Uncertainty in Detection of Volcanic Activity Using Infrasound Arrays: Examples From Mt. Etna, Italy

SD and LZ acknowledge the support from the EUROVOLC project under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 731070). The authors thank the staff of the Istituto Nazionale di Geofisica e Vulcanologia Sezione di Catania, in particular Salvo Rapisarda, Daniele Pellegrino, Mario Pulvirenti, and Danilo Contrafatto for their valuable support in the field.The injection of gas and pyroclastic material from volcanic vents into the atmosphere is a prolific source of acoustic waves. Infrasound arrays offer efficient, cost-effective, and near real-time solutions to track the rate and intensity of surface activity at volcanoes. Here, we present a simple framework for the analysis of acoustic array data, based on least-squares beamforming, that allows to evaluate the direction and speed of propagation of acoustic waves between source and array. The algorithms include a new and computationally efficient approach for quantitative assessment of the uncertainty on array measurements based on error propagation theory. We apply the algorithms to new data collected by two 6-element infrasound arrays deployed at Mt. Etna during the period July–August 2019. Our results demonstrate that the use of two infrasound arrays allowed detecting and tracking acoustic sources from multiple craters and active vents associated with degassing and ash-rich explosions, vigorous and frequent Strombolian activity, opening of new eruptive fractures and emplacement of lava flows. Finally, we discuss the potential use of metrics based on infrasound array analyses to inform eruption monitoring operations and early warning at volcanoes characterized by episodic intensification of activity.NERC Natural Environment Research Council NE/P00105X/1European Union (EU)Geoscientists without Borders grant from the Society of Exploration Geophysic

National and Regional Implications of Targeting the Conservation Reserve

Within the Conservation Reserve (CR) program, a change in program criteria could reduce the amount of erosion material entering our nation\u27s waterways. The inclusion of land adjacent to water bodies, flowing streams, and river waterways may reduce erosion from these lands and improve water quality. These buffer strip areas, removed from production and placed in the reserve with a vegetative cover, would limit sedimentation and act to prevent upland erosion materials from reaching waterway channels, thus enhancing the programs\u27 environmental benefits. This paper analyzes the economic benefits of including buffer strups as eligible CR land, and it reviews the problems of identifying such areas

Co-Eruptive Tremor from Bogoslof Volcano: Seismic Wavefield Composition at Regional Distances

We analyze seismic tremor recorded during eruptive activity over the course of the 2016–2017 eruption of Bogoslof volcano, Alaska. Only regional recordings of the tremor wavefield exist for Bogoslof, making it a challenge to place the recordings in context with other eruptions that are normally captured by local seismic data. We apply a technique of time-frequency polarization analysis to three-component seismic data to reveal the wavefield composition of Bogoslof eruption tremor.We find that at regional distances, the tremor is dominated by P-waves in the band from 1.5 to 10 Hz. Using this information, along with an enriched Bogoslof earthquake catalog, we obtain estimates of average reduced displacement (DR) for eruption tremor during 25 of the 70 Bogoslof events. DR reaches as high as approximately 40 cm2 for two of the major events, similar to other VEI~3 eruptions in Alaska. Overall, average reduced displacement displays a weak correlation to plume height during the first half of the 9-month-long eruption sequence, with a few notable exceptions. The two events with the highest DR values also generated measurable eruption tremor at very-long-periods (VLP) between 0.05 and 0.15 Hz

GDNF-Transfected Macrophages Produce Potent Neuroprotective Effects in Parkinson's Disease Mouse Model

The pathobiology of Parkinson's disease (PD) is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) projecting to the striatum. Currently, there are no treatments that can halt or reverse the course of PD; only palliative therapies, such as replacement strategies for missing neurotransmitters, exist. Thus, the successful brain delivery of neurotrophic factors that promote neuronal survival and reverse the disease progression is crucial. We demonstrated earlier systemically administered autologous macrophages can deliver nanoformulated antioxidant, catalase, to the SNpc providing potent anti-inflammatory effects in PD mouse models. Here we evaluated genetically-modified macrophages for active targeted brain delivery of glial cell-line derived neurotropic factor (GDNF). To capitalize on the beneficial properties afforded by alternatively activated macrophages, transfected with GDNF-encoded pDNA cells were further differentiated toward regenerative M2 phenotype. A systemic administration of GDNF-expressing macrophages significantly ameliorated neurodegeneration and neuroinflammation in PD mice. Behavioral studies confirmed neuroprotective effects of the macrophage-based drug delivery system. One of the suggested mechanisms of therapeutic effects is the release of exosomes containing the expressed neurotropic factor followed by the efficient GDNF transfer to target neurons. Such formulations can serve as a new technology based on cell-mediated active delivery of therapeutic proteins that attenuate and reverse progression of PD, and ultimately provide hope for those patients who are already significantly disabled by the disease

Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells

AbstractExosomes have recently come into focus as "natural nanoparticles" for use as drug delivery vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we developed different methods of loading exosomes released by macrophages with PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our studies demonstrated a nearly complete co-localization of airway-delivered exosomes with cancer cells in a model of murine Lewis lung carcinoma pulmonary metastases, and a potent anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers.From the Clinical EditorExosomes are membrane-derived natural vesicles of ~40 - 200 nm size. They have been under extensive research as novel drug delivery vehicles. In this article, the authors developed exosome-based system to carry formulation of PTX and showed efficacy in the treatment of multi-drug resistant cancer cells. This novel system may be further developed to carry other chemotherapeutic agents in the future

Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease

Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD

Extracellular Vesicles Released by Genetically Modified Macrophages Activate Autophagy and Produce Potent Neuroprotection in Mouse Model of Lysosomal Storage Disorder, Batten Disease

Over the recent decades, the use of extracellular vesicles (EVs) has attracted considerable attention. Herein, we report the development of a novel EV-based drug delivery system for the transport of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) to treat Batten disease (BD). Endogenous loading of macrophage-derived EVs was achieved through transfection of parent cells with TPP1-encoding pDNA. More than 20% ID/g was detected in the brain following a single intrathecal injection of EVs in a mouse model of BD, ceroid lipofuscinosis neuronal type 2 (CLN2) mice. Furthermore, the cumulative effect of EVs repetitive administrations in the brain was demonstrated. TPP1-loaded EVs (EV-TPP1) produced potent therapeutic effects, resulting in efficient elimination of lipofuscin aggregates in lysosomes, decreased inflammation, and improved neuronal survival in CLN2 mice. In terms of mechanism, EV-TPP1 treatments caused significant activation of the autophagy pathway, including altered expression of the autophagy-related proteins LC3 and P62, in the CLN2 mouse brain. We hypothesized that along with TPP1 delivery to the brain, EV-based formulations can enhance host cellular homeostasis, causing degradation of lipofuscin aggregates through the autophagy–lysosomal pathway. Overall, continued research into new and effective therapies for BD is crucial for improving the lives of those affected by this condition

ATLAS Beam Steering Mechanism (BSM) Lessons Learned

This paper describes the design, testing, and lessons learned during the development of the Advanced Topographic Laser Altimeter System (ATLAS) Beam Steering Mechanism (BSM). The BSM is a 2 degree-of-freedom tip-tilt mechanism for the purpose of pointing a flat mirror to tightly control the co-alignment of the transmitted laser and the receiver telescope of the ATLAS instrument. The high resolution needs of the mission resulted in sub-arcsecond pointing and knowledge requirements, which have been met. Development of the methodology to verify performance required significant effort. The BSM will fly as part of the Ice, Cloud, and Elevation Satellite II Mission (ICESat II), which is scheduled to be launched in 2017. The ICESat II primary mission is to map the Earth's surface topography for the determination of seasonal changes of ice sheet thickness and vegetation canopy thickness to establish long-term trends

Short-Term Forecasting and Detection of Explosions During the 2016–2017 Eruption of Bogoslof Volcano, Alaska

We describe a multidisciplinary approach to forecast, rapidly detect, and characterize explosive events during the 2016–2017 eruption of Bogoslof volcano, a back-arc shallow submarine volcano in Alaska’s Aleutian arc. The eruptive sequence began in December 2016 and included about 70 discrete explosive events. Because the volcano has no local monitoring stations, we used distant stations on the nearest volcanoes, Okmok (54 km) and Makushin (72 km), combined with regional infrasound sensors and lightning detection from the Worldwide Lightning Location Network (WWLLN). Pre-eruptive seismicity was detected for 12 events during the first half of the eruption; for all other events co-eruptive signals allowed for detection only. Monitoring of activity used a combination of scheduled checks combined with automated alarms. Alarms triggered on real-time data included real-time seismic amplitude measurement (RSAM); infrasound from several arrays, the closest being on Okmok; and lightning strokes detected from WWLLN within a 20-km radius of the volcano. During periods of unrest, a multidisciplinary response team of four people fulfilled specific roles to evaluate geophysical and remote-sensing data, run event-specific ash-cloud dispersion models, ensure interagency coordination, and develop and distribute of formalized warning products. Using this approach, for events that produced ash clouds ≥7.5 km above sea level, Alaska Volcano Observatory (AVO) called emergency response partners 15 min, and issued written notices 30 min, after event onset (mean times). Factors that affect timeliness of written warnings include event size and number of data streams available; bigger events and more data both decrease uncertainty and allow for faster warnings. In remote areas where airborne ash is the primary hazard, the approach used at Bogoslof is an effective strategy for hazard mitigation

Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins

Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson’s disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle (‘nanozyme’) with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices