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We examined Henslow’s Sparrow (Centronyx henslowii) response to prescribed fire at 32 grasslands at Big Oaks National Wildlife Refuge in southeastern Indiana from 1999 to 2009. We burned grasslands in the spring between 1999 and 2007 and monitored Henslow’s Sparrows for up to 4 yr after treatment. We used linear mixed models to analyze our data. Henslow’s Sparrow counts were correlated with time since prescribed fire and grassland size. The estimated changes in mean Henslow’s Sparrow density relative to pre-burn densities were –0.19, 1.15, 0.74, and –0.68 birds ha –1 for 1 to 4 breeding seasons after a spring burn, respectively. We found that Henslow’s Sparrows preferred larger grasslands both during the first breeding season after prescribed fire, when vegetation was presumed to possess less litter and structural density, and during the fourth breeding season after fire, when vegetation was presumed to be a more ideal composition, but preferred smaller grasslands in the interim. Thus, grassland size shapes the magnitude of Henslow’s Sparrow population response to fire, with populations in smaller grasslands experiencing greater amplitude changes. Larger grasslands might provide more habitat diversity following prescribed fire, attenuating population change. On average, Henslow’s Sparrows responded positively to prescribed fire in a network of grasslands and cumulative net change in densities were highest three breeding seasons after a burn suggesting that maintaining this burn frequency would be beneficial to Henslow’s Sparrow abundance.

The behavior of fission gases in molten fuel salt reactors governs activity transport from the reactor and can also affect the performance of the reactor itself. The gas solubility can be described thermodynamically by Henry’s law. However, the coupling of the condensed and gas phases depends on the interfacial area, which is difficult to measure or even to estimate. Surfaces of materials in the reactor will include disperse phases in the salt and porosity within the structural materials, covering a range of compositions and sizes. These attributes can affect measurements of fundamental properties such as gas solubility. Methods to obtain gas solubility, surface tension, interfacial energies, and bubble gas transport are reviewed. Recent data from manometric experiments are interpreted based on xenon sorption onto salt-wetted quartz.

The need to predict acoustic propagation through marine sediments that contain gas bubbles has become increasingly important for civil engineering and climate studies. There are relatively few in situ acoustic wave propagation studies of muddy intertidal sediments, in which bubbles of biogenic gas (generally methane, a potent greenhouse gas) are commonly found. We used a single experimental rig to conduct two in situ intertidal acoustical experiments to improve understanding of acoustic remote sensing of gassy sediments, eventually including gas bubble size distributions. In the first experiment, we measured sediment sound speed and attenuation between four aligned hydrophones for a quasi-plane wave propagating along the array. The second experiment involved a focused insonified sediment volume created by two transducers emitting coincident sound beams at different frequencies that generated bubble-mediated acoustic signals at combination frequencies. The results from sediment core analyses, and comparison of in situ acoustic velocity and attenuation values with those of water-saturated sediments, together provide ample evidence for the presence of in situ gas bubbles in the insonified volumes of sediments. These datasets are suitable for linear and non-linear inversion studies that estimate in situ greenhouse gas bubble populations, needed for future acoustical remote sensing applications.

In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others. We found that Cav-1 expression plays a critical role in both HSA uptake and response to albumin-based chemotherapies. As such, developing a novel albumin-based chemotherapy that is more selective for tumors with high Cav-1 expression or high levels of caveolar-endocytosis could have significant implications in biomarker-directed therapy. Herein, we present the development of a novel and effective HSA-SN-38 conjugate (SSH20). We find that SSH20 uptake decreases significantly by immunofluorescence assays and western blotting after silencing of Cav-1 expression through RNA interference. Decreased drug sensitivity occurs in Cav-1-depleted cells using cytotoxicity assays. Importantly, we find significantly reduced sensitivity to SSH20 in Cav-1-silenced tumors compared to Cav-1-expressing tumors in vivo. Notably, we show that SSH20 is significantly more potent than irinotecan in vitro and in vivo. Together, we have developed a novel HSA-conjugated chemotherapy that is potent, effective, safe, and demonstrates improved efficacy in high Cav-1-expressing tumors., Graphical abstract, In this study, the authors have developed and established a novel albumin-SN-38 conjugate (SSH20) and tested it in pre-clinical models of pancreatic and lung cancer. The advantageous properties inherent to SN-38 conjugation to albumin and targeted delivery make SSH20 an attractive candidate for further preclinical and potential clinical study.

