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Signals of opportunity (SoOp) reflectometry (SoOp-R) is a maturing field for geophysical remote sensing as evidenced by the growing number of airborne and spaceborne experiments. As this approach receives more attention, it is worth analyzing SoOp-R's capabilities to retrieve subsurface soil moisture (SM) by leveraging communication and navigation satellite transmitters. In this research, the Cramer–Rao lower bound (CRLB) is used to identify the effects of variable SoOp-R parameters on the best achievable estimation error for root-zone soil moisture (RZSM). This study investigates the use of multiple frequency, polarization, and incidence angle measurement configurations on a two-layered dielectric profile. The results also detail the effects of variable SM conditions on the capability of SoOp-R systems to predict subsurface SM. The most prevalent observation is the importance of using at least two frequencies to limit uncertainties from subsurface SM estimates. If at least two frequencies are used, the CRLB of a profile is retrievable within the root-zone depending on the surface SM content as well as the number of independent measurements of the profile. For a depth of 30 cm, it is observed that a CRLB corresponding to 4% RZSM estimation accuracy is achievable with as few as two dual-frequency-based SoOp-R measurements. For this depth, increasing number of measurements provided by polarization and incidence angle allow for sensing of increasingly wet SM profile structures. This study, overall, details a methodology by which SoOp-R receiver system can be designed to achieve a desired CRLB using a tradeoff study between the available measurements and SM profile.

SigNals Of Opportunity: P-band Investigation (SNOOPI) will be the first on-orbit demonstration of remote sensing using Signals of Opportunity (SoOp) in P-band (240–380 MHz). P-band is needed to penetrate through dense vegetation and into the root zone. The longer wavelength of P-band also increases the unwrapping interval for phase observations. These observations hold the potential for spaceborne remote sensing of root-zone soil moisture (RZSM) and snow water equivalent (SWE), two variables identified as priorities in the 2017–2027 Decadal Survey for Earth Science and Applications from Space. SNOOPI will provide in-space validation of both the P-band SoOp technique and a science instrument prototype. SNOOPI technology validation goals will be met by targeting observations within 9 km of the SMAP calibration/validation sites in the continental United States. A secondary priority is collection of continuous phase data over snow-covered regions. These goals are evaluated under constraints of a limited data budget and mission lifetime, with a launch readiness in early 2022. Updates on the development of measurement models and mission planning to support SNOOPI are provided. A ground-based station will be deployed to monitor the noncooperative sources, in order to reduce risk due to uncertainty in knowledge of the broadcast power, spectrum shape, and orbital position.

Following the launch of multiple global navigation satellite system (GNSS) reflectometry (GNSS-R) missions, the Signals of Opportunity (SoOp) method has proven to be a powerful tool for geophysical parameter retrieval for land applications such as soil moisture. Having demonstrated the feasibility of the SoOp techniques at P- and S-band, the development of SoOp measurements beyond the GNSS frequency regime is highly anticipated. The SoOp Coherent Bistatic (SCoBi) model and simulator, developed in 2017 and open-sourced in 2018, has been made available to provide multifrequency, fully polarimetric SoOp simulations for ground-based applications through the joint use of analytical wave theory and distorted Borne approximation to evaluate land contributions from multilayer dielectric profiles composed of soil moisture, vegetation, and surface roughness effects. This paper describes the advancement of SCoBi from a ground-and airborne-based model to a spaceborne model. This extension allows for fully polarimetric, complex delay-Doppler map (DDM) simulations through evaluation of the coherent superposition of electric fields emerging from a grid of oriented facets. The model generates a grid of facets by determining the geometry of contributing elements from digital elevation models, with each element providing its contribution under a flat-earth assumption. This module will enable the analysis of fully polarimetric scattering from frequencies available across the ultra-high frequency (UHF) regime.

SigNals of Opportunity: P-band Investigation (SNOOPI) will be an in-space technology demonstration of reflectometry using 240–380 MHz communications transmissions. SNOOPI will both demonstrate essential techniques for root-zone soil moisture (RZSM) and snow water equivalent (SWE) remote sensing as well as provide in-space validation of prototype instrument technology. This paper presents results from studies conducted to define key parameters of the SNOOPI mission, including orbital coverage, signal processing, and the estimated power from the non-cooperative sources.

The potentiality of Signals of Opportunity (SoOp) over land can be investigated by advanced forward and inverse modeling and simulation tools to provide viable measurements for Earth science data products over land. This research investigates various inversion techniques that can leverage SoOp sources for land-based Earth science measurements by applying them to simulated soil moisture profiles over bare- and vegetated- soils. Forward modeling is accomplished using Mississippi State University’s Signals of Opportunity Coherent Bistatic Scattering Model (SCoBi), a new, open-source electromagnetic scattering model that can determine coherent received signals at a receiving antenna through application of Maxwell’s equations at discrete scattering soil layer boundaries in conjunction with the distorted Born approximation to describe vegetation propagation and scattering. The results of the forward model are used in various inverse methods to investigate the potentiality of using multiple SoOp sources for Soil Moisture Profile (SMP) retrieval. Multiple SMPs are analyzed by SCoBi to determine the sensitivity of soil moisture variation to SoOp transmitter characteristics such as polarization and elevation angle. Simultaneously, SoOp measurements conducted at Purdue University’s Agronomy Center for Research and Education (ACRE) are used to determine the impact that changes in both physical SMPs and vegetation canopies have on the scattered SoOp. The characteristics of the scattering surfaces, vegetation, and SMPs at the ACRE facility are modeled within SCoBi to observe patterns and relationships captured in reflectivity measurements that are caused by vegetation growth periods as well as rain and drought effects manifested by changing SMPs.

SigNals of Opportunity: P-band Investigation (SNOOPI) will be the first on-orbit demonstration of remote sensing using Signals of Opportunity (SoOp) in P-band (240-380 MHz). P-band SoOp has the potential for spaceborne remote sensing of root-zone soil moisture (RZSM) and snow water equivalent (SWE), two variables identified as priorities in the 2017-2027 Decadal Survey for Earth Science and Applications from Space. P-band is needed to penetrate through dense vegetation and into the root zone. SNOOPI will provide inspace validation of both the technique of P-band SoOp and a science instrument prototype. This is a necessary risk-reduction step on the path to a science mission, which will verify important assumptions about reflected signal coherence, robustness to the RFI environment, and our ability to capture and process the reflected signal from orbit. SoOp observations will be used to estimate the complex reflection coefficient over various land surface conditions. These will be used to verify models and show that P-band SoOp can meet working requirements for future RZSM and SWE missions. The SNOOPI instrument design builds upon the heritage of a low noise front end (LNFE), developed from an airborne demonstrator, and a digital back end (DBE) evolved from the Cion, TriG and Blackjack GPS receivers. Success with SNOOPI will retire the critical risks associated with a P-band SoOp satellite instrument and exit at TRL-7. Not only would this instrument enable direct measurements of RZSM and SWE which are not presently possible, it’s size, weight, power and cost (SWaP-C) would also be orders of magnitude smaller than comparable monostatic radars due to the re-utilization of existing, powerful, anthropogenic signals.

A multilayer module is incorporated into the Signals of Opportunity (SoOp) Coherent Bistatic Scattering model (SCoBi) for determining the reflections and propagation of electric fields within a series of multilayer dielectric slabs. This module can be used in conjunction with other SCoBi components to simulate complex, bistatic simulation schemes that include features such as surface roughness, vegetation, antenna effects, and multilayer soil moisture interactions on reflected signals. This paper introduces the physics underlying the multilayer module and utilizes it to perform a simulation study of the response of SoOp-R measurements with respect to subsurface soil moisture parameters. For a frequency range of 100&ndash, 2400 MHz, it is seen that the SoOp-R response to a single dielectric slab is mostly frequency insensitive, however, the SoOp-R response to multilayer dielectric slabs will vary between frequencies. The relationship between SoOp-R reflectivity and the contributing depth is visualized, and the results show that SoOp-R measurements can display sensitivity to soil moisture below the penetration depth. By simulation of simple soil moisture profiles with different wetting and drying gradients, the dielectric contrast between layers is shown to be the greatest contributing factor to subsurface soil moisture sensitivity. Overall, it is observed that different frequencies can sense different areas of a soil moisture profile, and this behavior can enable subsurface soil moisture data products from SoOp-R observations.

Routine, repeatable radar measurements of soil moisture are expected to be achievable through the use of frequencies with penetration depths that reach the root-zone of given vegetation structures within soil. Due to the size, weight, power, cost, and legal constraints of creating spaceborne radar transmitters, the practice of reutilizing existing satellite navigation/communication systems for spaceborne radar applications is gaining attention from research communities under the title "Signal of Opportunity" (SoOp). The use of SoOp transmitters as a free source of illuminators is expected to be a viable tool for the remote sensing of soil moisture at depths below 5 centimeters. However, the returns of a radar signal can be representative of many types of soil moisture profiles, and the returned radar signals do not indicate the depth of the contained soil moisture. To this end, this paper is intended to better understand the various effects that radar parameters have on a returned radar signal given a known, simple soil moisture profile in order to help determine the feasibility of using multiple (SoOp) transmitters to determine soil moisture profiles. In order to accomplish this, the recently developed SoOp Coherent Bistatic (SCoBi) scattering model is used to determine the relative permittivity of a given soil moisture profile as well as determine the complex reflection coefficients of the incident signals upon the surface.

Root zone soil moisture (RZSM) is an essential variable in meteorology, hydrology, and agriculture. A penetration depth sufficient to sense RZSM requires frequencies below about 500 MHz (I- and P-band). Active or passive microwave sensing in these bands presents substantial technical challenges due to antenna size, radio frequency interference (RFI) and competition for spectrum. Bistatic radar using Signal of Opportunity (SoOp) (e.g. digital satellite transmitters) offers an alternative approach, through reutilizing powerful signals already occupying bands allocated for communications. Airborne experiments using 240–270 MHz sources were conducted in October 2016, followed by a campaign using 360–380 MHz from a fixed tower location in an agricultural research site during the 2017 growing season. A new campaign that will also include I-band (137 MHz) is presently being installed in advance of the 2018 season. This paper will summarize activities to support the reduction of data from these campaigns and development of soil moisture profile retrievals.

Root zone soil moisture (RZSM) is an essential variable in meteorology, hydrology, and agriculture. Current methods in passive and active microwave remote sensing at L-band (e.g. SMOS or SMAP) are limited to a sensing depth of less than 10 cm. Observing RZSM (water in the top meter of soil) will require lower frequencies (P-band), presenting significant difficulties for a spaceborne instrument, due to the required antenna size, the presence of radio-frequency interference (RFI), and competition for spectrum allocations (in the case of active radar). Bistatic radar using Signal of Opportunity (SoOp) (e.g. digital satellite transmitters) offers the possibility of remote sensing using powerful signals already occupying bands allocated for communications. This paper will present early results from the first airborne campaign to study P-band reflectometry for soil moisture, conducted in Oklahoma between October 17–26, 2016. A geosynchronous communication satellite, transmitting a 25 KHz data signal on a 260.375 MHz carrier was uses at the signal source. Preliminary assessment of the data showed high reflectivity over a lake and consistent results between subsequent overflights of the watershed. Recently, a tower experiment has started using a 20 MHz wide signal centered at 370 MHz. Linearly polarized measurements were made over bare soil between 25-May-2017 and 8-June-2017 observing a strong reflected signal. Corn is being planted on the field and measurements will be made throughout the growing season.

