Downwind Coning Concept Rotor for a 25 MW Offshore Wind Turbine

The size of offshore wind turbines over the next decade is expected to continually increase due to reduced balance of station costs per MW and also the higher wind energy at increased altitudes that can lead to higher capacity factors. However, there are challenges that may limit the degree of upscaling which is possible. In this paper, a two-bladed downwind turbine system is upscaled from 13.2 MW to 25 MW, by redesigning aerodynamics, structures, and controls. In particular, three 25 MW rotors have been developed: V1 is the upscaled model, V2 is a partial redesigned model, and V3 is a fully redesigned model. Despite their radically large sizes, it is found that these 25 MW turbine rotors satisfy this limited set of design drivers at the rated condition and that larger blade lengths are possible with cone-wise load-alignment. In addition, flapwise morphing (varying the cone angle with a wind-speed schedule) is investigated in terms of minimizing mean and fluctuating root bending loads using steady inflow proxies for the maximum and damage equivalent load moments. The resulting series of 25 MW rotors, which are the largest ever designed, can be a useful baseline for further development and assessment. </div

Highly Stretchable Miniature Strain Sensor for Large Dynamic Strain Measurement

This thesis aims to develop a new type of highly stretchable strain sensor to measure large deformation of a specimen subjected to dynamic loading. The sensor was based on the piezo-resistive response of carbon nanotube(CNT)/polydimethysiloxane (PDMS) composites thin films, some nickel particles were added into the sensor composite to improve the sensor performance. The piezo-resistive response of CNT composite gives high frequency response in strain measurement, while the ultra-soft PDMS matrix provides high flexibility and ductility for large strain measuring large strain (up to 26%) with an excellent linearity and a fast frequency response under quasi-static test, the delay time for high strain rate test is just 30 μs. This stretchable strain sensor is also able to exhibit much higher sensitivities, with a gauge factor of as high as 80, than conventional foil strain gauges

Production of <it>N</it>^<it>α</it>-acetylated thymosin α1 in <it>Escherichia coli</it>

Abstract Background Thymosin α1 (Tα1), a 28-amino acid Nα-acetylated peptide, has a powerful general immunostimulating activity. Although biosynthesis is an attractive means of large-scale manufacture, to date, Tα1 can only be chemosynthesized because of two obstacles to its biosynthesis: the difficulties in expressing small peptides and obtaining Nα-acetylation. In this study, we describe a novel production process for Nα-acetylated Tα1 in Escherichia coli. Results To obtain recombinant Nα-acetylated Tα1 efficiently, a fusion protein, Tα1-Intein, was constructed, in which Tα1 was fused to the N-terminus of the smallest mini-intein, Spl DnaX (136 amino acids long, from Spirulina platensis), and a His tag was added at the C-terminus. Because Tα1 was placed at the N-terminus of the Tα1-Intein fusion protein, Tα1 could be fully acetylated when the Tα1-Intein fusion protein was co-expressed with RimJ (a known prokaryotic Nα-acetyltransferase) in Escherichia coli. After purification by Ni-Sepharose affinity chromatography, the Tα1-Intein fusion protein was induced by the thiols β-mercaptoethanol or d,l-dithiothreitol, or by increasing the temperature, to release Tα1 through intein-mediated N-terminal cleavage. Under the optimal conditions, more than 90% of the Tα1-Intein fusion protein was thiolyzed, and 24.5 mg Tα1 was obtained from 1 L of culture media. The purity was 98% after a series of chromatographic purification steps. The molecular weight of recombinant Tα1 was determined to be 3107.44 Da by mass spectrometry, which was nearly identical to that of the synthetic version (3107.42 Da). The whole sequence of recombinant Tα1 was identified by tandem mass spectrometry and its N-terminal serine residue was shown to be acetylated. Conclusions The present data demonstrate that Nα-acetylated Tα1 can be efficiently produced in recombinant E. coli. This bioprocess could be used as an alternative to chemosynthesis for the production of Tα1. The described methodologies may also be helpful for the biosynthesis of similar peptides.</p

Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2‐positive gastric cancer

Abstract Background Trastuzumab is a first‐line targeted therapy for human epidermal growth factor receptor‐2 (HER2)‐positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment‐mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. Methods Trastuzumab‐sensitive and trastuzumab‐resistant HER2‐positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi‐scale agent‐based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. Results Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab‐resistant HER2‐positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor‐derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab‐resistant HER2‐positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa‐B (NF‐κB) p65 and drove GLS1 microvesicle secretion through IQ motif‐containing GTPase‐activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2‐positive gastric cancer. Conclusions This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro‐angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2‐positive gastric cancer. A combination of anti‐glutamine metabolism, anti‐angiogenesis, and pro‐M1 polarization therapy may provide a new insight into reversing trastuzumab resistance

Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis

Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis