Development of multi-use platforms at sea:Barriers to realising Blue Growth

The recent H2020 Blue Growth projects MARIBE and MUSES investigated the potential of a variety of different combinations of economic activities in co-location or integrated in multi-use platforms. Both projects identified barriers - including regulatory, financing, liability and insurance issues; environmental concerns; stakeholder perceptions; and lack of appropriate skills – that hamper the development of multi-use platforms. The H2020 MARIBE project concluded that further funding for multi-use demonstrations should be provided to increase investor confidence and bring multi-use through the so-called Valley of Death. The H2020 MUSES project concluded that multi-use needs to be proactively facilitated and incentivised through public regulatory bodies and respective support programmes. This paper combines and analyses results from both projects in order to identify key research gaps and actions required for the continued development of multi-use platforms, based on a structured critical review of available peer-reviewed literature on the topic as well as reports of both the MUSES and MARIBE projects. Research gaps and actions are analysed based on a multi-use platform typology to inform developers, policy makers, academia and investors for future development of multi-use at sea

Mobilising investors for Blue Growth

The European Union's Blue Growth Strategy is a long term strategy to support sustainable growth in the marine and maritime sectors, aiming to contribute to innovation and economic growth (European Commission, 2012). The EU sees the financial sector as a key partner to bring about transition to sustainable consumption and production. However, knowledge about investment behavior, experience with working with these investors, and ways to engage investors in the Blue Growth sectors is lacking. This paper examines this knowledge gap. It characterizes investors and identifies investor behavior, investors' motives, and conditions and criteria relevant for investors to invest in Blue Growth sectors. The presented results are derived from a literature study on investors and investment behavior, an electronic survey and in-depth interviews. Stereotypical images of private equity bankers or wealthy individuals do not do justice to the diversity of investors involved in the Blue Growth sectors. These sectors are still in development and various risks reduce the willingness to invest. Risk mitigation should be seen as a shared responsibility of entrepreneurs, investors and governments. Government support must go further than financial support for research and development or technological demonstration projects. Proven technologies get stuck in the Valley of Death as investors alone are not willing to take the risk associated with upscaling of promising technologies. Tied in a reciprocal relationship, governments need to attract private investors—their capital, knowledge, and networks—to further grow of the Blue Growth sectors while investors need stable, predictable, and effective government support schemes to mitigate their financial risks

The small heat shock protein 20 RSI2 interacts with and is required for stability and function of tomato resistance protein I-2

Race-specific disease resistance in plants depends on the presence of resistance (R) genes. Most R genes encode NB-ARC-LRR proteins that carry a C-terminal leucine-rich repeat (LRR). Of the few proteins found to interact with the LRR domain, most have proposed (co)chaperone activity. Here, we report the identification of RSI2 (Required for Stability of I-2) as a protein that interacts with the LRR domain of the tomato R protein I-2. RSI2 belongs to the family of small heat shock proteins (sHSPs or HSP20s). HSP20s are ATP-independent chaperones that form oligomeric complexes with client proteins to prevent unfolding and subsequent aggregation. Silencing of RSI2-related HSP20s in Nicotiana benthamiana compromised the hypersensitive response that is normally induced by auto-active variants of I-2 and Mi-1, a second tomato R protein. As many HSP20s have chaperone properties, the involvement of RSI2 and other R protein (co)chaperones in I-2 and Mi-1 protein stability was examined. RSI2 silencing compromised the accumulation of full-length I-2 in planta, but did not affect Mi-1 levels. Silencing of heat shock protein 90 (HSP90) and SGT1 led to an almost complete loss of full-length I-2 accumulation and a reduction in Mi-1 protein levels. In contrast to SGT1 and HSP90, RSI2 silencing led to accumulation of I-2 breakdown products. This difference suggests that RSI2 and HSP90/SGT1 chaperone the I-2 protein using different molecular mechanisms. We conclude that I-2 protein function requires RSI2, either through direct interaction with, and stabilization of I-2 protein or by affecting signalling components involved in initiation of the hypersensitive response

The effect of cavity-filling mutations on the thermostability of Bacillus stearothermophilus neutral protease

Cavities in the hydrophobic core of the neutral protease of Bacillus stearothermophilus were analyzed using a three-dimensional model that was inferred from the crystal structure of thermolysin, the highly homologous neutral protease of B.thermoproteolyticus (85% sequence identity). Site-directed mutagenesis was used to fill some of these cavities, thereby improving hydrophobic packing in the protein interior. The mutations had small effects on the thermostability, even after drastic changes, such as Leu284 --> Trp and Met168 --> Trp. The effects on T50, the temperature at which 50% of the enzyme is irreversibly inactivated in 30 min, ranged from 0.0 to +0.4-degrees-C. These results can be explained by assuming that the mutations have positive and negative structural effects of approximately the same magnitude. Alternatively, it could be envisaged that the local unfolding steps, which render the enzyme susceptible towards autolysis and which are rate limiting in the process of thermal inactivation, are only slightly affected by alterations in the hydrophobic core

Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer

<p>Abstract</p> <p>Background</p> <p>Infection with high risk Human Papilloma Virus (HPV) is associated with cancer of the cervix, vagina, penis, vulva, anus and some cases of head and neck carcinomas. The HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore potential targets for T cell mediated adoptive immunotherapy. Effective immunotherapy is dependent on the presence of both CD4+ and CD8+ T cells. However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer.</p> <p>Methods</p> <p>HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively) directed against HPV16 antigens. Functional analysis was performed by interferon-γ secretion, proliferation and cytokine production assays.</p> <p>Results</p> <p>Introduction of HPV16 specific TCRs into blood derived CD4+ recipient T cells resulted in recognition of the relevant HPV16 epitope as determined by IFN-γ secretion. Importantly, we also show recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented HPV16E7 epitope by A9 TCR transgenic CD4+ T cells.</p> <p>Conclusion</p> <p>Our data indicate that TCR transfer is feasible as an alternative strategy to generate human HPV16 specific CD4+ T helper cells for the treatment of patients suffering from cervical cancer and other HPV16 induced malignancies.</p

Colistin dry powder inhalation with the Twincer (TM):An effective and more patient friendly alternative to nebulization

BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates

Business case for mussel aquaculture in offshore wind farms in the North Sea

The European Blue Growth strategy aims to expand the new maritime sectors of aquaculture, energy, biotechnology, coastal tourism and mineral mining. Growth of these sectors will increases pressure on the seas, particularly on those areas that are densely used by traditional sectors such as fisheries and transport. This has triggered interest in developing multiuse of space and multiuse platforms at sea. This paper assesses the feasibility of offshore mussel production project in wind farms by design and ex-ante evaluation of a mussel aquaculture system in the North Sea. A system for mussel cultivation in the Dutch Borssele offshore wind farm was designed, producing both mussel seed and consumption-sized mussels with semi-submerged longlines. Based on the economic model and the risk assessment, this paper concludes that mussel aquaculture is an appealing commercial model for increased returns in offshore wind farms. The economic models shows that the internal rate of return and net present value are positive and based on the sensitivity analysis, it can be concluded that these results are robust

Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age

BACKGROUND: Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain. OBJECTIVE: We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age. METHODS: This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2'-bis-(4 chlorophenyl)1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH-CB-107),4OH-CB-146,4OH-CB-187,2,2',4,4'-tetrabromodipheryl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocy-clododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5-6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior. RESULTS: Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform, dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration. CONCLUSIONS: Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern