Evaluation of the potential of Raman microspectroscopy for prediction of chemotherapeutic response to cisplatin in lung adenocarcinoma

The study of the interaction of anticancer drugs with mammalian cells in vitro is important to elucidate the mechanisms of action of the drug on its biological targets. In this context, Raman spectroscopy is a potential candidate for high throughput, non-invasive analysis. To explore this potential, the interaction of cis-diamminedichloroplatinum(II) (cisplatin) with a human lung adenocarcinoma cell line (A549) was investigated using Raman microspectroscopy. The results were correlated with parallel measurements from the MTT cytotoxicity assay, which yielded an IC(50) value of 1.2 ± 0.2 μM. To further confirm the spectral results, Raman spectra were also acquired from DNA extracted from A549 cells exposed to cisplatin and from unexposed controls. Partial least squares (PLS) multivariate regression and PLS Jackknifing were employed to highlight spectral regions which varied in a statistically significant manner with exposure to cisplatin and with the resultant changes in cellular physiology measured by the MTT assay. The results demonstrate the potential of the cellular Raman spectrum to non-invasively elucidate spectral changes that have their origin either in the biochemical interaction of external agents with the cell or its physiological response, allowing the prediction of the cellular response and the identification of the origin of the chemotherapeutic response at a molecular level in the cell.     

Developing and Maintaining an Equity Index Fund

An index fund is a portfolio of shares designed to replicate the investment performance of a market index. The index represents the behaviour of the market as a whole. This paper describes the selection of an index fund which minimizes expected tracking error. Using a multivariate model of returns on shares, a development of a univariate model by Taylor, the selection problem is formulated as a quadratic programme. The effects of various constraints on tracking error are demonstrated. Several policies for the readjustment of a fund are examined in the context of the differing objectives of fund managers. As a general rule, regular readjustment is shown to be a more expensive policy than irregular updating.     

Stress-intensity factors for a semi-infinite plane crack with a wavy front

The stress-intensity factors for a semi-infinite plane crack with a wavy front are determined when the crack faces are subjected to normal and shearing tractions. The results are derived using asymptotic methods and are valid to O(²) where =A/1; A is the amplitude and is the wavelength of the wavy front. The normal and shearing tractions are in the form of line loads parallel to the crack front.The results are then used to evaluate, in a qualitative manner, the growth characteristics of a semi-infinite plance crack with a wavy front under combined mode loading. This provides a possible explanation of crack front segmentation observed experimentally.     

Synthesis and Evaluation of GdIII‐Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate‐Specific Membrane Antigen

Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight Gd^III‐based PSMA‐targeted contrast agents containing one to three Gd^III chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging.     

A Three-Channel Spectrometer for Wide-Field Imaging of Anisotropic Plasmonic Nanoparticles

A three-channel spectrometer (3CS) based on a commercial digital camera was developed to distinguish among tens of large (>100 nm), anisotropic plasmonic particles with various shapes, orientations, and compositions on a surface simultaneously. Using band pass filters and polarizers, the contrast of 3CS images could be enhanced to identify specific orientation and composition characteristics of gold and gold-silver nanopyramids and as well as the direction of the longest arm of gold nanostars.     

Bond Index Funds — A Duration Approach

Index funds can be used by investment managers as a method of ensuring that their portfolio performs as well as the general market. Methods have been proposed for creating index funds for the stock market, and in this paper a method for creating an index fund for a sector of the bond market is suggested. The underlying indexing mechanism uses the duration moments of the portfolio to capture the various aspects of the sector and its response to changes in the yield curve. The initial results suggest that a relatively small basic set of bonds can be used to model the movements of a particular market segment.     

Synthesis of multimeric MR contrast agents for cellular imaging

We have prepared a series of molecular multimeric MR contrast agents for cell labeling that are easy to synthesize, relatively low molecular weight, and biocompatible. The relaxivities of the agents range from 17 to 85 mM(-1) s(-1). Cellular uptake is concentration dependent and viability is excellent. MR images of cell pellets reveal a marked increase in observed signal intensity.     

Mechanisms of ZnII-activated magnetic resonance imaging agents

We report on the mechanism of a series of Zn (II)-activated magnetic resonance contrast agents that modulate the access of water to a paramagnetic Gd (III) ion to create an increase in relaxivity upon binding of Zn (II). In the absence and presence of Zn (II), the coordination at the Gd (III) center is modulated by appended Zn (II) binding groups. These groups were systematically varied to optimize the change in coordination upon Zn (II) binding. We observe that at least one appended aminoacetate must be present as a coordinating group to bind Gd (III) and effectively inhibit access of water. At least two binding groups are required to efficiently bind Zn (II), creating an unsaturated complex and allowing access of water. (13)C isotopic labeling of the acetate binding groups for NMR spectroscopy provides evidence of a change in the metal coordination of these groups upon the addition of Zn (II) supporting our proposed mechanism of activation as presented.