Development of a polymer theranostic for prostate cancer

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where [similar]95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs

The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers

The present work demonstrates a novel strategy to synthesize orthogonally bio-engineered magnetonanohybrids (MNPs) through the design of versatile, biocompatible linkers whose structure includes: (i) a robust anchor to bind with metal-oxide surfaces; (ii) tailored surface groups to act as spacers and (iii) a general method to implement orthogonal functionalizations of the substrate via ``click chemistry''. Ligands that possess the synthetic generality of features (i)-(iii) are categorized as ``universal ligands''. Herein, we report the synthesis of a novel, azido-terminated poly(ethylene glycol) (PEG) silane that can easily self-assemble on MNPs through hetero-condensation between surface hydroxyl groups and the silane end of the ligand, and simultaneously provide multiple clickable sites for high density, chemoselective bio-conjugation. To establish the universal-ligand-strategy, we clicked alkyl-functionalized folate onto the surface of PEGylated MNPs. By further integrating a near-infrared fluorescent (NIRF) marker (Alexa-Fluor 647) with MNPs, we demonstrated their folate-receptor mediated internalization inside cancer cells and subsequent translocation into lysosomes and mitochondria. Ex vivo NIRF imaging established that the azido-PEG-silane developed in course of the study can effectively reduce the sequestration of MNPs by macrophage organs (viz. liver and spleen). These folate-PEG-MNPs were not only stealth and noncytotoxic but their dual optical and magnetic properties aided in tracking their whereabouts through combined magnetic resonance and optical imaging. Together, these results provided a strong motivation for the future use of the ``universal ligand'' strategy towards development of ``smart'' nanohybrids for theragnostic applications.

Determination of electric field at and near the focus of a cylindrical lens for applications in fluorescence microscopy

We present an explicit computable integral solution of the electric field generated at the focal region of a cylindrical lens. This representation is based on vectorial diffraction theory and further enables the computation of the system point spread function of a cylindrical lens. It is assumed that there is no back-scattering and the contribution from the evanescent field is negligible. Stationary phase approximation along with the Fresnel transmission coefficients are employed for evaluating the polarization dependent electric field components. Studies were carried out to determine the polarization effects and to calculate the system resolution. The effect of s -, p - and randomly polarized light is studied on the fixed sample (electric dipole is fixed in space). Proposed approach allows better understanding of electric field effects at the focus of a cylindrical aplanatic system. This opens up future developments in the field of fluorescence microscopy and optical imaging. (C) 2013 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.

High speed digital holographic interferometry for hypersonic flow visualization

Optical imaging techniques have played a major role in understanding the flow dynamics of varieties of fluid flows, particularly in the study of hypersonic flows. Schlieren and shadowgraph techniques have been the flow diagnostic tools for the investigation of compressible flows since more than a century. However these techniques provide only the qualitative information about the flow field. Other optical techniques such as holographic interferometry and laser induced fluorescence (LIF) have been used extensively for extracting quantitative information about the high speed flows. In this paper we present the application of digital holographic interferometry (DHI) technique integrated with short duration hypersonic shock tunnel facility having 1 ms test time, for quantitative flow visualization. Dynamics of the flow fields in hypersonic/supersonic speeds around different test models is visualized with DHI using a high-speed digital camera (0.2 million fps). These visualization results are compared with schlieren visualization and CFD simulation results. Fringe analysis is carried out to estimate the density of the flow field.

Environments of extended radio sources in the Australia Telescope Low-Brightness Survey

We present a study of the environments of extended radio sources in the Australia Telescope Low-Brightness Survey (ATLBS). The radio sources were selected from the ATLBS Extended Source Sample, which is a well defined sample containing the most extended of radio sources in the ATLBS sky survey regions. The environments were analysed using 4-m Cerro-Tololo Inter-American Observatory Blanco telescope observations carried out for ATLBS fields in the Sloan Digital Sky Survey r(') band. We have estimated the properties of the environments using smoothed density maps derived from galaxy catalogues constructed using these optical imaging data. The angular distribution of galaxy density relative to the axes of the radio sources has been quantified by defining anisotropy parameters that are estimated using a new method presented here. Examining the anisotropy parameters for a subsample of extended double radio sources that includes all sources with pronounced asymmetry in lobe extents, we find good evidence for environmental anisotropy being the dominant cause for lobe asymmetry in that higher galaxy density occurs almost always on the side of the shorter lobe, and this validates the usefulness of the method proposed and adopted here. The environmental anisotropy parameters have been used to examine and compare the environments of Fanaroff-Riley Class I (FRI) and Fanaroff-Riley Class II (FRII) radio sources in two redshift regimes (z < 0.5 and z > 0.5). Wide-angle tail sources and head-tail sources lie in the most overdense environments. The head-tail source environments (for the HT sources in our sample) display dipolar anisotropy in that higher galaxy density appears to lie in the direction of the tails. Excluding the head-tail and wide-angle tail sources, subsamples of FRI and FRII sources from the ATLBS appear to lie in similar moderately overdense environments, with no evidence for redshift evolution in the regimes studied herein.

