Environmental Risks and Benefits of Nano-Enabled Clean Energy Technologies

Engineered nanomaterials (ENMs) are increasingly incorporated into clean energy technologies due to observed improvement in technological and system performance. Though these materials could revolutionize many products and technologies, increased use of ENMs can also introduce uncertainty and risks that are difficult to predict. Increase in ENM use could significantly increase ENM releases to the environment across their life cycle, from material synthesis to end-of-life. To address knowledge gaps and uncertainties, this work assesses a portfolio of ENMs from a systems perspective. First, characterization and quantification methods were developed for three carbonaceous ENMs, fullerenes (C60, C70, and derivative PCBM), which have promising application in solar technologies. Empirical ecotoxicity assays and predation studies were performed to determine ecotoxicity and predation effects. Next, an integrated model predicted potential risks of ENM accumulation by estimating potential manufacturing locations, spatial concentrations, and potential ecological risks. This was followed by an adaption of portfolio optimization, a model traditionally used to optimize investment performance, to model potential environmental and economic risks and simultaneous performance benefits and inform safe nano-enabled design. Ecotoxicity findings demonstrate differences among fullerenes where organisms exposed to fullerenes also experienced significantly increased predation risk, underscoring the need to consider potential system-level effects. Based on manufacturing locations, potential ENM exposure may be within buffer distances of sensitive ecosystems. However, modeled ENM accumulation would only reach levels associated with ecotoxicity risk under extreme scenarios. Future ENM use-patterns can be informed by the portfolio optimization approach, where optimal portfolios are determined by the materials-mix that yielded the greatest overall performance return while minimizing the portfolio risks. These novel methods and tools contribute to the knowledge of the benefits and risks of ENMs, which will help to guide more responsible and proactive policy and planning around ENM development and use

investigating integrin ανβ6 activation status in breast cancer

PhDbackground The extracellular matrix receptor integrin ανβ6 is known to potentiate breast cancer (BrCa) cell invasion, metastasis and tumour-trophic growth factor receptor crosstalk during tumourigenesis. Monoclonal antibody blockade of ανβ6 diminishes invasion in vitro and arrests BrCa tumour growth and metastasis in vivo. Aberrant integrin activation status has been implicated in progression to metastatic disease in BrCa; with differential internalisation and endocytic trafficking kinetics reported for active versus inactive integrin species in malignant disease. Despite its emerging potential for targeted therapy, little is known regarding regulation of integrin ανβ6–mediated activation and signalling during progression to an invasive, metastatic state. It is hypothesised that the aetiopathological significance of integrin ανβ6 during neoplastic transformation and malignant progression in BrCa is dependent specifically upon its activation status and associated conformation, since this active state will permit establishment of known integrin–mediated oncogenic signalling underpinning acquisition of a malignant phenotype, including activation of invasion and metastasis. results Canonical integrin activation studies using divalent cations and cognate ligand stimulation indicated antibodies 6.2E5 and 6.2G2 recognise activation-associated epitopes, which are also ligand-induced binding sites (LIBS) in live-labelled cells by FCM and IMF. However, their utility to discriminate the active fraction distinct from the total or inactive fractions of ανβ6 by IHC in primary BrCa samples could not be robustly established. Evaluation of the 6.2E5 and 6.2G2 epitopes in the MCF10 isogenic model revealed that relative surface abundance of these active epitopes determined by FCM was not significantly altered; but their subcellular redistribution upon neoplastic transformation and malignant progression was observed by IMF, implicating derailed internalisation and trafficking of active ανβ6 during breast tumourigenesis and metastatic disease progression. Proteomic interrogation and network analysis of the 2D-enriched adhesion assays identified 7 novel putative molecular regulators of a ligand-engaged, activated ανβ6–mediated adhesion environment (DMBT-1, MARCKS, MXRA5, SEPT6, SEPT9, MYH9, MYH10) in the BT-20 TNBC cell line. Functional validation of these candidate mediators of the “β6 adhesome” by siRNA strategies was not achieved due to inconsistent stable knockdown. Phosphoproteomic definition of LAP ligand-engaged, active ανβ6–mediated signalling (“β6 kinome”) during receptor-ligand internalisation revealed EGFR-dependency for downstream ERK1/2 signal activation in BT-20 and SUM159, but not MDA-MB-468 TNBC cells. Kinase substrate enrichment analysis (KSEA) identified 5 novel putative mediators of downstream ανβ6 signalling (COT, MAPKAPK2, PDPK1, Nuak1, TBK1) and implicated Akt1 isoform-specific activation downstream of ανβ6–LAP internalisation. Following LAP-induced ανβ6 activation and internalisation, EGFR underwent phosphorylation at multiple known activation sites, including a residue (Thr693) critical for EGFR receptor internalisation; suggesting integrin ανβ6–EGFR reciprocity during respective receptor activation and internalisation. conclusion The active conformer of integrin ανβ6 may be studied using antibodies 6.2E5 and 6.2G2 in live-labelled cells by FCM and IMF. Subcellular redistribution of activation-associated epitopes during BrCa progression implicates derailed internalisation and intracellular trafficking kinetics of active ανβ6 during tumourigenesis, while protein expression studies identified 7 putative molecular regulators of ligand-engaged, active ανβ6–mediated adhesion. Integrin ανβ6-mediated signalling during internalisation revealed an ανβ6–EGFRAkt1 signalling axis during breast tumourigenesis and disease progression, while further understanding of integrin biology and growth factor receptor crosstalk may provide additional rationale for potential combination therapies in breast cancer.Cancer Research UK

