Doctor of Philosophy

Fusarium mycotoxins, such as deoxynivalenol (DON), are ubiquitous contaminants of cereal grains. When Fusarium-damaged grains are used in feeds, DON and other mycotoxins are a potential health risk to poultry with adverse effects, such as reductions in feed intake, growth, and feed efficiency and increased disease susceptibility. With increasing prevalence of Fusarium-contaminated grain worldwide, growing demand for high-quality protein like poultry, and a shift to antibiotic-free poultry production systems, it is important to re-evaluate threshold concentrations for Fusarium mycotoxins in poultry diets that are reflected in the current guidance values. Therefore, five animal feeding trials were conducted to better characterize sub-lethal responses to Fusarium mycotoxins (primarily DON) in broiler chickens and understand how exposure factors affect broiler responses to contaminated diets. For all trials, experimental diets were prepared with a source of clean wheat (< 0.5 mg/kg DON) or naturally Fusarium-contaminated wheat (~ 11.4 mg/kg DON) reflecting diets that would be encountered in broiler production. In the first study, the effects of timing and duration of exposure to contaminated diets on growth performance and intestinal mucosa structures were examined in a 34-d feeding trial. Starter diets (0.41 and 6.62 mg/kg DON), provided from 1 to 21 day of age (d), and grower diets (0.54 and 7.90 mg/kg DON) provided from 22 to 34 d. Birds fed the DON-contaminated diet over the first 14 d did not exhibit any changes in growth performance; however, growth suppression was observed in the birds fed DON-contaminated diets during the grower phase. Histopathological analysis of the ileal region revealed that birds provided the DON diets throughout the entire trial (1 to 34 d) had shorter villi and shallower crypt than control birds. Based on these results, the grower phase was targeted for the second study where two trials were conducted to determine the effect of short-term exposure (7 days, 21 to 27 d) to DON-contaminated diets on feed preference and feeding behaviour. Three wheat-based experimental diets (control, low and high DON) were prepared and contained 0.14, 2.27 and 5.84 mg/kg DON, respectively. In the preference trial, birds were randomly assigned to one of the three diet pairs (control vs. low, control vs. high and low vs. high DON). In the feeding behaviour trial, birds were randomly assigned to one of the three treatments and received either control, low or high DON diets. The activity of birds was recorded for three 1-h periods daily and birds’ behaviour at the feeder was observed. In the preference trial, broilers preferred the control diet over low or high DON diets. There was no preference indicated between the low vs high DON diets. Behavioural observations revealed that birds fed the DON diet spent more time at the feeder as compared to controls during the observation periods. In the third study, a 28-d pair-feeding trial was conducted to determine whether the performance and gastrointestinal effects of Fusarium mycotoxins (primarily DON) are due to a DON-induced reduction in feed intake. Birds were fed either DON-contaminated diets (2.4 to 3.0 mg/kg) or control diets (< 0.1 mg/kg DON). The amount of control diet provided to the pair-fed birds was based on feed consumption of DON treatment at the similar age. During the starter phase, DON-fed birds consumed less feed than control birds while during the grower phase, DON-fed birds had lower feed intake and weight gain than control birds. The pair-fed birds had lower feed intake and weight gain compared to DON-fed birds during the starter period and did not differ during the grower period. Since DON-fed birds and restricted-fed birds with similar (reduced) feed intake had equally suppressed performance, the contribution of dietary DON to growth suppression in broilers is considered independent from other toxic effects of DON. In the final study, a 32-d feeding trial was conducted to determine the efficacy of a yeast cell wall-based feed additive in counteracting the performance effects of mycotoxins in broilers fed a naturally DON-contaminated diet (1.8 to 2.0 mg/kg). The DON-contaminated diet depressed growth performance, while supplementation of the feed additive increased feed intake, weight gain and body weight in birds when included in contaminated diets during the grower stage. Overall, there was a consistent reduction of feed intake, weight gain and feed efficiency in response to low to moderate concentrations of DON-contaminated diets across the individual feeding trials conducted in this research. Broiler chickens are apparently more sensitive to DON-contaminated diets than previously estimated particularly during later stages of growth. In addition to the performance effects, DON contamination reduces diet palatability and alters broiler feeding behaviour. Although difficult to confirm based on current data, reduced feed intake in broilers is most likely caused by DON-induced sensory aversion and/or anorexia. Based on results of this research, it is recommended to reevaluate the current 5 mg/kg threshold concentrations for DON for poultry to help protect birds from sub-clinical mycotoxin concentrations that can challenge poultry production

Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma

Homemade blenderized tube feeding improves gut microbiome communities in children with enteral nutrition

Enteral nutrition for children is supplied through nasogastric or gastrostomy tubes. Diet not only influences nutritional intake but also interacts with the composition and function of the gut microbiota. Homemade blenderized tube feeding has been administered to children receiving enteral nutrition, in addition to ready-made tube feeding. The purpose of this study was to evaluate the oral/gut microbial communities in children receiving enteral nutrition with or without homemade blenderized tube feeding. Among a total of 30 children, 6 receiving mainly ready-made tube feeding (RTF) and 5 receiving mainly homemade blenderized tube feeding (HBTF) were analyzed in this study. Oral and gut microbiota community profiles were evaluated through 16S rRNA sequencing of saliva and fecal samples. The α-diversity representing the number of observed features, Shannon index, and Chao1 in the gut were significantly increased in HBTF only in the gut microbiome but not in the oral microbiome. In addition, the relative abundances of the phylum Proteobacteria, class Gammaproteobacteria, and genus Escherichia-Shigella were significantly low, whereas that of the genus Ruminococcus was significantly high in the gut of children with HBTF, indicating HBTF altered the gut microbial composition and reducing health risks. Metagenome prediction showed enrichment of carbon fixation pathways in prokaryotes at oral and gut microbiomes in children receiving HBTF. In addition, more complex network structures were observed in the oral cavity and gut in the HBTF group than in the RTF group. In conclusion, HBTF not only provides satisfaction and enjoyment during meals with the family but also alters the gut microbial composition to a healthy state

Vulnerability of blockchain technologies to quantum attacks

Quantum computation represents a threat to many cryptographic protocols in operation today. It has been esti- mated that by 2035, there will exist a quantum computer capable of breaking the vital cryptographic scheme RSA2048. Blockchain technologies rely on cryptographic protocols for many of their essential sub-routines. Some of these protocols, but not all, are open to quantum attacks. Here we analyze the major blockchain-based cryp- tocurrencies deployed today—including Bitcoin, Ethereum, Litecoin and ZCash, and determine their risk exposure to quantum attacks. We finish with a comparative analysis of the studied cryptocurrencies and their underlying blockchain technologies and their relative levels of vulnerability to quantum attacks

A Situation-Aware Scheme for Efficient Device Authentication in Smart Grid-Enabled Home Area Networks

Home area networks (HANs) are the most vulnerable part of smart grids since they are not directly controlled by utilities. Device authentication is one of most important mechanisms to protect the security of smart grid-enabled HANs (SG-HANs). In this paper, we propose a situation-aware scheme for efficient device authentication in SG-HANs. The proposed scheme utilizes the security risk information assessed by the smart home system with a situational awareness feature. A suitable authentication protocol with adequate security protection and computational and communication complexity is then selected based on the assessed security risk level. A protocol design of the proposed scheme considering two security risk levels is presented in the paper. The security of the design is verified by using both formal verification and informal security analysis. Our performance analysis demonstrates that the proposed scheme is efficient in terms of computational and communication costs

Performance effects of feed-borne Fusarium mycotoxins on broiler chickens: Influences of timing and duration of exposure