Deformation field heterogeneity in punch indentation

Plastic heterogeneity in indentation is fundamental for understanding mechanics of hardness testing and impression-based deformation processing methods. The heterogeneous deformation underlying plane-strain indentation was investigated in plastic loading of copper by a flat punch. Deformation parameters were measured, in situ, by tracking the motion of asperities in high-speed optical imaging. These measurements were coupled with multi-scale analyses of strength, microstructure and crystallographic texture in the vicinity of the indentation. Self-consistency is demonstrated in description of the deformation field using the in situ mechanics-based measurements and post-mortem materials characterization. Salient features of the punch indentation process elucidated include, among others, the presence of a dead-metal zone underneath the indenter, regions of intense strain rate (e. g. slip lines) and extent of the plastic flow field. Perhaps more intriguing are the transitions between shear-type and compression-type deformation modes over the indentation region that were quantified by the high-resolution crystallographic texture measurements. The evolution of the field concomitant to the progress of indentation is discussed and primary differences between the mechanics of indentation for a rigid perfectly plastic material and a strain-hardening material are described.

Detection of quantum well induced single degenerate-transition-dipoles in ZnO nanorods

Quantifying and characterising atomic defects in nanocrystals is difficult and low-throughput using the existing methods such as high resolution transmission electron microscopy (HRTEM). In this article, using a defocused wide-field optical imaging technique, we demonstrate that a single ultrahigh-piezoelectric ZnO nanorod contains a single defect site. We model the observed dipole-emission patterns from optical imaging with a multi-dimensional dipole and find that the experimentally observed dipole pattern and model-calculated patterns are in excellent agreement. This agreement suggests the presence of vertically oriented degenerate-transition-dipoles in vertically aligned ZnO nanorods. The HRTEM of the ZnO nanorod shows the presence of a stacking fault, which generates a localised quantum well induced degenerate-transition-dipole. Finally, we elucidate that defocused wide-field imaging can be widely used to characterise defects in nanomaterials to answer many difficult questions concerning the performance of low-dimensional devices, such as in energy harvesting, advanced metal-oxide-semiconductor storage, and nanoelectromechanical and nanophotonic devices.

Coral Remote Sensing Workshop: Proceedings and Recommendations, 17-18 September, Sheraton, Brickell Ave, Miami FL

Coral reefs exist in warm, clear, and relatively shallow marine waters worldwide. These complex assemblages of marine organisms are unique, in that they support highly diverse, luxuriant, and essentially self-sustaining ecosystems in otherwise nutrient-poor and unproductive waters. Coral reefs are highly valued for their great beauty and for their contribution to marine productivity. Coral reefs are favorite destinations for recreational diving and snorkeling, as well as commercial and recreational fishing activities. The Florida Keys reef tract draws an estimated 2 million tourists each year, contributing nearly $800 million to the economy. However, these reef systems represent a very delicate ecological balance, and can be easily damaged and degraded by direct or indirect human contact. Indirect impacts from human activity occurs in a number of different forms, including runoff of sediments, nutrients, and other pollutants associated with forest harvesting, agricultural practices, urbanization, coastal construction, and industrial activities. Direct impacts occur through overfishing and other destructive fishing practices, mining of corals, and overuse of many reef areas, including damage from souvenir collection, boat anchoring, and diver contact. In order to protect and manage coral reefs within U.S. territorial waters, the National Oceanic and Atmospheric Administration (NOAA) of the U.S. Department of Commerce has been directed to establish and maintain a system of national marine sanctuaries and reserves, and to monitor the condition of corals and other marine organisms within these areas. To help carry out this mandate the NOAA Coastal Services Center convened a workshop in September, 1996, to identify current and emerging sensor technologies, including satellite, airborne, and underwater systems with potential application for detecting and monitoring corals. For reef systems occurring within depths of 10 meters or less (Figure 1), mapping location and monitoring the condition of corals can be accomplished through use of aerial photography combined with diver surveys. However, corals can exist in depths greater than 90 meters (Figure 2), well below the limits of traditional optical imaging systems such as aerial or surface photography or videography. Although specialized scuba systems can allow diving to these depths, the thousands of square kilometers included within these management areas make diver surveys for deeper coral monitoring impractical. For these reasons, NOAA is investigating satellite and airborne sensor systems, as well as technologies which can facilitate the location, mapping, and monitoring of corals in deeper waters. The following systems were discussed as having potential application for detecting, mapping, and assessing the condition of corals. However, no single system is capable of accomplishing all three of these objectives under all depths and conditions within which corals exist. Systems were evaluated for their capabilities, including advantages and disadvantages, relative to their ability to detect and discriminate corals under a variety of conditions. (PDF contains 55 pages)

