The presence of vestibular pathology is tested in an embodiment wherein the subject is placed on a support surface that is sway-referenced about an axis co-linear with the subject's ankle joints, if the subject is standing, or the subject's hip joints, if the subject is sitting. After the subject has assumed a position of equilibrium, a controlled external stimulus, such as an electrical, a caloric or a barometric stimulus, is applied to one or both of the subject's inner ears. It is then determined whether the stimulus produces a significant subject sway-response. In an alternative embodiment, the sway-response is monitored with the subject placed on a support surface that is sway-referenced about an axis perpendicular to the axis that is co-linear with the subject's ankle or hip joints. In another embodiment, the subject's visual orientation information is disrupted by means of a sway-referenced visual enclosure. In a further embodiment, the subject's head is aligned such that the sensitive axis of one vestibular end organ is aligned with the sway-reference axis.

The inner ear vestibular system is composed of two laterally symmetric sets of end organs (see for example Chapters 3 and 4 in Wilson, V. J., Melvill Jones, G., Mammalian Vestibular Physiology, Plenum Press, New York, 365 pp (1979). Each ear contains fine spatially specific end organs for sensing head accelerations. In each ear three semicircular canals sense angular, accelerations in three approximately orthogonal axes. The utricular otoliths sense the sum of gravity and linear head accelerations in a plane inclined approximately 30 degrees from horizontal. Function of the saccule is less understood but is believed to include gravity and linear acceleration along an approximately vertical axis. Thus, individual vestibular end organs are involved in maintaining different components of posture and equilibrium. The horizontal canals are used primarily to control horizontal plane eye and head movements, while the vertical canals and otoliths help maintain front-to-back and side-to-side balance of the head and trunk. The spatial and functional specificity within the vestibular system provides an opportunity for selectively determining the extent of pathology of individual end organs by observing both head, eye, and body responses to vestibular stimulation.
It is also known that the canal and otolith end organs sense different frequency components of linear and angular motion. Canals sense angular acceleration frequencies over the range of 0.1 to approximately 5 Hz, while the otoliths sense lower frequency linear accelerations in the range of 0 to 0.1 Hz (Meary, J. L., the vestibular system and human dynamic space orientation, NASA CR-628 (1966)). Thus, the use of frequency selective signals is another possible means for isolating the function, of individual vestibular end organs.
Vestibular pathology frequently affects only a portion of the vestibular end organs, sometimes in one ear and other times distributed either equally or unequally among the organs of the two ears (see, for example, Schuknecht, H. F., Pathology of the ear, Harvard University Press, Cambridge, Mass. (1974)). While, the treatment of choice for the patient with vestibular pathology depends on the distribution and extent of involvement among the ten end organs, the symptoms of the individual patient frequently do not reveal which organs are affected. Hence, objective methods for assessing the function of individual vestibular end organs are essential to the comprehensive vestibular examination.
To test vestibular functions head acceleration, stimuli can be imposed with precise time course, amplitude, and spatial specificity. However, precise acceleration stimuli cannot be effectively used to test vestibular end organs individually, because the lateral symmetry of the two inner ears means that acceleration in any one axis will always excite end organs in both ears. Hence, several alternative means for selective stimulation of end organs in a single ear have been developed using non-physiologic inputs: (1) Using so called "galvanic" vestibular stimulation, end organs of one ear can be electrically excited by passing small currents between two or more surface electrodes affixed to the mastoid bone of the ear or other locations on the head (see, for example, Nashner, L. M., Wolfson, P., Influence of head position and proprioceptive cues on short latency postural reflexes evoked by galvanic stimulation of the human labyrinth, Brain Research 67: 255-268 (1974)). (2) The so called "caloric" stimulus excites the horizontal semicircular canal end organ of one ear by creating a thermally induced pressure gradient within the horizontal canal (see, for example, Dayal, V. S., Farkashidy, J., Kuzin, B., Clinical evaluation of the hot caloric test as a screening procedure, Laryngoscope 83: 1433 (1973)). (3) In some instances changes in air pressure between the external canal and middle ear spaces of one ear can excite one or more end organs in that ear (see for example Daspit, C. P. Churchill, D., Linthicum, F. H., Diagnosis of perilymph fistula using ENG and impedance, Laryngoscope 90: 217-223 (1980).
Various attempts have been made to use the "galvanic" vestibular stimulus as a clinical diagnostic tool (for examples, Ishihara, A., Galvanic stimulation of the labyrinth, Jap. J. Otol. Tokyo 24: 482 (1918); Fischer, J. J., Galvanic reaction, The labyrinth, Grune and Stratton Inc, New York (1956); Pfaltz, C. R., Koike, Y., Galvanic test in central vestibular lesion, Acta, Otolarying. (Stockh) 65: 161 (1968)). In this test the vestibular end organs are selectively stimulated by passing small electrical currents between electrodes placed in different configurations on the mastoid bones. Placing one electrode on each mastoid bone stimulates receptors in both inner ears in opposite directions, while two electrodes placed on a single mastoid bone stimulate receptors of one ear selectively. While the time course, amplitude, and frequency of electrical current stimuli can be precisely controlled, the distribution of stimulation among the 5 end organs of the stimulated ear can be accomplished only to a limited degree by altering the placement of the electrodes. Responses to electrical vestibular stimulation can be monitored as movements of the eyes (for example, Hozawa, J., A clinical consideration on the nature of electrically stimulated nystagmus, Otologica, Tokyo 33: 939 (1961)) or in the standing subject as body swaying (for example, Coats, A. C., Stolz, M. S., the recorded body sway response to galvanic stimulation of the labyrinth, Laryngoscope 79: 85 (1969); Coats, A. C., Effects of varying stimulus parameters on the galvanic body sway response, Ann. Otol. 82: 96 (1973)).
Electrical stimulation of the vestibular receptor organs is a potentially useful clinical diagnostic method, because it can be used to quantify receptor function of one ear at a time and because the time course and frequency of stimulation can be precisely controlled. Electrical vestibular testing for this or any other purpose, however, is not currently a standard of practice in the clinic. This is because relatively large currents are required to produce postural or eye movement responses when the subject is tested under passive seated or reclining positions. Large stimulus levels can cause the patient significant discomfort. Furthermore, the resulting eye movement and sway responses are small, making the repeatability and reliability of the resulting measurements poor.
The use of "caloric" stimulation is already a standard practice in the currently used clinical vestibular examination, and several manufacturers produce caloric stimulation devices for this purpose. With the caloric test, the patient assumes a passive reclining position on a chair or bed. The head is positioned tilted 30 degrees back so that the plane of the horizontal canals is oriented roughly vertical. Then, hot or cold water is introduced to one ear and the amplitude and duration of nystagmoid eye movement responses are observed subjectively or measured using electronystagmography (ENG's). Alternatively, bilateral stimuli can be imposed by introducing thermal stimuli of either the same or opposite temperatures to the two ears simultaneously.
The caloric test is currently used by clinicians to identify asymmetries in function between the two ears. The sensitivity and specificity of this method is limited, however, for several reasons. First, with currently available methods, the thermal input stimulates only the horizontal canals and therefore does not detect asymmetries involving the vertical canals or otoliths. Second, the amplitude and frequency of the thermal stimulus cannot be controlled precisely, because heat conduction through the temporal bone is slow and varies among patients. Thus, the time course of the thermal vestibular stimulus is also slow and tests only the lowest frequency component of the horizontal canal response. Third, patients frequently become dizzy, motion sick, or nauseous with the caloric test.
The third method for selectively stimulating one or more vestibular end organs is to alter the pressure between the external and middle ear spaces. As with the caloric vestibular test, pressure stimuli are introduced with the patient in a passive seated or standing position.

Apparatus and method for determining the presence of vestibular pathology


Animal-free meninge fermentation media and process is developed based upon use of a chemically defined medium. To improve polysaccharide production, fed-batch fermentation is examined using different feed solutions and feeding strategies. A feed solution containing glucose, amino acids, and trace metal elements produces Group A polysaccharide at approximately 3 times the level observed with batch fermentation. This process is used successfully to produce polysaccharides of N. meningitidis serotypes A, C, Y and W-135 and is run reproducibly at the 20L scale and can be scaled to 400L or more.

