Synthesis of nanomaterials for biomedical applications

The field of nanotechnology is growing vastly, both as a field of research and in commercial applications. This rapid growth calls for synthesis methods which can produce high quality nanomaterials, while being scalable. This thesis describes an investigation into the use of a continuous hydrothermal reactor for the synthesis of nanomaterials, with potential use in three different biomedical applications – bone scaffolds, fluorescent biomarkers, and MRI contrast agents. The first chapter of this thesis provides an overview of nanotechnology: the advantages of nanoscale, the commercial industries which can benefit, and the predominant methods currently used to produce nanomaterials. Some advantages and drawbacks of each synthesis route are given, concluding with a description of the Nozzle reactor – the patented technology used for nanomaterial synthesis in this Thesis. Chapter 2 then focusses on the characterisation techniques used in this thesis, detailing the principles of how data is obtained, as well as highlighting the limitations of each method. With the background information in place, chapters 3, 4 and 5 describe more specific nanomaterials and how they can be applied to each of the aforementioned biomedical fields. These chapters provide the technical details of how various nanomaterials can be synthesised using the Nozzle reactor, and the structural data (crystallinity, particle size) obtained from these samples. Furthermore, the functional properties of these nanomaterials are tested and the results, along with a discussion of any trends, are presented. Finally, this thesis concludes with a summary of the results described and emphasises the key areas where further work can be conducted

Synthesis of nanomaterials for biomedical applications

The field of nanotechnology is growing vastly, both as a field of research and in commercial applications. This rapid growth calls for synthesis methods which can produce high quality nanomaterials, while being scalable. This thesis describes an investigation into the use of a continuous hydrothermal reactor for the synthesis of nanomaterials, with potential use in three different biomedical applications – bone scaffolds, fluorescent biomarkers, and MRI contrast agents. The first chapter of this thesis provides an overview of nanotechnology: the advantages of nanoscale, the commercial industries which can benefit, and the predominant methods currently used to produce nanomaterials. Some advantages and drawbacks of each synthesis route are given, concluding with a description of the Nozzle reactor – the patented technology used for nanomaterial synthesis in this Thesis. Chapter 2 then focusses on the characterisation techniques used in this thesis, detailing the principles of how data is obtained, as well as highlighting the limitations of each method. With the background information in place, chapters 3, 4 and 5 describe more specific nanomaterials and how they can be applied to each of the aforementioned biomedical fields. These chapters provide the technical details of how various nanomaterials can be synthesised using the Nozzle reactor, and the structural data (crystallinity, particle size) obtained from these samples. Furthermore, the functional properties of these nanomaterials are tested and the results, along with a discussion of any trends, are presented. Finally, this thesis concludes with a summary of the results described and emphasises the key areas where further work can be conducted

Murine Surf4 is essential for early embryonic development

Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Heterozygous Surf4+/- mice exhibit grossly normal appearance, behavior, body weight, fecundity, and organ development, with no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol, and a detectable accumulation of intrahepatic apoliprotein B. Homozygous Surf4-/- mice exhibit embryonic lethality, with complete loss of all Surf4-/- offspring between embryonic days 3.5 and 9.5. In contrast to the milder murine phenotypes associated with deficiency of known SURF4 cargoes, the embryonic lethality of Surf4-/- mice implies the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development

Investigation on Photovoltaic Performance based on Matchstick-Like Cu2S–In2S3Heterostructure Nanocrystals and Polymer

In this paper, we synthesized a novel type II cuprous sulfide (Cu2S)–indium sulfide (In2S3) heterostructure nanocrystals with matchstick-like morphology in pure dodecanethiol. The photovoltaic properties of the heterostructure nanocrystals were investigated based on the blends of the nanocrystals and poly(2-methoxy-5-(2′-ethylhexoxy)-p-phenylenevinylene) (MEH-PPV). In comparison with the photovoltaic properties of the blends of Cu2S or In2S3nanocrystals alone and MEH-PPV, the power conversion efficiency of the hybrid device based on blend of Cu2S–In2S3and MEH-PPV is enhanced by ~3–5 times. This improvement is consistent with the improved exciton dissociation or separation and better charge transport abilities in type II heterostructure nanocrystals

Reabilitação protética da disfunção velofaríngea: prótese de palato e obturador faríngeo

