High-dimension profiling data generate a multifunctional peptide-mimic chemo-structure by connecting conserved fragments based on the neutrophil immune defense CAP37 protein as an in-silico antibacterial and woundhealing candidate agent

CAP37, a protein constitutively EXPRESSED in human neutrophils and induced in responseto infection in corneal epithelial cells, plays a significant role in host defense against infection. Initiallyidentified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Delineation of thedomains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use have alsobeen explored. Novel findings of a multifunctional domain between a 120 and 146 have also been reported.Here, in Biogenea Pharmaceuticals Ltd we for the first time generated a multifunctional peptide-mimicchemo-structure by connecting conserved fragments based on the neutrophil immune defense CAP37 proteinas an in-silico antibacterial and wound-healing canditate agent. This in silico effort was accomplished byutilizing various generated descriptors of proteins, compounds and their interactions resulting in aperformance/cost evaluation study for a GPU-based drug discovery application on volunteer computingapproaches based on Automated Structure-Activity Relationship Minings in Connecting Chemical Structureto Biological Profiles for the generation of novel Computational biomodeling of 3D drug-protein binding freeenergy evaluation

PiNNwall: heterogeneous electrode models from integrating machine learning and atomistic simulation

Electrochemical energy storage always involves the capacitive process. The prevailing electrode model used in the molecular simulation of polarizable electrode-electrolyte systems is the Siepmann-Sprik model developed for perfect metal electrodes. This model has been recently extended to study the metallicity in the electrode model by including the Thomas-Fermi screening length. Nevertheless, a further extension to heterogeneous electrode models requires introducing chemical specificity which does not have any analytical recipes. Here, we address this challenge by integrating the atomistic machine learning code (PiNN) for generating the base charge and response kernel and the classical molecular dynamics code (MetalWalls) dedicated to the modelling of electrochemical systems, and this leads to the development of the PiNNwall interface. Apart from the cases of chemically doped graphene and graphene oxide electrodes as shown in this study, the PiNNwall interface also allows us to probe polarized oxide surfaces in which both the proton charge and the electronic charge can coexist. Therefore, this work opens the door for modelling heterogeneous and complex electrode materials often found in energy storage systems

Radiation Effects in Metal Oxides and Carbides

MD simulations of SiO2, TiO2, Cr2O3, Al2O3, MgO, and SiC, are performed to: (a) calculate TDE probability distributions and dependence on crystallographic direction, and (b) determine the number and types of defects formed with low- and high-energy PKAs and projectiles. In addition, a qualitative comparison of the MD simulation results of radiation damage in TiO2, MgO, and crystalline and amorphous SiC thin films are compared with those of in situ TEM ion beam irradiation experiments at the Sandia National Laboratories’ I3TEM facility. The TDE probability distributions show strong anisotropy and those with 50% probability agree well with the reported experimental values. Results show that MgO and TiO2 are the most radiation hard of all metal oxides investigated and that the lost long-range order in TiO2 during the ballistic phase of interaction by a 46 keV Ti projectile, reemerges as most of the produced defects anneal within tens of picoseconds. The MD simulations of Si PKAs of up to 100 keV in 3C-SiC shows only dispersed subcascades forming. The sizes of defect clusters in 3C-SiC are in general agreement with the in situ TEM irradiation experiments using a 1.7 MeV Au3+ ion beam. The defect structures show contrast changes ranging from 9.1 to 83.5 nm2, which is in general agreement with the MD simulation values ranging from 5 to 76 nm2. SiC amorphization is not observed in the MD simulations. The stored potential energy due to defect production in 3C-SiC is ~10% of the 10-100 keV Si PKAs in the MD simulations, and indistinguishable in a-SiC. Simulations using single and multiple Au projectiles show that the extent of the defect cascades strongly depend on the number of projectiles and that defect structures are in general agreement with those induced by single 1.7 MeV Au3+ ion strikes in the in situ TEM experiments. The MD simulations with 10, 20-keV projectiles in MgO produces a void of 102,500 vacancies during the ballistic phase, decreasing to 5,000 vacancies after annealing. Simulated SAED patterns and RDFs show local amorphization of MgO at the peak of the ballistic phase, which partially recrystallizes during the annealing phase

