Developments and applications of the aluminium-[18F]fluoride method for biomolecule radiolabelling

The development of novel methods to efficiently synthesise new radiotracers is an active area of research in nuclear medicine. One major advancement is the development of the aluminium-[18F]fluoride ([18F]AlF) method, which has enabled facile and efficient radiofluorination reactions. The [18F]AlF2+ complex, described as a pseudo-radiometal, combines the convenience of radiometal-based synthetic approaches with the favourable decay characteristics of fluorine-18. These advantages have led to the widespread implementation of the [18F]AlF method for producing new radiotracers, with an array of clinical trials already being reported. This thesis aims to further expand on the applications of the [18F]AlF method and develop new approaches to allow its incorporation into biomolecules. Firstly, the utility of the [18F]AlF method in enabling facile 18F-labelling of microbubbles was developed to enable their whole-body distributions to be tracked. An [18F]AlF-labelled tetrazine was synthesised in excellent radiochemical yield and used to radiolabel trans-cyclooctene-functionalised microbubbles via the efficient inverse-electron-demand Diels-Alder (IEDDA) reaction. To further improve the accessibility of 18F-labelled microbubbles, a kit-based approach was successfully developed. This approach allows microbubbles to be radiolabelled with minimal radiochemical expertise, which potentially facilitates the development of new lipid-based microbubble formulations. In addition, the [18F]AlF-labelled microbubbles were also successfully applied for evaluating the effects ultrasound-mediated microbubble destruction and sonoporation in enhancing the delivery of radioactivity to tumours, further demonstrating the utility of the [18F]AlF method in enabling different biological phenomena to be studied. This thesis also investigated the potential to improve on the current [18F]AlF-labelling methodologies. To facilitate [18F]AlF-labelling under milder conditions, the development of new chelators was undertaken. Whilst initial studies using aluminium-salen complexes showed their potential for 18F-labelling, conclusive evidence on the formation of an Al-F bond was not obtained, necessitating further optimisation of the ligand structure and fluorination conditions. Finally, the ability to site-selectively radiolabel biomolecules by [18F]AlF was explored using the π-clamp-mediated cysteine conjugation method. Two approaches were developed: (i) a prosthetic group approach, and (ii) a direct [18F]AlF-labelling approach. Both approaches demonstrated the utility of the [18F]AlF method to be used for site-selectively radiolabelling octreotate as the model peptide, providing the potential for translation to larger biomolecules. In summary, the work presented herein provides an extension to the current toolkit of radiolabelling microbubbles and biomolecules using the [18F]AlF method, which ultimately seeks to expand on the available strategies for producing new radiotracers.Open Acces

Development Of Bismuth Nanoparticles For Lead And Cadmium Sensors Application

In this study, bismuth nanoparticles (BiNPs) were synthesized using the hydrothermal method and deposited on Indium Tin Oxide (ITO) electrodes to modify the electrodes. Several synthesis parameters were studied: the effect of hydrothermal reaction period, the effect of volume of hydrazine hydrate and the effect of reaction temperature. The properties of BiNPs were then characterized using X-ray Diffractometer (XRD), Scanning Electron Microscope (SEM) and Transmission Electron Microscopy (TEM). XRD analysis proved that pure bismuth with Rhombohedral structure of R-3m space group (ICDD Reference Code: 98-002-1658) was obtained for all samples. The synthesized BiNPs powders were in the size range of 73.0 nm to 150.0 nm with varying hydrothermal synthesis parameters. The synthesized BiNPs were then drop-casted on ITO electrodes, air dried and subjected to cyclic voltammetry (CV) and differential pulse anodic stripping voltammetry (DPASV) analyses. The BiNPs/ITO modified electrodes showed good performance in terms of detecting heavy metals with limit of detection of 2.5 μg/L for Pb(II). Besides, with 0.1 wt.% of Nafion solution, the BiNPs/ITO electrode was successfully applied for simultaneous detection of Pb(II) and Cd(II) for the interference studies. Finally, the BiNPs/ITO electrode was successfully applied to the practical use for the determination of Pb(II) in seawater sample. The results showed that BiNPs modified electrodes can be used for heavy metals sensors

