Melanocortin 1 receptor targeted imaging of melanoma with gold nanocages and positron emission tomography

Purpose: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. Method: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. Results: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. Conclusion: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics. </jats:sec

A Survey of Natural Language Generation

This paper offers a comprehensive review of the research on Natural Language Generation (NLG) over the past two decades, especially in relation to data-to-text generation and text-to-text generation deep learning methods, as well as new applications of NLG technology. This survey aims to (a) give the latest synthesis of deep learning research on the NLG core tasks, as well as the architectures adopted in the field; (b) detail meticulously and comprehensively various NLG tasks and datasets, and draw attention to the challenges in NLG evaluation, focusing on different evaluation methods and their relationships; (c) highlight some future emphasis and relatively recent research issues that arise due to the increasing synergy between NLG and other artificial intelligence areas, such as computer vision, text and computational creativity.Comment: Accepted by ACM Computing Survey (CSUR) 202

Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound

This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release

An enzyme-sensitive probe for photoacoustic imaging and fluorescence detection of protease activity

A gold nanocage and dye conjugate has been demonstrated for use with photoacoustic imaging and fluorescence detection of protease activity. The detection sensitivity could be maximized by using gold nanocages with a localized surface plasmon resonance peak away from the emission peak of the dye. These hybrids can be potentially used as multimodal contrast agents for molecular imaging.NIH[DP1 OD000798, P30 CA91842]; NCI[R01 CA13852701]; Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital; Washington University School of Medicine; China Scholarship Council; NSF[ECS-0335765

Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound

This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Gold nanocages and related nanostructures for plasmonic and biomedical applications

Gold nanocages and related nanostructures have shown great potential in applications ranging from catalysis to theranostics. To make full use of these nanomaterials, it is crucial for us to precisely control their size, shape, and structure, since their physiochemical properties are determined by these parameters. This dissertation is focused on the synthesis of Au nanocages and their derivatives for photonic and biomedical applications. I start with the synthesis of Cu-doped Au nanocages through the co-reduction of Au and Cu precursors in the presence of pre-synthesized Au nanocages, and then demonstrate their use as a PET tracer when 64Cu is involved. With the insights gained from this study, I carry out a systematic study to examine the deposition of Pd on Au nanocages, and reveal the relationship between the reduction kinetics of metal precursors and the deposition behaviors. In the third project, I demonstrate the synthesis of compact Au nanorattles with edge length as small as 15 nm, through a two-step procedure that combines the deposition of Au on Ag nanocubes to enhance their physical robustness and a galvanic reaction to complete the synthesis. Finally, I demonstrate the synthesis of Ag@Au core-sheath nanowires through the deposition of Au on Ag nanowires in a galvanic-free manner, in an effort to improve their stability against various oxidants. The mechanistic understanding achieved in this dissertation paves the road for the rational design and controlled synthesis of colloidal noble-metal nanomaterials with desired sizes, shapes, compositions, and structures.Ph.D

Self-assembly and encapsulation of metal nanoparticles

This thesis contains three parts. In the first part, magnetic nanoparticles (γ-Fe2O3, Fe3O4, fePt) were prepared, followed by phase-transferring into water. In presence of a hydrophobic surface ligand (2,3-naphthalenediol or oleic acid), amphiphilic block co-polymer (MagNPs) in a mixture solvent of H2O/DMF. With the help of small amount of alcohol, well-separated MagNPs can be encapsulated and separated by centrifugation. In the second part, a new type of polymer encapsulated Surface Enhanced Raman Scattering (SERS) label was developed. Au nanoparticles (AuNPs), Au nanorods (AuNRs), Ag nanoparticles (AgNPs) and Ag nanocubes (AgNCs) were prepared, on which a layer of hydrophobic Raman analytes were assembled. In presence of PS-b-PAA and water, micelles were formed around Au/Ag nanostructures. Three different molecules were used as Raman analytes and multiplexing were achieved. The polymer shell can protect the metal core from oxidation and aggregation; meanwhile provides a site for functionalization. SERS enhancement factors were estimated for different-sized Au/Ag nanoparticles. In the last part, AuNPs coated with 2- naphthalenediol were found to aggregate into linear chains in DMF/H2O mixture solutions in presence of acid (HCl) or salt (NaCl). With the help of PS-b-PAA, the linear AuNP chains can be encapsulated by forming micelles. The core shell structures can trap and retain the morphology of aggregated AuNPs at any time in solution, as well as ruling out the ambiguity caused by TEM preparation. The formation of the linear AuNPs chain was studied by TEM and UV-vis spectroscopy, and electrostatic repulsion was believed to be the main reason leading to the unique 1D aggregation.​Master of Scienc