Challenges and emerging technical solutions in on-growing salmon farming

Farming of Atlantic salmon has grown rapidly from its start in the early 1970s until today, with production approaching two million tonnes. Sea cages are the dominant production system for the on-growing stage of salmon farming. It represents an effective production system with lower investment and running costs than land-based systems. The development and improvement of the sea cage farming system has been one of the most important factors for the growth of the salmon farming industry. However, during recent years certain problems related to their placement in the open marine environment have proved highly challenging, increasing operating costs and impacting on industry public relations. The problems are mainly due to parasites, diseases and escape of fish. In this article, emerging technical solutions for solving those problems are described

Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field

[EN] We report here the on-command cargo controlled delivery using an alternating magnetic field (AMF) from magnetic silica mesoporous supports capped with a lipid bilayer. © 2012 The Royal Society of Chemistry.Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and CTQ2008-00690) and the Generalitat Valenciana (project PROMETEO/2009/016) is gratefully acknowledged. E. B. thanks the Spanish Ministry of Education (MEC) for his Jose Castillejo fellowship (JC2010-0090).Bringas, E.; Köysüren, Ö.; Quach, DV.; Mahmoudi, M.; Aznar Gimeno, E.; Roehling, JD.; Marcos Martínez, MD.... (2012). Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications. 48:5647-5649. https://doi.org/10.1039/C2CC31563GS5647564948Aznar, E., Martínez-Máñez, R., & Sancenón, F. (2009). Controlled release using mesoporous materials containing gate-like scaffoldings. Expert Opinion on Drug Delivery, 6(6), 643-655. doi:10.1517/17425240902895980Cotí, K. K., Belowich, M. E., Liong, M., Ambrogio, M. W., Lau, Y. A., Khatib, H. A., … Stoddart, J. F. (2009). Mechanised nanoparticles for drug delivery. Nanoscale, 1(1), 16. doi:10.1039/b9nr00162jLai, C.-Y., Trewyn, B. G., Jeftinija, D. M., Jeftinija, K., Xu, S., Jeftinija, S., & Lin, V. S.-Y. (2003). A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society, 125(15), 4451-4459. doi:10.1021/ja028650lPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Liu, R., Liao, P., Liu, J., & Feng, P. (2011). Responsive Polymer-Coated Mesoporous Silica as a pH-Sensitive Nanocarrier for Controlled Release. Langmuir, 27(6), 3095-3099. doi:10.1021/la104973jCliment, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Amorós, P., & Guillem, C. (2009). pH- and Photo-Switched Release of Guest Molecules from Mesoporous Silica Supports. Journal of the American Chemical Society, 131(19), 6833-6843. doi:10.1021/ja810011pFu, Q., Rao, G. V. R., Ista, L. K., Wu, Y., Andrzejewski, B. P., Sklar, L. A., … López, G. P. (2003). Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials. Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Thomas, C. R., Ferris, D. P., Lee, J.-H., Choi, E., Cho, M. H., Kim, E. S., … Zink, J. I. (2010). Noninvasive Remote-Controlled Release of Drug Molecules in Vitro Using Magnetic Actuation of Mechanized Nanoparticles. Journal of the American Chemical Society, 132(31), 10623-10625. doi:10.1021/ja1022267Ruiz-Hernández, E., Baeza, A., & Vallet-Regí, M. (2011). Smart Drug Delivery through DNA/Magnetic Nanoparticle Gates. ACS Nano, 5(2), 1259-1266. doi:10.1021/nn1029229Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 50(47), 11172-11175. doi:10.1002/anie.201102756Bruce, I. J., Taylor, J., Todd, M., Davies, M. J., Borioni, E., Sangregorio, C., & Sen, T. (2004). Synthesis, characterisation and application of silica-magnetite nanocomposites. Journal of Magnetism and Magnetic Materials, 284, 145-160. doi:10.1016/j.jmmm.2004.06.032Sen, T., Magdassi, S., Nizri, G., & Bruce, I. J. (2006). Dispersion of magnetic nanoparticles in suspension. Micro & Nano Letters, 1(1), 39. doi:10.1049/mnl:20065033Zhang, L., Longo, M. L., & Stroeve, P. (2000). Mobile Phospholipid Bilayers Supported on a Polyion/Alkylthiol Layer Pair. Langmuir, 16(11), 5093-5099. doi:10.1021/la9913405Liu, J., Stace-Naughton, A., Jiang, X., & Brinker, C. J. (2009). Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles. Journal of the American Chemical Society, 131(4), 1354-1355. doi:10.1021/ja808018yLiu, J., Jiang, X., Ashley, C., & Brinker, C. J. (2009). Electrostatically Mediated Liposome Fusion and Lipid Exchange with a Nanoparticle-Supported Bilayer for Control of Surface Charge, Drug Containment, and Delivery. Journal of the American Chemical Society, 131(22), 7567-7569. doi:10.1021/ja902039yAshley, C. E., Carnes, E. C., Phillips, G. K., Padilla, D., Durfee, P. N., Brown, P. A., … Brinker, C. J. (2011). The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nature Materials, 10(5), 389-397. doi:10.1038/nmat2992Hoare, T., Timko, B. P., Santamaria, J., Goya, G. F., Irusta, S., Lau, S., … Kohane, D. S. (2011). Magnetically Triggered Nanocomposite Membranes: A Versatile Platform for Triggered Drug Release. Nano Letters, 11(3), 1395-1400. doi:10.1021/nl200494tNappini, S., Bonini, M., Bombelli, F. B., Pineider, F., Sangregorio, C., Baglioni, P., & Nordèn, B. (2011). Controlled drug release under a low frequency magnetic field: effect of the citrate coating on magnetoliposomes stability. Soft Matter, 7(3), 1025-1037. doi:10.1039/c0sm00789gMalam, Y., Loizidou, M., & Seifalian, A. M. (2009). Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends in Pharmacological Sciences, 30(11), 592-599. doi:10.1016/j.tips.2009.08.004Mahmoudi, M., Laurent, S., Shokrgozar, M. A., & Hosseinkhani, M. (2011). Toxicity Evaluations of Superparamagnetic Iron Oxide Nanoparticles: Cell «Vision» versus Physicochemical Properties of Nanoparticles. ACS Nano, 5(9), 7263-7276. doi:10.1021/nn2021088Mahmoudi, M., Azadmanesh, K., Shokrgozar, M. A., Journeay, W. S., & Laurent, S. (2011). Effect of Nanoparticles on the Cell Life Cycle. Chemical Reviews, 111(5), 3407-3432. doi:10.1021/cr100316

