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Autonomous data collection is rapidly becoming an integral part of water quality monitoring, particularly for agencies looking to manage and protect aquatic ecosystems. While beneficial, it is unclear how the collection of these data can be applied in spatially complex large lakes (e.g., Laurentian Great Lakes) given the spatial heterogeneity of the ecosystem. To address this potential shortcoming in large lakes, we assessed the synchrony of sensor variables between 10 pairs of static buoys in the western basin of Lake Erie (western basin surface area =  3,282 km 2 ). Within western Lake Erie, water temperature was highly synchronous whereas dissolved oxygen, turbidity, chlorophyll and phycocyanin were asynchronous. The extent of this asynchrony was higher with increasing spatial distance between buoys. We found that between pairs of static buoys, temperature, dissolved oxygen, and turbidity all experienced decreasing correlations with increasing distance. Our results show that if researchers intend to leverage these data to answer important questions and provide real-time applications related to environmental issues like harmful algal/cyanobacterial blooms, monitoring networks need to be designed carefully with spatial complexity in mind. While autonomous data collection has many benefits, the reliance on a single or limited network of anchored monitoring buoys in large lake ecosystems has a high probability of missing important spatial features of these systems.

Populations of scoter and loon species that winter in the Atlantic are understudied in North America, but coastal observatories may provide the data required to fill some of the knowledge gaps. The migration of scoters and loons has been monitored at the Point Lepreau Bird Observatory (PLBO) in the Bay of Fundy every spring since 1996, but little peer-reviewed research based on the resultant database has been published. Using data collected over 18 years at the Bay of Fundy (2000–2017), our objectives were to (1) determine the most accurate method of modeling hourly migration rates for Surf (Melanitta perspicillata), White-winged (M. deglandi), and Black (M. americana) scoters, and Red-throated (Gavia stellata) and Common (G. immer) loons, and (2) assess trends in hourly migration rates for our five focal species to determine if the numbers of migrants passing PLBO have changed over time. We calculated hourly migration rates for each of our five focal species and evaluated drivers (i. e., timing and environmental conditions) of migration and annual trends using zero-inflated generalized linear mixed models (GLMMs). We found that drivers of migration differed among species. Specifically, hourly migration rates decreased with increasing tide height for all species except Red-throated Loons. In addition, hourly migration rates increased with increasing wind vector (i. e., a tailwind) for the three scoter species, but decreased with increasing wind vector for the two loon species. Scoter migration rates peaked daily between 11:00 and 13:00 UTC, but we found no daily peak for either loon species. Peak hourly migration rates of Black and Surf scoters occurred from 12 to 26 April, but migration rates of White-winged Scoters and both loon species continued to increase throughout our migration-monitoring window. Finally, we found no changes in hourly migration rates over time for any of our focal species, suggesting no changes in abundance over the 18 years of data collection. Our study reveals the importance and utility of long-term, coastal observation stations, and we recommend their continued funding and use as valuable sources of monitoring data. Las poblaciones de especies de negrones y colimbos que pasan el invierno en el Atlántico están poco estudiadas en América del Norte, pero los observatorios costeros pueden proporcionar los datos necesarios para llenar algunos de los vacíos de conocimiento. La migración de negrones y colimbos ha sido monitoreada en el Observatorio de Aves Point Lepreau (PLBO) en la Bahía de Fundy cada primavera desde 1996, pero se han publicado pocos estudias arbitrados por pares basados en la base de datos resultante. Utilizando los datos recopilados durante 18 años en la Bahía de Fundy (2000–2017), nuestros objetivos fueron (1) determinar el método más preciso para modelar las tasas de migración por hora para el Negrón costero (Melanitta perspicillata), el aliblanco (M. deglandi), y el americano (M. americana), y el Colimbo chico (Gavia stellata) y grande (G. immer), y (2) evalúan las tendencias en las tasas de migración por hora para nuestras cinco especies focales para determinar si el número de migrantes que pasan PLBO han cambiado con el tiempo. Calculamos las tasas de migración por hora para cada una de nuestras cinco especies focales y evaluamos los factores impulsores (es decir, el tiempo y las condiciones ambientales) de la migración y las tendencias anuales utilizando modelos mixtos lineales generalizados inflados a cero (GLMM). Encontramos que los impulsores de la migración diferen entre las especies. Específicamente, las tasas de migración por hora disminuyeron con el aumento de la altura de la marea para todas las especies, excepto para el Colimbo chico. Además, las tasas de migración por hora aumentaron al aumentar el vector de viento (es decir, un viento de cola) para las tres especies de negrones, pero disminuyeron al aumentar el vector de viento para las dos especies de colimbos. Las tasas de migración de negrones alcanzaron su punto máximo diariamente entre las 11:00 y las 13:00 UTC, pero no encontramos un pico diario para ninguna de las especies de colimbos. Las tasas pico de migración por hora del Negrón americano y costero ocurrieron del 12 al 26 de abril, pero las tasas de migración del Negrón aliblanco y ambas especies de colimbos continuaron aumentando a lo largo de nuestra ventana de monitoreo de la migración. Finalmente, no encontramos cambios en las tasas de migración por hora a lo largo del tiempo para ninguna de nuestras especies focales, lo que sugiere que no hubo cambios en la abundancia durante los 18 años de recopilación de datos. Nuestro estudio revela la importancia y utilidad de las estaciones de observación costera a largo plazo, y recomendamos su financiamiento continuo y su uso como valiosas fuentes de datos de monitoreo.

