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Honours Projects for 2015

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SCHOOL OF CHEMISTRY AND FORENSIC SCIENCE

Bachelor of Science (Honours) in Applied Chemistry

2015 PROJECTS

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The value of an Honours degree

An Honours degree provides an opportunity to be involved in a research program in an area that

interests you, and provides training in research techniques and experience with modern research

instrumentation. The Honours programme adds a new dimension to the skills that you have acquired

during your undergraduate years and enhances your immediate employment prospects and, more

significantly, your future career potential. An Honours degree provides a pathway to postgraduate

research degrees (MSc or PhD), with possible financial support from an Australian Postgraduate

Award (APA) or some other postgraduate scholarship.

Eligibility

Applicants must have completed a UTS recognised bachelor's degree in a relevant discipline at an

appropriate level. The honours program is normally open to students who have attained at least a

credit average over the final two-thirds of the undergraduate program..

Assessment

In the Honours year, students undertake original research projects under the supervision of

academic staff. Students write a thesis about the project and present a talk on the outcomes. There

is also a coursework component, with assessment tasks on advanced chemistry topics.

Choosing a project

It is advisable to contact a potential supervisor and discuss a project during the semester prior to

enrolment in the Honours project. A number of research projects are on offer in the school and are

outlined in this booklet. Feel free to discuss any of these with the appropriate supervisor.

If you have an interest in carrying out a project in an area that is not listed, it may be possible to

arrange suitable supervision. For instance, a number of previous students have carried out their

work-based projects in conjunction with the CSIRO, ANSTO or an industrial partner.

How to apply

After discussing deciding on a project with a supervisor, fill out the forms available at:

http://www.uts.edu.au/future-students/science/go-further/honours-program/school-chemistry-and-

forensic-science-honours

Applications should be submitted by November 28, 2014 to be considered for a first round offer, but

final round applications are accepted until January 31, 2015. Students generally begin work on their

project in February. There are Autumn and Spring semester intakes for the programme.

Advice

If you have any questions about the programme, please feel free to discuss them with the Chemistry

Honours Coordinator, A/Prof. Andrew McDonagh ([email protected]).

mailto:[email protected]


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PROJECTS OFFERED IN 2015


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Title Screening for lung infections: volatile profiling of Pseudomonas

aeruginosa in cystic fibrosis patients

Nature of problem

work is intended to

address

Chronic Pseudomonas aeruginosa infection is a

hallmark of cystic fibrosis lung disease (see

image). Current techniques used to screen

patients for this infection are both cumbersome

and highly invasive. New techniques involving

the chemical analysis of volatile biomarkers in

breath samples have demonstrated their potential

as non-invasive screening tools. Importantly, Pseudomonas bacteria have a

distinct metabolism which can produce bacteria-specific volatile organic

compounds (VOCs) in exhaled air, allowing for rapid diagnosis and

treatment.

This project will chemically profile the VOCs produced by P. aeruginosa

which are characteristic of chronic lung infections in cystic fibrosis patients.

The results of the project will assist in determining bacteria-specific

biomarkers which can be used as a screening tool for detecting lung infection

in cystic fibrosis patients. This information will assist with the long term goal

of developing a portable instrument which can rapidly detect this infection on

the breath of cystic fibrosis patients.

Outline of

goals/objectives

The goals of this project are as follows:

To optimise a gas chromatography-mass spectrometry method for the

analysis of volatile compounds produced by P. aeruginosa

To compare the volatile profiles of breath samples collected from a

control group with a clinical group of cystic fibrosis patients

To identify P. aeruginosa specific volatile biomarkers which can be

used to rapidly screen cystic fibrosis patients for bacterial lung

infection

UTS supervisor Professor Shari Forbes

External supervisor Clinical Associate Professor Peter Middleton (Westmead Millennium

Institute for Medical Research, University of Sydney)

Contact information [email protected]



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Title Profiling the Scent of Training Aids for Blood-detection Dogs

Nature of problem

work is intended to

address

Blood-detection dogs are a specialised scent-

detection canine trained to detect the scent of

latent blood at a crime scene. Their

sensitivity is superior to presumptive chemical

tests in identifying the presence of both

visible and latent blood traces. Blood-

detection dogs are trained on a variety of

training aids including fresh human blood,

degraded cadaver blood, and animal blood.

It is currently unknown what chemical scent is produced by these training

aids and whether they produce different scent profiles recognisable by the

dogs. Police dog units have reported different responses from the dogs based

on the type of blood used during training. It is important to identify the

chemical differences in blood scent to ensure the dogs are being trained on

the most typical scent they will encounter at a crime scene.

Outline of

goals/objectives The purpose of this project is to chemically profile fresh human blood,

degraded cadaver blood, and a range of animal blood samples to

compare their chemical scent profiles.

The headspace of the blood samples will be collected using solid phase

micro-extraction (SPME) and analysed by gas chromatography-mass

spectrometry.

The chemical scent profile will be compared to the response of the

blood-detection dog during training.

Special requirements Ethics approval for the use of blood samples

Industry/Ext partner NSW Police Force Dog Unit

UTS supervisor Professor Shari Forbes, Dr Katie Nizio


[email protected]




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Title Decomposition chemistry: establishing the volatile profile of human

remains during the early post-mortem period

Nature of problem

work is intended to

address

Following a natural or man-made disaster, search and rescue teams are

rapidly deployed to locate both living and deceased victims. Once the living

have been located, the task of the search team becomes more challenging as

they seek to locate victim remains in the disaster scene. Cadaver-detection

dogs are often used to locate victims in mass disaster investigations however

this presents a challenging environment as it is not known whether the scent

of a recently deceased victim resembles the living (human scent) or the dead

(decomposition odour).

The aim of this project is to chemically analyse soft tissue to determine the

volatile profile immediately after death and during the early postmortem

period, mimicking the timeframe when victims are typically recovered from

mass disasters. This profile will be compared to the literature available about

human scent to determine similarities or differences with respect to ante-

mortem and post-mortem volatile profiles.