Initial results from the first airborne campaign to evaluate P-band reflectometry for soil moisture remote sensing are presented. P-band radiation has a penetration depth of 10–20 cm, compared to around 5 cm for L-band. This offers the possibility of measuring Root-Zone Soil Moisture (RZSM), a capability that does not presently exist in spaceborne remote sensing. Signals of Opportunity Airborne Demonstrator (SoOp-AD) is a brassboard P-band reflectometry demonstration instrument, developed under the NASA Instrument Incubator Program (IIP-13). Soil reflectivity is estimated from the cross-correlation of direct and reflected signals from a geostationary communication satellite. SoOp-AD will demonstrate key technological advancements on the roadmap to a spaceborne instrument, including an FPGA-based correlator array and “smart antenna” nullsteering in the post-processing stage. The first airborne tests of SoOp-AD were conducted around the ARS Micronet in Little Washita, OK. Initial results confirm the assumption of coherent scattering, show the water-land transition over Lake Ellsworth, and present reasonable values for reflectivity over the instrumented area.

Low frequency observations are desired for soil moisture and biomass remote sensing. Long wavelengths are needed to penetrate vegetation and Earth's land surface. In addition to the technical challenges of developing Earth observing spaceflight instruments operating at low frequencies, the radio frequency spectrum allocated to remote sensing is limited. Signal-of-opportunity remote sensing offers the chance to use existing signals exploiting their allocated spectrum to make Earth science measurements. We have made observations of the radio frequency environment around 240–270 MHz and will discuss properties of desired and undesired signals.

Bipolar vessel sealing has been successfully introduced in a variety of procedures like prostatectomy, hysterectomy, and nephrectomy. In this study, we evaluated a new sealing mode—the thermoSEAL® mode (TSM)—operated with the VIO3 generator in an ex vivo and in vivo animal study and compared the results with the commercially available BiClamp mode (BCM), operated with the VIO300D generator. Two different instruments were used in combination with both modes, BiCision® and BiClamp® 201T (Erbe Elektromedizin GmbH). In the ex vivo experiment, the sealing of renal arteries was evaluated using both instruments and modes. For the in vivo study, different types of arteries and veins were sealed using both modes and instruments in a side-by-side comparison for acute complications in a total of four animals. Mean burst pressure was in all cases significantly above 360 mmHg (p 90%) were noted for both instruments and modes. While both modes used with two different instruments reveal high safety characterized by a high burst pressure, low thermal damage (ex vivo) zones, and high sealing rates (in vivo), the thermoSEAL® mode convinces by its fast sealing speed probably helping to reduce operation time.

Intense Langmuir-probe measurements were carried out in the toroidal low-temperature plasma of the torsatron TJ-K in order to investigate the origin and dynamics of intermittent transport events, so-called blobs, at the transition from closed to open field lines. The statistical properties of the fluctuations at the plasma boundary agree with observations made in fusion edge plasmas. Blobs were found to be generated locally through a change in turbulence drive across the separatrix. The non-linear spectral energy transfer from small-scale fluctuations into large-scale flows was measured with a 128-probe array. The results point to the transfer being a key loss channel for turbulence energy leading to a reduction in turbulent transport. Earlier observations [M.A. Pedrosa et al., Phys. Rev. Lett. 100, 215003 (2008)] of enhanced long-range correlations in the plasma potential through externally induced shear flows in TJ-II stellarator were verified. The newly measured correlation of zonal vorticity and Reynolds stress at induced flow shear indicates an enhancement of zonal-flow drive (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal. New treatment options for T2D will likely include fixed dose combinations with metformin, which may require preclinical combination toxicology studies. To date, there are few published reports evaluating the toxicity of metformin alone to aid in the design of these studies. Therefore, to understand the toxicity of metformin alone, Crl:CD(SD) rats were administered metformin at 0, 200, 600, 900 or 1200 mg/kg/day by oral gavage for 13 weeks. Administration of > or =900 mg/kg/day resulted in moribundity/mortality and clinical signs of toxicity. Other adverse findings included increased incidence of minimal necrosis with minimal to slight inflammation of the parotid salivary gland for males given 1200 mg/kg/day, body weight loss and clinical signs in rats given > or =600 mg/kg/day. Metformin was also associated with evidence of minimal metabolic acidosis (increased serum lactate and beta-hydroxybutyric acid and decreased serum bicarbonate and urine pH) at doses > or =600 mg/kg/day. There were no significant sex differences in mean AUC(0-24) or C(max) nor were there significant differences in mean AUC(0-24) or C(max) following repeated dosing compared to a single dose. The no observable adverse effect level (NOAEL) was 200 mg/kg/day (mean AUC(0-24)=41.1 microg h/mL; mean C(max)=10.3 microg/mL based on gender average week 13 values). These effects should be taken into consideration when assessing potential toxicities of metformin in fixed dose combinations.

Zusammenfassung: Asteroid Bodies an Candida-Zellen sind haufig in Vaginalmaterial von Kolpitis-Patientinnen zu beobachten. Die Asteroid Bodies stellen die morphologisch extreme Auspragung des umfassenderen Phanomens der Bildung von Antigen-Antikorper-Prazipitaten auf der Ausenseite der Pilzzellwand in der chronischen Infektsituation dar. Derartige Zellwandauflagen sind pathognomonisch. Das Antigenmaterial ist im Uberschus vorhanden. Antigen-Antikorper-Komplexe werden in das Infektionsmilieu in betrachtlichen Quantitaten freigesetzt. Bei der selten beobachteten Phagocytose der Pilzzellen geht die massive Antigen-Antikorper-Schicht der Zellwandoberflache verloren. Summary: Candida asteroid bodies can often be observed in vaginal scrapings of colpitis patients. Asteroid bodies are the morphologically extreme expression of the more common phenomenon of building up of antigen-antibody precipitates on the external surface of fungal cells in chronic infections. Such external cell wall layers are pathognomonic. Antigenic material is present in excess. Antigen-antibody complexes are liberated into the site of infection in remarkable quantities. The external cell wall layer is liberated from the Candida cells during phagocytosis – a process which can only rarely be observed.

Bipolar electrothermal vessel sealing is a widely used method for the sealing of blood vessels and tissue of up to several millimeters diameter. Despite their wide-spread usage, instruments and generator modes are often traditionally developed and enhanced. A systematic investigation of the thermofusion process and the subsequent derivation of new model-based control strategies have the potential to improve the vessel sealing process and reduce unwanted side-effects. Based on a previously developed mathematical model of bipolar vessel sealing, optimization based control strategies are developed that could possibly reduce the thermal damage to the lateral tissue. Assuming that it is sufficient to ensure a certain tissue temperature for successful thermofusion, it is shown that the lateral damage could be significantly reduced by optimizing the generator voltage. Furthermore it is shown, that an optimized voltage trajectory may still reduce the lateral damage to some extent if it is assumed that tissue desiccation is required. Additionally, optimally pulsed voltage strategies are presented and compared to currently employed typical generator modes. The results illustrate that optimized control strategies can potentially reduce the thermal damage to the lateral tissue and thus make bipolar vessel sealing more suitable for surgical procedures in the vicinity of sensitive structures, particularly nerves.

Radiofrequency-induced thermofusion is a frequently used electrosurgical procedure for the sealing of blood vessels. A disadvantage of vessel sealing instruments is that the generated thermal energy spreads to the surrounding tissue and may irreversibly damage it. This is particularly problematic when operating close to sensitive structures such as nerves. Given their advantages, there is nonetheless a lot of interest in using bipolar vessel sealing for surgical procedures. To select instruments that may be safely used in such cases, it is important to reliably quantify the thermal spread to the surrounding tissue. Mathematical models can help to evaluate the transient behavior, that is the evolution of the thermal spread over time, more precisely. A finite element model allows for a detailed analysis of inhomogeneities in the spatial temperature distribution. As a first step towards a finite model of the bipolar vessel sealing process, a model of the coagulation of chicken egg white is presented here. Egg white has thermal and electrical properties that are very similar to tissue, making it suitable as a substitute for the analysis of the coagulation process. It has the additional advantage, that the spatial and temporal evolution of the thermal spread can be visually gauged. The presented model describes the experimentally observed spatial temperature distribution, the shape of the coagulated egg white, and the formation of hotspots. Furthermore, it is shown that the model can correctly predict the shape of the coagulated egg white in further experiments.

Fischer 344 rats (60/sex/group) were given daily subcutaneou s injections of recombinant human parathyroi d hormone (PTH)(1-34) for 2 years at doses of 0, 5, 30, or 75 μg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects of once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH(1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75- μg/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.

Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Thirteen-week gavage studies were conducted by administering the drug in deionized water to F344/N rats and B6C3F1 mice once daily, 5 days per week for up to 13 consecutive weeks, at doses of 0, 63, 125, 250, 500, and 1,000 mg/kg body weight. No significant drug-related effects were observed in body weight, survival, clinical, and necropsy results. Significant organ weight increases were seen in the liver, lungs, and spleen of both species and the kidneys of rats, mainly in groups treated with 250 mg/kg/day and above. Hematological analysis indicated increases for both species in the white blood cell and lymphocyte counts. Sites of toxicity identified histopathologically were the rectum, liver, mesenteric and mandibular lymph nodes (both sexes), spleen (mice only), and lungs and kidneys (rats only). Lesions consisted mainly of infiltration into multiple tissues of vacuolated histiocytes, which, by histochemical investigation, indicated the presence of neutral and acidic mucins and lipidic material within the vacuoles. Transmission electron microscopy identified these vacuoles as lysosomal structures that exhibited a variety of contents. On the basis of our findings, we propose that Elmiron was absorbed through the focally disrupted rectal mucosa, was deposited in the lamina propria, accumulated within macrophages, and then was distributed by these cells or as a free chemical via the lymphatics and blood, to the various organ sites manifesting histiocytic infi ltration. The cytoplasmic membrane-bound structures within macrophages were lysosomes containing membranous material of cellular origin and, perhaps, remnants of the deposited test material, Elmiron.

Bipolar radiofrequency-induced thermofusion has become a widely accepted method successfully used in open and particularly in minimally-invasive surgery for the sealing of blood vessels and tissue of up to several millimeters diameter. Despite its wide-spread application, the thermofusion process itself is not well understood on a quantitative and dynamic level, and manufacturers largely rely on trial-and-error methods to improve existing instruments. To predict the effect of alternative generator control strategies and to allow for a more systematic approach to improve thermofusion instruments, a mathematical model of the thermofusion process is developed. The system equations describe the spatial and temporal evolution of the tissue temperature due to Joule heating and heat transfer, and the loss of tissue water due to vaporization. The resulting effects on the tissue properties, most importantly the electrical resistivity, heat capacity and thermal conductivity, are considered as well. Experimental results indicate that the extent of the lateral thermal damage is directly affected by Joule heating of the lateral tissue. The experimental findings are supported by simulation results using the proposed mathematical model of thermofusion.