The seed maturation program only occurs during late embryogenesis, and repression of the program is pivotal for seedling development. However, the mechanism through which this repression is achieved in vegetative tissues is poorly understood. Here we report a microRNA (miRNA)-mediated repression mechanism operating in leaves. To understand the repression of the embryonic program in seedlings, we have conducted a genetic screen using a seed maturation gene reporter transgenic line in Arabidopsis (Arabidopsis thaliana) for the isolation of mutants that ectopically express seed maturation genes in leaves. One of the mutants identified from the screen is a weak allele of ARGONAUTE1 (AGO1) that encodes an effector protein for small RNAs. We first show that it is the defect in the accumulation of miRNAs rather than other small RNAs that causes the ectopic seed gene expression in ago1. We then demonstrate that overexpression of miR166 suppresses the derepression of the seed gene reporter in ago1 and that, conversely, the specific loss of miR166 causes ectopic expression of seed maturation genes. Further, we show that ectopic expression of miR166 targets, type III homeodomain-leucine zipper (HD-ZIPIII) genes PHABULOSA (PHB) and PHAVOLUTA (PHV), is sufficient to activate seed maturation genes in vegetative tissues. Lastly, we show that PHB binds the promoter of LEAFY COTYLEDON2 (LEC2), which encodes a master regulator of seed maturation. Therefore, this study establishes a core module composed of a miRNA, its target genes (PHB and PHV), and the direct target of PHB (LEC2) as an underlying mechanism that keeps the seed maturation program off during vegetative development

Conditional Knockout of NMDA Receptors in Dopamine Neurons Prevents Nicotine-Conditioned Place Preference

Nicotine from smoking tobacco produces one of the most common forms of addictive behavior and has major societal and health consequences. It is known that nicotine triggers tobacco addiction by activating nicotine acetylcholine receptors (nAChRs) in the midbrain dopaminergic reward system, primarily via the ventral tegmental area. Heterogeneity of cell populations in the region has made it difficult for pharmacology-based analyses to precisely assess the functional significance of glutamatergic inputs to dopamine neurons in nicotine addiction. By generating dopamine neuron-specific NR1 knockout mice using cre/loxP-mediated method, we demonstrate that genetic inactivation of the NMDA receptors in ventral tegmental area dopamine neurons selectively prevents nicotine-conditioned place preference. Interestingly, the mutant mice exhibit normal performances in the conditioned place aversion induced by aversive air puffs. Therefore, this selective effect on addictive drug-induced reinforcement behavior suggests that NMDA receptors in the dopamine neurons are critical for the development of nicotine addiction

Probing and controlling fluorescence blinking of single semiconductor nanoparticles

In this review we present an overview of the experimental and theoretical development on fluorescence intermittency (blinking) and the roles of electron transfer in semiconductor crystalline nanoparticles. Blinking is a very interesting phenomenon commonly observed in single molecule/particle experiments. Under continuous laser illumination, the fluorescence time trace of these single nanoparticles exhibit random light and dark periods. Since its first observation in the mid-1990s, this intriguing phenomenon has attracted wide attention among researchers from many disciplines. We will first present the historical background of the discovery and the observation of unusual inverse power-law dependence for the waiting time distributions of light and dark periods. Then, we will describe our theoretical modeling efforts to elucidate the causes for the power-law behavior, to probe the roles of electron transfer in blinking, and eventually to control blinking and to achieve complete suppression of the blinking, which is an annoying feature in many applications of quantum dots as light sources and fluorescence labels for biomedical imaging

Synergistic repression of the embryonic programme by SET DOMAIN GROUP 8 and EMBRYONIC FLOWER 2 in Arabidopsis seedlings

The seed maturation programme occurs only during the late phase of embryo development, and repression of the maturation genes is pivotal for seedling development. However, mechanisms that repress the expression of this programme in vegetative tissues are not well understood. A genetic screen was performed for mutants that express maturation genes in leaves. Here, it is shown that mutations affecting SDG8 (SET DOMAIN GROUP 8), a putative histone methyltransferase, cause ectopic expression of a subset of maturation genes in leaves. Further, to investigate the relationship between SDG8 and the Polycomb Group (PcG) proteins, which are known to repress many developmentally important genes including seed maturation genes, double mutants were made and formation of somatic embryos was observed on mutant seedlings with mutations in both SDG8 and EMF2 (EMBRYONIC FLOWER 2). Analysis of histone methylation status at the chromatin sites of a number of maturation loci revealed a synergistic effect of emf2 and sdg8 on the deposition of the active histone mark which is the trimethylation of Lys4 on histone 3 (H3K4me3). This is consistent with high expression of these genes and formation of somatic embryos in the emf2 sdg8 double mutants. Interestingly, a double mutant of sdg8 and vrn2 (vernalization2), a paralogue of EMF2, grew and developed normally to maturity. These observations demonstrate a functional cooperative interplay between SDG8 and an EMF2-containing PcG complex in maintaining vegetative cell identity by repressing seed genes to promote seedling development. The work also indicates the functional specificities of PcG complexes in Arabidopsis

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe