Test lab.(scanners)(includes related articles) (Evaluation)by Mike Hudnall, Peter Scisco, David Sears, David English, Robert Bixby, Tony Roberts, Tom BenfordScanners have won their rightful place on the desktop. Publishers no longerhave to make do with clip art from third parties, artists are able to transfertheir work instantly to electronic formats, and writers can import text fromprinted sources almost as easily as cutting and pasting it from anotherapplication.The strong demand for low-cost scanning alternatives has resulted in a crowdedfield of manufacturers and marketers, each trying to outdo the rest byoffering convenience and high-powered applications as premiums with thepurchase of a hand scanner.This month's Test Lab covers hand scanners with a focus on graphics. Today'sscanner manufacturers offer a wide variety of prices, capabilities, andbundles. Some might include low-cost DOS software; others take advantage ofthe Windows environment. Some scanners even work with OCR (Optical CharacterRecognition) software. If you see a package here that looks attractive, checkwith the manufacturer for additional options.Few peripheral devices place such heavy processing demands on a personalcomputer as scanners do, and you may discover that installation is not assimple as slipping in a card.
Editors found themselves reading installationmanuals carefully (for some it was the first time they'd ever had to readone), trying Windows in different modes, editing PIF files, and in one case,trying different computers to make their scanners operate properly. Althoughscanners are, in the main, user-friendly after installation, more work needsto be done to make them easier to install.
Fortunately, most scanners comewith free technical support and friendly, helpful support personnel.Whether you're a teacher, an artist, a writer, or a desktop publisher, ifyou're in the market for a hand scanner, you've never had more choices orlower costs.THE COMPLETE HALF-PAGESCANNER/GSSteady-handed I'm definitely not, as the family photo album will clearly show.However, I found that the Complete Half-Page Scanner/GS offers smooth,dependable scanning-and up to 256 shades of gray.I approached this product evaluation with a combination of eager anticipationand trepidation. On the one hand, I was eager to see how this unimposingdevice could scan line art for a newsletter or photos for a family history.On the other, I had struggled enough with interrupt and address conflicts toknow that I could be letting myself in for some tedious tinkering with DIPswitches, jumpers, and software settings. The installation proved to bereasonably easy-default settings worked on one computer but not on another.This scanner comes with its own special version of Image-In, a Windows programused for both image scanning and image enhancement. Unfortunately, my firstattempts at scanning with this product left members of my family looking likethe Coneheads, owing to an intermittent blurring effect. Line art I scannedalso came out with odd intermittent blurs or 'garbage.' Some experimentingwith Windows settings revealed that this odd effect occurred on my computeronly with Windows operating in Standard and Enhanced modes. Running theprogram in Real mode solved the problem, and my family looked as normal aspossible-at least without any appearance of cranial abnormalities.In combination with the Image-In software, this scanner gives you a number ofattractive features.
You can scan images with resolutions up to 400 dots perinch or with up to 256 shades of gray, adjust brightness, and manipulate thescanned image in a number of ways. Edit the gray-map; enhance edges; andsharpen, blur, rotate, or flip the image. You can save your scanned images ina number of popular formats, including PCX, TIFF, BMP, and PostScript EPS.The scanner itself performed well. I found the design comfortable and thecontrols workable.
In addition to the button that initiates the scan, thescanner includes a brightness control, a gray-levels switch, and a resolutionswitch. For optimal scanning, the resolution and gray levels must be set inconcert: To scan at 256 gray scales required that the scanner be set for 100dpi; to scan at 16 gray scales, 200 dpi; and to scan in monochrome, 300 or 400dpi.I found the documentation very good for the most part, offering helpfulillustrations, tips, coverage of the available features, and even a shortcourse.
Particularly useful to me were the examples of images modified withthe program's various features. A section devoted to troubleshooting would bea welcome addition to the next version of the program.As I managed to use the scanner only in Real mode with my PC, I found it adisadvantage to move from Image-In to a program like WinRix, which requiresEnhanced mode. However, I can live with this limitation, and the folks at TheComplete PC assure me that this package is designed to to work in Enhancedmode.The smooth operation, numerous software features, and reliability of TheComplete Half-Page Scanner/GS make up for the limitations I experienced. Andas I'm not involved in heavy-duty desktop publishing, the price and featuressuit me well and make this an attractive package.DFI CHS-4000COLOR HANDYSCANNERAre you an aspiring desktop publisher looking for color scanning capabilities,but you don't want to shell out a pile of money for a color flatbed scanner?Take heart. The CHS-4000 Color Handy Scanner from DFI offers full-colordesktop scanning capabilities as well as superb black-and-white scanning.It's easy to use and flexible in its operation.Installation of this scanner is reasonably uncomplicated. The Handy Scanner'sbus board plugs into an empty 16-bit slot in your PC. Attach the scanner tothe board, and then use the scanner's Exerciser software to scan images andsave them in PCX format.
