Improved detection of drug cytotoxicity in the soft agar colony formation assay through use of a metabolizable tetrazolium salt

Use of a metabolizable tetrazolium salt was observed to facilitate assessments of tumor cell drug sensitivity in the soft-agar colony formation assay. Enzyme-mediated staining permits discrimination between viable and non-viable groups of cells so that drug-induced cytotoxicity is clearly identifiable by visual inspection as well as by computerized image analysis. The technique appears to be especially useful in the evaluation of primary tumor cell cultures which often contain substantial numbers of non-viable cellular aggregates.     

Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb

Skeletal muscle fiber and architectural properties both contribute to the functional behavior of a muscle. This study uses discriminant analysis and mathematical modeling to identify the structurally and functionally significant properties. The architectural properties of fiber length, muscle length, and pennation angle are found to be the most structurally significant parameters, whereas fiber length, muscle length, and fiber type distribution are found to be most functionally determining. Architectural speed and fiber type do not appear to be complimentary (i.e., the architectural determinant of sspeed, fiber length, is not associated with fibers of high intrinsic velocity). However, there does seem to be a synergistic relation between the two property classes and force production. Muscles with large physiological cross sectional areas (PCSAs) tend to contain a greater proportion of larger, faster fibers. Structurally or morphologically significant parameters are not always found to have a large functional effect. Pennation angle, though one of the most structurally significant variables, was found to have very little functional effect. © 1994 Wiley-Liss, Inc.     

Solvent interaction analysis as a proteomic approach to structure-based biomarker discovery and clinical diagnostics

Proteins have several measurable features in biological fluids that may change under pathological conditions. The current disease biomarker discovery is mostly based on protein concentration in the sample as the measurable feature. Changes in protein structures, such as post-translational modifications and in protein–partner interactions are known to accompany pathological processes. Changes in glycosylation profiles are well-established for many plasma proteins in various types of cancer and other diseases. The solvent interaction analysis method is based on protein partitioning in aqueous two-phase systems and is highly sensitive to changes in protein structure and protein–protein- and protein–partner interactions while independent of the protein concentration in the biological sample. It provides quantitative index: partition coefficient representing changes in protein structure and interactions with partners. The fundamentals of the method are presented with multiple examples of applications of the method to discover and monitor structural protein biomarkers as disease-specific diagnostic indicators.     

The decomposition of apparent stresses in disturbed pulsatile flow in the presence of large scale organized structures

Flow disturbance phenomena that occur in unsteady-in-the-mean flows (i.e. pulsatile or oscillating) at moderate Reynolds numbers are analyzed in both the time domain and the frequency domain. The analysis utilizes variable decomposition into a time-varying underlying waveform and flow disturbances which are composed of large scale organized structures and random fluctuations. A practical technique which incorporates time domain phase conditioning, trend removal, and frequency domain matched filtering, is presented and examined using simulated data of known statistical behavior. The applicability of the method is shown by the decomposition of the simulated data and the technique is then applied to experimental data obtained in pulsatile flow through a constricted tube by means of a laser Doppler anemometer. The cross-sectional area reduction at the constriction throat was 90%. The Womersley parameter in the experiments was 5.3 and the Reynolds number based on the average flow rate per cycle was 300 with a minimum/maximum value of 55/600 based on the instantaneous flow rate. Measurements were taken in the flow region downstream of the constriction throat which included several interesting flow disturbance phenomena. The results of the decomposed flow phenomena demonstrate the significant role of large scale organized structures in such flows. This is particularly important when analyzing blood flow in the large arteries in the presence of severe stenosis or behind prosthetic devices in an attempt to estimate the 'turbulent' stress which act on cellular elements. Estimation of the apparent stress tensor is of importance in an effort to elucidate the mechanical factors which influence the durability of red blood cells under abnormal conditions.