Whether biliary proliferative lesions in nonclinical species are predictive of potential hepatotoxicity in humans depends, at least in part, on the nature and severity of such changes in the nonclinical species. We reviewed published literature (clinical and nonclinical) and experimental data from rat toxicology studies conducted by GlaxoSmithKline and the National Institute of Environmental Health Sciences’ National Toxicology Program in an effort to better characterize the relative risk of hepatobiliary effects in humans. Available evidence supports the interpretation that minimal “typical” appearing bile duct hyperplasia limited to the portal triads may be considered non-adverse in the rat and is of little to no concern to humans. The toxicological relevance of mild to moderate “typical” hyperplasia is less certain, and may be considered adverse in the rat and potentially pose a risk for humans, particularly if accompanied by evidence of hepatobiliary injury or functional compromise. In addition, any proliferative lesion that includes atypical or dysplastic epithelial changes, oval cell proliferation, and/or significant extension beyond the portal tracts is considered more ominous and may be considered adverse in the rat.

The three-dimensional structure of drift-wave turbulence and turbulent transport is investigated in plasmas of the stellarator experiment TJ-K. By means of two poloidal Langmuir probe arrays placed at different toroidal positions, density and potential fluctuations are recorded simultaneously at 128 positions on a single flux surface. From these data, the spatial drift-wave turbulence pattern including perpendicular and parallel structure sizes are obtained using a cross-correlation technique. A comparison with the magnetic field structure indicates an initially perfect alignment of turbulent structures with magnetic field lines. Passing over regions with different field-line pitches according to the local variation of the rotational transform, however, results in a measured displacement of turbulent structures with respect to the field lines during their radial propagation. A reduction in the perpendicular correlation lengths in regions of high absolute values of local magnetic shear is found. Prominent and poloidally narrow turbulent transport maxima are measured at different toroidal positions. They are connected by the magnetic field lines and located in regions of negative normal curvature. The poloidal propagation pattern of turbulent structures and the exact position of the transport maximum depend on the magnetic field direction.

The development of the electron density profile and its dependences after the L–H transition have been investigated. Only electron cyclotron resonance heated H-modes have been analysed to exclude core particle fuelling. While the density gradient in the edge transport barrier increases significantly after the L–H transition, the pedestal top temperature rises continuously with the applied heating power and shows no pronounced change at the transition. The H-mode density saturates at a level which correlates with the neutral gas density in the divertor prior to the L–H transition. Although the density build-up varies with the available deuterium inventory, the initial increase in the edge density gradient is similar. This has been observed independent of the L-mode plasma collisionality (ν * ≈ 2.8–5.5). The analysis of electron density and temperature profiles reveals that L–H and H–L transitions occur at similar pedestal top pressures, but the pedestal top densities are always higher at the time of the H–L back transition.

The ASDEX Upgrade programme is directed towards physics input to critical elements of the ITER design and the preparation of ITER operation, as well as addressing physics issues for a future DEMO design. After the finalization of the tungsten coating of the plasma facing components, the re-availability of all flywheel-generators allowed high-power operation with up to 20 MW heating power at I p up to 1.2 MA. Implementation of alternative ECRH schemes (140 GHz O2- and X3-mode) facilitated central heating above n e = 1.2 × 1020 m−3 and low q 95 operation at B t = 1.8 T. Central O2-mode heating was successfully used in high P/R discharges with 20 MW total heating power and divertor load control with nitrogen seeding. Improved energy confinement is obtained with nitrogen seeding both for type-I and type-III ELMy conditions. The main contributor is increased plasma temperature, no significant changes in the density profile have been observed. This behaviour may be explained by higher pedestal temperatures caused by ion dilution in combination with a pressure limited pedestal and hollow nitrogen profiles. Core particle transport simulations with gyrokinetic calculations have been benchmarked by dedicated discharges using variations of the ECRH deposition location. The reaction of normalized electron density gradients to variations of temperature gradients and the T e/T i ratio could be well reproduced. Doppler reflectometry studies at the L–H transition allowed the disentanglement of the interplay between the oscillatory geodesic acoustic modes, turbulent fluctuations and the mean equilibrium E × B flow in the edge negative E r well region just inside the separatrix. Improved pedestal diagnostics revealed also a refined picture of the pedestal transport in the fully developed H-mode type-I ELM cycle. Impurity ion transport turned out to be neoclassical in between ELMs. Electron and energy transport remain anomalous, but exhibit different recovery time scales after an ELM. After recovery of the pre-ELM profiles, strong fluctuations develop in the gradients of n e and T e. The occurrence of the next ELM cannot be explained by the local current diffusion time scale, since this turns out to be too short. Fast ion losses induced by shear Alfvén eigenmodes have been investigated by time-resolved energy and pitch angle measurements. This allowed the separation of the convective and diffusive loss mechanisms.

This addendum applies to papers authored by contributors from the Axially Symmetric Divertor Experiment (ASDEX) Upgrade Team published in Review of Scientific Instruments. This addendum provides the full list of ASDEX Upgrade Team contributors and their affiliations.

