to diabetes, based on clinical predictors of diabetes and on economic disadvantage. Differences among these groups were then characterized by their prominent social and cultural factors. Understanding these differences offers a critical refinement important for designing effective local policies and targeted community interventions to prevent type 2 diabetes. This paper emphasizes the qualitative analysis and its implications.

In this commentary, we build on discussions that emerged during the workshop "Isotope-based studies of water partitioning and plant-soil interactions in forested and agricultural environments" held in San Casciano Val di Pesa, Italy, in September 2017. Quantifying and understanding how water cycles through the Earth's critical zone is important to provide society and policy makers with the scientific background to manage water resources sustainably, especially considering the ever-increasing worldwide concern about water scarcity. Stable isotopes of hydrogen and oxygen in water have proven to be a powerful tool to track water fluxes in the critical zone. However, both mechanistic complexities (e.g., mixing and fractionation processes, heterogeneity of natural systems) and practical methodological issues (e.g., lack of standard protocols to sample specific compartments, such as soil water and xylem water) limit the application of stable water isotopes in critical zone science. In this commentary, we examine some of the opportunities and critical challenges of using isotope-based ecohydrological applications, and outline new perspectives focused on interdisciplinary research opportunities for this important tool in water and environmental science.

n this commentary, we summarize and build upon discussions that emerged during the workshop "Isotope-based studies of water partitioning and plant–soil interactions in forested and agricultural environments" held in San Casciano in Val di Pesa, Italy, in September 2017. Quantifying and understanding how water cycles through the Earth's critical zone is important to provide society and policymakers with the scientific background to manage water resources sustainably, especially considering the ever-increasing worldwide concern about water scarcity. Stable isotopes of hydrogen and oxygen in water have proven to be a powerful tool for tracking water fluxes in the critical zone. However, both mechanistic complexities (e.g. mixing and fractionation processes, heterogeneity of natural systems) and methodological issues (e.g. lack of standard protocols to sample specific compartments, such as soil water and xylem water) limit the application of stable water isotopes in critical-zone science. In this commentary, we examine some of the opportunities and critical challenges of isotope-based ecohydrological applications and outline new perspectives focused on interdisciplinary research opportunities for this important tool in water and environmental science., Biogeosciences, 15 (21), ISSN:1726-4170

Stable isotope signatures provide an integral fingerprint of origin, flow paths, transport processes, and residence times of water in the environment. However, the full potential of stable isotopes to quantitatively characterize subsurface water dynamics is yet unfolded due to the difficulty in obtaining extensive, detailed, and repeated measurements of pore water in the unsaturated and saturated zone. This paper presents a functional and cost-efficient system for non-destructive continual in situ monitoring of pore water stable isotope signatures with high resolution. Automatic controllable valve arrays are used to continuously extract diluted water vapor in soil air via a branching network of small microporous probes into a commercial laser-based isotope analyzer. Normalized liquid-phase isotope signatures are then obtained based on a specific on-site calibration approach along with basic corrections for instrument bias and temperature dependent isotopic fractionation. The system was applied to sample depth profiles on three experimental plots with varied vegetation cover in southwest Germany. Two methods (i.e., based on advective versus diffusive vapor extraction) and two modes of sampling (i.e., using multiple permanently installed probes versus a single repeatedly inserted probe) were tested and compared. The results show that the isotope distribution along natural profiles could be resolved with sufficiently high accuracy and precision at sampling intervals of less than four minutes. The presented in situ approaches may thereby be used interchangeably with each other and with concurrent laboratory-based direct equilibration measurements of destructively collected samples. It is thus found that the introduced sampling techniques provide powerful tools towards a detailed quantitative understanding of dynamic and heterogeneous shallow subsurface and vadose zone processes.

This paper explores the challenges of model parameterization and process representation when simulating multiple hydrologic responses from a highly controlled unsaturated flow and transport experiment with a physically-based model. The experiment, conducted at the Landscape Evolution Observatory (LEO), involved alternate injections of water and deuterium enriched water into an initially very dry hillslope. The multivariate observations included point measures of water content and tracer concentration in the soil, total storage within the hillslope, and integrated fluxes of water and solute through the seepage face. The simulations were performed with a three-dimensional finite element model that solves the Richards and advection-dispersion equations. Integrated flow, integrated transport, distributed flow, and distributed transport responses were successively analyzed, with parameterization choices at each step supported by standard model performance metrics. In the first steps of our analysis, where seepage face flow, water storage, and average concentration at the seepage face were the target responses, an adequate match between measured and simulated variables was obtained using a simple parameterization consistent with that from a prior flow-only experiment at LEO. When passing to the distributed responses, it was necessary to introduce heterogeneity to additional soil hydraulic parameters to obtain an adequate match for the point-scale flow response. Augmented heterogeneity also improved the match against point measures of tracer concentration, although model performance here was considerably poorer. This suggests that still greater complexity is needed in the model parameterization, or that there may be gaps in process representation for simulating solute transport phenomena in very dry soils.