Credential hardening by using touchstroke dynamics

Today, reliance on digital devices for daily routines has been shifted towards portable mobile devices. Therefore, the need for security enhancements within this platform is imminent. Numerous research works have been performed on strengthening password authentication by using keystroke dynamics biometrics, which involve computer keyboards and cellular phones as input devices. Nevertheless, experiments performed specifically on touch screen devices are relatively lacking. This paper describes a novel technique to strengthen security authentication systems on touch screen devices via a new sub variant behavioural biometrics called touchstroke dynamics. We capitalize on the high resolution timing latency and the pressure information on touch screen panel as feature data. Following this a light weight algorithm is introduced to calculate the similarity between feature vectors. In addition, a fusion approach is proposed to enhance the overall performance of the system to an equal error rate of 7.71% (short input) and 6.27% (long input)

MetaFun: Meta-Learning with Iterative Functional Updates

We develop a functional encoder-decoder approach to supervised meta-learning, where labeled data is encoded into an infinite-dimensional functional representation rather than a finite-dimensional one. Furthermore, rather than directly producing the representation, we learn a neural update rule resembling functional gradient descent which iteratively improves the representation. The final representation is used to condition the decoder to make predictions on unlabeled data. Our approach is the first to demonstrates the success of encoder-decoder style meta-learning methods like conditional neural processes on large-scale few-shot classification benchmarks such as miniImageNet and tieredImageNet, where it achieves state-of-the-art performance

HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?

AIMS: Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser. METHODS: The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations. RESULTS: The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia. CONCLUSION: The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level

Posttraumatic Pseudoaneurysm in Scalp Treated by Direct Puncture Embolization Using N-Butyl-2-Cyanoacrylate: a Case Report

Here, we report a case of scalp pseudoaneurysm which was treated by direct puncture embolization using n-butyl-2-cyanoacrylate. The patient had a history of blunt trauma in the previous two months. Ultrasound-guided manual compression was initially attempted, but the results were unsatisfactory. Direct puncture embolization was then performed, and the pseudoaneurysm was completely obliterated. Non-surgical treatment options for pseudoaneurysm are briefly discussed

Concurrent inheritance of deletional a-thalassaemia in Malays with HbE trait

Introduction: HbE is the commonest beta haemoglobin (Hb) variant in Southeast Asia. It causes a reduction in synthesis of the beta-globin E chain. Studies indicate HbE coinherited with a-thalassaemia leads to milder clinical phenotype. This study investigates the commitant inheritance of a-thalassaemia in Malays with HbE. Methods: Four hundred and fourteen (414) blood samples were screened for haemoglobinopathy using primarily the first three steps of the BHES [ (B) blood counts, blood film; (H), HPLC; (E) electrophoresis; (S), stability ] protocol. Complete blood cell analyser, Hb typing with cation exchange high-performance liquid chromatography (HPLC) and Hb electrophoresis at an alkaline pH (pH 8.5) Forty-five (10.9%) were identified as HbE trait and DNA analysis was done for deletional a-thalassaemia using a single-tube multiplex-PCR assay. Results: Among the 45 subjects with HbE trait, 4 (8.9%) were found to have alpha-thalassaemia -2 (a) (a-37 kb deletion) and 1 (2.2%) the alpha-thalassaemia-1 (a0) (---SEA 20.5 kb deletion) defects respectively. Discussion: These findings show that 11.1% of Malays with HbE inherit alpha-thalassaemia concurrently. The most prevalent interaction found was a double heterozygote for HbE /a-thalassaemia 2, followed by HbE/a-thalassaemia 1. Conclusion: Molecular screening of deletional a-thalassaemia identified its concurrent inheritance in 11.1%o of Malays who were HbE carriers. This information will guide genetic counseling and the planning of treatment modalities in patients with HbE alpha-thalassaemia