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1. Field of the Invention
This invention relates to an aquarium especially designed to promote a healthy environment for aquatic life
2. Description of Related Art including Information Disclosed under .sctn..sctn.1.97 to 1.99
A limited search has been made through the Patent and Trademark Office classificaiton system for art pertinent to the present invention and the following patents were developed:
______________________________________ 654,138 to Dennett 4,605,984 to Fiedler 2,753,491 to Legge 4,664,469 to Sachs 3,379,932 to Legge 4,680,668 to Belkin 3,797,459 to Harris ______________________________________ | {
"pile_set_name": "USPTO Backgrounds"
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The intake manifold designed by the original equipment manufacturer (OEM) generally prioritizes performance for a particular vehicle without regard to complexity of the manifold's design or cost. One such OEM intake manifold has seven molded elements that require four different welds and eleven discrete manufacturing processes to assemble a manifold. Because OEM intake manifolds are also specific to a particular vehicle, vehicle trim line, and/or engine option, different vehicles utilizing the same engine block may still have multiple permutations of the manifold in order to match the specifics of that vehicle. This variation results in multiple product SKUs that necessitate increased handling and storage space. This variation also cause the aftermarket replacement manifolds to be more difficult to produce and expensive.
The aftermarket desires a solution to the prior art problems that reduces the number of parts and simplifies the manufacturing process with resulting efficiencies in inventory management. | {
"pile_set_name": "USPTO Backgrounds"
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OFDMA and single carrier FDMA have been selected as the downlink and uplink multiple access schemes for the E-UTRA air interface currently been studied in 3GPP (which is a standard based collaboration looking at the future evolution of third generation mobile telecommunication systems). Under the E-UTRA system, a base station which communicates with a number of user devices allocates the total amount of time/frequency resource (depending on bandwidth) among as many simultaneous users as possible, in order to enable efficient and fast link adaptation and to attain maximum multi-user diversity gain. The resource allocated to each user device is based on the instantaneous channel conditions between the user device and the base station and is informed through a control channel monitored by the user device. | {
"pile_set_name": "USPTO Backgrounds"
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(a) Field of the Invention
The present invention is concerned with a power amplifying circuit and more particularly, it relates to a power amplifier capable of changing over the supply voltage and thereby shifting the load line.
(B) Description of the Prior Art
Discussion will hereunder be made on the conventional emitter follower power amplifier by referring to FIG. 1. FIG. 1 shows a known single-ended push-pull power amplifying circuit of the emitter follower type. The respective emitters of the transistors Q.sub.1 and Q.sub.2 are connected to one end of a load resistor R.sub.L through respective resistors R.sub.el and R.sub.e2 having small resistances intended for the prevention of excessive current flow and for a stabilization of operation. The other end of the load R.sub.L is grounded. The respective collectors of these two transistors Q.sub.1 and Q.sub.2 are connected to a positive and a negative supply voltage source +V.sub.1 and -V.sub.1, respectively. The respective bases of the transistors Q.sub.1 and Q.sub.2 are applied with an input signal e.sub.i via a positive and a negative biasing voltage source +E.sub.b and -E.sub.b, respectively. In order to increase the peak output power in the above-mentioned power amplifying circuit, it is necessary to elevate the voltages of the supply voltage sources + V.sub.1 and -V.sub.1 in order to obtain a broader operative range. However, in case the voltages of the supply voltage sources +V.sub.1 and -V.sub.1 are elevated, the collector-emitter voltage between the transistors Q.sub.1 and Q.sub.2 relative to a certain load current will become higher, so that the collector loss, i.e., the power loss due to the collector current, will become increased.
Let us now refer to FIG. 2 which shows schematic characteristic curves of an amplifying transistor.
The ordinate represents the collector current and the abscissa represents the collector-to-emitter voltage. As shown in the figure, the current curves are assumed to take a constant value in the active region. Lines l.sub.1 and l.sub.2 represent examples of load line for a low and a high supply voltage V.sub.1 and V.sub.2. When the supply voltage is low at V.sub.1, the collector-to-emitter voltage is low and hence the power loss in the element is small. When a large input signal is supplied, however, the output current may be clipped at point F as shown by the dotted line on the left. To allow large signals to be amplified without distortion, the load line should be shifted rightwards. Namely, the supply voltage should be increased. The load line l.sub.2 represents the case under such increased supply voltage V.sub.2 with the same load resistance. In this case, the operative region may be expanded to DE compared to BA on the line l.sub.1. Thus, large signal amplification is made possible. In such case, however, the power loss in the element increases. Namely, for the similar output current I.sub.c, the power consumed in the element is I.sub.c .multidot.(V.sub.2) for the load line l.sub.2 in contrast to I.sub.c .multidot.V.sub. 1 for the load line l.sub.1. Thus, the power loss is increased by I.sub.c .multidot.(V.sub.2 -V.sub.1 ) for providing the same output current. In this way, according to the conventional power amplifier, large output current and low power consumption have been the contradicting problems. | {
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1. Field of the Invention
The present invention relates to an inkjet head in which a drive circuit member is mounted on a laminated-type inkjet head member, and an image forming apparatus having the same.
2. Description of the Related Art
In the related art, as a type of printer, there is known an inkjet printer that prints on a medium such as a paper sheet by moving an inkjet head, which discharges a liquid such as ink, relative to the medium.
In order to selectively drive nozzles that discharge droplets in inkjet heads mounted in inkjet printers, a drive circuit member including a drive integrated circuit (IC) is used. The drive circuit member is connected to an electromechanical transducer such as a piezoelectric element or a heater which generates force to discharge the liquid. As for techniques for mounting the drive circuit member, there is some known techniques, a flip chip bonding technique, a wire bonding technique, and so on.
As such an inkjet head, the following structure is known. The structure includes a pressure generating chamber communicating with a nozzle; a vibrating plate forming a part of the pressure generating chamber; a piezoelectric element which is arranged in the vibrating plate, particularly in the surface opposing the pressure generating chamber and which generates a change in the internal pressure of the pressure generating chamber; and a drive circuit member having a drive element to drive the piezoelectric element. In the structure, the drive circuit member is bonded to a terminal provided in the piezoelectric element using the flip chip bonding technique, and is mounted on an ink tank plate as a fluid path forming plate. Furthermore, a liquid supply plate as a protection plate is bonded to the ink tank plate (for example, refer to Japanese Patent Application Laid-open No. 2006-116767).
There is also known an inkjet head in which the drive circuit member is mounted through a wire connector after the liquid supply plate is bonded to the ink tank plate (for example, refer to Japanese Patent Application Laid-open No. 2009-267428).
However, since the sealing material to be coated on the ink tank plate to protect a connector portion of the drive circuit member is apt to wetly spread, it wetly spreads on the ink tank plate. Therefore, in a case where a liquid supply plate as a protection plate is bonded to the ink tank plate as in the inkjet head disclosed in Japanese Patent Application Laid-open No. 2009-267428, it is necessary to avoid an area where the sealing material wetly spreads in order to obtain an excellent bonding state without any void. This results in the inkjet head having a large size. Since the area where no wet-spreading of the sealing material appears is not supported by the liquid supply plate, the inkjet head has a weak structural strength there and hence is susceptible to deformation caused by an external force, resulting in the reliability being not guaranteed.
Similarly, in the inkjet head disclosed in Japanese Patent Application Laid-open No. 2009-267428, in a case where another member is additionally stacked on the liquid supply plate where the drive circuit member is mounted, the member must be stacked avoiding the area where the sealing material wetly spreads. This causes a large-sized head and reduces a structural strength.
In addition, since it is necessary to perform mounting, typically, at a high temperature of 150° C. to 300° C. in order to increase the strength of the electrical connection portion of the drive circuit member, an adhesive used to bond other members may be degraded to generate bonding errors, or a material which can be used as a constituent member is problematically limited to those having heat resistance. | {
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A type system can be used in programming languages to aid in the detection and prevention of programming or run-time errors. A “typed” programming language can contain a set of types that are declared for software items such as variables, functions, etc. These types can be checked versus a set of rules during compilation of a program written in the language. If the source code written in the typed language violates one of the type rules, a compiler error is determined.
Typed intermediate languages for use in compilers have received significant study in the research community over the past few years. They enhance the reliability and robustness of compilers, as well as provide a systematic way to track and check information needed by garbage collectors. The idea is to have an intermediate representation that has types attached to it and that can be type-checked in a manner analogous to type-checking for source programs. However, a typed intermediate language is more difficult to implement because types that represent items made explicit during the compilation process are necessary.
A typed intermediate language is even more difficult to implement if it must represent a number of different high-level programming languages. The different languages not only have different primitive operations and types, but the high-level programming languages have different levels of typing. For instance, some languages, such as assembly languages, are generally untyped. In other words, they have no type system. Of the languages that are typed, some are strongly typed while others are more loosely typed. For instance, C++ is generally considered a loosely typed language, whereas ML or Pascal are considered strongly typed languages. Further, some languages that are loosely typed have smaller sub-sets of the language that allow for a majority of the code sections within a program to be strongly typed, while other code sections are loosely typed. For example, C# and Microsoft Intermediate Language used in .NET (MSIL) allow this. Therefore, a typed intermediate language used to represent any of these high-level languages must be able to represent different types strengths. Likewise, the type system of such a typed intermediate language must be able to implement different rules depending on characteristics of the code being type checked.
Another problem arises when a typed intermediate language is lowered throughout the process of compilation. The lowering of a language refers to the process of changing the form of a language from a higher level form, such as what a programmer would write, to a lower level, such as to an intermediate language. The language can then be further lowered from the intermediate language to levels closer to what a computer executes, such as machine-dependent native code. In order to type-check an intermediate language that is lowered to different levels during the compilation process, a different set of rules must be used for each representation.
Attempts to create typed intermediate languages often fall short of solving the problems discussed above. For instance, Cedilla Systems' Special J compiler uses a typed intermediate language. However, this compiler is specific to the Java source language and therefore did not need to process multiple languages that may, for instance, have non-type-safe code. Additionally, this compiler only uses one set of rules for type-checking and therefore could not be used for multiple levels of compilation. In the research community, typed intermediate languages often tend to be highly specific to the source language and difficult to engineer (and design the types) for the multiple stages of compilation. | {
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This invention relates to a method of conducting hormone replacement therapy (HRT) and to dispensers and kits adapted to practice the method.
