The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP

Empirical exploration of air traffic and human dynamics in terminal airspaces

Air traffic is widely known as a complex, task-critical techno-social system, with numerous interactions between airspace, procedures, aircraft and air traffic controllers. In order to develop and deploy high-level operational concepts and automation systems scientifically and effectively, it is essential to conduct an in-depth investigation on the intrinsic traffic-human dynamics and characteristics, which is not widely seen in the literature. To fill this gap, we propose a multi-layer network to model and analyze air traffic systems. A Route-based Airspace Network (RAN) and Flight Trajectory Network (FTN) encapsulate critical physical and operational characteristics; an Integrated Flow-Driven Network (IFDN) and Interrelated Conflict-Communication Network (ICCN) are formulated to represent air traffic flow transmissions and intervention from air traffic controllers, respectively. Furthermore, a set of analytical metrics including network variables, complex network attributes, controllers' cognitive complexity, and chaotic metrics are introduced and applied in a case study of Guangzhou terminal airspace. Empirical results show the existence of fundamental diagram and macroscopic fundamental diagram at the route, sector and terminal levels. Moreover, the dynamics and underlying mechanisms of "ATCOs-flow" interactions are revealed and interpreted by adaptive meta-cognition strategies based on network analysis of the ICCN. Finally, at the system level, chaos is identified in conflict system and human behavioral system when traffic switch to the semi-stable or congested phase. This study offers analytical tools for understanding the complex human-flow interactions at potentially a broad range of air traffic systems, and underpins future developments and automation of intelligent air traffic management systems.Comment: 30 pages, 28 figures, currently under revie

Performance and cost analysis of all-optical switching: OBS and OCS

This paper presents a study of performance and cost analysis of optical circuit switching (OCS) and optical burstswitching (OBS) by proposing the clear images of their node architectures and cost formulations. Then, we apply servicelevel agreement (SLA) of the high quality of service application in the terms of network blocking probability and averagenetwork delay to demonstrate OCS and OBS performances, their investment costs, and network dimensioning methodology.Applying SLA to our studies can illustrate the impact of contention resolution and blocking resolution schemes to theperformances and costs of OBS and OCS, accordingly. The simulations illustrate that OBS applying WC gives the bestperformance among all architectures deploying the same offered bandwidth. The investigations also show that WC is a majortechnique contributing high performance gain to both OCS and OBS. Especially for OBS, WC is an important scheme allowingOBS high data grooming property as its performance gain contributing to OBS is much higher than those of OCS. For thecost analysis, OCS is the most economic among all architectures. BA provides the most cost effectiveness among all OBScontention resolution schemes. Lastly, FDL is the least cost effective scheme as it gives little performance enhancement butadds more cost to the network

Integrated and joint optimisation of runway-taxiway-apron operations on airport surface

Airports are the main bottlenecks in the Air Traffic Management (ATM) system. The predicted 84% increase in global air traffic in the next two decades has rendered the improvement of airport operational efficiency a key issue in ATM. Although the operations on runways, taxiways, and aprons are highly interconnected and interdependent, the current practice is not integrated and piecemeal, and overly relies on the experience of air traffic controllers and stand allocators to manage operations, which has resulted in sub-optimal performance of the airport surface in terms of operational efficiency, capacity, and safety. This thesis proposes a mixed qualitative-quantitative methodology for integrated and joint optimisation of runways, taxiways, and aprons, aiming to improve the efficiency of airport surface operations by integrating the operations of all three resources and optimising their coordination. This is achieved through a two-stage optimisation procedure: (1) the Integrated Apron and Runway Assignment (IARA) model, which optimises the apron and runway allocations for individual aircraft on a pre-tactical level, and (2) the Integrated Dynamic Routing and Off-block (IDRO) model, which generates taxiing routes and off-block timing decisions for aircraft on an operational (real-time) level. This two-stage procedure considers the interdependencies of the operations of different airport resources, detailed network configurations, air traffic flow characteristics, and operational rules and constraints. The proposed framework is implemented and assessed in a case study at Beijing Capital International Airport. Compared to the current operations, the proposed apron-runway assignment reduces total taxiing distance, average taxiing time, taxiing conflicts, runway queuing time and fuel consumption respectively by 15.5%, 15.28%, 45.1%, [58.7%, 35.3%, 16%] (RWY01, RWY36R, RWY36L) and 6.6%; gated assignment is increased by 11.8%. The operational feasibility of this proposed framework is further validated qualitatively by subject matter experts (SMEs). The potential impact of the integrated apron-runway-taxiway operation is explored with a discussion of its real-world implementation issues and recommendations for industrial and academic practice.Open Acces