In-Depth on the Fouling and Antifouling of Ion-Exchange Membranes

The use of ion-exchange membranes (IEMs) has accelerated over the past two decades in a wide variety of industrial processes (electrodialysis, electro-electrodialysis, electrolysis, dialysis, etc.) for applications related to chemical, pharmaceutical and food industries, energy production, water treatments, etc. Organic and mineral fouling (or scaling) phenomena are two major factors limiting the efficiencies of IEMs processes and performances (reduction of the IEMs selectivity and stability, increase of their electrical resistance, deduction of the energy efficiency of the process, etc.) leading to significant economic losses. The current washing, cleaning and sterilization processes (anti-fouling treatments) make it possible to recover some of the IEMs performances, but frequently induce degradation on the membrane material. Another essential point in the fouling studies is the choice of the best and appropriate analysis and diagnostic technique to evaluate this or that magnitude, or observe this or that object on the surface or in the mass of the membrane. This book is focused on recent advancements in techniques for diagnosing and characterizing the fouling effects on membranes, in mechanisms governing this complex phenomenon, and in the various innovative and economically viable solutions for reducing fouling

Bead Modeling of Transport Properties of Macromolecules in Free Solution and in a Gel

On the bead modeling methodology, or BMM, a macromolecule is modeled as a rigid, non-overlapping bead array with arbitrary radii. The BMM approach was pioneered by Kirkwood and coworkers (Kirkwood, J.G., Macromolecules, E.P. Auer (Ed.), Gordon and Breach, New York, 1967; Kirkwood, J.G., Riseman, J., J. Chem. Phys., 1948, 16, 565) and applied to such transport properties as diffusion, sedimentation, and viscosity. With the availability of computers, a number of investigators extended the work to account for the detailed shape of biomolecules in the 1970s. A principle objective of my research has been to apply the BMM approach to more complex transport phenomena such as transport in a gel, electrophoresis (free solution and in a gel), and also transport in more complex media (such as the viscosity of alkanes and benzene). Variables considered by the BMM include the number of beads (N), the radii of the beads, net charge and charge distribution, conformations, salt type, and salt concentration. The BMM has been extended to: (1) account for the existence of a gel; (2) characterize the charge and secondary structure of macromolecules; (3) account more accurately for hydrodynamic interaction (remove the orientationnal preaveraging approximation of hydrodynamic interaction); (4) study the effect of ion relaxation for particles in arbitrary size, shape, and charge; (5) consider the salt dependence of electrokinetic properties; (6) account for the formation of possible complex between guest ions and BGE ions. We also did diffusion constant measurement by NMR for amino acids and short peptides in 10%D2O-90% H2O at room temperature and applied to our modeling study by BMM

Removal of Enteric Viruses By Ultrafiltration Membranes

Application of low pressure membranes in drinking water treatment, including both microfiltration (MF) and ultrafiltration (UF), have witnessed a rapid increase in the past decades. Low pressure membranes are considered a good technology in retrofitting existing conventional drinking water treatment plants or in newly constructed plants to meet the stringent regulations for drinking water treatment that aim at preventing health risks of waterborne diseases. Enteric viruses are one of the major types of waterborne pathogens, and they can be commonly found and are persistent in the environment. Both the United States and Canada require a 99.99% (4-log) removal of viruses during the drinking water treatment train. Unlike MF membranes, UF membranes have a very good potential for removing enteric viruses from the water due to their smaller pores comparable to the size of viruses. Drinking water regulations/guidelines in both the United States and Canada do not grant UF membranes any removal credit for viruses by default; however they have the provision that, in certain cases, virus removal credit may be granted based on pilot scale challenge testing. A better understanding of the interaction between the UF membranes and virus rejection can help to establish a removal credit for UF membranes. An essential part of this will be the effect of the membrane operation on the rejection of viruses to determine if UF membranes can offer a consistent removal of viruses. Membrane fouling is one of the major problems in membrane operation and it can affect the rejection characteristics of the membrane and improve its performance. The aim of this study was to investigate the removal of virus surrogates (MS2 and φX174 bacteriophage) using a commercial UF membrane under different conditions, to obtain information about the removal mechanisms of viruses. The experimental filtration unit was designed to have similar conditions like the full scale membrane treatment plants. The UF membrane used in this study provided very good removal of both MS2 and φX174 bacteriophage. The obtained results were consistent and in agreement with the expected removals based on the membrane characterization results and types of virus surrogate. As part of this work, a detailed study to improve methods for characterizing the pore size distribution of membranes was conducted. In the second part of the study, two different types of surface waters were used to study the effect of membrane fouling on virus removal. It was found that mainly hydraulically irreversible fouling could significantly improve the virus removal by UF membranes. Different cleaning regimes that are used in treatment plants had varying effects on virus removal. After maintenance cleaning, virus removal remained higher than that of clean membranes, and only chemical cleaning was effective for completely removing membrane foulants and returning virus removal back to base levels. Advanced analytical techniques were used to define the nature of the fouling layer on the membrane surface and how the foulants affected the rejection of viruses. Finally, our study showed that UF membranes are a robust treatment technology for removing different types of enteric virus surrogates from water under different operational conditions. Close monitoring of the UF unit performance and direct integrity testing can possibly detect membrane problems that can affect the rejection of viruses. Based on the virus physical characteristics and a detailed study of the membrane surface characteristics, especially the pore size distribution of the membrane, the removal of the specific virus can be closely estimated

Ruthenium (II) complexes with terpyridine derivatives: what is the lifetime of the excited state dependent on?