In recent years, the emergence of targeted covalent inhibitors which bind to the G12C mutant of KRAS have offered a solution to this previously intractable target. Inhibitors of KRASG12C tend to be structurally complex, displaying features such as atropisomerism, chiral centres and a reactive covalent warhead. Such molecules result in lengthy and challenging syntheses, and as a consequence critical decisions need to be made at the design level to maximise the chances of success. Here we take a retrospective look into how computational chemistry can help guide and prioritise medicinal chemistry efforts in the context of a series of conformationally restricted tetracyclic quinolines.

Molten chloride salts (including MgCl2, KCl, NaCl, and ZnCl2) are being considered for heat transfer media for renewable (solar) and nuclear power generators, as fuel carrier for nuclear reactors, and as thermal energy storage media. Impurities such as oxygen, hydroxides, moisture, and sulfur are known to negatively influence the corrosion of materials in contact with the salt (e.g., structural metals). Commercially available chloride salts come with a range of impurities. Before using the chloride salts at high temperature, it is desirable to remove the impurities to increase the performance of the salt and reduce corrosion. In this study, we tested the use of thionyl chloride vaporized into a stream of argon to react with oxygenated impurities in a mixture of MgCl2-KCl-NaCl, removing them as HCl and SO2. The reagent was bubbled through the salt when both above and below the melting point. The reaction was followed using thermocouple data from the salt and by Fourier transform infrared (FTIR) spectroscopy on the exhaust of the reactor. The reaction kinetics were followed by comparing the peaks from SO2 product to SOCl2 reagent in the FTIR spectra. The purity of the salt was assessed at the end of the purification process by x-ray diffraction and inductively coupled plasma analysis. Although the process was effective in removing the oxygen content of the mixture, ternary compounds were formed in the process, including KNiCl3 and KMgCl3. The nickel in KNiCl3 came from the reaction between the salt and the nickel vessel. Thus, these experiments suggest that improvements to the process must be made before using SOCl2 vapors for the purification of chloride salts.

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34, 95%CI 1.27–11.38, p = 0.017) and OS (HR = 2.89, 95%CI 1.10–4.76, p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39, 95%CI 1.03–5.54, p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71, 95%CI 1.14–6.48, p = 0.025), DR (HR = 1.93, 95%CI 1.10–3.38, p = 0.022), and OS (HR = 1.97, 95%CI 1.17–3.34, p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p &lt, 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

The three-dimensional conformations adopted by a free ligand in solution impact bioactivity and physicochemical properties. Solution 1D NMR spectra inherently contain information on ligand conformational flexibility and three-dimensional shape, as well as the propensity of the free ligand to fully preorganize into the bioactive conformation. Herein we discuss some key learnings, distilled from our experience developing potent and selective synthetic macrocyclic inhibitors, including Mcl-1 clinical candidate AZD5991. Case studies have been selected from recent oncology research projects, demonstrating how 1D NMR conformational signatures can complement X-ray protein-ligand structural information to guide medicinal chemistry optimization. Learning to extract free ligand conformational information from routinely available 1D NMR signatures has proven to be fast enough to guide medicinal chemistry decisions within design cycles for compound optimization.

