The linear theory of wave packets propagating in the whistler mode

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Exploration and Development of Valorisation Routes for Citrus and Potato Waste using Green Methodologies

This thesis aimed to establish biorefinery schemes for two large-volume waste feedstocks (citrus juicing waste and potato waste) adhering to the 12 principles of green chemistry and in accordance with the Sustainable Development Goals set out by the United Nations. A citrus waste biorefinery based around microwave technology was developed, with multiple products. Citrus oil was extracted via microwave-assisted steam distillation (2.4% dry weight) with comparable quality citrus oil extracted via conventional steam distillation. High-methoxyl pectin was extracted under acid-free conditions with microwaves (15.36% dry weight). Pectin showed good gelling capabilities and passed industrial food standard tests. The cellulosic residue remaining after microwave extractions showed good water binding capacity for use as a rheology modifier. Collaboration with Brazilian company Agroterenas generated a map of processing and waste treatment at a modern citrus juicing plant. Industrial citrus juicing waste from Agroterenas was subjected to microwave-assisted pectin extraction (21.19% dry weight). The impact of Huanglongbing disease (HLB) on pectin content was explored with a reduction of 38% in infected oranges. Proteins were successfully extracted from waste potatoes and identified by SDS-PAGE followed by MALDI-TOF/TOF-MS. The protease inhibitors present in the protein were isolated and purified for potential application as appetite suppressants. The purified protease inhibitors were subjected to crystallisation screening with the aim of gaining a crystal structure of the protein. While crystals were obtained, work is needed to obtain a crystal with good diffraction. Complexation studies were performed on the protease inhibitor and its target enzymes, trypsin and chymotrypsin. A stable complex was isolated via size exclusion chromatography and analysed via SDS-PAGE and LC-MS/MS demonstrating that all three proteins were present. Finally, pectin from citrus waste was tested in a materials application. Porous, carbonaceous materials created from the pectin dubbed ‘Pecbon’ were tested in CO2 capture and compared to activated carbon. Pecbon carbonised to 800 C (P800) was found to adsorb 2.050.24 mmol/g CO2 showing similar performance to activated carbon (2.120.05 mmol/g)

Potential Utilization of Unavoidable Food Supply Chain Wastes – Valorisation of Pea Vine Wastes

Combating food waste is a vital 21st century global challenge befitting of green and sustainable chemistry. Prevention is the first and foremost route for reduction of food waste, but inevitably, there are unavoidable food losses as a result of primary and secondary processing that represents an interesting green and sustainable chemistry valorization opportunity. Herein, pea vine waste (Pisum sativum) as an unavoidable food supply chain waste is explored as the source for (bio)­renewable chemicals and materials and as a potential bioenergy source. Through a cascade approach simulating a potential biorefinery, pea vine waste was subjected to pseudosubcritical water extraction as a green extraction methodology technique to extract potential platform molecules: 5-hydroxy furfural (HMF); ethanoic acid; sugars (levoglucosenone, rhamnose, xylose, fructose, glucose and sucrose); and a precipitated biopolymer showing pectinaceous and starch-like characteristics as evidenced by infrared spectroscopy, solid-state ¹³C NMR, and thermogravimetric analysis. The postextraction residues of pea vine waste were further subjected to microwave pyrolysis to produce a bio-oil and a biochar. The bio-oil is rich in phenolic compounds while the biochar has a gross calorific value of 26.6 MJ kg^–1 and thus may be used as a potential source of bioenergy. While peas alone have been explored previously, the work within represents the first study of valorization of pea vine wastes, a real as-received industrial problematic waste source, using a cascade approach of pseudo-sub-critical water and microwave pyrolysis simulating a potential biorefinery

Acid-free microwave-assisted hydrothermal extraction of pectin and porous cellulose from mango peel waste-towards a zero waste mango biorefinery : Towards a Zero Waste Mango Biorefinery

Mango is the second most consumed tropical fruit after banana and the by-products of mango processing (peel, kernel and seed) roughly comprise 35-60% of the total fruit weight, thus representing a potentially high volume resource of exploitable biobased chemicals and materials. Herein, conversion and characterisation of waste mango peels from three different cultivars (Alphonso, Honey and Tommy Atkins) into pectin and porous cellulose using low temperature microwave-assisted acid-free hydrolytic conditions is reported. Microwave-assisted acid-free extraction yielded up to 11.63% (dry weight basis) of pectin which was characterised by IR, NMR (both solution and solid phase) and TGA which showed close similarity to commercial (acid extracted) pectin. The degree of esterification of pectin was determined by 13C NMR (75.6-86.2%) and titrimetry (79.3-87.7%) and the pectin showed excellent gelling ability. The molecular weight as determined by GPC was in the range 14130 (Honey)-25540 (Tommy Atkins). Porosity measurements on the depectinated residue, i.e., residual cellulosic matter showed mesoporous characteristics: average pore diameter, 9.3 nm (Alphonso)-10.5 nm (Honey), however with poor surface area 16.3 m2 g-1 (Honey)-26.0 m2 g-1. Interestingly, a second microwave hydrothermal treatment on these residues retained mesoporosity whilst significantly increasing surface area (88.8 m2 g-1 (Honey)-124.0 m2 g-1 (Alphonso)) and pore volume by approximately six-fold. This is the first detailed combined study of microwave-assisted extraction to yield pectin and mesoporous cellulose towards a potential zero waste mango biorefinery