1. Field of the Invention
This invention relates to the field of vaccine preparation and, in particular, fermentation of Neisseria bacteria, particularly N. meningitidis, for the production of polysaccharide for use in vaccines.
2. Summary of the Related Art
N. meningitidis causes both endemic and epidemic disease, principally meningitis and meningococcemia. As a result of the control of Haemophilus influenzae type b infections, N. meningitidis has become the leading cause of bacterial meningitis in children and young adults in the United States (US), with an estimated 2,600 cases each year. (Recommendation of the Advisory Committee on Immunization Practices (ACIP). "Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks." MMWR 46: No. RR-5, 1997 6 (hereinafter "ACIP"); CDC 1, Laboratory-based surveillance for meningococcal disease in selected areas—United States, 1989-1991, MMWR 42: No SS-2, 1993 (hereinafter "CDC 1").) The case-fatality rate is 13% for meningitis disease (defined as the isolation of N. meningitidis from cerebrospinal fluid) and 11.5% for persons who have N. meningitidis isolated from blood (ACIP, CDC 1) despite therapy with antimicrobial agents (e.g., penicillin) to which US strains remain clinically sensitive. (ACIP)
Based on multistate surveillance conducted during 1989 to 1991, serogroup B organisms accounted for 46% of all cases and serogroup C for 45%; serogroups W-135 and Y and strains that could not be serotyped accounted for most of the remaining cases. (ACIP, CDC 1) Recent data indicate that the proportion of cases caused by serogroup Y strains is increasing. (ACIP) In 1995, among the 30 states reporting supplemental data on culture-confirmed cases of meningococcal disease, serogroup Y accounted for 21% of cases. (CDC. Serogroup Y Meningococcal Disease—Illinois, Connecticut, and Selected Areas, United States, 1989-1996. MMWR 46:Vol. 45, 1010-1013, 1996 (hereinafter "CDC 2").) Serogroup A, which rarely causes disease in the US, is the most common cause of epidemics in Africa and Asia. A statewide serogroup B epidemic has been reported in the US. (CDC. Serogroup B meningococcal disease—Oregon 1994. MMWR 44: 121-124,1995 (hereinafter "CDC 3").) N. meningitidis vaccines comprise group specific polysaccharide antigens. Several discoveries impacted the future of meningococcal polysaccharide vaccines and demonstrated the significance of anti-capsular antibodies in protection. (Frasch, "Meningococcal vaccines; past, present and future," in Meningococcal Disease, ed. K. Cartwright. John Wiley and Sons Ltd, 1995.) In the late 1930s, serogroup-specific antigens of meningococcal serogroups A and C were identified as polysaccharides. (CDC 3) During the mid 1940s, investigators demonstrated that the protection of mice by anti-serogroup A meningococcal horse serum was directly related to its content of anti-polysaccharide antibodies. (Frasch) Meningococcal polysaccharide vaccines were first demonstrated to be immunogenic in humans by Gotschlich and his co-workers in the 1960s when immunization of US Army recruits with serogroup A and C polysaccharides induced protective antibodies. Id. The investigators recorded a significantly reduced acquisition rate of serogroup C carriage among vaccinated recruits compared with unvaccinated individuals. Id.
Meningitidis polysaccharide manufacture requires fermentation of N. meningitidis. Current good manufacturing practice (cGMP) imposes several criteria to medium development for microbial fermentation for the production of biologics. Ideally, the medium should contain only essential components, be easily prepared in a reproducible manner, and support robust high-cell density culture. A chemically defined medium is inherently more reproducible than a complex medium. Furthermore, a chemically defined medium enables discrete analysis of the effect of each component and strict control of medium formulation through identity and purity testing of raw materials. Finally, the fermentation medium should support the cultivation of the microorganism in question to high-cell density to improve volumetric productivity and to generate a final culture whose composition and physiological condition is suitable for downstream processing.
Catlin [J. Inf. Dis. 128:178-194, 1973], described a complex chemically defined medium named NEDF, containing approximately 54 ingredients, including all twenty naturally occurring amino acids, for growth of Neisseria. In addition, Catlin described a medium called MCDA containing 18 ingredients (in mM: NaCl, 100; KCl, 2.5; NH4Cl, 7.5; Na2HPO4, 7.5; KH2PO4, 1.25; Na3C6H5O7.2H2O, 2.2; MgSO4.7H2O, 2.5; MnSO4.H2O, 0.0075; L-glutamic acid, 8.0; L-arginine.HCL 0.5; glycine, 2.0; L-serine, 0.2; L-cysteine HCl.H2O, 0.06; sodium lactate, 6.25 mg of 60% syrup/mL of medium; glycerin, 0.5% (v/v); washed purified agar, 1% (wt/vol) CaCl2.2H2O, 0.25; Fe2(SO4)3, 0.01) which was reported to support growth of Neisseria meningitidis on agar. The ability of MCDA to support growth in liquid medium (that is absent addition of agar) was not reported. La Scolea et al., [Applied Microbiology 28:70-76, 1974] reported on a defined minimal medium named GGM for the growth of Neisseria gonorrhoeae. The medium contained minimal salts, eight amino acids, two nitrogen bases, vitamins, coenzymes, metabolic intermediates and miscellaneous components. La Scolea et al. reported growth of this strain to an optical density of 400 Klett units. An absorbance of 1 at 600 nm is considered equivalent to 500 Klett units [see Gerhardt et al., Manual of Methods for General Bacteriology, 1981, ASM., p. 197]. Therefore, the maximum reported growth density achieved by LaScolea et al., was less than about one (1) absorbance unit. SU 1750689 A1 described a method for preparing polysaccharide-protein vaccines against Neisseria meningitidis B. A defined medium was described having the following composition, g/L:
Sodium L-glutamate1.30 ± 0.10L-cysteine hydrochloride0.03 ± 0.01Potassium chloride0.09 ± 0.01Sodium chloride6.00 ± 1.00Magnesium sulfate heptahydrate0.06 ± 0.01Ammonium chloride1.25 ± 0.01Disubstituted sodium phosphate2.50 ± 0.20dodecahydrateTrisubstituted sodium citrate0.50 ± 0.10Glucose1.60 ± 0.20
In this medium, it is reported that Neisseria may be cultured to a final optical density of 1.5±0.2 on the FEK-56M scale. This is an unfamiliar scale for optical density determination. However, based on the available carbon sources in the above noted medium, it is predictable that the maximum absorbance achievable would be in the range of about 1.5 absorbance units.
U.S. Pat. No. 5,494,808 reports a large-scale, high-cell density (5 g/L dry cell weight, and an optical density of between about 10-13 at 600 nm) fermentation process for the cultivation of N. meningitidis. This patent disclose the following medium (called "MC.6") for culturing Neisseria meningitidis for isolation of OMPC ("Outer Membrane Protein Complex") (all values in mg/L):
NaCl5800K2HPO44000NH4Cl1000K2SO41000Glucose10,000L-Gutamic Acid3900L-Arginine150Glycine250L-Serine500L-Cysteine.HCl100MgCl2.6H2O400CaCl2.2H2O28Fe(III) Citrate40
MENOMUNE® A/C/Y/W-135, Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined, for subcutaneous use, is a freeze-dried preparation of the group-specific polysaccharide antigens from Neisseria meningitidis, Group A, Group C, Group Y and Group W-135. N. meningitidis are cultivated with Mueller Hinton agar1 and Watson Scherp2 media. The purified polysaccharide is extracted from the Neisseria meningitidis cells and separated from the media by procedures which include centrifugation, detergent precipitation, alcohol precipitation, solvent or organic extraction and diafiltration.

Animal component free meningococcal polysaccharide fermentation and seedbank development


Methods, systems, and devices for encrypting and decrypting data. In one implementation, an encryption method includes inputting plaintext into a recurrent artificial neural network, identifying topological structures in patterns of activity in the recurrent artificial neural network, wherein the patterns of activity are responsive to the input of the plaintext, representing the identified topological structures in a binary sequence of length L and implementing a permutation of the set of all binary codewords of length L. The implemented permutation is a function from the set of binary codewords of length L to itself that is injective and surjective.

Cryptographic encryption provides secure communications between parties even in the event that a third party (commonly called an "adversary") intercepts the communication. Encrypted communications are encoded such that only authorized recipient(s) can access the communications. In general, the communications themselves are referred to as "plaintext," which is a term that encompasses both textual and other messages. The algorithm that encrypts the communications is commonly referred to as a "cipher" and the encrypted communications are referred to as "ciphertext." Although the ciphertext may be intercepted or otherwise available to an adversary, decoding the ciphertext to access the encrypted communication is generally very difficult.
In general, encryption can be classified as "symmetric key" or "public key." In symmetric key encryption, the same key is used for encrypting plaintext and decrypting ciphertext. Since both the sending and receiving parties must have access to the same symmetric key, the symmetric key must be exchanged over a secure channel to ensure privacy. In public key encryption, the encryption key can be published and used by many parties to encrypt plaintext. However, only the intended recipients should have access to the decryption key that enables ciphertext to be decrypting.
In any case, improved cryptographic encryption would be beneficial in many contexts, including data storage, communications, digital signatures, authentication, and electronic commerce.


Esterquats based on natural fats and oils can be directly produced by subjecting fatty acid glyerine ester to ester interchange, in the presence of alkaline and/or alkaline earth boron hydrides and hypophosphoric acid or their alkaline and/or alkaline earth salts and possibly free fatty acid, with hydroxy-functionalised tertiary amines and quaternising the resultant products in the manner known per se.

1. Field of the Invention
This invention relates to a process for the production of esterquats, in which fatty acid glycerol esters are directly transesterified with tertiary hydroxyamines and then quaternized, and to the use of the products for the production of surface-active formulations.
2. Statement of Related Art
In recent years, quaternized fatty acid triethanolamine ester salts, socalled "esterquats", have acquired increasing significance as ecotoxicologically safe raw materials for fabric softeners cf. O. Ponsati in C.R. CED Congress, Barcelona, 167 (1992) and R. Puchta in C.R. CED Congress, Sitges, 59 (1993)!.
According to the teaching of International patent application WO 91/01295 (Henkel), esterquats are normally produced from triethanolamine or adducts of ethylene oxide with triethanolamine which, in a first step, are partly esterified with linear C.sub.16/18 fatty acids in the presence of hypophosphorous acid and subsequently treated with air. The fatty acid triethanolamine esters are then quaternized, for example with alkyl halides or, preferably, dialkyl sulfates.
Instead of fatty acids themselves, it is desirable for economic reasons directly to use natural fats and oils, from which the fatty acids are obtained, as starting materials for the production of esterquats. However, according to studies conducted by applicants, application of this principle on an industrial scale has hitherto been prevented by the fact that transesterification in the presence of the alkaline catalysts typically used for this type of reaction, namely potassium hydroxide or sodium methylate, generally involves overly long reactor possession times and, in general, leads to discolored products which have to be bleached in an additional, expensive process step.
Accordingly, the problem addressed by the present invention was to provide a process for the production of esterquats based on fats and oils as starting materials which would not have any of the disadvantages mentioned above.

