Creating a Fontan fenestration in a child with dextrocardia and interrupted inferior vena cava

Plastic bronchitis is a rare life-threatening complication of the Fontan operation. Transcatheter Fontan fenestration can ameliorate symptoms by decompressing elevated venous pressures. Transcatheter creation of a fenestration can be technically challenging in cases with complex venous anatomy. We report a case of a 5-year-old boy with heterotaxy, dextrocardia with unbalanced atrioventricular canal (AVC), atrial and visceral situs inversus, left-sided superior vena cava (SVC), and left-sided interrupted inferior vena cava (IVC) with azygos continuation. With few modifications to the equipment, a successful Fontan fenestration with stent implantation was performed via transjugular approach. At 2-year follow-up, his symptoms of plastic bronchitis improved significantly

Qualitative SERS analysis of G-quadruplex DNAs using selective stabilising ligands

Nucleic acids are of key biological importance due to their range of functions and ability to form various different structures, with an example of emerging significance being quadruplexes formed by guanine-rich sequences. These guanine rich sequences are found in different regions of the genome such as telomeres, gene promoters and introns and UTRs of mRNAs. Here a new approach has been developed that utilises surface enhanced Raman scattering (SERS) for the detection of the formation of G-quadruplexes. Three G-quadruplex stabilising ligands that each have their own unique SERS response were used in this study and their ability to act as reporters assessed. A SERS response was only obtained from the ligands in the absence of G-quadruplex formation. This resulted in an "on/off" method which was successfully used to qualitatively detect the formation of G-quadruplex using quadruplex-forming sequences such as human telomeric and C-MYC promoter DNAs. The unique SERS spectra of each stabilising ligand offer the potential for use of SERS to study higher order DNA structures. This work shows that the ligands used can act simultaneously as a potential therapeutic stabilising agent and a SERS reporter, therefore allowing the use of SERS as a method of analysis of the formation of G-quadruplex DNAs

Carrier Transport and Electrical Conduction in Alloy-Mediated Graphene on Silicon

University of Technology Sydney. Faculty of Engineering and Information Technology.The possibility of graphene-based micro- and nanoelectronic devices that exploit the extraordinary electronic properties of graphene is the biggest inspiration behind the accelerated development of graphene science and technology. Although the remarkable efforts for establishing graphene as a new electronic material began over 15 years ago, the actual realisation of graphene devices on a large-scale remains elusive, mainly due to feasibility, cost-effectiveness and compatibility issues with the existing semiconductor technology and processes. Significant advancements have been achieved in the synthesis and establishment of transport properties of epitaxial graphene (EG) on 4H- and 6H-SiC, while equivalent progress using silicon (Si) as a platform (via a thin film of 3C-SiC) with reliable electrical transport measurements has not been elucidated to date, due to limitations such as non-uniform coverage of graphene on 3C-SiC/Si and high density of defects within the 3C-SiC. In this work, we first show that the heteroepitaxial 3C-SiC on Si as the substrate should be carefully approached, as the 3C-SiC/Si heterojunction is electrically unstable and prone to severe leakage or parallel conduction. Subsequently, we find that the interface instability is due to the diffusion of carbon into the silicon matrix during the 3C-SiC growth, creating electrically active interstitial carbon. We overcome these challenges using 3C-SiC on a highly-resistive silicon substrate. By addressing the parallel conduction issue of the 3C-SiC/Si heteroepitaxial system, in this work, we isolate the charge transport properties of epitaxial graphene (EG) grown directly on 3C-SiC over large areas via an alloy-mediated method and present corresponding physical ab-initio models. Here, we study the properties of EG synthesised on 3C-SiC(100) and 3C-SiC(111). The transport properties of EG on 3C-SiC follow a similar power-law dependence of sheet carrier concentration and mobility and comparable sheet resistance values with the EG on bulk-SiC – although the grain sizes for both are vastly different. Furthermore, we find that the transport properties of graphene within the observed regime are dominated by the substrate interaction, resulting in a large p-type doping, especially for the graphene on 3C-SiC(100). In the case of EG on 3C-SiC(111), the presence of buffer layer reduces the substrate interaction and the charge transfer up to an extent. This work demonstrates a more compelling need to focus on the engineering of the graphene-substrate interface as opposed to graphene grain sizes in order to tune the charge transport properties of the epitaxial graphene for the integration of 2D materials in functional nanosystems

A Framework for Service Differentiation and Optimization in Multi-hop Wireless Networks