HRT in women during the menopausal and post-menopausal period of their lives to prevent or at least diminish the adverse physiological effects thereof, such as bone loss and resultant structural deformation, is now conventional therapy, irrespective of whether the menopause is surgically induced or is the result of the normal aging process. HRT usually involves either the concurrent administration of both an estrogen and a progestogen on a constant, e.g., daily, basis or constant administration of an estrogen and intermittent, e.g., on the 10th to 14th days of a 28 day cycle, administration of the progestogen, at respective dosages which often are changed during the period of HRT, depending on the symptoms currently being displayed by an individual as a result of the menopausal state, the HRT or both. Those doses may be changed infrequently, e.g., every six months or longer at the time the individual visits her doctor for a routine examination, or more often, e.g., from month to month or even more frequently, if the individual is experiencing undesirable menstrual symptoms, e.g., irregular menses, break through bleeding, which is a common consequence of an imbalance of estrogens and progestogens in a continuous combined HRT regimin, excessive blood flow, severe bleeding pain or cramps or a number of other symptoms consistent with the dosage of one or both of the estrogen and the progestogen being too high and thereby creating hormonal side effects, e.g., breast tenderness, nausea, edema, menstrual disorders, etc., or too low and thereby limiting the efficacy of the HRT or creating other side effects. Moreover, because menopause involves a gradual reduction in circulating serum estrogen and progestogen levels, it is usually desirable to initiate HRT during the perimenopausal period at lower dosages of the estrogen and/or progestogen and gradually increase the dosage thereof as menopause progresses. In addition, a full replacement dosage of estrogens may not be tolerable in a postmenopausal woman whose body has been adapting to estrogen deficiency over a certain period and who may experience breast tension, nausea, oedema and other typical side-effects when receiving the full dosage. In these women, one may wish to start with a very small dosage and increase it only gradually until symptoms have disappeared or plasma levels have reached premenopausal values. Modifying the progesterone dosage level also is frequently necessary during menopause to deal with menses irregularities.
Thus, a fixed combination of an estrogen dosage and a progestogen dosage that is suitable for all menopausal women is impossible to design, for a variety of reasons. One reason is the wide variation from individual to individual in the resorption rate which exists with all modes of administration except intraveneous, which is not practiced in HRT. These differences in bioavailability can reach 100% or more. For example, the bioavailability of estradiol orally averages 5% of the oral dose, which means that in an individual it can be as low as 3% or as high as 6%. Another reason why a fixed combination is not suitable is because of variations in body weight and fat mass proportion, which has an endrocrine function because it contains enzymes to transform hormonal precursors into estrogens. A third reason is the interaction between estrogens and progestogens, i.e., progestogens may only become effective in the presence of estrogens because they stimulate the production of progestogen recepton.
Consequently, estrogens and progestogen which are formulated commercially for HRT typically are sold as combined estrogen/progestogen tablets in more than one dosage strengths. However, the physician is still limited as to the size of the single dose of the estrogen and the progesterone which can be prescribed by those commercially available. Moreover, providing an estrogen/progestogen combination in tablets of multiple strengths adds to the manufacturing cost of producing a combination of a specific estrogen and a specific progestogen and increases significantly the inventory required of pharmacies to make any commercially available combination available to the patients to whom it is prescribed. Therefore, some pharmacies do not stock their estrogen/progestogen products in tablet form in all of the dosage strengths which are commercially available, which can limit the flexibility desired by physicians in a dosage protocol for an individual patient, which ideally is customized in accordance with the symptoms of that patient which are currently manifested by her.
For the foregoing reasons, there is a need in HRT for a method of administering successive doses of a specific estrogen and a specific progestogen whereby the dosage of either or both can readily be changed by the attending physician or even, if desired by the physician, by the patient, without the necessity of either the patient physically altering the physical form of that daily dosage, e.g., by cutting a tablet into segments, or the doctor prescribing a different form thereof, e.g., tablets of one or both of the hormones in higher or lower strengths. There is also a need for an HRT method which does not require the manufacturer to produce a plurality of products of different strengths in order to practice the method. There is a further need for a method of self-administering the hormones during HRT by which the individual doses of the estrogen and the progestogen can easily and inexpensively and accurately be altered separately or simultaneously at various times during long term HRT without changing the prescribed dosage form for that patient.
There also is a need for a dispenser of the hormones which are prescribed and a kit comprising the dispenser for the HRT which permit the strength of the individual doses of the estrogen, of the progestogen or of both to be altered as frequently as and to the precise degree which the attending physician deems desirable.
The method of this invention meets these needs by employing in HRT a specific estrogen and a specific progestogen contained in separate extrudable pharmaceutical compositions and administering the compositions concurrently, i.e., either simultaneously as a mixture or in succession as separate extrudates.
The dispensers and kits of this invention meet these needs by dispensing the extrudable pharmaceutical compositions in metered or measured extruded segments.
There are a number of prior patents which disclose devices for dispensing a plurality of flowable materials, i.e., an extrudable solid or a viscous liquid. For a review of that art, see U.S. Pat. No. 5,020,694 and the references cited therein. See also U.S. Pat. Nos. 4,334,787, 4,687,663, 4,826,048, 4,838,457, 5,152,432, 5,240,146 and 5,339,990. Some of these, e.g., U.S. Pat. Nos. 4,240,146, 4,838,457 and 4,826,048, disclose dispensers which comprise means for varying the ratio and/or the quantity of the respective flowable materials which are dispensed in a single dispensing manipulator of the device. In U.S. Pat. No. 5,240,146, both the dosage of two separate injectable pharmaceutical compositions and the ratio thereof can be varied.
None of the prior art devices are directed specifically to the HRT method of this invention which involves, inter alia, one or more of transdermal administration, dosage and estrogen/progestogen ratio regulation and control; administration of the estrogen and the progestogen as extrudable semi-solids; a device or kit for administration of the estrogen and the progestogen which is simple and preferably contains a safeguard against the wrong dose of estrogen or progestogen or ratio thereof inadvertently being self-administered. | {
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Motors of this kind can be used in a variety of applications for example in automotive engineering for drives supporting brake system control, or pumps and fans. Other application areas include ventilator fans in power supply units, or spindle motors in disk drives for data processing systems, just to mention a few.
An electronically-commutated, brushless DC motor basically consists of a shaft, a rotor assembly equipped with one or more permanent magnets mounted on the shaft, and a stator assembly which incorporates a stator component and phase windings. Two bearings are mounted at an axial distance to each other on the shaft to support the rotor assembly and stator assembly relative to each other.
FIG. 1 illustrates a schematic circuit diagram of an electronic control for a three-phase DC motor. The DC motor has three phase windings (U, 12; V, 14; W, 16), schematically illustrated in FIG. 1 in star connection 10. The three windings 12, 14, 16 are connected between a positive supply busbar 18 and a negative supply busbar 20. The positive supply busbar 18 conveys the potential +UBAT, the negative supply busbar 20 conveys the potential −UBAT. The phase windings 12, 14, 16 are connected in accordance with control signals with the supply buses 18, 20 via six power switching components (T1, 22; T2, 24; T3, 26; T4, 28; T5, 30; T6, 32). The power switching components 22 to 32 are preferably power transistors. They are equipped with control connections, designated G1 to G6 in FIG. 1. The control connections correspond in particular with the power transistor gates. The application of suitable control signals to the power transistor gates energizes the phase windings 12 to 16 in the DC motor in order to control its operation. Methods for controlling a brushless electronically-commutated DC motor which are referred to are, for example, described in DE 10033561 A1 and U.S. Pat. No. 6,400,109 B1.
One differentiates between square-wave and sinusoidal motors when dealing with DC motors, particularly three-phase DC motors as used in industrial applications in automotive engineering. Square-wave energizing means that the current applied to the phase windings flows in a square pattern. The current is activated to a specified value at a given moment in time and deactivated again at another specified moment in time. Such motors usually have a trapezoidal induced voltage. FIG. 2A schematically illustrates the induced voltages of a square-wave energized or square-wave commutated motor. Switching of the phase currents should occur during operation if two induced voltages intersect, this then minimizing the torque ripple generated. Information pertaining to the respective rotor is required to switch the phase currents at the correct instance.
Detailed information about the rotor position is required if the current is not only to be activated and deactivated, but also controlled in direct relation to the rotor position. Current control i(φ) is practical, as torque formation can be influenced by suitable setting of i(φ):T(φ)=KT(φ)*i(φ)
For example, a consistent torque can be achieved on the basis of the following equations: sin 2 ( φ ) + sin 2 ( φ - π 2 ) = 1 or sin 2 ( φ ) + sin 2 ( φ - 2 π 3 ) + sin 2 ( φ - 4 π 3 ) = 1 if the induced voltage Uind(φ) and, consequently, KE(φ) and/or KT(φ) and the current i(φ) have a sinusoidal flow, voltage and current are in phase and the individual motor phases (e.g. 90 electrical degrees in the case of a two-phase motor and 120 electrical degrees in the case of a three-phase motor) are shifted in relation to each other.
FIG. 2B illustrates the induced voltages of a three-phase motor. Energizing of the DC motor phases should be realized as illustrated in FIG. 2C. It consists of six sections during an electrical cycle.
The exact position of the rotor must be known to generate a sinusoidal current directly dependent on the rotor position and, consequently, the induced voltage. Decoders or resolvers are among the devices utilized in the prior art to record the rotor position. These are rotor position sensors which operate with a specific resolution NINC and can indicate the angular position of the rotor with an angular resolution of: φ INC = 360 ∘ N INC
The current i(φ) for energizing the motor phases can be controlled in a suitable number of stages, relative to the rotor position sensor resolution.
A resolver is, in principle, similar to a transformer with a primary winding and two secondary windings. The winding ratio and polarity of the primary and secondary windings varies, depending on the angular position of the shaft. The resolver has at least two secondary windings at an angle of 90° to each other which are stationary fittings (stator). The primary winding is mounted on the resolver shaft and is termed the rotor. The stator output signals have the same frequency if the alternating voltage is induced at a constant frequency in the primary winding, but they are offset by 90°. A sinusoidal signal and co-sinusoidal signal are thus received. The peak resolver voltage varies as the shaft rotates.
