•Experimental and theoretical investigation of a PV–TEG system has been conducted.•Poly-Si and dye-sensitized solar cells have been employed.•Thermoelectric generators of different thermoelement ...length have been tested.•A wide range considering cell’s operating temperature has been examined.
Although photovoltaics have been established as the dominant technology considering the field of solar energy conversion systems, issues regarding their relatively low efficiency still remain practically unsolved. Very recently, the possibility of combining photovoltaic (PV) cells and thermoelectric generators (TEGs) in hybrid systems, as a means of improving the overall conversion efficiency, has attracted particular attention. In this paper, the performance of a tandem PV–TEG hybrid, employing poly-Si as well as dye-sensitized solar cells, has been examined experimentally. Thermoelectric devices of different thermoelement geometry have been tested in order to identify the corresponding performance effect. In addition, the outcomes of the experimental process have been exploited in order to evaluate the performance of the system under real operating conditions. The analysis conducted indicates that the utilization of TEGs with shorter thermoelements results in enhanced power output levels, when conditions of actual operation are considered. Moreover, although improved power output is obtained by the setup employing the polycrystalline cell, dye-sensitized technology could become particularly attractive when the incorporation of solar cells in PV–TEG hybrids operating under conditions of elevated temperature is examined.
Patients with follicular lymphoma (FL) with early relapse after initial chemoimmunotherapy, refractory disease, or histologic transformation (tFL) have limited progression-free and overall survival. ...We report efficacy and long-term follow-up of 21 patients with relapsed/refractory (R/R) FL (n = 8) and tFL (n = 13) treated on a phase 1/2 clinical trial with cyclophosphamide and fludarabine lymphodepletion followed by infusion of 2 × 106 CD19-directed chimeric antigen receptor–modified T (CAR-T) cells per kilogram. The complete remission (CR) rates by the Lugano criteria were 88% and 46% for patients with FL and tFL, respectively. All patients with FL who achieved CR remained in remission at a median follow-up of 24 months. The median duration of response for patients with tFL was 10.2 months at a median follow-up of 38 months. Cytokine release syndrome occurred in 50% and 39%, and neurotoxicity in 50% and 23% of patients with FL and tFL, respectively, with no severe adverse events (grade ≥3). No significant differences in CAR-T cell in vivo expansion/persistence were observed between FL and tFL patients. CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R FL with or without transformation, with durable remission in a high proportion of FL patients. This trial was registered at clinicaltrials.gov as #NCT01865617.
•CD19 CAR-T cell immunotherapy results in high CR rates in FL with or without transformation.•Sustained remissions were observed in all patients with FL without transformation achieving CR.
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Today, Vortex Generators (VGs) are becoming an integral part of a Wind Turbine blade design. However, the challenges involved in the computation of the flow around VGs are yet to be dealt with in a ...satisfactory manner. A large number of VG models for Reynolds Averaged Navier Stokes (RANS) solvers has been proposed and, among them, the Bender–Anderson–Yagle (BAY) model (ASME Pap. FEDSM99-6919) is one of the most popular, due to its ease of use and relatively low requirements for user input. In the present paper a thorough investigation on the performance and application of the BAY model for aerodynamic VG flows is presented. A fully resolved RANS simulation is validated against experiments and then used as a benchmark for the BAY model simulations. A case relevant to wind turbines is examined, which deals with the flow past a wind turbine airfoil at Reynolds number 0.87e6. When the grid related errors are excluded, it is found that the generated vortices are weaker in the BAY model simulations than in the fully resolved computation. The latter finding is linked to an inherent deficiency of the model, which is first found in this study and which is explained in detail.
•Most detailed analysis of the BAY model to date.•First time the BAY model was applied to a Fully Resolved grid.•Model inherent deficiency highlighted.•Identification of areas and ways to improve the model.
The use of passive vortex generators (VGs) as a simple and effective way to delay or suppress separation on an airfoil optimized for wind turbine blades is examined experimentally. The profile ...experiences three-dimensional separation of the Stall Cell type. Pressure, Flow Visualization and Stereo Particle Image Velocimetry experiments are discussed for the case of triangular counter rotating VGs with common flow up. For a Reynolds number of 0.87×106, Stall Cell formation is delayed for 5°, and lift increases up to α=15°. In total, maximum lift increases by 44%, while drag increases by 0.002 at pre-stall angles of attack. At α=16° the flow bifurcates between separated and attached flow conditions. At α=10° the flow is examined in detail and an investigation on the turbulence characteristics is carried out by correlating Reynolds stresses production to time averaged flow gradients. Strong turbulent interaction is observed between the two vortices and the underlying flow up to 37.2 VG heights downstream of the VGs, while further downstream (up to 47.2 VG heights) diffusion governs the flow. A wandering motion of the VG vortices leads to increased v`v`¯ normal stress values between the two vortices.
Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease–negative (MRD-negative) complete remission (CR) rates in ...patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated. We studied patients with relapsed/refractory B-ALL enrolled in a phase 1/2 clinical trial evaluating lymphodepletion chemotherapy followed by CD19 CAR T-cell therapy at our institution. Forty-five (85%) of 53 patients who received CD19 CAR T-cell therapy and were evaluable for response achieved MRD-negative CR by high-resolution flow cytometry. With a median follow-up of 30.9 months, event-free survival (EFS) and overall survival (OS) were significantly better in the patients who achieved MRD-negative CR compared with those who did not (median EFS, 7.6 vs 0.8 months; P < .0001; median OS, 20.0 vs 5.0 months; P = .014). In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by IGH deep sequencing was associated with better EFS (P = .034). Stepwise multivariable modeling in patients achieving MRD-negative CR showed that lower prelymphodepletion lactate dehydrogenase concentration (hazard ratio HR, 1.38 per 100 U/L increment increase), higher prelymphodepletion platelet count (HR, 0.74 per 50 000/μL increment increase), incorporation of fludarabine into the lymphodepletion regimen (HR, 0.25), and allogeneic hematopoietic cell transplantation (HCT) after CAR T-cell therapy (HR, 0.39) were associated with better EFS. These data allow identification of patients at higher risk of relapse after CAR T-cell immunotherapy who might benefit from consolidation strategies such as allogeneic HCT. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
•Baseline platelet count, lactate dehydrogenase, and lymphodepletion regimen impact EFS in patients in MRD-negative CR after CD19 CAR T-cell.•Allogeneic HCT after CD19 CAR T-cell therapy is well tolerated and may improve EFS.
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Factors associated with durable remission after CD19 chimeric antigen receptor (CAR)-modified T-cell immunotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) have not been identified. We report ...multivariable analyses of factors affecting response and progression-free survival (PFS) in patients with aggressive NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by 2 × 106 CD19-directed CAR T cells/kg. The best overall response rate was 51%, with 40% of patients achieving complete remission. The median PFS of patients with aggressive NHL who achieved complete remission was 20.0 months (median follow-up, 26.9 months). Multivariable analysis of clinical and treatment characteristics, serum biomarkers, and CAR T-cell manufacturing and pharmacokinetic data showed that a lower pre-lymphodepletion serum lactate dehydrogenase (LDH) level and a favorable cytokine profile, defined as serum day 0 monocyte chemoattractant protein-1 (MCP-1) and peak interleukin-7 (IL-7) concentrations above the median, were associated with better PFS. MCP-1 and IL-7 concentrations increased after lymphodepletion, and higher intensity of cyclophosphamide and fludarabine lymphodepletion was associated with higher probability of a favorable cytokine profile. PFS was superior in patients who received high-intensity lymphodepletion and achieved a favorable cytokine profile compared with those who received the same intensity of lymphodepletion without achieving a favorable cytokine profile. Even in high-risk patients with pre-lymphodepletion serum LDH levels above normal, a favorable cytokine profile after lymphodepletion was associated with a low risk of a PFS event. Strategies to augment the cytokine response to lymphodepletion could be tested in future studies of CD19 CAR T-cell immunotherapy for aggressive B-cell NHL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
•LDH, MCP-1, and IL-7 are independently associated with PFS in patients with aggressive NHL after CD19 CAR T-cell immunotherapy.•Higher intensity of cyclophosphamide and fludarabine lymphodepletion is associated with higher probability of a favorable cytokine profile.
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•The proposed solver confines the Eulerian grid close to solid boundaries.•The issue of far-field conditions is successfully addressed.•The presence of solid boundaries in particle methods is taken ...into account.•A significantly less diffusive method than standard 2nd order CFD is proposed.