Predictions of hydrologic system response to natural and anthropogenic forcing are highly uncertain due to the heterogeneity of the land surface and subsurface. Landscape heterogeneity results in spatiotemporal variability of hydrological states and fluxes, scale-dependent flow and transport properties, and incomplete process understanding. Recent community activities, such as Prediction in Ungauged Basins of International Association of Hydrological Sciences, have recognized the impasse current catchment hydrology is facing and have called for a focused research agenda toward new hydrological theory at the watershed scale. This new hydrological theory should recognize the dominant control of landscape heterogeneity on hydrological processes, should explore novel ways to account for its effect at the watershed scale, and should build on an interdisciplinary understanding of how feedback mechanisms between hydrology, biogeochemistry, pedology, geomorphology, and ecology affect catchment evolution and functioning.

When engaging in playful teasing, understanding the norms for acceptable teasing is critical. The present study surveyed beliefs concerning prescriptive and descriptive norms for teasing among 101 male and 88 female college students. Participants viewed a number of topics as unacceptable for teasing and indicated that a high percentage of common topics for teasing were more closely associated with the teasing of one sex. Both sexes expected men to experience being less upset by teasing, and to be more likely to reciprocate the teasing.

Field studies analyzing the stable isotope composition of xylem water are providing important information on ecosystem water relations. However, the capacity of stable isotopes to characterize the functioning of plants in their environment has not been fully explored because of methodological constraints on the extent and resolution at which samples could be collected and analysed. Here, we introduce an in situ method offering the potential to continuously monitor the stable isotope composition of tree xylem water via its vapour phase using a commercial laser-based isotope analyser and compact microporous probes installed into the xylem. Our technique enables efficient high-frequency measurement with intervals of only a few minutes per sample while eliminating the need for costly and cumbersome destructive collection of plant material and laboratory-based processing. We present field observations of xylem water hydrogen and oxygen isotope compositions obtained over several days including a labelled irrigation event and compare them against results from concurrent destructive sampling with cryogenic distillation and mass spectrometric analysis. The data demonstrate that temporal changes as well as spatial patterns of integration in xylem water isotope composition can be resolved through direct measurement. The new technique can therefore present a valuable tool to study the hydraulic architecture and water utilization of trees.

Plants rely primarily on rainfall infiltrating their root zones - a supply that is inherently variable, and fluctuations are predicted to increase on most of the Earth's surface. Yet, interrelationships between water availability and plant use on short timescales are difficult to quantify and remain poorly understood. To overcome previous methodological limitations, we coupled high-resolution in situ observations of stable isotopes in soil and transpiration water. We applied the approach along with Bayesian mixing modeling to track the fate of (2) H-labeled rain pulses following drought through soil and plants of deciduous tree ecosystems. We resolve how rainwater infiltrates the root zones in a nonequilibrium process and show that tree species differ in their ability to quickly acquire the newly available source. Sessile oak (Quercus petraea) adjusted root uptake to vertical water availability patterns under drought, but readjustment toward the rewetted topsoil was delayed. By contrast, European beech (Fagus sylvatica) readily utilized water from all soil depths independent of water depletion, enabling faster uptake of rainwater. Our results demonstrate that species-specific plasticity and responses to water supply fluctuations on short timescales can now be identified and must be considered to predict vegetation functional dynamics and water cycling under current and future climatic conditions.

