Seven 3-methylidene-1H-indol-2(3H)-ones related to the multiple-receptor tyrosine kinase inhibitor sunitinib

The solid-state structures of a series of seven substituted 3-methylidene-1H-indol-2(3H)-one derivatives have been determined by single-crystal X-ray diffraction and are compared in detail. Six of the structures {(3Z)-3-(1H-pyrrol-2- ylmethylidene)-1H-indol-2(3H)-one, C13H10N2O, (2a); (3Z)-3-( 2-thienylmethylidene)-1H-indol-2(3H)-one, C13H9NOS, (2b); (3E)-3-(2-furylmethylidene)-1H-indol-2(3H)-one monohydrate, C13H9NO2 center dot H2O, (3a); 3-(1-methylethylidene)-1H-indol- 2(3H)-one, C11H11NO, (4a); 3-cyclohexylidene-1H-indol- 2(3H)-one, C14H15NO, (4c); and spiro[1,3-dioxane-2,3'-indolin]- 2'-one, C11H11NO3, (5)} display, as expected, intermolecular hydrogen bonding (N-H center dot center dot center dot O=C) between the 1H-indol-2(3H)-one units. However, methyl 3-(1-methylethylidene)- 2-oxo-2,3-dihydro-1H-indole-1-carboxylate, C13H13NO3, (4b), a carbamate analogue of (4a) lacking an N-H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules

Redefining Palliative Care-A New Consensus-Based Definition.

The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. The main objective of this article is to present the research behind the new definition. The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span

A monolithic integrated photonic microwave filter

[EN] Meeting the increasing demand for capacity in wireless networks requires the harnessing of higher regions in the radiofrequency spectrum, reducing cell size, as well as more compact, agile and power-efficient base stations that are capable of smoothly interfacing the radio and fibre segments. Fully functional microwave photonic chips are promising candidates in attempts to meet these goals. In recent years, many integrated microwave photonic chips have been reported in different technologies. To the best of our knowledge, none has monolithically integrated all the main active and passive optoelectronic components. Here, we report the first demonstration of a tunable microwave photonics filter that is monolithically integrated into an indium phosphide chip. The reconfigurable radiofrequency photonic filter includes all the necessary elements (for example, lasers, modulators and photodetectors), and its response can be tuned by means of control electric currents. This is an important step in demonstrating the feasibility of integrated and programmable microwave photonic processors.The authors acknowledge financial support from the Spanish Centro para el Desarrollo Tecnologico Industrial (CDTI) through the NEOTEC start-up programme, the European Commission through the 7th Research Framework Programme project, Photonic Advanced Research and Development for Integrated Generic Manufacturing (FP7-PARADIGM), the Generalitat Valenciana through the Programa para grupos de Investigacion de Excelencia (PROMETEO) project code 2013/012, the Spanish Ministerio de Economia y Comercio (MINECO) via project TEC2013-42332-P, PIF4ESP, and the Unwersitat Politecnica de Valencia (UPVOV) through projects 10-3E-492 and 08-3E-008 funded by the Fondos Europeos de Desarrollo Regional (FEDER). J.S. Fandino acknowledges financial support from Formacion de Profesorado Universitario (FPU) grant AP2010-1595.Sanchez Fandiño, JA.; Muñoz Muñoz, P.; Doménech Gómez, JD.; Capmany Francoy, J. (2017). A monolithic integrated photonic microwave filter. Nature Photonics. 11(2):124-129. https://doi.org/10.1038/NPHOTON.2016.233S124129112Novak, D. et al. Radio-over-fiber technologies for emerging wireless systems. IEEE J. Quantum Electron. 52, 1–11 (2016).Waterhouse, R. & Novak, D. Realizing 5G: microwave photonics for 5G mobile wireless systems. IEEE Microw. Mag. 16, 84–92 (2015).Won, R. Microwave photonics shines. Nat. Photon. 5, 736 (2011).Capmany, J. & Novak, D. Microwave photonics combines two worlds. Nat. Photon. 1, 319–330 (2007).Yao, J. Microwave photonics. J. Lightw. Technol. 27, 314–335 (2009).Andrews, J. G. et al. What will 5G be? IEEE J. Sel. Areas Commun. 32, 1065–1082 (2014).Gosh, A., et al. 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Integrated InP–InGaAsP tuneable coupled ring optical bandpass filters with zero insertion loss. Opt. Express 19, 7816–7826 (2011).Fandiño, J. S. & Muñoz, P. Photonics-based microwave frequency measurement using a double-sideband suppressed-carrier modulation and an InP integrated ring-assisted Mach–Zehnder interferometer filter. Opt. Lett. 38, 4316–4319 (2013).Burla, M. et al. On-chip ultra-wideband microwave photonic phase shifter and true time delay line based on a single phase-shifted waveguide Bragg grating. In IEEE International Topical Meeting on Microwave Photonics 92–95 (IEEE, 2013).Shi, W., Veerasubramanian, V., Patel, D. & Plant, D. Tuneable nanophotonic delay lines using linearly chirped contradirectioinal couplers with uniform Bragg gratings. Opt. Lett. 39, 701–703 (2014).Guan, B. et al. CMOS compatible reconfigurable silicon photonic lattice filters using cascaded unit cells for RF-photonic processing. IEEE J. Sel. Top. Quantum Electron. 20, 359–368 (2014).Khan, M. H. et al. Ultrabroad-bandwidth arbitrary radiofrequency waveform generation with a silicon photonic chip-based spectral shaper. Nat. Photon. 4, 117–122 (2010).Pagani, M. et al. Instantaneous frequency measurement system using four-wave mixing in an ultra-compact long silicon waveguide. In Proc. 41st European Conf. on Optical Communication (ECOC) 1–3 (IEEE, 2015).Khilo, A. et al. Photonic ADC: overcoming the bottleneck of electronic jitter. Opt. Express 20, 4454–4469 (2012).Wang, J. et al. Reconfigurable radio-frequency arbitrary waveforms synthesized in a silicon photonic chip. Nat. Commun. 6, 5957 (2015).Marpaung, D. et al. Si3N4 ring resonator-based microwave photonic notch filter with an ultrahigh peak rejection. Opt. Express 21, 23286–23294 (2013).Zhuang, L. et al. Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links. Opt. Express 21, 25999–26013 (2013).Marpaung, D., Chevalier, L., Burla, M. & Roeloffzen, C. Impulse radio ultrawideband pulse shaper based on a programmable photonic chip frequency discriminator. Opt. Express 19, 24838–24848 (2011).Marpaung, D. On-chip photonic-assisted instantaneous microwave frequency measurement system. IEEE Photon. Technol. Lett. 25, 837–840 (2013).Burla, M. et al. On-chip CMOS compatible reconfigurable optical delay line with separate carrier tuning for microwave photonic signal processing. Opt. Express 19, 21475–21484 (2011).Tan, K. et al. Photonic-chip-based all-optical ultra-wideband pulse generation via XPM and birefringence in a chalcogenide waveguide. Opt. Express 21, 2003–2011 (2013).Pagani, M. et al. Tuneable wideband microwave photonic phase shifter using on-chip stimulated Brillouin scattering. Opt. Express 22, 28810–28818 (2014).Pérez, D., Gasulla, I. & Capmany, J. Software-defined reconfigurable microwave photonics processor. Opt. Express 23, 14640–14654 (2015).Capmany, J., Gasulla, I. & Pérez, D. 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Transport of Anthocyanins and other Flavonoids by the Arabidopsis ATP-Binding Cassette Transporter AtABCC2

