Hydrocracking is a versatile petroleum refining process, which enjoys widespread and growing use in the refining industry. Hydrocracking has the ability to process a wide range of difficult feedstocks into a variety of desirable products. Feedstocks, which may be treated by this process, include heavy naphthas, kerosenes, refractory catalytically cracked cycle stocks and high boiling virgin and coker gas oils. At high severities, hydrocracking can convert these materials to gasoline and lower boiling paraffins; lesser severities permit the higher boiling feedstocks to be converted into lighter distillates such as diesel fuels and aviation kerosenes.
Hydrocracking is conventionally carried out at moderate temperatures of 350° C. to 450° C. (650° F. to 850° F.) and at high pressures, over 7,000 kPa (1,000 psig) because the thermodynamics of the hydrocracking process become unfavorable at higher temperatures. In addition, high hydrogen pressures, usually at least 800 psig are usually required to prevent catalyst aging and so to maintain sufficient activity to enable the process to be operated with a fixed bed of catalyst for periods of one to two years without the need for regeneration.
Environmental concerns, especially with sulfur oxides and nitrogen oxides emissions, have led petroleum refiners to depend more heavily than in the past on hydrodesulfurization and hydrocracking processes. Availability of by-product hydrogen from naphtha reforming no doubt has also cooperated to foster this dependence. Other factors too, have come into play to make hydroprocessing of increasing importance. Among these factors is that high quality crude oils for lube and fuels refineries are expected to progressively become more scarce. Also, refineries that include a fluid catalytic cracking (FCC) plant generate large volumes of dealkylated, aromatic refractory effluents, commonly known as FCC Cycle Oils. Decrease in demand for the fuel oil products into which these FCC Cycle Oils were previously incorporated has added to the practice of working them off by incorporation with a hydrocracker feedstock. The hydrocracking process, unlike catalytic cracking, is able to effectively upgrade these otherwise refractory materials.
Hydrocracking is an established petroleum refining process. The hydrocracking feedstock is invariably hydrotreated before being passed to the hydrocracker in order to remove sulfur and nitrogen compounds as well as metals and, in addition, to saturate olefins and to effect a partial saturation of aromatics. The sulfur, nitrogen and oxygen compounds may be removed as inorganic sulfur, nitrogen and water prior to hydrocracking although interstage separation may be omitted, as in the Unicracking-JHC process. Although the presence of large quantities of ammonia may result in a suppression of cracking activity in the subsequent hydrocracking step, this may be offset by an increase in the severity of the hydrocracking operation.
In the hydrotreater, a number of different hydrogenation reactions take place including olefin and aromatic ring saturation but the severity of the operation is limited so as to minimize cracking. The hydrotreated feed is then passed to the hydrocracker in which various cracking and hydrogenation reactions occur.
In the hydrocracker, the cracking reactions provide olefins for hydrogenation while hydrogenation in turn provides heat for cracking since the hydrogenation reactions are exothermic while the cracking reactions are endothermic; the reaction generally proceeds with generation of excessive heat because the amount of heat released by the exothermic hydrogenation reactions usually is much greater than the amount of heat consumed by the endothermic cracking reactions. This surplus of heat causes the reactor temperature to increase and accelerate the reaction rate, but control is provided by the use of hydrogen quench.
Conventional hydrocracking catalysts combine an acidic function and a hydrogenation function. The acidic function in the catalyst is provided by a porous solid carrier such as alumina, silica-alumina, or by a composite of a crystalline zeolite such as faujasite, Zeolite X, Zeolite Y or mordenite with an amorphous carrier such as silica-alumina. The use of a porous solid with a relatively large pore size in excess of 7 A is generally required because the bulky, polycyclic aromatic compounds which constitute a large portion of the typical feedstock require pore sizes of this magnitude in order to gain access to the internal pore structure of the catalyst where the bulk of the cracking reactions take place.
The hydrogenation function in the hydrocracking catalyst is provided by a transition metal or combination of metals. Noble metals of Group VIIIA of the Periodic Table, especially platinum or palladium may be used, but generally, base metals of Groups IVA, VIA and VIIIA are preferred because of their lower cost and relatively greater resistance to the effects of poisoning by contaminants. The preferred base metals for use as hydrogenation components are chromium, molybdenum, tungsten, cobalt and nickel; and, combinations of metals such as nickel-molybdenum, cobalt-molybdenum, cobalt-nickel, nickel-tungsten, cobalt-nickel-molybdenum and nickel-tungsten-titanium have been shown to be very effective and useful.
The porous support, which provides the acidic functionality in the catalyst, may comprise either an amorphous or a crystalline material or both. Amorphous materials have significant advantages for processing very high boiling feeds which contain significant quantities of bulky polycyclic materials (aromatics as well as polynaphthenes) since the amorphous materials usually possesses pores extending over a wide range of sizes and the larger pores, frequently in the size range of 100 to 400 Angstroms are large enough to provide entry of the bulky components of the feed into the interior structure of the material where the acid-catalyzed reactions may take place. Typical amorphous materials of this kind include alumina and silica-alumina and mixtures of the two, possibly modified with other inorganic oxides such as silica, magnesia or titania.
Crystalline materials, especially the large pore size zeolites such as zeolites X and Y, have been found to be useful for a number of hydrocracking applications since they have the advantage, as compared to the amorphous materials, of possessing a greater degree of activity, which enables the hydrocracking to be carried out at lower temperatures at which the accompanying hydrogenation reactions are thermodynamically favored. In addition, the crystalline catalysts tend to be more stable in operation than the amorphous materials such as alumina. The crystalline materials may, however, not be suitable for all applications since even the largest pore sizes in these materials, typically about 7.4 Angstroms in the X and Y zeolites, are too small to permit access by various bulky species in the feed. For this reason, hydrocracking of residuals fractions and high boiling feeds has generally required an amorphous catalyst of rather lower activity.
The crystalline hydrocracking catalysts generally tend to produce significant quantities of gasoline boiling range materials (approximately 330° F.-, 165° C.-) materials as product. Since hydrocracked gasolines tend to be of relatively low octane and require further treatment as by reforming before the product can be blended into the refinery gasoline pool, hydrocracking is usually not an attractive route for the production of gasoline. On the other hand, it is favorable to the production of distillate fractions, especially jet fuels, heating oils and diesel fuels since the hydrocracking process reduces the heteroatom impurities characteristically present in these fractions to the low level desirable for these products.
U.S. Pat. No. 8,372,772, issued Feb. 12, 2013, discloses a hydrocracking catalyst comprising zeolite crystallized as a layer on the surface of a porous alumina-containing matrix, the matrix being shaped by extrusion and arranged in a configuration to provide macropores in which the zeolite layer is provided on the walls of the macropores. The in-situ produced Y-fauajasite on matrix provides acidic functionality in the catalyst and is also used as a support for hydrogenating metals.
U.S. patent applications (Pub. Nos. 2004/0220046 A1 and 2004/0235642 A1) teach preparation methods for structurally enhanced zeolite microsphere FCC catalysts where zeolite crystallizes on the walls of the pores of the matrix.
As is known in the industry, the hydrocracking process is a fixed-bed process with catalysts in shaped forms of extrudates, pellets or spheres. The particle size is much larger than FCC microspheres. While the above-mentioned U.S. Pat. No. 8,372,772 discloses in-situ crystallization of pre-shaped particles, such as extrudates, the patent does not otherwise provide a specific method which provides sufficient exchange of nutrients between the liquid phase and the solid phase to provide crystallization and allows the zeolite to form on the pore walls, as well as maintain the porosity and integrity of the extrudate.


Some missile systems require the use of vans which must accompany the missile in the field. Some of these vans carry material such as repair parts and test equipment which are necessary to the successful operation of the missile. Storage means must be provided in the vans for safely storing the material. The storage means typically is in the form of cabinets having a plurality of drawers therein which must be tightly secured against accidental opening while the vans travel over rough terrain with the missile as the missile is positioned in the field.
Cabinets are manufactured with built-in latches for securing the drawers in secured relation. However such latches are not capable of securing the drawers when the cabinets are subjected to vibrations such as encountered when the cabinets are mounted in vans and moved over rough terrain. In the past, the drawers have been additionally secured by various type of locking devices including barn door type of locking devices (hasps and staple) or the like. Usually such type of locking devices include a separate padlock or pin for attachment to each individual drawer for secured relation thereof to the cabinet. Each individual locking device must include a loosely carried pin or padlock.
It is an object of the present invention, therefore, to provide a locking device which is self storing.
It is a further object of the present invention to provide such a locking device which will maintain drawers in secured relation in cabinets while said cabinets are transported over rough terrain