Adeno-associated viral vector serotype 9-based gene therapy for Niemann-Pick disease type A

Niemann-Pick disease type A (NPD-A) is a lysosomal storage disorder characterized by neurodegeneration and early death. It is caused by loss-of-function mutations in the gene encoding for acid sphingomyelinase (ASM), which hydrolyzes sphingomyelin into ceramide. Here, we evaluated the safety of cerebellomedullary (CM) cistern injection of adeno-associated viral vector serotype 9 encoding human ASM (AAV9-hASM) in nonhuman primates (NHP). We also evaluated its therapeutic benefit in a mouse model of the disease (ASM-KO mice). We found that CM injection in NHP resulted in widespread transgene expression within brain and spinal cord cells without signs of toxicity. CM injection in the ASM-KO mouse model resulted in hASM expression in cerebrospinal fluid and in different brain areas without triggering an inflammatory response. In contrast, direct cerebellar injection of AAV9-hASM triggered immune response. We also identified a minimally effective therapeutic dose for CM injection of AAV9-hASM in mice. Two months after administration, the treatment prevented motor and memory impairment, sphingomyelin (SM) accumulation, lysosomal enlargement, and neuronal death in ASM-KO mice. ASM activity was also detected in plasma from AAV9-hASM CM-injected ASM-KO mice, along with reduced SM amount and decreased inflammation in the liver. Our results support CM injection for future AAV9-based clinical trials in NPD-A as well as other lysosomal storage brain disorders.Nation Foundation and by grants from the Spanish Ministry of Economy and Competitivity (SAF-2014-57539-R and SAF2017-87698-R) to M.D.L. and from NIH-NINDS (R01NS073940) to K.S.B. A.P.-C. was a recipient of the FPU predoctoral fellowship from the Spanish Ministry of Economy and Competitivity and Fundación Ramón Areces to the Centro Biología Molecular Severo Ochoa

Autonomous and Lagrangian ocean observations for Atlantic tropical cyclone studies and forecasts

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 92–103, doi:10.5670/oceanog.2017.227.The tropical Atlantic basin is one of seven global regions where tropical cyclones (TCs) commonly originate, intensify, and affect highly populated coastal areas. Under appropriate atmospheric conditions, TC intensification can be linked to upper-ocean properties. Errors in Atlantic TC intensification forecasts have not been significantly reduced during the last 25 years. The combined use of in situ and satellite observations, particularly of temperature and salinity ahead of TCs, has the potential to improve the representation of the ocean, more accurately initialize hurricane intensity forecast models, and identify areas where TCs may intensify. However, a sustained in situ ocean observing system in the tropical North Atlantic Ocean and Caribbean Sea dedicated to measuring subsurface temperature, salinity, and density fields in support of TC intensity studies and forecasts has yet to be designed and implemented. Autonomous and Lagrangian platforms and sensors offer cost-effective opportunities to accomplish this objective. Here, we highlight recent efforts to use autonomous platforms and sensors, including surface drifters, profiling floats, underwater gliders, and dropsondes, to better understand air-sea processes during high-wind events, particularly those geared toward improving hurricane intensity forecasts. Real-time data availability is key for assimilation into numerical weather forecast models.The NOAA/AOML component of this work was originally funded by the Disaster Relief Appropriations Act of 2013, also known as the Sandy Supplemental, and is currently funded through NOAA research grant NA14OAR4830103 by AOML and CARICOOS, as well as NOAA’s Integrated Ocean Observing System (IOOS). The TEMPESTS component of this work is supported by NOAA through the Cooperative Institute for the North Atlantic Region (NA13OAR4830233) with additional analysis support from the WHOI Summer Student Fellowship Program, Nortek Student Equipment Grant, and the Rutgers University Teledyne Webb Graduate Student Fellowship Program. The drifter component of this work is funded through NOAA grant NA15OAR4320071(11.432) in support of the Global Drifter Program