Purpose/objective(s) Laboratory experiments show that activation of β-catenin signaling promotes pancreatic cancer (PC) growth, but studies addressing its prognostic value in patients (pts) are scarce and with conflicting results. This question has been examined using samples from a large prospective clinical trial. Materials/methods NRG/RTOG 9704 was a phase III trial which compared 5-fluorouracil - to gemcitabine-based chemotherapy in pts after pancreatectomy. All pts received 5-fluorouracil -based chemoradiotherapy. Quantitative immunofluorescence analysis for β-catenin was performed on a tissue microarray developed from these pts. β-catenin and its active form (total, nuclear, and cytoplasmic) were assayed in pan-cytokeratin positive tumor cells. Assay performers were blinded to all clinical outcomes. Scores were dichotomized at their median. OS and DFS were estimated univariately with the Kaplan-Meier method and groups compared using the log-rank test. Cox proportional hazards models were used to identify the impact of expression on OS and DFS. The following variables were included in the models: β-catenin, treatment, age, gender, race, CA19-9, tumor location, nodal involvement, tumor diameter, and surgical margin status. Results Of 451 eligible pts, 141 samples were analyzable. There were no significant differences in baseline characteristics/outcomes for pts with and without tissue. For cytoplasmic β-catenin univariately, levels ≥ median were associated with better OS [HR (95% CI): 0.65 (0.45, 0.93); P = 0.02] and DFS [HR (95% CI): 0.70 (0.49, 0.99); P = 0.04]. On multivariable analysis, levels ≥ median were associated with better OS [HR (95% CI): 0.63 (0.43, 0.92), P = 0.02], after adjusting for CA19-9, age, and race, with a 37% risk reduction of death. There was a trend towards better DFS for pts with levels ≥ median [HR (95% CI): 0.70 (0.48, 1.01), P = 0.054], after adjusting for CA19-9. For cytoplasmic active β-catenin univariately, levels ≥ median were associated with better OS [HR (95% CI): 0.65 (0.45, 0.94); P = 0.02], that remained significant on multivariable analysis [HR (95% CI): 0.64 (0.44, 0.94); P = 0.02]. There were no associations with efficacy for nuclear or total β-catenin, nor in its active form. Conclusion In this high-quality database from a prospective phase III clinical trial, cytoplasmic β-catenin and cytoplasmic active β-catenin are statistically significantly associated with OS and DFS and with OS, respectively, independent of other known prognostic factors. In agreement with one previous publication, high levels of cytoplasmic β-catenin, which is transcriptionally silent, were associated with a reduced risk of death. The significant magnitude of these effects makes them clinically relevant, warranting further investigation. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI).

ATM inhibitors, such as 7, have demonstrated the antitumor potential of ATM inhibition when combined with DNA double-strand break-inducing agents in mouse xenograft models. However, the properties of 7 result in a relatively high predicted clinically efficacious dose. In an attempt to minimize attrition during clinical development, we sought to identify ATM inhibitors with a low predicted clinical dose (50 mg) and focused on strategies to increase both ATM potency and predicted human pharmacokinetic half-life (predominantly through the increase of volume of distribution). These efforts resulted in the discovery of 64 (AZD0156), an exceptionally potent and selective inhibitor of ATM based on an imidazo[4,5- c]quinolin-2-one core. 64 has good preclinical phamacokinetics, a low predicted clinical dose, and a high maximum absorbable dose. 64 has been shown to potentiate the efficacy of the approved drugs irinotecan and olaparib in disease relevant mouse models and is currently undergoing clinical evaluation with these agents.

Engineering demonstration reactors are nuclear reactors built to establish proof of concept for technology options that have never been built. Examples of engineering demonstration reactors include Peach Bottom 1 for high temperature gas-cooled reactors and the Experimental Breeder Reactor-II for sodium-cooled fast reactors. Engineering demonstrations have historically played a vital role in advancing the technology readiness level of reactor concepts. This paper details a preconceptual design for a fluoride salt-cooled engineering demonstration reactor. The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output. It would use tristructural-isotropic (TRISO) particle fuel in compacts within prismatic graphite blocks. FLiBe (2 7LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is an intermediate step to enable near-term commercial FHRs. The design philosophy of the FHR DR was focused on safety, near-term deployment, and flexibility. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated as an engineering demonstration with minimal risk and cost. These technologies include TRISO particle fuel, replaceable core structures, and consistent structural material selection for core structures and the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Important capabilities to be demonstrated by building and operating the FHR DR include: • core design methodologies, • heat exchanger performance (including passive decay heat removal), • pump performance, • reactivity control, • salt chemistry control to maximize plant life, • salt procurement, handling, maintenance and ultimate disposal, and • tritium management. Non-nuclear separate and integral test efforts (e.g., heated salt loops or loops using simulant fluids) are necessary to develop the technologies that will be demonstrated in the FHR DR.

