A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2 /week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel

Dynamics of sun-induced chlorophyll fluorescence and reflectance to detect stress-induced variations in canopy photosynthesis

Passive measurement of sun-induced chlorophyll fluorescence (F) represents the most promising tool to quantify changes in photosynthetic functioning on a large scale. However, the complex relationship between this signal and other photosynthesis-related processes restricts its interpretation under stress conditions. To address this issue, we conducted a field campaign by combining daily airborne and ground-based measurements of F (normalized to photosynthetically active radiation), reflectance and surface temperature and related the observed changes to stress-induced variations in photosynthesis. A lawn carpet was sprayed with different doses of the herbicide Dicuran. Canopy-level measurements of gross primary productivity indicated dosage-dependent inhibition of photosynthesis by the herbicide. Dosage-dependent changes in normalized F were also detected. After spraying, we first observed a rapid increase in normalized F and in the Photochemical Reflectance Index, possibly due to the blockage of electron transport by Dicuran and the resultant impairment of xanthophyll-mediated non-photochemical quenching. This initial increase was followed by a gradual decrease in both signals, which coincided with a decline in pigment-related reflectance indices. In parallel, we also detected a canopy temperature increase after the treatment. These results demonstrate the potential of using F coupled with relevant reflectance indices to estimate stress-induced changes in canopy photosynthesis

Winegrowers’ decision-making: A pan-European perspective on pesticide use and inter-row management

European viticultural landscapes not only support a significant share of rural livelihoods and cultural traditions, but also conserve biodiversity and sustain various ecosystem services. Winegrowers' practices of inter-row management (including whether to have vegetation in the inter-rows, type of vegetation, duration of vegetation cover, and soil tillage) and pesticide use (including herbicides in the inter-rows, fungicides, insecticides, and pheromone dispensers as an alternative) can affect these services. This study aims to understand winegrowers' decision-making driven by their personal characteristics, attitudes and beliefs towards viticultural practices, physical properties of vineyards, and farm management characteristics in five European winegrowing regions. These include Palatinate in Germany, Leithaberg in Austria, Tarnave in Romania, Bordeaux in France, and Montilla-Moriles in Spain. Based on a questionnaire survey, we constructed decision trees for each behaviour per case study as well as in a generic European model. We found factors that best explain how winegrowers manage their inter-rows and use pesticides. Results showed that not only do behaviours of winegrowers vary drastically across the case studies, but also the factors that explain most behaviours: farmers' attitudes and beliefs and farm management characteristics. This implies the importance of attitudes and beliefs – which are under-researched as compared to other factors – in understanding farmers’ behaviour. With the driving factors found to vary per case study, our results also imply the need for locally-adapted policies. Furthermore, our results suggest that the effects of climate change on European viticultural landscapes concern not only shifting production regions and changes in yields, but also changing pressure of pests and diseases. Any long-term behavioural change requires efforts from many stakeholders.This research was funded by the research project SECBIVIT which was funded through the 2017–2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, with the funding organisations: Agencia Estatal de Investigación (Ministerio de ciencia e innovación/Spain), Austrian Science Fund (FWF) (grant number I 4025-B32), Federal Ministry of Education and Research (BMBF/Germany) through VDI/VDE Innovation + Technik GmbH, DLR Projektträger, French National Research Agency (ANR), Netherlands Organisation for Scientific Research (NWO), National Science Foundation (Grant #1850943) and Romanian Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI). We would like to thank all winegrowers who participated in the focus groups, online questionnaires and personal interviews and the extension services who distributed our online questionnaire through their e-mail distribution list (DLR-Rheinpfalz)

Washington 'Redskins' - Disparaging Term or Valuable Tradition?: Legal and Economic Issues Concerning Harjo v. Pro-Football, Inc.