In commercial practice, broiler chickens may be exposed to Fusarium mycotoxins either during specific growth stages or throughout the entire production cycle. A 34-day feeding trial was conducted to identify sensitive periods for mycotoxin effects during the growth cycle of broiler chickens. A total of 420 newly-hatched Ross 308 male broilers were randomly assigned to 60 cages with 7 birds/cage. Sources of clean wheat (<0.5 mg/kg deoxynivalenol [DON]) and Fusarium-contaminated wheat (11.4 mg/kg DON) were used to formulate the starter diets (0.41 and 6.62 mg/kg DON) provided from 1 to 21 d of age and the grower diets (0.54 and 7.90 mg/kg DON) provided from 22 to 34 d. Control and DON diets were provided to broilers according to treatments (control, DON 1 to 14 d, DON 15 to 21 d, DON 22 to 34 d and DON 1 to 34 d). Birds were monitored daily for morbidity or mortality. Broiler growth performance (body weight, average daily gain, average daily feed intake and feed to gain ratio) was measured weekly. Segments of duodenum, jejunum and ileum were collected at 21 and 34 d and morphometric parameters (villus height, crypt depth, villus width, muscularis thickness and villi:crypt ratio) were measured. Birds fed the DON starter diet during the first 14 d did not exhibit any changes in growth performance; however, growth performance was suppressed in birds fed DON-contaminated diets during the grower period (22 to 34 d). At 34 d, birds that received the DON grower diet (DON 22 to 34 d and DON 1 to 34 d) were lighter (1,433 vs. 1,695 g) than birds fed the control diet. Feed to gain ratio was higher in birds fed the DON grower diet from 22 to 28 d (1.77 vs. 1.56) and 28 to 34 d (2.24 vs. 1.85) compared with corresponding controls. These results suggest that providing older broiler chicks (22 to 34 d) feed contaminated with Fusarium mycotoxins (specifically DON) may result in production losses. Histopathological analysis of the ileum region revealed that birds provided the DON diets throughout the entire trial (1 to 34 d) had shorter villi (506 vs. 680 μm) and shallower crypt (85 vs. 115 μm) than control birds. Taken together, these results indicate that DON-induced growth suppression may be a result of adverse effects on intestinal morphology during later growth phases of broilers. Keywords: Deoxynivalenol, Chicken, Sensitive period, Feed contamination, Intestin

Using different levels of glycerine, glucose or sucrose in broiler starter diets to overcome negative effects of delayed feed access on growth performance

Two trials were conducted to evaluate the inclusion of glycerine, glucose or sucrose in broiler starter diets to overcome negative effects of delayed feed access. In trial 1, 2160 newly hatched chicks (mixed sexed) were randomly assigned to two feeding programs (immediate vs. 36h delayed feed access). Nine starter diets prepared with crude glycerine, glucose or sucrose fed at 0, 4 or 8% levels, were fed during the first 14 days post hatch. In trial 2, 720 male and 720 female newly hatched chicks were randomly assigned to two feeding programs (immediate vs. 48h delayed feed access). Starter diets fed during the first 14 days of feed access, consisted of a control, 8% glycerine or 8% glucose. In both trials, a common grower and finisher diet were fed during days 14-24 and 25-35 respectively. Body weight and feed consumed were measured on 7, 14, 24 and 35 days. In trial 1, all 8% diet fed birds were heavier compared to the control on day 35 post hatch (2259 vs. 2198 g, PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

An experimental and modeling study on polyoxymethylene dimethyl ether 3 (PODE3) oxidation in a jet stirred reactor

Polyoxymethylene dimethyl ether (PODEn, n ≥ 1) is a class of oxygenated fuels containing unique carbon-oxygen chain structure and a promising alternative fuel for diesel engines. In this study, low-temperature oxidation characteristics of PODE3 were studied experimentally and numerically. Experiments were performed in a jet-stirred reactor (JSR) at equivalence ratios of 0.5, 1.0 and 2.0, in the temperature range of 500 to 950 K, and at atmospheric pressure. Mole fractions of PODE3, O2, H2, CO, CO2, CH3OH and C1-C2 hydrocarbons were measured by gas chromatograph (GC). Experimental measurements were compared with the simulation results based on two literature low-temperature oxidation models, denoted as the He model and the Cai model, respectively. Good agreement was obtained between the measured and simulated fuel consumption profiles, while a deviation was observed between the experimental and simulation results on the mole fractions of O2 and intermediate products at medium temperatures. Reaction pathway analyses based on the two models were performed, revealing that the second O2-addition reaction pathway is more significant in the prediction by the Cai model than that by the He model. Sensitivity analyses pointed out that the most important reactions affecting fuel consumption are the H-abstraction reactions of PODE3, and the decomposition of H2O2 and the consumption of CH2O become more sensitive at medium temperatures