Process for the production of esterquats


Optical fiber connector comprises a ferrule receiving an optical fiber and a sleeve member for holding the ferrule. The body of the ferrule is made of glass on which a thin layer is deposited for reinforcement of the body. The thin layer may be made by hydrolysis, chemical vapor deposition, spray coating etc. The ferrule of the optical fiber connector is inexpensive, easy to assemble and suitable for mass production.

The present invention relates to an optical fiber connector, and more particularly to the structure of a ferrule of an optical fiber connector.
An optical fiber connector is a device used in almost every optical communication device or other optical equipment, and is provided for coupling two optical fibers or an optical fiber with a light-emitting or light-receiving device or the like.
An example of a conventional optical fiber connector is described, for example, in Japanese Patent Laid-open Publication No. Hei-2-253207. FIG. 4 shows an optical fiber connector of this type which comprises a ferrule 2 made of ceramic, and a sleeve member 3 made of stainless steel supporting and securing the rear part of the ferrule 2 at the front bore 3A of the sleeve member 3. The ferrule 2 receives within a central orifice thereof an optical fiber 1 composed of a core and a clad layer.
It is necessary to manufacture the ferrule 2 depicted in FIG. 4 out of a stiff material, e.g. ceramic as in the case of the publication above mentioned, and it is not practical to manufacture the ferrule out of a cheep and brittle glass material, since the glass ferrule would be split by even a moderate external force, causing disconnection of the optical fiber 1. Consequently, an optical fiber connector of this type is expensive due to the expensive material for the ferrule.
Besides, to manufacture the ferrule 2 shown in FIG. 4, it is necessary to grind the outer surface of the ferrule with good accuracy. As shown in FIG. 5, such grinding is usually carried out with a grinding tool 10 the position of which is adjustable in the directions shown by arrows A, and co-operative supporting means 9 rotatably supporting the ferrule 2 at the both ends of the ferrule. The grinding of the work-piece is carried out one by one, so that the ferrule of this type is not adapted for mass production.
FIG. 6 shows another type of a conventional optical fiber connector in which a glass capillary tube 7 for receiving an optical fiber 1 is protected by a sleeve member 8 made of stainless steel. The sleeve member 8 entirely covers at the front part thereof the capillary tube 7 made of a brittle material, i.e. glass, thus avoiding the problem relating to a glass ferrule having the shape depicted in FIG. 4. The optical fiber connector shown in FIG. 6 is, however, also expensive due to the complicated structure of the sleeve member 8 receiving entirely the glass capillary tube 7 and holding the front end of the outer sheath 6 of the optical fiber cable. This structure is also necessary to grind the outer surface of the ferrule with good accuracy.

Optical fiber connector having a glass ferrule covered by a thin reinforcing layer


A computer-implemented process for smoothing and compression of data having an ordered list of points including a first point, a second point and a third point, each of the points being on the perimeter of a polygon. The method includes determining whether the triangle defined by line segments joining the first, second, and third points has a point of significance in its interior; and if no point of significance is present in the region, removing the second point of the ordered list of points.

1. Field of the Invention
This invention relates in general to a system and method for compression of data points having at least two coordinates, and more particularly to data in vector or raster format, and to a method for smoothing and compression of polyline data.
2. Background Information
Clustering algorithms have been developed in support of various disciplines, including biology (e.g., clustering bacterial growth), physics (e.g., clustering high-energy particles), demographics (e.g., clustering populations), medicine (e.g., identifying clusters of tumors), and information technology (e.g., data mining, compression, and sorting; image classification, segmentation, and retrieval).
Some aspects of clustering are described in: Barnard, J. M., "Agglomerative hierarchical clustering package from Barnard Chemical Information, Ltd.", Daylight EUROMUG Meeting, Basel, Switzerland (1996); Can, F. and Ozkarahan, E. A., "Concepts and effectiveness of the cover-coefficient-based clustering methodology for text databases", ACM TODS 15(4): 483-512 (December 1990); Cormen, T. H., Leiserson, C. E., and Rivest, R. L., "Introduction to Algorithms", Second Edition, MIT Press and McGraw-Hill, Cambridge, Mass. (2001); Day, W. H. E. and H. Edelsbrunner, "Efficient algorithms for agglomerative hierarchical clustering methods", Journal of Classification, 1(1), pp. 7-24 (1984); Downs, G., "Clustering in chemistry", MathFIT workshop, Belfast (2001); Downs, G. M. and J. M. Barnard, "Clustering methods and their uses in computational chemistry", Reviews in Computational Chemistry, Vol. 18, Ch. 1, pp. 5-40 (2003); U.S. Pat. No. 6,218,965 B1 to Gendron, M. L., Wischow, P. B., Trenchard, M. E., Lohrenz, M. C., Riedlinger L. M., and Mehaffey, M. J., "Moving Map Composer", Halkidi, M., Batistakis Y., and Vazirgiannis, M., "Cluster validity methods: Part II", SIGMOD Record (2002); Hartigan, J. A., "Clustering Algorithms", John Wiley and Sons, Inc., New York, N.Y. (1975); Hartigan, J. A. and Wong, M. A., "A K-means clustering algorithm", Applied Statistics, Vol. 28, 100-108 (1979); Ho, T. K. and Nagy G., "OCR with no shape training", Proceedings of the 15th International Conference on Pattern Recognition, pp. 27-30, Barcelona, Spain, 2000; Hobby, J. and T. K. Ho, "Enhancing degraded document images via bitmap clustering and averaging", Proceedings of the 4th International Conference on Document Analysis and Recognition, pp. 394-400, Ulm, Germany, (1997); Hoppner, F., Klawonn, F., Kruse R., and Runkler, T., "Fuzzy Cluster Analysis", John Wiley and Sons, Inc., Chicester, England, (1999); Jain, A. K., M. N. Murty, and P. J. Flynn, "Data clustering: a review", ACM Computing Surveys, Vol. 31, Issue 3, pp. 264-323 (1999); JMPIN V.4.0.4 statistical analysis software package, SAS Institute Inc., Cary, N.C. (2003); Layne, G., M. Gendron and M. Lohrenz, "POS Polyline Smoothing: Reduction of Polyline Vertices", Proceedings of the Tenth International Conference on Industry, Engineering and Management Systems, Cocoa Beach, Fla., March, 2004; Sibson, R., "SLINK: An Optimally Efficient Algorithm for the Single-Link Cluster Method", Comput. J. 16(1): 30-34(1973); Spiegel, M. R., "Schaum's outline of theory and problems of probability and statistics", Schaum's outline series, McGraw-Hill, New York, N.Y. (1975); Voorhees, E. M. "The effectiveness and efficiency of agglomerative hierarchic clustering in Document Retrieval", Ph.D. Thesis, Cornell University, N.Y. (1985a); Voorhees, E. M., "The cluster hypothesis revisited", Proceedings of the 8th Annual International ACM SIGIR Conference on Research and Development in Information Retrieval, pp. 188-196 (1985); and Yoon, J. P., Raghavan, V., and Chakilam, V., "BitCube: a three-dimensional bitmap indexing for XML documents", Journal of Intelligent Information Systems, 17:241-252 (2001).
U.S. patent application Publication No. 20040233197 to Liu et al. discloses a method for data compression for reducing the complexity of lines representing handwriting. Curve smoothing for lines CAD generated lines is disclosed in U.S. patent application Publication No. 20030025697 to Gupta.

System and method for smoothing and compression of polyline data

The United States of America as represented by the Secretary of the Navy


An assay to screen potential inhibitors of the C4 acid cycle in plants. The assay involves testing inhibition of C4 enzymes by incubating a mixture that includes pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase and malate dehydrogenase and their substrates with a potential inhibitor. Detection of inhibition depends on comparing the resulting levels of NADH or NAD+ in the test mixture to the levels of NADH or NAD+ in a control.