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.

This investigation compares and proposes finite element modeling techniques and procedures, which can be used to define key structural parameters that often dominate the overall response behavior of bridge structures. The techniques and procedures are implemented to generate several different model versions of a single highly skewed bridge structure, the Gavin Canyon Under Crossing Bridge #53-1797L, which failed during the 1994 Northridge earthquake in California. The seismic response of the different model versions are investigated and compared using a nonlinear dynamic time-history analysis.The investigation primarily focuses on modeling mechanisms of the bridge structure that are often ignored, or highly simplified, in a standard analysis. Attention is focused on the manner in which the bridge superstructure, pile groups and abutments, in-span hinges, and column plastic-hinge regions are modeled.The structure models range from various versions of traditional Equivalent Beam models, using 3-D frame elements, to Full-Grillage 3-D models which use a combination of 3-D frame and quadrilateral shell elements to model the superstructure, as to fully distribute the participating mass.Base models of the bridge structure are constructed using linear elastic frame and shell elements, and include nonlinear spring models at the abutments and in-span hinges. Subsequent model versions include nonlinear bending characteristics of the columns, within potential plastic-hinge regions, and are compared with and without soil-spring models at the column base. The comparisons are used to determine the extent at which the overall seismic response is affected by the inclusion of soil-structure effects, structural nonlinearities, and mass distribution.The primary analysis software used is the SAP2000 finite element analysis program v7.44 (CSI 1998). The pile analysis software used for determination of pile group stiffness is the nonlinear soil-pile interaction analysis program from the Federal Highway Administration (FHWA), COM624P.

I for one will not start cheering until Chuck Martin sticks his tail and SE2 between his legs, or near proximity, and heads for Nevada or Arizona where they should have been...

God-and-country conferees and sign-waving protesters competed for attention - but didn't clash - on Saturday at the Greater Fort Lauderdale-Broward County Convention Center as the \"Reclaiming America for Christ\" conference went into its last full day. Inside, conservative speakers sounded alarms to their 700 listeners not only about homosexual rights but also about abortion, school prayer, pornography, deficit spending and perceived media bias against conservative Protestants. The protests were timed to coincide with the appearance by Beverly LaHaye, head of the 600,000-member Concerned Women For America. Gay rights activist Mel White accused LaHaye of being \"irresponsible in her rhetoric\" because she had a \"violent speech pattern.\"

Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)—a small-molecule targeted inhibitor of mutated IDH1—in patients with previously treated IDH1-mutant cholangiocarcinoma. This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8–10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6–4·2] vs 1·4 months [1·4–1·6]; hazard ratio 0·37; 95% CI 0·25–0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. Agios Pharmaceuticals.

Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.

Regulatory pressure along with environmental and human health concerns drive the development of soil fumigation alternatives such as soil biosolarization (SBS). SBS involves tarping soil that is at field capacity with a transparent film following amendment with certain organic materials. Heating via the greenhouse effect results in an increase of the soil temperature. The organic amendments can promote microbial activity that can enhance pest inactivation by depleting oxygen, producing biopesticidal fermentation products, and competing with pests. The properties of the organic amendments can heavily influence the type and magnitude of these effects. This study evaluated the viability of chitin as a novel SBS soil amendment to influence soil fungal and bacterial microbial communities, including control of the plant pathogen Fusarium oxysporum f.sp. lactucae (FOL). Changes to FOL and the broader soil microbiota were monitored in response to biosolarization using 0.1% (by dry weight) amendment with chitin (Rootguard). FOL suppression was only observed in chitin amended soils that were incubated at room temperature, not under solarized conditions. Conversely, it decreased solarization efficacy in the upper (0-10 cm) soil layer. The presence of chitin also showed increase in FOL under anaerobic and fluctuating temperature regime conditions. Biosolarization with chitin amendment did exhibit an impact on the overall soil microbial community. The fungal genus Mortierella and the bacterial family Chitinophagaceae were consistently enriched in biosolarized soils with chitin amendment. This study showed low potential FOL suppression due chitin amendment at the studied levels. However, chitin amendment showed a higher impact on the fungal community than the bacterial community. The impact of these microbial changes on crop protection and yields need to be studied in the long-term.