Applications of monolithic solid-phase extraction in chromatography-based clinical chemistry assays

Complex matrices, for example urine, serum, plasma, and whole blood, which are common in clinical chemistry testing, contain many non-analyte compounds that can interfere with either detection or in-source ionization in chromatography-based assays. To overcome this problem, analytes are extracted by protein precipitation, solid-phase extraction (SPE), and liquid–liquid extraction. With correct chemistry and well controlled material SPE may furnish clean specimens with consistent performance. Traditionally, SPE has been performed with particle-based adsorbents, but monolithic SPE is attracting increasing interest of clinical laboratories. Monoliths, solid pieces of stationary phase, have bimodal structures consisting of macropores, which enable passage of solvent, and mesopores, in which analytes are separated. This structure results in low back-pressure with separation capabilities similar to those of particle-based adsorbents. Monoliths also enable increased sample throughput, reduced solvent use, varied support formats, and/or automation. However, many of these monoliths are not commercially available. In this review, application of monoliths to purification of samples from humans before chromatography-based assays will be critically reviewed.     

BPHZ renormalization of λφ4 field theory in curved spacetime

A proof is given to all orders in perturbation theory of the renormalizability of λφ⁴ field theory in curved spacetime. The proof is based on the BPHZ definition of a renormalized Feynman integrand and uses dimensional regularization to ensure that products of Feynman propagators are well-defined distributions. The explicit structure of the pole terms in the Feynman integrand is obtained using a local momentum space representation of the Feynman propagator and is shown to be of a form which can be cancelled by counterterms in the scalar field Lagrangian. The proof given is, technically, only valid for metrics which have been analytically continued to Euclidean (++++) signature.     

Determination of pharmaceutical compounds in skin by imaging matrix-assisted laser desorption/ionisation mass spectrometry

Matrix-assisted laser desorption/ionisation (MALDI) quadrupole time-of-flight mass spectrometry (Q-TOFMS) has been used to detect and image the distribution of a xenobiotic substance in skin. Porcine epidermal tissue was treated with 'Nizoral', a medicated shampoo containing ketoconazole (+/-)-1-acetyl-4-[p-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) as active ingredient. Following incubation for 1 h at 37 degrees C all excess formulation was washed from the surface. A cross-section of the drug-treated tissue was then blotted onto a cellulose membrane, precoated in matrix (alpha-cyano-4-hydroxycinnamic acid (CHCA)), by airspray deposition. In separate experiments the tissue surface was treated with Nizoral within a triangular former, and subsequently blotted onto a matrix-coated membrane. Sample membranes were then mounted into the recess of specialised MALDI targets with adhesive tape. All samples were analysed by MALDI-TOFMS using an Applied Biosystem 'Q-star Pulsar i' hybrid Q-TOF mass spectrometer fitted with an orthagonal MALDI ion source and imaging software. Detection of the protonated molecule was readily achievable by this technique. Treatment of the tissue within a template gave rise to images depicting the expected distribution of the drug, demonstrating that this technique is capable of producing spatially useful data. Ion images demonstrating the permeation of the applied compound into the skin were achieved by imaging a cross-sectional imprint of treated tissue. A calibration graph for the determination of ketoconazole was prepared using the sodium adduct of the matrix ion as an internal standard. This enabled construction of a quantitative profile of drug in skin. Conventional haematoxylin and eosin staining and microscopy methods were employed to obtain a histological image of the porcine epidermal tissue. Superimposing the mass spectrometric and histological images appeared to indicate drug permeation into the dermal tissue layer.     

A unified approach to the effects of symmetry and periodicity on boundary-value problems

A generalized approach to the effects of symmetry and periodicity on boundary-value problems is presented, especially as it pertains to the guiding structures encountered in electromagnetics. Several examples of structures and their dispersion behavior are given, and the theory predicts well that other authors claim.     