The invention described below relates to an assay procedure for screening potential inhibitors of plant enzymes. In particular, the invention relates to an assay procedure which can be used for the high-throughput screening of potential inhibitors of enzymes of the C4 acid cycle in plants.
The majority of plants can be divided into C3 and C4 plants, depending on the mechanism the plant uses to incorporate CO2 into organic compounds. In C3 plants, CO2 is initially added onto a five-carbon compound forming an unstable six carbon compound which dissociates into two stable three carbon compounds, hence the C3 name. On the other hand, the first stable compound formed in C4 plants is a four carbon compound. An extra biochemical pathway exists in the leaves of C4 plants which allows them to fix CO2 more efficiently and, under certain environmental conditions, to grow more rapidly than their C3 counterparts. In addition, C4 plants use water and nitrogen more efficiently than C3 plants. Together, these properties enable C4 plants to compete favourably with many of the world""s crops, most of which are C3 plants for example, wheat, rice, barley and oats. It follows then that many of the weeds which have an adverse effect on agricultural production throughout the world are C4 plants. Typical examples are nutgrass (Cyperus rotundus), couch grass (Cynodon dactylon), barnyard grass (Echinochloa spp.), Johnson grass (Sorghum halopense), and goose grass (Eleusine indicia). Nutgrass is a particularly serious global problem being present in more than 100 countries and affecting more than 50 crop species. For efficient agricultural production there is an obvious and pressing need for control of C4 weed species. To date, however, no herbicide specific for C4 weeds has been provided.
Crucial to the C4 acid cycle this being the cycle that fixes CO2 in C4 plants are the following enzymes: pyruvate orthophosphate dikinase (pyruvate,Pi dikinase); phosphoenolpyruvate carboxylase; and, NADP-malate dehydrogenase. The pathway involving these enzymes includes the step which incorporates atmospheric CO2 and creates the products which feed into the sugar-producing Calvin cycle. Interruption of this biochemical pathway should, therefore, adversely affect photosynthesis in C4 plants.
Attempts to develop a C4-specific herbicide have involved designing structural analogues of substrates of the C4 acid cycle enzymes. Those exhibiting inhibitory effects have been further modified to maximise their effect. The only report of a compound which specifically inhibited a C4 enzyme related to 3,3-dichloro-2(dihydroxy-phosphinoylmethyl)propenoate which acts on phosphoenolpyruvate carboxylase (see C. L. D. Jenkins et al., Biochem. Int. 14, 219-226 [1987]; H. G. McFadden et al., Aust. J. Chem. 40, 1619-1629 [1987]; C. L. D. Jenkins, Plant Physiol. 89, 1231-1237 [1989]; and, H. G. McFadden et al., Aust. J. Chem. 4, 301-314 [1989]). However, the compound was found to have no effect on the growth of C4 plants. At present, none of the compounds known to inhibit enzymes of the C4 acid cycle has herbicidal activity.
Nevertheless, inhibiting the C4 acid cycle to kill C4 plants remains a promising herbicidal strategy. It has been shown that C4 plants transformed by molecular means (antisense technology) to decrease the level of pyruvate, Pi dikinase or phosphoenolpyruvate carboxylase, enzymes specific to the C4 acid cycle, are incapable of surviving unless grown under high CO2 conditions (see J. P. Maroco et al., Plant Physiol. 116, 823-832 [1998]). Therefore, it follows that a compound that inhibits either pyruvate, Pi dikinase or phosphoenolpyruvate carboxylase might be an efficient and selective herbicide, thus preventing the deleterious effect of C4 weeds on C3 crops.
Marine organisms are an abundant source of compounds of benefit to humans. Many pharmaceuticals are isolated from plants or are derivatives of compounds first identified in marine organisms. Compounds of marine origin are also known which are enzyme inhibitors. Thus, it is reasonable to assume that because of the diversity of the compounds produced by marine organisms there are likely to be some that are inhibitors of C4 acid cycle enzymes.
In the absence of an indication that an organism produces a compound having desired properties, identification of useful compounds in marine organisms usually entails the screening of extracts from thousands of organisms. However, the known assays for the above three C4 enzymes, which are spectrophotometric assays, are large-volume assays and are not suitable for the screening of large numbers of samples. There is thus a need for an assay which can be used to screen large numbers of samples for potential inhibitors of the C4 acid cycle enzymes.
The object of the invention is to provide a high-throughput assay which can be used to screen potential inhibitors of enzymes of the C4 acid cycle in plants.
According to a first embodiment of the invention, there is provided an assay for inhibitors of C4 acid cycle enzymes of plants, the assay comprising:
a) testing for inhibition of at least one of pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase or malate dehydrogenase by:
i) including a sample containing the potential inhibitor in a test mixture comprising pyruvate orthophosphate dikinase and substrates thereof, phosphoenolpyruvate carboxylase and the substrate bicarbonate, and malate dehydrogenase and the substrate NADH;
ii) incubating said test mixture under conditions appropriate for the conversion of pyruvate to malate with oxidation of NADH; and
iii) detecting inhibition of at least one of said pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase or malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (a)(ii);
b) testing for inhibition of phosphoenol pyruvate carboxylase or malate dehydrogenase with any sample which contains an inhibitor of at least one of said pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase or malate dehydrogenase by:
i) including said sample in a test mixture comprising phosphoenolpyruvate carboxylase and substrates thereof, and malate dehydrogenase and the substrate NADH;
ii) incubating said test mixture under conditions appropriate for the conversion of phosphoenolpyruvate to malate with oxidation of NADH; and
iii) detecting inhibition of said phosphoenolpyruvate carboxylase or malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (b)(ii);
c) testing for inhibition of malate dehydrogenase with any sample which contains an inhibitor of said phosphoenolpyruvate carboxylase or malate dehydrogenase by:
i) including said sample in a test mixture comprising malate dehydrogenase, oxaloacetate and NADH or including oxaloacetate in said test mixture from a(ii) or b(ii);
ii) incubating said test mixture under conditions appropriate for the conversion of oxaloacetate to malate with oxidation of NADH; and
iii) detecting inhibition of said malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (c)(ii).
According to a second embodiment of the invention, there is provided an assay for inhibitors of C4 acid cycle enzymes of plants, the assay comprising:
a) testing for inhibition of at least one of pyruvate orthophosphate dikinase, phospho-enolpyruvate carboxylase or malate dehydrogenase by:
i) including a sample containing the potential inhibitor in a test mixture comprising pyruvate orthophosphate dikinase and substrates thereof, phosphoenolpyruvate carboxylase and the substrate bicarbonate, and malate dehydrogenase and the substrate NADH; and
ii) incubating said test mixture under conditions appropriate for the conversion of pyruvate to malate with oxidation of NADH;
iii) detecting inhibition of at least one of said pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase or malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (a)(ii);
b) testing for inhibition of phosphoenolpyruvate carboxylase or malate dehydrogenase with any sample which contains an inhibitor of at least one of said pyruvate orthophosphate dikinase, phosphoenolpyruvate carboxylase or malate dehydrogenase by:
i) including phosphoenolpyruvate in said test mixture from (a)(ii);
ii) incubating said test mixture under said conditions used in step (a)(ii); and
iii) detecting inhibition of said phosphoenolpyruvate carboxylase or malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (a)(ii);
c) testing for inhibition of malate dehydrogenase with any sample which contains an inhibitor of phosphoenolpyruvate carboxylase or malate dehydrogenase by:
i) including oxaloacetate in said test mixture from (a)(ii) or b(ii) or including said sample in a test mixture comprising malate dehydrogenase, oxaloacetate and NADH;
ii) incubating said test mixture under said conditions used in step (a)(ii); and
iii) detecting inhibition of said malate dehydrogenase by comparing the level of NADH or NAD+ in said test mixture with the level of NADH or NAD+ in a control mixture incubated under the same conditions as in (a)(ii).
Other aspects of the invention and the best mode of carrying out the invention will become apparent from a reading of the following detailed description.
The following abbreviations are used hereafter:
ATP adenosine triphosphate
AMP adenosine monophosphate
Pi inorganic phosphate
PPi inorganic pyrophosphate
NADH nicotinamide-adenine dinucleotide (reduced form)
NAD+ nicotinamide-adenine dinucleotide (oxidised form)
PPDK pyruvate orthophosphate dikinase (EC 18.104.22.168)
PEP C phosphoenolpyruvate carboxylase (EC 188.8.131.52)
MDH NAD-malate dehydrogenase (EC 184.108.40.206)
HEPES N-[2-hydroxyethyl]piperazine-Nxe2x80x2-[2-ethanesulfonic acid]
OAA Oxaloacetate
The term xe2x80x9ccomprisingxe2x80x9d as used in the above definition of the embodiments and hereafter denotes a mixture or composition which includes at least the specified components but should not be interpreted as meaning that the mixture or composition consists of only those components. Mixtures and compositions can include other ingredients known to those of skill in the art as normal components of mixtures for the assay of enzymes. Examples of these other ingredients include buffers with a suitable pKa to allow control of the assay mixture within the desired pH range such as HEPES, 2-(N-Morpholino)ethanesulphonic acid (MES), 3-N-Morpholino)propanesulphonic acid (MOPS) or Tris(hydroxymethyl)aminomethane (Tris) but excluding phosphate buffers which will interfere with the reaction; reducing agents such as dithiothreitol or xcex2-mercaptoethanol and salts such as the salts of mono and divalent options. For example PPDK is a divalent cation dependent enzyme and requires the presence of a divalent cation, such as Mg2+, Ca2+ and Mn2+. PEP C is also divalent cation dependent, being dependent on the presence of a divalent metal cation. Other salts, such as ammonium sulphate may be added to improve the performance of the assay.
The present inventors have found that the activities of the C4 plant enzymes PPDK and PEP C can conveniently be assayed in a microtitre plate format using the procedures summarised above thus allowing for the screening of a large number of potential inhibitors of these enzymes or of samples suspected of containing inhibitors. The reactions involved in the assay are as follows:
in which the abbreviations set out above have been used. The MDH used for the final reaction in the above sequence is preferably not the C4 plant NADP-dependent enzyme, but is instead the ubiquitous NAD-dependent enzyme. Use of the ubiquitous NAD-dependent enzyme in assays allows elimination of inhibitors that might have a general effect on plants in not being specific for C4 plant enzymes.
As NADH is a substrate for the enzyme catalysing the final reaction in the sequence, the progress of the reaction can be measured via the oxidation of NADH which has a maximal absorbance at 340 nm (range, 300-400 nm). Equally, the reaction can be monitored for the production of NAD+ by the maximal absorbance of NAD+ at approximately 260 nm (range, 230-290 nm). If the latter approach is taken, microtitre plates which have little or no UV absorbing properties are required.
With reference to the assay according to the first embodiment of the invention, step (a) of this assay constitutes a primary screening procedure for compounds active against C4 plant enzymes. Samples identified as containing an active constituent that is, a constituent that reduces the amount of NAD+ formed and thus inhibits at least one of PPDK, PEP C or MDH are then subjected to a secondary screening to determine the enzyme specificity of the inhibitor. The secondary screening is done by assaying individual enzymes in accordance with steps (b) and (c) of the first embodiment and/or by carrying out a physiological assay in accordance with the second embodiment of the invention.
As indicated above, assays can be performed in 96-well microtitre plates. Plates can have wells with round or flat bottoms and can be made of any material that does not have an appreciable absorbance at the wavelength to be measured (260 or 340 nm). The usual volume of a reaction mixture is about 100 xcexcl but this can be adjusted to suit the capacity of the microtitre plate. All that is required is that the absorbance value initially attained is significantly different to the background absorbance of the microtitre plate plus the absorbance of the assay mixture minus NADH or NAD+.
A general description of the method of carrying out a primary screening that is, a screening using the assay according to step (a) of the first embodiment of the invention follows. Typical components of mixtures for this assay and the concentrations of components are set out in Table I
With regard to the enzymes, assay mixtures typically comprise the following: PPDK, 0.005 units; PEC C; 1 unit; and, MDH, 2 units.
Although a pH of 8.0 is given in Table I above, assays can be performed within a pH range of 6.0 to 9.5.
All mixture components save for at least one of the PPDK substrates are added to wells of a microtitre plate. In addition to test wells to which the test sample is added, positive and negative control wells are also prepared. Positive controls include all assay components save for the test sample. However, an equal volume of test sample solvent (for example, water, methanol, ethanol, DMSO, or mixtures thereof) is added to positive controls. Both test sample and substrate used to initiate the reaction are omitted from the negative control but suitable volumes of the appropriate solvent are added in place of these components. Test wells are typically prepared in duplicate but samples can be tested singly or in greater than two replicates.
After all components have been added to the test and control wells, the plate is usually allowed to equilibrate at room temperature (20-30xc2x0 C.) for 5 minutes to allow dispersion of test samples and control solvent through the reaction mixtures to give a consistent absorbance reading. This equilibration can be for as little as 1 minute but can also be for up to several hours as the enzymes and other assay components are stable. After equilibration, the absorbance at 340 nm (or 260 nm) is measured using a spectrophotometric plate reader. This measurement is defined as the initial absorbance, A0. The reaction is started by adding, to all but the negative control wells, the substrate pyruvate to the desired final concentration. Alternatively, the test and positive control assay mixtures can be made with pyruvate and without ATP. The reaction is then initiated with ATP.
Plates are incubated at 20 to 30xc2x0 C. until the reaction is complete as evidenced by a constant reading for the positive controls. This is usually reached after 10 to 60 minutes depending on the amount and activity of the enzymes. The absorbance is then again measured at 340 nm (or 260 nm) to determine the final absorbance, Aend. To obtain a percent inhibition for an extract being tested, the difference between A0 and Aend for the test sample is standardised against the difference between A0 and Aend for the positive control.
In the individual enzyme approach to secondary screening of sample extracts having inhibitory activity, the first step is to test active samples against PEP C and MDH. This is step (b) of the first embodiment defined above. Typical components of a PEP C/MDH assay mixture are set out in the following table.
The PEP C/MDH assay is carried out in essentially the same manner as the primary screening assay. If the reaction is not inhibited, specific inhibition of PPDK by active extracts from the primary screen is indicated.
If inhibition is observed in the PEP C and MDH assay, a further assay is conducted in which active extracts are tested against MDH alone. This second step of the secondary screening corresponds to step (c) of the first embodiment. Typical components of an MDH assay mixture are set out in the following table.
If the MDH reaction is not inhibited, the step 1 result can be interpreted as indicating that the inhibitor acts on either PEP C only, or PEP C and PPDK, but not on MDH.
Active extracts identified in the primary screen can also be tested using the physiological assay according to the second embodiment. Inhibition of PPDK is first assessed with the physiological assay using the components listed above in Table I and using essentially the same procedure as for the primary screen. Inhibition of PEP C is then tested by adding the substrate, phosphoenol pyruvate, to the reaction mixture. If an inhibitor is specific for PPDK, no inhibition of PEP C is seen at this stage for the extract containing such an inhibitor. If, however, inhibition is seen, the MDH substrate oxaloacetate is added and the effect of the inhibitor on this enzyme assessed. As with the isolated enzyme approach, normal MDH activity indicates that the inhibitor acts on either PEP C only, or PEP C and PPDK, but not on MDH.
With the assays described above, compounds, or at least extracts containing such compounds, can be identified that are specific inhibitors of the C4 plant enzymes, PPDK and PEP C. The ability to differentiate between inhibitors of these enzymes and inhibitors of MDH allows elimination of those compounds that also act on the more catholic enzyme MDH and thus would not be useful as specific C4 plant herbicides.
It should be noted that while it is not necessary to subject samples which show no inhibition in step a) to further steps b) and c), or to subject samples inactive in step b) to step c), it may be convenient, especially when performing a high throughput assay, to subject all samples to steps a), b) and c) regardless of whether inhibition is seen in steps a) and b). Subjecting all samples to all steps may serve as a useful cross check.
The assays according to the invention can be used to screen for potential inhibitors derived from any source including plants, animals, bacteria, fungi and protozoans. Crude aqueous or organic extracts can be tested, typical organic solvents being methanol, ethanol, dimethylsulfoxide (DMSO) or any combination thereof. Extracts can be acidic or basic provided that any alteration of pH of reaction mixtures on addition of extract does not interfere with the progress of reactions. Compounds able to be tested in the assays include any isolated natural or synthetic product, or any combination of compounds whether produced by combinatorial, purification, or synthetic processes.
The C4 plant enzymes PPDK and PEP C can be prepared by any of the methods known to those of skill in the art. For example, Chapter 3 of Methods in Plant Biochemistry, Vol. 3 (Academic Press Limited, London, England, 1990, pp. 39-72), which is by Anthony R. Ashton et al. and is entitled xe2x80x9cEnzymes of C4 Photosynthesisxe2x80x9d, includes summaries of methods for the purification of PPDK and PEP C. The entire content of Chapter 3 of this volume is incorporated herein by cross-reference. MDH is widely available from commercial sources.
Having broadly described the assays according to the invention, the results of application of the assays to the screening of extracts of marine organisms for inhibitors of PPDK and PEP C will now be provided as a non-limiting example of the invention.

