Utilizing Polymer Topology in Peptide-Based Block Copolymers: Unique Aqueous Assembly and Responsive Behavior

This document details work in the area of amphiphilic polypeptide-based block copolymers that are able to self-assemble into well-defined nanostructures in aqueous solution. The main focus of this work is to understand the impacts of polymer topology on self-assembly behavior and response to external stimulus, particularly pH. Poly(L-lysine) and poly(L-glutamic acid) are two pH-responsive, hydrophilic polypeptides that possess the unique property of undergoing α-helix to random coil secondary structure transitions with pH, and this responsiveness can lead to global morphology changes such as changes in aggregate size or even morphology transitions. These polypeptides are synthesized via ring opening polymerization of N-carboxyanhydrides (ROP of NCAs), and a combination of different reactive initiators and efficient coupling chemistries are used to develop systems with different topologies. Three topologies that will be discussed in this dissertation are AB2 star, ABA linear triblock, and BAB linear triblock copolymers. Significantly, our work on polypeptide-based AB2 star polymers, often referred to as lipid mimetics given their structural resemblance to phospholipids, has identified that many different hydrophobic B moieties can be covalently linked to a polar, hydrophilic polypeptide to result in polymeric molecules that spontaneously assemble into well-equilibrated vesicle bilayers; changes in vesicle size and chain density at the vesicle interface result through helix-coil transitions of the polypeptide. Both ABA and BAB linear triblock copolymers express dynamic aggregation behavior through morphological transitions (i.e., spherical micelle-to-vesicle) with pH, and we identify that these transitions are experienced around the helix-coil transition of the polypeptide. We further demonstrate temperature responsiveness of linear triblock copolymers by employing hydrophobic B blocks that show a lower critical solution temperature (LCST). We employ a combination of light scattering and microscopy techniques, as well as circular dichroism (CD) spectroscopy to gain an in-depth understanding of self-assembly properties. The unique self-assembly properties that we have identified for these polypeptide hybrid block copolymers are proving useful in the area of controlled drug delivery vehicles. We show that the responsive nature of these assemblies can be used to tune release of doxorubicin hydrochloride (Dox HCl), a chemotherapeutic, at different pH and salt concentrations

Extrapolating the Excitation Energy of Polythiophene from Thiophene Oligomers

Organic semiconductors are used solar cells and as energy transferring materials. They can be separated into oligomers and polymers. In current computational studies oligomers are used to extrapolate the behavior of polymers. To do so many oligomers are created to extrapolate trends based on oligomer size. In this study a computer program was created to enable the quick and efficient production of oligomers ranging from 1 to 166 monomer units in length. The code was used to create thiophene oligomers. Through applying a linear fit, W. Khun fit and a polynomial fit excitation energy was predicted to be 2.001±0.002 eV, 2.04±0.06 eV, and 2.012±0.001 respectively. The study shows that the computer program was able to create accurate models of thiophene oligomers

The Effect of COVID-19 Related Stress on Self Perceived Level of Health Behaviors

In our presentation, we looked to answer if Covid-19 related stress impacted health behaviors. In past research, any disruption in ones everyday routine can cause stress, thus changing their behavior. We looked to see how significantly the pandemic\u27s stress has impacted people\u27s health behaviors. We hypothesize that the pandemic will have had a negative impact on health behaviors in individuals

The Bane of the Ancients: A Software Adaptation of the Tabletop Role-Playing Adventure

This project is the adaptation of a tabletop role-playing experience into an interactive computer program, with an emphasis on effective storytelling, world-building, combat, and player choice. The story provided by the customer, “The Bane of the Ancients”, was initially designed within the Dungeon Crawl Classics framework. Translation of this design into a digital format required many creative and technical additions to the original concept, including sound and art design, music composition, world building and structuring, and development of interaction mechanics and physics. The digital experience was built on top of the Godot engine for its ease of adoption in regards with the chosen style. The software utilizes a top-down art style to convey storytelling and interactive elements. The development of the software followed an agile development cycle with two-week sprints to allow for flexibility and efficiency while working closely with the customer. The scope of our prototype was limited to the first act of the written story so that sufficient time and resources can be devoted to implementing all requested features

Human olfactory mesenchymal stromal cell transplants promote remyelination and earlier improvement in gait co-ordination after spinal cord injury

Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site. Transplanted animals also showed reduced cavitation. Several functional outcome measures including end-point electrophysiological testing of dorsal column conduction and weekly behavioural testing of BBB, weight bearing and pain, showed no difference between transplanted and control animals. However, gait analysis revealed an earlier recovery of co-ordination between forelimb and hindlimb stepping in transplanted animals. This improvement in gait may be associated with the enhanced myelination in ventral and lateral white matter, where fibre tracts important for locomotion reside. Autologous transplantation of mesenchymal stromal cells from the olfactory mucosa may therefore be therapeutically beneficial in the treatment of spinal cord injury

Bevacizumab-induced subungual hemorrhage

Exudative (wet) age-related macular degeneration can be treated with the vascular endothelial growth factor (VEGF)-inhibiting monoclonal antibody bevacizumab. Currently, bevacizumab therapy is associated with known skin-related side effects, such as rash, mucosal hemorrhage, and hemorrhagic ulcers. While subungual "splinter" hemorrhage is a documented side effect of VEGF receptor antagonists and Raf protein inhibitors, there are no prior reports of bevacizumab-induced subungual hemorrhage to the best of our knowledge. Thus, we present the case of a 71-year-old female diagnosed with bilateral age-related macular degeneration, who, during six months of intravitreal bevacizumab treatment, began noticing fingernail discoloration, described as similar to that of a bruise. Given our patient's history of bevacizumab therapy and the documented reports of bevacizumab-associated mucosal and ulcerative hemorrhage, we hypothesize that the discoloration and hemorrhage are likely unreported adverse effects associated with bevacizumab therapy

Investigations into long tract function following spinal cord injury and cell transplant therapy

Traumatic spinal cord injury (SCI) leads to severe functional deficits for which there are currently no effective treatments. About 50% of SCIs are incomplete leaving varying numbers of spared axons intact whilst damaging the cells which ensheathe them. These spared fibres provide targets for therapeutic interventions which aim to maximise their potential for supporting residual functions. In preclinical studies, functional outcomes are most commonly assessed using behavioural approaches. However they are unable to provide information on the mechanisms of recovery or differentiate between mechanisms occurring in the spinal cord and compensatory mechanisms occurring in the brain. This study had two main aims: firstly to develop an electrophysiological protocol for assessing transmission in the ascending dorsal column pathway, to use this protocol to characterise the effects of contusion injuries of different severities and to investigate the time course of changes to long tract function following SCI. The second aim of this project was to use this protocol combined with behavioural testing to investigate the use of human lamina-propria mesenchymal stem cells (hLP-MSCs) as a potential therapy for spinal cord injury. An electrophysiological approach was used to investigate function in rats subjected to T9 contusion injuries of the dorsal columns. Changes in the function of this pathway were assessed by recording sensory evoked potentials (SEPs) from the surface of the exposed somatosensory cortex, following stimulation of the contralateral sciatic nerve. Functional effects of increasing injury severities were investigated in normal animals and animals 6 weeks after receiving contusion injuries of increasing severity. Maximum SEP amplitudes and isopotential plot areas were reduced with injury severity, and latency to sciatic SEP onset was seen to increase in a graded fashion with increasing injury severity. SEP mapping revealed that the region of cortex from which SEPs could be recorded at or greater than certain amplitudes remained focused in the same location with increasing injury severity. Animals were investigated at different time points from acute up to 6 months post injury. Acute investigation revealed that sciatic SEPs are ablated immediately following injury and after incomplete recovery stabilise within hours of injury. Maximum sciatic SEP amplitudes and cortical areas both show 2 phases of recovery: One at 2 weeks post injury and one at 6 months. Onset latencies are seen to increase initially before gradually returning nearer to normal levels by 6 months. SEP mapping revealed that the region of cortex from which SEPs could be recorded at or greater than certain amplitudes remained focused in the same location with increasing post injury survival time. Histological observations confirmed that the injury causes substantial damage to the dorsal columns. To assess the effects of potential therapeutic hLP-MSC transplants, the functional effects of T9 150 Kdyn contusion injuries were investigated in medium injected controls and 3 week delayed hLP-MSC transplanted Sprague Dawley rats, at 10 weeks post injury. Behavioural testing was performed throughout, with terminal electrophysiological and immunohistological investigations performed at the end of the study. Animals were behaviourally tested at pre- and post-operative time points for the duration of the experiment. Electrophysiological recordings suggest some recovery of function with time after injury. Two phases of recovery are seen, one at about 2 weeks after injury and the other at about 6 months after injury; however other measurements suggest hLP-MSC transplants had little or no effect on the functional integrity of the dorsal column pathway. Open field locomotor testing using the Basso, Beattie and Bresnahan (BBB) locomotor scale revealed no differences between the recoveries of cell transplanted and control groups. Gait analysis was performed using the Digigait™ Imaging System revealing a trend for earlier recovery of co-ordination between forelimbs and hindlimbs in hLP-MSC transplanted animals compared to control animals. Moreover the step sequence data also suggested a better recovery of co-ordinated stepping in transplanted compared to medium injected animals. Dynamic weight bearing apparatus (BIOSEB) was used to measure the percentage of body weight borne on the forepaws and hindpaws, this demonstrated no effect of transplanted cells on postural changes. hLP-MSC transplants did not increase indicators of neuropathic pain in our model suggesting they are unlikely to exacerbate neuropathic pain following spinal cord injury. At present there are no immunohistochemical (IHC) markers that can be used to differentiate axons which have been remyelinated with central-type myelination from those which survived the injury. Thus, the degree of peripheral-type myelination was investigated as a simple way of assessing remyelination. This suggested that there was a greater degree of remyelination in transplanted animals, and that this was specifically in areas where transplanted cells were located

