Nine years after the Severe Acute Respiratory Syndrome (SARS) pandemic in 2003, a novel human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), emerged in the Middle East in 2012 and was believed to be of animal origin. Molecular study on the genome of MERS-CoV showed that it belongs to lineage C betacoronavirus and is closely related to the previously described Tylonycteris bat coronavirus HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat coronavirus HKU5 (Pi-BatCoV HKU5) identified in Tylonycteris pachypus and Pipistrellus abramus respectively. In this study, 597 respiratory and 934 alimentary specimens from 1174 bats of 12 different species were collected in 20 sampling sites of Hong Kong over seven years from November 2005 to November 2012. Degenerate primers designed from alignment of RdRp genes of lineage C betacoronaviruses were able to amplify partial RdRp sequences in two bat species only in this study, including 8 lesser bamboo bats and 34 Japanese pipistrelle, with 200-bp sequences shared 99-100% and 96-100% nucleotide identities to Ty-BatCoV HKU4 and Pi-BatCoV HKU5 respectively. Phylogenetic analysis showed that Ty-BatCoV HKU4 and Pi-BatCoV HKU5 were closely related to but still distinct from MERS-CoV, implying that the two bat coronaviruses are probably not the direct ancestor virus of MERS-CoV. The infection of Pi-BatCoV HKU5 is independent of sex (P = 0.494) but juvenile Japanese pipistrelles were more susceptible to the infection (P = 0.000101) while the infection of Ty-BatCoV HKU4 is independent of both sex (P = 0.464) and age (P = 0.193). Additionally, the mean body weight of the adult lesser bamboo bats positive for Ty-BatCoV HKU4 was significantly lower than that of the negative ones (P = 0.03). On the other hand, there was no significant difference in the mean body weights between the positive and negative bats for Pi-BatCoV HKU5 among the juvenile Japanese pipistrelles (P = 0.06). Continuous surveillance study of coronaviruses on different bat species as well as other potential intermediate animal hosts should be carried on the evolution study of the lineage C betacoronaviruses. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

abstract / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

When energy relaxation between electrons and the lattice is slow, an elevated electronic temperature different from that of the lattice persists. In this regime, hot charge carriers control the energy transport in a material. In this thesis, I show how hot carriers can dominate graphene's response enabling it to exhibit novel properties. First, I examine how light is converted to electrical currents in graphene and show that hot carriers play an integral role in this multi-stage process. I show that photocurrent in graphene p-n junctions is dominated by a Photo-thermoelectric effect in which a light-induced elevated hot carrier temperature drives a thermoelectric current. Furthermore, I show that the generation and cooling of hot carriers in graphene during photoexcitation proceeds in an unusual way. In the former, carrier-carrier scattering dominates the initial photoexcitation cascade enabling efficient hot carrier generation. In the latter, a new cooling mechanism - disorder-assisted scattering (supercollisions) - dominates electron-lattice cooling over a wide range of temperatures (including room temperature). Second, I examine the transport characteristics of double layer graphene heterostructures (specifically, G/h-BN/G heterostructures). I show that Coulomb coupling results in vertical (out-of-plane) energy transfer between electrons in proximal (but electrically insulated) graphene layers. This couples lateral (in-plane) charge and energy transport of electrons in the two layers to give rise to a new energy-driven Coulomb drag (inter-layer transresistance) that dominates when the two layers are at charge neutrality. Third, I examine energy transport in charge neutral graphene. I show that the combination of fast carrier-carrier scattering, high electronic quality, and slow electron-lattice cooling (hot carriers) gives rise to a regime of ballistic heat transport. This manifest as electronic energy waves with velocity on the order of graphene's Fermi velocity. The new phenomena enabled by hot carriers and the ideas/approaches described in this thesis provide a basis with which to exploit hot carrier effects in graphene and opens new vistas for controlling and harnessing energy flows on the nanoscale. / Engineering and Applied Sciences

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

No description available.