Assay for screening inhibitors of C4 plant enzymes

James Cook University of North Queensland


A power supply device produces, on a plurality of accesses, a plurality of voltages coming from a plurality of accumulator assemblies formed by at least one accumulator element and connected in series by at least one series connection. The power supply device includes a back-up provision for mitigating discharges of at least one of the accumulator assemblies.

The invention relates to a power supply device for producing on a plurality of accesses a plurality of voltages coming from a plurality of accumulator assemblies formed by at least one accumulator element and connected in series by at least one series connection.
The invention also relates to an apparatus comprising such a device.
Such a device finds highly significant applications notably in the field of cordless telephone sets. Actually, these sets comprise, on the one hand, high-frequency circuits which call for relatively high voltages, and, on the other hand, logic circuits which call for less high voltages.
A device of this type is described in European Patent No. 0 624 944. This known device makes use of DC voltage converters which are considered costly, cumbersome and heavy. They are thus not suitable for the application discussed above where, for reasons that the apparatus must be portable, a small weight and as small dimensions as possible are needed while a reasonable cost price is maintained.
The invention proposes a device of the type mentioned in the opening paragraph which largely remedies the drawbacks of price, size and weight presented by the known device.

Electric power supply device for producing a plurality of voltages and apparatus comprising such a device


The invention relates to a method of fabricating a flash memory device. According to the method, select transistors and memory cells are formed on, and junctions are formed in a semiconductor substrate. The semiconductor substrate between a select transistor and an adjacent memory cell are over etched using a hard mask pattern. Accordingly, migration of electrons can be prohibited and program disturbance characteristics can be improved. Further, a void is formed between the memory cells. Accordingly, an interference phenomenon between the memory cells can be reduced and, therefore, the reliability of a flash memory device can be improved.

