Phase-shifting interferometry suffers from two main sources of error: phase-shift miscalibration and detector nonlinearity. Algorithms that calculate the phase of a measured wave front require a high degree of tolerance for these error sources. An extended method for deriving such error-compensating algorithms patterned on the sequential application of the averaging technique is proposed here. Two classes of algorithms were derived. One class is based on the popular three-frame technique, and the other class is based on the 4-frame technique. The derivation of algorithms in these classes was calculated for algorithms with up to six frames. The new 5-frame algorithm and two new 6-frame algorithms have smaller phase errors caused by phase-shifter miscalibration than any of the common 3-, 4- or 5-frame algorithms. An analysis of the errors resulting from algorithms in both classes is provided by computer simulation and by an investigation of the spectra of sampling functions.

This manuscript has been reproduced from the microfiim master. UMI films the text directly from the original or copy submitted. Thus, some thesis arKi dissertation copies are in typewriter face, while others may t)e from any type of computer printer.The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely aftoct reproduction.In the unlikely event that the author dkj not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a rx>te will indicate the deletk>n.Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, t)eginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps.Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6' x 9" black and white photographic prints are availat)le for any photographs or illustrations appearing in this copy for an additkxial charge. Contact UMI directly to order. I was fortunate to be chosen by TRDI, Japan Defense Agency, to pursue graduate study and research at the Optical Science Center (OSC) at the University of Arizona (UA). I would like to thank them for giving me the chance to conduct graduate research here at OSC.Of course, I am grateful to my husband, who is conducting his own Ph.D research at the University of Iowa, and my parents for their patience and love. Without them this work would never have come into existence.Finally, I wish to thank my former roommate, Ying, who left two kittens, DaBao and SanBao when she moved to South Carolina. The kittens have been great compan ions along with the huge mess they create every day. I will miss the kittens terribly when I go back to Japan. Wavelet transform analysis of a correlogram 54 FIGURE 2.8. Surface profiles obtained from various vertical scanning algorithms. 59 FIGURE 2.9. Number of operations required for each algorithm 62 FIGURE 2.10. Simulated correlograms of 90° scanning step with 0-10% Gaussian distribution random noise of maximum contrast 65 FIGURE 2.11. Simulated correlograms of 270° scanning step with 0-10% Gaus sian distribution random noise of maximum contrast 66 11LIST OF FIGURES-Continued FIGURE 2.12. Surface profile obtained from simulated correlograms with 6% Gaussian distribution random noise of maximum contrast 67 FIGURE 2.13. Simulated correlograms with 10% periodic motor noise 70 FIGURE 2.14. Surface profile obteiined from simulated correlograms with 10% periodic motor noise 71 The work proceeds with a discussion of the phase change upon reflection and its influence on the coherence envelope. Then phase meeisurement interferometry methods are reviewed. The emphasis is in errors in phase measurement resulting from using a white light source instead of a monochromatic light source ...

A critical event in the apoptotic cascade is the proteolytic activation of procaspases to active caspases. The caspase autoactivating compound PAC-1 induces cancer cell apoptosis and exhibits antitumor activity in murine xenograft models when administered orally as a lipid-based formulation or implanted s.c. as a cholesterol pellet. However, high doses of PAC-1 were found to induce neurotoxicity, prompting us to design and assess a novel PAC-1 derivative called S-PAC-1. Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell apoptosis. However, S-PAC-1 did not induce neurotoxicity in mice or dogs. Continuous i.v. infusion of S-PAC-1 in dogs led to a steady-state plasma concentration of ∼10 μmol/L for 24 to 72 hours. In a small efficacy trial of S-PAC-1, evaluation of six pet dogs with lymphoma revealed that S-PAC-1 was well tolerated and that the treatments induced partial tumor regression or stable disease in four of six subjects. Our results support this canine setting for further evaluation of small-molecule procaspase-3 activators, including S-PAC-1, a compound that is an excellent candidate for further clinical evaluation as a novel cancer chemotherapeutic. Cancer Res; 70(18); 7232-41. ©2010 AACR.

We present five different eight-point phase-shifting algorithms, each with a different window function. The window function plays a crucial role in determining the phase (wavefront) because it significantly influences phase error. We begin with a simple eight-point algorithm that uses a rectangular window function. We then present alternative algorithms with triangular and bell-shaped window functions that were derived from a new error-reducing multiple-averaging technique. The algorithms with simple (rectangular and triangular) window functions show a large phase error, whereas the algorithms with bell-shaped window functions are considerably less sensitive to different phase-error sources. We demonstrate that the shape of the window function significantly influences phase error.

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Cancer and many other diseases are characterized by changes in cell morphology, motion, and mechanical rigidity. However, in live cell cytology, stimulus-induced morphologic changes typically take 10-30 min to detect. Here, we employ live-cell interferometry (LCI) to visualize the rapid response of a whole cell to mechanical stimulation, on a time scale of seconds, and we detect cytoskeletal remodeling behavior within 200 s. This behavior involved small, rapid changes in cell content and miniscule changes in shape; it would be difficult to detect with conventional or phase contrast microscopy alone and is beyond the dynamic capability of AFM. We demonstrate that LCI provides a rapid, quantitative reconstruction of the cell body with no labeling. This is an advantage over traditional microscopy and flow cytometry, which require cell surface tagging and/or destructive cell fixation for labeling.

PAC-1 is a preferential small molecule activator of procaspase-3 and has potential to become a novel and effective anticancer agent. The rational development of PAC-1 for translational oncologic applications would be advanced by coupling relevant in vitro cytotoxicity studies with pharmacokinetic investigations conducted in large mammalian models possessing similar metabolism and physiology as people. In the present study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 hours that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 ± 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 hours in duration. Using the dog as a large mammalian model, PAC-1 can be safely administered as an intravenous CRI while achieving predicted in vitro cytotoxic concentrations.

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