Moment properties of estimators for an exponential regression with type 1 censoring

b

Improved estimators for the shape parameter in gamma regression

A regression model is considered in which the response variables have gamma distributions with a common shape parameter. A review is given of existing estimators for the shape parameter. Bias expressions for the maximum likelihood estimates of the regression coe f f i c i ent s and the shape parameter are developed. A new estima t o r f o r t h e shape parameter based on bias correction for the maximum likelihood estimator is shown to have markedly better variance and mean square error properties in small to moderate sized samples. Approximations to the low order moments of the Pearson statistic are derived for gamma regression models with general link functions. These are used for the case of a logarithmic link to develop new estimators for the shape parameter which have better moment properties than the estimators based on the Pearson statistic which have been used previously. Finally, the small sample variance and mean square error efficiencies of the estimators relative to the maximum likelihood estimator are evaluated by simulation for the case of a single explanatory variable and a logarithmic link, for a range of sample sizes less than or equal to 100

Degradation on wood by insects and the effects on furniture production

In the tropics, biodegradation of wood progresses rapidly due to the biologically favourable temperatures and humidity conditions all year round. The population growth rate of insects is high and they reproduce throughout the year. To understand the degradation caused by insects on wood and how it can affect furniture production, the nature of the particular insect attack and the characteristic forms of damage must be understood. In this paper, the characteristic habits of major insect pests, particularly ambrosia beetles, powderpost beetles and termites are described. The diagnostic signs of infestation and how the different forms of damage affect furniture production are discussed. Precautionary as well as remedial measures are also described

Doctor of Philosophy

dissertationIt is well documented that more than 50% of all human cancers have a mutated p53 gene status, rendering it inactive. The resulting tumor-derived p53 variants, similar to wild-type (wt) p53, retain their ability to oligomerize via the tetramerization domain. Upon hetero-oligomerization, mutant p53 enforces a dominant negative effect over active wt-p53 in cancer cells. To overcome this barrier, we have designed a chimeric superactive p53 (p53-CC) with an alternative oligomerization domain (CC) from breakpoint cluster region (Bcr). This approach led to the hypothesis that swapping the oligomerization domain of p53 with an alternative oligomerization domain will prevent hetero-oligomerization and transdominant inhibition by mutant p53 in cancer cells. The tumor suppressor activity of the chimeric p53-CC was evaluated in vitro and found to be similar to that of wt-p53 regardless of cancer type or endogenous p53 status. However, co-immunoprecipitation and viral transduction of p53-CC and wt-p53 into a breast cancer cell line that harbors a tumor derived transdominant mutant p53 validated that p53-CC indeed evades sequestration and consequent transdominant inhibition by endogenous mutant p53. Following proof-of-concept studies, the superior tumor suppressor activity of p53-CC and its ability to cause tumor regression of the MDA-MB-468 aggressive p53-dominant negative breast cancer tumor model was demonstrated in vivo. In addition, the underlying differential mechanisms of activity for p53-CC and wt-p53 delivered using viral-mediated gene therapy approach in the MDA-MB-468 tumor model were investigated. Finally, since domain swapping to create p53-CC could result in p53-CC interacting with endogenous Bcr, which is ubiquitous in cells, modifications on the CC domain were necessary to minimize potential interactions with Bcr. Hence, the possible design of mutations that will improve homo-dimerization of CC mutants and disfavor hetero-oligomerization with wild-type CC (CCwt) were investigated, with the goal of minimizing potential interactions with endogenous Bcr in cells. Indeed, the resulting lead candidate p53-CCmutE34K-R55E avoided binding to endogenous Bcr and retained p53 tumor suppressor activity. Although breast cancer was the main focus of this dissertation, the application of this research extends to many other types of cancer, including the deadliest cancers (pancreatic, lung, and ovarian), which currently lack effective treatments