Loading requirements for dry cask storage of spent nuclear fuel are driven primarily by decay heat capacity limitations, which themselves are determined through recommended limits on peak cladding temperature within the cask. This study examines the relative sensitivity of peak material temperatures within the cask to parameters that influence both the stored fuel residual decay heat as well as heat removal mechanisms. These parameters include the detailed reactor operating history parameters (e.g., soluble boron concentrations and the presence of burnable poisons) as well as factors that influence heat removal, including non-dominant processes (such as conduction from the fuel basket to the canister and radiation within the canister) and ambient environmental conditions. By examining the factors that drive heat removal from the cask alongside well-understood factors that drive decay heat, it is therefore possible to make a contextual analysis of the most important parameters to evaluation of peak material temperatures within the cask. The goal of this analysis is to afford modelers the ability to develop best-estimate thermal models for vertical dry cask storage systems useful for material degradation studies. In contrast to more conservative bounding analyses used for safety and licensing studies (which are primarily intended to illustrate that recommended temperature limits are not exceeded), material degradation phenomena are frequently temperature-dependent, requiring best-estimate thermal models to properly evaluate. The canister-level parameters that have the greatest impact on peak fuel material temperatures drive convective heat transfer in the cask annulus (comprised of the region between the storage canister and the concrete overpack) and within the canister basket. These parameters include the ambient air temperature, the canister fill gas pressure, and the pressure drop between the annular region inlet and outlet. Other cask design parameters which would be expected to contribute substantially to the peak clad temperature were overall proved to be of marginal significance, including material properties such as the fuel basket thermal conductivity and emissivity, along with frictional flow losses from the spacer grid. Meanwhile, factors that drive conduction from the fuel basket region and material properties which drive radiative transport between the fuel and basket likewise exhibit low sensitivity for peak clad temperature estimates. Fuel irradiation history parameters that drive decay heat (such as the discharge burnup and average moderator density) nevertheless dominate peak clad temperature sensitivity. While the assembly power history significantly influences short-term decay heat post-discharge, it manifests minimal sensitivity for cooling times over 10 years and is thus of negligible importance for assemblies stored in wet storage for at least this time.

In boiling water reactors, the shroud dome, separators, and dryers above the core are made of approximately 100,000 kg of stainless steel. During a severe accident in which the coolant boils away and exothermic oxidation of zirconium occurs, gases (steam and hydrogen) are superheated in the core region and pass through the upper internals. In this scenario, the upper internals can also be heated by thermal radiation from the hot degrading core. Historically, models of the upper internals have been relatively simple in severe accident codes. The upper internals are typically modeled in MELCOR as two lumped volumes with simplified heat transfer characteristics and no structural integrity considerations, and with limited ability to oxidize, melt, and relocate. The potential for and the subsequent impact of the upper internals to heat up, oxidize, fail, and relocate during a severe accident was investigated. A higher fidelity representation of the shroud dome, steam separators, and steam driers was developed in MELCOR v1.8.6 by extending the core region upwards. The MELCOR modeling effort entailed adding 45 additional core cells and control volumes, 98 flow paths, and numerous control functions. The model accounts for the mechanical loading and structural integrity, oxidation, melting, flow area blockage, and relocation of the various components. Consistent with a previous study, the results indicate that the upper internals can reach high temperatures during a severe accident sufficient to lose their structural integrity and relocate. The additional 100 metric tons of stainless steel debris influences the subsequent in-vessel and ex-vessel accident progression.

Lower head failure and corium-concrete interaction were predicted to occur at Fukushima Daiichi Unit 1 (1F1) by several different system-level code analyses, including MELCOR v2.1 and MAAP5. Althou...

The reactor accidents at Fukushima Daiichi have rekindled interest in light water reactor (LWR) severe accident phenomenology. Postevent analyses have identified several areas that may warrant addi...

Proteins of the bromodomain and extraterminal (BET) family, in particular bromodomain-containing protein 4 (BRD4), are of great interest as biological targets. BET proteins contain two separate bromodomains, and existing inhibitors bind to them monovalently. Here we describe the discovery and characterization of probe compound biBET, capable of engaging both bromodomains simultaneously in a bivalent, in cis binding mode. The evidence provided here was obtained in a variety of biophysical and cellular experiments. The bivalent binding results in very high cellular potency for BRD4 binding and pharmacological responses such as disruption of BRD4-mediator complex subunit 1 foci with an EC50 of 100 pM. These compounds will be of considerable utility as BET/BRD4 chemical probes. This work illustrates a novel concept in ligand design-simultaneous targeting of two separate domains with a drug-like small molecule-providing precedent for a potentially more effective paradigm for developing ligands for other multi-domain proteins.