I\u27ll never change the name of the Redskins. You have my word on that. In addition to that, it\u27s really what the Redskins mean that\u27s not quite out there.., what it means is tradition. It means winning. It means a great tradition for the franchise. -Daniel Snyder (owner of the Washington Redskins). A long habit of not thinking a thing wrong gives it a superficial appearance of being right, and raises at first a formidable outcry in defense of custom. -Thomas Paine

Multi-Scale Evaluation of Drone-Based Multispectral Surface Reflectance and Vegetation Indices in Operational Conditions

This is the final version. Available from MDPI via the DOI in this record. Compact multi-spectral sensors that can be mounted on lightweight drones are now widely available and applied within the geo- and environmental sciences. However; the spatial consistency and radiometric quality of data from such sensors is relatively poorly explored beyond the lab; in operational settings and against other sensors. This study explores the extent to which accurate hemispherical-conical reflectance factors (HCRF) and vegetation indices (specifically: normalised difference vegetation index (NDVI) and chlorophyll red-edge index (CHL)) can be derived from a low-cost multispectral drone-mounted sensor (Parrot Sequoia). The drone datasets were assessed using reference panels and a high quality 1 m resolution reference dataset collected near-simultaneously by an airborne imaging spectrometer (HyPlant). Relative errors relating to the radiometric calibration to HCRF values were in the 4 to 15% range whereas deviations assessed for a maize field case study were larger (5 to 28%). Drone-derived vegetation indices showed relatively good agreement for NDVI with both HyPlant and Sentinel 2 products (R2 = 0.91). The HCRF; NDVI and CHL products from the Sequoia showed bias for high and low reflective surfaces. The spatial consistency of the products was high with minimal view angle effects in visible bands. In summary; compact multi-spectral sensors such as the Parrot Sequoia show good potential for use in index-based vegetation monitoring studies across scales but care must be taken when assuming derived HCRF to represent the true optical properties of the imaged surface.European Space Agency (ESA)European Union’s Horizon 202

Chapter X: The Tour de France: a success story in spite of competitive imbalance and doping

International audienceThe chapter goes as follows. In the first section it is demonstrated how the Tour de France is a high quality product. This is a result from its accurate design, its management, its economic model and its finance structure, both in comparison to other mega-sporting events and with reference to tournament theory. It is not easy to assess the competitive balance in the Tour de France since, as was demonstrated in chapter 10, it is at the same time an individual and a team sport contest. After reviewing some results published in literature so far, a new metrics for evaluating competitive balanced in the Tour de France is presented in section 2. Finally, the Tour de France cannot ignore doping as a potential threat to fan attendance and TV viewing. We therefore discuss the issue of doping and a new procedure to deal with doping in section 3

Characterization of wheat genotypes for drought tolerance and water use efficiency.

ABSTRACT: The selection of wheat genotypes according to their drought tolerance is essential to off-season cultivation. The objective of this work was to characterize wheat genotypes through yield and components, morphological characteristics under water stress, and irrigated water use efficiency in the Cerrado region in Brazil. Genotypes were planted during the winters of 2016 and 2017 since there is no precipitation during this season and water levels can be measured. They were then submitted to four water regimes: WR1, WR2, WR3, and WR4, representing 100 %, 83 %, 50 %, and 30 % of evapotranspiration replacement. The following variables were evaluated: peduncle length (PL), number of ears m?2 (NE m?2), hectoliter weight (HW), thousand grain weight (TGW), drought resistance index (DRI), irrigated water use efficiency (IWUE) and yield. Most variables showed correlation with yield and can be a useful tool for breeding programs. PL and HW were best correlated with yield. BRS 264 (irrigated biotype) was productive in treatments receiving the greatest number of irrigation treatments. Given that WR1 registered the highest water level, it was not expected that the rainfed biotype (BR18) would show a higher yield than an irrigated biotype (BRS254). BRS404 (rainfed biotype) was the most productive under moderate stress treatment (WR3). Aliança (rainfed biotype) showed a higher yield under severe stress. Rainfed biotypes presented a higher DRI than the irrigated ones. These genotypes can be used as a reference in breeding programs under each water regime in which their performance was outstanding. None of the variables studied contributed to the selection of the most efficient wheat genotypes in the IWU

Reconstruction of cellular variability from spatiotemporal patterns of Dictyostelium discoideum

Variability in cell properties can be an important driving mechanism behind spatiotemporal patterns in biological systems, as the degree of cell-to-cell differences determines the capacity of cells to locally synchronize and, consequently, form patterns on a larger spatial scale. In principle, certain features of spatial patterns emerging with time may be regulated by variability or, more specifically, by certain constellations of cell-to-cell differences. Similarly, measuring variability in a system (i.e. the spatial distribution of cell-cell differences) may help predict properties of later-stage patterns