The Exerciser program is bare-bones-a simple menuwith options for setting the scan mode, vertical and horizontal resolutions,brightness, hue, contrast, dither pattern, gamma correction, and display mode(monochrome, EGA, or VGA). You can also save and load PCX files from themenu, as well as start your scan.Although very simple compared with full-blown imaging software, the Exercisersoftware will let you get started with your Handy Scanner right away. Andbecause you can save your files as PCX files, you can import them later intomost desktop publishing and illustration programs or convert them to differentfile formats like TIFF or EPS.In addition, the Handy Scanner package includes a copy of PC Paintbrush IVPlus, which you can use instead of the scanner's Exercise program; however,you should be aware that PC Paintbrush IV Plus requires an expanded memorydriver to work properly. If you're running extended memory in a 386-class PC,you can create expanded memory support by using the EMM386.SYS driver fromyour DOS directory.Other system requirements include one megabyte of memory and four megabytes ofavailable hard disk space. You should also have a VGA display capable of 256colors at 640 x 400 resolution to view the results.With practice and patience, you'll soon be producing high-quality color scanswith the Handy Scanner.
The unit itself provides plenty of constructivefeedback during operation through its use of LED indicators. And though thesoftware is without frills, it's suitable for grabbing images that can laterbe enhanced.KYE GENISCANGS-B105G PLUSTake a quick image-grabbing safari with the GS-B105G, stalking new Windowswallpaper or newspaper articles for the family newsletter. You'll see themerits of a multipurpose scanner.The GS-B105G scanner will scan in resolutions from 100 to 400 dpi, and in theself-explanatory modes of black-and-white, low dither, high dither, andVGA-true 256 gray scale. You adjust these settings via switches on eitherside of the scanner. A thumb wheel controls contrast, and an astutely placedstart button rounds out the physical controls.Manipulating images couldn't be simpler, using the included iPhoto software.This Windows application concentrates on processing your raw data through anumber of filters. Although color or black-and-white photographs already scanwith remarkable clarity and speed thanks to the hardware when set for 256 grayscale, you reserve the right to enhance, average, sharpen, or blur yourscanned image.
These effects turn your PC into a photo-processing lab.Most people don't run Windows under true 256-color mode for the sake of speed.To see fair reproductions of your stunning full-gray images, convert them to16-color BMP files with iPhoto. A nifty iPhoto option makes the step down inquality less noticeable with choices of gray, pseudo color, and firelight (redand yellow scale) remapped palettes. Toy with the Hue and Saturation slidersto tweak the colors into acceptability.You'll find a second scanning program-a gray-scale version of ColorMaestro-bundled with the GS-B105G. This software offers more features commonto paint programs and doesn't require Windows to run. I found Color Maestroless satisfactory, though, because of its extreme slowness and constant diskaccessing.How many times have you found yourself with only hardcopies of a documentafter a terrible hard drive crash?
Install the included optical characterreader (OCR) software, CAT OCR, and replace your files with a few passes ofthe GS-B105G. Output your OCR work in WordStar, WordPerfect, and ASCIIformats. If CAT OCR's reasonably effective reference font doesn't meet yourstandards for speed or accuracy, you can build your own specializedfont-recognition library. This process takes only minutes.Windows veterans will need the concise manuals only for advanced work;neophytes will be scanning everything in sight just moments after a cursoryreading. A marvel of simplicity and winning design, the speedy GS-B105Gsoftware and hardware bundle makes scanning as effortless as using a mouse.KYE GENISCANGS-C105 PLUSDoes anyone really need a color hand scanner? A year or two ago, I would'vesaid that you should consider one only if you're looking to dabble in high-endcolor desktop publishing.
But now with Windows and multimedia playing alarger part in our software lives and high-resolution monitors multiplyinglike rabbits, we have more ways than ever to use scanned color images.KYE International offers two inexpensive color-hand scanner packages that letyou enter the age of color without having to take out a second mortgage onyour house. The $649 GS-C105 package includes a 256-color hand scanner, theDOS-based Color Maestro program, and an interface card. The GS-C105 Pluspackage costs just $50 more and adds two programs: CAT OCR for OCR textscanning and the Windows-based iPhoto for sophisticated gray-scale and colorimage manipulation (including support for 24-bit display adapters). Whileonly a masochist would want to do a lot of OCR work with a graphics-based handscanner, iPhoto adds extra file formats, editing tools, and image-processingcapabilities that you might want to take advantage of.But be warned-you must have expanded memory (also known as EMS or LIM memory)in order to perform 256-color scans.
If you don't have expanded memory butyou do have DOS 5.0, you can use DOS's built-in expanded memory manager,EMM386, to convert your extended memory to expanded memory. (Put a RAM switchafter DEVICE=C:DOSEMM386.EXE in your CONFIG.SYS file; check your DOS 5.0manual for details.) If you don't have DOS 5.0, you can use QEMM-386, 386Max,BlueMax, Turbo EMS, or another expanded memory manager to convert yourextended memory to expanded. Without expanded memory, you'll only be able tocaputre 2- and 16-color images. In addition, Color Maestro supports many ofthe higher-resolution modes of the popular Super VGA cards, and iPhotosupports any resolution that's supported by Windows.Despite unevern documentation and the occasional software glitch, the GeniScanGS-C105 Plus will reward the patient user with excellent-quality color images.For frequent use, consider a $1,200-$2,000 flatbed color scanner.
