Wafer-scale fabrication of target arrays for stable generation of proton beams by laser-plasma interaction

[EN] Large-scale fabrication of targets for laser-driven acceleration of ion beams is a prerequisite to establish suitable applications, and to keep up with the challenge of increasing repetition rate of currently available high-power lasers. Here we present manufacturing and test results of large arrays of solid targets for TNSA laser-driven ion acceleration. By applying micro-electro-mechanical-system (MEMS) based methods allowing for parallel processing of thousands of targets on a single Si wafer, sub-micrometric, thin-layer metallic membranes were fabricated by combining photolithography, physical and chemical vapor deposition, selective etching, and Si micromachining. These structures were characterized by using optical and atomic force microscopy. Their performance for the production of laser-driven proton beams was tested on a purpose-made table-top Ti:Sapphire laser system running at 3 TW peak power with a contrast over ASE of 108. We have performed several test series achieving maximum proton energy values around 2 MeV.This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM. This project has been financed by the Spanish Ministry for Economy and Competitiveness within the Retos- Colaboración 2015 initiative, ref. RTC-2015-3278-1. P. Mur has received a grant of the Garantía Juvenil 2015 program.Zaffino, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Sánchez, I.; Mur, P.; Bellido-Millán, PJ.; Lera, R.... (2018). Wafer-scale fabrication of target arrays for stable generation of proton beams by laser-plasma interaction. Journal of Physics: Conference Series (Online). 1079. https://doi.org/10.1088/1742-6596/1079/1/012007S0120071079Abedi, S., Dorranian, D., Abari, M. E., & Shokri, B. (2011). Relativistic effects in the interaction of high intensity ultra-short laser pulse with collisional underdense plasma. Physics of Plasmas, 18(9), 093108. doi:10.1063/1.3633529Antici, P., Fuchs, J., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Pépin, H. (2007). Energetic protons generated by ultrahigh contrast laser pulses interacting with ultrathin targets. Physics of Plasmas, 14(3), 030701. doi:10.1063/1.2480610Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.18500

Efficient proton acceleration from a 3 TW table-top laser interacting with submicrometric mass-produced solid targets