The coil output signal is converted by an analog/digital converter, the two highest converter output signal bit values indicating the quadrant in which the shaft is, and the remaining bits the shaft angle at the start of each quadrant. The analog/digital converter output signal is always a binary number.
Decoders (also known as incremental decoders) generate two output signals using a glass disk (to give an example) in which uniform subdivisions are etched. There is a light source on one side of the disk and two light detectors on the other. The glass disk is mounted on the shaft, the light source and detectors being stationary components. The detectors record an interruption in the light beam caused by the disk when the disk rotates. A relative shaft rotation can be determined by counting the transitions from light to dark. Two detectors are used if the rotational direction is also to be recorded. Decoders of the type described can only record incremental shaft rotation. The absolute shaft position is recorded by a third sensor with the assistance of a so-called zero index or zero reference track.
The rotor position sensor provides data required for current control. A problem arises here, namely that the angular position of the rotor position sensor relative to the rotor is initially unknown. The prior art thus requires mechanical adjusting of the rotor position sensor relative to the rotor so that the rotor position sensor zero index coincides with a known specific rotor angular position. In particular the zero index should be adjusted relative to a certain known commutation position. Mechanical adjustment is relatively time consuming and inaccurate. | {
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Catalyst compositions based on well defined donor ligand containing metal complexes, referred to as post-metallocene complexes have been shown to give products having narrow molecular weight distribution and high molecular weights. However, these catalysts often have poor high temperature stability and suffer from poor catalytic efficiencies, especially at elevated polymerization temperatures. When employed to prepare propylene containing polymers, especially polypropylene, propylene/ethylene copolymers, and ethylene/propylene rubber (EP) modified polypropylene, the resulting polymer tacticity, molecular weight and catalyst efficiency are often deficient.
Examples of the foregoing post metallocene catalysts are disclosed in U.S. Pat. No. 6,827,976 and US2004/0010103, where Group 3-6 or Lanthanide metal complexes, preferably Group 4 metal complexes, of bridged divalent aromatic ligands containing a divalent Lewis base chelating group are disclosed for use in olefin polymerizations.
Higher solution reaction temperatures are particularly desired for propylene polymerizations in order to reduce energy consumption and improve operating efficiency. However, the use of higher reaction temperatures often results in poor conversions, lower polymer molecular weight, and reduced polymer tacticity. Accordingly, selection of catalyst compositions capable of formation of isotactic polypropylene at increased efficiency at elevated reaction temperatures is highly desired.
We have now discovered that certain metal complexes may be employed in a highly efficient solution polymerization process to prepare propylene polymers, including propylene homopolymers and copolymers of propylene with one or more comonomers. We have also discovered that a continuous process can be employed to prepare the foregoing propylene polymers in increased yield and efficiency. In particular, the present inventors have discovered an improved continuous solution polymerization process for preparing such polymers that is characterized by high polymerization efficiency and productivity. | {
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This invention relates to a process for the preparation of alcohols by the addition of organometallic reagents to ketones. More particularly, this invention relates to the reaction of 1-phenyl-2-(1H-1,2,4-triazol-1-yl)ethanone derivatives with organometallic compounds derived from alpha-haloalkylpyrimidines to form tertiary alcohols.
The reaction of organometallic compounds derived from alkyl halides with aldehydes and ketones to form secondary and tertiary alcohols, respectively, is well established in the field of organic chemistry. Many different metals and metal derivatives have been reported as being useful in this type of reaction, including lithium, magnesium, aluminium, tin and zinc, together with salts thereof. For example, A. R. Gangloff et al, J. Org. Chem., 57, 4797-4799 (1992) discloses that 2-(bromomethyl)-4-carbethoxy-1,3-oxazole reacts with zinc dust to form an organozinc derivative which undergoes nucleophilic addition to aldehydes and ketones. Also, Chollet et al, Synth. Comm., 19 (11 and 12), 2167-2173 (1989) reports the reaction of organozinc derivatives of bromoesters with aldehydes and ketones.
Certain compounds prepared according to the present process are disclosed in European Patent Application Publication numbers 0357241 and 0440372.
It has now been surprisingly found that certain 1-phenyl-2-(1H-1,2,4-triazol-1-yl)ethanone derivatives may be reacted with organometallic compounds derived from certain alpha-haloalkylpyrimidine derivatives to form tertiary alcohols in good to excellent yields and with high stereoselectivity using reaction conditions that are particularly suitable for the bulk synthesis of the product.
This finding has been found to be particularly useful for the synthesis of (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-1,2,4-triazol-1-yl)butan-2-ol, a key intermediate for the preparation of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, a compound having antifungal activity. The syntheses of both of these compounds have been described in European Patent Application Publication number 0440372. In this Application, (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol is prepared by the chromatographic separation of the two pairs of enantiomers obtained from the addition of an organolithium derivative of 4-chloro-6-ethyl-5-fluoropyrimidine to 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone at from xe2x88x9270 to xe2x88x9250xc2x0 C. The best stereoselectivity that has been obtained in this addition is a 1.1:1 molar ratio in favour of the 2R,3S/2S,3R enantiomeric pair with the total isolated yield of all four stereoisomers being only about 50%, the low yield being thought to be due to a competing enolisation reaction. These factors, coupled with the need to operate the addition reaction at very low temperatures and under very dilute conditions, together with the difficulty in separating approximately equimolar amounts of the two pairs of enantiomers at the end of the reaction with the 2R,3R/2S,3S enantiomeric pair being unwanted, mean that the process is extremely unsuitable for the economic preparation of the required 2R,3S/2S,3R intermediate on a large scale.
In contrast, for example, it has now been found that a 9:1 molar ratio of the 2R,3S/2S,3R to the 2R,3R/2S,3S enantiomeric pair of 3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol and a 65% isolated total yield of all the enantiomers (as the hydrochloride salts) can be obtained under the reaction conditions according to the present invention that are highly suitable for large scale synthesis of the product.
However, higher isolated yields have been obtained and higher molar ratios (both in situ and in respect of isolated product) have been determined by varying the reaction conditions in accordance with the present invention.
Similar results have been obtained with a range of alpha-haloalkyl-pyrimidine substrates.
Considerable economic advantages result from the yields and stereospecificity achieved.
The present invention provides a process for the preparation of a compound of the formula:
or an acid addition or base salt thereof, wherein
R is phenyl optionally substituted by 1 to 3 substituents each independently selected from halo and trifluoromethyl;
R1 is C1-C6 alkyl; and
xe2x80x9cHetxe2x80x9d is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo, oxo, benzyl and benzyloxy,
comprising reaction of a compound of the formula:
wherein R is as previously defined for a compound of the formula (I), with a compound of the formula:
wherein R1 and xe2x80x9cHetxe2x80x9d are as previously defined for a compound of the formula (I) and X is chloro, bromo or iodo, in the presence of zinc, iodine and/or a Lewis acid and an aprotic organic solvent: said process being optionally followed by formation of an acid addition or base salt of the product.
Optionally, lead can also be present in the reaction, either as the metal per se or in the form of a suitable salt, e.g. a lead (II) halide. It can be added separately or be inherently present in the zinc used.
In the above definitions, alkyl and alkoxy groups containing three or more carbon atoms may be straight- or branched-chain and xe2x80x9chaloxe2x80x9d means fluoro, chloro, bromo or iodo.
Preferably, R is phenyl optionally substituted by 1 to 3 halo substituents.
More preferably, R is phenyl substituted by 1 or 2 substituents each independently selected from fluoro and chloro.
Yet more preferably, R is phenyl substituted by 1 or 2 fluoro substituents.
Most preferably, R is 2,4-difluorophenyl.
Preferably, R1 is C1-C4 alkyl.
More preferably, R1 is methyl or ethyl.
Most preferably, R1 is methyl.
Preferably, xe2x80x9cHetxe2x80x9d is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from halo, oxo and benzyl.
More preferably, xe2x80x9cHetxe2x80x9d is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from fluoro, chloro, oxo and benzyl.
Yet more preferably, xe2x80x9cHetxe2x80x9d is pyrimidinyl substituted by 1 to 3 substituents each independently selected from fluoro and chloro.
Preferred examples of xe2x80x9cHetxe2x80x9d include pyrimidin-4-yl, 4-chloro-5-fluoropyrimidin-6-yl, 5-fluoropyrimidin-4-yl, 2-chloro-5-fluoropyrimidin-6-yl, 2,4-dichloro-5-fluoropyrimidin-6-yl, 4-chloropyrimidin-6-yl and 1-benzyl-5-fluoropyrimidin-6-on-4-yl.
Most preferably, xe2x80x9cHetxe2x80x9d is 4-chloro-5-fluoropyrimidin-6-yl.
Preferably, X is bromo or iodo.
Most preferably, X is bromo.
The compound of the formula (II) may be an enolisable ketone. Most preferably, the compound of formula (II) is 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone.
Preferably the compound of the formula (III) is selected from 6-(1-bromoethyl)-2,4-dichloro-5-fluoropyrimidine, 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine, 6-(1-bromoethyl)-2-chloro-5-fluoropyrimidine, 4-(1-bromoethyl)pyrimidine, 4-(1-bromoethyl)-6-chloropyrimidine, 4-(1-bromoethyl)-5-fluoropyrimidine and 1-benzyl-4-(1-bromoethyl)-5-fluoropyrimidin-6-one.
Most preferably, the compound of the formula (III) is 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine.
The reaction is carried out in the presence of a suitable aprotic organic solvent such as tetrahydrofuran, toluene, 1,2-dimethoxyethane or methylene chloride, or a mixture of two or more thereof. It is highly desirable to dry the solvent before use to remove substantially all traces of water. Drying can be achieved using a desiccant such as magnesium sulphate, sodium sulphate or molecular sieves, by distillation from a metal such as lithium, sodium or potassium or by azeotropic distillation.
The preferred solvent for the reaction is tetrahydrofuran.
It is also preferable to carry out the reaction under a dry, inert atmosphere such as by using dry nitrogen or argon gas.