But foroccasional use and a relatively inexpensive introduction to color scanning,take a good look at either of KYE's color-scanner bundles.LOGITECH SCANMANMODEL 256Plug a scanner into your computer, and you plug into a whole new level ofversatility. I've had no regrets since hooking up a Logitech ScanMan Model256 gray-scale scanner as part of a desktop publishing setup.Scanning materials for publication is not easy, but Logitech's scanner sportsexcellent controls and includes Ansel, an outstanding image editor.ScanMan installs easily, with the only stumbling block being possibleconflicts with I/O base addresses and IRQs. The ScanMan adapter board fits ineither an 8-bit or a 16-bit slot, but using the latter is preferred because itpermits the ScanMan to use IRQ 11 or 12. This ensures you'll avoid conflictswith mouse and COM ports, but if trouble arises, you'll find plenty of help inthe manual.Once you have installed the system, fire up Windows, run Ansel, calibrate yourscanner, and start scanning.Scanner controls include a resolution switch, to select resolutions rangingfrom 100 to 400 dpi; an image mode switch, to choose either black-and-whitemode or 16-, 64-, or 256-gray-scale modes; and a contrast dial, to minimizeproblems in your original. ScanMan also includes a scan speed indicator tohelp you avoid losing data by scanning too fast.Working with black-and-white line art is less difficult than working withgray-scale images, but the image-editing software provides excellent tools forboth.Once an image is scanned, Ansel permits you to enlarge the image and modify itpixel by pixel. A black-and-white logo scanned for use in a newsletter orbrochure cleans up nicely with Ansel.Ansel also allows you to rotate, flip, and crop images; and the softwareincludes a 'deskew' option that helps you straighten an imperfectly scannedimage. Gray-scale images can be lightened, darkened, sharpened, smoothed, orequalized.
By working with a combination of these tools, you can produceimages that look beautiful-on your computer monitor. Transferring theseimages to the printed page with satisfactory contrast and clarity takesexperimentation.Printing controls are extensive.
If your printer allows it, you can print thegray scales, or you have the option of using dithering or error diffusion tosimulate gray shades. You have full control over output size, and you canselect from a series of borders if you'd like your artwork framed.Exporting to other applications is easily accomplished. Files can be saved inTIFF, EPS, PCX, and BMP formats. In saving your files, you can control theresulting document's dpi and image size.Although ScanMan's scanning window is only four inches wide, larger documentscan be accommodated using Ansel's stitch feature, which permits you to scanitems in segments and match the segments up onscreen. It's not easy, but witha steady hand and some practice, you can put together seamless images.The ScanMan 256 gray-scale scanner hardware/software combination is a solidvalue and a worthy desktop publishing tool.MARSTEK M-800WFor black-and-white scanning, this Marstek model provides adequate, if notexceptional, capabilities. It boasts several good features, such as easyinstallation and sound software support.
But those features must be balancedagainst weak documentation and unimpressive use of the Windows environment.The M-800W will scan at 800-dpi resolution, an impressive capability fordesktop publishers and others looking for high-quality images to enhance theirdocuments and publications.
Generally speaking, on-line handwriting analysis iscurrently employed for two distinct applications: identity verificationand input of handwritten letters and numbers into acomputer. These two applications have sharply contrasting operationalrequirements and goals. Handwriting analysis for identityverification senses features of handwriting which are distinctfor each individual and thus can be used to unambiguously identifya given individual. In contrast, handwriting analysis foralphanumeric input to a computer seeks to minimize the effect ofthe very features which are important for identity verificationand to concentrate on universal handwriting characteristics whichcan be associated with given symbols independently of the individualwriter.
Position digitization through ultrasonic position digitisation is well known inthe prior art, as for example in U.S. Patents 3,731,273; 4,317,672; 4,578,674;4,654,648; 4,758,691; 4,814,552; 4,862,152; 4,991,148; 5,142,506; 5,214,615;5,239,139; and 5,280,457. Other publications describing ultrasonic positiondigitisation include 'A sonic pen: a digital stylus system' by Brenner and DeBruyne,IEEE Transactions on Computers, vol.
6, June 1970, pp. 546-548;'Compact Large-Area Graphic Digitizer for PC' by DeBruyne, IEEE ComputerGraphics and Application, December 1986, pp. 49-53; IBM Technical DisclosureBulletin, vol. 3, August 1969, p. 390; and 'US cursor position detection',IBM Technical Disclosure Bulletin, vol. 11, April 1985.
The present invention will be understood and appreciatedfrom the following detailed description, taken in conjunctionwith the drawings in which:. Fig. 1A is a simplified semi-pictorial semi-block diagramillustration of handwriting recognition apparatus constructedand operative in accordance with a preferred embodiment of thepresent invention;. Fig.
1B is a simplified semi-pictorial semi-block diagramillustration of handwriting recognition apparatus constructedand operative in accordance with an alternative preferredembodiment of the present invention;. Figs. 2A through 2H are schematic drawings of preferredstructures of portions of the apparatus of Figs.
1A and1B;. Fig. 3 is a simplified block diagram of the handwritingrecognition apparatus of Figs. 1A and 1B;. Fig.