Ocean observations in support of studies and forecasts of tropical and extratropical cyclones

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Domingues, R., Kuwano-Yoshida, A., Chardon-Maldonado, P., Todd, R. E., Halliwell, G., Kim, H., Lin, I., Sato, K., Narazaki, T., Shay, L. K., Miles, T., Glenn, S., Zhang, J. A., Jayne, S. R., Centurioni, L., Le Henaff, M., Foltz, G. R., Bringas, F., Ali, M. M., DiMarco, S. F., Hosoda, S., Fukuoka, T., LaCour, B., Mehra, A., Sanabia, E. R., Gyakum, J. R., Dong, J., Knaff, J. A., & Goni, G. Ocean observations in support of studies and forecasts of tropical and extratropical cyclones. Frontiers in Marine Science, 6, (2019): 446, doi:10.3389/fmars.2019.00446.Over the past decade, measurements from the climate-oriented ocean observing system have been key to advancing the understanding of extreme weather events that originate and intensify over the ocean, such as tropical cyclones (TCs) and extratropical bomb cyclones (ECs). In order to foster further advancements to predict and better understand these extreme weather events, a need for a dedicated observing system component specifically to support studies and forecasts of TCs and ECs has been identified, but such a system has not yet been implemented. New technologies, pilot networks, targeted deployments of instruments, and state-of-the art coupled numerical models have enabled advances in research and forecast capabilities and illustrate a potential framework for future development. Here, applications and key results made possible by the different ocean observing efforts in support of studies and forecasts of TCs and ECs, as well as recent advances in observing technologies and strategies are reviewed. Then a vision and specific recommendations for the next decade are discussed.This study was supported by the National Oceanic and Atmospheric Administration and JSPS KAKENHI (Grant Numbers: JP17K19093, JP16K12591, and JP16H01846)

Class III peroxidases PRX01, PRX44, and PRX73 potentially target extensins during root hair growth in Arabidopsis thaliana

Root hair cells are important sensors of soil conditions. Expanding several hundred times their original size, root hairs grow towards and absorb water-soluble nutrients. This rapid growth is oscillatory and is mediated by continuous remodelling of the cell wall. Root hair cell walls contain polysaccharides and hydroxyproline-rich glycoproteins including extensins (EXTs). Class-III peroxidases (PRXs) are secreted into the apoplastic space and are thought to trigger either cell wall loosening, mediated by oxygen radical species, or polymerization of cell wall components, including the Tyr-mediated assembly of EXT networks (EXT-PRXs). The precise role of these EXT-PRXs is unknown. Using genetic, biochemical, and modeling approaches, we identified and characterized three root hair-specific putative EXT-PRXs, PRX01, PRX44, and PRX73. The triple mutant prx01,44,73 and the PRX44 and PRX73 overexpressors had opposite phenotypes with respect to root hair growth, peroxidase activity and ROS production with a clear impact on cell wall thickness. Modeling and docking calculations suggested that these three putative EXT-PRXs may interact with non-O-glycosylated sections of EXT peptides that reduce the Tyr-to-Tyr intra-chain distances in EXT aggregates and thereby may enhance Tyr crosslinking. These results suggest that these three putative EXT-PRXs control cell wall properties during the polar expansion of root hair cells.Fil: Marzol, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Borassi, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ranocha, Philippe. Instituto National de Recherches Agronomiques. Centre de Recherches de Toulouse; FranciaFil: Aptekmann, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Bringas, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Pennington, Janice. University of Wisconsin; Estados UnidosFil: Paez Valencia, Julio. University of Wisconsin; Estados UnidosFil: Martinez Pacheco, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rodriguez Garcia, Diana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rondon Guerrero, Yossmayer del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Carignani Sardoy, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mangano, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Fleming, Margaret. State University of Colorado - Fort Collins; Estados UnidosFil: Mishler Elmore, John W.. Ohio University; Estados UnidosFil: Blanco Herrera, Francisca. Universidad Andrés Bello and Millennium Institute for Integrative Biology (iBio). Facultad de Ciencias de la Vida. Centro de Biotecnología Vegeta; ChileFil: Bedinger, Patricia. State University of Colorado - Fort Collins; Estados UnidosFil: Dunand, Christophe. Instituto National de Recherches Agronomiques. Centre de Recherches de Toulouse; FranciaFil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Nadra, Alejandro Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Held, Michael. Ohio University; Estados UnidosFil: Otegui, Marisa S.. University of Wisconsin; Estados UnidosFil: Estevez, Jose Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Andrés Bello; Chil