Outline of

goals/objectives


To optimise a method for collecting volatile samples from soft tissue

To analyse the volatile samples using gas chromatography-mass

spectrometry

To determine variations in the postmortem volatile profile over time

To conduct a literature review of human scent and compare the ante-

mortem and post-mortem volatile profiles

UTS supervisor Professor Shari Forbes and Dr Katie Nizio


[email protected]




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Title Silica Hydrothermal Synthesis of Amorphous from Industrial Wastes

Project Description Amorphous silica is a growing commodity product used in a range of applications such

as high surface area fillers for rubber in car tires resulting in significantly reduced fuel

consumption to use as a thickening agent in toothpastes and cosmetics. Due to the

high surface area and porosity, amorphous silica also has potential application as

catalysts supports and may be used in a range of nutrient and drug delivery

applications. Currently, silica is sources through the calcining of quartz at high

temperature in the presence of soda to form a water soluble silica glass which is then

neutralised to precipitate the high surface area amorphous silica. The high

temperature route results in high energy consumption which can be avoided if

hydrothermal (autoclaving) techniques are employed.

Hydrothermal methods for the production of waterglass (soluble silica glass) from

aluminosilicates are known, but are not currently commercially available. This study

proposes to investigate the conditions of hydrothermal synthesis of silica waterglasses

by autoclaving aluminosilicate industrial wastes such as fly ash, bottom ash and

pitchstone fines in the presence of sodium hydroxide. Subsequent precipitation of the

silica with nitric acid yields high surface area high purity amorphous silicas. Methods of

characterisation will be Raman spectroscopy which is sensitive to silica structure, gas

adsorption to determine surface area and porosity characterisation and differential

scanning calorimetry which can also be applied to porosity characterisation. Scanning

electron microscopy will also be pursued.

In addition to the high surface area silica, by-products of the process are

aluminosilicates which depending on the hydrothermal conditions can yield zeolites.

Zeolites are important minerals in that they have many industrial applications in

particular catalysis. These aluminosilicate by-products will be characterised by Raman

spectroscopy, crystallography and thermogravimetric analysis.

Supervisor Dr Paul Thomas




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Title Calorimetric Investigation of the Hydration of High Sulphate Cement at

Elevated Temperature

Project Description Precast concrete elements are commonly manufactured for the construction of

bridges, tunnels, culverts, pipes and drains as high strength elements and are cured

at elevated temperature within a 24 hour period (as oppose to 28 days at ambient

temperature). The chemistry of the cement curing, however, is altered by the use of

elevated temperature. In particular, the hydration of tricalcium aluminate (C3A)

present in cement as a by-product of clinker process is affected. C3A hydrates rapidly

on the addition of water and is extremely exothermic causing acceleration of

Portland cement hydration. The hydration of the C3A may be inhibited by reaction of

the hydrated C3A with sulphate to form the mineral ettringite. Sulphate is added

typically in the form of gypsum which is interground with the cement clinker, a glassy

calcium silicate formed in the kiln during cement manufacture. The sulphate ions

react with the calcium aluminate hydrate to form ettringite which inhibits further

hydration of the calcium aluminate through the formation of an impermeable layer.

In the manufacture of precast concrete elements at elevated temperature, however,

the sulphate becomes more soluble and the ettringite decomposes as the sulphate is

dissolved into solution. Further hydration of the C3A results in increased temperature

and flash setting of the cement. At elevated temperature the formation of ettringite

is inhibited by the solubility of the sulphate, however, after curing, and once the

temperature has returned to ambient, the solubility of the sulphate decreases and

sulphate becomes available once again for ettringite formation. This delayed

ettringite formation, which is accompanied by a large volume increase, occurs in the

hardened state and can result in the cracking and failure of precast concrete

elements. In order to prevent these deleterious processes from occurring, an

understanding of the formation conditions is necessary. This project, therefore,

investigates the reaction chemistry of high sulphate cements at elevated

temperature using adiabatic calorimetry and differential scanning calorimetry in

conjunction phase analysis using crystallography. A greater understanding of the

reactions involved, in particular in the formation of delayed ettringite, will help to

minimise hazardous degradation of precast concrete elements in construction.

Supervisors Paul Thomas (CFS), Kirk Vessalas (Civil Engineering)

Additional Information Financial Support for this project is available through industrial funding from

Humes Australia.

Contact information Please contact Paul Thomas ([email protected]) for further details.



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Title The Influence of the Composition of Supplementary Cementitious Materials (SCM)

In mitigating Alkali Silica Reaction (ASR)

Project Description Alkali Silica Reaction (ASR) is caused by slow reactions of alkalis from Portland

cement and certain reactive silica in aggregates. ASR can cause expansion and

premature deterioration of concrete structures. This potential reaction is

traditionally detected by accelerated expansion tests of cement mortar and concrete

by means of increasing the availability of alkali and temperature. Two such test

methods have recently been agreed and published by Standards Australia in 2014.

A range of supplementary cementitious materials (SCM), such as fly ash and ground

granulated blast furnace slag (slag), have been found effective in mitigating the ASR.

The effectiveness of an SCM to mitigate ASR appears to depend on its composition,

its dosage and the degrees of reactivity of the aggregate. This study will investigate

the influence of the composition of SCMs and other physical properties on the ASR

and the kinetics of the reaction in cement mortar and/or concrete with and without

the SCM. The outcomes will provide guidance on the selection of SCMs based on

their composition in ASR mitigation.

Supervisors Paul Thomas (CFS), Kirk Vessalas (Civil Engineering)

Additional Information Financial Support for this project has been informally approved through the Centre

for Built Infrastructure Research (CBIR) and Cement and Concrete Aggregates

Australia (CCAA).

Contact information Please contact Paul Thomas ([email protected]) for further details.



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Title The detection of clandestine drugs in polymers: GC-MS profiling of

volatile compounds available to drug-detection dogs

Project Description There exists a variety of approaches by smugglers to move drugs across

borders. Attempts have been made to transport drugs, such as cocaine, by

disguising an odour that could be potentially detected by trained drug-

detection dogs. Drugs are often wrapped in plastic bags or materials, but now

smugglers are attempting more sophisticated approaches that involve the

impregnation or dissolution of drugs into polymer matrices in the belief that

detection will be more difficult. The drugs are then extracted in clandestine

laboratories.