Microscopy and Analysis

Microscopes represent tools of the utmost importance for a wide range of disciplines. Without them, it would have been impossible to stand where we stand today in terms of understanding the structure and functions of organelles and cells, tissue composition and metabolism, or the causes behind various pathologies and their progression. Our knowledge on basic and advanced materials is also intimately intertwined to the realm of microscopy, and progress in key fields of micro- and nanotechnologies critically depends on high-resolution imaging systems. This volume includes a series of chapters that address highly significant scientific subjects from diverse areas of microscopy and analysis. Authoritative voices in their fields present in this volume their work or review recent trends, concepts, and applications, in a manner that is accessible to a broad readership audience from both within and outside their specialist area

Rare Earth Elements analysis to identify anthropogenic signatures at Valle del Serpis (Spain) Neolithic settlements

Due to their particular geochemical properties and stability Rare Earth Elements (REE) can act as a ‘fingerprint’ for soils, and as a consequence have been employed in a variety of different archaeological scenarios in order to identify past human activities.In this study, for the first time, we apply REE signatures in different Spanish Neolithic settlements, all located in the Valle del Serpis region. More than 100 Neolithic settlements have been identified in this area, and most of these open sites are characterised by dark brown strata that are in contrast with the light brown soils of the valley. These dark brown deposits are usually covered by paleosols and have been interpreted as markers of anthropogenic activities. However, in order to demonstrate whether these strata are anthropogenic or natural features requires a better understand-ing of soil development processes. A total of fifty samples were taken across six different sites, and from each site the sam-pling was carried out at different depths through 3m deep sections. Four sites are clearly associated with archaeological findings (sites BF, LP, PB and AC); another one is from a natural section near the Neolithic site of Mas d’Is (MD) and has been radiocarbon dated to the beginning of the Holocene (7751-7611 cal BC); and the last corresponds to a place of uncertain attribution (BK). Major, minor and trace elements including REE were determined using XRF and ICP- MS, with Principal Components Analysis (PCA) used to statistically analyze these data. Results were then compared with the strata soil properties analysed by XRD and particle size analysis, and cross-referenced with archaeological data to aid interpretation. The results demonstrate that REE analyses provide significant details regarding anthropogenic activities and strata development history, and in this instance confirm and elaborate on the archaeological interpretation that these dark brown deposits are evidence of a region-wide agricultural system in the Neolithic Valle del Serpis

The source of the building stones from the Sagunto Castle archaeological area and its surroundings

A multidisciplinary study was carried out on the building stones of the masonries belonging to the Castle of Sagunto (Valencia, Spain), an important historical and archeological complex, characterized by several construction phases from the Roman Period to the Modern Ages. For the first time, the stones of the Sagunto Castle have been analysed to determine their chemical, mineralogical and petrographic features, the main physical and mechanical properties, and to understand their decay, use and recycling dynamics in the different building during the entire occupational period. Geochemical and mineralogical analyses employing X-ray fluorescence (XRF), inductively coupled plasma mass spectrometry (ICP-MS) and X-ray diffraction (XRD) were carried out together with optical and electronic microscope analysis to observe the stone macro- and micro-structures. The collected data were processed by Principal Component Analysis (PCA) to highlight differences among the studied structures. The results show that the stones employed to build Sagunto`s structures during the different historical periods are related to a specific quarried area located nearby Sagunto Castle hill and differences between the studied samples are mostly related to the conservation state of the buildings. Therefore, geochemical analyses confirm the origin of the raw materials, while petrographic and physical analyses have been useful to evaluate the conservation state of the studied Sagunto Castle structures