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This paper reports the initial results of a pilot study investigating the relationships among long-term land use, settlements, historic population, and their potential influence for understanding and evaluating current and future land use. Most of our work to date has been focused on evaluating chang- ing patterns of historic settlement and its relationship to what we know about the historic environment and landscape. Here, we instead rely on remotely-sensed big data as a first step to see how patterns of past land use are correlated with what we know about current land use and land cover. The pilot study initiates a broader research agenda that better incorporates what we know about past landscapes into contemporary land use decisions and to offer critical insights into how the future could be shaped by integrating information about the past. As a first step, the analysis is intentionally broad so that our next steps can provide the fidelity and resolution to offer place based information for design and planning. Nevertheless, it offers a unique window of perception into current land use and a platform for operationalizing evolutionary uses of the past for better managing, designing, and planning complex land systems and moving beyond analogic uses. 

Infection with hepatitis B virus (HBV) is a main risk factor for hepatocellular carcinoma (HCC). Extracellular vesicles, such as exosomes, play an important role in tumor development and metastasis, including regulation of HBV-related HCC. In this study, we have characterized exosome microRNA and proteins released in vitro from hepatitis B virus (HBV)-related HCC cell lines SNU-423 and SNU-182 and immortalized normal hepatocyte cell lines (THLE2 and THLE3) using microRNA sequencing and mass spectrometry. Bioinformatics, including functional enrichment and network analysis, combined with survival analysis using data related to HCC in The Cancer Genome Atlas (TCGA) database, were applied to examine the prognostic significance of the results. More than 40 microRNAs and 200 proteins were significantly dysregulated (p < 0.05) in the exosomes released from HCC cells in comparison with the normal liver cells. The functional analysis of the differentially expressed exosomal miRNAs (i.e., mir-483, mir-133a, mir-34a, mir-155, mir-183, mir-182), their predicted targets, and exosomal differentially expressed proteins (i.e., POSTN, STAM, EXOC8, SNX9, COL1A2, IDH1, FN1) showed correlation with pathways associated with HBV, virus activity and invasion, exosome formation and adhesion, and exogenous protein binding. The results from this study may help in our understanding of the role of HBV infection in the development of HCC and in the development of new targets for treatment or non-invasive predictive biomarkers of HCC. 

Abstract There is about to be an abrupt step-change in the use of coastal seas around the globe, specifically by the addition of large-scale offshore renewable energy (ORE) developments to combat climate change. Developing this sustainable energy supply will require trade-offs between both direct and indirect environmental effects, as well as spatial conflicts with marine uses like shipping, fishing, and recreation. However, the nexus between drivers, such as changes in the bio-physical environment from the introduction of structures and extraction of energy, and the consequent impacts on ecosystem services delivery and natural capital assets is poorly understood and rarely considered through a whole ecosystem perspective. Future marine planning needs to assess these changes as part of national policy level assessments but also to inform practitioners about the benefits and trade-offs between different uses of natural resources when making decisions to balance environmental and energy sustainability and socio-economic impacts. To address this shortfall, we propose an ecosystem-based natural capital evaluation framework that builds on a dynamic Bayesian modelling approach which accounts for the multiplicity of interactions between physical (e.g. bottom temperature), biological (e.g. net primary production) indicators and anthropogenic marine use (i.e. fishing) and their changes across space and over time. The proposed assessment framework measures ecosystem change, changes in ecosystem goods and services and changes in socio-economic value in response to ORE deployment scenarios as well as climate change, to provide objective information for decision processes seeking to integrate new uses into our marine ecosystems. Such a framework has the potential of exploring the likely outcomes in the same metrics (both ecological and socio-economic) from alternative management and climate scenarios, such that objective judgements and decisions can be made, as to how to balance the benefits and trade-offs between a range of marine uses to deliver long-term environmental sustainability, economic benefits, and social welfare. 

Abstract The offshore windfarm industry has great potential for sustainable energy but requires space. The ability of fisheries to harvest within these windfarms varies. This has created a conflict between these two industries and discussions are hampered by differing approaches to the marine environment, a lack of understanding of what each industries requires, the significant money at stake, and the values the public place on marine conservation. To characterize, standardize, and quantify the scientific data addressing these concerns requires a framework. The framework should categorize data on spatial scales of 1 cm2 to 1 km2 (individual turbines/fishing vessels), 1–1000 km2 (companies), and >1000 km2 (regions), and by their ecological, economic, cultural, and institutional impacts. The framework should be repeated over temporal scales of the windfarm: pre-development (1–3 years), construction (1–2 years), post-construction (20–40 years), and decommission. Balancing the metrics used to describe the two industries will allow people to communicate clearly in an organized systematic way, hopefully resulting in a continuing supply of sustainable sea food and renewable energy to an increasingly hungry world. 

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone. 

Combination nanodrugs are promising therapeutic agents for cancer treatment. However, they often require the use of complex nanovehicles for transportation into the tumor site. Herein, a new class of carrier-free ionic nanomaterials (INMs) is presented, which are self-assembled by the drug molecules themselves. In this regard, a photothermal therapy (PTT) mechanism is combined with a chemotherapy (chemo) mechanism using ionic liquid chemistry to develop a combination drug to deliver multiple cytotoxic mechanisms simultaneously. Nanodrugs were developed from an ionic material-based chemo-PTT combination drug by using a simple reprecipitation method. Detailed examination of the photophysical properties (absorption, fluorescence emission, quantum yield, radiative and non-radiative rate) of the INMs revealed significant spectral changes which are directly related to their therapeutic effect. The reactive oxygen species quantum yield and the light to heat conversion efficiency of the photothermal agents were shown to be enhanced in combination nanomedicines as compared to their respective parent compounds. The ionic nanodrugs exhibited an improved dark and light cytotoxicity in vitro as compared to either the chemotherapeutic or photothermal parent compounds individually, due to a synergistic effect of the combined therapies, improved photophysical properties and their nanoparticles’ morphology that enhanced the cellular uptake of the drugs. This study presents a general framework for the development of carrier-free dual-mechanism nanotherapeutics.