This project will involve the development of an analytical method to

determine if the odour of the drug can be detected when incorporated into

common polymers. Two dimensional gas chromatography- time-of-flight

mass spectrometry (GC x GC - TOFMS) will be used to identify

characteristic volatiles that may prove to be effective markers for the

detection of particular drugs hidden in polymers. The volatile profile will be

correlated to the response of drug-detection dogs to similar samples.

Outline of

goals/objectives


To optimise a method for collecting and analysing volatile samples

from drug impregnated polymers using two dimensional GC-MS

To identify the volatile profile that is available for detection by drug-

detection dogs

To compare the volatile profile with the response of drug-detection

dogs when exposed to drug-impregnated polymers

Supervisors Prof. Shari Forbes, A/Prof. Barbara Stuart, Dr Shanlin Fu and

Dr Mark Tahtouh (Australian Federal Police)

Contact information [email protected], [email protected]




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Title Chlorinated nucleosides - novel mediators or biomarkers of disease?

Project Description Chlorine is a potent disinfectant, which is present in aqueous solution, as hypochlorous acid (HOCl), and molecular chlorine (Cl2). Although used widely to kill harmful bacteria in both drinking water and swimming pools, it is also responsible for the formation of numerous disinfection by-products (DBPs), which can modify DNA, and have been implicated in cancer development. HOCl is also produced in the body by activated leukocytes via the myeloperoxidase-catalysed reaction of H2O2 with Cl- ions. The chemistry of HOCl in biological systems has attracted considerable attention, as excessive or misplaced production of this oxidant during prolonged inflammation, damages tissue and causes disease. HOCl chlorinates the nucleoside building blocks of RNA and DNA, and these products are seen in diseased tissue. Currently it is not known whether RNA / DNA chlorination is simply a consequence of the disease process, or whether these modified nucleosides play a role in disease pathology.

This project will build on our novel data showing that chlorinated nucleosides perturb the expression of key stress and toxicity genes, which has a significant impact on cellular function. These cellular changes are detrimental to function, and may play a role in disease development. This has important toxicological significance for chlorinated drinking water supplies, in addition to providing novel insights into inflammation-induced disease. We will use a mass spectrometry approach to assess the extent and rate of uptake and turnover of chlorinated nucleosides by different human vascular cells and a molecular biology approach to define the consequences of chlorinated nucleosides on vascular cell function.

Supervisors: Dr Shanlin Fu (University of Technology Sydney), Associate Professor Clare Hawkins (The Heart Research Institute, Sydney)


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Title Radical-Mediated Protein Damage: Products, Mechanisms and Consequences

Project Description Free radicals are generated in biological systems as by-products of normal cellular

redox processes, or via the interaction of cells and tissues with a number of external

agents (e.g. smoke, radiation, asbestos, drugs). It is well established that amino acids,

peptides and proteins are major targets for radicals, with protein oxidation occurring

during the normal aging process, and in various human diseases including

atherosclerosis (hardening of the arteries) and cataracts. Free-radical mediated damage

to proteins is also relevant to the food, agricultural and pharmaceutical industries, as it

is involved in plant stress, food spoilage and sterilisation of foods/pharmaceuticals

(using radiation). Numerous radical species (e.g. hydroxyl (HO), peroxyl (ROO

),

superoxide (O2)) can be generated in these systems, but their reactivity differs

widely. Aromatic amino acid side chains (e.g. tyrosine (Tyr), tryptophan (Trp),

histidine (His)) are well established targets for radical damage, and the formation of

diTyr crosslinks results in radical-induced protein aggregation. However, recent data

indicate that alternative mechanisms and products that involve Trp radicals are also

likely to be important in these processes.

This project will initially focus on the characterisation of products generated on a well-

defined series of Trp-containing peptides that have been exposed to a variety of radical

generating systems. The aim of the project will be to identify and characterise novel

products (e.g. dimeric species) and quantify their abundance relative to established Trp

oxidation products (e.g. kynurenine, N-formyl-kynurenine). The results obtained from

initial studies of simple model peptides will be extended to more complex

peptides/model proteins as well as proteins that are relevant to the development of

human disease. The data will enable the potential development of novel biomarkers for

evaluating the contribution of radical-induced damage in disease processes. A further

direction for the project will be to examine the efficacy of novel antioxidants in

preventing or reversing this damage.

This project will use a wide variety of analytical chemical methods, including UV/Vis

spectroscopy, EPR spectroscopy, mass spectrometry (MS), HPLC/UPLC and LC/MS,

as well as some biochemical approaches e.g. cell culture, gel electrophoresis. This

project would suit someone with a chemistry/biochemistry background with a strong

interest in analytical and protein chemistry.

Supervisors: Dr Shanlin Fu (University of Technology Sydney)

Dr David Pattison (The Heart Research Institute, Sydney)


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Title Pesticide Residue Testing, Analysis for Australian Grown Fruits and Vegetables

Using QuEChERS, QQQ LC-MS and QTOF LC-MS Techniques

Project Description Most vegetable products available in local grocery stores are grown using

conventional agricultural practice involving the use of pesticides. Pesticide residues

in food continue to be the target of studies due to the uncertainty concerning adverse

effects of those residues on human health after a lengthy exposure at low levels.

More than 1000 active ingredients have been utilised and are formulated in thousands

of different commercial products. They include a variety of compounds, mainly

insecticides, herbicides and fungicides, with very different physico-chemical

characteristics and large differences in polarity, volatility and persistence.

Consequently, in order to ensure food safety for consumers and to facilitate

international trade, regulatory bodies around the world have established maximum

residue levels (MRLs) for pesticide residues in food commodities; that is, the

maximum amount of pesticide residue and its toxic metabolites allowed on a

commodity should not be exceeded if good agricultural practice is adhered to during

the use of the pesticide.