We completed a novel assessment to determine the unquantified and uncredited safety margins (i.e., the difference between the licensing basis and as-loaded calculations) available in as-loaded spent nuclear fuel (SNF) casks. This assessment was performed as part of a broader effort to assess issues and uncertainties related to the continued safety of casks during extended storage and transportability following extended storage periods. Detailed analyses crediting the actual as-loaded cask inventory were performed for each of the casks at three decommissioned pressurized water reactor (PWR) sites to determine their characteristics relative to regulatory safety criteria for criticality, thermal, and shielding performance. These detailed analyses were performed in an automated fashion by employing a comprehensive and integrated data and analysis tool—Used Nuclear Fuel-Storage, Transportation & Disposal Analysis Resource and Data System (UNF-STD calculated decay heat margins ranged from 4 to almost 22 kW (as of 2014); and significant uncredited transportation dose rate margins were also observed. The results demonstrate that, at least for the casks analyzed here, significant uncredited safety margins are available that could potentially be used to compensate for SNF assembly and canister structural performance related uncertainties associatedmore » with long-term storage and subsequent transportation. The results also suggest that these inherent margins associated with how casks are loaded could support future changes in cask licensing to directly or indirectly credit the margins. Work continues to quantify the uncredited safety margins in the SNF casks loaded at other nuclear reactor sites.« less

B-cell lymphoma 6 (BCL6) inhibition is a promising mechanism for treating hematological cancers but high quality chemical probes are necessary to evaluate its therapeutic potential. Here we report potent BCL6 inhibitors that demonstrate cellular target engagement and exhibit exquisite selectivity for BCL6 based on mass spectrometry analyses following chemical proteomic pull down. Importantly, a proteolysis-targeting chimera (PROTAC) was also developed and shown to significantly degrade BCL6 in a number of diffuse large B-cell lymphoma (DLBCL) cell lines, but neither BCL6 inhibition nor degradation selectively induced marked phenotypic response. To investigate, we monitored PROTAC directed BCL6 degradation in DLBCL OCI-Ly1 cells by immunofluorescence and discovered a residual BCL6 population. Analysis of subcellular fractions also showed incomplete BCL6 degradation in all fractions despite having measurable PROTAC concentrations, together providing a rationale for the weak antiproliferative response seen with both BCL6 inhibitor and degrader. In summary, we have developed potent and selective BCL6 inhibitors and a BCL6 PROTAC that effectively degraded BCL6, but both modalities failed to induce a significant phenotypic response in DLBCL despite achieving cellular concentrations.

[Image: see text] We report the discovery of a novel series of 3-cinnoline carboxamides as highly potent and selective ataxia telangiectasia mutated (ATM) kinase inhibitors. Optimization of this series focusing on potency and physicochemical properties (especially permeability) led to the identification of compound 21, a highly potent ATM inhibitor (ATM cell IC(50) 0.0028 μM) with excellent kinase selectivity and favorable physicochemical and pharmacokinetics properties. In vivo, 21 in combination with irinotecan showed tumor regression in the SW620 colorectal tumor xenograft model, superior inhibition to irinotecan alone. Compound 21 was selected for preclinical evaluation alongside AZD0156.

Summary 1. While many ecosystems depend on fire to maintain biodiversity, non-native plant invasions can enhance fire intensity, suppressing native species and generating a fire–invasion feedback. These dynamics have been observed in arid and semi-arid ecosystems, but fire–invasion interactions in temperate deciduous forests, where prescribed fires are often used as management tools to enhance native diversity, have rarely been investigated. 2. Here we evaluated the effects of a widespread invasive grass on fire behaviour in eastern deciduous forests in the USA and the potential effects of fire and invasions on tree regeneration. We planted native trees into invaded and uninvaded forests, quantified fuel loads, then applied landscape-scale prescribed fires and no-burn controls, and measured fire behaviour and tree seedling and invasive plant performance. 3. Our results show that fires in invaded habitats were significantly more intense, including higher fire temperatures, longer duration and higher flame heights, even though invasions did not alter total fuel loads. The invasion plus fire treatment suppressed native tree seedling survival by 54% compared to invasions without fire, and invasions reduced natural tree recruitment by 66%. 4. We also show that invasive plant biomass did not change from one season to the next in plots where fire was applied, but invader biomass declined significantly in unburned reference plots, suggesting a positive invasive grass–fire feedback. 5. Synthesis and applications. These findings demonstrate that fire–invasion interactions can have significant consequences for invaded temperate forest ecosystems by increasing fire intensity and reducing tree establishment while promoting invasive plant persistence. To encourage tree regeneration and slow invasive spread, we recommend that forest managers remove invasions prior to applying prescribed fires or avoid the use of fire in habitats invaded by non-native grasses.