The invention relates to a method of fabricating a flash memory device and, more particularly, to a method of fabricating a flash memory device that reduces disturbance between gates.
A flash memory device includes a cell region including a memory cell, and a peripheral ("peri") region including transistors for transferring a driving voltage. The cell region is described in detail below.
The cell region comprises strings having a plurality of memory cells connected in series. Each string includes a plurality of memory cells and a select transistor formed at both ends of the string. The memory cell has a structure in which a tunnel insulating film, a floating gate, a dielectric layer, and a control gate are sequentially laminated over a semiconductor substrate. Meanwhile, the select transistor has the same structure as that of the memory cell, but has a floating gate and a control gate in contact with each other through a contact hole formed in the dielectric layer.
Memory cells included in different strings share word lines and are connected to each other, and they are operated in response to voltage applied to the word lines. Select transistors included in different strings are connected through a select line and are operated in response to voltage applied to the select line.
In particular, in the case of a NAND flash memory device, as the level of integration increases, the distance between memory cells narrows. Thus, an interference phenomenon may occur between adjacent memory cells. The interference phenomenon is generally generated between adjacent floating gates and may also be generated due to an increased capacitance between the floating gates.
When a program operation in a flash memory device is performed, a program disturbance characteristic may be degraded. This is described in more detail below.
The program operation is performed by applying a program voltage to a selected word line in order to inject electrons into the floating gate of a selected memory cell. However, since a plurality of memory cells are connected to the word line, the program operation may be performed even on the memory cells on which the program operation should not be performed. To prevent this problem, channel boosting is generated in strings on which the program operation should not be performed so as to prevent electrons from being introduced to the floating gate.
Upon channel boosting, a junction region between the source select transistor and an adjacent memory cell is boosted to a specific voltage (for example, 8V) and a gate of the source transistor is grounded. In this condition, a gate induced drain leakage (GIDL) may be generated at a portion where the source select transistor and the junction overlap each other. Of an electron-hole pair generated in the junction, electrons can rapidly migrate to a channel region to which a high bias is applied. This degrades a program disturbance characteristic. In particular, this phenomenon is very pronounced between the select transistor and an adjacent memory cell.

Method of fabricating flash memory device


A method of detecting tasks performed by users wherein a single task is a sequence of web URLs invocation. Task patterns are detected in web logs to identify tasks performed by users and analyze task trends over time, across corporate divisions and geographies. A grammar-based framework is used to model and detect tasks from web log patterns. The framework has two components: a declarative unit—to generate a task grammar, and a processing unit—to detect tasks from access logs by generating a state machine for applying the task grammar to the tokens associated with the access records. By analyzing user tasks, rather than just URLs, useful business information can be extracted.

1. Field of Invention
The present invention relates generally to the field of web usage mining. More specifically, the present invention is related to analysis of access logs (e.g., web access logs) to provide insight into user behaviors.
2. Discussion of Prior Art
Enterprise-level Web analytics tools that transform Web log data into valuable e-business intelligence are becoming increasingly important since they provide a clear picture of the overall health and integrity of any e-business infrastructure. As a result, Web usage mining—the application of data mining techniques to discover usage patterns from Web log data—has been an active area of research and commercialization. By capturing, analyzing, storing, and reporting on web site usage, such tools provide essential metrics on visitor site interactions and the site's overall performance. This insight is often used to optimize the site for increased customer loyalty and e-business effectiveness. Usage characterization, Web site performance improvement, personalization, adaptive site modification, and market intelligence are some of the applications of Web usage mining as described in the articles entitled "Discovery of Interesting Usage Patterns from Web Data" and "Web Usage Mining: Discovery and Applications of Usage Patterns from Web Data," both by Cooley et al.
Identification of user interests, understanding user behavior, and tracking the popularity of pages are key ingredients to being successful in a competitive eCommerce marketplace. Web logs are studied and analyzed to indicate where a decrease in investment or possible change in web navigation should occur due to less visited Web or product pages. In commercial products, Web site effectiveness is frequently measured by correlating Web usage and traffic information with performance and availability metrics.
Path analysis is usually the basis of many Web analytics tools—its goal is to help understand a visitor's navigation of a web site. Path analysis can be simply defined as the list of pages that a visitor traverses in one visit. While this provides the exact, complete path for each visitor, it may not provide useful insights in terms of visitor behaviors. Therefore, various modifications of path analysis have been proposed such as a focused path analysis (limited list of pages, in order, that a visitor traverses in arriving at or departing from a particular page). Further enhancements include grouping site URLs and performing a path analysis on these groups rather than individual URLs. Ultimately, the path analysis serves to classify visits as "success" or "failure" against certain business objectives of making a sale and can be the basis of web site redesign. Another technique for getting insight into behavior is to look at the most popular behavior—i.e., tracking the frequency of each URL or group to understand flow.
Pattern discovery from Web logs draws upon methods and algorithms developed from several fields such as statistics, data mining, machine learning and pattern recognition as described in the articles entitled "Fast Algorithms for Mining Association Rules," by Agrawal et al.; "Mining Sequential Patterns," by Agrawal et al.; "From Data Mining to Knowledge Discovery: An Overview," by Fayyad et al.; "Data Mining: An Overview from Database Perspective," by Chen et al.; "From User Access Patterns to Dynamic Hypertext Linking," by Jacobsen et al.; and "Towards On-Line Analytical Mining in Large Databases," by Jiawei Han. Statistical techniques are the most common method to extract knowledge about visitors to a Web site. By analyzing the session file, one can perform different kinds of descriptive statistical analyses (frequency, mean, median, etc.) on variables such as age views, viewing time and length of a navigational path. Many Web traffic analysis tools produce a periodic report containing statistical information such as the most frequently accessed pages, average view time of a page or average length of a path through a site. Despite lacking in the depth of its analysis, this type of knowledge can be potentially useful for improving the system performance, enhancing the security of the system, facilitating the site modification task, and providing support for marketing decisions. Some examples of commercial products based on this type of analysis are Netperceptions®, Netzero®, Surfaid analytics, Truste: Building a Web you can believe in, and Webtrends® log analyzer.
Association rule generation can be used to relate pages that are most often referenced together in a single server session. Association rules refer to sets of pages that are accessed together with a support value exceeding some specified threshold. For example, association rule discovery using the a-priori algorithm described in the article entitled "Fast Algorithms for Mining Association Rules," by Agrawal et al., may reveal a correlation between users who visited a page containing electronic products to those who access a page about sporting equipment. However, with association rule discovery, the notion of a transaction for market-basket analysis does not take into consideration the order in which items are selected. The technique of sequential pattern discovery attempts to find inter-session patterns such that the presence of a set of items is followed by another item in a time-ordered set of sessions or episodes. By using this approach, Web marketers can predict future visit patterns which will be helpful in placing advertisements aimed at certain user groups.
Other types of temporal analysis that can be performed on sequential patterns include trend analysis, change point detection, or similarity analysis as described in the article entitled "Mining Sequential Patterns," by Agrawal et al. Dependency modeling is another useful pattern discovery task in Web Mining. The goal in dependency modeling is to develop a model capable of representing significant dependencies among the various variables in the Web domain. There are several probabilistic learning techniques that can be employed to model the browsing behavior of users. Such techniques include Hidden Markov Models and Bayesian Belief Networks as described in articles entitled "Link Prediction and Path Analysis Using Markov Chains," by R. R. Sarukkai, and "On Learning Video Browsing Behavior from User Interactions," by Westphal et al. The article entitled "The Link Prediction Problem for Social Networks," by Kleinberg et al., develops approaches to link prediction based on measures of the proximity of nodes in a network.
Projects described in articles entitled "Discovery of Interesting Usage Patterns from Web Data," by Cooley et al.; "Web Usage Mining for Web Site Evaluation," by Spiliopoulou, M.; "Speedtracer: A Web Usage Mining and Analysis Tool," by Wu et al.; "Discovering Web Access Patterns and Trends by Applying OLAP and Data Mining Technology on Web Logs," by Zaiane et al.; and "Knowledge Discovery from Users Web-Page Navigation," by Shahabi et al., have focused on Web Usage Mining in general, without specific focus of their Web mining techniques. The SpeedTracer project makes use of referrer and agent information in the preprocessing routines to identify users and server sessions in the absence of additional client side information. The Web Utilization Miner (WUM) system as described in the article entitled "WUM: A Web Utilization Miner," by Spiliopoulou et al., provides a robust mining language in order to specify characteristics of discovered frequent paths that are interesting to the analyst. In their approach, individual navigation paths, called trails, are combined into an aggregated tree structure.
A concept hierarchy, also known as taxonomy, generalizes concrete URLs into more abstract concepts. Concept hierarchies are also useful in data mining, especially for market-basket analysis as described in the article entitled "Data Mining Techniques for Marketing, Sales," by Berry et al. The analyst groups individual products into more general concepts, with the effect of also grouping purchases of the products together. Thus, associations that are too rare among individual products become apparent when the product groups are studied.
Sequence miners as described in the article entitled "Mining Sequential Patterns," by Agrawal et al., discover typical usage patterns by determining accesses to pages that occur frequently together in the same order. Only the designer of the site is aware of the larger tasks within which all detected patterns must be analyzed and evaluated. It would be much more efficient to automatically test the miner's results against the expectations of the designer. Therefore, enhancements need to be made in the field of miners so that more than just frequent sequences are found.
The patent to Howard et al. (U.S. Pat. No. 6,278,966 B1), assigned to International Business Machines Corporation, provides for a Method and System for Emulating Web Site Traffic to Identify Web Site Usage Patterns. It discusses a method for emulating behaviors of web site visitors for producing web site trend analysis data. Data mining association rules are applied to simulated traffic and used to identify usage patterns for users of a web site. Actions of users are tracked and reference distributions are developed that are compared to a site's usage distributions as obtained from actual visitors to the site. The reference distributions are used to implement statistical methods that measure relative information content.
The patent application publication to Tamayo et al. (2002/0083067 A1) provides for an Enterprise Web Mining System and Method. It discusses a method of enterprise web mining wherein a plurality of data mining models are generated using data that is collected from a plurality of data sources such as account or user based data, complementary external data, web server data and web transaction data. Predictions or recommendations are provided using the data mining models.
The patent to Papierniak et al. (U.S. Pat. No. 6,151,601), assigned to NCR Corporation, provides for a Computer Architecture and Method for Collecting, Analyzing and/or Transforming Internet and/or Electronic Commerce Data for Storage Into a Data Storage Area. It illustrates a method for effectively collecting, translating, refining, and analyzing Internet and/or electronic commerce data to provide useful marketing information. Web data is integrated with business data from a plurality of sources.
The patent to Martin et al. (U.S. Pat. No. 6,338,066 B1), assigned to International Business Machines Corporation, provides for a Surfaid Predictor: Web-Based System for Predicting Surfer Behavior. Web surfers behavior is predicted based on past surfer behavior. Multiple models of surfer behavior are generated by randomly selecting sample sessions from a web log.
The patent application publication to Lee et al. (2002/0198939 A1), assigned to International Business Machines Corporation, provides for a System and Method for Collecting and Analyzing Information about Content Requested in a Network (World Wide Web) Environment. A method for collecting, analyzing, aggregating and storing information about the content of one or more web pages served by a server on a network is discussed.
The patent application publication to McGuire (2003/0126613 A1) provides for a System and Method for Visualizing User Activity. It discusses a method for analyzing web server logs or other computer generated activity logs and converting the information contained in the logs, i.e., the log data into a visual, audio or audio/visual recreation of a user's accessing of a web site.
In contrast to Internet eCommerce sites that may optimize web site design to make a sale or obtain some personal information about a user, intranet Web applications have a different goal. Many corporate processes, such as procurement, human resources, travel reservations, and expense reimbursement, have a Web front that accesses, displays, and updates data on different backend servers. As an example, a global corporation such as IBM has over 1,000 Web applications supporting its business processes for its 300,000+ world-wide employees. The purpose of a web site, in this case, is to support a given process that needs to be performed in the most efficient manner. Free-form discovery of popular visitor paths is not necessarily insightful in evaluating the efficacy of such web sites. Instead, the web site is typically designed with a set of features to meet a set of requirements of the process it serves. Metrics that are relevant to evaluating such web sites are task-oriented—e.g., how effective was the site in getting the task accomplished, how long it takes to complete a specific task, what are the trends over time across different user populations in the corporation, etc.
One of the main problems with web logs analysis is that a single task performed by a user is composed of accessing multiple URLs. The same task may be performed in different ways, yet resulting with the same outcome. For example, upon accessing the website to buy a product, the product description page could be reached in a number of ways where the user could click to buy, which would lead to same final outcome, buying of the product. Thus, the sequence of URLs that the user accesses to buy the product is one task. Hence, it is beneficial to perform analysis of tasks rather than just sequences of URLs that the user accesses in a session. Thus, it is valuable to process a sequence of URLs and detect the semantics of the different tasks performed by the user.
The references and techniques described above provide for web log and user activity analysis. However, none of them discuss the ability to define patterns that represent entire tasks of interest using a formal grammar. Whatever the precise merits, features, and advantages of the above cited references, none of them achieves or fulfills the purposes of the present invention.