The zinc used in the reaction may be zinc powder derived from a commercial source or it may be freshly generated in situ by the reduction of a zinc halide (e.g. zinc chloride) using lithium, sodium or potassium (see, e.g., R. D. Rieke, Acc. Chem. Res., 10, 301 (1977)). The zinc powder may be activated prior to use by stirring a slurry of the powder for several hours in a suitable solvent, e.g. tetrahydrofuran.
Optionally, the reaction is carried out in the additional presence of lead.
The zinc powder obtained commercially may contain small amounts of lead as an impurity and the lead content can be up to about 2000 parts per million (0.20 weight %) depending on the source. However, it is generally preferred to increase the lead content by adding lead in the form of lead powder to the reaction mixture. Lead powder is commercially available.
Preferably, when used, the amount of lead present in the reaction is 2000 ppm (0.2 wt %) or more relative to the amount of zinc present. More preferably, the amount of lead present is from 2000 to 100,000 ppm (0.2 to 10 weight %). Most preferably, the amount of lead present is about 50,000 ppm (5 wt %).
Iodine is generally used in its commercially available crystalline form. It is suspected that its role in the reaction is in the in situ generation of zinc iodide, possibly, when lead is also present, in conjunction with lead (II) iodide as well, both of which may function as catalysts.
Iodine, when used, may be introduced into the reaction vessel before, during or after the compounds of the formulae (II) and (III) have been added. Alternatively, it can be added in at least two stages, for example, one portion can be added to the reaction vessel before, and the second portion can be added when, the compounds of the formulae (II) and (III) are added.
Suitable Lewis acids for use in the reaction include zinc chloride, zinc bromide, zinc iodide, titanium (IV) isopropoxide, chlorotitanium triisopropoxide, titanium tetrachloride, trimethyl borate, boron trifluoride (etherate), iron (III) chloride and diethylaluminium chloride.
Preferred Lewis acids are zinc bromide, zinc iodide and, particularly, zinc chloride.
Iodine is preferably used rather than separately adding a Lewis acid.
Optionally, both iodine and a Lewis acid may be used in the above process.
The reaction may be carried out at from xe2x88x9215xc2x0 C. to the reflux temperature of the mixture. Preferably, it is carried out at from xe2x88x9210 to +30xc2x0 C. and most preferably from xe2x88x9210xc2x0 C. to +15xc2x0 C.
The reaction almost certainly proceeds via formation of an organozinc species derived from the in situ reaction of zinc with a compound of the formula (III) that is used as a starting material.
The reaction may be carried out by the following general procedure. is Iodine and/or a suitable Lewis acid are/is added to a stirred mixture of zinc, optionally lead, and a suitable aprotic organic solvent. The mixture is cooled and a solution of a compound of the formula (II), a compound of the formula (III) and, optionally, further iodine in a suitable aprotic organic solvent is added, cooling the mixture during the addition. The mixture is stirred for a further short period before being warmed to room temperature. The reaction is quenched by adding glacial acetic acid followed by water and conventional work-up techniques can then be used in order to isolate the required product.
The process is optionally followed by formation of an acid addition or a base salt of the product. Formation of an acid addition salt is preferred and suitable salts include the hydrochloride, hydrobromide, hydroiodide, sulphate, nitrate, methanesulphonate, camphorsulphonate, R-(xe2x88x92)-10-camphorsulphonate, (+)-3-bromo-10-camphorsulphonate, (xe2x88x92)-3-bromo-8-camphorsulphonate, phosphate, para-toluenesulphonate and benzenesulphonate salts. The hydrochloride salt is particularly preferred.
A compound of the formula (I) produced by the process of the invention contains two or more asymmetric carbon atoms and therefore exists in four or more stereoisomeric forms.
The reaction generally proceeds with high stereoselectivity in favour of the (2R,3S/2S,3R) enantiomeric pair of a compound of the formula (I), i.e.
where the asterixes (*) indicate the subject asymmetric carbon atoms.
Separation of diastereoisomers may be achieved by conventional techniques, e.g. by fractional crystallisation, chromatography or H.P.L.C. of a stereoisomeric mixture of a compound of the formula (I) or a suitable salt or derivative thereof. Resolution of enantiomers of a compound of the formula (I) may be achieved by H.P.L.C. of the corresponding racemate using a suitable chiral support or by fractional crystallisation of the diastereoisomeric salts formed by reaction of the corresponding racemate with a suitable optically active acid, e.g. R-(xe2x88x92)-10-camphorsulphonic acid.
The process is preferably used to prepare 3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol from the starting materials 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone and 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine. High stereoselectivity can be achieved in the reaction with, for example, a 9:1 molar ratio of the 2R,3S/2S,3R to the 2R,3R/2S,3S enantiomeric pair being obtained if the reaction conditions are carefully controlled. In addition, for example, a 65% isolated total yield (as the hydrochloride salts) of all the enantiomers has been obtained.
The reaction product, which contains a far higher proportion of (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride, can be reduced to provide (2R,3S/2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol which can be resolved to provide (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol by the method described in European Patent Application Publication number 0440372.
In a further aspect, the present invention provides a process for the preparation of a compound of the formula:
or an acid addition salt thereof, wherein R and R1 are as previously defined for a compound of the formula (I) and R2 is H or fluoro, which comprises the steps of:
(a) reaction of a compound of the formula:
wherein R is as defined for a compound of the formula (IV), with a compound of the formula:
wherein X is chloro, bromo or iodo, R1 and R2 are as previously defined for a compound of the formula (IV) and either R3 and R4 are each independently selected from chloro and bromo or one of R3 and R4 is chloro or bromo and the other is H, in the presence of zinc, iodine and/or a Lewis acid and an aprotic organic solvent, to provide a compound of the formula:
wherein R, R1, R2, R3 and R4 are as previously defined for this step (a);
(b) optionally converting the compound of the formula (IA) to an acid addition salt thereof;
(c) reduction of the compound of the formula (IA) or an acid addition salt thereof to provide the compound of the formula (IV); and
(d) optionally converting the compound of the formula (IV) to an acid addition salt thereof.
The reactions conditions, including the preferred conditions, used for step (a) are as previously described for the preparation of a compound of the formula (I). Again, optionally, lead can also be present in step (a).
The reduction in step (c) can be carried out under any conditions suitable for the replacement of one or more of the R3/R4 groups where R3/R4 is chloro or bromo by hydrogen.
The reduction may be carried out under conventional hydrogenation conditions using a suitable catalyst, e.g. palladium-on-charcoal, optionally in the presence of a suitable base, e.g. sodium acetate, and in a suitable solvent, e.g. ethanol, under a hydrogen atmosphere.
Preferably, the reduction is carried out under transfer hydrogenation conditions using a suitable catalyst, e.g. palladium or rhodium, a suitable hydrogen donor, e.g. ammonium or potassium formate, and in a suitable solvent, e.g. methanol. The reaction is preferably carried out at the reflux temperature of the solvent and under a nitrogen atmosphere.
Examples of acid additions salts in step (b) include the hydrochloride, nitrate, methanesulphonate, p-toluenesulphonate, camphorsulphonate, R-(xe2x88x92)-10-camphorsulphonate, (+)-3-bromo-10-camphorsulphonate and (xe2x88x92)-3-bromo-8-camphorsulphonate salts. Preferred acid addition salts in step (b) are the hydrochloride, methanesulphonate and p-toluenesulphonate salts.
A preferred acid addition salt in step (d) is the R-(xe2x88x92)-10-camphorsulphonate which may be used to resolve enantiomers of the compound of the formula (IV). A S-(+)-10-camphorsulphonate salt may also be generated and used for this purpose.
In this process for the preparation of a compound of the formula (IV):
(i) Preferably, R is phenyl optionally substituted by 1 to 3 halo substituents.
More preferably, R is phenyl substituted by 1 or 2 substituents each independently selected from fluoro and chloro.
Yet more preferably, R is phenyl substituted by 1 or 2 fluoro substituents.
Most preferably, R is 2,4-difluorophenyl.
(ii) Preferably, R1 is C1-C4 alkyl.
More preferably, R1 is methyl or ethyl.
Most preferably, R1 is methyl.
(iii) Preferably, X is bromo or iodo.
Most preferably, X is bromo.
(iv) Preferably, R2 is fluoro.
(v) Preferably, R3 is chloro and R4 is H, R3 is H and R4 is chloro or R3 and R4 are both chloro.
(vi) Preferred compounds of the formula (IIIA) include:
6-(1-bromoethyl)-2,4-dichloro-5-fluoropyrimidine,
6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine,
6-(1-bromoethyl)-2-chloro-5-fluoropyrimidine and
4-(1-bromoethyl)-6-chloropyrimidine.
(vii) Preferred compounds of the formula (IA) include:
3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,
3-(2-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,
3-(2,4-dichloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol and
3-(4-chloropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,
and the acid addition salts thereof, particularly the hydrochloride, methanesulphonate and p-toluenesulphonate salts.
(viii) Preferred compounds of the formula (IV) include:
2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol and
2-(2,4-difluorophenyl)-3-(pyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,
and the acid addition salts thereof, particularly the S-(+)- or R-(xe2x88x92)-10-camphorsulphonate salts.
The preparations of the starting materials used in the process of the present invention are conventional and appropriate reagents and reaction conditions for their preparation as well as procedures for isolating the desired products will be well known to those skilled in the art with reference to literature precedents and the Preparations hereto.
