Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β

Cord blood (CB)-derived natural killer (NK) cells that are genetically engineered to express a chimeric antigen receptor (CAR) are an attractive off-the-shelf therapy for the treatment of cancer, demonstrating a robust safety profile in vivo. For poor prognosis brain tumors such as glioblastoma multiforme (GBM), novel therapies are urgently needed. Although CAR-T cells demonstrate efficacy in preclinical GBM models, an off-the-shelf product may exhibit unwanted side effects like graft-versus-host disease. Hence, we developed an off-the-shelf CAR-NK cell approach using a B7H3 CAR and showed that CAR-transduced NK cells have robust cytolytic activity against GBM cells in vitro. However, transforming growth factor (TGF)-β within the tumor microenvironment has devastating effects on the cytolytic activity of both unmodified and CAR-transduced NK cells. To overcome this potent immune suppression, we demonstrated that co-transducing NK cells with a B7H3 CAR and a TGF-β dominant negative receptor (DNR) preserves cytolytic function in the presence of exogenous TGF-β. This study demonstrates that a novel DNR and CAR co-expression strategy may be a promising therapeutic for recalcitrant CNS tumors like GBM

Unconventional Cosmology

I review two cosmological paradigms which are alternative to the current inflationary scenario. The first alternative is the "matter bounce", a non-singular bouncing cosmology with a matter-dominated phase of contraction. The second is an "emergent" scenario, which can be implemented in the context of "string gas cosmology". I will compare these scenarios with the inflationary one and demonstrate that all three lead to an approximately scale-invariant spectrum of cosmological perturbations.Comment: 45 pages, 10 figures; invited lectures at the 6th Aegean Summer School "Quantum Gravity and Quantum Cosmology", Chora, Naxos, Greece, Sept. 12 - 17 2012, to be publ. in the proceedings; these lecture notes form an updated version of arXiv:1003.1745 and arXiv:1103.227

Polymer-stable magnesium nanocomposites prepared by laser ablation for efficient hydrogen storage

Hydrogen is a promising alternative energy carrier that can potentially facilitate the transition from fossil fuels to sources of clean energy because of its prominent advantages such as high energy density (142 MJ per kg), great variety of potential sources (for example water, biomass, organic matter), and low environmental impact (water is the sole combustion product). However, due to its light weight, the efficient storage of hydrogen is still an issue investigated intensely. Various solid media have been considered in that respect among which magnesium hydride stands out as a candidate offering distinct advantages. Recent theoretical work indicates that MgH2 becomes less thermodynamically stable as particle diameter decreases below 2 nm. Our DFT (density functional theory) modeling studies have shown that the smallest enthalpy change, corresponding to 2 unit-cell thickness (1.6 {\AA} Mg/3.0{\AA} MgH2) of the film, is 57.7 kJ/molMg. This enthalpy change is over 10 kJ per molMg smaller than that of the bulk. It is important to note that the range of enthalpy change for systems that are suitable for mobile storage applications is 15 to 24 kJ permolH at 298 K. The important key for the development of air/stable Mg/nanocrystals is the use of PMMA (polymethylmethacrylate) as an encapsulation agent. In our work we use laser ablation, a non-electrochemical method, for producing well dispersed nanoparticles without the presence of any long range aggregation. The observed improved hydrogenation characteristics of the polymer/stable Mg-nanoparticles are associated to the preparation procedure and in any case the polymer laser ablation is a new approach for the production of air/protected and inexpensive Mg/nanoparticles.Comment: Hydrogen Storage, Mg - Nanoparticles, Polymer Matrix Composites, Laser Ablation, to appear in International Journal of Hydrogen Energy, 201

Gamma Prime Precipitate Evolution During Aging of a Model Nickel-Based Superalloy

The microstructural stability of nickel-based superalloys is critical for maintaining alloy performance during service in gas turbine engines. In this study, the precipitate evolution in a model polycrystalline Ni-based superalloy during aging to 1000 hours has been studied via transmission electron microscopy, atom probe tomography and neutron diffraction. Variations in phase composition and precipitate morphology, size and volume fraction were observed during aging, whilst the constrained lattice misfit remained constant at approximately zero. The experimental composition of the γ matrix phase was consistent with thermodynamic equilibrium predictions, whilst significant differences were identified between the experimental and predicted results from the γʹ phase. These results have implications for the evolution of mechanical properties in service and their prediction using modeling methods.The authors wish to acknowledge Mrs. S. Rhodes, Dr. H.T. Pang, Dr. D.M. Collins, and Dr. O.M.D.M. Messé for their assistance with the experiments performed. Funding was provided by the EPSRC/Rolls-Royce Strategic Partnership under EP/M005607/1 and EP/H022309/1. The Oxford Atom Probe facility was funded by the EPSRC under EP/M022803/1. Neutron diffraction beam time was supported through the Canadian Neutron Beam Centre under Experiment number 1258

Estimation of error variance in ANOVA model and order restricted scale parameters

Two-level orthogonal arrays, Stein’s estimator, Squared error loss, Uniform improvement, Simple tree order restriction, Isotonic regression estimator, Random effects model,