Logitech Scanman 256 Manual Software
4A is a simplified flow chart illustrating theteaching process performed by the handwriting recognition apparatusof Figs. 1A and 1B;. Fig. 4B is a simplified flow chart illustrating therecognition process performed by the handwriting recognitionapparatus of Figs.
1A and 1B;. Figs. 5A through 5D are graphical depictions of dataillustrating a preferred method for a portion of the teaching andrecognition processes performed by the handwriting recognitionapparatus of Figs.
1A and 1B;. Fig.
6A is a simplified illustration of a preferredmechanical structure of the digitizing pen/accelerometer of Fig.1A;. Fig. 6B is a simplified illustration of a preferredmechanical structure of the digitizing pen/accelerometer of Fig.1B;.
Fig. 7 is a simplified semi-pictorial semi-blockdiagram of handwriting recognition apparatus constructed andoperative in accordance with another alternative preferredembodiment of the present invention;. Fig. 8 is a simplified block diagram of the handwritingrecognition apparatus of Fig. 9A is a simplified flow chart illustrating theteaching process performed by the handwriting recognition apparatusof Fig. 9B is a simplified flow chart illustrating therecognition process performed by the handwriting recognitionapparatus of Fig. 7.DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS.
The data from the one or more accelerometers in pen 10is termed herein 'accelerometer data'. Accelerometer data andlocation data from graphic tablet 12 are each sent through separatecables to a control circuit 40. Alternatively, the accelerometerdata and location data may be sent through a single cable.According to a still further alternative, the accelerometer dataand location data may be sent through any kind of appropriatecommunication link, such as ultrasonic, infrared, or by any othersuitable means. During teaching the user writes symbols from a pre-arrangedscript known to data processor 50, and the associatedsymbols appear on symbol display 60 during the writing. Preferably,the pre-arranged script contains several repetitions of eachsymbol. Preferably, based on the experience of the inventor, thesymbols should occur in different parts of a word, such asbeginning, middle, and end, throughout the pre-arranged script.The functionality of data processor 50 during the teaching processis more fully described below with reference to Fig.
A plurality of ultrasonic receivers 85, such as modelMA40S3R commercially available from Murata Electronics, GMBH,Halbeinstrabe 21-23, D-8500, Nurnberg, Germany, are located atpredetermined positions in proximity to writing surface 75. Archon classic 2010 pc shooting. Inthe case where writing surface 75 comprises a typical sheet ofpaper or a typical computer display screen, two ultrasonic receivers85 are typically sufficient to determine the position ofpen 10. In the case where writing surface 75 is large comparedto a typical sheet of paper or a typical computer display screen,more than two receivers are preferred. Control circuit 90 sends signals to pen 10, triggeringultrasonic transmitter 80 to emit a sequence of pulses. Typically,control circuit 90 sends a burst of pulses, each burst separatedfrom the next burst by a specific time period. Preferably,four closely spaced pulses are sent in each burst, and the burstsare separated by 25 microseconds. Reference is now additionallymade to Fig.
2C, which is a schematic drawing of a preferredstructure of the portion of control circuit 90 which sends signalsto pen 10. Control circuit 90 restarts the counters includedtherein at the beginning of each burst. Each of the ultrasonicreceivers 85 receives the ultrasonic sound waves emitted byultrasonic transmitter 80 as part of the burst, and sends asignal to control circuit 90.
Upon receipt of a signal from oneof the ultrasonic receivers 85, control circuit 90 stops theassociated counter. Reference is now additionally made to Figs.2D through 2H, which are schematic drawings of a preferred structureof the portion of control circuit 90 comprising the counters,DSP, and associated electronic circuits. Control circuit 90 then computes the position of thetip of pen 10 using triangulation as follows.
The counter valuerepresents the time between the transmission of a pulse by ultrasonictransmitter 80 and the receipt of the pulse by the one ofultrasonic receivers 85 associated with the counter. Because thespeed of sound in air is taken to be isotropic, the counter valuealso represents the distance between ultrasonic transmitter 80and the one of ultrasonic receivers 85 associated with the counter.The position of pen 10 is then computed by applying thePythagorean theorem. The positions determined by control circuit 90 fromultrasound data are taken to specify the direction of movement,and the number of peaks in the noise component as described aboveare taken to specify the distance traversed. Data processor 50computes, from the direction of movement and the distance traversed,updated and more accurate position data. Preferably, thesample rate of the acceleration data used to compute the noise isgreater than the data transmission rate of ultrasound data fromcontrol circuit 90. During teaching the user writes symbols from a pre-arrangedscript known to data processor 50, and the associatedsymbols appear on symbol display 60 during the writing.
Preferably,the pre-arranged script contains several repetitions of eachsymbol. Preferably, based on the experience of the inventor, thesymbols should occur in different parts of a word, such asbeginning, middle, and end, throughout the pre-arranged script.The functionality of data processor 50 during the teaching processis more fully described below with reference to Fig.
Pen 10, when moved by the user of the handwritingrecognition apparatus, transmits data describing the accelerationsof pen 10 over time to teaching control 130 and/or handwritingrecognition control 150. Pen 10 also provides, in conjunctionwith graphic tablet 12, data describing the positionstraced out over time by the tip of pen 10 as pen 10 is moved bythe user over the surface of graphic tablet 12. Alternatively,in the case of the apparatus of Fig. 1B, position data is providedby control circuit 90 as described above. The combined data preferably comprises the X,Y coordinatesof the position of the tip of the pen 10 in the grid of thetablet and the tablet contact status of pen 10, i.e. Whether ornot it is in contact with the tablet surface.