In this project, the QuEChERS (Quick-Easy-Cheap-Effective-Rugged-Safe) sample

preparation technique developed by Anastassiades et al. will be used to extract

pesticide residues from fruits and vegetables followed by a dispersive solid phase

extraction clean-up of the extract. The extract will be then analysed by both QQQ

LC-MS and Q-TOF LC-MS.

Supervisors

Dr. Shanlin Fu and Dr. Linda Xiao


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Title Design of precursor molecules for electron beam induced nano-chemistry

Project description Electron beam induced chemistry (EBIC) is a cutting edge technique for the fabrication and editing of advanced functional materials at the nano-scale. Emerging EBIC applications include the fabrication of next-generation optoelectronic devices made from diamond, chemical manipulation of single photon emitters (Fig. 1), and electrical contacting of carbon nanotubes.

In order to expand the applications of EBIC, understanding of the underlying chemical pathways and reaction mechanisms must be improved. Recent advances made at UTS have made it possible to identify the properties of precursor molecules that lead to extraordinary EBIC performance. The present project will use this knowledge to design, synthesize and test a new generation of precursor molecules. The honours student will focus on the design and chemical synthesis phases of the project, and will have the opportunity to collaborate with a team of PhD students working on EBIC development and applications of the synthesized precursors.

Figure 1: Chemical switching of the quantum states of single photon emitters by EBIC. The emitters are embedded in nanoparticles processed by a scanned electron beam.

Supervisors Prof. Milos Toth, Dr. Charlene Lobo, Dr Andrew McDonagh



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Project title Characterization of the activities of model catalyst microarrays fabricated using electron beam induced chemistry

Project description Electron beam induced deposition is a new technique for fabricating nanoscale devices and sensors in which a substrate is irradiated in the presence of a gas that contains the atoms of interest. The electron beam dissociates surface-adsorbed (rather than gas-phase) precursor molecules, thereby leading to highly localised ‘3D printing’ of structures with a spatial resolution of ~10 nm.

This project will build on recent work on e-beam fabrication of high purity Pt nanoparticle arrays (C. Elbadawi, M. Toth & C. Lobo, ACS Appl. Mat. Interfaces, 2013) by investigating their activity for key catalytic reactions such as the oxidation reduction reaction in fuel cells, and reduction of CO2 to carbon-based fuels. The project will involve assessment of the activities of e-beam fabricated Pt films and microarrays by cyclic voltammetry. Characterization of the structure and electronic states of the catalyst particles will also be conducted using synchrotron x-ray diffraction and x-ray photoelectron spectroscopy. The project will be conducted in close collaboration with physics PhD students involved in fabrication of the arrays and characterization of their properties by complementary techniques.

Experimental techniques

Cyclic voltammetry, synchrotron x-ray diffraction, XPS

Supervisor Dr. Charlene Lobo A/Prof Andrew McDonagh



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Title Alkaloid-like molecules: AChE inhibitors as potential treatment of

Alzheimer’s disease

Description Background Our earlier work on the Bridging Ritter reactions of natural products such as limonene with a variety of nitriles under Bridging Ritter reaction conditions, provided cyclic imine 1, in one single step. Cyclic imines have been used in our group to generate alkaloid-like compounds for drug discovery. These alkaloid-like compounds were shown to be strong AChE inhibitors. One of the primary roles of acetylcholinesterase (AChE) is the hydrolysis of the neurotransmitter acetylcholine (ACh) to inactive choline and acetate in cholinergic synapses. Reversible AChE inhibitors, for example, the natural alkaloid Galanthamine (Reminyl), is an approved drug for the treatment of Alzheimer’s disease (AD).4

(a) Synthesis of cyclic imine 1(b) Galanthamine in the AChE catalytic site. Synthesis The cyclic imine 2 will be synthesis, using our standards condition from (+)-limonene. These compounds will be used as the central intermediates, in two sequential steps of reduction and reductive alkylation, to generate novel and relatively complex alkaloid-like molecules. Biological assays Since the natural alkaloids often exhibit a rich spectrum of biological activity, and it would be likely the case for the alkaloid-like molecules.5 Therefore the potential biological activity of synthesised compounds will be assessed for AChE inhibitory activity.

Project aims 1. To synthesise optically active cyclic imine 1 from (R)-(+)-limonene, via the Bridging Ritter reaction.

2. To synthesise alkaloid-like compounds from imine 1. 3. To assess the biological activities of synthesised compounds for AChE

inhibitory activity 4. To assess SAR (structure activity relationship) of synthesized compounds via

computer-aided molecular modeling study.

Supervisor A/Prof. Alison Ung


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Title Discovery of AChE inhibitors using STD NMR

Project Description

Background One of the primary roles of acetylcholinesterase (AChE) is the hydrolysis of the neurotransmitter acetylcholine (ACh) to inactive choline and acetate in cholinergic synapses. Reversible AChE inhibitors such as the natural alkaloid Galanthamine (Reminyl) is an approved drug for the treatment of Alzheimer’s disease (AD). The object of this medicinal chemistry project is to understand the molecular interactions between AChE inhibitors and the enzyme which would assist in discovery of useful AChE inhibitors suitable for drug development for the treatment of AD.

Practical aspects of STD NMR in drug screening The simplicity of the Saturation transfer difference (STD) NMR method allows for adaptability to an array of different compound interactions. Its practicality in ligand screening versus other methods makes it very useful technique for investigating protein-ligand interaction in solution. The technique can be easily implemented on our existing 500MHz Agilent NMR using Biopack® protocols.

The technique provides the mapping of the binding epitopes (ISTD = Io – Isat) of the ligand (inhibitor) in the binding pocket of the protein (i.e. AChE enzyme). I

The technique further allows the dissociate constant (KD) to be determined according to Eq. 1.

Figure 1. The selective saturation of receptor signals is obtained from the transfer of saturation from the protein to the ligand (green A, B, C). Intensity of the signal is increased for parts of the ligand that are in closest contact with the protein when binding (B). Figure 2. The spectrum of the selective saturation of receptor signals (Isat) is subtracted from the 1H NMR reference spectrum (IO) to yield the difference spectrum (ISTD=IO-Isat).

eq.1

Project aims the qualitative manner in which an AChE inhibitor binds to the enzyme,

ligand mapping via a direct characterisation of moieties of ligand interaction through identification of the individual protons of an inhibitor necessary for binding,

identify the specific binding pocket within AChE enzyme;

and to determine the dissociation constant (KD) between the protein and the inhibitor.

