Alteration of early dendritic cell activation by cancer cell lines predisposes immunosuppression, which cannot be reversed by TLR4 stimulation

Dendritic cells (DCs) have shown promise for use in cancer vaccine and cancer immunotherapy studies. However, we demonstrate that cancer cell lines can negatively interfere with DC generation in granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived cultures, although cancer cells are able to enhance CD80 cell surface activation marker and cytokine secretion. Furthermore, in the presence of cancer cells, GM-CSF-derived DCs are unable to stimulate T-cells. Additional stimulation with toll-like receptor 4 cannot fully reverse the suppressive effect of cancer cells or supernatant. Hence, it is imperative to understand the immunosuppressive effects of cancer on DCs in order for DC-based cancer immunotherapy to be successful

Glycine microparticles loaded with functionalized nanoparticles for pulmonary delivery

The use of nanoparticles for pulmonary delivery poses challenges such as the presence of anatomical barriers and the loss of bioactive components. Excipients are often used to facilitate delivery. Excipients suitable for nanoparticle delivery are still being explored. Herein we introduce for the first time, spray-dried glycine microparticle-based excipients loaded with nanoparticles of the size range known to be taken up by alveolar macrophages. Using a microfluidic jet spray dryer, we produced glycine microparticles-based excipients which are spherical, uniform, cenospheric (hollow at core), and “coral-like” with average diameter of 60 ± 10 μm, 29 ± 0.8% porosity, and showed their effective loading with glycine coated iron oxide superparamagnetic nanoparticles (GSPIONs). Our loading protocol with nanoparticles further increased microsphere porosity and improved aerodynamic performance unlike the dense, solid commercial excipient, Lactohale200™. This demonstrates a feasible approach for delivery of such nanoparticles in the lung

Weyl-Underhill-Emmrich quantization and the Stratonovich-Weyl quantizer

Weyl-Underhill-Emmrich (WUE) quantization and its generalization are considered. It is shown that an axiomatic definition of the Stratonovich-Weyl (SW) quantizer leads to severe difficulties. Quantization on the cylinder within the WUE formalism is discussed.Comment: 15+1 pages, no figure

A novel approach for non‐invasive lung imaging and targeting lung immune cells

Despite developments in pulmonary radiotherapy, radiation‐induced lung toxicity remains a problem. More sensitive lung imaging able to increase the accuracy of diagnosis and radiotherapy may help reduce this problem. Super‐paramagnetic iron oxide nanoparticles are used in imaging, but without further modification can cause unwanted toxicity and inflammation. Complex carbohydrate and polymer‐based coatings have been used, but simpler compounds may provide additional benefits. Herein, we designed and generated super‐paramagnetic iron oxide nanoparticles coated with the neutral natural dietary amino acid glycine (GSPIONs), to support non‐invasive lung imaging and determined particle biodistribution, as well as understanding the impact of the interaction of these nanoparticles with lung immune cells. These GSPIONs were characterized to be crystalline, colloidally stable, with a size of 12 ± 5 nm and a hydrodynamic diameter of 84.19 ± 18 nm. Carbon, Hydrogen, Nitrogen (CHN) elemental analysis estimated approximately 20.2 × 103 glycine molecules present per nanoparticle. We demonstrated that it is possible to determine the biodistribution of the GSPIONs in the lung using three‐dimensional (3D) ultra‐short echo time magnetic resonance imaging. The GSPIONs were found to be taken up selectively by alveolar macrophages and neutrophils in the lung. In addition, the GSPIONs did not cause changes to airway resistance or induce inflammatory cytokines. Alveolar macrophages and neutrophils are critical regulators of pulmonary inflammatory diseases, including allergies, infections, asthma and chronic obstructive pulmonary disease (COPD). Therefore, pulmonary Magnetic Resonance (MR) imaging and preferential targeting of these lung resident cells by our nanoparticles offer precise imaging tools, which can be utilized to develop precision targeted radiotherapy as well as diagnostic tools for lung cancer, thereby having the potential to reduce the pulmonary complications of radiation

Charged Rotating Black Holes in Four-Dimensional Gauged and Ungauged Supergravities

We study four-dimensional non-extremal charged rotating black holes in ungauged and gauged supergravity. In the ungauged case, we obtain rotating black holes with four independent charges, as solutions of N=2 supergravity coupled to three abelian vector multiplets. This is done by reducing the theory along the time direction to three dimensions, where it has an O(4,4) global symmetry. Applied to the reduction of the uncharged Kerr metric, O(1,1)^4\subset O(4,4) transformations generate new solutions that correspond, after lifting back to four dimensions, to the introduction of four independent electromagnetic charges. In the case where these charges are set pairwise equal, we then generalise the four-dimensional rotating black holes to solutions of gauged N=4 supergravity, with mass, angular momentum and two independent electromagnetic charges. The dilaton and axion fields are non-constant. We also find generalisations of the gauged and ungauged solutions to include the NUT parameter, and for the ungauged solutions, the acceleration parameter too. The solutions in gauged supergravity provide new gravitational backgrounds for a further study of the AdS_4/CFT_3 correspondence at non-zero temperature.Comment: Latex, 30 page

Pair Production of Topological anti de Sitter Black Holes

The pair creation of black holes with event horizons of non-trivial topology is described. The spacetimes are all limiting cases of the cosmological $C$ metric. They are generalizations of the $(2+1)$ dimensional black hole and have asymptotically anti de Sitter behaviour. Domain walls instantons can mediate their pair creation for a wide range of mass and charge.Comment: 4 pages, uses late