The status may beoperationally indicated as 'pen up', 'pen down', or 'pen out ofproximity with the tablet', in the case of the Wacom TabletProcessor specified above. The combined data also preferablycomprises the average value of the accelerometer data pointscorresponding to a single graphic tablet data point. The statusof pen 10 may be derived from signals transmitted by graphictablet 12, by a switch operatively associated with the tip of pen10, as described below with reference to step 212, or by othermeans. STEP 212: Identify pen-surface contact termination.The data from step 210 may not include the surface contact statusof pen 10. In this case, the surface contact status of pen 10may be derived from the acceleration data.
The accelerationdata is filtered to remove components other than noise. Forexample, the acceleration data is filtered by a Butterworthdigital filter described in Digital Filter Design by T.W.
Parksand C.S Burrus, published by John Wiley & Sons, 1987, chapter 7,section 7.3.3, using the 4th order lowpass digital filter withcut-off frequency of 0.7 to 0.9. The filtered acceleration data is then integrated overtime.
The slope of the integrated filtered acceleration data isthen analyzed to determine the point at which the slope exceeds athreshold value. The point at which the slope exceeds thethreshold value is taken to be the first point with status 'pendown'. The point at which the slope falls below a thresholdvalue is taken to be the first point with status 'pen up'; thethreshold value may or may not be the same as the previouslydescribed threshold value.
In the case of determining pen statusbased on accelerometer data there is no status 'pen out of proximity'. If the pen comprises a single accelerometer, the parameterspreferably comprise the following:. number of points before normalization;. normalized signal of pen status;.
normalized signal of accelerations;. sine of the angle α which angle is defined as the anglebetween the vector associated with the current data point(X i,Y i,AccZ i) and the XY plane as shown in Fig. 5A;. cosine of the angle α;. sine of the angle β which angle is defined as the anglebetween the vector that connects the point before the previouspoint (X i-2,Y i-2,AccZ i-2) and the current point (X i,Y i,AccZ i),and the vector that connects the current point with the pointafter the subsequent point (X i+2,Y i+2,AccZ i+2) in space(X,Y,AccZ) as shown in Fig. 5B;. and cosine of the angle β.
Let the non-orthogonal signals be denoted by the vectoru=(u 1,u 2,u 3) T and the orthogonal signals be denoted by the vectoru'=(u' 1,u' 2,u' 3) T, where T denotes the transpose. Then u'=A 0A -1uwhere A is a vector of static sensitivity vectors A=(A 1,A 2,A 3) ofthe three- accelerometers. The static sensitivity vector iscomputed from the outputs of the accelerometers during a definedorientation without movement. A 0 is a diagonalized matrix ofsensitivity of the orthogonal coordinate system comprising thenorms of A 1, A 2, and A 3. When the pen comprises, for example, three accelerometers,the parameters preferably comprise those mentioned aboveplus the following parameters:.
sine of the angle α' which angle is defined as theangle between the vector associated with the current data point(AccX i,AccY i,AccZ i) and the AccXAccY plane as shown in Fig. 5C;. cosine of the angle α';.
sine of the angle β' which angle is defined as theangle between the vector that connects the point before theprevious data point (AccX i-2,AccY i-2,AccZ i-2) and the currentpoint (AccX i,AccY i,AccZ i), and the vector that connects thecurrent point with the point after the subsequent point(AccX i+2,AccY i+2,AccZ i+2) in space (AccX,AccY,AccZ) as shown inFig. 5D;. and cosine of the angle β'. STEP 250: Generalize parameters. The parameters ofthe symbol being learned represent a specific instance of thesymbol. The symbol prototype stored by the system is to representthe general characteristics of the symbol as drawn by thatperson. Therefore, the parameters of the symbol being learnedare generalized by some suitable means, such as by computation ofthe average of the value of each parameter from previous instancesof the symbol along with the value of each parameter fromthe current instance of the symbol.
In accordance with another device,parameters which come from graphic tablet dataare combined and compared together, and parameters from accelerometerdata are separately combined and compared, thus producingtwo measures of comparison between the sample and the prototype.Appendix B is a computer listing in the C programing languagecomprising routines that are a preferred implementation of step300. The routines comprise the following, which are found insection IV, 'recognition procedures': defkclass; defkletter;defkword; defkrow; mutmetric; metricdiry; metricdirx;together with various definitions used by the routines.
The database of previous confusions provides informationthat allows the correction of the choice of the correctsymbol based on previous incorrect identifications. The databaseof previous confusions comprises, for each symbol, a list ofother symbols which have been confused with the first symbol; forexample, that the symbol 'f' has often been confused with thesymbol 'b'. When such an entry is found comprising previousconfusions for a symbol in the list, the symbol or symbols thathave previously been confused with the symbol in the list areadded to the list. In accordance with the previous example, ifthe symbol 'f' is found in the list, then the symbol 'b' is addedto the list. Reference is now additionally made to Fig.
