Although it is relatively easy to perceive and report the sensation of discomfort caused by the presence of an offending light source of high luminance, no one has yet found a reliable objective correlate of discomfor...
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Although it is relatively easy to perceive and report the sensation of discomfort caused by the presence of an offending light source of high luminance, no one has yet found a reliable objective correlate of discomfort glare. In order to find an objectively measured correlate of discomfort glare, we have examined electrical activity associated with the two major facial muscles that surround the eye: the orbicularis oculi and the corrugator supercilii. We have made electromyographic (EMG) recordings using small silver-silver chloride electrodes applied to the skin above the muscles and measured electrical potentials while changing lighting glare conditions. Intensities varied over a range of glare luminance determined by a separate procedure according to subjective ratings. For this subjective method, subjects indicated the level of discomfort by marking a visual analog scale (VAS) punctuated with four descriptions of discomfort level: perceptible, annoying, disturbing, and intolerable. We have determined that the VAS is much more reliable with much less variability than the previously used border between comfort and discomfort (BCD) method. For 20 subjects, discomfort glare was assessed under three conditions: 2-degree-diameter glare source with low room illumination, 2-degree glare source with medium room illumination, and 1-degree glare source with medium room illumination. The glare source was a projector beam, 11 degrees to the right of a fixation target on a video monitor. Six different glare luminance levels were presented for 2-s periods. Each glare level was presented six times in a randomized order giving 36 presentations. EMG responses were subjected to Fourier analysis and the power frequency spectrum was determined with appropriate digital filtering used to eliminate powerline artifacts. Blinking causes an artifact whose power spectrum is markedly different and can be determined independently of the glare source. The integrated power spectrum of the EMG
Many industrial processes used to produce chemicals and pharmaceuticals would benefit from enzymes that function under extreme conditions. Enzymes from extremophilic microorganisms have evolved to function in a variet...
Many industrial processes used to produce chemicals and pharmaceuticals would benefit from enzymes that function under extreme conditions. Enzymes from extremophilic microorganisms have evolved to function in a variety of extreme environments, and bioprospecting for these microorganisms has led to the discovery of new enzymes with high tolerance to nonnatural conditions. However, bioprospecting is inherently limited by the diversity of enzymes evolved by nature. Protein engineering has also been successful in generating extremophilic enzymes by both rational mutagenesis and directed evolution, but screening for activity under extreme conditions can be difficult. This review examines the emerging synergy between bioprospecting and protein engineering in developing extremophilic enzymes. Specific topics include unnatural industrial conditions relevant to biocatalysis, biophysical properties of extremophilic enzymes, and industrially relevant extremophilic enzymes found either in nature or through protein engineering.
Microfluidic systems are attracting increasing interest for the high-throughput measurement of cellular biophysical properties and for the creation of engineered cellular microenvironments. Here we review recent appli...
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Microfluidic systems are attracting increasing interest for the high-throughput measurement of cellular biophysical properties and for the creation of engineered cellular microenvironments. Here we review recent applications of microfluidic technologies to the mechanics of living cells and synthetic cell-mimetic systems. We begin by discussing the use of microfluidic devices to dissect the mechanics of cellular mimics, such as capsules and vesicles. We then explore applications to circulating cells, including erythrocytes and other normal blood cells, and rare populations with potential disease diagnostic value, such as circulating tumor cells. We conclude by discussing how microfluidic devices have been used to investigate the mechanics, chemotaxis, and invasive migration of adherent cells. In these ways, microfluidic technologies represent an increasingly important toolbox for investigating cellular mechanics and motility at high throughput and in a format that lends itself to clinical translation.
Solid tumors are characterized by a remodeled and stiffened extracellular matrix. The extracellular matrix is not a passive by-product of the tumor, but actively compromises tissue-specific differentiation, enhances t...
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Solid tumors are characterized by a remodeled and stiffened extracellular matrix. The extracellular matrix is not a passive by-product of the tumor, but actively compromises tissue-specific differentiation, enhances tumor cell proliferation and survival, and fosters tumor cell invasion and migration. The tumor extracellular matrix also influences the behavior of the stromal cells, which through vicious, feedforward-reinforcing pathways promote tumor progression and compromise treatment efficacy. To investigate how the tumor extracellular matrix alters cancer phenotype and treatment, a number of three-dimensional, organotypic culture models have been developed that employ a variety of materials, including natural matrices, collagen, fibrin, and reconstituted basement membrane gels, as well as synthetic hydrogel materials such as polyacrylamide and polyethylene glycol. These models have been used to interrogate how specific microenvironmental features modify tumor and stromal cell function and to identify the molecular mechanisms that regulate tumorigenesis and therapeutic efficacy. To translate these findings into more effective treatment strategies for patients, clinically informed studies are needed that incorporate computational modeling and in vivo validation.
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