Impedance responses and size-dependent resonances in topolectrical circuits via the method of images

Resonances in an electric circuit occur when capacitive and inductive components are present together. Such resonances appear in admittance measurements depending on the circuit's parameters and the driving AC frequency. In this study, we analyze the impedance characteristics of nontrivial topolectrical circuits such as one- and two-dimensional Su-Schrieffer-Heeger circuits and reveal that size-dependent anomalous impedance resonances inevitably arise in finite $LC$ circuits. Through the \textit{method of images}, we study how resonance modes in a multi-dimensional circuit array can be nontrivially modified by the reflection and interference of current from the structure and boundaries of the lattice. We derive analytic expressions for the impedance across two corner nodes of various lattice networks with homogeneous and heterogeneous circuit elements. We also derive the irregular dependency of the impedance resonance on the lattice size, and provide integral and dimensionally-reduced expressions for the impedance in three dimensions and above.Comment: 24 pages, 10 figure

Screening of actinobacteria for novel antimalarial compounds

The success of our first-line antimalarial treatments is threatened by increased drug resistance in Plasmodium parasites. This makes the development of novel drugs critical to combat malaria. Historically, natural products have been an excellent source of novel antimalarial compounds and thus are an ideal place to search for potential drugs. Filamentous members of the bacterial phylum, Actinobacteria, are well-known antibiotic producers, but their antimalarial potential has not been well investigated. This makes these actinobacteria a potentially valuable source of novel antimalarial compounds. To evaluate the antimalarial potential of the filamentous actinobacteria, uncharacterized environmental actinobacterial strains from the Meyers laboratory culture collection, as well as the type strains of new actinobacterial species identified and characterized in the Meyers laboratory, were screened for antiplasmodial activity against drug-sensitive Plasmodium falciparum, NF54. Liquid cultures were extracted using the mid-polar solvent, ethyl acetate, with the aim of discovering drug-like molecules that can be administered orally. Thirty-one strains of actinobacteria belonging to eight genera (Actinomadura, Amycolatopsis, Gordonia, Kribbella, Micromonospora, Nocardia, Nonomuraea, and Streptomyces) were screened revealing fourteen active strains. Eight strains were identified for further study as the displayed antiplasmodial efficacy matching predefined criteria. Of these eight candidates, Streptomyces strain PR3 was selected, as it showed excellent antiplasmodial efficacy, no cytotoxicity against Chinese Hamster Ovary (CHO) or liver HepG2 cell lines, no haemotoxicity, and was easy to culture. Bioassay-guided fractionation of the crude extracts of strain PR3, supported by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analysis, was conducted to isolate and identify the compounds responsible for the antiplasmodial activity. During purification by solid phase extraction (SPE), a novel class of compounds was isolated. The structure of these compounds was elucidated by HRMS and NMR analysis and determined to be a series of crown ethers with a methylated backbone. These methylated crown ethers (MCE) were not produced by strain PR3, but by the cyclization of polypropylene glycol (PPG) oligomers from Amberlite® XAD-16N 20–60 mesh resin under aqueous conditions. The MCEs displayed weak antiplasmodial activity against P. falciparum NF54, without cytotoxicity against the Chinese Hamster Ovary, HepG2 cell lines, nor human erythrocytes. To the author's knowledge, the MCEs are novel compounds, and this is the first time the cyclization of PPG oligomers into crown ethers has been reported. As the MCEs were not responsible for strain PR3's potent antiplasmodial activity, further study was conducted. Using the Global Natural Product Social molecular networking (GNPS) workflow, genome mining, and NMR analysis, it was revealed that the cyclodepsipeptides, valinomycin, montanastatin, and nine other novel analogues were responsible for the high antiplasmodial activity detected. A review of the literature revealed that the structure of four of these analogues had been predicted, based on MS/MS and the biosynthesis of valinomycin. Using the same described biosynthetic logic and MS/MS analysis, two new cyclodepsipeptides, compounds 1054 and 1068, were elucidated. Unfortunately, chromatographic systems developed were unable to purify the cyclodepsipeptides, and individual evaluation of their antiplasmodial efficacy and host selectivity was not possible. The fraction containing the cyclodepsipeptides exhibited strong antiplasmodial activity against the drug-sensitive, NF54 and multidrug-resistant K1, strains of P. falciparum. No cytotoxicity was displayed against the CHO cell line and no haemotoxicity was seen against human erythrocytes. Moderate toxicity was exhibited against the liver HepG2 cell line; however, the selectivity index of the cyclodepsipeptides suggested that they are selectively targeting the Plasmodium parasites. Overall, these results are positive, and further study of the individual cyclodepsipeptides is warranted. During the investigation, discrepancies were noticed between different fractions in terms of antiplasmodial activity. These fractions contained both the MCEs and, cyclodepsipeptides along with a range of impurities, yet they displayed potent antiplasmodial activity. Further study suggested that combination of the MCEs and cyclodepsipeptides elicits a synergistic response and improves antiplasmodial efficacy. This was determined independently using two models, the fixed-ratio isobologram method and the CompuSyn programme based on the massaction law principle. The workflow developed during this investigation demonstrates how new technologies can be used to dereplicate and elucidate bioactive natural products. This workflow can be utilized to continue this research and identify new natural products that can combat malari