6A which isa simplified illustration of a preferred mechanical structure ofthe digitizing pen/accelerometer 10 of Fig. Pen 10 may comprisean electromagnetic pen such as a WACOM SP-200 availablefrom WACOM Computer Systems GmbH, Hellersbergstrasse 4, W-4040Neuss 1, Germany, or any other suitable pen designed for use witha suitable model of graphic tablet. Pen 10 also comprises anelectromagnetic coil 410 which operates in conjunction withgraphic tablet 12 to provide and indication of the location ofthe point of pen 10. Pen 10 further comprises an ink refill 420which provides the ability to write on paper or on anothersurface. The data from pen 10 and scanner 500 may be transmittedto acceleration teaching control 630 or OCR teaching control 635respectively. Transmission to acceleration teaching control 630or OCR teaching control 635 occurs for each person who is to usethe system for handwriting recognition before the person uses thesystem for handwriting recognition for the first time.
Transmissionto acceleration teaching control 630 or OCR teaching control635 also occurs when recognition errors are detected; use ofacceleration teaching control 630 or OCR teaching control 635when recognition errors are detected is termed herein adaptiveteaching. Acceleration teaching control 630 or OCR teachingcontrol 635 operates on the data received, which data representshand movements by the user when writing a symbol, together withmanually-provided identification of the symbol codes that areassociated with the data. Acceleration teaching control 630 thenupdates database 640, a per-person per-symbol acceleration database;OCR teaching control 635 updates database 645, a per-personper-symbol OCR database. Database 640 and database 645 compriseprototypes of accelerations and symbol shape for each symbol,comprising data specific to each person for each symbol. The output of acceleration handwriting recognitioncontrol 650 comprises a list of symbol codes and their respectiveprobabilities. An acceleration handwriting recognition post-processingcircuit 660, chooses the correct symbol code based onthe list of symbol codes and probabilities, and on post-processinginformation which preferably comprises a database of previousconfusions and a dictionary.
The output of acceleration handwritingrecognition post-processing circuit 660 is a list ofsymbol codes and/or words sorted by likelihood. Receiving an output indication of the handwriting and providing an outputindication of symbols represented by the handwriting,wherein said step of providing an output indication of symbols employs inputfrom a digitizer (12) to provide a first output representing identification of symbolsalong a first identification channel and employs input from said at least oneaccelerometer (25) to provide a second output representing identification of symbolsalong a second identification channel and selects between the first and second outputsbased on predetermined criteria.
Intel CS630Sony DSC-P1Sony DSC-P10Pentax.istDLStarted with the crappy Intel pocket cam - basically a Web cam you could take with you. Fixed memory, 640x480 pics. That didn't last long.Got the Sony DSC-P1 from my dad - said it was too complicated for him.Dropped that one, upgraded to a DSC-P10. Worked great for a couple years, got really frustrated with lack of manual control, missed shots from lag, flash power/recharge timeGot the DL last year - love it probably last body for a while - spend money on new lenses!
My first digital was a no name Taiwanese product with internal memory and no display or viewfinder. It took 240x120 256 color pictures that blurred if blood pulsed through either your or your subject's veins during it's atrociously long exposure cycle. It took 15 seconds between images of which it could only store about a dozen in memory. It was roughly the same shape and thickness of a stack of 5 credit cards, brushed aluminum finish.Still it was a proof of concept and got me started with digital photography. Much like my handheld 1 bit black and white Logitech Scanman scanner convinced me that scanning would someday be a worthwhile technology. Agfa ePhoto 1280»I still have the box and all the original equipment. That camera was like $700.00 and a totally impulse purchase considering I didn't even own a computer at the time.
I think I purchased it in 1996 or 1997. I'd take pictures, then take the card reader to work and upload my pictures to the now defunct PhotoPoint using my employer's dial-up connection. I eventually got my pictures back from Photopoint, but I had to pay $32.00 per CD to do so.My current camera is on a holiday without me shooting caribou herds south of Fairbanks. That camera is a Canon Powershot A70.I really want an SLR and more than that I want to learn the technical aspects of photography and post processing.
Nothing against the fine photographic artists at DSLR, but the mass amounts of information and opinions available here and elsewhere on the internet is too mind-boggling and confusing for me to even begin to comprehend.
FIELD OF THE INVENTIONThis invention relates to a fermentation process for high-yield production of plasmid DNA in E.coli strains. In the disclosed process, a slow growth rate of E.coli cells is controlled and maintained by an automated nutrient feed scheme based on dissolved oxygen concentration (DOC) and pH. This controlled slow growth rate allows high plasmid DNA stability during the host cell replication. As a result, high yield production of plasmid DNA is achieved. The method of this invention has the following advantages when used as a manufacturing process for plasmid DNA production:1.
Easy to operate and highly reproducible due to its automated nutrient feeding control scheme.2. Applicable to a variety of DNA plasmids and E. Coli host strains, because the nutrient concentration-associated changes in DOC and pH are common phenomena in certain media formulations.3. Various desired growth rates may be achieved by adjusting the nutrient feed rate with different set points of DOC and pH.