A modified IEEE 488.1 bus interface increases, by as much as a factor of eight, the rate at which inter-instrument data transfers can be performed. The bus interface state machines presented in the ANSI/IEEE Std 488.1-1987 have been modified so that if all the devices involved in a particular data transfer are equipped to handle high speed data transfers, then a modified data transmission methodology is used so as to enable multiline messages to be transmitted at a higher speed than would otherwise be possible. If any of the devices involved in a particular data transfer does not have an interface equipped to handle high speed data transfers, this condition is automatically detected by the interfaces with high speed capability, and then the standard data transmission methodology is used. The high speed data transmission mode is totally transparent to the controller software in that it does not require any changes to the controller software nor to the device drivers and device application programs.

Microprocessors are used today for performing the internal operations of modern instruments. Additionally, computers and microprocessors are used to control test and measurement systems. The primary method used for interconnecting and communicating between instruments and control computers (controllers) is the IEEE 488 bus.
The IEEE 488 bus is essentially an electrical signal transmission bus with a predefined set of lines. A set of predefined protocols govern the methodology for transferring information over the bus from a controller to specified devices, and vice versa. By using an industry standard bus, the manufacturers of a wide variety of instruments can ensure that standard software packages and interface circuits can be used to connect their instruments to microprocessor based controllers. That is, purchasers of these instruments do not need to buy a different customized controller for each instrument, because all such instruments use the same set of signal lines and the same set of communication protocols.
IEEE 488-1978, as well as the newer IEEE 488.1-1987 standard, defines a data settling time, T1, that is used by all devices (instruments and controllers) that source "multiline" messages (i.e., messages containing multiple bits transmitted parallel) onto the IEEE 488.1 bus. IEEE Standards 488-1978 and 488.1-1987 allow different values for T1, depending on the configuration of the system and on the type of data line drivers used by the device performing the source handshake. The maximum multiline data transfer rate that is compatible with these standards is 1 megabyte per second. However, advances in instrumentation are making this data transfer rate limitation a bottleneck in terms of inter-instrument communication. The inventors of the present invention believe that there is a need for an inter-instrument communication standard that can achieve higher data transfer rates. The present invention provides a backwards-compatible modification of the IEEE 488.1 bus standard that can achieve data transfer speeds of up to 8 megabytes per second.

High speed IEEE 488 bus interface system and method


An electronics circuit for accurately digitizing an analog audio or like data signal into a digital equivalent signal by introducing dither into the analog signal and then subsequently removing the dither from the digitized signal prior to its conversion to an analog signal which is a substantial replica of the incoming analog audio or like data signal. The electronics circuit of the present invention is characterized by a first pseudo-random number generator which generates digital random noise signals or dither for addition to the digital equivalent signal and a second pseudo-random number generator which generates subtractive digital random noise signals for the subsequent removal of dither from the digital equivalent signal prior its conversion to the analog replica signal.

1. Field of the Invention
The present invention relates generally to the conversion of electric signals from analog to digital form. More specifically, the present invention relates to a digital circuit for translating an analog audio or like analog signal into an equivalent digital signal with the addition of dither which is an artificially created noise signal and then subsequently removing the dither from the digital signal thereby reducing noise and distortion.
2. Description of the Prior Art
The pulse code modulation (PCM) or digital processing of analog audio signals has become, or is becoming, the mainstream of high fidelity sound recording and reproduction with the advent and ever increasing commercial acceptance of compact discs. The digital processing of analog signals in the low to high frequency range is also becoming highly useful for analyzing the performance of weapons systems such as guided missiles. For example, the analog data acquired by a guided missile during flight is converted to its digital equivalent and then placed in a digital PCM frame for transmission to a ground station for analysis.
There are, however, some problems left unsolved in the art of digital processing of analog signals. For example, there is a significant difference between the samples of an analog signal and the quantized values of the samples which is generally referred to as "quantization noise". This difference becomes particularly pronounced when the input analog signal is low and there are only a small number of quantization steps, thereby, for example, distorting the reproduced sound as higher harmonics in high fidelity sound systems.
A prior art solution to this quantization noise problem has been the use of dither which is intended to turn the quantization noise into broad band white noise which has little or no effect on reproduced sound or the like and which is generally referred to as "white noise". One system of the prior art adds an analog dither signal, converted from the output from a digital dither generator by a digital to analog converter, to the incoming analog audio or analog data signal. The combined analog data and dither is digitized by an analog to digital converter and then fed to a subtractor circuit. The subtractor is also supplied the digital dither directly from the dither generator. The subtractor circuit then subtracts the dither component from the digital data and dither signal.
A second system of the prior art uses an analog dither generator in combination with a second analog to digital converter for digitizing the analog dither prior to its delivery to the subtractor. In this prior art system, analog dither is added directly to the analog data signal. The resulting dither added data signal is then digitized by the first analog to digital converter and the analog dither is digitized by the second analog to digital converter preparatory to application to the two inputs of the subtractor circuit.
While partially satisfactory for their intended purpose of removing noise and distortion from a digitized analog signal, these prior art systems ordinarily leave something to be desired in that dither components remain in the digitized data signal which manifest themselves as noise or distortion upon sound reproduction or reproduction as an analog signal for visualization and subsequent analysis. In addition, prior art systems for removing noise and distortion from a digitized analog signal often use digital signal processors as dither signal generators. Thus, such prior art systems are often complex in design as well as being expensive to manufacture.
Accordingly, it is an object of the present invention to provide an electronics circuit for accurately converting an analog audio or like data signal into its digital equivalent.
It is another object of the present invention to provide an electronics circuit for adding dither to an analog audio or like data signal and then removing dither from the digital equivalent signal and then converting the digital signal to an analog signal which is a replica of the analog audio or like data signal.
It is a further object of the present invention to provide a reliable yet relatively simplistic and inexpensive electronics circuitry for converting an analog audio or like data signal into its digital equivalent and then reconverting the digital equivalent signal to its analog equivalent signal by the removal of dither from the digital equivalent signal.
It is yet a further object of the present invention to provide electronics circuitry which is capable of operation with high resolution and conversion accuracy.
The above and other novel features and advantages of the present invention and the manner of realizing them will become more apparent and the invention will be best understood from a study of the following description and appended claims, with reference to the attached drawings.