Doctor of Philosophy

dissertationThree decades have passed since the discovery of HIV and still no viable vaccine technologies exist to prevent the spread of the virus. The concept of interrupting HIV transmission with oral or topical antiretroviral drugs (ARV), also known as pre-exposureprophylaxis (PrEP), has been proven in several clinical efficacy trials. One PrEP strategy has been to formulate the ARV tenofovir (TFV) into topically applied vaginal gels. However, the vaginal gel approach has met with mixed results, likely due to poor user adherence. Globally, high incidence of HIV infection correlates with high incidence of unintended pregnancy, especially in resource-poor regions. Combining HIV PrEP with contraception into a single, easy-to-use product could have a synergistic effect, further motivating women to protect themselves against HIV infection. Thus, a concerted effort is underway to develop long-acting multipurpose prevention technologies (MPT) capable of simultaneously preventing sexual HIV transmission and pregnancy. The nearly half-century-old technology of the intravaginal ring (IVR) has undergone a renaissance in the past decade due to the potential of IVR to leverage both the principles of topical HIV PrEP and of long-acting controlled drug release systems. This dissertation details several new observations and innovations regarding drug delivery from intravaginal rings (IVR). First, an injection-molded, hydrophilic poly(ether urethane) (HPEU) matrix IVR capable of sustained release of milligram-per-day quantities of TFV over 90 days is described. In the final two chapters, a secondiv generation reservoir TFV IVR is combined with a reservoir poly(ether urethane) segment that releases microdoses of the contraceptive progestin levonorgestrel (LNG), in a multisegment IVR design, concluding with assessments of product stability and in vivo pharmacokinetics in order to confirm the suitability of the IVR for clinical investigation. This dissertation represents an engineer's approach to designing and testing IVR, which are most commonly considered a pharmaceutical product rather than a medical device. Accordingly, much attention is given to the development and usage of mathematical models for drug release and mechanical properties from IVR, and in general to a mechanistic understanding of the underlying mechanisms of their operation

Automatic Control and Routing of Marine Vessels

Due to the intensive development of the global economy, many problems are constantly emerging connected to the safety of ships’ motion in the context of increasing marine traffic. These problems seem to be especially significant for the further development of marine transportation services, with the need to considerably increase their efficiency and reliability. One of the most commonly used approaches to ensuring safety and efficiency is the wide implementation of various automated systems for guidance and control, including such popular systems as marine autopilots, dynamic positioning systems, speed control systems, automatic routing installations, etc. This Special Issue focuses on various problems related to the analysis, design, modelling, and operation of the aforementioned systems. It covers such actual problems as tracking control, path following control, ship weather routing, course keeping control, control of autonomous underwater vehicles, ship collision avoidance. These problems are investigated using methods such as neural networks, sliding mode control, genetic algorithms, L2-gain approach, optimal damping concept, fuzzy logic and others. This Special Issue is intended to present and discuss significant contemporary problems in the areas of automatic control and the routing of marine vessels