Determining the soil hydraulic properties is a prerequisite to physically model transient water flow and solute transport in the vadose zone. Estimating these properties by inverse modelling techniques has become more common within the last 2 decades. While these inverse approaches usually fit simulations to hydrometric data, we expanded the methodology by using independent information about the stable isotope composition of the soil pore water depth profile as a single or additional optimization target. To demonstrate the potential and limits of this approach, we compared the results of three inverse modelling strategies where the fitting targets were (a) pore water isotope concentrations, (b) a combination of pore water isotope concentrations and soil moisture time series, and (c) a two-step approach using first soil moisture data to determine water flow parameters and then the pore water stable isotope concentrations to estimate the solute transport parameters. The analyses were conducted at three study sites with different soil properties and vegetation. The transient unsaturated water flow was simulated by solving the Richards equation numerically with the finite-element code of HYDRUS-1D. The transport of deuterium was simulated with the advection-dispersion equation, and a modified version of HYDRUS was used, allowing deuterium loss during evaporation. The Mualem–van Genuchten and the longitudinal dispersivity parameters were determined for two major soil horizons at each site. The results show that approach (a), using only the pore water isotope content, cannot substitute hydrometric information to derive parameter sets that reflect the observed soil moisture dynamics but gives comparable results when the parameter space is constrained by pedotransfer functions. Approaches (b) and (c), using both the isotope profiles and the soil moisture time series, resulted in good simulation results with regard to the Kling–Gupta efficiency and good parameter identifiability. However, approach (b) has the advantage that it considers the isotope data not only for the solute transport parameters but also for water flow and root water uptake, and thus increases parameter realism. Approaches (b) and (c) both outcompeted simulations run with parameters derived from pedotransfer functions, which did not result in an acceptable representation of the soil moisture dynamics and pore water stable isotope composition. Overall, parameters based on this new approach that includes isotope data lead to similar model performances regarding the water balance and soil moisture dynamics and better parameter identifiability than the conventional inverse model approaches limited to hydrometric fitting targets. If only data from isotope profiles in combination with textural information is available, the results are still satisfactory. This method has the additional advantage that it will not only allow us to estimate water balance and response times but also site-specific time variant transit times or solute breakthrough within the soil profile.

AIMS: To analyse the significance of antibodies to p53 protein as a serological marker for changes in p53 gene expression in patients with hepatocellular carcinoma. METHODS: Thirty eight patients with hepatocellular carcinoma, 19 showing accumulation of p53 protein by immunohistochemistry and 19 having no accumulation, were studied. The presence of anti-p53 was tested using a novel ELISA utilising a recombinant p53 protein as a capture system and verified by western blotting. p53 gene mutations were sought by single strand conformational polymorphism and DNA sequencing analyses. RESULTS: Of 19 patients with p53 protein accumulation in tumour tissue, 10 (52%) had antibodies to p53 in serum by ELISA. Four patients with p53 negative immunohistochemistry also had detectable anti-p53. Western blot analysis confirmed the specificity of the ELISA positive serum samples. The presence of anti-p53 was independent of serum alpha-fetoprotein and was detected in 50% of small tumours while only 8% were alpha-fetoprotein positive. Mutations affecting exons 5 and 6 seem to be more frequently associated with development of anti-p53, than mutations in exons 7 or 8. CONCLUSIONS: The ELISA for anti-p53 is a convenient and specific tet for the detection of humoral response to alterations in p53 gene expression and could be of value in the diagnosis and characterisation of patients with hepatocellular carcinoma.

Background Chronic idiopathic enteropathies (CIE) in dogs are complex diseases of unknown origin. AST-120 is a spherical carbon adsorbent preparation with a high adsorption ability for low molecular substances. Objectives Evaluation of the clinical efficacy of AST-120 in dogs with CIE. Animals Ten client-owned dogs with mild (n = 7) to moderate (n = 3) CIE. Methods Explorative, prospective, randomized, placebo-controlled, double-blinded pilot study. Dogs with chronic diarrhea and no or insufficient response to an elimination diet were included. The dogs received either AST-120 (n = 5) or placebo (n = 5) for a duration of 21 days. The canine inflammatory bowel disease activity index (CIBDAI) was used to assess disease severity at baseline and clinical outcome after 3 weeks of treatment. Furthermore, changes in body weight and the parameters stool consistency and frequency were compared within and between groups. Results The mean CIBDAI score decreased from 5.6 (SD 1.5) to 2.0 (SD 1.2) in the AST-120 group (P = .125) and from 4.8 (SD .8) to 3.6 (SD 2.3) in the placebo group (P = .688). Compared with baseline, posttreatment CIBDAI scores decreased more than 60% in 4/5 dogs treated with AST-120 and in 1/5 dogs treated with placebo (P = .206). Changes in CIBDAI scores, body weights, stool consistency, and frequency within and between groups did not achieve statistical significance after 3 weeks of treatment. No adverse effects of AST-120 were noted. Conclusions and Clinical Importance This study investigated potential efficacy of AST-120 as an alternative therapy in dogs with mild-to-moderate CIE.