BACKGROUND OF THE INVENTIONFermentation has long been a key technology for mass production of biological products. An economically sound fermentation process usually has to demonstrate the following advantages: optimal cell production, maximum product accumulation and minimum nutrient consumption. In most industrial applications, fed-batch cultures have been found preferable over batch cultures because during a fed-batch fermentation an optical cell growth rate and nutrient consumption rate can be achieved by controlling the nutrient feeding in a desired range. A successful fed-batch culture can reach a maximum cell density of over 100 g/L cell dry weight (Mori et al., Journal of Chemical Enqineerinq of Japan 12:3)).
Thus the highest levels of volumetric productivity can be achieved. In a batch culture it is generally necessary to provide a high initial concentration of nutrients in order to sustain cell growth over an extended time.
As a result, substrate inhibition may occur in the early stages of cell growth, followed by a nutrient deficiency in the late stages of fermentation. Consequently, an optimal cell growth rate and product accumulation rate can hardly be obtained in a batch culture.A number of nutrient feeding strategies have been explored as a means of controlling cell growth in fed-batch cultures.
The strategies can be divided into two groups: non-feed-back control and feed-back control. The former includes controlling the nutrient feeding rate according to a pre-determined, constant or exponential profile (Yamane et al., J.Ferment.Technol. This type of feeding scheme requires that the cell performs reproducibly each time in both the inoculum and early batch culture stages to warrant the match of the feeding rate to the actual cell growth rate. This is a kind of very stringent control which may work very consistently, but could easily get off track if cell activity changes due to any environmental fluctuation. Feed-back control, on the other hand, can react based on demand and is directly correlated to the cell activities actually existing throughout the fermentation.
The control parameters which have been used for feed-back controls include respiratory quotient (Wang et al., Biotechnol.Bioeng. 19:)); pH (Nishio et al., J.Ferment. Technol.55:151-155(1977)), (Kim et al., Biotechnol Lett. 14:811-816(1992)); or DOC (Mori et al., Journal of Chemical Encineering of Japan 12:3)), (Yano et al., J. 56:416-420(1978)), (Cutayar et al., Biotechnol Lett.
11:155-160(1989)).With the advancement of recombinant DNA technology, the above fermentation technology has been further developed for production of recombinant proteins in recombinant organisms such as E.coli and many other cell cultures. A number of recombinant proteins which are produced by fermentation technology such as recombinant human insulin (Humulin®, Lilly), recombinant erythropoietin (Epogen®, Amgen), recombinant tissue plasminogen activator (Activase®, Genentech), and recombinant interferon (Roferon®, Roche), are now available for human pharmaceutical use.Some of these successful production fermentation processes for recombinant proteins have also been published in scientific journals or patents (Fieschko et al., Chem. 45:229-240(1986)), (Riesenberg et al., Patent No. However, most production scale fermentation processes (published or unpublished) for recombinant proteins are either a batch culture (Flodh. Acta Paediatr. 325:1-9.(1986)) or a fed-batch batch culture with a manual feed control scheme ((Fieschko et al., Chem. These processes are hardly reproducible, and require labor-intensive 'baby sitting' by experienced personnel.
Moreover, the conditions under which the process is operated are certainly not optimized.Most biotechnology companies do not spend time in developing an efficient fermentation process with an optimized control strategy because they frequently face short deadlines in putting their products on the market. Another reason is related to regulatory compliance. Some believe that an automated fermentation process with optimized computer controls is too complicated for validation purposes. As a result, few feed-back controlled fermentation processes have ever been developed for pharmaceutical production purposes.More recently, it has been shown that plasmid DNA can be used as a non-viral gene delivery system for clinical applications (Wang et al., Proc. USA 90:4156-4160 (1993). For such applications, which include gene therapy and genetic immunization, the plasmids themselves rather than the expressed proteins are the desired pharmaceutical products.
Accordingly, there is a need for pharmaceutically acceptable large scale processes for production of intact plasmid DNA. Although it is natural to think that it might be possible to produce plasmid DNA with the fermentation technology developed for recombinant proteins, the biological processes involved are fundamentally different due to different end products: plasmid DNA vs. Since cells are required to produce plasmid DNA in large quantities rather than proteins, precursor pools will be different: nucleotides vs. Secondly, plasmid production requires a different synthetic pathway than protein: DNA replication vs. Transcription and translation.
Thirdly, plasmid DNA is susceptible to degradation by nucleases rather than proteases. The undesired by-products of plasmid production will also be different: proteins, RNA, chromosomal DNA and other forms of DNA vs. DNA and RNA for protein products.
Furthermore, in order to obtain a high yield of plasmid DNA at the end of fermentation, cell growth rate may need to be regulated because a fast (close to maximum) growth rate may result in significant plasmid loss during fermentation (Zabriskie et al. Enzyme Microb. These factors may require special control strategies for fermentation of plasmid DNA. Specifically, an optimal cell growth rate and nutrient environment have to be identified and maintained to sustain a high plasmid DNA stability and-integrity.Recombinant bacterial plasmids for pharmaceutical applications typically contain large segments of insert DNA for disease targets, as well as the expression vectors themselves which typically comprise marker genes for selection purposes, origin sequences for DNA replication in bacteria, and eukaryotic promoter and other regulatory sequences for expression in mammalian cells. Such plasmid molecules tend to be large, on the order of 10 6 -10 7 daltons(5-20 kb), and particularly susceptible to mutations during fermentation. Therefore, a successful plasmid fermentation process has to provide a culture environment which maximizes the conversion of energy and substrates to plasmid DNA with high stability and integrity, while minimizing other by-products such as protein, RNAs and other DNAs as much as possible.This invention demonstrates that the above goals can be achieved through a careful medium formulation and an automated feed-back controlled nutrient feeding strategy based on DOC (dissolved oxygen concentration) and pH.
The process is based on the principle that when the carbon source in the culture is about to be completely depleted, DOC will rise rapidly. This is presumably due to a slowing down of respiratory activity (i.e., oxidative reactions). If the demand for the carbon source is not met, the pH of the culture will rise too. This phenomenon is probably caused by the consumption of metabolic fatty acids (e.g., acetic acid et al.) by cells as an alternative carbon source. The increase in pH could also be caused by production of ammonium ions as a result of protein degradation. Based upon the above, we designed an automated process using both pH and DO controllers to control the nutrient feeding rates. The DO controller also controls the agitation rate and the pH controller also controls the addition of base to the fermentation medium.
By adjusting DO and pH control set points, the cell specific growth rate was decreased about 10 fold. As a result, plasmid DNA yield was increased by about 10 fold. BRIEF DESCRIPTION OF THE DRAWINGSFIG. Time course of the controlling parameters: pH and DO.
Agitation and nutrient pump output during the DO/pH stat feed-back controlled fermentation.FIG. Profiles of cell growth in the DO/pH stat feed-back controlled fermentation and a manual fed-batch culture.FIG. Production of plasmid DNA in the DO/pH stat feed-back controlled fermentation and a manual fed-batch culture.
DETAILED DESCRIPTION OF THE INVENTIONSeed culture preparation.E.coli strain DH10b (Gibco BRL, Life Technologies, Inc., Gaithersburg, Md.) containing a 7.2 Kb plasmid with Col E1 origin and HIV-1 env gene was cultured in a flask of seed medium on a rotary shaker at 37° C. For 16 hours.
The seed medium consisted of Na 2 HPO 4 6 g, KH 2 PO 4 3 g, (NH 4) 2 SO 4 3 g, MgSO 4.7H 2 O 0.25 g, glucose 5 g, and yeast extract log per liter. The seed volume is 1% of fermentor batch medium.
The growth of the seed was measured by optical density at 600 nm with Spectrophotometer UV-1201 (Simadzu, Columbia, Md.). A typical OD range of 3-4 was seen after 16 hours of incubation.Fermentor Operation.A lab scale fermentation was carried out in a 7L stirred reactor, Bioflo3000 (New Brunswick Scientific, Edison, N.J.). The reactor was equipped with a built-in digital controller for pH, temperature, agitation, DO and a nutrient feed pump.
The above control parameters could also be set and controlled using the AFS fermentation process software through a PC (Advanced Fermentation Software, Ver. 3.42, New Brunswick Scientific Co., Edison, N.J.). The AFS software is designed to monitor such common parameters as temperature, pH, DOC, and agitation.In this experiment, the control scheme is as follows: The pH controller drives a base pump and the DO controller can control agitation speed through assigning controlling set points on the AFS software. If the value of the pH drops below the set point (7.0), the controller will automatically activate a peristaltic pump to add NH 4 OH until the pH is brought back to 7.0. If the DOC drops below the set point (30%), the controller will send signals to increase the agitation speed until the DOC rises above the set point. When the DOC set point is reached agitation rate will remain unchanged until a further increase is triggered.
The above set points can be set either on the controllers or on the AFS software. The nutrient is fed via a peristaltic pump which is controlled through the programming of the AFS software as below: if DOC 50%, or pH 7.2, the nutrient pump=1 (i.e., activated); if DOC 7.2 or DOC 50%, the software will send signals to activate the nutrient pump. The method according to claim 15, wherein said plasmid is a recombinant plasmid which contains a gene encoding a desired polypeptide suitable for expression in a mammalian cell.
Crsi standard bends. CRSI Foundation works with the CRSI Education Committee in designing and implementing programs.Notice to Researchers:The CRSI Foundation would like to inform you that the 2018 research funds have already been allocated to research related to high strength reinforcing steel. Please visit the website again for future updates. CRSI Education and Research FoundationThe CRSI Foundation is a nonprofit educational foundation responsible for funding and administering graduate and undergraduate scholarships for architectural and/or engineering students; and scholarships and/or training programs at vocational/technical schools which offer programs in estimating and/or detailing of reinforcing steel.
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Please enter 5 or 9 numbers for the ZIP Code. Scantron SCANMARK Es Optical Mark Reader Scanner eBayFor additional information, see the Global Shipping Program terms and conditions – opens in a new window or tab No additional import charges on delivery Delivery: Get the item you ordered or get your money back. Other offers may also be available.
Why won’t my scanner work? Seller assumes all responsibility for this listing. Scantron SCANMARK ES2260 Test Scan Grader Scorecard ReaderLearn more – opens in a new window or tab. Some cosmetic wear on unit. What happens if I laid down on the scanner at the store? Select a valid country.
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