[EN] Thin layer membranes with controllable features and material arrangements are often used as target materials for laser driven particle accelerators. Reduced cost, large scale fabrication of such membranes with high reproducibility, and good stability are central for the efficient production of proton beams. These characteristics are of growing importance in the context of advanced laser light sources where increased repetition rates boost the need for consumable targets with design and properties adjusted to study the different phenomena arising in ultra-intense laser-plasma interaction. Wepresent the fabrication of sub-micrometric thin-layer gold or aluminum membranes in a silicon wafer frame by using nano/micro-electro-mechanical-system (N/MEMS) processing which are suitable for rapid patterning and machining of many samples at the same time and allowing for high-throughput production of targets for laser-driven acceleration. Obtained targets were tested for laserproton acceleration through the Target Normal Sheath Acceleration mechanism (TNSA) in a series of experiments carried out on a purpose-made table-top Ti:Sa running at 3 TW peak power and 10 Hz diode pump rate with a contrast over ASE of 10(8)The authors highly appreciate the collaboration of Radosys (Budapest) which provided CR-39 detector material, etching bath, and readout equipment. This project has been financed by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1. P Mur has received a grant of the Garantia Juvenil 2015 program. This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM.Zaffino, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Sánchez, I.; Mur, P.; Quirión, D.; Bellido-Millán, PJ.... (2018). Efficient proton acceleration from a 3 TW table-top laser interacting with submicrometric mass-produced solid targets. Journal of Physics Communications. 2(4):1-6. https://doi.org/10.1088/2399-6528/aabc25S1624Borghesi, M., Campbell, D. H., Schiavi, A., Haines, M. G., Willi, O., MacKinnon, A. J., … Bulanov, S. (2002). Electric field detection in laser-plasma interaction experiments via the proton imaging technique. Physics of Plasmas, 9(5), 2214-2220. doi:10.1063/1.1459457Ledingham, K., Bolton, P., Shikazono, N., & Ma, C.-M. (2014). Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress. Applied Sciences, 4(3), 402-443. doi:10.3390/app4030402Spindloe, C., Arthur, G., Hall, F., Tomlinson, S., Potter, R., Kar, S., … Tolley, M. K. (2016). High volume fabrication of laser targets using MEMS techniques. Journal of Physics: Conference Series, 713, 012002. doi:10.1088/1742-6596/713/1/012002Schomburg, W. K. (2011). Thin Films. RWTHedition, 9-20. doi:10.1007/978-3-642-19489-4_4Bellido, P., Lera, R., Seimetz, M., Cruz, A. R. la, Torres-Peirò, S., Galán, M., … Benlloch, J. M. (2017). Characterization of protons accelerated from a 3 TW table-top laser system. Journal of Instrumentation, 12(05), T05001-T05001. doi:10.1088/1748-0221/12/05/t05001Mayer, M. (1999). SIMNRA, a simulation program for the analysis of NRA, RBS and ERDA. AIP Conference Proceedings. doi:10.1063/1.59188Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.185002Dollar, F., Reed, S. A., Matsuoka, T., Bulanov, S. S., Chvykov, V., Kalintchenko, G., … Maksimchuk, A. (2013). High-intensity laser-driven proton acceleration enhancement from hydrogen containing ultrathin targets. Applied Physics Letters, 103(14), 141117. doi:10.1063/1.4824361Neely, D., Foster, P., Robinson, A., Lindau, F., Lundh, O., Persson, A., … McKenna, P. (2006). Enhanced proton beams from ultrathin targets driven by high contrast laser pulses. Applied Physics Letters, 89(2), 021502. doi:10.1063/1.2220011Green, J. S., Carroll, D. C., Brenner, C., Dromey, B., Foster, P. S., Kar, S., … Zepf, M. (2010). Enhanced proton flux in the MeV range by defocused laser irradiation. New Journal of Physics, 12(8), 085012. doi:10.1088/1367-2630/12/8/085012Giuffrida, L., Svensson, K., Psikal, J., Dalui, M., Ekerfelt, H., Gallardo Gonzalez, I., … Margarone, D. (2017). Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets. Physical Review Accelerators and Beams, 20(8). doi:10.1103/physrevaccelbeams.20.08130

Spectral characterization of laser-accelerated protons with CR-39 nuclear track detector

CR-39 nuclear track material is frequently used for the detection of protons accelerated in laser-plasma interactions. The measurement of track densities allows for determination of particle angular distributions, and information on the kinetic energy can be obtained by the use of passive absorbers. We present a precise method of measuring spectral distributions of laser-accelerated protons in a single etching and analysis process. We make use of a one-to-one relation between proton energy and track size and present a precise calibration based on monoenergetic particle beams. While this relation is limited to proton energies below 1 MeV, we show that the range of spectral measurements can be significantly extended by simultaneous use of absorbers of suitable thicknesses. Examples from laser-plasma interactions are presented, and quantitative results on proton energies and particle numbers are compared to those obtained from a time-of-flight detector. The spectrum end points of continuous energy distributions have been determined with both detector types and coincide within 50-100 keV