1. Field of the Invention
The present invention relates to a detecting device for detecting a transfer object, such as a document sheet or recording paper, in a facsimile machine, a printer, a copying machine or an image scanner for example.
2. Description of the Related Art
In a facsimile machine for example, it is necessary to detect the movement or presence of a transfer object, such as a document sheet or a recording paper sheet, in a transfer path for controlling the operation of the facsimile machine. For this purpose, a detecting device is provided which comprises an actuator and a sensor.
More specifically, as shown in FIG. 8, a prior detecting device comprises an actuator 100 and a sensor 101. The actuator 100 includes a horizontal shaft 100a, a first arm 100b extending upwardly from the shaft 100a, and a second arm 100c extending downwardly from one end of the shaft 100a. The sensor 101 is mounted on a circuit board 102.
In the absence of a transfer object (not shown) in the transfer path, the first arm 100b of the actuator 100 projects into the transfer path. On the other hand, when a transfer object is present in the transfer path, the first arm 100b comes into engagement with the transfer object and is thereby pressed downwardly. In this way, the actuator 100 pivots up and down about the horizontal shaft 100a in response to the presence and absence of a transfer object.
The second arm 100c of the actuator 100 is bent to extend first obliquely and then substantially vertically. Since the second arm 100c is thus bent, the actual orientation of the second arm may be represented by an effective length line EL which passes through the center of the actuator shaft 100a and the lower end of the second arm 100c. In the absence of a transfer object in the transfer path, the angle .theta. between the effective length line EL of the second arm 100c and a vertical line VL passing through the center of the shaft 100a is less than 45.degree..
The lower end of the second arm 100c is provided with a reflector 103 which faces the sensor 101 when the second arm 100c is pivoted down due to the absence of a transfer object. Further, the reflector 103 has a rounded stopper projection 104 which comes into resting contact with the circuit board 102, thereby maintaining a predetermined clearance H.sub.1 between the reflector 103 and the circuit board 102.
The sensor 101 is a reflection type sensor which has a light emitting portion and a light receiving portion. When the actuator 100 is pivoted to bring the stopper projection 104 into contact with the circuit board 102, the light emitted from the light emitting portion of the sensor 101 is reflected on the reflector 103 for incidence into the light receiving portion of the sensor 101, so that the sensor 101 notifies the absence of a transfer object. On the other hand, when the second arm 100c of the actuator 100 is pivoted up due to the presence of a transfer object, the reflector 103 becomes far from the sensor 101 to come completely out of the light reflecting position (see the phantom line in the center of FIG. 8), so that the sensor 101 notifies the presence of a transfer object.
Normally, the circuit board 102 is mounted at a standard distance H.sub.0 from the actuator shaft 100a to make the reflector 103 substantially parallel to the upper surface of the sensor 101 in facing relation thereto (see the center representation in FIG. 8) when the stopper projection 104 of the reflector 104 comes into contact with the circuit board 102. However, it is possible, due to some production or assembly error, that the circuit board 102 may positionally deviate from the standard distance position H.sub.0 relative to the actuator shaft 100a. If the circuit board 102 is erroneously positioned at a distance (H.sub.0 -.DELTA.H) or (H.sub.0 .DELTA.H) from the actuator shaft 100a (see the left and right representations in FIG. 8), the orientation of the reflector 103 becomes improper relative to the upper surface of the sensor 101. As a result, the sensor 101 may fail to provide a reliable detection of a transfer object. Such a disadvantage will become particularly remarkable as the angle .theta. between the effective length line EL of the actuator second arm 100c and the vertical line VL is small.


The present invention relates to photopolymer materials sensitive to infrared, near infrared, red and green light radiation for initiating polymerization and to applications of such photopolymer, like holographic polymer dispersed liquid crystal (H-PDLC) or reversible dye doped photopolymer (RDDP) materials, for making optical devices. The invention relates to holographic polymer dispersed liquid crystal and reversible dye materials having improved electrical and optical switching properties.
Infrared (IR) diode sources are largely used in integrated photonic circuits and the list of their applications grows very rapidly. The management of the radiation of these sources requires the fabrication of optical elements such as lenses, interconnects, modulators, etc. Holographic diffractive elements are emerging as very promising for these applications. These include wavelength selective holographic interconnects (1 to N, or M to N), couplers, lenses, mirrors. Today, a new class of Holographic Photopolymer Dispersed Liquid Crystal Materials (H-PDLCs) is considered to be one of the most viable technologies for the development of reflective color displays, switchable holographic optical elements (such as Bragg gratings for Wavelength Division Multiplexing (WDM) devices), switchable-focus lenses, etc. See for example Crawford et al., xe2x80x9cReflective color LCDs based on H-PDLC and PSCT technologiesxe2x80x9d, J Soc. Information Display, 1996, 5(1); Domash et al., xe2x80x9cElectronically switchable waveguide Bragg gratings for WDM routingxe2x80x9d, 1997 Digest of the IEEE. /LEOS Summer Topical Meetings: Vertical-Cavity Lasers/Technologies for a Global Information Infrastructure/WDM Components Technology; and Domash et al., xe2x80x9cSwitchable-focus lenses in holographic polymer dispersed liquid crystalxe2x80x9d, Proceedings of the SPIExe2x80x94The International Society for Optical Engineering, vol. 2689, (Diffractive and Holographic Optics Technology III, San Jose, Calif., USA, 1-2 Feb. 1996.) SPIE-Int. Soc. Opt. Eng, 1996. p. 188-94.
Commercially available holographic materials are generally sensitive in the UV/visible part of the spectrum only. Thus, the actual fabrication of above-mentioned elements requires an initial recording step, where a UV-Visible laser source is used, and then, a further adaptation or adjustment of the obtained element for utilization with near IR wavelengths (e.g. 800-850 nm or 1300-1500 nm), which are used in local or long distance communication systems. Due to strong astigmatism and divergence of the used diode lasers, this work is difficult and has poor efficiency. It would therefore be highly desirable to provide in situ recording of holographic diffractive elements with lasers, which are already integrated in the given photonic circuit, thus providing self-alignment of the photonic circuits. Thus, there is a need to extend the sensitivity of these materials up to communication wavelengths. Namely, for in situ holographic recording of optical components with diode lasers operating in the 800-855 nm, among which there are Vertical Cavity Surface Emitting Lasers (VCSEL), it is important to have H-PDLC material with suitable holographic characteristics, which include high sensitivity and diffraction efficiency of the recording, low scattering and noise level, and low switching voltage.
Up to now, the sensitivity of the existing H-PDLC materials has been extended up to 790 nm (Natarajan et al., Report on Photonics West 98, San Jose, January 1998). Photopolymerizable materials have been recently proposed with sensitivity in the 800-850 nm area, for example in co-pending application Ser. No. 09/503,207, filed on Feb. 14, 2000. See also EP 0 223 587; EP 0 387 087; EP 0 389 067; U.S. Pat. No. 4,343,891; Chatterjee et al., J. Am. Chem. Soc., 1990, 112, 6329; Schuster et l, Photochem. Photobiol. A: Chem., 1992, 65, 191; Chatterjee et al., J. Am. Chem. Soc., 1988, 110, 2326; Cooper et al., J. Am. Chem. Soc., 1963, 85, 1590; and Noiret et al., Pure and Applied Optics, 1994, 3(1), 55-71. Imaging applications with low resolution (such as printing plates) were also successfully explored. Some of the materials were the subject of the study for holographic gratings recording and only very low level of performance was achieved (7% of diffraction efficiency at sensitivity of about 300-500 mJ/cm2), as reported in the mentioned Noiret et al. article supra. This low level of performance makes such polymers impractical for commercial application. All the above materials still suffer from limitations such as spatial resolution, diffraction efficiency etc.
In accordance with the present invention, there is now provided a photopolymerizable formulation sensitive to light in a green to infrared region of the optical spectrum comprising:
a) a photopolymerizable monomer, oligomer or mixtures thereof;
b) a photoinitiator sensitive to light in the green to infrared region;
c) an additive for increasing the refractive index and decreasing the viscosity of the formulation; and
d) an optional filler having optical properties selected to contrast with optical properties of a polymer resulting from photopolymerization of the monomer, oligomer or mixtures thereof.
Preferably, the formulation comprises filler, which is a liquid crystal or a reversible dye, or combinations thereof, or any other filler materials such as mesogens having polar or functional groups. The liquid crystal preferably has a polar group attached to ends of the molecule chain elements, whereby droplets of LC matter are more efficiently formed in the polymer dispersed in the liquid crystal material. Larger droplets allow for more efficient optical state switching.
In a second aspect of the invention, there is provided a process for making an optical device comprising the steps of:
preparing a photopolymerizable formulation sensitive to light from green to infrared region of the optical spectrum, the formulation comprising
a) a photopolymerizable monomer, oligomer or mixtures thereof;
b) a photoinitiator sensitive to light in the region
c) an additive for increasing the refractive index and decreasing the viscosity of the formulation; and
d) an optional filler having optical properties selected to contrast with optical properties of a polymer resulting from photopolymerization of the monomer, oligomer or mixtures thereof;
applying a layer of the formulation on an optical element;
first exposing the optical element comprising the formulation to a light source emitting light in the region, to polymerize the formulation and produce a recording pattern on the optical element; and
optionally second exposing the optical element to the light to polymerize any remaining portion of the formulation not polymerized during first exposing, thereby producing said optical device.
Finally, in a third aspect of the present invention, there is provided a process of making an optical connection between at least two waveguides or light guides of an optical element by photopolymerization, the process comprising the steps of:
preparing a photopolymerizable formulation sensitive to light from green to infrared region of the optical spectrum, the formulation comprising:
a) a photopolymerizable monomer, oligomer or mixtures thereof;
b) a photoinitiator sensitive to light in the green to infrared region;
c) an additive to increase the refractive index and decrease the viscosity of the formulation; and
d) an optional filler;
applying a sufficient amount of the formulation between the waveguides or light guides of the optical element to be connected; and
exposing the optical element to a light source emitting light in the region to polymerize the formulation, thereby making an optical connection between the at least two waveguides or light guides.
Preferably, the light is transmitted during the exposing through at least one of the at least two waveguides or light guides. While a filler is also optional in the case of optically coupling waveguides or light guides, a filler having the desired optical properties is preferred to reduce the amount of polymer used and to impart desirable physical properties to the formulation.


A CD-ROM appendix is included in this disclosure. Specifically, Appendix B is a plurality of tables utilized by the computer source code listing. The CD-ROM is submitted at the same time as this preliminary amendment, and is hereby incorporated by reference. The only file on the CD-ROM is entitled, xe2x80x9c10932-43 CD-ROM Appendix.xe2x80x9d The file size is 790 KB and the file was created on Nov. 27, 2001. The machine format is IBM-PC and the operating system used to create the file is MS-Windows.
1. Technical Field
The present invention relates generally to speech encoding and decoding in voice communication systems; and, more particularly, it relates to various techniques used with code-excited linear prediction coding to obtain high quality speech reproduction through a limited bit rate communication channel.
2. Related Art
Signal modeling and parameter estimation play significant roles in communicating voice information with limited bandwidth constraints. To model basic speech sounds, speech signals are sampled as a discrete waveform to be digitally processed. In one type of signal coding technique called LPC (linear predictive coding), the signal value at any particular time index is modeled as a linear function of previous values. A subsequent signal is thus linearly predictable according to an earlier value. As a result, efficient signal representations can be determined by estimating and applying certain prediction parameters to represent the signal.
Applying LPC techniques, a conventional source encoder operates on speech signals to extract modeling and parameter information for communication to a conventional source decoder via a communication channel. Once received, the decoder attempts to reconstruct a counterpart signal for playback that sounds to a human ear like the original speech.
A certain amount of communication channel bandwidth is required to communicate the modeling and parameter information to the decoder. In embodiments, for example where the channel bandwidth is shared and real-time reconstruction is necessary, a reduction in the required bandwidth proves beneficial. However, using conventional modeling techniques, the quality requirements in the reproduced speech limit the reduction of such bandwidth below certain levels.
Speech encoding becomes increasingly difficult as transmission bit rates decrease. Particularly for noise encoding, perceptual quality diminishes significantly at lower bit rates. Straightforward code-excited linear prediction (CELP) is used in many speech codecs, and it can be very effective method of encoding speech at relatively high transmission rates. However, even this method may fail to provide perceptually accurate signal reproduction at lower bit rates. One such reason is that the pulse like excitation for noise signals becomes more sparse at these lower bit rates as less bits are available for coding and transmission, thereby resulting in annoying distortion of the noise signal upon reproduction.
Many communication systems operate at bit rates that vary with any number of factors including total traffic on the communication system. For such variable rate communication systems, the inability to detect low bit rates and to handle the coding of noise at those lower bit rates in an effective manner often can result in perceptually inaccurate reproduction of the speech signal. This inaccurate reproduction could be avoided if a more effective method for encoding noise at those low bit rates were identified.
Additionally, the inability to determine the optimal encoding mode for a given noise signal at a given bit rate also results in an inefficient use of encoding resources. For a given speech signal having a particular noise component, the ability to selectively apply an optimal coding scheme at a given bit rate would provide more efficient use of an encoder processing circuit. Moreover, the ability to select the optimal encoding mode for type of noise signal would further maximize the available encoding resources while providing a more perceptually accurate reproduction of the noise signal.
A random codebook is implemented utilizing overlap in order to reduce storage space. This arrangement necessitates reference to a table or other index that lists the energies for each codebook vector. Accordingly, the table or other index, and the respective energy values, must be stored, thereby adding computational and storage complexity to such a system.
The present invention re-uses each table codevector entry in a random table with xe2x80x9cLxe2x80x9d codevectors, each of dimension xe2x80x9cN.xe2x80x9d That is, for example, an exemplary codebook contains codevectors V0, V1, . . . , VL, with each codevector Vx being of dimension N and having elements C0, C1, . . . , CN-1, CN. Each codevector of dimension N is normalized to an energy value of unity, thereby reducing computational complexity to a minimum.
Each codebook entry essentially acts as a circular buffer whereby N different random codebook vectors are generated by specifying a starting point at each different element in a given codevector. In one embodiment, each of the different N codevectors then has unity energy.
The dimension of each table entry is identical to the dimension of the required random codevector and every element in a particular table entry will be in any codevector derived from this table entry. This arrangement dramatically reduces the necessary storage capacity of a given system, while maintaining minimal computational complexity.
Other aspects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.


A slender structure is very sensitive to dynamic loading. A high building, long span bridge, skyscraper and other similar structures may lose their function or in some serious cases may be destroyed under dynamic loading. In general, the kind of damage induced by the dynamic loading can be divided into two kinds, namely functional and safety loss.
In order to solve this kind of problem, it is conventional to increase the strength and ductility of load bearing structures. This is the usual practice in earthquake-resistance design for civil works. Another method is to employ some measure to reduce the response of the structure to such vibration.
The methods of reducing vibration of the structure generally can be divided into two classes, namely passive control and active control. The so-called passive control is usually carried out by increasing or decreasing a number of springs in the structure to change the stiffness of the structure, so that its natural frequency can be adjusted to depart from the frequency of dynamic loading.
Alternatively, a mass-spring damper may be installed on the structure to concentrate vibration energy in the mass-spring damper, so that the goal of reducing the vibration of main structure can be reached.
Another method is to arrange weak spots at some specific positions on the structure. In this way, strong vibrations will force these weak spots to produce plastic strains, by which energy consumption of the total structure can be increased. A common point of the passive control is that the dynamic characteristics of the structure are fixed after completing the structure, and the stress status of struts in the structure is completely determined by the time history of the loading. It is not necessary or even possible to take initiative action to change the characteristics. Therefore the designer must grasp in advance the complete characteristics of dynamic loading, such as magnitude and spectrum, so that an effect of the vibration reduction by these methods can be assured.
The so-called active control generally means installing a mechanism, such as an oil or air pressure mechanism, which can give additive force to the structure or change the status of inner forces in a part of the struts in the structure. Though theoretically the active control method can achieve a very good effect, it has a problem of stability in actual application, and also a large amount of energy has to be supplied. Furthermore, the mechanism itself is unreliable. Its range of applications, and especially applications for reducing the vibration of civil engineering and construction under dynamic loading, are much less than passive control cases.
As mentioned above passive control has the fault that its effect is poor, and active control has the faults that it is unreliable and requires a large amount of energy.


