Browsing by Author "Patel, R."
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Item Open Access Aromatic Stacking Facilitated Self-Assembly of Ultrashort Ionic Complementary Peptide Sequence: β‑Sheet Nanofibers with Remarkable Gelation and Interfacial Properties(ACS Publications, 2020-05-13) Wychowaniec, J.; Patel, R.; Leach, J.; Mathomes, R.; Chhabria, V.; Patil-Sen, Y.; Hidalgo-Bastida, A.; Forbes, R.; Hayes, J.; Elsawy, M.Understanding peptide self-assembly mechanisms and stability of the formed assemblies is crucial for the development of functional nanomaterials. Herein, we have adopted a rational design approach to demonstrate how a minimal structural modification to a nonassembling ultrashort ionic selfcomplementary tetrapeptide FEFK (Phe4) remarkably enhanced the stability of self-assembly into β-sheet nanofibers and induced hydrogelation. This was achieved by replacing flexible phenylalanine residue (F) by the rigid phenylglycine (Phg), resulting in a constrained analogue PhgEPhgK (Phg4), which positioned aromatic rings in an orientation favorable for aromatic stacking. Phg4 self-assembly into stable β-sheet ladders was facilitated by π-staking of aromatic side chains alongside hydrogen bonding between backbone amides along the nanofiber axis. The contribution of these noncovalent interactions in stabilizing self-assembly was predicted by in silico modeling using molecular dynamics simulations and semiempirical quantum mechanics calculations. In aqueous medium, Phg4 β-sheet nanofibers entangled at a critical gelation concentration ≥20 mg/mL forming a network of nanofibrous hydrogels. Phg4 also demonstrated a unique surface activity in the presence of immiscible oils and was superior to commercial emulsifiers in stabilizing oil-in-water (O/W) emulsions. This was attributed to interfacial adsorption of amphiphilic nanofibrils forming nanofibrilized microspheres. To our knowledge, Phg4 is the shortest ionic self-complementary peptide rationally designed to self-assemble into stable β-sheet nanofibers capable of gelation and emulsification. Our results suggest that ultrashort ionic-complementary constrained peptides or UICPs have significant potential for the development of cost-effective, sustainable, and multifunctional soft bionanomaterials.Item Open Access Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application(MDPI, 2021-12-01) Cordeiro, Ana Sara; Patil-Sen, Y.; Shivkumar, M.; Patel, R.; Khedr, A.; Elsawy, M.Viral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians.Item Open Access Pressure control in district metering areas with boundary and internal pressure reducing valves(ASCE, 2008-08-17) Ulanicki, Bogumil; AbdelMeguid, Hossam Saadeldin; Bounds, Peter; Patel, R.Despite operational improvements over the last 10-15 years, water utilities still are losing a significant amount of potable water from their networks through leakage. The leakage is managed on the one hand by reactive and proactive maintenance and on the other hand by pressure control to reduce background leakage from connection and joints. This paper is based on experience from the Process Control – Water Software Systems group which was involved in many pressure control projects and the current Neptune project (www.neptune.ac.uk). A fast and efficient method to calculate time schedules and flow modulation curves is presented. Both time and flow modulation can be applied to a single inlet DMA. Time modulation can be applied to a multi-inlet district metering area (DMA) but this is not always possible for flow modulation due to the risk of hunting. It is convenient to distinguish between boundary and internal pressure reducing valves (PRVs), the decision variable for a boundary valve is a PRV set-point whereas for the internal valves it is a valve resistance. The resistance is then automatically translated into a set-point for field implementation. The time modulation methodology is based on solving a nonlinear programming problem with equality constraints represented by a hydraulic model with a pressure dependent leakage term and inequality constraints representing operational requirements (e.g. pressure at critical nodes). The cost of boundary flows which include leakage flows is minimized. An extended content model with pressure dependent leakage is simulated to provide a starting point for quick convergence. Optimal time schedules are converted into flow modulation curves by plotting scatter plots of flows against heads.The algorithm has been implemented as a module in the FINESSE package and allows complete pressure control tasks to be solved. A user needs to provide an hydraulic model, eakage information and leakage characteristic – leakage area and the exponent in the pressure power law. The program calculates time schedules and also flow modulation curves for single and multi-inlet PRVs. Evaluation of optimal control strategies and benefit analysis in terms of leakage reduction for two case studies provided by Yorkshire Water Services is included.Item Metadata only Pressure control in district metering areas with boundary and internal pressure reducing valves.(ASCE, 2009) Ulanicki, Bogumil; AbdelMeguid, Hossam Saadeldin; Bounds, Peter; Patel, R.