Design,Synthesis, and Evaluation of an 18F‐Labeled Radiotracer Based on Celecoxib–NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase‐2 (COX‐2)

A series of novel fluorine‐containing cyclooxygenase‐2 (COX‐2) inhibitors was designed and synthesized based on the previously reported fluorescent COX‐2 imaging agent celecoxib–NBD ( 3 ; NBD=7‐nitrobenzofurazan). In vitro COX‐1/COX‐2 inhibitory data show that N‐(4‐fluorobenzyl)‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide ( 5 ; IC₅₀=0.36 μM , SI>277) and N‐fluoromethyl‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide ( 6 ; IC₅₀=0.24 μM , SI>416) are potent and selective COX‐2 inhibitors. Compound 5 was selected for radiolabeling with the short‐lived positron emitter fluorine‐18 (¹⁸F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [¹⁸F] 5 was analyzed in vitro and in vivo using human colorectal cancer model HCA‐7. Although radiotracer uptake into COX‐2‐expressing HCA‐7 cells was high, no evidence for COX‐2‐specific binding was found. Radiotracer uptake into HCA‐7 tumors in vivo was low and similar to that of muscle, used as reference tissue.     

Envelope tracking using transient waveform switching shaping supply modulation

A novel supply modulation scheme for envelope tracking for a power amplifier in a transmitter is proposed, which follows a control principle that is fundamentally different from the existing ones. Instead of regulating the supply modulator's output in accordance with a given reference signal, the system utilizes a look‐ahead window and synthesizes pulses for the supply modulator such that its output tracks the envelope of the radio frequency signal amplified by the power amplifier, while minimizing its switching rate. Simulation results for a 5 MHz Long Term Evolution signal with 16 quadrature amplitude modulation indicates that the proposed technique provides very high average efficiency (84%) while maintaining a very low ratio between the switching frequency and the envelope bandwidth. Copyright © 2013 John Wiley & Sons, Ltd.     

A robust optimisation model for aggregate and detailed planning of a multi-site procurement-production-distribution system

The planning problem in the context of a multi-site procurement-production-distribution system (MSPPDS) considered in this paper is motivated from a real life case of a multinational consumer goods company. A robust optimisation model considering model robustness and solution robustness in the objective function is developed for integrated planning in three dimensions. Detailed production, procurement and distribution plans are integrated; countrywide aggregate production plan is integrated with a detailed plan. Similarly the detailed production plans from the previous planning cycle are integrated with current production plans. Constraints on storage space, production capacity and the time lag between procurement, production and distribution activities are captured in the model. Procurement and production plans are treated as ‘here-and-now’ decisions and the distribution plans are treated as ‘wait-and-see’ decisions to be implemented based on the realised demand scenario. The model is illustrated using an example problem and also successfully applied to the data of a consumer goods company involving 104,000 variables (with 832 integer variables) and 21,000 constraints.     

Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

A predictive mathematical model for tablet dissolution was developed and implemented in an end-to-end integrated continuous manufacturing pilot plant. The tablets were produced for immediate release with a proprietary extrusion-molding-coating (EMC) unit operation. Besides the mass balance of API solute in the buffer solution, the model consisted of the dissolution, diffusion, and population balance of API particles in the swollen tablet, which was mainly controlled by the swelling and erosion of the polymeric excipient matrix. An equivalence study was investigated by comparing the model prediction to the experiments that were conducted according to USP42-NF37 General Chapter <711> Dissolution, during which the drug dose level was varied in a range from 60 to 80 wt%. Consistent equivalence was demonstrated with the similarity factor f₂ > 50 for all sampled tablets. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.     

Multi-agent Path Planning with Heterogenous Interactions in Tight Spaces

By starting with the assumption that motion is fundamentally a decision making problem, we use the world-line concept from Special Relativity as the inspiration for a novel multi-agent path planning method. We have identified a particular set of problems that have so far been overlooked by previous works. We present our solution for the global path planning problem for each agent and ensure smooth local collision avoidance for each pair of agents in the scene. We accomplish this by modelling the collision-free trajectories of the agents through 2D space and time as rods in 3D. We obtain smooth trajectories by solving a non-linear optimization problem with a quasi-Newton interior point solver, initializing the solver with a non-intersecting configuration from a modified Dijkstra's algorithm. This space–time formulation allows us to simulate previously ignored phenomena such as highly heterogeneous interactions in very constrained environments. It also provides a solution for scenes with unnaturally symmetric agent alignments without the need for jittering agent positions or velocities.     

Study of weakly nonlinear double-diffusive magnetoconvection under concentration modulation

This article explains the heat and mass transfer of electrically conducting Newtonian fluid in double-diffusive magnetoconvective flow. We have considered two infinite horizontal plates at a constant distance apart under the concentration-modulated boundary condition. A constant magnetic field is considered in vertically upward directions, which generates an induced magnetic field. We have used the weakly nonlinear analysis to obtain the heat and mass transfer rate using the Ginzburg–Landau equation. The software MATHEMATICA is used to determine the solution of the Ginzburg–Landau equation by inbuilt function. The effects of physical parameters that occurred in the study on the Nusselt number and Sherwood number have been examined graphically. Modulation has a negligible effect on the threshold value of the thermal Rayleigh number, that is, on stationary convection. Moreover, it was found that the Chandrasekhar number, magnetic-Prandtl number, amplitude of modulation, and frequency of modulation are proportional to the heat and mass transports.     

A Comprehensive Review on Barium Titanate Nanoparticles as a Persuasive Piezoelectric Material for Biomedical Applications: Prospects and Challenges

Stimulation of cells with electrical cues is an imperative approach to interact with biological systems and has been exploited in clinical practices over a wide range of pathological ailments. This bioelectric interface has been extensively explored with the help of piezoelectric materials, leading to remarkable advancement in the past two decades. Among other members of this fraternity, colloidal perovskite barium titanate (BaTiO₃) has gained substantial interest due to its noteworthy properties which includes high dielectric constant and excellent ferroelectric properties along with acceptable biocompatibility. Significant progression is witnessed for BaTiO₃ nanoparticles (BaTiO₃ NPs) as potent candidates for biomedical applications and in wearable bioelectronics, making them a promising personal healthcare platform. The current review highlights the nanostructured piezoelectric bio interface of BaTiO₃ NPs in applications comprising drug delivery, tissue engineering, bioimaging, bioelectronics, and wearable devices. Particular attention has been dedicated toward the fabrication routes of BaTiO₃ NPs along with different approaches for its surface modifications. This review offers a comprehensive discussion on the utility of BaTiO₃ NPs as active devices rather than passive structural unit behaving as carriers for biomolecules. The employment of BaTiO₃ NPs presents new scenarios and opportunity in the vast field of nanomedicines for biomedical applications.