Development of a few TW Ti:Sa laser system at 100 Hz for proton acceleration

[EN] We report the development of a table-top high peak power Titanium:Sapphire (Ti:Sa) CPA laser working at 100 Hz capable of delivering 205 mJ, 55 fs pulses. Every amplification stage is pumped by Nd-doped solid-state lasers and fully powered by diodes. Thermal effects in the Ti:Sa amplifiers are compensated passively with optics. This system is intended to be used for proton acceleration experiments at high repetition rates.Centro para el Desarrollo Tecnológico Industrial (CDTI, Spain) within the INNPRONTA program, Grant no. IPT-20111027.Lera, R.; Bellido-Millán, PJ.; Sánchez, I.; Mur, P.; Seimetz, M.; Benlloch Baviera, JM.; Roso, L.... (2019). Development of a few TW Ti:Sa laser system at 100 Hz for proton acceleration. Applied Physics B. 125(1):1-8. https://doi.org/10.1007/s00340-018-7113-8S181251P. Zeitoun, G. Faivre, S. Sebban, T. Mocek, A. Hallou, M. Fajardo, D. Aubert, P. Balcou, F. Burgy, D. Douillet, S. Kazamias, G. de Lachèze-Murel, T. Lefrou, S. le Pape, P. Mercère, H. Merdji, A.S. Morlens, J.P. Rousseau, C. Valentin, Nature 431(7007), 426–429 (2004)V. Malka, S. Fritzler, E. Lefebvre, M.-M. Aleonard, F. Burgy, J.-P. Chambaret, J.-F. Chemin, K. Krushelnick, G. Malka, S.P.D. Mangles, Z. Najmudin, M. Pittman, J.-P. Rousseau, J.-N. Scheurer, B. Walton, A.E. Dangor, Science 298(5598), 1596–1600 (2002)H. Daido, M. Nishiuchi, A.S. Pirozhkov, Rep. Progress Phys. 75(5), 056401 (2012)A. Macchi, M. Borghesi, M. Passoni, Rev. Mod. Phys. 85, 751–793 (2013)T. Tajima, J.M. Dawson, Phys. Rev. Lett. 43, 267–270 (1979)M. Noaman-ul Haq, H. Ahmed, T. Sokollik, L. Yu, Z. Liu, X. Yuan, F. Yuan, M. Mirzaie, X. Ge, L. Chen, J. Zhang, Phys. Rev. Accel. Beams 20, 041301 (2017)D. Strickland, G. Mourou, Opt. Commun. 53(3), 219–221 (1985)G. Cheriaux, B. Walker, L.F. Dimauro, P. Rousseau, F. Salin, J.P. Chambaret, Opt. Lett. 21(6), 414–416 (1996)P. Tournois, Opt. Commun. 140(4), 245–249 (1997)R. Soulard, A. Brignon, S. Raby, E. Durand, R. Moncorgé, Appl. Phys. B 106(2), 295–300 (2012)J. Liu, L. Ge, L. Feng, H. Jiang, H. Su, T. Zhou, J. Wang, Q. Gao, J. Li, Chin. Opt. Lett. 14(5), 051404 (2016)A. Maleki, M.K. Tehrani, H. Saghafifar, M.H.M. Dindarlu, H. Ebadian, Laser Phys. 26(2), 025003 (2016)R. Lera, F. Valle-Brozas, S. Torres-Peiró, A.R. de-la Cruz, M. Galán, P. Bellido, M. Seimetz, J.M. Benlloch, L. Roso, Appl. Opt. 55(33), 9573–9576 (2016)R. Lausten, P. Balling, J. Opt. Soc. Am. B 20(7), 1479–1485 (2003)I. Nam, M. Kim, T.H. Lee, S.W. Lee, H. Suk, Curr. Appl. Phys. 15(4), 468–472 (2015)E. Treacy, IEEE J. Quantum Electron. 5(9), 454–458 (1969)A. Trisorio, S. Grabielle, M. Divall, N. Forget, C.P. Hauri, Opt. Lett. 37(14), 2892–2894 (2012)Y.-H. Cha, Y.-W. Lee, S.M. Nam, J.M. Han, Y.J. Rhee, B.D. Yoo, B.C. Lee, Y.U. Jeong, Appl. Opt. 46(28), 6854–6858 (2007)P. Bellido, R. Lera, M. Seimetz, A.R. de la Cruz, S. Torres-Peiró, M. Galán, P. Mur, I. Sánchez, R. Zaffino, L. Vidal, A. Soriano, S. Sánchez, F. Sánchez, M. Rodríguez-Álvarez, J. Rigla, L. Moliner, A. Iborra, L. Hernández, D. Grau-Ruiz, A. González, J. García-Garrigos, E. Díaz-Caballero, P. Conde, A. Aguilar, L. Roso, J. Benlloch, J. Instrum. 12(05), T05001 (2017