The present invention also provides the following novel compounds:
(i) (2R,3S)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol;
(ii) an acid addition salt of (2R,3S/2S,3R)- or (2R,3S)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol and preferably a hydrochloride, nitrate, methanesulphonate, p-toluenesulphonate, camphorsulphonate, R-(xe2x88x92)-10-camphorsulphonate, (+)-3-bromo-10-camphorsulphonate or (xe2x88x92)-3-bromo-8-camphorsulphonate salt;
(iii) 3-(2,4-dichloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, or the (2R,3S/2S,3R)- or (2R,3S)-form thereof, or an acid addition salt of any thereof;
(iv) 3-(2-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, or the (2R,3S/2S,3R)- or (2R,3S)-form thereof, or an acid addition salt of any thereof;
(v) 3-(1-benzyl-5-fluoropyrimidin-6-on-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, or the (2R,3S/2S,3R)- or (2R,3S)-form thereof, or an acid addition salt of any thereof;
(vi) 3-(4-chloropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, or the (2R,3S/2S,3R)- or (2R,3S)-form thereof, or an acid addition salt of any thereof;
(vii) 6-(1-bromoethyl)-2,4-dichloro-5-fluoropyrimidine;
(viii) 4-(1-bromoethyl)-6-chloropyrimidine;
(ix) 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine;
(x) 1-benzyl-4-(1-bromoethyl)-5-fluoropyrimidin-6-one;
(xi) 6-(1-bromoethyl)-2-chloro-5-fluoropyrimidine;
(xii) 4-(1-bromoethyl)-5-fluoropyrimidine;
(xiii) 2-chloro-6-ethyl-5-fluoro4-hydroxypyrimidine, ammonium salt. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
The invention pertains to an optical waveguide component comprising a substrate, a core-matching refractive index lower cladding layer, a core layer, a core-matching refractive index upper cladding layer, and a low refractive index top cladding.
2. Description of the Related Art
Such a component is known from, e.g., International patent application WO 97/01782. This publication concerns optical components having an at least penta-layered polymer structure on a substrate comprising: a) a low refractive index bottom cladding layer, b) a core-matching refractive index lower cladding layer, c) a core layer, d) a core-matching refractive index upper cladding layer, and e) a low refractive index top cladding layer.
With this specific layer structure optimum confinement in the direction of the thickness of the stack of layers (also denoted as transverse direction} can be obtained, which results in less loss of light and an improved switching efficiency. However, present and future applications of optical devices require crosstalk to be as low as possible.
Accordingly, it is an object of the present invention to further reduce crosstalk. This is achieved, in the components described in the first paragraph, by leaving out the low refractive index bottom cladding layer and employing a single core-matching refractive index lower cladding layer which has a thickness sufficient to avoid substantial capture and/or absorption by the substrate of a guided mode in the core layer, whereas slab modes, quasi-guided modes and/scattered light leak to the substrate.
It was found that, in the penta-layered components, slab modes, quasi-guided modes and/or scattered light (sometimes also referred to as radiation modes and stray light respectively) become trapped between the lower and upper cladding layers, with the core layer and the core-matching refractive index cladding layers serving as a (composite) core. By leaving out the bottom cladding layer, making sure that the slab modes, quasi-guided modes and/scattered light leak to the substrate, and selecting the thickness of the core-matching refractive index tower cladding layer such that substantial absorption of a guided mode by the substrate is avoided, crosstalk and other detrimental phenomena are significantly reduced. Once captured or absorbed by the substrate, the said modes cannot have any interaction with the guide mode(s) in the core layer and a decrease of the optical performance is avoided. E.g., for an 1xc3x972 optical switch, avoiding interaction between a guided mode in the core layer and slab modes, quasi-guided modes and/scattered light will result in a considerably improved isolation (defined as the ratio of the optical power in an output in the on-state and the optical power in an output in the off-state).
Capture and/or absorption of the guided mode should preferably be smaller than 0.01 dB/cm, more preferably smaller than 0.001 dB/cm.
Leaking of slab modes, quasi-guided modes and/or scattered light to the substrate can be achieved by using a substrate that has a refractive index higher than that of the core-matching refractive index lower cladding layer and/or that functions as an absorber of the said undesirable modes. Any material that absorbs and dissipates light in the optical frequencies used in the structure in question will do. Examples of suitable materials are metals such as titanium, silver, gold, or nickel or non-transparent dielectric polymers containing a dye. It is noted that the substrate may comprise one or more (usually very thin) top layers or coatings, e.g., to promote adhesion to the core-matching refractive index lower cladding layer.
The components according to the invention allow high switching speeds and high confinement of a guided mode, require less power for switching and, due to the capture or absorption by the substrate of slab modes, quasi-guided modes and/or scattered light, exhibit less crosstalk.
It is noted that EP 642 052 discloses a polymeric thermo-optical device comprising a polymeric core layer sandwiched between two cladding layers having a refractive index lower than that of the guiding layer. A heating element is placed against one of the cladding layers and this layer has a lower refractive index than the other cladding layer. In a particularly preferred embodiment, the lower cladding layer is made up of two sublayers to provide optical isolation from the substrate. Thus, the gist of EP 642 052 runs counter to that of the present invention. | {
"pile_set_name": "USPTO Backgrounds"
} |
This invention relates to 2,3,4,5-tetrahydro-1H-3-benzazepines having anti-psychotic activity, and also to the synthesis of .alpha.-substituted-arylacetamides, especially fused-ring nitrogen heterocycles, in particular dihydroindoles, 1,2,3,4-tetrahydroisoquinolines and 1,2,3,4,5,6-hexahydro-3-benzazocines, and most particularly 2,3,4,5-tetrahydro-1H-3-benzazepines.
Dihydroindoles, 1,2,3,4-tetrahydroisoquinolines, 1,2,3,4,5,6-hexahydro-3-benzazocines, and particularly 2,3,4,5-tetrahydro-1H-3-benzazepines are known to have useful pharmacological properties. For example, U.S. Pat. Nos. 3,393,192, 3,609,138, 4,011,319, 4,284,555 and 4,477,378, and British Patent Specification no. 1,118,688, all describe 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having various activities described as antibacterial effects, central nervous system effects and hypotensive effects.
Weinstock et al. in Drugs of the Future, Vol. 10, No. 8, pp. 645-697 (1985) discuss the profound effect that 1-phenyl substituents have on the dopaminergic activity of certain types of benzazepines; see in particular Table II on page 666.
European Patent Application No. 83105610.6 (published as 0 096 838) discloses certain 1-aryloxy-2,3,4,5-tetrahydro-1H-3-benzazepines optionally having alkoxy substituents in the 7- and/or 8-position; these compounds are disclosed as having utility in treating depression.
U.S. Pat. No. 5,015,639 describes and claims 2,3,4,5-tetrahydro-1H-3-benzazepines lacking a 1-phenyl group but having instead a variety of 1-substituents including a group of the formula ##STR1## wherein m is 0 or 1, and each of the groups R.sup.9, which can be the same or different, is a hydrogen atom or an alkyl, alkoxy, alkoxyalkyl, aralkyl or aryl group. These compounds have good anti-dopaminergic activity, and in particular show surprising selectivity for the D-1 subclassification of dopaminergic receptors. Iorio et al., Pharmacol. Exp. Ther. (1983), 226, page 462, and Iorio et al. in Neurobiology of Central D.sub.1 -Dopamine Receptors, pages 1-14 in Advances in Experimental Medicine and Biology 204, Eds. Creese and Breese, Plenum, New York, 1986, have also evaluated the effects of benzazepines on dopamine receptors. Charifson et al., J. Med. Chem. (1988), 31, pages 1941-1946, have similarly evaluated 1,2,3,4-tetrahydroisoquinolines.
International Application No. PCT/US 91/04046 describes and claims (inter alia) compounds having the structural formula A ##STR2## and the pharmaceutically acceptable salts thereof, wherein: R.sup.10 represents H, C.sub.1-4 -alkyl, allyl or cyclopropylmethyl;
R.sup.11 represents C.sub.3-8 -cycloalkyl or C.sub.5-8 -cycloalkenyl; PA1 R.sup.12 represents C.sub.1-4 -alkyl; and PA1 R.sup.13 represents (inter alia) R.sup.12, H or R.sup.12 CO. PA1 wherein R.sup.4 is selected from aromatic groups, 1-alkenyl groups and 1-cycloalkenyl groups; PA1 and X is a leaving group, e.g., --OSO.sub.2 F or an activated ester group. PA1 R.sup.4 is a 1-cycloalkenyl group; PA1 R is an alkyl, alkenyl, aryl, aralkyl, cycloalkyl or cycloalkylalkyl group; PA1 and Y is an oxygen atom or H.sub.2 ; PA1 and their non-toxic salts with bases when R.sup.1 is or contains a hydroxy group; PA1 and their non-toxic acid addition salts when Y is H.sub.2.
These compounds are useful in the treatment of psychoses, depression, pain and hypertension.
Ciufolini et al., Tetrahedron Letters 1987, Vol. 28 No. 2, 171-174, have described a `model` intramolecular arylation of 2-[2-(2-iodophenyl)ethyl]-indane-1,3-dione with tetrakis(triphenyphosphine)palladium(0), to yield a spiro(indane-1,3-dione-2,1'-indane), in experiments on the synthesis of Friedricamycin. In further studies of prototype substrates and also of substrates used in studies of the synthesis of Friedricamycin, Ciufolini et al., J. Org. Chem. [Communications] 1988, 53, 4149-4151, have described intramolecular arylations of `soft` enolates (i.e., enolates having a pK.sub.a <15) catalyzed by zerovalent palladium. A phenyl halide moiety in one part of the molecule was condensed with an enol in another part of the molecule to provide a benzo-fused five- or sixmembered homocyclic or heterocyclic ring; but compounds with a fused four-membered ring could not be produced. One example in Table I therein shows the formation of an indolone by intramolecular condensation of an N-methyl-N-(2-ethoxycarbonylpropanoyl)-2-iodoanilide. In an adaptation of this method, Piers et al., J. Org. Chem. 1990, 55, 3454-3455, have disclosed a five-membered ring annulation method based on Pd(0)-catalyzed intramolecular coupling of a vinyl iodide function with an enolate anion function; in this method, the enolate anion was in a saturated five- or six-membered ring.
A modification of the reaction disclosed by Ciufolini et al. was published by Negishi et al., J. Am. Chem. Soc., 1989, 111, 8018-8020. Using compounds analogous to those which, in the hands of Ciufolini et al., had failed to produce compounds with a fused four-membered ring, there were able to effect a cyclization in the presence of carbon monoxide under pressure: the product was a ketone with its carbonyl group (provided by the carbon monoxide) in a fused five-membered ring. They were similarly able to produce analogous ketones with the carbonyl group in a fused six- or seven-membered ring, and even effect the cyclization on non-cyclic intermediates to produce unfused cyclopentenones.