An estimated 5-10% of breast cancers are hereditary in nature and are due to the presence of a mutation in a breast cancer predisposition gene; approximately half of these cases possess a mutation in BRCA1 or BRCA2. Many BRCA1/BRCA2 mutations result in a truncated protein and hence are unequivocally disease-causing. However another class of mutations, the Variants of Unknown Significance (VUS), are more problematic as the effect of these mutations on protein function is unclear. The inability to classify these mutations as disease causing generates significant problems in risk evaluation, counseling and preventive care. Accordingly we sought to determine whether carriers of either a BRCA1 or BRCA2 mutation could be identified from non-carriers based on the gene expression patterns of non-cancerous cells. EBV-transformed lymphoblastoid cell lines established from BRCA1/BRCA2 mutation carriers and normal individuals were obtained through the NIH Breast Cancer Family Registries. Cell lines were mock-irradiated or treated with ionizing radiation (2 Gy). Following a recovery period of 6 hours total RNA was extracted and whole genome gene expression profiling was carried out. Molecular classifiers comparing the baseline expression profiles and the radiation-dependent expression profiles of BRCA1/BRCA2 mutation carriers to control individuals were created using a Support Vector Machine (SVM) coupled with a recursive feature removal (RFR) algorithm. Our results suggest that cell populations derived from BRCA1/BRCA2 mutation carriers display unique expression phenotypes from those of control individuals in both the basal and radiation-induced cases. In the task of classification using baseline expression, the BRCA1-classifier correctly classified 15/18 test samples using feature selection based on the training set only, while feature selection using the entire dataset (AD) improved classification to 16/18 samples. The BRCA2-baseline classifier correctly classified 13/17 and 14/17 (AD) samples, respectively. In the task of radiation-dependent classification, the BRCA1-IR classifier correctly classified 12/18 and 16/18 (AD) test samples respectively while the BRCA2-IR classifier correctly classified 13/17 and 16/17 (AD) test samples respectively. These results suggest the possibility of development of this assay into a novel hereditary breast cancer screening diagnostic able to accurately identify the presence of BRCA1 or BRCA2 mutations via a functional assay thereby improving patient outcomes. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2008-03-27 15:38:19.269 / Canadian Breast Cancer Foundation-Ontario Chapter, Department of Pathology & Molecular Medicine Clinical Trust Fund

Various strains of Bacillus thuringiensis Mt.) produce crystalline endotoxins specific for larvae of different insect classes. Two strains, B.t. subspp. israelensis and kurstaki produce similar 130 kDa toxins encoded by the CryIVB gene (toxic to Diptera) and the CryIA gene (toxic to Lepidoptera), respectively. The N-terminal region of the CryIVB gene was cloned into the Escherichia coli expression vector pKX223-3. A mosquitocidal transformant was obtained as determined by mosquito bioassays. The gene fragment, if stable, can be cloned into cyanobacteria to achieve biological control of mosquito-borne diseases. A second goal was to identify the binding specificity domain of the CryIVB gene which encodes the portion of the protein toxin that binds the insect midgut causing cell lysis and death. Two potential insect binding specificity domains identified by computer analyses were switched with a known binding specificity region of the CryIA gene. The polymerase chain reaction was utilized to obtain gene fragments of the CryIVB gene which replaced the CryIA gene binding specificity domain. The resulting recombinant clones carrying the CryIA gene containing the .000nd proposed insect binding specificity domain of the CryIVB gene were fotsd to be mosquitocidal. / Department of Biology

The ultimate goal of this research was to perform a domain exchange between a computer identified insect specificity region of the mosquito larvicidal protein Cry IVB and a previously identified domain in a related protein toxin which targets lepidopteran insect larvae. If the insect specificity domain has been correctly identified, an exchange of DNA in this manner transfers the toxicity of one peptide to another by an exchange of the insect specificity domains. New, chimeric peptides may be designed which will target a larger spectrum of insect larvae.In previous research a domain exchange was performed between the two genes carried on plasmid vectors in E. coli and low levels of toxicity to mosquito larvae were observed. Initial efforts of this research attempted to identify these recombinants. However, stability was not achieved by sequential colony screens. Furthermore, a recently published three-dimensional structural model for all the B. thuringiensis crystalline toxins became available and it was quickly determined that the first exchanges excluded most of the f3-sheet domain that is responsible for insect cell receptor binding, the feature that gives the toxins their specificity. Therefore, it was decided that a larger, more inclusive region of Cry IVB DNA must be exchanged between the two toxins.Extensive computer analyses of the Cry IVB sequence and retroactive comparison of these sequences to the three-dimensional model yielded a fragment of DNA that encoded more than 60% of the putative insect specificity domain. Oligonucleotide primers were subsequently designed to flank this region so that the polymerase chain reaction could be employed to amplify the region. Additionally, the primers were engineered to contain terminal restriction endonuclease sites to ease in the exchange of the domain encoding region into Cry IA(c). The region of Cry IVB DNA flanked by the oligonucleotide primers was successfully amplified by the PCR and cloned into the plasmid vector pUC 19 as a reservoir for a future domain exchange. / Department of Biology

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1985. / Bibliography: leaves 301-319. / Photocopy. / xxii, 319 leaves, bound ill., maps 29 cm

Thesis (Ph. D.)--University of Hawaii at Manoa, 1990. / Includes bibliographical references (leaves 92-108) / Microfiche. / ix, 108 leaves, bound ill. 29 cm