A new paradigm towards advanced Li-based batteries: a true polymeric approach

Initially limited to portable consumer electronics, the field of lithium ion batteries (LIBs) is rapidly expanding toward performance-demanding applications such as electric vehicles and load levelling of electric grids. The success of LIBs is owed to high energy density, lightweight, rapid charge/discharge, and long lifetime. However, safety issues deriving from the use of flammable liquid organic electrolytes are at present one of the major drawbacks of this technology. Solid polymer electrolytes (SPEs), representing a lithium salt associated with a polar neutral polymer or with an ion-conducting polymer matrix have been proposed to replace liquid electrolytes in LIBs. Among other benefits, SPEs offer inherent thermal stability, nonflammability and good mechanical stability. Moreover, they do not require liquid electrolyte confinement and, therefore, enable the production of flexible and thinner batteries. Despite the mentioned advantages, the intrinsic low ionic conductivity of polymer electrolytes have precluded their use in real devices so far, and significant research efforts are still required to address this open issue. Considering such a scenario, the research work during this Ph.D. career has been focused on the development of novel high-performance polymer electrolytes for applications in LIBs. The goal has been pursued exploiting a series of smart engineering strategies and synthetic pathways. All of the newly designed materials were characterized in terms of their physicochemical and electrochemical properties, and their performance evaluated in lab-scale lithium cell prototypes. In the first part of this Ph.D. work, UV-induced crosslinking has demonstrated to be a versatile tool for preparing different families of quasi-solid polymer electrolytes based on polyethylene oxide (PEO). In the past decades, this polymer has been intensively studied since its ability to complex and transport alkali metal cations. At ambient temperature, the ionic conductivity of lithium salt complexes in PEO is limited by the semicristalline domains, and ion conduction is limited to the amorphous phase. Recently, combinations of high molecular weight PEO, lithium salts and low molecular weight plasticizer have been explored as polymer based electrolyte. Despite an increase of ionic conductivity, the mechanical stability of the composite was poor when the content of plasticizer exceeded a certain limit. In this thesis a solution to this problem was proposed: highly conductive PEO based polymer electrolytes were prepared via UV induced crosslinking in the presence of a lithium salt (lithium bis(trifluoromethanesulfonyl) imide, LiTFSI) and various high boiling point liquid plasticizers. A room temperature ionic liquid, namely 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide (EMITFSI) was used in the former case, whereas tetraethylene glycol dimethyl ether (TEGDME) was employed in the latter. In both systems, ionic conductivity substantially increased upon incorporation of the plasticizer (up to 10-4 S cm-1 at 25 °C). Noteworthy, the obtained crosslinking assured the mechanical properties to be well retained despite the high plasticizer content (up to 45% wt). Moreover, the prepared SPE showed outstanding characteristics in terms of thermal stability (> 170 °C) and electrochemical stability window (>4.5 V in both cases). Finally, the prepared materials were successfully tested in lithium cells prototypes. An in situ polymerization method was developed to obtain an improved interfacial adhesion between the polymer electrolyte and the cells electrodes. Lab-scale lithium cells were assembled and tested up to hundred cycles of full charge and discharge, showing excellent performance at different operating temperatures and applied current rates. Given the promising prospect of the developed materials, along with the easiness of the proposed process, the newly developed preparation method has led to a pending international patent. In the course of the Ph.D. work, the attention was also focused on single-ion conducting polymer electrolytes. In typical SPE, most of the ionic current is carried by the anion of the lithium salt, corresponding to a lithium transference number (t+) ranging from 0.1-0.4. Consequently, only 10-40% of the ionic current is useful to the lithium-ion cell chemistry and strong salt concentration gradients are established during battery operation with deleterious effects on performance and battery lifetime. High transference number polymer electrolytes were proposed to reduce significantly concentration polarization. This new class of materials is composed of negatively charged polymer backbones having lithium-ion counter ions. Since anionic moieties are covalently bonded to the polymer backbone, lithium ions are the only mobile ionic species, thus preventing polarization phenomena. A specifically developed anionic monomer, namely lithium 1-[3-(methacryloxy) propylsulfonyl]-1(trifluoromethanesulfonyl)imide (LiMTFSI), was synthetized and used to prepare the single-ion conducting polymer electrolytes. Different macromolecular architectures were prepared: random or block copolymers with poly(ethylene glycol) methyl ether methacrylate (PEGM) and crosslinked networks with poly(ethyleneglycol) dimethacrylate. All the proposed systems showed lithium transference number approaching the unity. For comparison, previously described SPEs based on EMITFSI and TEGDME showed t+ of 0.17 and 0.32, respectively. Remarkably, the electrochemical stability window of both proposed system exceeded 4.5 V. Moreover, by changing the polyelectrolyte microstructure, it was also possible to tailor the ionic conductivity of the proposed SPEs. In particular, single-ion block SPE exhibited ionic conductivity values as high as 10-5 S cm-1 at 55 °C; and prolonged cycling in prototype lithium cells was demonstrated at 70 °C. The ionic conductivity of single-ion crosslinked networks was substantially enhanced (up to 8.6 × 10‒5 S cm-1 at 20 °C) by the incorporation of propylene carbonate as liquid plasticizer. The obtained gel electrolytes were tested in lab-scale lithium cells, which showed outstanding performance in terms of rate capability (up to 5C and 1C current rates respectively at 70 °C and ambient temperature) and cycling stability upon prolonged cycling (more than 3 months of un-interrupted testing), outperforming the current reports on single-ion conducting systems. In conclusion, the strategies presented in this PhD work in terms of performance optimization of different polymer electrolytes, as well as the engineering and synthetic procedures suggested will optimistically represent reliable solutions for the scientific community for the development of the next-generation of safe, cost-effective and environmentally friendly lithium-ion as well as lithium metal batteries