Characterization of protons accelerated from a 3 TW table-top laser system

[EN] We report on benchmark tests of a 3 TW/50 fs, table-top laser system specifically developed for proton acceleration with an intrinsic pump rate up to 100 Hz. In two series of single-shot measurements differing in pulse energy and contrast the successful operation of the diode pumped laser is demonstrated. Protons have been accelerated up to 1.6 MeV in interactions of laser pulses focused on aluminium and mylar foils between 0.8 and 25 mu m thickness. Their spectral distributions and maximum energies are consistent with former experiments under similar conditions. These results show the suitability of our system and provide a reference for studies of laser targets at high repetition rate and possible applications.This project has been funded by Centro para el Desarrollo Tecnologico Industrial (CDTI, Spain) within the INNPRONTA program, grant no. IPT-20111027, by EUROSTARS project E9113, and by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1.Bellido-Millán, PJ.; Lera, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Torres Peiró, S.; Galán, M.; Mur, P.... (2017). Characterization of protons accelerated from a 3 TW table-top laser system. Journal of Instrumentation. 12:1-12. https://doi.org/10.1088/1748-0221/12/05/T05001S11212Daido, H., Nishiuchi, M., & Pirozhkov, A. S. (2012). Review of laser-driven ion sources and their applications. Reports on Progress in Physics, 75(5), 056401. doi:10.1088/0034-4885/75/5/056401Macchi, A., Borghesi, M., & Passoni, M. (2013). Ion acceleration by superintense laser-plasma interaction. Reviews of Modern Physics, 85(2), 751-793. doi:10.1103/revmodphys.85.751Ledingham, K., Bolton, P., Shikazono, N., & Ma, C.-M. (2014). Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress. Applied Sciences, 4(3), 402-443. doi:10.3390/app4030402Kraft, S. D., Richter, C., Zeil, K., Baumann, M., Beyreuther, E., Bock, S., … Pawelke, J. (2010). Dose-dependent biological damage of tumour cells by laser-accelerated proton beams. New Journal of Physics, 12(8), 085003. doi:10.1088/1367-2630/12/8/085003Yogo, A., Sato, K., Nishikino, M., Mori, M., Teshima, T., Numasaki, H., … Daido, H. (2009). Application of laser-accelerated protons to the demonstration of DNA double-strand breaks in human cancer cells. Applied Physics Letters, 94(18), 181502. doi:10.1063/1.3126452Fritzler, S., Malka, V., Grillon, G., Rousseau, J. P., Burgy, F., Lefebvre, E., … Ledingham, K. W. D. (2003). Proton beams generated with high-intensity lasers: Applications to medical isotope production. Applied Physics Letters, 83(15), 3039-3041. doi:10.1063/1.1616661Kishimura, H., Morishita, H., Okano, Y. H., Okano, Y., Hironaka, Y., Kondo, K., … Nemoto, K. (2004). Enhanced generation of fast protons from a polymer-coated metal foil by a femtosecond intense laser field. Applied Physics Letters, 85(14), 2736-2738. doi:10.1063/1.1803915Nakamura, S., Iwashita, Y., Noda, A., Shirai, T., Tongu, H., Fukumi, A., … Wada, Y. (2006). Real-Time Optimization of Proton Production by Intense Short-Pulse Laser with Time-of-Flight Measurement. Japanese Journal of Applied Physics, 45(No. 34), L913-L916. doi:10.1143/jjap.45.l913Nishiuchi, M., Fukumi, A., Daido, H., Li, Z., Sagisaka, A., Ogura, K., … Nakamura, S. (2006). The laser proton acceleration in the strong charge separation regime. Physics Letters A, 357(4-5), 339-344. doi:10.1016/j.physleta.2006.04.053Yogo, A., Daido, H., Fukumi, A., Li, Z., Ogura, K., Sagisaka, A., … Itoh, A. (2007). Laser