Die Nitrido-Sodalithe M(6+(y/2)–x)H2x[P12N24]Zy mit M = Fe, Co, Ni, Mn; Z = Cl, Br, I; 0 ≤ x ≤ 4; y ≤ 2 wurden durch Umsetzung von HPN2 bzw. von [PN(NH2)2]3 mit dem jeweiligen Metallhalogenid MZ2 hergestellt (T = 700°C). Sie sind mit Zn(7–x)H2x[P12N24]Cl2 isotyp. Mit steigendem Ionenradius von Kationen oder Anionen findet man eine Aufweitung des Volumens. Dies ist mit einer Vergroserung des PNP-Winkels verbunden. Der Einflus der Kationen ist dabei starker als jener der Anionen. Durch Reaktion von [PN(NH2)2]3 mit dem jeweiligen Metallhalogenid MZ2 werden wasserstofffreie PN-Sodalithe als rontgenamorphe Pulver erhalten. Bei diesen Reaktionen setzt die Bildung der chlorhaltigen PN-Sodalithe schon unterhalb von 450°C ein. Nitrido-Sodalites. II. Synthesis, Crystal Structure, and Properties of M(6+(y/2)–x)H2x[P12N24]Zy with M = Fe, Co, Ni, Mn; Z = Cl, Br, I; 0 ≤ x ≤ 4; y ≤ 2 The nitrido sodalites M(6+(y/2)–x)H2x[P12N24]Zy with M = Fe, Co, Ni, Mn; Z = Cl, Br, I; 0 ≤ x ≤ 4; y ≤ 2 are obtained by the reaction of HPN2 or [PN(NH2)2]3 with the metal halogenide MZ2 (T = 700°C). The compounds are isotypic to Zn(7–x)H2x[P12N24]Cl2. An increase of the ionic radii of the cations or anions results in an expansion of the lattice which is caused by an increase of the PNP angle. The influence of the cation is more dominant than that of the anion. By reacting [PN(NH2)2]3 with metal halogenide (MZ2) hydrogen free, X-ray amorphous products are obtained. The formation of the chloride-containing PN-sodalite in this reaction begins at temperatures below 450°C.

Indirect immunofluorescence (IIFT) on in house HEp-2 cell preparations revealed a novel antibody giving a granular cytoplasmic pattern not described before, which on two commercial cell preparations revealed a "rings and rods" pattern. This pattern was also observed in four HCV-RNA carriers and prompted the identification of the reactive antigen and the evaluation of the antibody prevalence in HCV-RNA carriers and control groups.The antigen's molecular weight was determined by radioimmunoprecipitation of 35S-methionine labeled cell proteins. Expression library screening and sequencing was performed by standard techniques using an oligo(dT)-primed human HeLa cell cDNA expression library. Antibodies against the novel antigen Inositol-5'-monophosphatdehydrogenase 2 (IMPDH2) were analyzed by IIFT, western blot, line blot, and radioimmunoprecipitation assay (RIPA). IIFT was performed on commercial HEp-2 cells and cells cultivated in house for 24 - 60 hours, with or without the IMPDH2 inhibitors mycophenolic acid (MPA) or ribavirin, and subjected to various fixation conditions. Western and line blots were performed with IMPDH2 synthesized in E. coli, RIPA with 35S-methionine-IMPDH2 from in vitro transcription/translation products. Sera screened were positive for HCV-RNA (108), HBV-DNA (100), anti-mitochondrial (31), anti-actin (42), and anti-nuclear antibodies (51) and negative for HCV-RNA (100) and blood donors (100).IMPDH2 is capable of considerable intracellular rearrangements (upon action of inhibitors like MPA and ribavirin), which explains the contrasting immunofluorescence patterns in cells from different sources. By RIPA, proven to be the sole assay suitable for screening of anti-IMPDH2 in human sera, autoantibodies were found in 35.2% of HCV-RNA carriers and in low concentrations in 31% of anti-actin positive patients suspicious of autoimmune hepatitis. Antibodies reacted preferentially with conformational epitopes. Compared to the low concentration of anti-IMPDH2 found in other disease groups, high antibody concentrations were observed in HCV-RNA carriers.The common occurrence of anti-IMPDH2 in HCV-RNA carriers may be related to ribavirin therapy, causing intracellular aggregation of IMPDH2 thereby altering its immunogenicity. In this study the "rods and rings" immunofluorescence pattern observed could be ascribed to anti-IMPDH2. Anti-IMPDH2 may cause difficulties in interpretation of immunofluorescence patterns in routine autoantibody testing.