XBT Science: Assessment of Instrumental Biases and Errors

Expendable bathythermograph (XBT) data were the major component of the ocean temperature profile observations from the late 1960s through the early 2000s, and XBTs still continue to provide critical data to monitor surface and subsurface currents, meridional heat transport, and ocean heat content. Systematic errors have been identified in the XBT data, some of which originate from computing the depth in the profile using a theoretically and experimentally derived fall-rate equation (FRE). After in-depth studies of these biases and discussions held in several workshops dedicated to discussing XBT biases, the XBT science community met at the Fourth XBT Science Workshop and concluded that XBT biases consist of 1) errors in depth values due to the inadequacy of the probe motion description done by standard FRE and 2) independent pure temperature biases. The depth error and temperature bias are temperature dependent and may depend on the data acquisition and recording system. In addition, the depth bias also includes an offset term. Some biases affecting the XBT-derived temperature profiles vary with manufacturer/probe type and have been shown to be time dependent. Best practices for historical XBT data corrections, recommendations for future collection of metadata to accompany XBT data, impact of XBT biases on scientific applications, and challenges encountered are presented in this manuscript. Analysis of XBT data shows that, despite the existence of these biases, historical XBT data without bias corrections are still suitable for many scientific applications, and that bias-corrected data can be used for climate research

Non-PEGylated liposomes for convection-enhanced delivery of topotecan and gadodiamide in malignant glioma: initial experience

Convection-enhanced delivery (CED) of highly stable PEGylated liposomes encapsulating chemotherapeutic drugs has previously been effective against malignant glioma xenografts. We have developed a novel, convectable non-PEGylated liposomal formulation that can be used to encapsulate both the topoisomerase I inhibitor topotecan (topoCED™) and paramagnetic gadodiamide (gadoCED™), providing an ideal basis for real-time monitoring of drug distribution. Tissue retention of topoCED following single CED administration was significantly improved relative to free topotecan. At a dose of 10 μg (0.5 mg/ml), topoCED had a half-life in brain of approximately 1 day and increased the area under the concentration–time curve (AUC) by 28-fold over free topotecan (153.8 vs. 5.5 μg day/g). The combination of topoCED and gadoCED was found to co-convect well in both naïve rat brain and malignant glioma xenografts (correlation coefficients 0.97–0.99). In a U87MG cell assay, the 50% inhibitory concentration (IC50) of topoCED was approximately 0.8 μM at 48 and 72 h; its concentration–time curves were similar to free topotecan and unaffected by gadoCED. In a U87MG intracranial rat xenograft model, a two-dose CED regimen of topoCED co-infused with gadoCED greatly increased median overall survival at dose levels of 0.5 mg/ml (29.5 days) and 1.0 mg/ml (33.0 days) vs. control (20.0 days; P < 0.0001 for both comparisons). TopoCED at higher concentrations (1.6 mg/ml) co-infused with gadoCED showed no evidence of histopathological changes attributable to either agent. The positive results of tissue pharmacokinetics, co-convection, cytotoxicity, efficacy, and lack of toxicity of topoCED in a clinically meaningful dose range, combined with an ideal matched-liposome paramagnetic agent, gadoCED, implicates further clinical applications of this therapy in the treatment of malignant glioma

Ultrasound-Enhanced Drug Transport and Distribution in the Brain

Drug delivery in the brain is limited by slow drug diffusion in the brain tissue. This study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. In vitro exposure to ultrasound at various frequencies (85 kHz, 174 kHz, and 1 MHz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kDa across porcine brain tissue. A maximum enhancement of 24-fold was observed at 85 kHz and 1,200 J/cm2. In vivo exposure to 1-MHz ultrasound further demonstrated the ability of ultrasound to facilitate molecule distribution in the brain of a non-human primate. Finally, ultrasound under conditions similar to those used in vivo was shown to cause no damage to plasmid DNA, siRNA, adeno-associated virus, and fetal rat cortical neurons over a range of conditions. Altogether, these studies demonstrate that ultrasound can increase drug permeation in the brain in vitro and in vivo under conditions that did not cause detectable damage

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)