Flavonoids have important developmental, physiological, and ecological roles in plants and are primarily stored in the large central vacuole. Here we show that both an ATP-binding cassette (ABC) transporter(s) and an H+-antiporter(s) are involved in the uptake of cyanidin 3-O-glucoside (C3G) by Arabidopsis vacuolar membrane-enriched vesicles. We also demonstrate that vesicles isolated from yeast expressing the ABC protein AtABCC2 are capable of MgATP-dependent uptake of C3G and other anthocyanins. The uptake of C3G by AtABCC2 depended on the co-transport of glutathione (GSH). C3G was not altered during transport and a GSH conjugate was not formed. Vesicles from yeast expressing AtABCC2 also transported flavone and flavonol glucosides. We performed ligand docking studies to a homology model of AtABCC2 and probed the putative binding sites of C3G and GSH through site-directed mutagenesis and functional studies. These studies identified residues important for substrate recognition and transport activity in AtABCC2, and suggest that C3G and GSH bind closely, mutually enhancing each other’s binding. In conclusion, we suggest that AtABCC2 along with possibly other ABCC proteins are involved in the vacuolar transport of anthocyanins and other flavonoids in the vegetative tissue of Arabidopsis

Redefining palliative care-a new consensus-based definition

Context: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. Objective: The main objective of this article is to present the research behind the new definition. Methods: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. Results: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Conclusion: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span

Between-Population Outbreeding Affects Plant Defence

Between-population crosses may replenish genetic variation of populations, but may also result in outbreeding depression. Apart from direct effects on plant fitness, these outbreeding effects can also alter plant-herbivore interactions by influencing plant tolerance and resistance to herbivory. We investigated effects of experimental within- and between-population outbreeding on herbivore resistance, tolerance and plant fitness using plants from 13 to 19 Lychnis flos-cuculi populations. We found no evidence for outbreeding depression in resistance reflected by the amount of leaf area consumed. However, herbivore performance was greater when fed on plants from between-population compared to within-population crosses. This can reflect outbreeding depression in resistance and/or outbreeding effects on plant quality for the herbivores. The effects of type of cross on the relationship between herbivore damage and plant fitness varied among populations. This demonstrates how between-population outbreeding effects on tolerance range from outbreeding depression to outbreeding benefits among plant populations. Finally, herbivore damage strengthened the observed outbreeding effects on plant fitness in several populations. These results raise novel considerations on the impact of outbreeding on the joint evolution of resistance and tolerance, and on the evolution of multiple defence strategies