The synthesis, spectroscopic and electrochemical characterisation of ruthenium (II) polypyridyl mononuclear complexes containing 1,2,4-tnazole and tetrazole moiety are described. Chapter one is an introduction relating to the work described in the thesis. The methods of characterisation, which are described in chapter two, include High Performance Liquid Chromatography, 'H-NMR, UV/Visible spectroscopy, fluorimetry, electrochemistry, spectroelectrochemistry, mass spectrometry, and lifetime emission measurements. Chapter three describes the synthesis of the new set of ligands and their mononuclear Ruthenium (II) complexes. Chapter four contains an extensive characterisation of Ru(II)(bpy)2 moiety complexes containing a 5-(2-pyridyl)-l,2,4-triazole ligand, (Apy), or a 5-(2-pyridyl) tetrazole ligand, ([ ipy), and their comparison with the archetype Ru(bpy)s2+. The examination of the acid-base chemistry of the complexes by UV/Visible spectroscopy revealed important information about the location of the excited state. Chapter five explores the spectroscopic, photophysical and electrochemical properties of the new [Ru(tpy)fApyA)] complexes, where (ApyA)2' is the 2,6 di-(l,2,4- triaz-3-yl)-pyridine ligand. The new species was exhaustively studied especially because it revealed to be one of the few example, available in literature, of emitting Ru(H) terpiridine complexes, with a lifetime of the excited state in the order of 100 nanoseconds. Chapter six describes the synthesis of complexes containing (ApyA)2' and terpyridine derivatives or vice-versa terpyridine and (ApyA)2" derivative ligands. One of them will be used as a photsensitiser in a photovoltaic cell. Attachment of the [Ru(II)(tctpy)(ApyA)] complex to nanocrystalline TiC>2 films indicates incident photonto- current efficiency (IPCE) of greater than 60%. Chapter seven exptores the use of a new 2,6 di-(tetraz-5-yl)-pyndine ligand, (Upyl ]) ", and the spectroscopic, photophysical and electrochemical properties of its Ru(II) complexes. Chapter eight is an attempt to rationalise the collected data of the Ru(tpy) moiety. The change of the energy levels in relation to the different ligands is analysed. The correlations between spectroscopic, photophysical and electrochemical data of the new complexes and the existent ones created an extensive knowledge of the tridentate Ru(H) complexes, that increases their availability as a photosensitive building block for a supramolecular system. Some suggestions for future work are also considered in the final Chapter. Finally two appendices are included in this thesis. The first is a literature survey which synopsises the last ten years scientific papers, on the Ru-tpy moiety, includmg investigations of their properties, use in analytical research or their use as building blocks in supramolecolar systems. The second appendix refers to the publications, poster presentations and oral presentations made during the course of the research

Trihalomethanes : from precursors to management strategies

EngD ThesisInvestigation and characterisation of dissolved organic carbon (DOC) in raw and treated water from six case study sites located across Scotland identified the main aspects that influenced the formation of trihalomethanes (THMs) during and after disinfection. DOC and temperature were the main drivers of THMs found in this research. However, other variables such as bromide also played an important role in driving reactions towards brominated species of THMs. DOC quality, essentially of humic and fulvic origin remained constant along the year, but quantity affected THMs yields due to seasonal changes. Further DOC characterisation showed that treatment by coagulation or membrane filtration successfully removed hydrophobic DOC leaving a larger proportion of hydrophilic DOC in treated waters. This investigation identified two main groups of organic substances that corresponded to the hydrophilic fraction of DOC: phenolics and carboxylic acids. The final stage of the experimental work lead to the application of adsorption with activated carbon (AC) to remove these compounds from the treatment although at large doses. This work also presents a cost benefit analysis of two potential strategies to manage THMs precursors: the use of Ultraviolet (UV) scan sensors and AC adsorption. These technologies contribute to the enhancement of the industrial sponsors’ processes by improving compliance with regulatory quality and public health standards