Inhibition of the protein-protein interaction between B-cell lymphoma 6 (BCL6) and corepressors has been implicated as a therapeutic target in diffuse large B-cell lymphoma (DLBCL) cancers and profiling of potent and selective BCL6 inhibitors are critical to test this hypothesis. We identified a pyrazolo[1,5-a]pyrimidine series of BCL6 binders from a fragment screen in parallel with a virtual screen. Using structure-based drug design, binding affinity was increased 100000-fold. This involved displacing crystallographic water, forming new ligand-protein interactions and a macrocyclization to favor the bioactive conformation of the ligands. Optimization for slow off-rate constant kinetics was conducted as well as improving selectivity against an off-target kinase, CK2. Potency in a cellular BCL6 assay was further optimized to afford highly selective probe molecules. Only weak antiproliferative effects were observed across a number of DLBCL lines and a multiple myeloma cell line without a clear relationship to BCL6 potency. As a result, we conclude that the BCL6 hypothesis in DLBCL cancer remains unproven.

Crawfish Frogs (Lithobates areolatus) are a relatively widespread but understudied North American species suspected to be in steep decline. Discussions to petition this species for federal listing have begun and therefore effective techniques to survey and monitor populations must be developed. Crawfish Frogs produce unusually loud breeding calls, making call surveys the most efficient way to assess populations; however, their peak breeding period lasts for only a few nights, sometimes for only one night. We used automated calling survey techniques at two wetlands where the numbers of Crawfish Frog males present were known (±1%) for the entire length of the breeding season to examine detection probabilities in relation to season, time of day, weather variables, survey duration, and the numbers of males present. We then used these data to ask three simple but important questions: 1) When should researchers listen—that is, what times and under what environmental conditions should surveys for Crawfish Frogs ...

Crawfish Frogs (Lithobates areolatus) are a North American ranid, considered near threatened globally with populations in decline throughout their range. We studied populations of Crawfish Frogs on local and regional scales at their northeastern range limit to (1) assess the level of genetic diversity within populations, (2) estimate fine-scale genetic structure, and (3) estimate genetic differentiation between populations at the regional level. We used 10 microsatellite loci to genotype frogs collected from three regional sites in Indiana separated by 50–172 km and at one of these sites within a network of three breeding ponds

AB Purpose: Barefoot running (BF) is gaining popularity in the running community. Biomechanical changes occur with BF, especially when initial contact changes from rearfoot strike (RFS) to forefoot strike (FFS). Changes in lumbar spine range of motion (ROM), particularly involving lumbar lordosis, have been associated with increased low back pain. However, it is not known if changing from RFS to FFS affects lumbar lordosis or low back pain. The purpose of this study was to determine whether a change from RFS to FFS would change lumbar lordosis, influence shock attenuation, or change comfort levels in healthy recreational/experienced runners. Methods: Forty-three subjects performed a warm-up on the treadmill where a self-selected foot strike pattern was determined. Instructions on running RFS/FFS were taught, and two conditions were examined. Each condition consisted of 90 s of BF with RFS or FFS, order randomly assigned. A comfort questionnaire was completed after both conditions. Fifteen consecutive strides from each condition were extracted for analyses. Results: Statistically significant differences between FFS and RFS shock attenuation (P < 0.001), peak leg acceleration (P < 0.001), and overall lumbar ROM (P = 0.045) were found. There were no statistically significant differences between FFS and RFS in lumbar extension or lumbar flexion. There was a statistically significant difference between FFS and RFS for comfort/discomfort of the comfort questionnaire (P = .007). There were no statistically significant differences between other questions or the average of all questions. Conclusion: Change in foot strike from RFS to FFS decreased overall ROM in the lumbar spine but did not make a difference in flexion or extension in which the lumbar spine is positioned. Shock attenuation was greater in RFS. RFS was perceived a more comfortable running pattern.