In resource-constrained networks such as multi-hop wireless networks (MHWNs), service differentiation algorithms designed to address end users' interests (e.g. user satisfaction, QoS, etc.) should also consider efficient utilization of the scarce network resources in order to maximize the network's interests (e.g. revenue). For this very reason, service differentiation in MHWNs is quite different from the wired network scenario. We propose a service differentiation tool called the ``Investment Function'', which essentially captures the network's cumulative resource investment in a given packet at a given time. This investment value can be used by the network algorithm to implement specific service differentiation principles. As proof-of-concept, we use the investment function to improve fairness among simultaneous flows that traverse varying number of hops in a MHWN (multihop flow fairness). However, to attain the optimal value of a specific service differentiation objective, optimal service differentiation and investment function parameters may need to be computed. The optimal parameters can be computed by casting the service differentiation problem as a network flow problem in MHWNs, with the goal of optimizing the service differentiation objective. The capacity constraints for these problems require knowledge of the adjacent-node interference values, and constructing these constraints could be very expensive based on the transmission scheduling scheme used. As a result, even formulating the optimization problem may take unacceptable computational effort or memory or both. Under optimal scheduling, the adjacent node interference values (and thus the capacity constraints) are not only very expensive to compute, but also cannot be expressed in polynomial form. Therefore, existing optimization techniques cannot be directly applied to solve optimization problems in MHWNs. To develop an efficient optimization framework, we first model the MHWN as a Unit Disk Graph (UDG). The optimal transmission schedule in the MHWN is related to the chromatic number of the UDG, which is very expensive to compute. However, the clique number, which is a lower bound on the chromatic number, can be computed in polynomial time in UDGs. Through an empirical study, we obtain tighter bounds on the ratio of the chromatic number to clique number in UDGs, which enables us to leverage existing polynomial time clique-discovery algorithms to compute very close approximations to the chromatic number value. This approximation not only allows us to quickly formulate the capacity constraints in polynomial form, but also allows us to significantly deviate from the traditional approach of discovering all or most of the constraints \textit{a priori}; instead, we can discover the constraints as needed. We have integrated this approach of constraint-discovery into an active-set optimization algorithm (Gradient Projection method) to solve network flow problems in multi-hop wireless networks. Our results show significant memory and computational savings when compared to existing methods

Targeting GRP78 in Cancer with Nucleic Acid Bioconjugates

Nucleic acid bioconjugates have gained widespread use in medicinal chemistry research programs aimed at fighting human malignancies such as cancer, diabetes, genetic and infectious diseases. Their popularity stems from their ability to accelerate the drug development process by conjugating chemical functionality that may improve the pharmacology of a bioactive nucleoside. Moreover, this strategy has been proven to be effective with small molecule nucleoside analogs and those derived from lengthy oligonucleotide sequences. Considering these fruitful applications, my research and this thesis aims to explore the synthesis, characterization and therapeutic potential of novel classes of nucleic acid bioconjugates. These are based on, aminoacyl nucleolipids, from which a simple, versatile and efficient synthesis strategy has been developed for this new class of DNA binding molecules as described in Chapter 2 of this thesis. This bioconjugate exhibited GRP78 oncogene binding affinity (KD: 0.25 mM) as characterized by PAGE gel shift assays. Its binding affinity towards the GRP78 oncogene was also confirmed using circular dichorism spectroscopy, and thermal denaturation experiments. Moreover, dynamic light scattering experiments also demonstrated increases in particle sizes after binding of this molecule to the GRP78 oncogene. In a single dose (10 µM) screen against a panel of 60 cancer cell lines, the aminoacyl nucleolipid demonstrated selective anti-leukemic activity, highlighting its potential in anti-cancer research programs. In Chapter 3, the synthesis, biophysical properties and GRP78 DNA cleavage activity of a phthalocyanine-linked oligonucleotide will be highlighted for photodynamic oncogene therapy applications. The synthesis and characterization of cancer-targeting oligonucleotide (CTO) and its bio-conjugation to a chemically resilient photosensitizer, a carboxy-derived perfluorophthalocyanine (Pc), enabled the production of a unique bioconjugate for potential anti-cancer applications. In this study, the Pc-CTO demonstrated the ability to hybridize to complementary GRP78 DNA and mRNA oncogenes. In a photochemical oxidative cleavage assay, the Pc-CTO triggered significant degradation of the GRP78 oncogenes underscoring its potential in GRP78-targeting photodynamic therapy. In Chapter 4, a study into the design, synthesis and structure-function relationships of a new class of nucleic acid bioconjugates is presented. The diacylhydrazine-linked dinucleosides represent a novel class of nucleic acid bioconjugates that are proposed to improve the structural stability of turn conformations in DNA or RNA hairpin secondary structures. My advances in the synthesis, structure elucidation and biological evaluation of these putative hairpin mimics will be described. In sum, this thesis will serve to highlight my contributions to the flourishing field of nucleic acid bioconjugation for GRP78-targeting for anti-cancer applications