High Accuracy Liquid Propellant Slosh Predictions Using an Integrated CFD and Controls Analysis Interface

Coupling computational fluid dynamics (CFD) with a controls analysis tool elegantly allows for high accuracy predictions of the interaction between sloshing liquid propellants and th e control system of a launch vehicle. Instead of relying on mechanical analogs which are not valid during aU stages of flight, this method allows for a direct link between the vehicle dynamic environments calculated by the solver in the controls analysis tool to the fluid flow equations solved by the CFD code. This paper describes such a coupling methodology, presents the results of a series of test cases, and compares said results against equivalent results from extensively validated tools. The coupling methodology, described herein, has proven to be highly accurate in a variety of different cases

Integrated CFD and Controls Analysis Interface for High Accuracy Liquid Propellant Slosh Predictions

Coupling computational fluid dynamics (CFD) with a controls analysis tool elegantly allows for high accuracy predictions of the interaction between sloshing liquid propellants and the control system of a launch vehicle. Instead of relying on mechanical analogs which are n0t va lid during all stages of flight, this method allows for a direct link between the vehicle dynamic environments calculated by the solver in the controls analysis tool to the fluid now equations solved by the CFD code. This paper describes such a coupling methodology, presents the results of a series of test cases, and compares said results against equivalent results from extensively validated tools. The coupling methodology, described herein, has proven to be highly accurate in a variety of different cases

Resuspendable Powders of Lyophilized Chalcogen Particles with Activity against Microorganisms

Many organic sulfur, selenium and tellurium compounds show considerable activity against microorganisms, including bacteria and fungi. This pronounced activity is often due to the specific, oxidizing redox behavior of the chalcogen-chalcogen bond present in such molecules. Interestingly, similar chalcogen-chalcogen motifs are also found in the elemental forms of these elements, and while those materials are insoluble in aqueous media, it has recently been possible to unlock their biological activities using naturally produced or homogenized suspensions of respective chalcogen nanoparticles. Those suspensions can be employed readily and often effectively against common pathogenic microorganisms, still their practical uses are limited as such suspensions are difficult to transport, store and apply. Using mannitol as stabilizer, it is now possible to lyophilize such suspensions to produce solid forms of the nanoparticles, which upon resuspension in water essentially retain their initial size and exhibit considerable biological activity. The sequence of Nanosizing, Lyophilization and Resuspension (NaLyRe) eventually provides access to a range of lyophilized materials which may be considered as easy-to-handle, ready-to-use and at the same time as bioavailable, active forms of otherwise insoluble or sparingly substances. In the case of elemental sulfur, selenium and tellurium, this approach promises wider practical applications, for instance in the medical or agricultural arena