prepulse dependency of proton-energy distributions in ultraintense laser-foil interactions with an online time-of-flight technique. Physics of Plasmas, 14(4), 043104. doi:10.1063/1.2721066Robinson, A. P. L., Foster, P., Adams, D., Carroll, D. C., Dromey, B., Hawkes, S., … Neely, D. (2009). Spectral modification of laser-accelerated proton beams by self-generated magnetic fields. New Journal of Physics, 11(8), 083018. doi:10.1088/1367-2630/11/8/083018Nemoto, K., Maksimchuk, A., Banerjee, S., Flippo, K., Mourou, G., Umstadter, D., & Bychenkov, V. Y. (2001). Laser-triggered ion acceleration and table top isotope production. Applied Physics Letters, 78(5), 595-597. doi:10.1063/1.1343845Lee, K., Park, S. H., Cha, Y.-H., Lee, J. Y., Lee, Y. W., Yea, K.-H., & Jeong, Y. U. (2008). Generation of intense proton beams from plastic targets irradiated by an ultraintense laser pulse. Physical Review E, 78(5). doi:10.1103/physreve.78.056403Yogo, A., Daido, H., Bulanov, S. V., Nemoto, K., Oishi, Y., Nayuki, T., … Tajima, T. (2008). Laser ion acceleration via control of the near-critical density target. Physical Review E, 77(1). doi:10.1103/physreve.77.016401Lee, K., Lee, J. Y., Park, S. H., Cha, Y.-H., Lee, Y. W., Kim, K. N., & Jeong, Y. U. (2011). Dominant front-side acceleration of energetic proton beams from plastic targets irradiated by an ultraintense laser pulse. Physics of Plasmas, 18(1), 013101. doi:10.1063/1.3496058OKIHARA, S., SENTOKU, Y., SUEDA, K., SHIMIZU, S., SATO, F., MIYANAGA, N., … SAKABE, S. (2002). Energetic Proton Generation in a Thin Plastic Foil Irradiated by Intense Femtosecond Lasers. Journal of Nuclear Science and Technology, 39(1), 1-5. doi:10.1080/18811248.2002.9715150McKenna, P., Ledingham, K. W. D., Spencer, I., McCany, T., Singhal, R. P., Ziener, C., … Clark, E. L. (2002). Characterization of multiterawatt laser-solid interactions for proton acceleration. Review of Scientific Instruments, 73(12), 4176-4184. doi:10.1063/1.1516855Spencer, I., Ledingham, K. W. D., McKenna, P., McCanny, T., Singhal, R. P., Foster, P. S., … Davies, J. R. (2003). Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate tabletop-laser pulses interacting with solid targets. Physical Review E, 67(4). doi:10.1103/physreve.67.046402Kaluza, M., Schreiber, J., Santala, M. I. K., Tsakiris, G. D., Eidmann, K., Meyer-ter-Vehn, J., & Witte, K. J. (2004). Influence of the Laser Prepulse on Proton Acceleration in Thin-Foil Experiments. Physical Review Letters, 93(4). doi:10.1103/physrevlett.93.045003Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.185002Neely, D., Foster, P., Robinson, A., Lindau, F., Lundh, O., Persson, A., … McKenna, P. (2006). Enhanced proton beams from ultrathin targets driven by high contrast laser pulses. Applied Physics Letters, 89(2), 021502. doi:10.1063/1.2220011Steinke, S., Henig, A., Schnürer, M., Sokollik, T., Nickles, P. V., Jung, D., … Habs, D. (2010). Efficient ion acceleration by collective laser-driven electron dynamics with ultra-thin foil targets. Laser and Particle Beams, 28(1), 215-221. doi:10.1017/s0263034610000157Strickland, D., & Mourou, G. (1985). Compression of amplified chirped optical pulses. Optics Communications, 56(3), 219-221. doi:10.1016/0030-4018(85)90120-8Yogo, A., Kondo, K., Mori, M., Kiriyama, H., Ogura, K., Shimomura, T., … Bolton, P. R. (2014). Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers. Optics Express, 22(2), 2060. doi:10.1364/oe.22.002060Trisorio, A., Grabielle, S., Divall, M., Forget, N., & Hauri, C. P. (2012). Self-referenced spectral interferometry for ultrashort infrared pulse characterization. Optics Letters, 37(14), 2892. doi:10.1364/ol.37.002892Seimetz, M., Bellido, P., Soriano, A., Garcia Lopez, J., Jimenez-Ramos, M. C., Fernandez, B., … Benlloch, J. M. (2015). Calibration and Performance Tests of Detectors for Laser-Accelerated Protons. IEEE Transactions on Nuclear Science, 62(6), 3216-3224. doi:10.1109/tns.2015.2480682Nürnberg, F., Schollmeier, M., Brambrink, E., Blažević, A., Carroll, D. C., Flippo, K., … Roth, M. (2009). Radiochromic film imaging spectroscopy of laser-accelerated proton beams. Review of Scientific Instruments, 80(3), 033301. doi:10.1063/1.3086424Oishi, Y., Nayuki, T., Fujii, T., Takizawa, Y., Wang, X., Yamazaki, T., … Andreev, A. A. (2005). Dependence on laser intensity and pulse duration in proton acceleration by irradiation of ultrashort laser pulses on a Cu foil target. Physics of Plasmas, 12(7), 073102. doi:10.1063/1.1943436Nishiuchi, M., Daito, I., Ikegami, M., Daido, H., Mori, M., Orimo, S., … Yoshiyuki, T. (2009). Focusing and spectral enhancement of a repetition-rated, laser-driven, divergent multi-MeV proton beam using permanent quadrupole magnets. Applied Physics Letters, 94(6), 061107. doi:10.1063/1.3078291Antici, P., Fuchs, J., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Pépin, H. (2007). Energetic protons generated by ultrahigh contrast laser pulses interacting with ultrathin targets. Physics of Plasmas, 14(3), 030701. doi:10.1063/1.2480610Green, J. S., Carroll, D. C., Brenner, C., Dromey, B., Foster, P. S., Kar, S., … Zepf, M. (2010). Enhanced proton flux in the MeV range by defocused laser irradiation. New Journal of Physics, 12(8), 085012. doi:10.1088/1367-2630/12/8/085012Zeil, K., Kraft, S. D., Bock, S., Bussmann, M., Cowan, T. E., Kluge, T., … Schramm, U. (2010). The scaling of proton energies in ultrashort pulse laser plasma acceleration. New Journal of Physics, 12(4), 045015. doi:10.1088/1367-2630/12/4/045015Nishiuchi, M., Daido, H., Yogo, A., Orimo, S., Ogura, K., Ma, J., … Azuma, H. (2008). Efficient production of a collimated MeV proton beam from a polyimide target driven by an intense femtosecond laser pulse. Physics of Plasmas, 15(5), 053104. doi:10.1063/1.2928161Macchi, A., Sgattoni, A., Sinigardi, S., Borghesi, M., & Passoni, M. (2013). Advanced strategies for ion acceleration using high-power lasers. Plasma Physics and Controlled Fusion, 55(12), 124020. doi:10.1088/0741-3335/55/12/124020Fuchs, J., Antici, P., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Audebert, P. (2005). Laser-driven proton scaling laws and new paths towards energy increase. Nature Physics, 2(1), 48-54. doi:10.1038/nphys199Schwoerer, H., Pfotenhauer, S., Jäckel, O., Amthor, K.-U., Liesfeld, B., Ziegler, W., … Esirkepov, T. (2006). Laser-plasma acceleration of quasi-monoenergetic protons from microstructured targets. Nature, 439(7075), 445-448. doi:10.1038/nature04492Margarone, D., Klimo, O., Kim, I. J., Prokůpek, J., Limpouch, J., Jeong, T. M., … Korn, G. (2012). Laser-Driven Proton Acceleration Enhancement by Nanostructured Foils. Physical Review Letters, 109(23). doi:10.1103/physrevlett.109.234801Flippo, K. A., d’ Humières, E., Gaillard, S. A., Rassuchine, J., Gautier, D. C., Schollmeier, M., … Hegelich, B. M. (2008). Increased efficiency of short-pulse laser-generated proton beams from novel flat-top cone targets. Physics of Plasmas, 15(5), 056709. doi:10.1063/1.291812

