Efficient preliminary floating offshore wind turbine design and testing methodologies and application to a concrete spar design

The current key challenge in the floating offshore wind turbine industry and research is on designing economic floating systems that can compete with fixed-bottom offshore turbines in terms of levelized cost of energy. The preliminary platform design, as well as early experimental design assessments, are critical elements in the overall design process. In this contribution, a brief review of current floating offshore wind turbine platform pre-design and scaled testing methodologies is provided, with a focus on their ability to accommodate the coupled dynamic behaviour of floating offshore wind systems. The exemplary design and testing methodology for a monolithic concrete spar platform as performed within the European KIC AFOSP project is presented. Results from the experimental tests compared to numerical simulations are presented and analysed and show very good agreement for relevant basic dynamic platform properties. Extreme and fatigue loads and cost analysis of the AFOSP system confirm the viability of the presented design process. In summary, the exemplary application of the reduced design and testing methodology for AFOSP confirms that it represents a viable procedure during pre-design of floating offshore wind turbine platforms.Peer ReviewedPostprint (author’s final draft

Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules

Background: Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results: The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions: We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.[Figure not available: see fulltext.

Comparative levelized cost of energy analysis

To estimate the economic feasibility of floating and bottom-fixed substructures at various offshore sites, a generally applicable calculation tool has been developed. With this “LCOE calculation tool” it is possible to optimize the design and reduce the costs of deep offshore wind farms, by analyzing key aspects already during the planning and pre-design phase. Hereby the conducted breakdown of the several cost categories assists identifying main cost-drivers prior a final investment decision. Whereas the influence of varying site specific, technological and financial parameters on the cost-effectiveness is investigated in a sensitivity analysis. To validate and enlarge the tool’s dataset, the tool was applied to a real floating concept with the aim to compare the cost-effectiveness of floating solutions with their bottom-fixed counterparts.Peer ReviewedPostprint (published version

Modified antimetabolites-loaded lipid nanocapsules to enhance antitumor immunity

Introduction : Myeloid­derived suppressor cells (MDSCs) are critical players of tumor­induced immunosuppression in mouse models and cancer patients. They accumulate in the spleen and cancers of tumor­bearing hosts where they suppress T­cell activation, proliferation and cytotoxic function [1]. Previous studies demonstrated that some anticancer agents, in addition to their cytotoxic effects on tumor cells, were able to affect MDSCs. This occurs for antimetabolites like 5­fluorouracile (5­FU) and Gemcitabine (Gem) [2]. In this work, the potential activity of novel lipophilic 5­FU and Gem derivatives encapsulated into lipid nanocapsules (LNCs) to target monocytic (M­)MDSC subset and tumor cells (pancreatic B6KPC3) was assessed. The aim was to study the immunogenic and anticancer properties of innovative nanosystems. Methods: Gem and 5­FU were modified to obtain mono­lauroyl­derivatives (Gem­C12 and 5­FU­C12). The derivatives were purified by chromatography on silica column and characterized by nuclear magnetic resonance. Blank and loaded­LNCs were prepared using the phase inversion process [3]. Physico­chemical characterization (size, dispersity, zeta potential and encapsulation efficiency) was performed. To study the in vitro induction of M­MDSCs, the immunosuppressive activity and internalization assays of GemC­12­loaded LNCs, mouse bone marrow cells cultured in presence of GM­CSF and IL­6 were used. To investigate the efficacy of 5­FU­C12­loaded LNCs, B6KPC3 cells were employed. Finally, as a preliminary in vivo study, the biodistribution of fluorescent­loaded LNCs (i.v. or s.c.) using tumor­bearing mice (EG7­OVA subcutaneous model) was evaluated. Results: Lipophilic derivatives, 5FU­C12 and Gem­C12, were synthetized. The yield of the products recovered was 60% and 40% for 5FU­C12 and Gem­C12, respectively. Blank, 5FU­C12 and Gem­C12­loaded LNCs showed an average size of 60 nm, dispersity index below 0.1 and neutral surface charge. The encapsulation efficiency of drugs was close to 100%. In vitro and in vivo studies highlighted that Gem­C12­loaded LNCs were internalized and depleted selectively M­MDSCs. Using K6PC3, we demonstrated that 5­FU­C12­loaded LNCs exerted a toxic effect comparable to the commercial 5FU­solution. In vivo studies following i.v. or s.c. administration of fluorescent­loaded LNCs showed that LNCs reached peripheral tissues. As compared with i.v., following s.c. injection, fluorescent signal increased with time in the spleen, suggesting a slow LNCs absorption. Conclusions : In the present study, lipophilic 5­FU­C12 and Gem­C12­loaded LNC were obtained. Gem­C12­ loaded LNCs were able to target M­MDSCs in vivo and in vitro. Besides, 5­FU­C12­loaded LNCs showed efficacy as anticancer drug in a pancreatic cell line. Further in vitro and in vivo therapeutic evaluations would disclose the full potential of these novel LNCs.