Soluble glucan, an immunomodulator, and Walter Reed (WR)-2721, a radioprotectant, increase postirradiation survival when administered before and after exposure, respectively. Combined, these agents act synergistically through WR-2721's ability to spare hematopoietic stem/progenitor cells from radiation injury and glucan's ability to subsequently stimulate spared cells to proliferate. In this study, the histopathologic effects of WR-2721 (200 mg/kg, ip) and glucan (250 mg/kg, iv), at doses capable of increasing survival in lethally irradiated mice, were evaluated in unirradiated and irradiated female C3H/HeN mice. After treatment, whole body weights and wet organ weights of liver, spleen, and kidney, as well as gross and histologic changes in these and other tissues, were monitored on Days 1, 4, 7, 11, 15, 21, and 28. Morphometric studies of splenic white and red pulps were also performed. Soluble glucan, with or without WR-2721, in unirradiated groups, was associated with splenomegaly, transient morphometrically determined perturbations of white and red pulp areas, and histologic alterations of white pulp. In irradiated mice, splenic weight loss was initially dampened in glucan groups and accompanied by morphologic and histologic changes similar to those seen in unirradiated counterparts. The subsequent rebound of splenic parameters in irradiated mice was limited to WR-2721-treated mice and was associated with hematopoietic reconstitution. Glucan, with or without WR-2721, in unirradiated groups was associated with transient hepatomegaly and associated histologic changes. Similar changes in irradiated animals were seen only in the combined treatment group.

Turbulent transport at the transition from closed to open field lines has been investigated in the stellarator experiment TJ-K. It is found that drift-wave turbulence in the confined region is responsible for the generation of intermittent structures (so-called blobs) in the unconfined region. There the character of turbulence changes and a decoupling of density and potential fluctuations is observed. The poloidal propagation of the intermittent events can be understood in the framework of background flows caused by gradients in the equilibrium plasma pressure and potential profiles.

Two benzodiazepine compounds, midazolam and diazepam, were administered as adjunctive treatment to soman-exposed rhesus monkeys to evaluate their effects on acute soman intoxication. Monkeys were pretreated orally with pyridostigmine, exposed to soman, and treated i.m. with atropine, pralidoxime chloride (2-PAM), and with midazolam, diazepam or sterile water (control). All monkeys that received the benzodiazepines recovered sooner and exhibited no convulsions. Neuronal degenerative and necrotic lesions were decreased or eliminated in the entorhinal cortex, caudate nucleus, and hippocampus of those animals that received benzodiazepine therapy. These findings support the continued evaluation of drugs with anticonvulsant activity as standard adjunct therapy for soman intoxication.

In all species previously studied, inhalation of toxic doses of phosgene results in varying degrees of pulmonary edema, often after a symptom-free period. The sheep is an anatomically unique animal in which to study the development of pulmonary edema by monitoring the effluent from a catheterized caudal mediastinal lymph node. In addition, the size of the sheep is sufficient to permit placement of vascular monitoring devices and withdrawal of multiple biologic samples for analyses. In spite of this, there appear to be no published reports of sheep having ever been exposed to phosgene. This study was undertaken as a dose-ranging study, in order to permit subsequent studies of phosgene inhalation toxicity in a sheep lung lymph preparation. Accordingly, the LCt50 (24 hours) was estimated to be 13,300 mg-min/m3 (3325 ppm) by “up and down” subsequent dosage selection and moving average interpolation methods.

Inhalation of toxic doses of phosgene results in varying degrees of pulmonary edema, often after a symptom-free period. The sheep is an anatomically suitable animal in which to study the development of pulmonary edema during that symptom-free period. Five sheep were used in this study, and they were instrumented so as to provide simultaneous information on pulmonary vascular and interstitial fluid dynamics. Through a thoracotomy, the efferent duct of the caudal mediastinal lymph node was cannulated to monitor pulmonary lymph flow. The sheep were also instrumented with a carotid arterial catheter, a pulmonary artery catheter with thermistor, and a left atrial catheter to monitor systemic and pulmonary hemodynamics. After a 5– to 7-day recovery period, the sheep were given a 10-min nose and mouth exposure to 2.0–2.5 g/m3 of phosgene. Over the next 4 h, there was a two to threefold increase in pulmonary lymph flow, accompanied by a small but significant increase in mean pulmonary microvascular pressu...

ASDEX Upgrade has recently finished its transition towards an all-W divertor tokamak, by the exchange of the last remaining graphite tiles to W-coated ones. The plasma start-up was performed without prior boronization. It was found that the large He content in the plasma, resulting from DC glow discharges for conditioning, leads to a confinement reduction. After the change to D glow for inter-shot conditioning, the He content quickly dropped and, in parallel, the usual H-Mode confinement with H factors close to one was achieved. After the initial conditioning phase, oxygen concentrations similar to that in previous campaigns with boronizations could be achieved. Despite the removal of all macroscopic carbon sources, no strong change in C influxes and C content could be observed so far. The W concentrations are similar to the ones measured previously in discharges with old boronization and only partial coverage of the surfaces with W. Concomitantly it is found that although the W erosion flux in the divertor is larger than the W sources in the main chamber in most of the scenarios, it plays only a minor role for the W content in the main plasma. For large antenna distances and strong gas puffing, ICRH power coupling could be optimized to reduce the W influxes. This allowed a similar increase of stored energy as yielded with comparable beam power. However, a strong increase of radiated power and a loss of H-Mode was observed for conditions with high temperature edge plasma close to the antennas. The use of ECRH allowed keeping the central peaking of the W concentration low and even phases of improved H-modes have already been achieved.

International audience; This paper summarizes recent experimental characterization of radio frequency (RF)-induced scrape-off layer (SOL) modifications in ASDEX-Upgrade (AUG), JET and Tore Supra (TS). Geometrical aspects are emphasized: complex SOL patterns are observed by several indicators visualized in one or two dimensions transverse to the magnetic field lines. Results are ascribed to inhomogeneous RF-induced SOL biasing around powered ion cyclotron range of frequencies antennas and associated E × B 0 density convection (D'Ippolito et al 1993 Phys. Fluids B 5 3603). Within a simple RF sheath model (Perkins 1989 Nucl. Fusion 29 583), the shape of convective cells on TS can be interpreted in terms of RF-sheath generation by parallel RF currents. Some lessons are drawn for future machines.