Bridging formalisation and expert judgement in searches for studies for systematic reviews

Systematic reviews aim to use pre-specified and explicitly described methods. This entails an element of formalisation in which methods are described according to a fixed structure. However, qualitative studies show that too much emphasis on formalisation can obscure how expert judgement is required even after clearly defined methods are established. Thus, there is a gap between how systematic review methods are formalised in guidance and reported in systematic reviews, and how they are carried out in practice using undisclosed expert judgement. The aim of this thesis is to describe and bridge the gap between formalisation and expert judgement with respect to searching for studies for systematic reviews, with a particular focus on forward citation searching and web searching. Forward citation searching and web searching are useful search methods to consider due to observed variability in both if and how they are used in systematic reviews, in contrast to searches of bibliographic databases which are routine in almost all systematic reviews. To this end, the thesis seeks to fulfil three objectives: first, to formalise the conduct and reporting of forward citation searching and web searching in systematic reviews; secondly, to describe and evaluate the conduct and reporting of forward citation searching and web searching in systematic reviews; thirdly, to explore the role of expert judgement when using forward citation searching and web searching. Both aggregative and configurative review types are considered throughout. The findings show that formalised approaches to searching are apparent in guidance to different degrees. However, systematic reviews do not always reflect formalised guidance. Qualitative investigation describes hitherto hidden practical knowledge which underpins searching decisions. The thesis draws these findings together and proposes that guidance on searching for studies should be framed in terms of the practical understanding which informs how searching is undertaken rather than limited to describing recommended processes

Aeronautical engineering: A continuing bibliography with indexes (supplement 304)

This bibliography lists 453 reports, articles, and other documents introduced into the NASA scientific and technical information system in May 1994. Subject coverage includes: design, construction and testing of aircraft and aircraft engines; aircraft components, equipment, and systems; ground support systems; and theoretical and applied aspects of aerodynamics and general fluid dynamics

LC-MS based metabolomic investigation of the effects of phytohormones on cultured cells of Moringa oleifera

Abstract: Please refer to full text to view abstract.M.Sc. (Biochemistry