In Vivo Quantitative Study of Sized-Dependent Transport and Toxicity of Single Silver Nanoparticles Using Zebrafish Embryos

Nanomaterials possess distinctive physicochemical properties (e.g., small sizes and high surface area-to-volume ratios) and promise a wide variety of applications, ranging from the design of high quality consumer products to effective disease diagnosis and therapy. These properties can lead to toxic effects, potentially hindering advances in nanotechnology. In this study, we have synthesized and characterized purified and stable (nonaggregation) silver nanoparticles (Ag NPs, 41.6 ± 9.1 nm in average diameter) and utilized early developing (cleavage-stage) zebrafish embryos (critical aquatic and eco- species) as in vivo model organisms to probe the diffusion and toxicity of Ag NPs. We found that single Ag NPs (30-72 nm diameters) passively diffused into the embryos through chorionic pores via random Brownian motion and stayed inside the embryos throughout their entire development (120 hours-post-fertilization, hpf). Dose-and size-dependent toxic effects of the NPs on embryonic development were observed, showing the possibility of tuning biocompatibility and toxicity of the NPs. At lower concentrations of the NPs (≤0.02 nM), 75-91% of embryos developed into normal zebrafish. At the higher concentrations of NPs (≥0.20 nM), 100% of embryos became dead. At the concentrations in between (0.02-0.2 nM), embryos developed into various deformed zebrafish. Number and sizes of individual Ag NPs embedded in tissues of normal and deformed zebrafish at 120 hpf were quantitatively analyzed, showing deformed zebrafish with higher number of larger NPs than normal zebrafish and size-dependent nanotoxicity. By comparing with our previous studies of smaller Ag NPs (11.6 ± 3.5 nm), we found striking size-dependent nanotoxicity that, at the same molar concentration, the larger Ag NPs (41.6 ± 9.1 nm) are more toxic than the smaller Ag NPs (11.6 ± 3.5 nm)

Study of Charge-Dependent Transport and Toxicity of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos and Single Nanoparticle Plasmonic Spectroscopy

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs+ζ), negatively (Ag-CALNNS NPs−2ζ), and more negatively charged NPs (Ag-CALNNE NPs−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as a model molecule to create positive, neutral, and negative charges on the surface of the NPs at pH 4-10. We have studied their charge-dependent transport into early developing (cleavage-stage) zebrafish embryos and their effects on embryonic development using dark-field optical microscopy and spectroscopy (DFOMS). We found that all three Ag-peptide NPs passively diffused into the embryos via their chorionic pore canals, and stayed inside the embryos throughout their entire development (120 h), showing charge-independent diffusion modes and charge-dependent diffusion coefficients. Notably, the NPs create chargedependent toxic effects on embryonic development, showing that the Ag-CALNNK NPs+ζ (positively charged) are the most biocompatible while the Ag-CALNNE NPs−4ζ (more negatively charged) are the most toxic. By comparing with our previous studies of the same sized citrated Ag and Au NPs, the Ag-peptide NPs are much more biocompatible than the citrated Ag NPs, and nearly as biocompatible as the Au NPs, showing the dependence of nanotoxicity upon the surface charges, surface functional groups, and chemical compositions of the NPs. This study also demonstrates powerful applications of single NP plasmonic spectroscopy for quantitative analysis of single NPs in vivo and in tissues, and reveals the possibility of rational design of biocompatible NPs

Undrained expansion of a cylindrical cavity in clays with fabric anisotropy: theoretical solution

This paper presents a novel, exact, semi-analytical solution for the quasi-static undrained expansion of a cylindrical cavity in soft soils with fabric anisotropy. This is the first theoretical solution of the undrained expansion of a cylindrical cavity under plane strain conditions for soft soils with anisotropic behaviour of plastic nature. The solution is rigorously developed in detail, introducing a new stress invariant to deal with the soil fabric. The semianalytical solution requires numerical evaluation of a system of six first-order ordinary differential equations. The results agree with finite element analyses and show the influence of anisotropic plastic behaviour. The effective stresses at critical state are constant, and they may be analytically related to the undrained shear strength. The initial vertical cross-anisotropy caused by soil deposition changes towards a radial cross-anisotropy after cavity expansion. The analysis of the stress paths shows that proper modelling of anisotropic plastic behaviour involves modelling not only the initial fabric anisotropy but also its evolution with plastic straining.The research was initiated as part of GEO-INSTALL (Modelling Installation Effects in Geotechnical Engineering, PIAP-GA-2009-230638) and CREEP (Creep of Geomaterials, PIAP-GA-2011-286397) projects supported by the European Community through the programme Marie Curie Industry-Academia Partnerships and Pathways (IAPP) under the 7th Framework Programme