The Oral Microbiome of Site-Specific Dental Plaque in Health and Disease

According to the National Institutes of Health, dental caries is the leading chronic disease of children in the United States. Dental caries is biofilm-mediated, multifactorial and dynamic. Research using culturing techniques and high throughput 16S rRNA amplicon sequencing unraveled the taxonomic complexity of mixed microbial communities (microbiome) in dental biofilms (plaque) and their abundance differences. However, 16S rRNA sequencing fails to resolve taxonomic assignment beyond genus level for certain taxa, which is problematic in identifying potential antagonistic species within the same genus. The presented work addressed current shortcomings in dental microbiome research. First, dental plaque samples used in this study were collected from either caries-free (PF) teeth or caries-active teeth with lesions in the enamel layer (PE). This site-specific collection method provides a better understanding of the role of specific organisms and biological processes as teeth transition from health to disease. Second, deep sequencing was used to produce whole genome metagenomic data, i.e. complete or semi complete genomes drafted from mixed bacterial communities, potentially enhancing bacterial species detection, identifying rare species, and providing the gene content of the samples and their metabolic potential. Overall, the objective of this study was to provide species level taxonomic classification and metabolic potential of mixed microbial communities in plaque collected from site-specific dentition. Two different approaches to analyze whole genome metagenomic data were used and compared. (i) Read based taxonomic classification and supervised assembly where short reads are taxonomically classified prior to genome assembly. (ii) Contig based taxonomic classification and unsupervised assembly where an assembler is used to assemble reads into contigs directly. The contigs produced are then classified taxonomically. The read based taxonomic classification and supervised assembly approach outperformed the latter in an assessment of taxonomic assignment accuracy using a mock metagenomic data set. The taxonomic profiles for PF and PE reported by both approaches were virtually identical however their distributions showed variation. The taxonomic inter-sample similarities were reflected in the gene content information as both approaches reported minor metabolic potential differences between PF and PE. Noticeably, both approaches reported significantly enriched biological processes involved in sugar transport and metabolism in PE

The Effects of Artemisia Derived Natural Products on Adipogenesis

For the first time in human history, more people worldwide suffer from obesity than are undernourished. Numerous health complications are associated with obesity including cardiovascular disease, Type 2 Diabetes, cancers of reproductive tissues, stroke, depression, anxiety disorders, and Alzheimer’s disease. A deeper understanding of the anti-adipogenic effects and mechanism of action of sesquiterpene lactones may have pharmacological import in the continuing search for therapeutic modalities to ameliorate the effects of this global obesity epidemic. Dehydroleucodine (DhL), 11,13-dihydro-dehydroleucodine (DH-DhL), and dehydroparashin-B (DhP), sesquiterpene lactones extracted from or derived from compounds extracted from Artemisia douglasiana, were investigated for their anti-adipogenic effects on 3T1-L1 preadipocytes. Dehydroleucodine inhibited the expression of C/EBPa and PPARg, and also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. Dehydroleucodine arrested the cell cycle at the G0/G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Furthermore, DhL downregulated expression of histone demethylase JMJD2 as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPb and PPARg, respectively. 11,13-dihydro-dehydroleucodine blocked the accumulation of lipid droplets and inhibited the expression of PPARγ and C/EBPβ. Collectively, the results indicate that the inhibition of early stage preadipocyte differentiation by DH-DhL may be associated with cell cycle arrest at the G0/G1 phase. Dehydroparashin-B significantly decreased the accumulation of lipid content and downregulated the expression of CEBPβ, PPARγ and CEBPα as well as FAS. Interestingly, the addition of DhP inhibited the number as well as the size of the lipid droplets during the differentiation of 3T3-L1 preadipocytes. Taken together, this data suggests that DhP has an important inhibitory effect on cellular pathways regulating adipocyte differentiation

Mental Toll

This is a short reflection on my experience with Covid-19, virtual school, and anxiety throughout the pandemic. This is a reflection of the years 2020 and early 2021