Targeting GRP78 in Cancer with Nucleic Acid Bioconjugates

Nucleic acid bioconjugates have gained widespread use in medicinal chemistry research programs aimed at fighting human malignancies such as cancer, diabetes, genetic and infectious diseases. Their popularity stems from their ability to accelerate the drug development process by conjugating chemical functionality that may improve the pharmacology of a bioactive nucleoside. Moreover, this strategy has been proven to be effective with small molecule nucleoside analogs and those derived from lengthy oligonucleotide sequences. Considering these fruitful applications, my research and this thesis aims to explore the synthesis, characterization and therapeutic potential of novel classes of nucleic acid bioconjugates. These are based on, aminoacyl nucleolipids, from which a simple, versatile and efficient synthesis strategy has been developed for this new class of DNA binding molecules as described in Chapter 2 of this thesis. This bioconjugate exhibited GRP78 oncogene binding affinity (KD: 0.25 mM) as characterized by PAGE gel shift assays. Its binding affinity towards the GRP78 oncogene was also confirmed using circular dichorism spectroscopy, and thermal denaturation experiments. Moreover, dynamic light scattering experiments also demonstrated increases in particle sizes after binding of this molecule to the GRP78 oncogene. In a single dose (10 µM) screen against a panel of 60 cancer cell lines, the aminoacyl nucleolipid demonstrated selective anti-leukemic activity, highlighting its potential in anti-cancer research programs. In Chapter 3, the synthesis, biophysical properties and GRP78 DNA cleavage activity of a phthalocyanine-linked oligonucleotide will be highlighted for photodynamic oncogene therapy applications. The synthesis and characterization of cancer-targeting oligonucleotide (CTO) and its bio-conjugation to a chemically resilient photosensitizer, a carboxy-derived perfluorophthalocyanine (Pc), enabled the production of a unique bioconjugate for potential anti-cancer applications. In this study, the Pc-CTO demonstrated the ability to hybridize to complementary GRP78 DNA and mRNA oncogenes. In a photochemical oxidative cleavage assay, the Pc-CTO triggered significant degradation of the GRP78 oncogenes underscoring its potential in GRP78-targeting photodynamic therapy. In Chapter 4, a study into the design, synthesis and structure-function relationships of a new class of nucleic acid bioconjugates is presented. The diacylhydrazine-linked dinucleosides represent a novel class of nucleic acid bioconjugates that are proposed to improve the structural stability of turn conformations in DNA or RNA hairpin secondary structures. My advances in the synthesis, structure elucidation and biological evaluation of these putative hairpin mimics will be described. In sum, this thesis will serve to highlight my contributions to the flourishing field of nucleic acid bioconjugation for GRP78-targeting for anti-cancer applications

Planetary Entry Probe Dataset: Analysis and Rules of Thumb for Future Missions

Since the beginning of robotic interplanetary exploration nearly six decades ago, successful atmospheric entry has been accomplished at Venus, Earth, Mars, Jupiter, and Titan. More entry probe missions are planned to Venus, Titan, and Uranus in the next decade. Atmospheric entry subjects the vehicle to rapid deceleration and aerothermal loads which the vehicle must be designed for, to deliver the robotic instruments inside the atmosphere. The design of planetary probes and their mission architecture is complex, and involves various engineering constraints such as peak deceleration, heating rate, heating load, and communications which must be satisfied within the budget and schedule of cost constrained mission opportunities. Engineering design data from previous entry probe missions serve as a valuable reference for designing future missions. The present study compiles an augmented version of the blue book entry probe dataset, performs a comparative analysis of the entry conditions, and provides engineering rules of thumb for design of future missions. Using the dataset, the present study proposes a new empirical correlation which aims to more accurately predict the thermal protection system mass fraction for high heat load conditions during entry and aerocapture at Uranus and Neptune.Comment: 15 pages, 15 figure

Thermal Protection System Requirements for Future Planetary Entry and Aerocapture Missions

Thermal protection systems are a critical component of planetary exploration, enabling probes to enter the atmosphere and perform in-situ measurements. The aero-thermal conditions encountered during entry are destination and vehicle dependent, ranging from relatively benign conditions at Mars and Titan, to extreme conditions at Venus and Jupiter. The thermal protection system is a single-point-of-failure for both entry probe and aerocapture missions, and hence must be qualified using ground tests to ensure mission success. The high density Carbon-Phenolic which was used in the Galileo and the Pioneer Venus missions is no longer available due to the lack of the manufacturing base for its raw materials. To address the need for Venus and outer planet missions, NASA has developed the Heatshield for Extreme Environment Entry Technology (HEEET). The present study uses the Aerocapture Mission Analysis Tool (AMAT) to perform a comparative study of the thermal protection system requirements for various planetary destinations and the applicability of HEEET for future entry and aerocapture missions. The heat rate and stagnation pressure for aerocapture is significantly less compared to probe entry. The large heat loads during aerocapture present a challenge, but HEEET is capable of sustaining large heat loads within a reasonable TPS mass fraction.Comment: 14 pages, 12 figure