A variety of automated or semi-automated chemical analyzers are known which utilize cuvettes for the chemical testing of samples placed therein. Generally, a predetermined amount of liquid sample, such as biological fluid is placed in the cuvette which is then transported through the instrument. As the cuvette is transported, the instrument dispenses a quantity of reagent into the sample and monitors the resulting chemical reaction. Such monitoring is generally accomplished through use of an optical means which views the fluid sample through optically transparent portions of the cuvette.
In order to simplify the loading of the cuvettes into the instrument and facilitate their handling by the instrument once so loaded, proposals have been made to provide the cuvettes in the form of a continuous integral strip. The individual cuvettes of the strip are designed to be relatively rigid but the strip itself is provided with sufficient flexibility to ease its transport through the instrument.
Furthermore, by making the cuvettes in a continuous strip form, they can be manufactured relatively inexpensively from suitable plastic material, thereby permitting their disposal after use. This is an important feature since it avoids the requirement for washing the cuvettes after use and avoids any possibility of cross-contamination of fluid samples which could cause erroneous test results. A proposed cuvette system designed to meet these requirements is proposed in U.S. Pat. No. 4,263,256.
In commonly owned copending U.S. patent application Ser. No. 284,842 filed July 20, 1981 and entitles "Cuvette System For Automated Chemical Analyzer", now abandoned, the disclosure of which is hereby incorporated by reference in its entirety herein, there is described a cuvette belt which comprises a matching pair of formed elongated plastic strips which are joined together along corresponding faces thereof to form an integral belt. A series of regularly spaced cavities or chamber halves is formed transversely in each of the corresponding strip faces which define open-topped cuvette receptacles when the belt halves are joined. As described, the cuvette belt is made by forming strip plastic material with a series of regularly spaced transverse (laterally extending) elongated pockets so as to define two integral side-by-side belt halves. The formed strip is then divided longitudinally to separate the belt halves and the belt halves brought into register and joined together to form a completed cuvette belt.
Using such manufacturing techniques, cuvettes may be obtained with superior optical characteristics and dimensional accuracy previously obtainable only through use of injection molding techniques. This is important when optically analyzing samples in the cuvettes for which a precisely defined optical path through the cuvette is required. It is pointed out that it is possible by utilizing cold forming techniques to avoid optical degradation of the material due to heat. Further an optical portion of the material may be restrained by clamping or other forming techniques during the pocket forming operation to avoid stretching or other deformation of portions of the pocket which form the sides of the cuvette. In this manner essentially all stretching of the material during forming is limited to the side walls of the pockets and optical portions thereof are maintained stress-free and with a uniform thickness.
Reference is also made to commonly owned copending U.S. patent application Ser. No. 746,231 filed June 18, 1985, and entitled "Cuvette Belt Manufacture and Process", the disclosure of which application is hereby incorporated by reference in its entirety herein. In that application is disclosed an alternative method for making cuvette belts where they comprise a matching pair of plastic strips, each of which is formed with chamber halves, and which are joined together to form an integral cuvette belt with the chamber halves aligned to form the cuvettes.
According to that method, two strips of plastic material are identically formed with a series of regularly spaced transverse elongated pockets so as to define two integral side-by-side belt halves. The two formed strips are brought into register and joined together to form a composite strip defining two integral mirror image cuvette belts joined by their cuvette mouth ends. The composite strip is then divided longitudinally to separate the cuvette belts.
The present invention is particularly concerned with techniques for joining the formed plastic strips by heat sealing during the manufacture of such cuvettes while retaining the aforesaid optical characteristics.


1. Field of the Invention
The present invention relates to improvement in optical gas analyzers and more particularly, to refinements in non-dispersive infrared analyzers in order to obtain adequate performance for medical and other precision applications.
2. Description of Prior Art
The inventor of the present invention has contributed to the prior art devices in the area of infrared gas analyzers and this prior art as exemplified in U.S. Pat. No. 3,932,754 substantially sets forth one aspect of devices commercially utilized to date for non-medical applications. The inventor in setting forth to perfect instrumentation for medical applications found that the prior art teachings contained in the above referenced patent and others known in the art, lacked the degree of reliability and sophistication necessary for medical applications.
Towards this end, when dealing with instrumentation in life support systems in which the output of information is of a critical nature the degree of calibration and other performance standards, as hereinafter explained in detail, was not available with the prior art equipment. Accordingly, although the present invention will be particularly discussed with respect to the benefits it provides for medical application, these same advantages also lend themselves to industrial and other applications as well.


Consumer demand for Internet-based services has led to the widespread deployment of customer premise equipment (CPE) to provide various connectivity functions. The growth of home networking technologies has further expanded the range of devices installed at customer premises. The increased amount of voice, video and data traffic is driving the market for premise-based services. This growth is only expected to increase over time and the resulting costs of maintaining a complex assortment of CPE is also expected to increase. The cost of configuring new features and services on hardware network appliances is particularly burdensome because of the cost of sending technicians to customer sites.
Based on the foregoing, there is a need for an efficient approach to the remote management and support of network appliances installed at customer premises.


1. Field of the Invention
The present invention relates to a hose-in-hose or double walled hose, and, more particularly, to a hose-in-hose secondary coupler.
2. Description of the Related Art
It is known that hose-in-hoses have been used to transport liquid waste, such as nuclear waste, to a place away from the source.
A problem with current hose-in-hose configurations is that once the outer hose is disconnected via a coupler, the separated ends of the outer hoses must be physically pulled apart to allow access to the inner hose. Although on shorter lengths of hose this may not present much of a problem, as the length of the hose increases the difficulty in providing adequate force to pull apart the disconnected ends also increases. The ability to adequately separate the disconnected ends of the outer hose to a significant distance thereby allowing access to the inner hose relies on the strength of the end user. Furthermore, longer hoses may not be able to be separated at the coupler due to the weight of the individual hose ends.
What is needed is a device which allows access to the inner hose without the need to substantially move the two disconnected ends of the outer hose.


Tn U.S. Pat. No 3,612,793 issued on Oct. 12, 1971, to John O. Roeser and entitled "Electrical Switch Components And Switches Formed Thereby," there is shown and described a unitary combination switchblade and contact means For compact switch mechanisms. As can be seen from FIGS. 8, 9 and 10 of the '793 patent, the combination switchblade and contact means 16 comprises a pair of identical members 109a (109b) each being formed of a first end portion 110 a mid-portion 116 and a curvilinear second end portion 118. The first end portion 110 consists of a pair of spaced apart legs 112 and 114. The legs are spaced apart by a dimension D so as to receive therebetween a tension spring 120, as illustrated in FIG. 5. A combination strut and attachment means 124 is shear formed in the curvilinear second end portion 118 and includes a reverse curve portion 131 for mating with the end of the tension spring 120 (FIG. 5).
The curvilinear second end portion 118 further includes an upper contact portion 128 and a lower contact portion 130 which is separated from the upper contact portion 128 by means of the reverse curve portion 131. The legs 112 and 114 are provided with sharpened edges 132 for pivoting within opposed V-shaped notch portions 106 formed within an elongated metal member 74 of the actuating means 114. The lower contact portion 130 is located within the same plane as the first portion 110 and the mid-portion 116 However, the upper contact portion 128 is off-set from that same plane. The lower and 15 upper contact portions 128 and 130 define movable contact members which are adapted to be snapped between opposed fixed contact portions upon upper terminal members 134 and lower terminal members 136, as illustrated in FIG. 5.
The upper portions of the upper terminal members 134 are formed with an off-set transverse portion 116 having a depending upper fixed contact 148 (FIGS. 14 and 15). The upper fixed contacts 148 serve to make electrical contact engagement with the upper contact portions 128 of the movable contact members. The lower terminal members 136 are provided with portions 156 which serve as lower fixed contacts for electrical contact engagement with lower contact portions 130 of the movable contact members.
The combination switchblade and contact means 16 is assembled with other components so as to form a compact precision, snap-action push-button switch 10 and is illustrated in FIGS. 2, 5 and 6. In operation, when the button 72 of the actuator means 14 is depressed so as to move downwardly, this causes the elongated metal member 74 to also more downwardly against the bias of the return springs 76 and 78. Initially, the combination 15 switchblade and contact means is restrained by means of the lower fixed contact portions 156 so that the lower contact portions 130 of the movable contact members remain in contact therewith.
This contact continues until the pivot points 106 pass the center line of the tension spring 120. At that time, the movable contact members will snap overcenter and the upper contact portions 130 thereof will become engaged with the upper fixed contacts 148. This engagement continues until such time when the pressure upon the top of the button 72 is released, thereby causing the return springs 76 and 78 to return the metal member 74 and button 72 to their rest positions shown in FIGS. 1 and 2. As the metal member 74 returns past the center line of the tension spring 120, the movable contact members will snap overcenter again in the reverse direction.
The present invention represents an improvement over the combination switchblade and contact means described above in connection with the '793 patent. The upper contact portion 128 and the lower contact portion 130 upon the second end portion 118 of the switchblade and contact means 16 in the aforenoted patent experience a high degree of stress during the switching operations which tends to shorten the service lives of such components. It would therefore be desirable to provide a novel and improved switch butterfly assembly for use in precision snap action switches which has a unique configuration so as to reduce the stresses upon the movable contact portions, thereby prolonging the service lives thereof.


Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells (“Cellular and Molecular Immunology” (1991) (eds.) Abbas A. K., Lechtman, A. H., Pober, J. S.; W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women (“Cellular and Molecular Immunology” (1991) (eds.) Abbas, A. K., Lechtiman, A. H., Pober, J. S.; W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade, immunotherapy and other molecular methods have emerged as new and promising methods for treating melanoma.
Strong evidence that an immune response to cancer exists in humans is provided by the existence of lymphocytes within melanoma deposits. These lymphocytes, when isolated, are capable of recognizing specific tumor antigens on autologous and allogeneic melanomas in a major histocompatibility complex (MHC)-restricted fashion (Itoh et al. (1986), Cancer Res. 46: 3011-3017; Muul et al. (1987), J. Immunol. 138:989-995); Topalian et al. (1989) J. Immunol. 142: 3714-3725; Darrow et al. (1989) J. Immunol. 142: 3329-3335; Hom et al. (1991) J. Immunother. 10:153-164; Kawakami et al. (1992) J. Immunol. 148: 638-643; Hom et al. (1993) J. Immunother. 13:18-30; O'Neil et al. (1993) J. Immunol. 151: 1410-1418). Tumor infiltrating lymphocytes (TIL) from patients with metastatic melanoma recognize shared antigens including melanocyte-melanoma lineage specific tissue antigens in vitro (Kawakami et al. (1993) J. Immunother. 14: 88-93; Anichini et al. (1993) J. Exp. Med. 177: 989-998). The fact that many melanoma patients mount cellular and humoral responses against these tumors and that melanomas express both MHC antigens and tumor associated antigens (TAA) suggests that identification and characterization of additional melanoma antigens will be important for immunotherapy of patients with melanoma. However, there remains a need for new modalities for the treatment of melanoma and other cancers.


