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Scientists used the RTPP as finally constructed to analyze data in a variety of biomedical domains including optical microscope images of optical serial sections of brain tissue, stained bone marrow smears, and tissue cultures using phase contrast and differential interference optics. The latter was used in tracking cell membrane extents of macrophages in tissue culture over time as the cells tried to phagocytize various types of asbestos fibers. The goal was to better understand fiber carcinogenicity and the dynamics of fiber ingestion [8910]. The bone marrow smear image analysis was part of my Ph.D. dissertation [1112TR-653TR-655]. The RTPP was also used for 2D electrophoretic gel images for a variety of biological materials [1314151617181920212223242526272829303132], and for RNA electron micrographs of secondary structure, which was part of Bruce Shapiro's Ph.D. dissertation [333435363738TR-BAS78].

Lewis Lipkin, leader of the projectImage ModifiedFigure 1. Dr. Lewis Lipkin headed the project. His group started working on computer-controlled optical microscopy in the Perinatal Research Branch (PRB) of NINDB. The group later changed its name and institutes to the Image Processing Unit (IPU) in NCI in the Laboratory of Pathology. IPU later became the Image Processing Section (IPS) in NCI. The Section later became part of the Laboratory of Mathematical Biology (LMMB) in NCI under Dr. Charles DeLisi, Ph.D., and still later under Dr. Jacob Maizel, Ph.D.. The laboratory changed its name to the Laboratory of Experimental and Computational Biology (LECB) under Jake Maizel. The laboratory is currently refocused on nanobiology and is now called the Center for Computer Research Nanobiology Program (CCRNP) directed by Dr. Robert Blumenthal, Ph.D.(CCRNP has an additional research Web site).

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The 'mcrew' picture taken when RTPP was first runningImage Modified

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Figure 2. One of the first images taken using the RTPP was of the development group just after we got the Digital Equipment Corporation DECsystem-2020 interface to the RTPP buffer memory working. The image was one we called "mcrew" (i.e., 'machine crew'). Top row (L-R): Dan Kilgore, George Carman, and Morton Schultz. Bottom row (L-R): Earl Smith and Peter Lemkin. Not shown: Bruce Shapiro and Lew Lipkin who were integral parts of the RTPP design and development team.

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The DECsystem-2020 computerImage Modified

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Figure 3. The Digital Equipment Corporation DECsystem-2020 exit disclaimer running the TOPS-10 exit disclaimeroperating system. The system is shown with Bruce Shapiro, holding a removable 180MB "bathtub" size disk pack (on the left), and Peter Lemkin (on the right). It had 512K words, 36-bits/word, 256K word virtual space/user, a very powerful instruction set, and many high-level computer languages, including SAIL (Stanford Artificial Intelligence Language - see wikipedia.org entry on SAILexit disclaimer, that made implementing complex analysis algorithms much easier than on the PDP8e. SAIL was developed by Dan Swinehart and Bob Sproull of the Stanford AI Lab exit disclaimer in 1970. Sproull was at Division of Computer Research and Technology (DCRT) in the early 1970s and introduced the language to DCRT [the precursor of NIH's Center for Information Technology (CIT)]. Over time, we implemented more of the advanced image processing and pattern recognition algorithms in SAIL, using the RTPP as a sophisticated data acquisition and interactive graphics front-end. Later many of these algorithms were rewritten in C and UNIX using X-windows (we rewrote the C/UNIX/X-windows GELLAB-II exit disclaimer exploratory analysis system from the SAIL/TOPS-10/RTPP GELLAB-I), and in LISP (StructureLab with a Symbolics Lisp machine and later a Unix Platform) when the DECsystem-10/20 computer lines were phased out in favor of the VAX exit disclaimercomputer lines. Later still, much of the C code for GELLAB-II was converted and rewritten in Java and used as part of the Open2Dprot exit disclaimer project. We will discuss some of these projects later under the section Applications of the RTPP in Biomedical Research.

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RTPP block diagram from original design paperImage Modified

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Figure 4. The Real Time Picture Processor (RTPP) block diagram (reproduced with permission, from J. Histochem. Cytochem. [4], 1974). This shows additional parts of the system including a PDP11/20 message switcher to a PDP-10 Artificial Intelligence system PRDL (PRocedural Description Language) [5TR-15] originally being developed on NIH's DCRT (now CIT) PDP-10 facility. The early microscope also had a 1024x1024 8-bit galvanometer scanner that could be used in place of the Quantimet 720 scanner. The later microscope was built around a Zeiss Axiomat microscope. An early high-quality grayscale display (Dicomed 31) was also used to make high-quality display images. Its functionality was replaced by the Quantimet grayscale buffer-memory display. The PDP8e accessed the RTPP using the BMON2 software [40TR-21b]. The PDP-10 multiprocessor KL-10 system was a shared time-share computer at DCRT (now CIT). This was replaced in our design by a dedicated DECsystem-2020 when it became more cost-effective to have a dedicated computer. The DECsystem-2020 was a new microcoded processor that DEC was able to build for a fraction of the cost of the PDP-10. The PRDL [TR-15] and PROC10 [TR-8] image processing software were created to interface with the RTPP. We had considered creating a MAINSAIL(R)exit disclaimer compiler for use with the GPPASM (GPP assembler program) [TR-16] so that we could program the GPP in a SAIL-like language only available on large PDP-10 class systems. Later, a light box for films was used with the Quantimet vidicon scanner (see Figure 18) with changeable 35mm lenses (not shown in this block diagram - see Figure 5) to scan autoradiograph and wet 2D gels, RNA electron micrographs, and other transparencies.

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