Infraorbital nerve schwannoma presenting as an upper lip mass in an adolescent boy

10.1097/SAP.0b013e318248b8a2Annals of Plastic Surgery712196-197APCS

EPR-based oximetric imaging : a combination of single point-based spatial encoding and T1 weighting

Purpose: Spin-lattice relaxation time (T1)-weighted time-domain EPR oximetry is reported for in vivo applications using a paramagnetic probe, a trityl-based Oxo71. Methods: The R1 dependence of the trityl probe Oxo71 on pO2 was assessed using single point imaging (SPI) mode of spatial encoding combined with rapid repetition, similar to T1-weighted MRI, where R1 was determined from 22 repetition times ranging from 2.1–40.0 μs at 300 MHz. The pO2 maps of a phantom with three tubes containing 2 mM Oxo71 solutions equilibrated at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin-spin relaxation rate (R2*) simultaneously. Results: The pO2 maps derived from R1 and R2* agreed with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2 revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The standard deviations of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1-based estimation than R2*-based estimation (mean ± SD: 13.9 ± 1.77 mmHg and 18.3 ± 8.70 mmHg, respectively). The in vivo pO2 map obtained from R1-based assessment displayed a homogeneous profile in low pO2 regions in tumor xenografts, consistent with previous reports on R2*-based oximetric imaging. The scan time to obtain the R1 map can be significantly reduced using three repetition times ranging from 4.0‒12.0 μs. Conclusion: Using the SPI modality, R1-based oximetry imaging with useful spatial and oxygen resolutions for small animals was demonstrated

The superior lateral genicular artery flap for reconstruction of knee and proximal leg defects

10.5999/aps.2021.01123Archives of Plastic Surgery491108-11

A novel technique in full thickness lower eyelid reconstruction: The pedicled reverse-flow chondrocutaneous superior helix flap

10.1007/s00238-011-0625-7European Journal of Plastic Surgery356469-474EJPS

Breast reconstruction rate and profile in a Singapore patient population: A national university hospital experience

10.11622/smedj.2017035Singapore Medical Journal596300-304SIMJ

Use of intraoperative frozen section in the surgical management of patients with nonmelanoma skin cancer

Journal of Skin Cancer20214944570

EPR‐based oximetric imaging: a combination of single point‐based spatial encoding and T1 weighting

Purpose: Spin‐lattice relaxation rate (R1)‐based time‐domain EPR oximetry is reported for in vivo applications using a paramagnetic probe, a trityl‐based Oxo71. Methods: The R1 dependence of the trityl probe Oxo71 on partial oxygen pressure (pO2) was assessed using single‐point imaging mode of spatial encoding combined with rapid repetition, similar to T1‐weighted MRI, for which R1 was determined from 22 repetition times ranging from 2.1 to 40.0 μs at 300 MHz. The pO2 maps of a phantom with 3 tubes containing 2 mM Oxo71 solutions equilibrated at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin–spin relaxation rate (R2*) simultaneously. Results: The pO2 maps derived from R1 and R2* agreed with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2 revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The SDs of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1‐based estimation than R2*‐based estimation (mean ± SD: 13.9 ± 1.77 mmHg and 18.3 ± 8.70 mmHg, respectively). The in vivo pO2 map obtained from R1‐based assessment displayed a homogeneous profile in low pO2 regions in tumor xenografts, consistent with previous reports on R2*‐based oximetric imaging. The scan time to obtain the R1 map can be significantly reduced using 3 repetition times ranging from 4.0 to 12.0 μs. Conclusion: Using the single‐point imaging modality, R1‐based oximetry imaging with useful spatial and oxygen resolutions for small animals was demonstrated