A hybrid solver for external compressible flows is formulated by combining a standard finite volume Eulerian CFD solver with a Lagrangian (particle) one. The Eulerian domain is confined close to the solid boundaries and may be split in separate disjoint subsets. The Lagrangian domain covers the entire domain while the flow is represented by particles that carry complete flow information defined by mass, dilatation, vorticity and pressure. The Lagrangian part couples the two solvers by providing the outer boundary conditions to the Eulerian grid. On the other hand, the Eulerian solver communicates the presence of walls to the Lagrangian one, by updating the particle flow properties close to them. The formulation is completed by combining Helmholtz’s decomposition with the Particle Mesh technique which determines the velocity field that transports the particles, provides accurate outer boundary conditions for the Eulerian solver and decisively reduces the computational cost. In the present paper the inviscid flow around a NACA 0012 airfoil is considered from low to high subsonic conditions in steady and pitching mode. Hybrid predictions are compared to standard CFD results and verification of the proposed solver is carried out. The comparison shows that, if shocks are included in the Eulerian grid of the hybrid solver, the loads are accurately estimated, and that for the same resolution, the numerical diffusion in the wake is substantially reduced.
In recent years, traceability systems have been developed as practical tools for improving supply chain (SC) transparency and visibility, especially in health and safety-sensitive sectors like food ...and pharmaceuticals. Blockchain-related SC traceability research has received significant attention during the last several years, and arguably blockchain is currently the most promising technology for providing traceability-related services in SC networks. This paper provides a systematic literature review of the various technical implementation aspects of blockchain-enabled SC traceability systems. We apply different drivers for classifying the selected literature, such as (a) the various domains of the available blockchain-enabled SC traceability systems and relevant methodologies applied; (b) the implementation maturity of these traceability systems along with technical implementation details; and (c) the sustainability perspective (economic, environmental, social) prevalent to these implementations. We provide key takeaways regarding the open issues and challenges of current blockchain traceability implementations and fruitful future research areas. Despite the significant volume and plethora of blockchain-enabled SC traceability systems, academia has so far focused on unstructured experimentation of blockchain-associated SC traceability solutions, and there is a clear need for developing and testing real-life traceability solutions, especially taking into account feasibility and cost-related SC aspects.
Patients with follicular lymphoma (FL) with early relapse after initial chemoimmunotherapy, refractory disease, or histologic transformation (tFL) have limited progression-free and overall survival. ...We report efficacy and long-term follow-up of 21 patients with relapsed/refractory (R/R) FL (n = 8) and tFL (n = 13) treated on a phase 1/2 clinical trial with cyclophosphamide and fludarabine lymphodepletion followed by infusion of 2 × 106 CD19-directed chimeric antigen receptor-modified T (CAR-T) cells per kilogram. The complete remission (CR) rates by the Lugano criteria were 88% and 46% for patients with FL and tFL, respectively. All patients with FL who achieved CR remained in remission at a median follow-up of 24 months. The median duration of response for patients with tFL was 10.2 months at a median follow-up of 38 months. Cytokine release syndrome occurred in 50% and 39%, and neurotoxicity in 50% and 23% of patients with FL and tFL, respectively, with no severe adverse events (grade ≥3). No significant differences in CAR-T cell in vivo expansion/persistence were observed between FL and tFL patients. CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R FL with or without transformation, with durable remission in a high proportion of FL patients. This trial was registered at clinicaltrials.gov as #NCT01865617.
Urinary bladder cancer is a common malignancy, being characterized by substantial patient mortality and management cost. Its high somatic-mutation frequency and molecular heterogeneity usually ...renders tumors refractory to the applied regimens. Hitherto, methotrexate-vinblastine-adriamycin-cisplatin and gemcitabine-cisplatin represent the backbone of systemic chemotherapy. However, despite the initial chemosensitivity, the majority of treated patients will eventually develop chemoresistance, which severely reduces their survival expectancy. Since chromatin regulation genes are more frequently mutated in muscle-invasive bladder cancer, as compared to other epithelial tumors, targeted therapies against chromatin aberrations in chemoresistant clones may prove beneficial for the disease. "Acetyl-chromatin" homeostasis is regulated by the opposing functions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The HDAC/SIRT (super-)family contains 18 members, which are divided in five classes, with each family member being differentially expressed in normal urinary bladder tissues. Since a strong association between irregular HDAC expression/activity and tumorigenesis has been previously demonstrated, we herein attempt to review the accumulated published evidences that implicate HDACs/SIRTs as critical regulators in urothelial bladder cancer. Moreover, the most extensively investigated HDAC inhibitors (HDACis) are also analyzed, and the respective clinical trials are also described. Interestingly, it seems that HDACis should be preferably used in drug-combination therapeutic schemes, including radiation.
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