[1] Despite the availability of weather radar data at high spatial (1 km2) and temporal (5–15 min) resolution, ground-based rain gauges continue to be necessary for accurate estimation of storm rainfall input to catchments during flash flood events, especially in mountainous catchments. Given economical considerations, a long-standing problem in catchment hydrology is to establish optimal placement of a small number of rain gauges to acquire data on both rainfall depth and spatiotemporal variability of intensity during extreme storm events. Using weather radar observations and a dense network of 40 tipping bucket rain gauges, this study examines whether it is possible to determine a reliable “best” set of rain gauge locations for the Sabino Canyon catchment near Tucson, Arizona, USA, given its complex topography and dominant storm track pattern. High-quality rainfall data are used to evaluate all possible configurations of a “practical” network having from one to four rain gauges. A multicriteria design strategy is used to guide rain gauge placement, by simultaneously minimizing the residual percent bias and maximizing the coefficient of correlation between the estimated and true mean areal rainfall and minimizing the normalized spatial mean squared error between the estimated and true spatiotemporal rainfall distribution. The performance of the optimized rain gauge network was then compared against randomly designed network ensembles by evaluating the quality of streamflows predicted using the Kinematic Runoff and Erosion (KINEROS2) event-based rainfall-runoff model. Our results indicate that the multicriteria strategy provided a robust design by which a sparse but accurate network of rain gauges could be implemented for semiarid basins such as the one studied.

1I. Medizinische Klinik und Poliklinik, Universitat Mainz, 2Klinik und Poliklinik fur Radiologie, Universitat Mainz, 3Transplantationschirurgie und Chirurgie von Leber, Gallenwegen, Pankreas, Universitat Mainz, 4Wako Pure Chemical Industries, Ltd., Neuss, 5Labor Prof. Seelig und Kollegen, Karlsruhe 1 I . Background and aims The multikinase inhibitor sorafenib (Nexavar®) was approved for the therapy of advanced hepatocellular carcinoma (HCC) in 2008. Within the SHARP study a life-extension of 2,8 months with an acceptable profile of side-effects could be demonstrated for patients with Child-Pugh A liver cirrhosis.1 AFP-L3 (in %) is the fraction of Lens culinaris agglutinin-reactive AFP to total AFP and is also, like DCP (des-gamma-carboxyprothrombin), useful for early detection and prognosis assessment of HCC.2,3 Considering the shortcomings of RECIST criteria in the age of targeted therapy we have investigated in this study serum levels of AFP, AFP-L3 and DCP as potential markers for monitoring of the response to sorafenib therapy.

p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53.For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies.In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinomas. None of the sera of the control group was positive. Patients with anti-p53 have noticeably poorer prognosis (Log Rank Test, p0.005). After a period of 5 years, the overall survival rate of the p53-positive group was 24 % - less than half of that of the p53-negative group with a survival rate of 51 %.: The detection of p53 autoantibodies definitely permits a clearer prognostic assessment, which in turn influences clinical procedures. If p53 autoantibodies are detected in a patient during therapy, the applied therapeutic method should be reconsidered and the patient be more closely observed than other, p53 negative patients.

To study p53 gene mutation in human hepatocellular carcinoma (HCC) samples and the relationship between p53 gene mutation and hepatitis B virus (HBV) infection.DNA samples were prepared from 50 specimens of HCC patients that had been infected with HBV. Exons 5-9 were amplified with polymerase chain reaction (PCR), and then detected by single strand conformation polymorphism (SSCP).Over 26% (13/50) of p53 DNA samples were found to be mutated, mainly in exons 5-8 relating to 3,3,4,3 cases respectively and along with 4 suspicious samples.p53 gene mutation might be one of the causes of HCC, and HBV infection may be associated with such mutation in China.