Digital circuit for the introduction and later removal of dither from an analog signal

The United States of America as represented by the Secretary of the Navy


A display board assembly includes a display board having a planar surface and an edge extending along at least a portion of the planar surface. The display board assembly also includes a mounting member coupled to the display board. The mounting member defines a first gap adjacent the planar surface of the display board and a second gap adjacent the edge of the display board. The display board assembly further includes a display board accessory including a projection. The display board accessory is removably coupled to the mounting member in one of a first position, in which the projection is received in the first gap, and a second position, in which the projection is received in the second gap.

The present invention relates to display board assemblies.
Display boards, such as dry-erase boards, are commonly used to display information in classrooms or offices. Various accessories for use with display boards are sometimes mounted to surfaces or edges of the boards. These accessories are typically attached to the display boards using mounts (e.g., via screws, nails, adhesives, etc.) that may cause permanent damage to the boards. In addition, different types of mounts are usually required to connect each different type of accessory to the display boards.


A through-optical bench is the optical equivalent of a folded-optical system. Folded optics is generally found in cannon launched guided projectiles and always includes a mirror mounted on a gimbal. Inside the projectile the optical image is hidden behind the mirror and is not easily accessible by measurement instrument. In the through-optical bench the image is repositioned to where it is easily viewed; hence enabling a much finer process to improve manufacturing accuracy and throughput. The through-optical bench uses a collimated beam of light which passes through the seeker nose optical cluster, then through a mask which mimics the mirror, then through an identical optical cluster which substitutes for the reflection, and finally onto a screen to form a focused image directly viewable by a microscope. The clusters and mask simultaneously step through various yaw angles made possible by a reversing linkage that moves them as mirror images. A micrometer dial simulates the focusing shim for the particular seeker nose cluster.

Two kinds of semi-active laser guided air-frames have been commonly used by the military, one type is the rocket propelled missile and the other type is the howitzer projectile. Each uses a seeker head on the nose of the air-frame to collect laser radiation emitted by the target, and enable guidance. The dish reflector is well suited for the missile seeker while the lens and mirror combination is best for the projectile seeker.
The missile uses a parabolic dish reflector to track the radiation emanating from the target. The dish reflector is thin, light in weight, has a wide aperture, good focusing throughout its field-of-view and allows a compact seeker head antenna. Along with the low weight antenna comes a lighter servo or gyro to point it for tracking. A lighter missile results in greater range.
The cannon launched projectile is subject to high acceleration inside the tube, a much more severe environment than the missile. The thin reflector is not compatible with the high shock resistance required during cannon launch and so it must be stiffened. Nose-heavy means flight stability for a projectile; but the heavier reflector, together with the additional weight of the accompanying servo, translates either into a significant penalty in range, or a significant loss in tracking response needed to follow the radiation.
One of the proposed solutions for the cannon launched projectile has been folded optics. Folded optics affords wide aperture throughout its field-of-view, the shock resistance of a strap-down optical cluster, and a light weight gyro agile enough to track easily. Its reflecting system only works with a flat mirror which is usually polished on the face of the gyro rotor. This is acceptable from a fabrication point of view because making the flat micro surface is an old technology. That said, the folded system is notorious for two troublesome characteristics. One is that the focused image morphs or changes shape as the gyro tracks in pitch or yaw. Focusing this system requires checking its focus throughout its gimbal range. This leads to the second quirk. The image is not plainly visible. These two peculiarities add uncertainty to guidance parameters like gain and feedback and this uncertainty is generally considered a drawback to folded optics. The unpredictability in optical feedback discredits computer flight simulations. The only way to be sure of the projectile's value is the costly way; to build a few and fire them. However, control over optical feedback will make this trait an asset instead of a liability, will bring a substantial improvement to performance and uniformity from one projectile to the next, and will reduce an expensive risk.
Guidance systems that track with a gimbaled antenna in the nose and try to keep a bead on the target have historically been known as using proportional navigation. The mirror is always facing the radiation, even when the missile body turns away from it, and that is the orientation of most concern. The focused spot of light must be centered on a screen in order to indicate when the antenna is on track. Missile body motion can disturb that setting. Optical feedback appears as a second order term in a folded system's transfer function, but this peculiarity is not necessarily bad. It can either enhance or degrade flight stability in a cross-wind or sudden jump in the direction of laser radiation; conditions that typically occur on the battlefield. If feedback has a positive value, then the path of the projectile will spiral away from the target; and that's bad. If it is negative then the projectile will recover from the perturbation and continue to pursue the target; and that's good. This is the reason why precise focusing of the optics is so critical.
Plastic lenses made of polycarbonate are both compact and shock resistant when incorporated into a folded optical system. However the optical characteristics of the plastic lens is sensitive to process variations of molding and annealing, resulting in significant variations in optical characteristics from one lens to another. The lens of most concern is the large plastic objective lens behind the transparent windshield where laser radiation enters. Adjustments must be made for focus for each individual seeker head, because focus, flare and other characteristics are unique to each lens. Quality cannot be held to rigid dimensions or process certification. Each seeker must be focused individually, as the lenses are not interchangeable. This leads to a serious problem.
The focused image in a folded optical seeker head is not plainly visible because it is hidden behind the mirror. This is worth repeating and cannot be over emphasized. The image of the target inside a folded seeker cannot be viewed directly. It cannot be focused by viewing an image and turning a knob, as is the case of a microscope or pair of binoculars. A folded optical seeker is so compact that there is just no way to see inside of it without extraordinary modifications to the system.
Prior to the advent of the present invention, there was no other alternative to focusing each seeker except by indirect means. Focusing done electronically through the output from the photo detector was a long and tedious process requiring skilled technicians, sophisticated equipment, hours of time, and cool precise concentration. The manufacturing record of these systems is speckled with unanticipated delays, loss of schedule and uncontrollable costs. At this writing there is still a need for a measurement system and a method to aid the focusing of seeker heads used in cannon launched projectiles. To date this need has not been satisfied.

Shim dialer platform and process to compensate for optical variations in components used in the assembly of seeker heads with folded optics for semi-active laser guided cannon launched projectiles

The United States of America as represented by the Secretary of the Army


An electrical cable containing two or more twisted pairs of wires and having terminals at one end connected to corresponding wires is tested for possible mis-pairing of an assumed wire pair. At that end of the cable, all terminals except the two for the assumed wire pair are connected to ground. A test signal is then applied to a first terminal for the assumed wire pair, and at the same time a measurement is made of a response signal received at the second terminal for the assumed wire pair. The test signal is a time-varying signal. The strength of the response signal is compared to the test signal to establish whether the assumed pair of wires are in fact wound to each other.

It has long been known to test electrical circuits either to establish their continuity, or to discover open circuits, short circuits, or other mistakes that electricians may have made in connecting the wires. Many kinds of apparatus have been used for these purposes.
One type of manufactured cable is the so-called "satin cable", which is flat and has all its wires in a side-by-side relationship and encased in a cover material. While short circuits, open circuits, or grounds can still occur in this type of cable, the configuration of this cable as manufactured makes it essentially impossible to mix up wire pairs inside the cable, and also reduces the likelihood of mixing up wiring connections at the cable ends.
The twisted pair circuit enjoys an advantage for alternating current operation in that currents passing through it will have decreased interaction with the surrounding environment. Thus in telephone circuitry, for example, twisted-pair circuits that occupy a common housing have far less mutual interference or "cross-talk" between circuits than if only straight wires were used.
The present invention relates to cables having a plurality of twisted-pair circuits bundled together in a common package. In addition to the possibility of short circuits or open circuits, the use of this type of cable also involves a risk of mixing up wiring connections at the cable ends, or of mispairing the wires inside the cable even if they were correctly connected at the cable ends. When multiple circuits are present, the problem of complete and accurate testing is complicated and time-consuming.
Correctly assembling and installing twisted pair cable is a difficult task. The right-hand wire and the left-hand wire of a pair change places every time the wires are twisted by 180 degrees. Even with good techniques for color coding of the wires it is still relatively easy to make a mistake in connecting to the contacts or terminals at the cable ends. The wires may be connected to correct contacts or terminals at the ends of the cable, but nevertheless may have been mis-paired inside the cable, where the error is difficult to detect. The electrician may connect the wire ends in exactly the same manner at each end of the cable, but may have misunderstood the plan by which the wires were to be connected, so there may still be mis-paired wires inside the cable.
Heavy demands are made upon circuitry when wiring that would in earlier times have carried only voice signals is now required to carry data signals at binary digit rates of 100,000 or more bits per second. A very slight degradation in circuit performance can quite significantly increase the probability of error in data transmission.
While standard methods of testing have been very effective for most purposes, one of the most subtle and difficult problems is cross-talk or mutual interference between adjacent circuits that appear to be correctly wired, but in fact are not. Specifically, the following scenario may sometimes arise.
A cable containing four wires forming two separate two-wire circuits is connected at each of its ends to terminals or contacts A, B, C, and D. The wires of one wire pair are connected to the A and B terminals at each end of the cable, while the wires of the other wire pair are connected to the C and D terminals. The tests made for continuity, short circuits, open circuits, or grounds, disclose no problem. However, inside the cable package, wires A and C are twisted together and wires B and D are twisted together. In other words, the wires are mis-paired inside the cable. In actual operation of the circuits to transmit data signals, the cross-talk or mutual interference between the A-B circuit and the C-D circuit will therefore be intolerable.

Method for determining correct pairing of bundled twisted wire pair circuitry