This invention relates to electronic circuitry and, more particularly, to a charge pump for producing a negative substrate bias in a complementary metal oxide semiconductor (CMOS) integrated circuit.
MOS transistors are commonly used in electronic circuits such as dynamic random access memories (DRAMS). In an NMOS transistor, an N-type source region is separated from an N-type drain region by a P-type channel region. All three regions are formed in a P-type semiconductor substrate. By applying a positive voltage to a gate electrode disposed above the channel region, electrons gather in the channel region between the source region and the drain region to allow current to flow from the drain region to the source region. PMOS transistors have the same structure except the conductivity types of the various regions are reversed and a negative gate voltage is required to allow current to flow from the source region to the drain region.
It has been found that NMOS transistors operate better when the P-type substrate of the NMOS (or of the NMOS transistors in a CMOS circuit) is driven negative with respect to circuit ground, in other words there is a negative substrate bias. Such a negative substrate bias provides a number of advantages in terms of the overall circuit performance. More specifically, a negative substrate bias decreases the NMOS transistor source and drain capacitance, decreases the likelihood of latchup, decreases PN diode injection when a node is driven below ground, and decreases the effective body effect, all of which are desirable in CMOS circuits.
Typically a charge pump circuit is used to create the negative substrate bias. Once a negative substrate bias is achieved, however, it does not last forever. For example, when an NMOS transistor is conductive with a relatively high drain to source voltage, some of the electrons traveling from the source region to the drain region collide with atoms in the channel region with enough energy to cause electron/hole pairs to form. The positive gate voltage attracts the generated electrons to the surface of the channel while the positive drain voltage attracts them to the drain where they simply add to the normal flow of electrons from source to drain. The positively charged holes, by contrast, are repelled by the positively charged gate away from the channel region into the substrate. The substrate current created by the excess holes makes the substrate more positively charged, thus counteracting the negative substrate bias. In DRAMS, a substantial amount of substrate current is generated whenever the memory is read or written, since many transistors are switched on and off at that time. This component of substrate current may be orders of magnitude above the background (i.e., standby) leakage current of all the reverse biased P--N diodes throughout the circuit. Therefore, the charge pump must remove low substrate current during standby and high substrate current during high activity to maintain the negative substrate bias.
FIG. 1 is a conceptual schematic diagram of a charge pump 2 which includes a first switch 4 coupled between a positive power supply voltage (V.sub.cc) and, a first terminal 6 of a capacitance C1. A second switch 8 is coupled between a ground potential (V.sub.ss) and a second terminal 10 of capacitance C1. A third switch 12 is coupled between (V.sub.ss) and terminal 6 of capacitance C1, and a fourth switch 14 is coupled between the substrate (represented by the voltage (V.sub.bb)) and terminal 10 of capacitance C1. In operation, switches 4 and 8 are both closed (made conductive) for charging capacitance C1 to a voltage equal to the difference between (V.sub.cc) and (V.sub.ss). In FIG. 1, (V.sub.cc)=+5 volts and (V.sub.ss)=0 volts, so capacitance C1 charges with node 6 five volts more positive than node 10. Thereafter, switches 4 and 8 are opened and switches 12 and 14 are both closed. Since the positive terminal 6 of capacitance C1 is now coupled to a ground potential, the negative terminal 10 of capacitance C1 tries to drive V.sub.bb to negative 5 volts through switch 14. Thereafter, switches 12 and 14 are opened, and the sequence repeats itself. An oscillator (not shown) typically controls the repetitive switching sequence, and a detector (not shown) monitors the substrate voltage and controls the pumping operation to maintain the substrate at the proper negative voltage level.
As discussed in more detail below, known charge pumps consume a substantial amount of power (often 1 milliwatt or more even when no further pumping is required), often work against themselves by adding positive substrate current as they operate, and generally operate inefficiently.


This invention relates in general to die-casting machines and in particular to high-speed die-casting machines for the production of precision miniature castings where the weight of the produced casting generally does not exceed two ounces and the face of the die generally does not exceed approximately ten square inches. While these size limitations provide a suitable focus, many of the features of the present invention are applicable to much larger machines.
Heretofore, machines for the die casting of precision miniature pieces have been generally of the Dynacast type, a die-casting machine developed in the mid-1960's and the subject of several United States patents, including U.S. Pat. No. 3,364,981. This machine, at the time of its development, drastically changed the manufacture of miniature die-casting pieces which prior to the time of the U.S. Pat. No. 3,364,981 were manufactured in large conventional die-casting machines using multiple-cavity dies. However, the state of the art has remained practically unchanged during the last 20 years. At the expiration of the above-mentioned patent, the machine has been duplicated by several manufacturers with more or less the same features but without eliminating the various shortcomings.
One shortcoming of the Dynacast machine is the fact that the machine can use only two vertical cores and only occasionally a frontal core. The zinc injection system of the Dynacast machine is made by a gooseneck partially submerged into the liquid zinc of the melting pot. The gooseneck has a swiveling movement in order to bring the nozzle in contact with the die face and to move the nozzle away from the die face to break the runner from the liquid metal. Besides the mechanical elements needed for this movement (which adds complexity to the machine), this system reduces the speed at which the machine can operate. The position of the gooseneck precludes the use of a fourth core.
Another shortcoming of the Dynacast machine includes the way the level of the zinc in the neck of the gooseneck is controlled. This system leaves a certain amount of air ahead of the zinc in the neck of the gooseneck, which amount of air is variable and depends upon several parameters which are not easily controlled, such as the temperature of dies, size of the shots, speed of the machine and temperature of the nozzle. Another drawback of the Dynacast machine is the way the toggle mechanism operates in order to close the die halves and to create the force between them. This force generated between the dies varies, depending on the wear of the mechanical components of the toggles, temperature of the dies, temperature of the plate of the machine, and so forth.
A further drawback of the Dynacast machine is the fact that it cannot produce parts with what is known in the industry as a "hardware" finish; in other words, parts that do not need to be plated. The reason for such inability involves the way the zinc is injected into the die, the gating (which has to be small because of the subsequent separation from the part with the tumbling operation) and the system of heat transfer on the die. The parts from the Dynacast machine are ejected with the gates attached to them, and this requires a subsequent operation (tumbling) in order to separate the parts from the gate, with all of the negative attributes of such operation including surface pitting, dimensional alteration, and breaking of sharp corners.
The present invention provides a machine which is designed to overcome the above shortcomings and disadavantages. In order to achieve this object, the disclosed machine produces castings which may require up to four cores along the plane of the dies (substantially two vertical and two horizontal) and two cores in a plane perpendicular to the surface of the die with a total of six cores. The machine of the present invention produces castings with much less porosity than any other machine used today and with surface finish of the type as previously mentioned which is known in the industry as a hardware finish. The cast pieces can be trimmed automatically in the machine so that the pieces are separated from the gate, the gates being discharged in a separate container for a subsequent remelt.
Another reference of possible interest to the heat transfer aspects of the present invention is U.S. Pat. No. 4,248,289 which issued to Perella et al. This patent discloses a means to heat the heat-exchange medium, water, by electric immersion heaters to preheat the die aove the normal boiling point of water by controlling the internal pressure of the die-cooling cavity. Die cooling is accomplished by the heat of evaporation at the temperature and pressure required for best casting quality. The wall thickness of the die cavity to water cavity is sized according to the heat-transfer rate or the die-cavity material. As steam is produced within the cavity, make-up water is introduced to maintain a wetted surface.
In die-casting practice, the "coring" of a cast part encompasses many forms. The core may be in the form of an entry hole, round, square or otherwise, a hollow space, a countersunk or extended boss, an embossed face, or any shape that is required that is not formed by the two-part mold cavity. Some core requirements are parallel to the line of separation of the mold halves but are independent in movement. Other cores not in the line of mold separation movement must be positioned and supported either by devices integral with the die blocks or as a function of the die-casting machine. Those arrangements which are integral with the molding dies add substantially to the cost of the dies and are not practical for miniature casting work. Since the hydraulic pressure area of some cores can be equal to that of the die cavity, it is necessary to have equal support to that of the die cavity to lock the core in a fixed position. This may be accomplished by toggle movement to rapidly position the core in the die and then lock the position as securely as the main die-closing action.