Studies conducted under the auspices of International Life Sciences Institute (ILSI) have suggested that an alternative mouse carcinogenicity study may be substituted for the traditional 2-year mouse bioassay typically conducted to support the development of drug candidates. The purpose of this study was to characterize the carcinogenic potential of N-methyl- N-nitrosourea (MNU), a DNA alkylating agent, in p53+ /– knockout mice to determine its suitability as a positive control agent in an alternative carcinogenicity model. p53+ /– knockout mice were administered a single oral dose of 90 mg/kg and maintained for up to 13 weeks prior to evaluation of neoplasms. Treatment was generally well tolerated; however, 4 of 30 mice died between the days of 75 and 92 due to neoplasms. MNU-related macroscopic observations included enlargement of the thymus, spleen, mandibular and mesenteric lymph nodes; and pale liver, heart, kidney, and bone marrow, which correlated with the diagnosis of lymphoma of the hematopoietic system, noted in the thymus of all affected animals and in the spleen, liver, lungs, and kidneys of some animals. Other treatment-related single neoplasms included a squamous-cell carcinoma in the nonglandular stomach and leiomyosarcoma in the glandular stomach. Non-neoplastic proliferative lesions included acanthosis and hyperkeratosis in the nonglandular stomach, focal papillary hyperplasia of the nonglandular stomach, glandular hyperplasia of the stomach, and adenomatous hyperplasia of the duodenum or ileum. The increased incidence of neoplastic and proliferative changes in MNU-treated mice suggests MNU could serve as a positive control in alternative carcinogenicity studies conducted in p53+ /– knockout mice.

We describe and discuss microscopic findings in the brown adipose tissue (BAT) blood vessels of Han Wistar rats treated with GI262570X, a peroxisome proliferator-activated receptor- γ agonist (PPAR- γ agonist) by oral gavage for 28 days, 13 weeks, 27 weeks, and 2 years. Review of these studies revealed a consistent vascular change, consisting of multifocal fatty infiltration in the BAT of treated rats. A similar vascular change was not seen in other vessels or organs. Microscopically, fatty infiltration was characterized primarily by round, clear vacuoles within the tunica media and/or tunica adventitia of small and medium-sized arteries and arterioles. Occasionally, these vacuoles had peripherally located nuclei and morphologically resembled adipocytes, suggesting a well-characterized PPAR effect (ie, differentiation of stem cells or preadipocytes into mature adipocytes). However, administration of GI262570X up to 2 years failed to induce more severe or progressive lesions in the blood vessels of rat BAT and, in particular, did not result in induction of any atherosclerotic-like lesions or foam cell infiltration. At the longer exposure, there was an apparent reduction of severity and/or incidence, indicating a possible adaptive response. These results suggest that the possibility of generating atherosclerotic-like lesions through prolonged treatment of GI262570X (PPAR- γ agonist) is highly unlikely in rats.

Blob properties are studied in the scrape-off layer of the tokamak ASDEX Upgrade with a fast camera. The gas-puff imaging technique is used to investigate the detection rate as well as the blob size and velocity scaling. The experiments were performed in L- and H-mode phases of the same discharges to study the change in blob properties after the L-H transition. In both regimes the detection rate is of the order of a few thousand blobs per second, which is compatible with the picture of blob generation by edge micro instabilities. The blob size increases in H-mode, while the radial velocity decreases slightly. The changes are, however, not indicating a drastic change in the blob dynamics in both phases. The experimentally found blob properties were compared to predictions from a novel blob model including effects due to a finite ion temperature, which should be more appropriate for the conditions in the SOL of fusion plasmas.

Microscopic turbulence properties in the edge of toroidally confined fusion plasmas are studied by comparative analysis of experimental data from seven devices, collected in an international edge turbulence database. The database contains Langmuir probe measurements of fluctuations in the floating potential and ion saturation current across the last closed flux surface. They are used to address statistical properties and particle transport. Universal features of plasma edge turbulence such as an increase in skewness across the scrape-off layer (SOL) as footprints of density blobs are recovered in all devices. Analysis of the correlation lengths and times reveals power law scaling relations with macroscopic drift-wave parameters, albeit weaker than would be expected for drift-wave turbulence. As a result, the turbulent diffusivity scales with the inverse of the magnetic field strength, which is closer to Bohm-like scaling than to gyro-Bohm scaling. Nearly identical scaling relations are determined in the confined plasma edge and the SOL, pointing to a strong connection between drift-wave turbulence in the edge and blobs in the SOL. The contributions of blobs and holes (negative density spikes) to the radial particle transport are analyzed qualitatively with a conditional averaging approach. Blobs are connected to outward transport in the SOL of all devices whereas holes exhibit no uniform propagation pattern.