A Mouse Stromal Response to Tumor Invasion Predicts Prostate and Breast Cancer Patient Survival

Primary and metastatic tumor growth induces host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets, but also for identifying putative molecular signatures that may improve tumor classification and predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, we performed cDNA microarray analysis of laser-microdissected stromal cells derived from prostate intraepithelial neoplasia (PIN) and invasive cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes identified in the stromal reaction to tumor progression in this mouse model were observed to be expressed in several human cancers, and to cluster prostate and breast cancer patients into groups with statistically different clinical outcomes. Univariate Cox analysis showed that overexpression of these genes is associated with shorter survival and recurrence-free periods. Taken together, our observations provide evidence that the expression signature of the stromal response to tumor invasion in a mouse tumor model can be used to probe human cancer, and to provide a powerful prognostic indicator for some of the most frequent human malignancies

A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of Helicobacter pylori

Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B′, B′′) and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease

Arousal of Cancer-Associated Stroma: Overexpression of Palladin Activates Fibroblasts to Promote Tumor Invasion

Background: Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Principal Findings: Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (a-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduction of exogenous 90 kD palladin into normal human dermal fibroblasts (HDFs) induces activation of stromal fibroblasts into myofibroblasts as marked by induction of a-SMA and vimentin, and through the physical change of cell morphology. Moreover, palladin expression in the fibroblasts enhances cellular migration, invasion through the extracellular matrix, and creation of tunnels through which cancer cells can follow. The fibroblast invasion and creation of tunnels results from the development o

Etude aérodynamique d'un nouveau type d'aéromoteur

Généralités sur les moulins à axe vertical -- Champ de vitesses et de pressions d'un tourbillon -- Distribution des vitesses -- Distribution des pressions -- Calcul du rayon tourbillon -- Écoulement dans une roue à pâles hélicoidales -- Potentiel complexe de l'écoulement -- Éléments géométriques de la roue -- Calcul des circulations -- Coefficient de puissance -- Étude de l'hélice -- Forces aérodynamiques -- Rendement élémentaire théorique -- Puissance développée par un élément de surface travailleuse -- Calcul de l'incidence a e pour une rendement optimum -- Calcul des pertes par frottement -- Analyse du système proposé

Monolithic concrete off-shore floating sturcture for wind turbines

A new concept of a SPAR floating platform is being developed in the KIC-Innoenergy project AFOSP (Alternative Floating Platform Designs for Offshore Wind Turbines using Low Cost Materials). Members of the consortium are Gas Natural Fenosa, University of Stuttgart and Universitat Politècnica de Catalunya. The main differentiating aspects with respect to other SPAR prototypes are the monolithic nature of the whole structure, including both, the platform and the tower, the use of post-tensioned concrete as main material and the installation process. A comparison between similar steel and concrete designs demonstrates that the material cost for the concrete structure is around one third of the steel one. Considering that the concrete Oil & Gas platforms are virtually free of maintenance and have an extended lifetime, the real cost is less than 1/3 of the steel one, while the offshore tasks and the moorings systems have similar costs for both alternatives. Following a hydrostatic pre-design of the structure, coupled aero-servo-hydro-elastic analyses for a 5MW wind turbine have been performed by using an in-house FOWT model with a reduced number of degrees of freedom (DOF) and simplified aero- and hydrodynamics. With the obtained loads, the most relevant structural members have been checked, including a simplified fatigue limit state analysis, obtaining a lifetime over 50 years. Finally, a comprehensive cost analysis has been performed to obtain the Levelized Cost Of Energy (LCOE) for the developed platform.Postprint (published version

Monolithic concrete off-shore floating sturcture for wind turbines

A new concept of a SPAR floating platform is being developed in the KIC-Innoenergy project AFOSP (Alternative Floating Platform Designs for Offshore Wind Turbines using Low Cost Materials). Members of the consortium are Gas Natural Fenosa, University of Stuttgart and Universitat Politècnica de Catalunya. The main differentiating aspects with respect to other SPAR prototypes are the monolithic nature of the whole structure, including both, the platform and the tower, the use of post-tensioned concrete as main material and the installation process. A comparison between similar steel and concrete designs demonstrates that the material cost for the concrete structure is around one third of the steel one. Considering that the concrete Oil & Gas platforms are virtually free of maintenance and have an extended lifetime, the real cost is less than 1/3 of the steel one, while the offshore tasks and the moorings systems have similar costs for both alternatives. Following a hydrostatic pre-design of the structure, coupled aero-servo-hydro-elastic analyses for a 5MW wind turbine have been performed by using an in-house FOWT model with a reduced number of degrees of freedom (DOF) and simplified aero- and hydrodynamics. With the obtained loads, the most relevant structural members have been checked, including a simplified fatigue limit state analysis, obtaining a lifetime over 50 years. Finally, a comprehensive cost analysis has been performed to obtain the Levelized Cost Of Energy (LCOE) for the developed platform