The present invention relates to a tapping fitting for application to a pipe in order to direct fluid conducted therethrough to an ancillary device, such as a branch conduit or an outlet tap. The invention is particularly useful in electrofusion fittings for plastic pipes wherein the fitting is bonded to a plastic pipe by electrofusion, and is therefore described below with respect to this application, although it will be appreciated that the invention could also be used in other applications.
Tapping fittings of the foregoing type are known. They generally include a rotatable blade assembly formed with external threads threadedly received within the housing and including a cylindrical cutting blade such that rotation of the blade assembly moves it axially from an initial, retracted position within the housing, to a projected position, to cut a cylindrical slug from the plastic pipe to which the fitting is attached. Such tapping fittings are applied to the plastic pipe while the blade assembly is in its initial, retracted position, i.e., within the housing of the fitting. After the fitting has been so applied, the blade assembly is rotated from externally of the fitting to its projected position to cut a cylindrical slug from the plastic pipe, and then it is rotated in the opposite direction back to its initial, retracted position to remove the slug and retain it within the housing main section of the fitting. The fitting thus establishes communication between the plastic pipe and the ancillary device, and generally remains in place for the life of the installation.
Such tapping fittings have come into extensive use for tapping branch conduits to high-pressure liquid or gas supply pipes of a plastic material. The housing is generally made of polyethylene or of a similar plastic material as the pipe. It has been found, however, that the plastic material used for the housing tends to creep over a long period Of time. Transverse creep (i.e., transversely to the axial movement of the blade assembly) may result in the blade assembly jumping the threads; whereas axial creep may result in the failure of the valve to completely close.