In all these reactions catalyzed by a zerovalent metal, the enolate is generally stabilized by an adjacent activating group (such as estercarbonyl, keto-carbonyl or nitrite). | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
This invention relates to a novel bioactive substance which suppresses differentiation of undifferentiated cells.
2. Description of the Related Art
Human blood and lymph contain various types of cells and each cell plays important roles. For example, the erythrocyte carries oxygen; platelets have hemostatic action; and lymphocytes prevent infection. These various cells originate from hematopoietic stem cells in the bone marrow. Recently, it has been clarified that the hematopoietic stem cells are differentiated to various blood cells, osteoclasts and mast cells by stimulation of various cytokines in vivo and environmental factors. In the cytokines, there have been found, for example, erythropoietin (EPO) for differentiation to erythrocytes; granulocyte colony stimulating factor (G-CSF) for differentiation to leukocytes; and platelet growth factor (mpl ligand) for differentiation to megakaryocytes which are a platelet producing cells, and the former two have already been clinically applied.
The undifferentiated blood cells are generally classified into two groups consisting of blood precursor cells which are destined to differentiate to specific blood series and hematopoietic stem cells which have differentiation ability to all series and self-replication activity. The blood precursor cells can be identified by various colony assays, however identification method for the hematopoietic stem cells have not been established. In these cells, stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GMf-CSF), interleukin-6 (IL-6), interleukin-1 (IL-1), granulocyte colony stimulating factor (G-CSF) and oncostatin M have been reported to stimulate cell differentiation and proliferation. Trials for expansion of hematopoietic stem cells in vitro have been examined in order to replace bone marrow transplantation for applying hematopoietic stem cell transplantation therapy or gene therapy. However, when the hematopoietic stem cells are cultured in the presence of the above mentioned cytokines, multi-differentiation activities and self-replication activities, which are originally in the position of the hematopoietic stem cells, gradually disappeared and are changed to the blood cell precursors which are only to differentiate to specific series after 5 weeks of cultivation, and multi-differentiation activity which is one of the specific features of the hematopoietic stem cells, is lost (Wagner et al. Blood 86, 512-523, 1995).
For proliferation of the blood precursor cells, a single cytokine is not sufficient, but the synergistic action of several cytokines are important. Consequently, in order to proliferate the hematopoietic stem cells while maintaining specific features of the hematopoietic stem cells, it is necessary to add cytokines which suppress differentiation together with the cytokines which proliferate and differentiate the undifferentiated blood cells. In general, many cytokines which stimulate proliferation or differentiation of cells are known, but small numbers of cytokines which suppressed cell differentiation are known. For example, leukemia inhibitory factor (LIF) has an action of proliferation of mouse embryonic stem cells without differentiation, but it has no action against the hematopoietic stem cells or blood precursor cells. Transforming growth factor (TGF-xcex2) has suppressive action for proliferation against various cells, but no fixed actions against the hematopoietic stem cells or blood precursor cells.
Not only blood cells but also undifferentiated cells, especially stem cells are thought to be involved in tissue regeneration. These regeneration of tissues and poliferation of undifferentiated cells in each tissue can be applied in various ways by referring to the known reference (Katsutoshi Yoshizato, Regenerationxe2x80x94a mechanism of regeneration, 1996, Yodosha Pub1. Co.).
Notch is a receptor type membrane protein which is involved in regulation of nerve cells differentiation found in Drosophia. Homologues of the Notch are found in various animal kinds exceeding to the invertebrate and vertebrate including nematoda (Lin-12). Xenopus laevis (Xotch), mouse (Motch) or human (TAN-1). Ligand of the Notch in Drosophila are known. These are Drosophila Delta (Delta) and Drosophila Serrate (Serrate). Notch ligand homologues are found in various animal kinds as similar to the Notch of receptors (Artavanis-Tsakonas et al., Science 268, 225-232, 1995).
Human Notch homologue, TAN-1 is found widely in the tissues in vivo (Ellisen et al., Cell 66, 649-661, 1991). Two Notch analogous molecules other than TAN-1 are reported (Artavanis-Tsakonas et al., Science 268, 225-232, 1995). Expression of TAN-1 was also observed in CD34 positive cells in blood cells by PCR (Polymerase Chain Reaction) (Milner et al., Blood 83, 2057-2062, 1994). However, in relation to humans, gene cloning of human Delta and human Serrate, which are thought to be the Notch ligand, have not been reported.
In Drosophila Notch, binding with the ligand was studied and investigated in detail, and it was found that the Notch can be bound to the ligand with Ca++ at the binding region, which is a repeated amino acid sequence No. 11 and No. 12 in the amino acid sequence repeat of Epidemal Growth Factor (EGF) like repeating (Fehon et al., Cell 61, 523-534, 1990, Rebay et al., ibid. 67, 687-699, 1991 and Japan. Patent PCT Unexam. Pub1. 7-503123). EGF-like repeated sequences are conserved in Notch homologues of the other species. Consequently, the same mechanism in binding with ligand is estimated. An amino acid sequence which is called DSL (Delta-Serrate-Lag-2) near the amino acid terminal, and EGF-like repeated sequence as like in the receptor are conserved in the ligand (Artavanis-Tsakonas et al., Science 268, 225-232, 1995).
The sequence of DSL domain is not found except for the Notch ligand molecules, and is specific to Notch ligand molecule. A common sequence of DSL domain is shown in the sequence listing, SEQ ID NO: 1 in general formula, and comparison with human Delta-1 and human Serrate-1 of the present invention and known Notch ligand molecules are shown in FIG. 1.
EGF-like sequence has been found in thrombomodulin (Jackman et al., Proc. Natl. Acad. Sci. USA 83, 8834-8838, 1986), low density lipoprotein (LDL) receptor (Russell et al., Cell 37, 577-585, 1984), and blood coagulating factor (Furie et al., Cell 53, 505-518, 1988), and is thought to play important roles in extracellular coagulation and adhesion.
Recently, the vertebrate homologues of the cloned Drosophila Delta were found in chicken (C-Delta-1) and Xenopus laevis (X-Delta-1), and it was reported that X-Delta-1 had acted through Xotch in the generation of the protoneuron (Henrique et al., Nature 375, 787-790, 1995 and Chitnis et al., ibid. 375, 761-766,1995). Vertebrate homologue of Drosophila Serrate was found in rat as rat Jagged (Jagged)(Lindsell et al., Cell 80, 909-917, 1995). According to the Lindsell et al., mRNA of the rat Jagged is detected in the spinal cord of fetal rats. As a result of cocultivation of a myoblast cell line that is forced excess expressed rat Notch with a rat Jagged expression cell line, suppression of differentiation of the myoblast cell line is found. However, the rat Jagged has no action against the myoblast cell line without forced expression of the rat Notch.
Considering the above reports, the Notch and ligand thereto may be involved in the differentiation regulation of the nerve cells however, except for some myoblast cells, their actions against cells including blood cells, especially primary cells, are unknown.
In the Notch ligand molecule, from the viewpoint of the prior studies on Drosophila and nematodae,the Notch ligand has specifically a structure of DSL domain which is not found other than in the Notch ligand. Consequently, the fact of having DSL domain means equivalent to ligand molecule for the Notch receptor.
As mentioned above, concerning undifferentiated cells, proliferation that maintains their specificities has not been achieved. Major reasons are that factors suppressing differentiation of the undifferentiated cells are not sufficiently known. An object of the present invention is to provide a compound originated from novel factors which can suppress differentiation of the undifferentiated cells.
We have set up a hypothesis that the Notch and its ligand have action of differential regulation not only for neuroblasts and myoblasts but also for various undifferentiated cells, especially blood undifferentiated cells. However, in case of clinical application in the humans, prior known different species such as chicken or Xenopus laevos type notch ligand have problems of species specificities and antigenicities. Consesquently, to obtain previously unknown human Notch ligand is essentially required. We had an idea that a molecule having DSL domain and EGF-like domain which are common to Notch ligand molecules and a ligand of the human Notch (TAN-1 etc.), which is a human Delta homologue (hereinafter designated as human Delta) and human Serrate homologue (hereinafter designated as human Serrate), may be found. Also we have an idea that these findings may be a candidate for drugs useful for differential regulation of the undifferentiated cells. And we have tried to find out the same.
In order to find out human Notch ligands, we have analyzed amino acid sequences which are conserved in animals other than humans, and tried to find out genes by PCR using mixed primers of the corresponding DNA sequence. As a result of extensive studies, we have succeeded in isolation of cDNAs coding amino acid sequences of two new molecules, novel human Delta-1 and novel human Serrate-1, and have prepared the expression systems of protein having various forms using these cDNAs. Also we have established purification method of the proteins which were purified and isolated.
Amino acid sequences of novel human Delta-1 are shown in the sequence listings, SEQ ID NO: 2-4. DNA sequence coding these sequence is shown in the sequence listing, SEQ ID NO: 8. Amino acid sequence of novel human Serrate-1 is shown in the sequence listings, SEQ ID NO: 5-7. DNA sequence coding these sequence is shown in the sequence listing, SEQ ID NO: 10.
Physiological actions of the these prepared proteins were searched by using nerve undifferentiated cells, preadipocytes, hepatocytes, myoblasts, skin undifferentiated cells, blood undifferentiated cells and immuno undifferentiated cells. As a result, we have found that novel human Delta-1 and novel human Serrate-1 had an action of differentiation-suppressive action to primary blood undifferentiated cells, and had a physiological action to maintain undifferentiated state.
Such actions to the blood undifferentiated cells have never been reported previously, and is a new discovery. No significant toxic actions were noted in the toxicity studies on mice, and useful pharmaceutical effects were suggested. Consequently, the pharmaceutical preparations containing the molecule of the present invention, medium containing the molecule of the present invention, and the device having immobilized thereon the molecule of the present invention are novel drugs and medical materials which can maintain the blood undifferentiated cells in the undifferentiated condition. Antibodies against human Delta-1 and human Serrate-1 are prepared by using antigens of the said human Delta-1 and human Serrate-1, and purification method of the said antibodies are established. The present invention has been completed accordingly.
