Blade-explicit fluid structure interaction of a ducted high-solidity tidal turbine

This work elaborates a computational fluid dynamic (CFD) model utilised in the investigation of the structural performance concerning a ducted high-solidity tidal turbine in aligned and yawed inlet flows. Analysing the hydrodynamic performance at aligned flows portrayed the distinctive power curve at which energy is transferred via the fluid-structure interaction. At distinct bearing angles with the axis of the turbine, variations in the blade-interaction due to the presence of the duct was acknowledged within a limited angular range at distinct tip-speed ratio values. As a result of the hydrodynamic analysis, a structural investigation of the blades was discretely evaluated in an effort to acknowledge fluid-structure phenomena

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study

Colorectal cancerCàncer de còlonCáncer de colonBackground Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. Methods TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. Results At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. Conclusions TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy.This study was funded by Servier and Taiho

Periodization of carbohydrate intake: Short-term effect on performance

“Sleep-low” consists of a sequential periodization of carbohydrate (CHO) availability—low glycogen recovery after “train high” glycogen-depleting interval training, followed by an overnight-fast and light intensity training (“train low”) the following day. This strategy leads to an upregulation of several exercise-responsive signaling proteins, but the chronic effect on performance has received less attention. We investigated the effects of short-term exposure to this strategy on endurance performance. Methods: Following training familiarization, 11 trained cyclists were divided into two groups for a one-week intervention—one group implemented three cycles of periodized CHO intake to achieve the sleep-low strategy over six training sessions (SL, CHO intake: 6 g·kg-1·day-1), whereas the control group consumed an even distribution of CHO over the day (CON). Tests were a 2 h submaximal ride and a 20 km time trial. Results: SL improved their performance (mean: +3.2%; p < 0.05) compared to CON. The improvement was associated with a change in pacing strategy with higher power output during the second part of the test. No change in substrate utilization was observed after the training period for either group. Conclusion: Implementing the “sleep-low” strategy for one week improved performance by the same magnitude previously seen in a three-week intervention, without any significant changes in selected markers of metabolism. © 2016 by the authors; licensee MDPI, Basel, Switzerland.Background

Analysing fibre composite designs for high-solidity ducted tidal turbine blades

This study elaborates a one-way fluid-structure interaction numerical model utilised in investigating the structural mechanics concerning the rotor blades comprising a ducted high-solidity tidal turbine. Coupling hydrodynamic outcomes as structural inputs in effort of acknowledging the most applicable setup, distinct designs are investigated, solid blades and cored blades, implementing fibre-reinforced composite materials, analysed within criteria related to blade axial deformation, induced radial strains, and rotor specific mass

Neuropilin-2 Expression Promotes TGF-β1-Mediated Epithelial to Mesenchymal Transition in Colorectal Cancer Cells

Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors

A numerical structural analysis of ducted, high-solidity, fibre-composite tidal turbine rotor configurations in real flow conditions

Establishing a design and material evaluation of unique tidal turbine rotors in true hydrodynamic conditions by means of a numerical structural analysis has presented inadequacies in implementing spatial and temporal loading along the blade surfaces. This study puts forward a structural performance investigation of true-scale, ducted, high-solidity, fibre-composite tidal turbine rotor configurations in aligned and yawed flows by utilising outputs from unsteady blade-resolved computational fluid dynamic models as boundary condition loads within a finite-element numerical model. In implementation of the partitioned-approach fluid–structure interaction procedure, three distinct internal blade designs were analysed. Investigating criteria related to structural deformation and induced strains, hydrostatic & hydrodynamic analyses are put forward in representation of the rotor within the flow conditions at the installation depth. The resultant axial deflections for the proposed designs describe a maximum deflection-to-bladespan ratio of 0.04, inducing a maximum strain of 0.9%. A fatigue response analysis is undertaken to acknowledge the blade material properties required to prevent temporal failure

A numerical performance analysis of a ducted high-solidity tidal turbine

This study puts forward an investigation into the hydrodynamic performance concerning a ducted, high-solidity tidal turbine utilising blade-resolved computational fluid dynamics. The model achieves similarity values of over 0.96 with experimentation data regarding a three-bladed horizontal-axis tidal turbine in validation of three distinct parameters: power & torque coefficient, thrust coefficient, and wake velocity profiles. Accordingly, the model was employed for the analysis of a ducted, high-solidity turbine in axially-aligned flows at distinct free-stream velocities. The resultant hydrodynamic performance characteristics portrayed a peak power coefficient of 0.34, with a thrust coefficient of 0.97, at a nominal tip-speed ratio of 1.75. Coefficient trend agreement was attained between the numerical model and experimentation data established in literature and blade-element momentum theory; the model furthers the analysis by elaborating the temporal hydrodynamic features induced by the fluid-structure interaction in specification to the wake formation velocity profiles, pressure distribution along the blades and duct, mass flow rate, and vortex shedding effects to establish the characteristic flow physics of the tidal turbine

Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study

BACKGROUND: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. METHODS: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m2 on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). RESULTS: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy). CONCLUSIONS: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma

Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses

Several distinct innate lymphoid cell (ILC) populations have been recently identified and shown to play a critical role in the immediate immune defense. In the context of tumors, there is evidence to support a dual role for ILCs with pro-or antitumor effects, depending on the ILC subset and the type of cancer. This ambivalent role has been particularly well-described in colorectal cancer models (CRC), but the presence and the evolution of ILCs in the peripheral blood of metastatic CRC (mCRC) patients have not yet been explored. Here, we investigated the distribution of ILC subsets in 96 mCRC patients who were prospectively included in the "Epitopes-CRCO2" trial. Peripheral bloodmononuclear cells (PBMCs) were analyzed by flow cytometry at metastatic diagnosis and after 3-months of treatment. The treatments consisted of Oxaliplatin-based chemotherapies for 76% of the patients or Folfiri (5FU, Irinotecan) chemotherapies for 14% of patients. Compared to healthy donors, the frequency of total ILCs was dramatically increased at metastatic diagnosis. CD56(+) ILC1-like cells were expanded, whereas ILC2, NCR- ILCP and NCR+ ILCP subsets were decreased. Combined analysis with the systemic anti-telomerase hTERT Th1 CD4 response revealed that patients with low anti-TERT Th1 CD4 responses had the highest frequencies of total ILCs at diagnosis. Of those, 91% had synchronous metastases, and their median progression-free survival was 7.43 months (vs. 9.17 months for the other patients). In these patients, ILC1 and ILC2 were significantly decreased, whereas CD56(+) ILC1-like cells were significantly increased compared to patients with low frequency of total ILCs and high anti-TERT responses. After treatment, the NCR+ ILCP were further decreased irrespective of the chemotherapy regimen, whereas the balance between ILC1 and CD56(+) ILC1-like cells was modulated mainly by the Folfiri regimen in favor of ILC1. Altogether our results describe the effects of different chemotherapies on ILCs in mCRC patients. We also establish for the first time a link between frequency of ILCs and anti-tumor CD4 T cell responses in cancer patients. Thus, our study supports an interest in monitoring ILCs during cancer therapy to possibly identify predictive biomarkers in mCRC