It’s Alive! Animate Sources Produce Mnemonic Benefits

The mnemonic benefits of animate (e.g., Tiger) over inanimate (e.g., Table) stimuli have been demonstrated across several different memory paradigms. Given the ubiquity of inanimate, computer-generated voices we investigated if the animacy of a presentation source confers mnemonic benefits. We asked: is information delivered by a human voice better remembered than information presented by a computer-generated voice? Word-lists were presented auditorily by either a human or a computer-generated voice and memory was measured using a free recall assessment. In Experiment 1, words presented in a human voice were better remembered than words presented in a computer voice. Experiment 2 demonstrated that beliefs about the animacy of a computer-generated voice were not sufficient for any benefits to accrue, suggesting a possible boundary condition for the effect. Both experiments replicated the mnemonic benefits of animate words and demonstrated further extensions of the effect to spoken word presentation

Diet Significantly Influences the Immunopathology and Severity of Kidney Injury in Male C57Bl/6J Mice in a Model Dependent Manner

Diet is a leading causative risk factor for morbidity and mortality worldwide, yet it is rarely considered in the design of preclinical animal studies. Several of the nutritional inadequacies reported in Americans have been shown to be detrimental to kidney health; however, the mechanisms responsible are unclear and have been largely attributed to the development of diabetes or hypertension. Here, we set out to determine whether diet influences the susceptibility to kidney injury in male C57Bl/6 mice. Mice were fed a standard chow diet, a commercially available “Western” diet (WD), or a novel Americanized diet (AD) for 12 weeks prior to the induction of kidney injury using the folic acid nephropathy (FAN) or unilateral renal ischemia reperfusion injury (uIRI) models. In FAN, the mice that were fed the WD and AD had worse histological evidence of tissue injury and greater renal expression of genes associated with nephrotoxicity and monocyte infiltration as compared to mice fed chow. Mice fed the AD developed more severe renal hypertrophy following FAN, and gene expression data suggest the mechanism for FAN differed among the diets. Meanwhile, mice fed the WD had the greatest circulating interleukin-6 concentrations. In uIRI, no difference was observed in renal tissue injury between the diets; however, mice fed the WD and AD displayed evidence of suppressed inflammatory response. Taken together, our data support the hypothesis that diet directly impacts the severity and pathophysiology of kidney disease and is a critical experimental variable that needs to be considered in mechanistic preclinical animal studies

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity. METHODS: Hematopoietic progenitor (Lin-ve) cells from XIAPy/- mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/- recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays. RESULTS: In treated XIAPy/- mice, ~40% engraftment of gene-corrected Lin-ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/- mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP. CONCLUSION: Gene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency

Leveraging PET to image folate receptor α therapy of an antibody-drug conjugate

Background: The folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), IMGN853, shows great antitumor activity against FRα-expressing tumors in vivo, but patient selection and consequently therapy outcome are based on immunohistochemistry. The aim of this study is to develop an antibody-derived immuno-PET imaging agent strategy for targeting FRα in ovarian cancer as a predictor of treatment success. Methods: We developed [89Zr]Zr-DFO-M9346A, a humanized antibody-based radiotracer targeting tumorassociated FRα in the preclinical setting. [89Zr]Zr-DFO-M9346A’s binding ability was tested in an in vitro uptake assay using cell lines with varying FRα expression levels. The diagnostic potential of [89Zr]Zr-M9346A was evaluated in KB and OV90 subcutaneous xenografts. Following intravenous injection of [89Zr]Zr-DFO-M9346A (~90 μCi, 50 μg), PET imaging and biodistribution studies were performed. We determined the blood half-life of [89Zr]Zr-DFO-M9346A and compared it to the therapeutic, radioiodinated ADC [131I]-IMGN853. Finally, in vivo studies using IMG853 as a therapeutic, paired with [89Zr]Zr-DFO-M9346A as a companion diagnostic were performed using OV90 xenografts. Results: DFO-M9346A was labeled with Zr-89 at 37 °C within 60 min and isolated in labeling yields of 85.7 ± 5.7%, radiochemical purities of 98.0 ± 0.7%, and specific activities of 3.08 ± 0.43 mCi/mg. We observed high specificity for binding FRα positive cells in vitro. For PET and biodistribution studies, [89Zr]Zr-M9346A displayed remarkable in vivo performance in terms of excellent tumor uptake for KB and OV xenografts (45.8 ± 29.0 %IA/g and 26.1 ± 7.2 %IA/g), with low non-target tissue uptake in other organs such as kidneys (4.5 ± 1.2 %IA/g and 4.3 ± 0.7 %IA/g). A direct comparison of the blood half life of [89Zr]Zr-M9346A and [131I]-IMGN853 corroborated the equivalency of the radiopharmaceutical and the ADC, paving the way for a companion PET imaging study. Conclusions: We developed a new folate receptor-targeted 89Zr-labeled PET imaging agent with excellent pharmacokinetics in vivo. Good tumor uptake in subcutaneous KB and OV90 xenografts were obtained, and ADC therapy studies were performed with the precision predictor