Our objective was to examine breeding dispersal, burrow-use characteristics, and burrow habitat selection by Crawfish Frogs (Lithobates areolatus) in two distinct vegetation types (open grasslands and a mosaic of forest and transitioning grasslands) in southeastern Indiana, from March to August 2009 and 2010. We captured 14 frogs at their breeding ponds and tracked them to their burrows using radio telemetry. Once we identified their burrows, we compared habitat metrics at the burrows to random locations. We used an information-theoretic model selection approach to approximate the parsimony of logistic regression models comparing the habitat features of burrows to random, available sites. Frogs dispersed a straight-line average distance of 215 m and used an average of four burrows. They generally did not change burrows after June. Our top model included covariates for the number of burrows, canopy cover, and a site covariate. Our results suggested that habitat selection by Crawfish Frogs occurred...

Fluoride salt cooled high-temperature reactor (FHR) concepts include pumps for forced circulation of the primary and secondary coolants. As part of a cooperative research and development agreement between the Shanghai Institute of Applied Physics and the Oak Ridge National Laboratory (ORNL), a research project was initiated to aid in the development of pumps for high-temperature salts. The objectives of the task included characterization of the behavior of an existing ORNL LSTL pump; design and test a modified impeller and volute for improved pump characteristics; and finally, provide lessons learned, recommendations, and guidelines for salt pump development and design. The pump included on the liquid salt test loop (LSTL) at ORNL served as a case study. This report summarizes the progress to date. The report is organized as follows. First, there is a review, focused on pumps, of the significant amount of work on salts at ORNL during the 1950s 1970s. The existing pump on the LSTL is then described. Plans for hot and cold testing of the pump are then discussed, including the design for a cold shakedown test stand and the required LSTL modifications for hot testing. Initial hydraulic and vibration modeling of the LSTL pump is documented. Later,more » test data from the LSTL will be used to validate the modeling approaches, which could then be used for future pump design efforts. Some initial insights and test data from the pump are then provided. Finally, some preliminary design goals and requirements for a future LSTL pump are provided as examples of salt pump design considerations.« less

The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output (MWt). It would use tristructural-isotropic (TRISO) particle fuel within prismatic graphite blocks. FLiBe (2 LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is a necessary intermediate step to enable near-term commercial FHRs. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated within an acceptable budget and schedule. These technologies include TRISO particle fuel, replaceable core structural material, the use of that same material for the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Several preconceptual and conceptual design efforts that have been conducted on FHR concepts bear a significant influence on the FHR DR design. Specific designs include the Oak Ridge National Laboratory (ORNL) advanced high-temperature reactor (AHTR) with 3400/1500 MWt/megawatts of electric output (MWe), as well as a 125 MWt small modular AHTR (SmAHTR) from ORNL. Other important examples are the Mk1 pebble bed FHR (PB-FHR) concept from the University of California, Berkeley (UCB), and an FHR testmore » reactor design developed at the Massachusetts Institute of Technology (MIT). The MIT FHR test reactor is based on a prismatic fuel platform and is directly relevant to the present FHR DR design effort. These FHR concepts are based on reasonable assumptions for credible commercial prototypes. The FHR DR concept also directly benefits from the operating experience of the Molten Salt Reactor Experiment (MSRE), as well as the detailed design efforts for a large molten salt reactor concept and its breeder variant, the Molten Salt Breeder Reactor. The FHR DR technology is most representative of the 3400 MWt AHTR concept, and it will demonstrate key operational features of that design. The FHR DR will be closely scaled to the SmAHTR concept in power and flows, so any technologies demonstrated will be directly applicable to a reactor concept of that size. The FHR DR is not a commercial prototype design, but rather a DR that serves a cost and risk mitigation function for a later commercial prototype. It is expected to have a limited operational lifetime compared to a commercial plant. It is designed to be a low-cost reactor compared to more mature advanced prototype DRs. A primary reason to build the FHR DR is to learn about salt reactor technologies and demonstrate solutions to remaining technical gaps.« less