Supervisor A/Prof. Alison Ung and Dr Ronald Shimmon

KD: Dissociation Constant

[E]: concentration of Enzyme

[L]: concentration of Ligand


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Title Synthesis of Benzopthiophene FtsZ inhibitors as antibiotics

Project Description The increase of antibiotic resistance among an array of bacteria is of growing concern in both hospital and community settings. Particularly, Methicillin-resistant Staphylococcus aureus (MRSA) has shown resistance towards traditional targets and every class of antibiotics available. In 2011, roughly 80,000 cases of methicillin-resistant S. aureus (MRSA) infections occurred in the United States alone.1

At this alarming rate, there is an urgent need of the new class of antibiotics. Over the years, the traditional targets have been exhaustively exploited and became ineffective. However, essential proteins necessary for bacterial cell division are a relatively new area of research to effectively kill bacteria and prevent infection by reducing cell viability and cell growth.2,3 FtsZ (Filamentous temp.-sensitive protein Z), is one such emerging target.2 Inhibition of FtsZ (de)assembly has been shown to cause bacterial cell death and reduced the MRSA in the animal model.

Computer-aided molecular modelling has indicated that our proposed benzothiophene 1 binds into the FtsZ pocket in the same manner as that the patented FtsZ inhibitor, PC1907234 (shown in ball and stick, with excellent ligand efficiency. Based on these results, a series of novel benzothiophenes targeting FtsZ will be synthesised and investigated for their antibacterial activity.

(a) (b)

Fig 1. (a) Simulated docking of benzothiphene 1 (grey stick model) into FtsZ pocket, PC (ball and stick model), (b) Benzothiophene 1 pose-view and detailed interactions in the binding pocket.

Project aims 1. To synthesise benzothiophene 1 and its analogues (Fig 1)

2. To determine antibacterial activity (MIC) of the synthesised compounds

against S. aureus

3. To explore the FtsZ inhibitory activity of the synthesised compounds

4. To investigate SAR (structure activity relationship) of the synthesised

compound via computer-aided molecular modelling

Supervisors Assoc. Prof Alison Ung and Prof Elizabeth Harry


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Title Functionalized fluorescent nanodiamonds for bioapplications

Project description Fluorescent nanodiamonds (NDs) have attracted much interest from the biological community as an ultimate agent for biomedical applications, such as biomarkers, drug and gene delivery and biocatalysts, owing to their chemical inertness, biocompatibility, prolonged photostability (negligible photobleaching) and low toxicity. Colour centres in diamond possess an unprecedented photostability and exhibits single photon emission at room temperature. NDs are excellent candidates for surface modification for applications in biology or medicine, as carbon can be readily modified with functional groups. However, the surface functionalization of NDs can affect the compatibility and toxicity of the carbon-based material within living cells. Hence, the aim of this project is to investigate the effect of various surface functionalities of NDs upon interaction with living cells.

Techniques Confocal laser scanning microscopy, fluorescence microscopy, dynamic light scattering, zeta potential, FTIR, scanning electron microscopy, tissue culturing

Supervisors Dr Olga Shimoni, Dr Andrew McDonagh

Contact [email protected]


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Titles 1: Radiolabel AChE inhibitors as PET probes for imaging cerebral AChE.

2: Developing AChE substrate-type as PET radioprobes for measuring AChE activity.

Project description Background The central cholinergic system plays an important role in several brain functions, such as attention, memory, cognition, and consciousness. Acetylcholine-mediated neurotransmission within cholinergic synapses in the brain is terminated by the breakdown of the neurotransmitter acetylcholine (Ach) into the inactive components, by the acetylcholinesterase (AChE) enzyme. It is well established that symptoms of Alzheimer’s disease (AD) are related to low levels of ACh within the synaptic cleft, mainly in the cerebral cortex and hippocampus as determined by the post-mortem analysis of the brains of AD sufferers. One method for treating AD is the administration of AChE inhibitors, for instance, Galanthamine, a reversible AChE inhibitor is a FDA-approved drug for AD.

AChE activity has been reported as a marker for cholinergic neural activity. It has been demonstrated that the progressive reduction in cerebral AChE activity and is closely linked to the loss of neocortical cholinergic neurons is a characteristic of patients with AD.

[18F]fluorodeoxyglucose or FDG, the world’s most commonly prescribed fluorine-18 radiopharmaceutical is used to diagnose many forms of cancer and make early diagnosis of Alzheimer's disease through positron emission tomography (PET) imaging (see RHS image).

Object of the project Therefore, the imaging of AChE and its activity in the brain by PET represents a valuable tool for understanding of the AD progression. AChE inhibitors can be labeled with 18F or 125I as candidates for PET probes for the imaging of cerebral AChE. AChE substrates can also be synthesized and used as radioprobes not only for cerebral AChE imaging but also for measuring the effects of AChE inhibitors in an animal model.

Supervisors Associate Prof Alison Ung (UTS) Dr Tien Pham (ANSTO)

Campus UTS and ANSTO


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Title Development of ChipLC-ICP-MS

Description In this project, UTS and Agilent Technologies, the world’s leading vendor of analytical

instrumentation, will develop the world’s first hyphenated microfluidic chip liquid

chromatography–inductively coupled plasma–mass spectrometer (chipLC-ICP-MS) for the field

of metallomics.

Trace elements (<0.01%

of human body weight)

are critical in biological

processes. For example,

protein phosphorylation

cascades play a central

role in cell signaling and

development,

particularly in cancer

cells. Cyanocobalamin

(vitamin B12), which

forms two coenzymes

responsible for bio-

logical transformations,

contains cobalt. Iron in

haemoglobin binds

oxygen and carbon

dioxide, reactants and

products of cellular respiration. Copper and zinc are key components of superoxide dismutase,

an important enzyme in oxidation–reduction reactions. It is currently thought that around one-

third of all proteins in the human body contain at least one metal ion. These ions can act as

structural features or active sites for catalysis. Trace metals are so important to cell function that

cell chemistry must be characterised by the distribution of the metals and metalloids among

different biomolecules – defined as the ‘metallome’.

Hyphenated technologies such as liquid chromatography-inductively coupled plasma-mass

spectrometry (LC-ICP-MS) are the most effective way to detect trace elements in biological

samples. LC separates the sample fractions prior to detection by ICP-MS. ICP-MS has isotope

specificity, versatility (virtually any element can be detected), high sensitivity, and enormous

linear dynamic range (105–10

6) needed for efficient element detection. Figure 1 is one example

of the analysis of metallothionein isoforms by LC-ICP-MS. These isoforms are metal-binding

proteins associated with numerous disease states. Recent improvements in ICP-MS

instrumentation also detect non-metals such as phosphorous, expanding LC-ICP-MS analysis to

phosphorylated proteins.

Traditional standard (3 to 5 mm internal diameter) and narrow bore (1 to 2 mm internal

diameter) analytical LC columns are relatively easy to couple to ICP-MS due to compatible flow

rates. There are significant advantages in reducing the internal diameter of the separation column

including improved separation efficiencies, higher sensitivity and less solvent consumption.

However, reducing the internal diameter of the LC columns to micrometre-widths, also known

as nano-LC, presents new challenges. Hyphenation of nano-LC requires transport of eluents with

flow rates as low as 10 nL min-1

into the ICP-MS. This requires dedicated interfaces with sheath

flows to boost flow rates to levels capable of nebulisation; or employment of sheathless total-

consumption direct-injection nebulisers [8]. Further challengers include frequent blocking of the

capillary columns, requirements of sample pre-concentration prior to analysis with concentrator

columns and the minimisation of dead volumes to avoid band broadening leading to poor

separation efficiency.

All of these issues may be overcome by incorporation of the LC components into a

microfluidic lab-on-a-chip device.

The aim of this project is to design and fabricate an interface between a microfluidic liquid

chromatograph (chipLC) and ICP-MS.

Supervisors Philip Doble, David Bishop, Lucas Blanes

Contacts [email protected], Lucas Blanes( [email protected]), [email protected]

Figure 1: Separation metallothionein isoforms by LC-ICP-MS





25

Title Developing new clinical diagnostic tests: Vitamin B12 in medications and

biological samples

Description Advances in medicine and the new focus on personalized treatments mean that there

will be increasing reliance on in vitro diagnostics and a requirement for simpler, rapid

techniques. This project aims to develop new analytical techniques which will be

applicable to drugs, metabolites and biomarkers using vitamin B12 as a model

compound.

Vitamin B12 has been chosen because of its clinical relevance in a number of disease

states such as pernicious anaemia and neurological disorders and as it is currently

measured using a time-consuming competitive binding luminescence assay which

requires removal of serum binding proteins before measurement. Other short comings

of this complex assay are interfering factors; in May 2012 there was a voluntary recall

of a cobalamin assay reagent (Siemens Healthcare Diagnostics, NY) due to inference

issues. Additionally, vitamin supplements are not tightly regulated either by the TGA

or the FDA. For example recent studies in the US of Vitamin D in OTC supplement

products have shown that they contained between 52 and 135% of the labelled levels

which has significant implications for patients being treated for deficiency. Levels of

Vitamin B12 in multivitamins are further complicated by the ability of other

components such as Vitamin C to interact with cobalamin so that it forms inactive

analogues. These factors make its analysis of interest.

Aptamers are short synthetic strands of DNA, RNA or amino acids with complex

three dimensional structures that bind unique protein or small molecule targets with

exquisite specificity. Aptamer technology is relatively new and has the capability to

distinguish between closely related isoforms. These molecules can be tagged with

lanthanides and rapidly detected by microwave plasma - atomic emission

spectroscopy (MP-AES).

In this project you will use aptamers to Vitamin B12 for the development of novel

analytical protocols for use with MP-AES. These protocols will be tested by analysing

levels of Vitamin B12 in over the counter multivitamin preparations and in biological

specimens. Results will be compared to those obtained by conventional techniques.

The project may be expanded to include other clinically relevant drugs and

metabolites such as antibiotics, lithium compounds, insulin, intrinsic factor etc.

Supervisor Prof. Philip Doble

Contact For further information please contact Philip Doble [email protected]



26

Title Three dimensional multiplexed protein atlas of the mouse brain

Description The brain is the most complex organ in the human body. Animal models like the

laboratory mouse are commonly used to study diseases affecting the human brain.

Structural brain atlases are universal features of neuroscience laboratories. Atlases are

used to correlate features of disease with specific brain regions. Improving technology

has seen a move to functional brain atlases, where regional gene and protein expression

can be observed in conjunction with basic neuroanatomy via interactive software. This

project will develop the first interactive model of various proteins in the mouse brain

using advanced mass spectrometry techniques.

The aim of this project is to construct a standard three-dimensional atlas of metal -

transporter proteins in the C57BL/6 mouse brain using laser ablation-inductively

coupled plasma-mass spectrometry (LA-ICP-MS) and tagged antibodies.

Supervisor Philip Doble, David Bishop

Contact [email protected] or [email protected]




27

Title Developing new applications for next generation elemental analysis

instrumentation

Description Agilent Technologies is the world’s leading vendor of analytical instrumentation and

leads the way in atomic spectroscopy and elemental analysis innovation. Its optical

spectroscopy headquarters is located in Melbourne and has been the site of multiple

new product developments in the past 2 years that have pushed back some of the long-

term barriers in atomic spectroscopy. Agilent’s Microwave Plasma – Atomic Emission

Spectroscopy (MP-AES) is a prime example of the continuing innovation around

instrumentation. The MP-AES is a world’s first product that provides excellent

performance without the need for expensive, difficult to obtain and often hazardous

bottled gases, thereby allowing it to be used remotely, at a mine site for example, or in

developing countries where access to bottled gases is difficult if not impossible.