Effects of blanching on color, texture and sodium chloride content during storage time of frozen vegetable soybean modeling for commercial scale

Vegetable soybeans [Glycine max (L.) Merrill] are a green stage of soybeans, which have become increasingly popular among health-conscious Americans as an alternative low-fat and heart-healthy food. Vegetable soybeans (VSB) are also an excellent source of protein and fiber. However, the vast majority of the VSB consumed are imported, as they are not extensively grown and processed in the United States. The situation results in short supply and limited processing information. The purpose of this study was to investigate the effects of water blanching (at 86, 92, 98 °C for 1m30s, 2m, 2m30s) and steam blanching (at 86, 92, 98 °C for 1m30s, 2m, 2m30s, 2m50s) on color, texture and sodium chloride content of frozen VSB during six-month storage time. It was hypothesized in this study that decreasing in blanching time and temperature from the conventional commercial process (98 °C for 2m30s – water blanching and 98 °C for 2m50s – steam blanching) would not affect the quality attributes of frozen VSB. The results showed that blanching at temperatures lower than 98 °C for both methods did not completely inactive the peroxidase in VSB, which may cause quality losses during storage. Water blanching at shorter time than the control (2m30s) in commercial processing experiment did not effectively tenderize the texture of VSB. On the other hand, blanching time of all experiments can be reduced to 1m30s with comparable quality to the conventional processes. Blanching apparently affected quality of VSB while freezing and frozen storage had no significant effects on the final product. Optimal processing results in the improvement of production efficiency, increasing production yield and profits. Knowledge from this study is anticipated to be, more or less, supportive and informative for VSB producers in the United States and everyone who interested in this valuable commodity, vegetable soybeans. Advisors: Milford A. Hanna, Curtis L. Welle

Transient liquid phase bonding of an oxide dispersion strengthened superalloy

This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel University.Oxide dispersion strengthened (ODS) alloys have been developed with unique mechanical properties. However, in order to achieve commercial application an appropriate joining process is necessary which minimizes disruption to the alloy microstructure. Transient liquid phase (TLP) bonding is a promising joining method, but previous work has shown that the segregation of dispersoids within the joint region results in bonds with poor mechanical strengths. This research work was undertaken to further explore particulate segregation at the joint region when TLP bonding and to develop bonding techniques to prevent it. A Ni-Cr-Fe-Si-B interlayer was used to bond an alloy MA 758. The effects of parent alloy grain size, bonding temperature, and external pressure on the TLP bonding process were investigated. Three melting stages were identified for the interlayer, and the bonding temperature was chosen so that the interlayer was in the semi-solid state during bonding. This novel bonding mechanism is described and applied to counteract the segregation of Y203 dispersoids. The grain size of the parent alloy does not alter the particulate segregation behaviour. It is concluded that a low bonding temperature with moderate pressure applied during bonding is preferable for producing bonds with less disruption to the microstructures of the parent alloy. Joint shear tests revealed that a near parent alloy strength can be achieved. This study also shed some light on choosing the right bonding parameters suitable for joining the complicated alloy systems. A Ni-P interlayer was also used to bond the ODS alloy. Microstructural examination indicated that a thin joint width and less disruption to the parent grain structure were achieved when bonding the alloy in the fine grain state. The time for isothermal solidification was found to be shorter when compared with bonds made with the parent alloy in the recrystallized state. All these observations were attributed to the greater diffusivity of P along the grain boundaries than that of the bulk material. A high Cr content within the parent alloy changes the mechanism of the bonding process. The diffusion of Cr into the liquid interlayer has the effect of raising the solidus temperature, which not only accelerates the isothermal solidification process, but also reduces the extent of parent alloy dissolution