强散射体产生的像面散斑对比度与随机表面及成像系统关系的研究

We study the statistical properties of the image speckles produced by strong-scattering objects in the 4f optical imaging system. Using the generic expression of the complex amplitude of speckles and the approximation of the double-exponential function, we first obtain the ensemble average of the speckle intensity. Then we derive the variance of the speckle intensity based on the rotational transformation of the real and imaginary parts of the complex amplitude of speckles. We finally obtain the expression for the contrast of the. speckles, which is explicitly related to the statistical parameters of random surface and to the parameters of the imaging system. Our results are an obvious improvement compared with those reported in the literature, where the relations including such implicit quantities as the average size of the scattering grains of the random surface and the number of scattering grains are usually used. The results of this paper would be helpful for the characterization of random surface by speckle contrast.

超分辨远场生物荧光成像——突破光学衍射极限

长期以来,远场光学荧光显微镜凭借其非接触、无损伤、可探测样品内部等优点,一直是生命科学中最常用的观测工具。但由于衍射极限的存在,使传统的宽场光学显微镜横向和纵向的分辨率分别仅约为230 nm和1000 nm。为了揭示细胞内分子尺度的动态和结构特征,提高光学显微镜分辨率成为生命科学发展的迫切要求,在远场荧光显微镜的基础上,科学家们已经发展出许多实用的提高分辨率甚至超越分辨率极限的成像技术。例如,采用横向结构光照明提高横向分辨率到约100 nm,利用纵向驻波干涉效应将纵向分辨率提高5~10倍。然而,直到在光学荧光显微镜中引入非线性效应后,衍射极限才被真正突破,如受激荧光损耗显微镜利用非线性效应实现了30~50 nm的三维分辨率。另外应用荧光分子之间能量转移共振原理以及单荧光分子定位技术也可以突破衍射极限,甚至可以将分子定位精度提高到几个纳米的量级。

自由空间激光远距离传输的地面模拟研究

根据透镜的傅里叶变换性质，提出了采用光学傅里叶变换加级联光学成像放大并结合有限口径接收的方法来实现自由空间激光光束远距离传输的实验室模拟。由此原理设计了自由空间激光远距离传输模拟装置，该装置主要由大口径、长焦距的傅里叶变换平行光管和三级成像放大镜所组成，最大等效传输距离达2.4×10^5km，可用于星间激光通信终端综合通信性能的评估，在设定的误码率下测量终端可能的通信距离，或者在设定的作用通信距离下检测通信的误码率。

Three-dimensional superresolution by three-zone complex pupil filters

Complex pupil filters are introduced to improve the three-dimensional resolving power of an optical imaging system. Through the design of the essential parameters of such filters, the transmittance and radius of the first zone, three-dimensional superresolution is realized. The Strehl ratio and the transverse and axial gains of such filters are analyzed in detail. A series of simulation examples of such filters are also presented that prove that three-dimensional superresolution can be realized. The advantage of such filters is that it is easy to realize three-dimensional superresolution, and the disadvantage is that the sidelobes of the axial intensity distribution are too high. But this can be overcome by the application of a confocal system. (C) 2005 Optical Society of America.

复振幅光瞳滤波器的三维超分辨性能研究

超分辨技术中现有的纯振幅型或纯相位型光瞳滤波器，大部分只能实现轴向或横向超分辨而不能实现三维超分辨，三维超分辨在三维成像系统中有着重要的作用。因此为提高成像系统中的三维分辨能力，设计了一种复振幅光瞳滤波器，并对其三维超分辨性能进行了研究。详细分析了该光瞳滤波器的第一区半径和透射率对施特雷尔比、轴向和横向超分辨因子以及旁瓣能量的影响。通过一系列的模拟证明，借助于复振幅光瞳滤波器可以实现三维超分辨。该滤波器的优点是容易实现三维超分辨，且有比较高的施特雷尔比，缺点是三维超分辨的实现总是伴随着旁瓣能量的增加，但可

Dynamic readout of subdiffraction-limited pit arrays with a silver superlens

Recent theoretical and experimental results suggested that the silver superlens could be constructed through controlling silver thin film thickness and preparation conditions, and applied in subdiffraction-limited optical imaging and optical lithography. In this work, we report another significant application of silver superlens-ultrahigh density optical data storage. With the silver superlens the subdiffraction-limited pit arrays on an optical disk are dynamically read out and the carrier-to-noise ratio can reach 25 dB for the thin film thickness of 46 nm. The readout laser power and readout velocity have little effect on the carrier-to-noise ratio. Additionally, in our experiment the silver thin film thickness needs to be controlled in the range from 20 to 80 nm.