There are a number of projects available to students with an interest in developing

novel applications for the MP-AES and Agilent’s next generation Inductively Coupled

Plasma – Optical Emission Spectroscopy (ICP-OES), instruments that are used in labs

around the world for accurate measurement of trace levels of a broad range of

elements. Think measurement of mercury in drinking water, trace levels of gold in

mine tailings, melamine adulteration of milk and infant formula and lead in toys.

In these projects you will research and develop novel analytical protocols for use with

the MP-AES and/or ICP-OES in the fields of food and agriculture and environmental

analysis. Results will be compared to those obtained by other analytical measurement

techniques and a range of international standards. The protocols and results developed

will be used to establish real world applications for use by researchers and analytical

chemists around the world.

Students working on these projects will have the opportunity to spend time at Agilent’s

state of the art Spectroscopy Technology Innovation Centre in Melbourne.

Examples of projects available (actual project to be determined by mutual agreement,

based on the interests of the student), include developing protocols to determine:

Trace elements in drinking water

Major and trace elements in infant formula

Minor nutrients in fertilizers

Heavy metals in toys

Toxic elements in green ink

Supervisor Philip Doble


j



28

Title

Projects at the National Measurement Institute (NMI) - multiple projects available.

Example: Improved analytical methods for the screening of Endogenous Anabolic

Androgenic Steroids

Description Background The ASDTL is the only laboratory in the Oceania region accredited by

the World Anti-Doping Agency (WADA) to carry out doping control analysis in

human sport and as such performs virtually all of the sports drug testing carried out in

Australia and New Zealand. ASDTL complies with the requirements of ISO/IEC

17025:2005 and is accredited by NATA. Drug testing is not just carried out at major

sporting events but is a year round activity with the analysis of some 8000 samples per

year from a range of amateur and professional sports. Our research program aims to

improve analytical techniques used in our laboratory and to investigate new forms of

doping which are currently undetectable. We receive funding from the WADA, the

Department of Health’s Anti-Doping Research Program and the US Partnership for

Clean Competition.

Project Recent research has demonstrated the improved effectiveness of the athlete

steroid biological passport when alternative steroid metabolites are included into

routine analytical procedures. However, their implementation into routine steroid

profiling is not trivial as their concentrations are generally quite low (less than 50

ng/mL) and stable isotopically labelled internal standards are not available. As such,

improved instrument capabilities are required for their successful analysis. This project

aims to implement the best identified alternative steroid metabolites into routine

screening at ASDTL and to investigate new instrumental technology available to

improve their analysis for their future potential implementation into the athlete steroid

biological passport.

Supervisor A number of supervisors at NMI are offering projects to UTS students.

Contact Email [email protected] for the full list of projects available.

Contact [email protected] for information about NMI and

individual projects.



29

Titles 1. Creating improved electrodes for cochlear and vision implants. 2. Testing new tethered bilayer chemistries 3. Using tethered membranes to determine whether an ion channel prefers cations or anions. 4. Creating bacterial, mammalian and fungal tethered lipid bilayer models.

Description

1. Creating improved electrodes for cochlear and vision implants. This project aims to actually get cells to grow adjacent to gold electrodes using tethered bilayer lipid membranes. By investigating ways to grow cells directly onto gold we hope to demonstrate how to improve electrode design in cochlear and retinal implants. Student will learn to culture a cardio-myocyte cell line and to test their adhesion using fluorescence microscopy and impedance spectroscopy techniques.

Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)

2. Testing new tethered bilayer chemistries. In order to improve the function of tethered bilayers, unique tethering chemistries have been developed in cooperation our commercial partner SDx Tethered Membranes Pty Ltd. The electrode-tether binding properties of these chemistries will need to be tested in order to create new membrane models for antimicrobial research. Techniques the student will learn include impedance spectroscopy measures, surface chemistry and contact angle imaging. Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)

3. Using tethered membranes to determine whether an ion channel prefers cations or anions. This project uses bias voltages across a tethered bilayer lipid membrane to identify the preferred polarity of ion channel conductances. This project combines peptide ion channel research with physical chemistry. The student will learn advanced impedance spectroscopy techniques and physical chemistry interactions. The complexity of this project will suit students with good mathematical capabilities.

Supervisor: Dr Charles Cranfield, Co-supervisors A/Prof Stella Valenzuela and Prof Bruce Cornell (SDx Pty Ltd)

4. Creating bacterial, mammalian and fungal tethered lipid bilayer models. This project aims to create tethered bilayers using actual lipids from bacteria mammalian and fungal sources. These membranes can then be used to test new antimicrobial peptides. To ensure the validity of these membrane models, they will need to be tested using ablative mass spectroscopy techniques. As well as impedance spectroscopy, the student will receive training in Mass Spectrometry techniques from Dr Matt Padula.

Supervisor: Dr Charles Cranfield, Co-supervisors Dr Matt Padula and Prof Bruce Cornell (SDx Pty Ltd)


A lipid membrane tethered to a gold electrode


30

Title Novel nano-structured materials for high power energy storage

Description Greenhouse gas emissions from the consumption of fossil fuels are causing

disastrous climate change and global warming. The research and development of

electric vehicles to replace conventional vehicles has emerged as a solution to this

imminent problem. The progress of battery technology plays a key role in the

development of electric vehicles. This proposed project addresses the issues by the

development of innovative nano-structured materials for next generation batteries

with high capability, high power density and excellent retention. In this project, a

series of novel structured will be synthesised from wet-chemistry method. The

resultant nano-structured materials will be characterised by advanced instrumental

analyses such as scanning electron microscopy (SEM), transmission electron

microscopy (TEM), nitrogen adsorption, small angle X-ray diffraction (SAXRD),

and small-angle X-ray scattering (SAXS) to determine the micro-structure. Their

electrochemical performance will be investigated for high-power energy systems,

including lithium ion batteries, sodium ion batteries, lithium sulphur batteries and

lithium air batteries. In particular, in situ analyses (XRD & TEM) will be conducted

to investigate the working principle of energy storage systems. This project will

benefit UTS and Australia in the research forefront of nanotechnology, materials

engineering, energy storage and applied chemistry.

Experimental

techniques

Material synthesis, characterization and electrochemical measurement.