Identification of a novel polyfluorinated compound as a lead to inhibit human enzymes aldose reductase and AKR1B10 : structure determination of both ternary complexes and implications for drug design

Aldo-keto reductases (AKRs) are mostly monomeric enzymes which fold into a highly conserved ([alpha]/[beta])8 barrel, while their substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable external loops. The closely related human enzymes aldose reductase (AR or AKR1B1) and AKR1B10 are of biomedical interest because of their involvement in secondary diabetic complications (AR) and in cancer, e.g. hepatocellular carcinoma and smoking-related lung cancer (AKR1B10). After characterization of the IC50 values of both AKRs with a series of polyhalogenated compounds, 2,2',3,3',5,5',6,6'-octafluoro-4,4'-biphenyldiol (JF0064) was identified as a lead inhibitor of both enzymes with a new scaffold (a 1,1'-biphenyl-4,4'-diol). An ultrahigh-resolution X-ray structure of the AR-­NADP+-JF0064 complex has been determined at 0.85 Å resolution, allowing it to be observed that JF0064 interacts with the catalytic residue Tyr48 through a negatively charged hydroxyl group (i.e. the acidic phenol). The non-competitive inhibition pattern observed for JF0064 with both enzymes suggests that this acidic hydroxyl group is also present in the case of AKR1B10. Moreover, the combination of surface lysine methylation and the introduction of K125R and V301L mutations enabled the determination of the X-ray crystallo­graphic structure of the corresponding AKR1B10-NADP+-JF0064 complex. Comparison of the two structures has unveiled some important hints for subsequent structure-based drug-design efforts

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Envejecimiento de la población

&bull;Actividades b&aacute;sicas de la vida diaria en personas mayores y factores asociados &bull;Asociaci&oacute;n entre depresi&oacute;n y posesi&oacute;n de mascotas en personas mayores &bull;Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF &bull;Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura &bull;Caracterizaci&oacute;n de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) &bull;Comportamiento de las patolog&iacute;as incluidas como GES para el adulto mayor atendido en un Cesfam &bull;Contribuci&oacute;n de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid &bull;Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria &bull;Evaluaci&oacute;n del programa de discapacidad severa en Casablanca con la matriz de marco l&oacute;gico &bull;Factores asociados a satisfacci&oacute;n vital en una cohorte de adultos mayores de Santiago, Chile &bull;Pauta instrumental para la identificaci&oacute;n de riesgos para el adulto mayor autovalente, en su vivienda &bull;Perfil farmacol&oacute;gico del paciente geri&aacute;trico institucionalizado y posibles consecuencias en el deterioro cognitivo &bull;Programa de cuidados paliativos y alivio del dolor en Puerto Natales &bull;Rehabilitaci&oacute;n mandibular implantoprot&eacute;sica: efecto en calidad de vida relacionada con salud bucal en adultos mayores &bull;Salud bucodental en adultos mayores autovalentes de la Regi&oacute;n de Valpara&iacute;so &bull;Transici&oacute;n epidemiol&oacute;gica y el estudio de carga de enfermedad en Brasi

Carbon dioxide fluxes increase from day to night across European streams

Globally, inland waters emit over 2 Pg of carbon per year as carbon dioxide, of which the majority originates from streams and rivers. Despite the global significance of fluvial carbon dioxide emissions, little is known about their diel dynamics. Here we present a large-scale assessment of day- and night-time carbon dioxide fluxes at the water-air interface across 34 European streams. We directly measured fluxes four times between October 2016 and July 2017 using drifting chambers. Median fluxes are 1.4 and 2.1 mmol m−2 h−1 at midday and midnight, respectively, with night fluxes exceeding those during the day by 39%. We attribute diel carbon dioxide flux variability mainly to changes in the water partial pressure of carbon dioxide. However, no consistent drivers could be identified across sites. Our findings highlight widespread day-night changes in fluvial carbon dioxide fluxes and suggest that the time of day greatly influences measured carbon dioxide fluxes across European streams