Intraoperative fat embolism associated with cemented total hip arthroplasty is a well recognized complication. In a new sheep model allowing for standardized bilateral, simultaneous cement pressurization we studied the effectiveness of both pulsatile and syringe lavage of equal volume with regard to their cleansing capabilities as measured by fat and bone marrow intravasation. The operative procedure involved bilateral placement of intravenous catheters into the external iliac veins via retroperitoneal approach. After femoral neck osteotomies both femoral cavities were prepared for retrograde cement application. After randomization one side was lavaged with 250 ml irrigation using a bladder syringe, the contralateral femur with the identical volume but using a pulsatile lavage. A specially designed apparatus was used to allow for bilateral simultaneous cement pressurization. Venous blood from both iliac catheters was then collected, anticoagulated and a quantitative and qualitative fat analysis was performed. Despite equal volume manual lavage produced significantly higher fat and bone marrow intravasation (P0.001) than pulsatile lavage thus suggesting that not only the volume but also the quality of bone lavage is an essential factor influencing the risk of fat embolism and adverse cardiorespiratory effects. Our findings further emphasize the important role of pulsatile lavage in preventing fat and bone marrow embolisation during cemented total hip arthroplasty.

"Soluble liver antigen" (SLA) has been reported to be an infrequent but in certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18 as major antigenic components. Using precharacterized sera, we could confirm trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive protein. However, the reaction differed from that of cytokeratins 8 and 18 by molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and 18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver expression gene bank yielded no clones with sequence homology to cytokeratins. We conclude that reactivity in SLA positive sera is not mainly directed against cytokeratins 8/18 and recommend native antigen preparations for diagnostic use until the exact molecular nature of the 52 kD SLA antigen has been elucidated.

Mutations in the p53 tumour suppressor gene have been recently described in hepatocellular carcinomas (HCC) from high risk areas such as China and South Africa. Our study was designed to assess the importance of p53 aberrations in HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant role. We investigated 22 HCCs and, as controls, their corresponding tumour-free liver tissues, seven livers with primary biliary cirrhosis and four morphologically normal livers. p53 overexpression, which is usually associated with point mutations of the p53 gene, was detected in 10 of the 22 HCCs by immunoblotting and immunohistochemistry. p53 expression was restricted to the nucleus in the positive cells, while all cells in the control tissues were negative. There was no obvious etiological preference in the p53 positive tumours. Particularly, underlying chronic HBV infection did not appear to be associated with an increased rate of p53 overexpression in European HCCs. SSCP and sequence analysis of exons 5-8 of the p53 gene revealed point mutations in six out of eight tumours with increased steady state levels of p53. In conclusion, our study demonstrates increased p53 levels due to point mutations in a significant proportion of European HCCs. The codon 249 mutation, which was detected in one of the cases, is not predominant in these tumours.

The loss of the tumor-suppressor activity of p53, either by mutation or by interaction with the human papillomavirus (HPV) E6 protein, is considered to be an important mechanism in the carcinogenesis of cervical cancer. We have studied the cytological distribution of these proteins in human cervical carcinoma cell lines using polyclonal anti-p53 and monoclonal anti-E6 antibodies. The antibody specificity was confirmed by immunoblot and immunocompetition analyses. The intracellular localization of p53 and E6 was detected using the techniques of conventional and three-dimensional confocal microscopy. In the HPV-18 or -16 integrated cell lines, HeLa, CaSki and SiHa, viral oncoprotein E6 and endogenous tumor-suppressor protein, p53, were observed by immunofluorescence in the cytoplasm; p53 also had a weak punctate staining in the nuclei of HeLa and CaSki cells. In the HPV-negative cervical carcinoma cell lines, C-33A and HT-3, which have mutated p53, p53 was localized predominantly to the nucleus, with C-33A cells having elevated levels of p53 compared with the other cell lines. High spatial resolution imaging, using confocal microscopy, was performed on the cells after double fluorescence staining for p53 (fluorescein) and E6 (rhodamine). The images showed that both p53 and E6 had similar cytoplasmic distributions, which implied that these two proteins may exist as a cytoplasmic complex. To substantiate this implication, fluorescence resonance energy transfer microscopy was performed, which provided direct evidence of a close association between p53 and E6 within individual HeLa cells. The results from this study support the theory that p53 protein binds HPV-16/18 E6 protein in the cell cytoplasm, thus preventing p53 from exerting its tumor-suppressor function in the nucleus. Hence, inactivation of wild-type p53 by p53-E6 complex formation in cervical cancer may be a critical step in malignant transformation.