Diet is an important variable in rodent toxicology and carcinogenicity studies. Several diet models are now available for selection in rodent toxicology studies. Abundant data have clearly established a signiŽ cant correlation between average food (calorie) consumption, nutrient composition of the diet, adult body weight, the onset and incidences of speciŽ ed pathological endpoints, and survival (2, 3). Ad libitum feeding of common diets to rodents on long-term studies results in overeating, excessive caloric intake, higher body weights, decreased activity patterns, and earlier onset and higher incidences of some spontaneous degenerative diseases (nephropathy and cardiomyopathy), neoplasia (eg, pituitary and mammary tumors), and reduced survival. Reduced survival of the control animals in 2-year studies, often signiŽ cantly less than 50%, has heightened the industry’s awareness of these diet-related issues (2). The overeating problems in long-term rodent studies have been addressed by two different approaches: dietary modiŽ cation (change the nutrient contents of the diet) and dietary restriction (control the amount of food the animals can eat). Some of the early studies using dietary modiŽ cation were inconclusive, but more recently scientists at the National Toxicology Program and others have shown that control of the formulation of an ad libitum, nonpuriŽ ed diet source for laboratory animals (diet modiŽ cation) has a signiŽ cant effect on survival and the incidence and severity of several dietary and possibly age-associated pathology. More speciŽ cally, a diet (NTP-2000) with lower protein and higher fat and Ž ber ( 15% protein, 7–8.5% fat, and 9–14% crude Ž ber), when fed ad libitum to F344 rats, enhanced survival and reduced the incidence and/or severity of several common age-related

2-Cyclohexene-1-one (CHX) is a cyclic alpha,beta-unsaturated ketone with broad human exposure. CHX is an environmental pollutant and is present in tobacco smoke and in soft drinks sweetened with cyclamate. Interest in the toxicity of this class of compounds is due to their structural similarity to the cytotoxin acrolein. In a pilot study, rats and mice were exposed to 0, 20, 40, or 80 ppm CHX for 6 h/day. The study was terminated after 4 days due to acute toxicity in the high-dose groups. In a subsequent 14-day study, mice and rats were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day. All animals survived exposure until terminal sacrifice. Body weights were not significantly different from controls after 14 days of exposure. Liver/body weights were increased in male and female mice exposed to 5 and 10 ppm, and in male and female rats exposed to 10 ppm CHX. Ninety-day toxicity studies were conducted to provide data required to design chronic toxicity and carcinogenicity studies of CHX if it is determined such studies are necessary. Groups of 10 male and female F-344 rats and B6C3F1 mice were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day for 13 wk. All animals survived until sacrifice. Body weights were not significantly different from controls after 13 wk of exposure. Liver weights were increased in male and female mice exposed to 5 and 10 ppm and in male and female rats exposed to 10 ppm CHX. No adverse effects on bone-marrow micronuclei, sperm motility, or vaginal cytology were observed. Microscopic lesions included hyperplasia, and squamous metaplasia in the nasal cavity in rats and mice of both sexes at all doses. Nasal-cavity erosion and suppurative inflammation also occurred in high-dose mice. Larynx and lung were not affected in either sex or species. Dose-related hepatic centrilobular cytoplasmic vacuolation was seen in male rats only. These data suggest that CHX acts as an alkylating agent primarily producing toxicity at the exposure site.

Blob properties are studied in the scrape-off layer of the stellarator TJ-K. Langmuir probes and a fast camera are used to investigate the generation rate as well as the blob size and velocity scaling. Discharges with different ion species and magnetic field strengths provide access to a large range of plasma parameters. It was found that almost every large amplitude drift wave in the edge of the confined plasma triggers blob generation in the scrape-off layer, which implies that the birth rate of blobs is determined by the turbulence in the edge. Furthermore, the cross-field size of the blobs seems to correlate with the size of the generating drift waves. Since the observed radial propagation velocity of the blobs is well described by a size dependent blob velocity model, the size coupling between the drift waves and the blobs also has an impact on the blob velocities. Thus, the presented results imply that the dynamics in the edge have a large influence on the blob properties in the scrape-off layer.

Radiation with doses >7.5 Gy damages the canine intestinal mucosa, and pretreatment with WR2721 reduces this damage. However, the effects of radiation and of WR2721 onin vivo intestinal transport are unclear. Therefore, we determined canine survival, intestinal transport, and mucosal histology following unilateral abdominal irradiation. Isoperistaltic ileostomies were prepared in 23 dogs under general anesthesia and aseptic conditions. After a three-week recovery period, animals were given either placebo or WR2721, 150 mg/kg intravenously, 30 min prior to 10 Gy cobalt-60 abdominal irradiation. Ileal transport and histology were determined in both groups before exposure and one, four, and seven days after irradiation. Seven-day survival was significantly improved by pretreatment with WR2721 (91% vs 33%,P

Analyses of non-linear interactions in drift-wave turbulence were carried out in wavenumber space on experimental data obtained from multi-probe measurements in the toroidally confined plasma of the stellarator TJ-K. Recent results are reported. The inverse cascade of energy from small to large scales as typical for two-dimensional turbulence is verified. The transfer in k space is found to be governed by non-local processes. The same way, large-scale zonal flows (ZFs) are found to tap energy from small-scale turbulence, as consistent with the vortex-thinning mechanism. An enhancement of the correlation between ZF shear and Reynolds stress as a source of ZF energy is observed, when strong background shear flows are imposed, which comes along with increased long-range correlations.

The postmortem chemical fixation of brain routinely results in some degree of artifactual tissue changes which are difficult to differentiate from preexisting pathology. More specifically, by light microscopy of hematoxylin and eosin-stained sections, hyperchromatic, purple neurons are frequently seen in completely normal brains. Preexisting early neuronal degeneration, however, may result in similar staining characteristics. Thus, a fixation technique which minimizes the occurrence of these dark neurons and other artifacts would be beneficial in the interpretation of subtle brain pathology. This study was conducted to evaluate and compare several methods of tissue fixation to determine which technique produced the most artifact-free brain tissues. Rats in 9 groups of 10 each were euthanatized and their brains immediately fixed by intravascular perfusion or immersion in neutral buffered formalin (NBF) or Karnovsky's in Locke's buffer (KLB).

To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.

To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.