Covalent attachment of the plant natural product naringenin to small glass and ceramic beads

Background  

Natural products have numerous medicinal applications and play important roles in the biology of the organisms that accumulate them. Few methods are currently available for identifying proteins that bind to small molecules, therefore the discovery of cellular targets for natural products with pharmacological activity continues to pose a significant challenge in drug validation. Similarly, the identification of enzymes that participate in the biosynthesis or modification of natural products remains a formidable bottleneck for metabolic engineering. Flavonoids are one large group of natural products with a diverse number of functions in plants and in human health. The coupling of flavonoids to small ceramic and glass beads provides a first step in the development of high-throughput, solid-support base approaches to screen complex libraries to identify proteins that bind natural products.     

Determination of boron in food and biological reference materials by neutron capture prompt-γ activation

Summary Boron concentrations were determined by in-beam neutron capture prompt- activation analysis for 31 food and biological reference materials prepared by the National Institute of Standards and Technology, Agriculture Canada, the National Institute for Environmental Studies of Japan, and the International Atomic Energy Agency. Sensitivity and background enhancements that are consequences of neutron scattering in hydrogenous matrices such as biological reference materials are discussed, as are correction methods for nuclide interferences, with emphasis on sodium. The limit of quantitation for these materials is 1.0–2.5 g/g and the limit of detection is 0.3–0.8 g/g, depending on the irradiation time. For materials with boron levels 30 g/g (e.g., most botanicals), the total analytical uncertainty is 2%.Temporary summer employment at the United States Food and Drug Administration, 200 C St., SW, Washington, DC 20204, USA     

Neutron irradiation in activation analysis: A new rabbit for the NBSR

Two radiochemical separation methods were developed for the separation of ⁸⁸Y from a SrS target (3.2 g, pressed into a 19 mm disc) and Al (2.5 g, the capsule contained the target). The first method was based on solvent extraction technique using undiluted TBP/HNO₃ system and the second was an extraction chromatography using a column packed with TBP-impregnated Amberlite XAD-4 resin. A simple procedure was used for the impregnation of the XAD-4 resin with TBP. For both methods concentrated nitric acid was used for extraction/adsorption and 2M HCl for back extraction/elution of ⁸⁸Y. In terms of recovery of ⁸⁸Y, the solvent (TBP)-impregnated resin showed better results (average 91.2% compared to 88.9% with extraction).     

Oscillatory modes in a nonlinear second-order differential equation with delay

Solution properties of the nonlinear second-order delay-differential equation x(t)=–ax(t)+f[x(t–)] are studied wheref is a piecewise constant function which mimics negative feedback. We show that the solutions can be obtained by a simple geometrical construction which, in principle, can be implemented using a ruler and a compass. Analytical results guarantee the existence and stability properties of limit cycle solutions. Computer-aided constructions reveal a remarkable richness of different types of dynamical behaviors including a variety of unconventional bifurcation schemes.     

Quantitative Prompt Gamma Analysis Using a Focused Cold Neutron Beam

We report the first quantitative results using a focused cold neutron beam for prompt gamma activation analysis (PGAA). We have measured the prompt gamma signal from known Fe, Cr, Ti, B, and Cd specimens in the focusing geometry, from which we determine the sensitivities for these elements by the method of standard addition. Furthermore, we show results of measurements for homogeneous standard reference materials (boron in SRM 611 glass, and iron and chromium in a steel alloy SRM 160b) to verify the sensitivities determined. Finally, we present a position-dependent study of the Cr to Fe mass ratio in an industrial material, taking advantage of the narrowly focused beam. Existing problems for achieving routine quantitative analysis using the focused beam and suggestions for future directions are discussed.     

Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry.

Tamoxifen is an antiestrogen drug used to treat breast cancer. We have extracted tamoxifen and several of its metabolites from urine of patients with both metastatic (stage IV) and locally confined (stages I, II, and III) breast cancer. Analysis of these metabolites was performed by nonaqueous capillary electrophoresis with electrospray-mass spectrometry. Peak heights from extracted ion current electropherograms of the metabolites were used to establish a metabolic profile for each patient. We demonstrate substantial variation among patient profiles, statistically significant differences in the amount of urinary tamoxifen N-oxide found in stages I, II, and III compared to stage IV breast cancer patients, and statistically significant differences in the amount of 3,4-dihydroxytamoxifen found in progressors compared to nonprogressors with metastatic (stage IV) cancer.     

Chemosensitization of Cancer Cells via Gold Nanoparticle‐Induced Cell Cycle Regulation

We have previously shown that plasmonic nanoparticles conjugated with nuclear‐targeting and cytoplasm‐targeting peptides (NLS and RGD, respectively) are capable of altering the cell cycle of human oral squamous carcinoma cells (HSC‐3). In the present work, we show that this regulation of the cell cycle can be exploited to enhance the efficacy of a common chemotherapeutic agent, 5‐Fluorouracil, by pretreating cells with gold nanoparticles. Utilizing flow cytometry cell cycle analysis, we were able to quantify the 5‐Fluorouracil efficacy as an accumulation of cells in the S phase with a depletion of cells in the G2/M phase. Two gold nanoparticle sizes were tested in this work; 30 nm with a surface plasmon resonance at 530 nm and 15 nm with a surface plasmon resonance at 520 nm. The 30 nm nuclear‐targeted gold nanoparticles (NLS‐AuNPs) showed the greatest 5‐Fluorouracil efficacy enhancement when 5‐Fluorouracil treatment (500 μm , 48 h) is preceded by a 24‐h treatment with nanoparticles. In conclusion, we show that nuclear‐targeted 30 nm gold nanoparticles enhance 5‐Fluorouracil drug efficacy in HSC‐3 cells via regulation of the cell cycle, a chemosensitization technique that could potentially be expanded to different cell lines and different chemotherapies.     

Angular derivatives on bounded symmetric domains

In this paper we generalise the classical Julia-Wolff-Carathéodory theorem to holomorphic functions defined on bounded symmetric domains. This work comprises part of the Ph.D. thesis [13] of the first author who gratefully acknowledges the support of Forbairt Basic Research grant SC/97/614.