Ovarian cancer is the eighth most common type of cancer among women. The American Cancer Society estimates that about 22,220 new cases of ovarian cancer will be diagnosed in the United States during 2005. Ovarian cancer accounts for about 3% of all cancers in women. Because many ovarian cancers cannot be detected early in their development, they account for a disproportionate number of fatal cancers, being responsible for almost half the deaths from cancer of the female genital tract; more deaths than any other reproductive organ cancer. Older women are at higher risk. More than half of the deaths from ovarian cancer occur amongst women between 55 and 74 years of age. About 25% of ovarian cancer deaths occur amongst women between 35 and 54 years of age.
The main treatments for ovarian cancer are surgery, chemotherapy, and radiation therapy. Combinations of these treatments are used to treat ovarian cancer.
Surgery is the usual initial treatment for women diagnosed with ovarian cancer. The ovaries, the fallopian tubes, the uterus, and the cervix are usually removed. Staging during surgery (to find out whether the cancer has spread) generally involves removing lymph nodes, samples of tissue from the diaphragm and other organs in the abdomen, and fluid from the abdomen. If the cancer has spread, the surgeon usually removes as much of the cancer as possible. This reduces the amount of cancer that will have to be treated later with chemotherapy or radiation therapy
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy may be given to destroy any cancerous cells that may remain in the body after surgery, to control tumour growth, or to relieve symptoms of the disease. Most drugs used to treat ovarian cancer are given intravenously or directly into the abdomen through a catheter.
Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine or women receive a treatment called intraperitoneal therapy in which radioactive is put directly into the abdomen through a catheter.
Deciding on a particular course of treatment is typically based on a variety of prognostic parameters and markers [Fitzgibbons, et al. (2000) Arch. Pathol. Lab. Med. 124:966-978; Hamilton and Piccart (2000) Ann. Oncol. 11:647-663)], including genetic predisposition markers BRCA-1 and BRCA-2 [Robson (2000) J. Clin. Oncol. 18:113sup-118sup].
Although many ovarian cancer patients are effectively treated, the current therapies can all induce serious side effects, which diminish quality of life. Moreover, approximately 85% of the patients that have been effectively treated with platinum- and paclitaxel-based chemotherapy, including complete responses, relapse within two years after treatment.
The identification of novel therapeutic targets is essential for improving the current treatment of ovarian cancer patients. Recent advances in molecular medicine have increased the interest in tumour-specific cell surface antigens that could serve as targets for various immunotherapeutic or small molecule strategies.
Among the various elements of the immune system, T lymphocytes are probably the most adept to recognize and eliminate cells expressing foreign or tumour-associated antigens. Cytotoxic T Lymphocytes (CTLs) express the CD8 cell surface marker and are specialized at inducing lysis of the target cells with which they react via the perforin/granzyme and/or the Fas/Fas-L pathways. The T-cell receptor (TCR) for antigen of CTLs binds to a molecular complex on the surface of the target cell formed by small peptides (8-11) residues derived from processed foreign or tumour associated antigens, which associate with major histocompatibility complex (MHC) class I molecules.
The other major T-cell subset, helper T lymphocytes (HTLs or T helper cells), is characterized by the expression of CD4 surface marker. The T helper cells recognize slightly larger peptides (11-20 residues), also derived from foreign or tumour associated antigens, but in the context of MHC class II molecules, which are only expressed by specialized antigen presenting cells (APCs) such as B lymphocytes, macrophages and dendritic cells (DCs).
As a consequence of TCR stimulation of naive CTLs and HTLs by peptide/MHC complexes on APCs, the CTLs mature into effector killer cells capable of lysing (tumour) cells that express the corresponding peptide/MHC class I complex. Activated HTLs amplify CTL responses by making the APCs more effective at stimulating the naive CTLs and by producing lymphokines that stimulate the maturation and proliferation of CTLs. The potentiating effect of T helper cells occurs both in secondary lymphoid organs where the immune response is initiated and at the tumor site where CTL responses need to be sustained until the tumour cells are eliminated. Thus, one would predict that vaccines should stimulate both tumour-reactive CTLs and HTLs to generate effective antitumour immunity.
Antigens suitable for immunotherapeutic cancer strategies should be highly expressed in cancer tissues and ideally not in normal adult tissues. Expression in tissues that are dispensable for life, however, may be acceptable.
A number of antigens suitable for immunotherapeutic strategies in the treatment of ovarian tumors have been described so far, including MUC1, CTs, SP17 and Her2/neu.
Polymorphic epithelial mucin (MUC1) is a transmembrane protein, present at the apical surface of glandular epithelial cells. It is often overexpressed in ovarian cancer (in more than 90% of all ovarian cancers), and typically exhibits an altered glycosylation pattern, resulting in an antigenically distinct molecule. MUC1 is in early clinical trials as a vaccine target [Gilewski, et al. (2000) Clin. Cancer Res. 6:1693-1701; Scholl, et al. (2000) J. Immunother. 23:570-580]. The tumour-expressed protein is often detectable as tumor marker in the circulation [cf. Bon, et al. (1997) Clin. Chem. 43:585-593].
A unique class of differentiation antigens, the cancer/testis (CT) antigens, are not expressed in normal tissues except for testis and, in some cases, placenta. This fact makes CT antigens attractive targets for specific immunotherapy of cancer. The function of the majority of the CT antigens is currently unknown. Tammela et al. [Tamella, et al. (2004) Cancer Immunity 4:10-21] demonstrated that SCP-1, a CT antigen with a known role in gamete development, is expressed in 15% of ovarian cancer cases. It was suggested that because of its restricted expression in normal tissues and its aberrant expression in tumour tissues SCP-1 might serve as a potential target for vaccine therapy in ovarian cancer.
Another potential target for immunotherapy in patients with ovarian carcinoma is the sperm protein 17 (SP17). Sp17 was found to be expressed in the primary tumor cells from 70% of the patients with ovarian carcinoma. The restricted expression of Sp17 in normal tissue makes it an ideal target for tumour vaccine. A recombinant Sp17 protein was used with monocyte-derived dendritic cells and autologous peripheral blood mononuclear cells to generate Sp17 specific cytotoxic T-lymphocytes (CTLs). Human leukocyte antigen (HLA) class II restricted Sp17 specific CTLs were generated successfully from the peripheral blood of three patients with ovarian carcinoma at the time of disease presentation. These CTLs were able to lyse autologous Epstein-Barr virus-transformed lymphoblastoid cells in an Sp17-dependent manner. The CTLs also lysed Sp17-positive autologous tumour cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17-positive tumour cells. [Chiriva et al. (2002) Cancer 94(9):2447-2453]
Human epidermal growth factor receptor 2 (Her2/neu) is an oncogene that is activated by gene amplification with the increased expression of another (normal) gene product. Her2/neu is overexpressed in 20 to 30% of patients with breast and ovarian cancer. Initial studies to develop a peptide based HER-2/neu vaccine were performed in a rat model [Disis et al. (1999) Clinical Cancer Research 5:1289-1297]. No T-cell responses or anti-body responses were observed in animals immunized with intact rat neu protein. By marked contrast, tolerance to rat neu protein in rats, could be circumvented by immunization with a peptide based vaccine. Rats immunized with neu peptides designed for eliciting CD4+ T-cell responses, generated T-cell and antibody responses specific for both the immunizing peptides and the whole protein.
Brossart et al. demonstrated that patients with advanced breast and ovarian cancer could be efficiently vaccinated with autologues dendritic cells (DCs) pulsed with Her2/neu- or MUC1-derived peptides. In 5 out of 10 patients peptide specific CD8+ cytotoxic T lymphocytes could be detected in the peripheral blood. It was reported that MAGE-3- and CEA-peptide-specific CD8+ T cells were observed in one patient treated with MUC-1 peptide-pulsed DCs, and MUC-1 specific T-cells were observed in another patient after vaccination with HER2/neu derived peptides. It was suggested by Brossart et al. [Brossart et al. (2002) Transfus Apher Sci. 27(2):183-186] that this indicated that epitope spreading occurred in these patients upon treatment.
Epitope spreading is a recognized phenomenon of autoimmune responses and is believed to be an exacerbating factor in CD4+ T cell-mediated autoimmune diseases. The phenomenon has been demonstrated in murine relapsing-remitting experimental autoimmune encephaleomyelitis (EAE), Theiler's murine encephalomyelitis virus-induced demyelineating disease and diabetes in the non-obese diabetic (NOD) mouse. A model has been suggested for how epitope spreading in autoimmune diseases mediated by CD4+ T cells occurs. This model is supported by direct evidence that tissue damage, TCR ligation on CD4+ T cells by MHC class II-peptide complexes, CD40-CD40 ligand interactions and CD28-mediated co-stimulation are required for epitope spreading to become manifest. It is thought that an initiating self-antigen or a persistent viral epitope, presented in MHC class II molecules on the surface of professional antigen-presenting cells (APC) residing in the target tissue, causes the activation of CD4+ T cells specific for that antigen. This T cell activation results in chronic inflammation, leading to damage of the target tissue. Tissue debris is subsequently taken up by APC which have up-regulated expression of MHC class II and co-stimulatory molecules in response to inflammatory cytokines. These APC are then capable of activating CD4+ T cells specific for secondary tissue epitopes presented by the APC. The newly activated T cells then aid in destruction of the target tissue.
Due to the requirement for presentation by APC of exogenous antigen, epitope spreading has historically been thought of as a phenomenon unique to CD4+ T cell responses. However, recent data have indicated that cross-priming by APC can participate in the induction of CD8+ cytotoxic T lymphocyte (CTL) responses as well. In particular, bone marrow chimera studies in murine tumour models have shown that tumour-specific CTL are predominately restricted to the MHC of the host rather than that of the tumour, suggesting that indirect presentation by host APC is involved in the generation of tumour-specific CTL. Moreover, there is increasing evidence that a pathway exists whereby exogenous antigen can be presented for eventual peptide loading onto class I MHC molecules. This phenomenon is best described for dendritic cells (DC) and provides a cellular mechanism to explain the process of cross-priming. Collectively, these data suggest that it may be possible for epitope spreading to occur during a class I MHC-restricted CTL response. Because re-presentation of MHC class I-restricted tumour antigens is known to occur, it has been postulated that if tumour-bearing hosts could initiate a CTL response against a single tumour antigen, that following tumor cell damage caused by the CTL, epitope spreading might occur via a mechanism analogous to that described in CD4+ T cell-mediated autoimmune diseases. Unlike during an autoimmune response, however, CTL epitope spreading during an anti-tumour response could be beneficial to the host by possibly allowing for elimination of variant tumor cells that have lost expression of the antigen (antigen negative tumour cells). [Markiewicz et al., (2001) International Immunology 13:625-632].
Markiewicz et al found that immunization with the single tumour peptide P1A followed by tumour rejection led to CTL activity against a P1A− tumour, indicating that the phenomenon of epitope spreading is not limited to CD4+ T cell responses. The population of CTL included cells recognized the unrelated antigen PIE. Since this epitope was not included in the vaccine and is a mutated peptide not presented in normal tissues, the source of PIE antigen must have been the tumor cell challenge.
Because many patients have ovarian tumours that express neither one of the aforementioned antigens there is a need to uncover additional antigenic targets for immunotherapy to manage localized and metastatic disease. Accordingly, provided herein are molecular targets for immunotherapeutic intervention in ovarian cancers.
The zona pellucida (ZP) forms an extracellular glycoprotein matrix surrounding the developing and ovulated oocyte and the preimplantation embryo and is also detectable in atretic follicles. The ZP induces acrosome reaction on sperm, determines the species specificity for fertilization and prevents polyspermy in mammals. The zona pellucida contains four major glycoproteins, ZP1, ZP2, ZP3 and ZP4. In vitro studies in mice indicate that O-linked oligosaccharide side chains of ZP3 are involved in the primary binding of the sperm to the ZP3, while ZP2 contributes to the subsequent and persistent ZP binding and functions as a secondary sperm receptor.
The ZP glycoproteins have been studied extensively for the development of vaccines for the fertility control of animals and humans. The proposed vaccine action is the induction in female subjects of effective sustained, but reversible levels of ZP-specific antibodies that inhibit sperm-egg binding and/or prevent sperm penetration of the ZP. Passive immunization of female mice with rat monoclonal antibodies against mouse ZP2 or ZP3 resulted in localization of the antibodies to intra-ovarian oocytes and long-lasting but reversible contraception. Active immunization of female mice with ZP3-derived peptides ZP3328-342, comprising a B-cell epitope recognized by the ZP3-specific contraceptive antibody, also led to reversible albeit incomplete contraception. These ZP3 peptides also induced a T cell response to the ZP3 peptide. These CD4+ ZP3 specific T cells adoptively transfer autoimmune ovarian disease (AOD) to syngeneic recipients. Since the desired contraceptive effect of ZP3 immunization is known to be mediated by antibodies, an acceptable contraceptive ZP vaccine should induce an adequate antibody response without activation of ZP3-specific T cells. Indeed a chimeric peptide consisting of a foreign T-cell epitope from bovine ribonuclease (RNase) and a minimal and modified murine ZP3335-342 B cell epitope has been designed that elicits antibodies to ZP and has a significant contraceptive effect without causing significant oophoritis/AOD. The bovine RNase T-cell epitope stimulates helper T cell (helper T lymphocytes, HTL) responses in mice, thus potentiating the contraceptive effectiveness without inducing ZP(3)-specific T cell action and T-cell mediated ovarian damage.
Immunisation with (self)ZP antigen has also been used to study autoimmune ovarian disease (AOD). More in particular, animal models suitable for studying AOD have been reported wherein autoimmune disease was induced using ZP antigen vaccination. For example, it was demonstrated by Rhim et al. [Rhim et al. (1992) J. Clin. Invest. 89:28-35] that in B6AF1 mice T-cell and antibody response were induced by vaccination with mouse ZP3328-342 peptide. Further studies on truncated ZP3328-342 peptides substantiated that a T cell response is sufficient for induction of oophoritis; seven of such peptides lacking antibody binding sites, elicited severe oophoritis without concomitant antibody response. These peptides include a minimal oophoritogenic peptide of eight amino acids, ZP3330-337, which overlaps the seven amino acid antibody binding site, ZP3336-342, by two residues.
It was reported by Bagavant et al. [Bagavant et al. (1999) Biology of Reproduction 61:635-642] that transfer of ZP3 peptide-specific T-cells into naïve recipient mice resulted in granulomatous oophoritis and enhanced ovarian expression of IL-1, TNF-α and IFN-γ. However the ovarian function of cell recipients was normal and the mice remained fertile. Antibody to ZP3 alone does not cause any ovarian pathology. Co-transfer of pathogenic T cells and ZP antibody together targets the inflammation into developing follicles leading to their destruction and the development of ovarian atrophy. In another study Bagavant et al [Bagavant et al. (2002) American Journal of Pathology 160:141-149] demonstrated that ZP3 peptide (human ZP3328-341, macaque ZP3328-341 and mouse ZP3330-342) immunization in primates can elicit a T-cell response and cause ovarian immunopathology that is similar to murine AOD.
International patent application no. WO 2005/026735 (Buschmann et al.) relates to differentially expressed tumour-specific immunogenic membrane proteins and to their uses, in particular for finding at least one therapeutic molecule or compound which specifically regulates the expression of at least one of said membrane proteins, or for finding a therapeutic molecule that specifically binds to and/or interacts with any of said membrane proteins. The membrane protein can be SYPL, STOML2, RAGA, CLNS1A, PRNP, GNB2L1, GNG4, ITM2B, ITM1, TM9SF2, TM4SF6, OPRL1, LRP4, GLEPP1, TLR3 and/or ZP3. WO 2005/026735 teaches to administer the aforementioned therapeutic molecule or compound to neoplastic target cells for modulating proliferation, differentiation and/or cell migration of said neoplastic target cells. It is stated that the non-steroid dependent cancer to be treated results from the aberrant expression and/or biological activity of at least one of said immunogenic membrane proteins. It is also briefly mentioned in WO 2005/026735 that the development of a specific lesion, such as a pro-neoplastic lesion that can be found in epithelial tissues, into a neoplastic lesion can be inhibited by inoculating a subject with one of said membrane proteins adequate to produce antibody and/or T cell immune response. It is further specified that according to another embodiment the method comprises delivering one of the immunogenic membrane proteins via a vector directing expression of the said protein in vivo in order to induce such an immunological response to produce antibody to protect the subject from disease. Thus, WO 2005/026735, teaches several methods of suppressing the expression and/or biological activity of, amongst others, ZP3 membrane proteins in neoplastic target cells in order to modulate proliferation, differentiation and/or migration of said target cells, using either siRNA, receptor antagonists or antibody. WO 2005/026735 only discloses the expression of ZP3 membrane protein in certain colon cancer cells. No other reports of tumour associated expression of any ZP glycoprotein are known.