The present invention further relates to a polypeptide comprising amino acid sequence of SEQ ID NO: 1 of the sequence listing encoded in a gene of human origin, a polypeptide comprising at least amino acid sequence of SEQ ID NO: 2 or NO: 5 of the sequence listing, the polypeptide comprising amino acid sequence of SEQ ID NO: 3 of the sequence listing, the polypeptide comprising amino acid sequence of SEQ ID NO: 4 of the sequence listing, the polypeptide comprising amino acid sequence of SEQ ID NO: 6 of the sequence listing, the polypeptide comprising amino acid sequence of SEQ ID NO: 7 of the sequence listing, the polypeptide having differentiation suppressive action against undifferentiated cells, the polypeptide in which undifferentiated cells are undifferentiated cells other than those of the brain and nervous system or muscular system cells, and the polypeptide in which undifferentiated cells are the undifferentiated blood cells. The present invention also relates to a pharmaceutical composition containing the polypeptides, and the pharmaceutical composition in which use thereof is as a hematopoietic activator. The present invention further relates to a cell culture medium containing the polypeptides, and the cell culture medium in which the cell is the undifferentiated blood cell. The present invention still further relates to a DNA coding a polypeptide at least having amino acid sequence of SEQ ID NO: 2 or NO: 5 of the sequence listing, the DNA having DNA sequence 242-841 of SEQ ID NO: 8 or DNA sequence 502-1095 of SEQ ID NO: 10 of the sequence listing, the DNA coding the polypeptide having amino acid sequence of SEQ ID NO: 3 of the sequence listing, the DNA having DNA sequence 242-1801 of SEQ ID NO: 8 of the sequence listing, the DNA coding the polypeptide having amino acid sequence of SEQ ID NO: 4 of the seqeuence listing, the DNA having DNA sequence 242-2347 of SEQ ID NO: 8of the sequence listing, the DNA coding the polypeptide having amino acid sequence of SEQ ID NO: 6 of the seqeuence listing,the DNA having DNA sequence 502-3609 of SEQ ID NO: 10 of the sequence listing, the DNA coding the polypeptide having amino acid sequence of SEQ ID NO: 7 of the seqeuence listing, and the DNA having DNA sequence 502-4062 of SEQ ID NO: 10 of the sequence listing. The present invention still further relates to a recombinant DNA made by ligating a DNA selected from the groups of DNA hereinabove and a vector DNA which can express in the host cell, a cell transformed by the recombinant DNA, and a process for production of polypeptide by culturing cells and isolating the thus produced compound. The present invention still further relates to an antibody specifically recognizing the polypeptide having the amino acid sequence of SEQ ID NO: 4 of the sequence listing, and an antibody specifically recognizing the polypeptide having the amino acid sequence of SEQ ID NO: 7 of the sequence listing.
The present invention is explained in details in the following.
Preparation of cDNA necessary for gene manipulation, expression analysis by Northern blotting, screening by hybridization, preparation of recombinant DNA, determination of DNA base sequence and preparation of cDNA library, all of which are series of molecular biological experiments, can be performed according to a description of the conventional textbook for the experiments. The above conventional textbook of the experiments is, for example, Maniatis et al. ed. Molecular Cloning, A laboratory manual, 1989, Eds., Sambrook, J., Fritsch, E. F. and Maniatis, T., Cold Spring Harbor Laboratory Press.
A polypeptide of the present invention has at least one of the polypeptides in the sequence listing SEQ ID NO: 1-7. A mutant and allele which naturally occur in the nature are included in the polypeptide of the present invention unless the polypeptides of the sequence listing, SEQ ID NO: 1-7 lose their properties. Modification and substitution of amino acids are described in details in the patent application by the name of Benntt et al. (National Unexam. Pub1. WO96/2645) and can be prepared according to the description thereof.
A DNA sequence coding polypeptides of the sequence listing, SEQ ID NO: 2-4 is shown in the sequence listing, SEQ ID NO: 8, and a DNA sequence coding polypeptides of the sequence listing, SEQ ID NO: 5-7 is show in the sequence listing, SEQ ID NO: 10, together with their amino acid sequences. In these DNA sequences, even if amino acid level mutation is not generated, naturally isolated chromosomal DNA or cDNA thereof may have a possibility to mutate in the DNA base sequence as a result of degeneracy of genetic code without changing amino acid sequence coded by the DNA. A 5xe2x80x2-untranslated region and 3xe2x80x2-untranslated region are not involved in amino acid sequence determination of the polypeptide, so DNA sequences of these regions are easily mutated. The base sequence obtained by these degeneracies of genetic codes is included in the DNA of the present invention.
Undifferentiated cells in the present invention are defined as cells which can grow by specific stimulation, and cells which can be differentiated to the cells having specific functions as a result of the specific stimulations. These include undifferentiated cells of the skin tissues, undifferentiated cells of the brain and nervous systems, undifferentiated cells of the muscular systems and undifferentiated cells of the blood cells. These cells include the cells of self-replication activity which are called stem cells, and the cells having an ability to generate the cells of these lines. The differentiation-suppressive action means suppressive action for autonomous or heteronomous differentiation of the undifferentiated cells, and is an action for maintaining undifferentiated condition. The brain and nervous undifferentiated cells can be defined as cells having ability to differentiate to the cells of the brain or nerve having specific functions by specific stimulation. The undifferentiated cells of the muscular systems can be defined as cells having ability to differentiate to the muscular cells having specific functions by specific stimulation. The blood undifferentiated cells in the present invention can be defined as cell groups consisting of the blood precursor cells which are differentiated to the specific blood series identified by blood colony assay, and hematopoietic stem cells having differentiation to every series and self-replication activities.
In the sequence listing, amino acid sequence in SEQ ID NO: 1 shows general formula of common amino acid sequence of DSL domain which is a common domain structure of the Notch ligand molecules, and at least this domain structure corresponds to the sequence listing, amino acids 158-200 of the human Delta-1, or the sequence listing, amino acids 156-198 of the human Serrate-1.
The amino acid sequence in the sequence listing, SEQ ID NO: 2 is a sequence of the active center of the present invention of human Delta-1 minus the signal peptide, i.e. amino acid sequence from the amino terminal to DSL domain, and corresponds to an amino acid No. 1 to 200 in SEQ ID NO: 4 of the mature full length amino acid sequence of human Delta-1 of the present invention. The amino acid sequence in SEQ ID NO: 3 is amino acid sequence of extracellular domain of the present invention of human Delta-1 deleted the signal peptide, and corresponds to an amino acid No. 1 to 520 in SEQ ID NO: 4 of the mature full length amino acid sequence of human Delta-1 of the present invention. The amino acid sequence of SEQ ID NO: 4 is the mature full length amino acid sequence of the human Delta-1 of the present invention.
The amino acid sequence in the sequence listing, SEQ ID NO: 5 is a sequence of the active center of the present invention of human Serrate-1 minus the signal peptide, i.e. amino acid sequence from the amino terminal to DSL domain, and corresponds to an amino acid No. 1 to 198 in SEQ ID NO: 7 of the mature full length amino acid sequence of human Serrate-1 of the present invention. The amino acid sequence in SEQ ID NO: 6 is amino acid sequence of extracellular domain of the present invention of human Serrate-1 minus the signal peptide, and corresponds to an amino acid No. 1 to 1036 in SEQ ID NO: 7 of the mature full length amino acid sequence of human Serrate-1 of the present invention. The amino acid sequence of SEQ ID NO: 7 is the mature full length amino acid sequence of the human Serrate-1 of the present invention.
The sequence of SEQ ID NO: 8 is a total amino acid sequence of human Delta-1 of the present invention and cDNA coding the same, and the sequence of SEQ ID NO: 10 is total amino acid sequence of human Serrate-1 of the present invention and cDNA coding the same.
The left and right ends of the amino acid sequences in the sequence listings indicate amino terminal (hereinafter designated as N-terminal) and carboxyl terminal (hereinafter designated as C-terminal), respectively, and the left and right ends of the nucleotide sequences are 5xe2x80x2-terminal and 3xe2x80x2-terminal, respectively.
Cloning of human Notch ligand gene can be performed by the following method. During the evolution of the organisms, a part of amino acids sequences of the human Notch ligand is conserved. DNA sequence corresponding to the conserved amino acid sequence is designed, and is used as a primer of RT-PCR (Reverse Transcription Polymerase Chain Reaction), then a PCR template of the human origin is amplified by PCR reaction, thereby fragments of human Notch ligand can be obtainable. Furthermore, RT-PCR primer is prepared by applying the known DNA sequence information of the Notch ligand homologue of the organisms other than humans, and the known gene fragments can be possibly obtained from PCR template of the said organisms.
In order to perform PCR for obtaining fragments of human Notch ligand, PCR for DSL sequence is considered, but a large number of combinations of DNA sequence corresponding to amino acid sequence conserved in this region can be expected, and a design for PCR is difficult. As a result, PCR of the EGF-like sequence has to be selected. As explained hereinbefore,since EGF-like sequence is conserved in a large number of molecules, to obtain the fragments and identification are extremely difficult.
We have designed and prepared about 50 PCR primer sets, for example the primer set of the sequence shown in Example 1, PCR was performed with these primer sets by using PCR template of cDNA prepared from poly A+ RNA of various tissues of human origin, and more than 10 PCR products from each tissue were subcloned, as well as performing sequencing for more than 500 types. A clone having a desired sequence could be identified. Namely, the obtained PCR product is cloned in the cloning vector, transforming the host cells by using recombinant plasmid which contains the PCR product, culturing the host cells containing the recombinant plasmid on a large scale, purifying and isolating the recombinant plasmid, checking the DNA sequence of PCR product which is inserted into the cloning vector, and trying to obtain the gene fragment which may have a sequence of human Delta-1 by comparing with the sequence of the known Delta of other species. We have succeeded to find out the gene fragment which contains a part of cDNA of human Delta-1, the same sequence of DNA sequence from 1012 to 1375 described in the sequence listing, SEQ ID NO: 8.