Imaging of Phospholipids in Formalin Fixed Rat Brain Sections by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a valuable tool for the analysis of molecules directly from tissue. Imaging of phospholipids is gaining widespread interest, particularly as these lipids have been implicated in a variety of pathologic processes. Formalin fixation (FF) is the standard protocol used in histology laboratories worldwide to preserve tissue for analysis, in order to aid in the diagnosis and prognosis of diseases. This study assesses MALDI imaging of phospholipids directly in formalin fixed tissue, with a view to future analysis of archival tissue. This investigation proves the viability of MALDI-MSI for studying the distribution of lipids directly in formalin fixed tissue, without any pretreatment protocols. High quality molecular images for several phosphatidylcholine (PC) and sphingomyelin (SM) species are presented. Images correspond well with previously published data for the analysis of lipids directly from freshly prepared tissue. Different ionization pathways are observed when analyzing fixed tissue compared with fresh, and this change was found to be associated with formalin buffers employed in fixation protocols. The ability to analyze lipids directly from formalin fixed tissue opens up new doors in the investigation of disease profiles. Pathologic specimens taken for histologic investigation can be analyzed by MALDI-MS to provide greater information on the involvement of lipids in diseased tissue.     

Decomposition of a symmetric matrix

Summary An algorithm is presented to compute a triangular factorization and the inertia of a symmetric matrix. The algorithm is stable even when the matrix is not positive definite and is as fast as Cholesky. Programs for solving associated systems of linear equations are included.The authors gratefully acknowledge research support from NSF grant MCS75-06510, NSF grant MCS75-23333, and ONR contract N00014-69-A-0200-1017, respectively     

Backward-wave interaction using step periodic structures

Periodicities introduced into hollow waveguides with step and turn symmetry are shown to have characteristics useful for backward-wave interaction in microwave electron tubes. Using Floquet's theorem, it is shown that the modes of a hollow waveguide can be shifted in phase over one period of the structure. Interaction with the shifted backward-wave mode is then possible over a range of frequencies. A gyrotron backward-wave oscillator is particularly suited to this structure; the interaction could be magnetically tuned over a range of frequencies, while a low phase constant is maintained. A lower phase constant allows the electron beam to interact coherently with the backward wave over longer distances, since any velocity spread in the electron beam forces some of the electrons to be out of step with the backward wave, thus reducing efficiency. A solid waveguide has the added advantages of being easily built for high frequencies and rugged for high temperatures.     

An investigation into density-wave propagation within high-temperature superconducting plasmas for use in creating traveling-wave devices

This paper theoretically investigates a novel application of high-temperature superconductors where the superconductor serves as the active component in a microwave or millimeter traveling-wave amplifier. A guided electromagnetic wave interacts with a dc superconducting electron current to set up charge-density gradients within the superconducting electron "plasma." The electromagnetic wave gradually extracts energy from the superconducting electrons by traveling in phase synchronism with these charge gradients. The interaction mechanism is similar to that of a conventional traveling-wave tube amplifier or oscillator. We have modeled the wave behavior of superconducting electrons using the London equations and a two-fluid approach. Our model includes dissipation within the superconductor, and it shows that traveling-wave devices may be possible using high-quality thin-film superconductors in which dissipation is kept low.     

Adhesion mechanics of graphene membranes

The interaction of graphene with neighboring materials and structures plays an important role in its behavior, both scientifically and technologically. The interactions are complicated due to the interplay between surface forces and possibly nonlinear elastic behavior. Here we review recent experimental and theoretical advances in the understanding of graphene adhesion. We organize our discussion into experimental and theoretical efforts directed toward: graphene conformation to a substrate, determination of adhesion energy, and applications where graphene adhesion plays an important role. We conclude with a brief prospectus outlining open issues.     

A pivoting strategy for symmetric tridiagonal matrices

The LBL^T factorization of Bunch for solving linear systems involving a symmetric indefinite tridiagonal matrix T is a stable, efficient method. It computes a unit lower triangular matrix L and a block 1 × 1 and 2 × 2 matrix B such that T=LBL^T. Choosing the pivot size requires knowing a priori the largest element σ of T in magnitude. In some applications, it is required to factor T as it is formed without necessarily knowing σ. In this paper, we present a modification of the Bunch algorithm that can satisfy this requirement. We demonstrate that this modification exhibits the same bound on the growth factor as the Bunch algorithm and is likewise normwise backward stable. Copyright © 2005 John Wiley & Sons, Ltd.