Traditionally, mechanical devices have been used to latch and unlatch closures such as doors, trunks, hoods, lift gates and hatches and the like in automobiles and other vehicles. It is known, however, to utilize an electro-mechanical door latch mechanism for such applications for a variety of reasons including ease of operation, lower cost and weight, improved styling opportunities, and reduced complexity. For example, a user actuated switch can be employed to trigger the release of a mechanical latch. In this regard, an electrical switch is operable to provide an input to a controller for operating the mechanical latch when the switch is actuated. In addition, modern styling and ergonomic requirements may dictate the physical configuration of the switch. For example, the switch may need to comprise an aesthetically pleasing user actuation component (e.g., a low profile button) that is of adequate size and shape so as to be easily operated by a user under a wide variety of operating conditions in a wide variety of environments.
Known switch technology for such applications generally incorporates a button having a first electrically conductive material comprising protrusions having the shape of “pills” or spring-like “fingers” that are insert molded or otherwise attached to the underside of the button. A second electrically conductive material comprising a set of contacts is located opposite the button on a base portion of the switch assembly. The second electrically conductive material may typically be in the form of a plate, tracks or a printed circuit board, for example. The first electrically conductive material completes a circuit in the switch when the switch is actuated by depressing the button. For example, when the button is depressed, the first conductive material bridges the contacts of the second electrically conductive material thereby closing an electric circuit.
In one such known switch assembly configuration, the switch assembly is also sealed from the atmosphere. During its manufacture, a fixed volume air is captured in the space between the button and the base portion of the switch assembly. As such, when the ambient temperature of the switch assembly changes, so too does the volume of the air trapped within the switch assembly. Under hotter ambient temperature conditions the volume of air within the switch assembly expands; under colder ambient temperature conditions, the volume of air within the switch assembly contracts.
In such a design, changes in the switch assembly's operating environment, such as extreme changes in ambient temperature, for example, can impact the perceived operation of the switch to a user. For example, the switch assembly may not reliably provide satisfactory and perceptible tactile feedback to the user signifying actuation of the switch. In such a case, depression of the button may instead provide an unsatisfactory continuous resistance to the user causing the user to be unsure whether the switch has been properly actuated.
Consequently, it is desirable to provide a switch assembly having a reliable and cost-effective actuation mechanism that also provides satisfactory tactile feedback to a user for signifying proper actuation of the switch.


1. Field of the Invention
The subject invention applies to the provision and display of video information and has particular application to apparatus for displaying recorded video programs, although not being limited thereto.
2. Description of the Prior Art
The detrimental effect of flutter on the display of video signals is well known, as is the fact that video information recording and playback equipment is a typical, although by no means exclusive, source of flutter.
The thrust of prior-art endeavor has been to improve the equipment responsible for the flutter. For instance, design and precision of video recording and playback system, including video tape recorders, have been continuously improved toward a reduction of flutter to tolerable proportions. This has neither been consistently successful nor has it helped in realistically bringing the equipment in question within the reach of the public or of educational and other institutions on a large scale. Rather, the requisite improvements for an implementation of prior-art proposals in this area have greatly increased the complexity and expense of manufacture and design of the apparatus in question.
An aggrevating factor in this area has been the tendency of conventional television display sets to amplify the effect of flutter in received signals. The source of this problem has been traced to a phase lock loop or electronic flywheel circuit present in most sets for stabilizing synchronizing signals against noise above a certain frequency. In general, prior-art stabilization circuits of this type have the advantage of permitting the synchronization drive to adjust to synchronization frequency differences when switching stations or to drift occurring in any station, while at the same time rendering the synchronization drive relatively immune to frequently occurring noise disturbances.
However, it will now be shown that these otherwise beneficial stabilization circuits amplify the effect of flutter in certain instances. Ideally, the horizontal position of a picture element in a video display is related to the phasing of the corresponding horizontal sync pulse. In practice, this is no longer the case if the horizontal sync has been stabilized by the stabilizing circuit of the set to a relatively steady time averaged value.
For instance, the line rate as delivered by a video tape recorder in the playback mode will have a flutter component. If .nu..sub.o is the nominal horizontal sync frequency and A is the peak amplitude of a flutter component of frequency .apprch., then the delivered line rate .nu. will be EQU .nu.=.nu..sub.o [1+A sin 2.pi..psi.t] (1)
The horizontal position of a picture element ideally will be at some fixed phase with respect to the beginning of the particular line. If .phi..sub.h is the absolute phasing of the line beginning, we have ##EQU1## so that .phi..sub.h is EQU .phi..sub.h =2.pi..intg..nu..sub.o [1+A sin 2.pi..psi.t]dt (3)
Since we are interested in the excursion of the variational component due to flutter and the peak amplitude of the excursion, the integral is taken between EQU t =0 and t =1/4.psi. (4)
variational component is ##EQU2## or EQU .phi..sub.h =.nu..sub.o A/.psi. (6)
as the amplitude excursion of the screen element when the sync is stabilized in the television display set.
Since the horizontal sweep is linear with time, this excursion expressed as a fraction of screen width is ##EQU3##
wherein .GAMMA. is the peak amplitude of the excursion of a picture element and A is the peak amplitude of the flutter component whose frequency is .psi..
As to the effect of flutter on the image display, we are concerned with the ratio ##EQU4##
For a nominal horizontal sync frequency of .nu..sub.o =15, 750 Hz and a flutter component frequency of .psi.=100 Hz, we obtain a ratio .GAMMA./A of ##EQU5##
Video recording and playback machines in which all flutter components remain below 0.1% or A A.ltoreq. 0.001 are expensive and complex. But even at that low value, the effects of flutter due to the above mentioned stabilizing action is still very objectionable.
For instance, if we take the above example of equation (9), we find that the picture element would execute excursions with an amplitude of EQU 25.sup.. 10.sup..sup.-3 =0.025 (10)
as a fraction of screen width.
For a screen width of about 20 inches (508 millimeters), for instance, the excursion amplitude of picture elements would be about 0.5 inches (12.7 millimeters) or 1 inch (25.4 millimeters) peak-to-peak.
Such a deviation is intolerable on its face. To reduce such excursions to, say, 0.04 inches or about one millimeter under the permises of our above example, it would be necessary to reduce the flutter of the video recording and playback machine to about 4.10.sup..sup.-5 or 0.004%!
The general equation applying to these cases is ##EQU6## wherein: A is the peak amplitude of flutter;
.OMEGA. is the peak-to-peak excursion of the picture element on the display screen; PA1 .nu..sub.o is the nominal horizontal sync frequency; and PA1 .lambda. is the screen width.
The resulting precision requirements are far too stringent in most practical applications.
In their quest for a workable solution, proposals have been made which necessitate an invasion and modification of the existing circuitry of the television display set. With respect to such proposals, most experts in the field agree that systems which are inherently incapable of operation without invasion and modification of the existing receiver circuitry have practically no chance of widespread acceptance among television receiver owners.


The (+)-threo acid is an important raw material of the therapeutically active (2S,3S)-3-acetoxy-5-dimethylaminoethyl-2-(4-methoxyphenyl)-2,3-dihydro-1,5 -benzothiazepin-4(5H)-one hydrochloride (generic name: diltiazem), a known antianginal drug acting as a calcium antagonist.
There are several processes known from the literature for the preparation of the (+)-threo acid.
A resolution process using L-lysine as resolving agent is described in the published German patent application (DE-OS) No. 3,337,176. However, the particularly costly L-lysine is used in a 4-fold excess and,; in addition, it is difficult and expensive to recover L-lysine in its acid form from the mother liquors.
According to another method [Helv. Chim. Acta 67, 916 (1984)], the racemic threo acid is resolved by using cinchonidine in ethanol. This method is characterized by the use of an extraordinarily high amount of alcohol as solvent and by a 48-hour time demand of crystallization.
According to the method described in the U.S. Pat. No. 4,416,819, an equivalent amount of (+)-.alpha.-phenylethylamine each is employed for both forms of the racemic acid in order to resolve the racemic threo acid in water. In our own examinations, a (+)-threo acid with an optical purity of only 87%, [.alpha.].sub.D.sup.20 =+302.degree. (c=0.3, ethanol), was obtained in a yield of 79% when the resolution and subsequent crystallization of the diastereomeric salt were carried out by using the method cited above.
In the process described in the Hungarian patent specification No. 193,230, the acid addition salt of 0.5 to 0.6 molar equivalent of (+)-.alpha.-phenylethylamine is used as resolving agent; a method, useful to enrich the valuable (+)-threo acid in the remaining threo acid mixture is also described in the above specification.