Equipment used Internal: Furnace, oven, microwave oven, glovebox , X-ray diffraction (in situ),

Scanning Electron Microscope, Atomic Force Microscopy, Transmission electron

Microscopy. (Faculty of Science)

External: Neutron & Synchrotron X-ray diffraction (in situ), Transmission electron

Microscopy. (ANSTO, Synchrotron Mel., USyd)

Supervisor Hao LIU



31

Title New phthalocyanine complexes as photodynamic therapy agents

Description

Photodynamic therapy (PDT) is a procedure used as a treatment for cancer. PDT

utilises compounds that can react with molecular oxygen to produce cytotoxic reactive

oxygen species when irradiated with light. The reactive oxygen species cause damage

to tumour cells and can lead to cell death.

Photosensitisers are typically strongly coloured compounds (to absorb plenty of light)

and so phthalocyanine compounds are an ideal choice.

An example of a metal-containing phthalocyanine (RuPc).

This project involves the synthesis of new phthalocyanine complexes that have

potential as PDT agents. To do this, ligands will be attached to the complex that enable

the complex be absorbed, distributed and eliminated from the body.

The synthetic methods will rely on organic techniques but will be coupled with

inorganic coordination chemistry. The project will utilise NMR spectroscopy together

with other techniques to characterize the new compounds.

Name of

supervisor(s)

Dr Andrew McDonagh



32

Title New Metal and Metal Oxide Core/Shell Nanoparticles

Description

In this project, nanoparticles containing metal oxide cores coated with gold will be investigated.

The particles will then be examined by ablating them with a laser and analysing the masses of

the ablated materials under various conditions.

Background: Nanoparticles made of gold have proven to be extremely valuable as probes to

visualise important, individual features within biological specimens. However, if multiple

targets are to be imaged, then a solid gold particle provides no means of distinguishing between

the targets. As a solution to this problem, core−shell structures may be used as extremely

sensitive bio-imaging probes if they possess an appropriate metal oxide core and gold shell.

Project outcomes: This project will result in new nanoparticles and new knowledge about the

laser ablation of the new particles under various conditions. The particles may be applied to

biological material to enable imaging of molecule/particle interactions as well as their

interaction with light.

Techniques Nanoparticle synthesis, molecular synthesis, measurement of optical properties, laser ablation,

mass spectrometry, scanning electron microscopy.

Name of supervisor(s) Dr Andrew McDonagh



33

Title Nitro-containing anti-cancer lipids

.

Description

Populations with high dietary intakes of omega-3 polyunsaturated fatty acids (ω-3

PUFAs) found in oily fish have lower incidents and fatalities from breast cancer. The

anticancer activity of ω-3 PUFAS have been further established in experimental and

animal models of breast cancer. The primary way in which PUFAs influence cancer

progression is through their metabolic conversion by enzymes in the body to

biologically active molecules.

Our research group (UTS and Prof. Michael Murray at the University of Sydney)

recently discovered an ω-3 PUFA metabolite with anticancer activity that we proposed

was responsible for the beneficial effects of ω-3 PUFA against breast cancer. Using

this metabolite as a starting point for a drug discovery program, we have developed a

novel class of anticancer drug (see figure) that kills breast cancer cells and shrinks

tumor size and volume in mouse models of breast cancer. We have found that electron

withdrawing groups, such as CF3, attached to the phenyl ring improves cancer killing

ability.

To produce more active molecules we would like to synthesise analogues bearing very

strongly electron withdrawing nitro groups, however we are unable to prepare these

compounds using our current synthetic methods. This project will explore new

methods to synthesie these compounds and prepare a small series of nitro-containing

analogues. The breast cancer cell killing ability of the new compounds will be assessed

by our partners at the University of Sydney.

OH

O

N N

O

H H

NO2

Supervisor Dr Tristan Rawling



34

Title Atomistic simulations on graphene-based materials for hydrogen storage and in

Li-ion batteries

Description

Graphene was experimentally fabricated for the first time in 2004 and was found with

excellent electrical, mechanical and thermal properties. Graphene has shown

promising applications as ultra-sensitive gas sensors, transparent electrodes in liquid

crystal display devices, large capacity electrodes in Li-ion batteries and hydrogen

storage materials. In this project, to further explore graphene applications in electronic

devices, especially in Li-ion batteries, and hydrogen storage materials, atomistic

simulation method (using Materials Studio software and other first principle

calculation softwares) is used to predict the electronic and magnetic properties of

graphene in the presence of substrates and different kinds of defects, the interaction

between hydrogen or Li-ion and graphene related materials, then to determine the

hydrogen storage behaviors or the performance of Li-ion batteries.

Hydrogen storage in 3D graphene structure

Supervisors Dr. Zhimin Ao and Prof. Guoxiu Wang



35

Title An investigation into ion suppression in quantitative tandem mass

spectrometry:

Project Description Tandem mass spectrometry coupled to high performance liquid chromato-

graphy (HPLC) has seen increasing use in bioanalysis in Pathology

laboratories worldwide in recent years. It has one “Achilles heel” however

and that is the occurrence of ion suppression.

Tandem mass spectrometers have an ion source where the eluent from the

HPLC is evaporated and the compounds of interest are charged, prior to

entering the mass spectrometer proper. During ionisation, the presence of

other co-eluting compounds has been shown to influence the ionisation of

the analyte/s, resulting in poor quantitation. One approach to this has been

the use of stable isotopes as internal standards, to normalise for ion

suppression. Stable isotopes frequently have to be prepared by custom

synthesis, making their cost prohibited, or in some cases they are unable to

be prepared in this manner at all. In other cases, even the use of stable

isotopes does not normalise for this phenomenon. Another approach is to

use more extensive sample preparation, but this adds cost and takes time,

extending turn-around times for assay results.

A better understanding of ion suppression and the factors that cause and/or

influence it may lead to approaches that expedite bioanalysis and

substantially reduce the cost. This project will address this issue.

Supervisors Dr Alison Beavis, UTS

Dr Ross Norris, Scientific Head, Pharmacology & Toxicology

St Vincent's Hospital


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