Decreased sodium (Na(+)), chloride (Cl(-)), and water absorption, and increased potassium (K(+)) secretion, contribute to the pathogenesis of diarrhoea in ulcerative colitis. The cellular abnormalities underlying decreased Na(+) and Cl(-) absorption are becoming clearer, but the mechanism of increased K(+) secretion is unknown. Human colon is normally a K(+) secretory epithelium, making it likely that K(+) channels are expressed in the luminal (apical) membrane. Based on the assumption that these K(+) channels resembled the high conductance luminal K(+) (BK) channels previously identified in rat colon, we used molecular and patch clamp recording techniques to evaluate BK channel expression in normal and inflamed human colon, and the distribution and characteristics of these channels in normal colon. In normal colon, BK channel alpha-subunit protein was immunolocalized to surface cells and upper crypt cells. By contrast, in ulcerative colitis, although BK channel alpha-subunit protein expression was unchanged in surface cells, it extended along the entire crypt irrespective of whether the disease was active or quiescent. BK channel alpha-subunit protein and mRNA expression (evaluated by western blotting and real-time PCR, respectively) were similar in the normal ascending and sigmoid colon. Of the four possible beta-subunits (beta(1-4)), the beta(1)- and beta(3)-subunits were dominant. Voltage-dependent, barium-inhibitable, luminal K(+) channels with a unitary conductance of 214 pS were identified at low abundance in the luminal membrane of surface cells around the openings of sigmoid colonic crypts. We conclude that increased faecal K(+) losses in ulcerative colitis, and possibly other diseases associated with altered colonic K(+) transport, may reflect wider expression of luminal BK channels along the crypt axis.
Although strong-field physics with conventional lasers had already started in the 1960s,2 the scientific revolution started about 10 years ago. At that time, we demonstrated that ultrashort pulses at the 100-fs level could be amplified, without damaging the amplifying media, to the terawatt level, using a technique that we called Chirped Pulse Amplification (CPA).3 Since their inception in 1960, the peak power of lasers has evolved by a succession of leaps of three orders of magnitude. They were produced each time by decreasing the pulse duration accordingly. First the lasers were free runnin g, with a duration in the 10-ps and peak power in the kilowatt range. In 1962, modulation of the laser-cavity quality factor allowed the same ... . energy to be released in a nanosecond time scale, a thousand times shorter, to produce pulses in the megawatt range. In 1964, locking the longitudinal modes of the laser (mode locking) allowed the' laser pulse duration to be reduced by another factor of a thousand, down to the picosecond level, pushing the peak power a thousand times higher, to the gigawatt level. At this point, the intensities associated with the ultrashort pulses were becoming prohibitively high-i. e., in the GW/cm2 range. At these intensities, the index of refraction becomes linearly dependent on the intensity to vary like n = YZo + n21, where n is the index of refraction, no the index of refraction at low intensity, 722the nonlinear index of refraction, and I the intensity. The result is that, for a beam with a Gaussian radial intensity distribution, the center of the beam sees a larger index of refraction than its sides. The material becomes a positive lens and alters the beam wave-front quality to an unacceptable level, to the point where it can create filaments and irreversible damage to the laser system. The only way to increase the peak power was to increase the beam diameter at the expense of size, low ,repetition rate, and cost. Although the pulse duration kept decreasing, for about 20 years the intensity limitation in laser systems kept the peak power about constant at the gigawatt level for a cm2 beam, until 1985-87, when the technique of CPA was demonstrated. The CPA concept is illustrated in Fig. 2. The short pulse is first produced by an oscillator. After generation it is not amplified directly, but stretched by a large amount, 103 to 105, from femtosecond to nanosecond, reducing the intensity accordingly. The pulse intensity is now low enough that the stored energy can be safely extracted out of the amplifier, without fear of beam distortions and damage. Once the stored energy is fully extracted, the pulse is recompressed, ideally to its initial value. The key point of the CPA technique is that it decouples pulse fluence (energy/cm2) and pulse intensity (power/cm2). So it reconciles two apparently conflicting needs: to have (a) the highest fluence for efficient energy extraction and (b) minimum intensity to avoid the undesired nonlinear effects. CPA had a dramatic impact. First, we could for the ...
The absolute yields of multiply charged ions of the noble gases argon, krypton, and xenon as functions of laser intensity at ^=586 nm is reported. The measurements were performed with a well characterized picosecond dye laser in the range 10 13 to 4xl0 14 W/cm 2 . Charge states up to Ar +4 , Kr +5 , and Xe +6 were observed at the highest intensities. An extension of the Keldysh-Reiss-Faisal theory which accounts for the Coulomb field of the residual ion is presented and found to be in good agreement with the experimental results with no adjustable parameters.
We present Artifacts of the Presence Era, a digital installation that uses a geological metaphor to visualize the events in a physical space over time. The piece captures video and audio from a museum and constructs an impressionistic visualization of the evolving history in the space. Instead of creating a visualization tool for data analysis, we chose to produce a piece that functions as a souvenir of a particular time and place. We describe the design choices we made in creating this installation, the visualization techniques we developed, and the reactions we observed from users and the media. We suggest that the same approach can be applied to a more general set of visualization contexts, ranging from email archives to newsgroups conversations.
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