The ultrafast-rotating ($P_\mathrm{rot}\approx0.44 d$) fully convective single M4 dwarf V374 Peg is a well-known laboratory for studying intense stellar activity in a stable magnetic topology. As an observable proxy for the stellar magnetic field, we study the stability of the light curve, and thus the spot configuration. We also measure the occurrence rate of flares and coronal mass ejections (CMEs). We analyse spectroscopic observations, $BV(RI)_C$ photometry covering 5 years, and additional $R_C$ photometry that expands the temporal base over 16 years. The light curve suggests an almost rigid-body rotation, and a spot configuration that is stable over about 16 years, confirming the previous indications of a very stable magnetic field. We observed small changes on a nightly timescale, and frequent flaring, including a possible sympathetic flare. The strongest flares seem to be more concentrated around the phase where the light curve indicates a smaller active region. Spectral data suggest a complex CME with falling-back and re-ejected material, with a maximal projected velocity of $\approx$675km/s. We observed a CME rate much lower than expected from extrapolations of the solar flare-CME relation to active stars., Comment: 15 figures, 4 tables, accepted for publication in A&A

Effective high-temperature thermal energy exchange and delivery at temperatures over 600°C has the potential of significant impact by reducing both the capital and operating cost of energy conversion and transport systems. It is one of the key technologies necessary for efficient hydrogen production and could potentially enhance efficiencies of high-temperature solar systems. Today, there are no standard commercially available high-performance heat transfer fluids above 600°C. High pressures associated with water and gaseous coolants (such as helium) at elevated temperatures impose limiting design conditions for the materials in most energy systems. Liquid salts offer high-temperature capabilities at low vapor pressures, good heat transport properties, and reasonable costs and are therefore leading candidate fluids for next-generation energy production. Liquid-fluoride-salt-cooled, graphite-moderated reactors, referred to as Fluoride Salt Reactors (FHRs), are specifically designed to exploit the excellent heat transfer properties of liquid fluoride salts while maximizing their thermal efficiency and minimizing cost. The FHR s outstanding heat transfer properties, combined with its fully passive safety, make this reactor the most technologically desirable nuclear power reactor class for next-generation energy production. Multiple FHR designs are presently being considered. These range from the Pebble Bed Advanced High Temperature Reactor (PB-AHTR) [1] design originally developed by UC-Berkeleymore » to the Small Advanced High-Temperature Reactor (SmAHTR) and the large scale FHR both being developed at ORNL [2]. The value of high-temperature, molten-salt-cooled reactors is also recognized internationally, and Czechoslovakia, France, India, and China all have salt-cooled reactor development under way. The liquid salt experiment presently being developed uses the PB-AHTR as its focus. One core design of the PB-AHTR features multiple 20 cm diameter, 3.2 m long fuel channels with 3 cm diameter graphite-based fuel pebbles slowly circulating up through the core. Molten salt coolant (FLiBe) at 700°C flows concurrently (at significantly higher velocity) with the pebbles and is used to remove heat generated in the reactor core (approximately 1280 W/pebble), and supply it to a power conversion system. Refueling equipment continuously sorts spent fuel pebbles and replaces spent or damaged pebbles with fresh fuel. By combining greater or fewer numbers of pebble channel assemblies, multiple reactor designs with varying power levels can be offered. The PB-AHTR design is discussed in detail in Reference [1] and is shown schematically in Fig. 1. Fig. 1. PB-AHTR concept (drawing taken from Peterson et al., Design and Development of the Modular PB-AHTR Proceedings of ICApp 08). Pebble behavior within the core is a key issue in proving the viability of this concept. This includes understanding the behavior of the pebbles thermally, hydraulically, and mechanically (quantifying pebble wear characteristics, flow channel wear, etc). The experiment being developed is an initial step in characterizing the pebble behavior under realistic PB-AHTR operating conditions. It focuses on thermal and hydraulic behavior of a static pebble bed using a convective salt loop to provide prototypic fluid conditions to the bed, and a unique inductive heating technique to provide prototypic heating in the pebbles. The facility design is sufficiently versatile to allow a variety of other experimentation to be performed in the future. The facility can accommodate testing of scaled reactor components or sub-components such as flow diodes, salt-to-salt heat exchangers, and improved pump designs as well as testing of refueling equipment, high temperature instrumentation, and other reactor core designs.« less