We have also designed and prepared about 50 PCR primer sets, for example the primer set of the sequence shown in Example 3, and PCR was performed with these primer sets by using PCR template of cDNA prepared from poly A+ RNA of various tissues of human origin, and more than 10 PCR products from each tissue were subcloned, as well as performing sequencing for more than 500 types. A clone having a desired sequence could be identified. Namely, the obtained PCR product is cloned in the cloning vector, transforming the host cells by using recombinant plasmid which contains the PCR product, culturing the host cells containing the recombinant plasmid on a large scale, purifying and isolating the recombinant plasmid, checking the DNA sequence of PCR product which is inserted into the cloning vector, and trying to obtain the gene fragment which may have a sequence of human Serrate-1 by comparing with the sequence of the known Serrate of other species. We have succeeded to find out the gene fragment which contains a part of cDNA of human Serrate-1, the same sequence of DNA sequence from 1272 to 1737 described in the sequence listing, SEQ ID NO: 10.
A full length of the objective gene can be obtained from the human genomic gene library or cDNA library by using the thus obtained human Delta-1 fragment or human Serrate-1 gene fragment. The full length cloning can be made by isotope labelling and non-isotope labelling with the partial cloning gene, and screening the library by hybridization or other method. Isotope labelling can be performed by, for example, terminal labelling by using [32P] xcex3-ATP and T4 polynucleotide kinase, or other labelling methods such as nick translation or primer extension method can be applied. In another method, human originated cDNA library is ligated into the expression vector, expressing by COS-7 or other cells, and screening the objective gene by expression cloning to isolate cDNA of the ligand. In the expression cloning, a cell sorter fractionation method which is applied with binding with polypeptide containing amino acid sequence of prior known 4 Notches such as TAN-1, and a detection method by film emulsion using radioisotope can be mentioned. In this specification, methods for obtaining genes of human Delta-1 and human Serrate-1 are explained, and in addition to that obtaining the Notch ligand homologue gene of the other organism is important for analysis of ligand action. This may be made by the same treatment. The obtained gene is subjected to DNA sequence determination and amino acid sequence can be estimated.
As shown in Example 2, gene fragments containing human Delta-1 PCR product are labelled with radioisotope to prepare hybridization probe, screening is preformed using cDNA of human placenta origin as the screening library, DNA sequences of the thus obtained clones, are determined, and the clone is obtained DNA nucleotide sequence shown in the sequence listing, SEQ ID NO: 8, and shown to name the amino acid sequence coded in the sequence listing, SEQ ID NO: 4. We have succeeded in cloning cDNA coding full length of amino acids sequence of human Delta-1.
These sequences were compared with the data base (Genbank release 89, June, 1995), and found that these were novel sequences. The said amino acid sequence was analyzed in hydrophilic part and hydrophobic part according to a method by Kyte-Doolittle (J. Mol. Biol. 157: 105, 1982). A result indicated that human Delta-1 of the present invention is expressed on cells as a cellular membrane protein having a transmembrane domain.
As shown in Example 4, gene fragments containing human Serrate-1 PCR product are labelled with radioisotope to prepare hybridization probe, screening is preformed using cDNA of human placenta origin as the screening library, DNA sequences of the thus obtained clones are determined, and the clone is obtained containing DNA nucleotide sequence shown in the sequence listing, SEQ ID NO: 10, and shown to have the amino acid sequence coded in the sequence listing, SEQ ID NO: 7. In this screening, an intracellular part of gene sequence coding a full length of amino acids sequence, namely a peripheral part of termination codon can not be cloned. Consequently, as shown in Example 4, gene cloning is performed by RACE method (rapid amplification of cDNA ends, Frohman et al., Proc. Natl. Acad. Sci. U.S.A. 85, 8998-9002, 1988) and finally succeeded in cloning of cDNA coding full length of amino acid sequence of human Serrate-1.
These sequences were compared with the data base (Genbank release 89, June, 1995), and found that these were novel sequences. The said amino acid sequence was analyzed in hydrophilic part and hydrophobic part according to a method by Kyte-Doolittle (J. Mol. Biol. 157: 105, 1982). A result indicated that human Serrate-1 of the present invention is expressed on cells as a cellular membrane protein having a transmembrane domain.
Examples of plasmids integrated with cDNA are, for example, E. coli originated pBR322, pUC18, pUC19, pUC118 and pUC119 (Takara Shuzo Co. Japan), but other plasmids can be used if they can replicate and proliferate in the host cells. Examples of phage vectors integrated with cDNA are, for example, xcexgt10 and xcexgt11, but other vectors can be used if they can grow in the host cells. The thus obtained plasmids are transduced into suitable host cells such as genus Escherichia and genus Bacillus using calcium chloride method. Examples of the above genus Escherichia are Eseherichia coli K12HB101, MC1061, LE392 and JM109. Example of the above genus Bacillus is Bacillus subtilis MI114. Phage vector can be introduced into the proliferated E. coli by the in vitro packaging method (Enquist and Sternberg Meth. Enzymd., 68, 281-1979).
According to the analysis of amino acid sequence of the human Delta-1, amino acid sequence of a precursor of human Delta-1 consists of 723 amino acids residue shown in the sequence listing, SEQ ID NO: 8, and the signal peptide domain is estimated to correspond to an amino acid sequence of 21 amino acids residue from No.xe2x88x9221 methionine to No. xe2x88x921 serine of the sequence listing; extracellular domain: 520 amino acids residue from No. 1 serine to No. 520 glycine; transmembrane domain: 32 amino acids residue from No. 521 proline to No. 552 leucine; and intracellular domain: 150 amino acids region from No. 553 glutamine to No. 702 valine. These domains are estimated domain construction from amino acid sequences, and actual presence form may differ from the above structure, and constitutional amino acids of each domain hereinabove defined may have possibility to change 5 to 10 amino acids sequence.
According to a comparison in amino acid sequence of human Delta-1 and Delta homologue of the other organisms, the homologies with Drosophila Delta, chicken Delta and Xenopus laevis are 47.6%, 83.3% and 76.2%, respectively. The human Delta-1 of the present invention is different from these Deltas and is novel substance which is clarified at first by the present inventors. Search from all of organisms in the above data base indicated that polypeptides having the identical sequence of the human Delta-1 could not be found.
The homologues of Notch ligand have evolutionally conserved common sequence, i.e. repeated DSL sequence and EGF-like sequence. As a result of comparison with amino acid sequence of human Delta-1, these conserved sequence is estimated. Namely, DSL sequence corresponds to 43 amino acids residue from No. 158 cysteine to No. 200 cysteine of the amino acid sequence in the sequence listing, SEQ ID NO: 4. EGF-like sequence exists with 8 repeats wherein, in the amino acid sequence in the sequence listing, SEQ ID NO: 4, the first EGF-like sequence from No. 205 cysteine to No. 233 cysteine; the second EGF-like sequence from No. 236 cysteine to No. 264 cysteine; the third EGF-like sequence from No. 271 cysteine to No. 304 cysteine; the fourth EGF-like sequence from No. 311 cysteine to No. 342 cysteine; the fifth EGF-like sequence from No. 349 cysteine to No. 381 cysteine; the sixth EGF-like sequence from No. 388 cysteine to No. 419 cysteine; the seventh EGF-like sequence from No. 426 cysteine to No. 457 cysteine; and the eighth EGF-like sequence from No. 464 cysteine to No. 495 cysteine.
A part of sugar chain attached is estimated from amino acid sequence of the human Delta-1 may be No. 456 asparagine residue in the sequence listing, SEQ ID NO: 4 as a possible binding site of N-glycoside bonding for N-acetyl-D-glucosamine. O-glycoside bond of N-acetyl-D-galactosamine is estimated to be a serine or threonine residue rich part. Protein bound with sugar chain is generally thought to be stable in vivo and to have strong physiological activity. Consequently, in the amino acid sequence of polypeptide having sequence of the sequence listing, SEQ ID NO: 2, 3 or 4, polypeptides having N-glucoside or O-glucoside bond with sugar chain of N-acetyl-D-glucosamine or N-acetyl-D-galactosamine is included in the present invention.
According to the analysis of amino acid sequence of the human Serrate-1, amino acid sequence of a precursor of human Serrate-1 consists of 1218 amino acids residue shown in the sequence listing, SEQ ID NO: 10, and the signal peptide domain is estimated to correspond 31 amino acids residue in the amino acid sequence from No. xe2x88x9231 methionine to No. xe2x88x921 alanine of the sequence listing; extracellular domain: 1036 amino acids residue from No. 1 serine to No. 1036 asparagine; transmembrane domain: 26 amino acids residue from No. 1037 phenylalanine to No. 1062 leucine; and intracellular domain: 106 amino acids domain from No. 1063 arginine to No. 1187 valine. These domains are estimated domain construction from amino acid sequences, and actual presence form may differ from the above structure, and constitutional amino acids of each domain hereinabove defined may have possibility to change 5 to 10 amino acids sequence.
According to a comparison in amino acid sequence of human Serrate-1 and Serrate homologue of the other organisms, the homologies with Drosophila Serrate, and rat Jagged are 32.1% and 95.3%, respectively. The human Serrate-1 of the present invention is different from these Serrates and is novel substance which is clarified at first by the present inventors. Search from all of organisms in the above data base indicated that polypeptides having the identical sequence of the human Serrate-1 could not find out.
The homologues of Notch ligand have evolutionally conserved common sequence, i.e. repeated DSL sequence and EGF-like sequence. As a result of comparison with amino acid sequence of human Serrate-1 and other Notch ligand homologues, these conserved sequence is estimated. Namely, DSL sequence corresponds to 43 amino acids residue from No. 156 cysteine to No. 198 cysteine of the amino acid sequence in the sequence listing, SEQ ID NO: 7. EGF-like sequence exists with 16 repeats wherein, in the amino acid sequence in the sequence listing, SEQ ID NO: 7, the first EGF-like sequence from No. 205 cysteine to No. 231 cysteine; the second EGF-like sequence from No. 234 cysteine to No. 262 cysteine; the third EGF-like sequence from No. 269 cysteine to No. 302 cysteine; the fourth EGF-like sequence from No. 309 cysteine to No. 340 cysteine; the fifth EGF-like sequence from No. 346 cysteine to No. 378 cysteine; the sixth EGF-like sequence from No. 385 cysteine to No. 416 cysteine; the seventh EGF-like sequence from No. 423 cysteine to No. 453 cysteine; the eighth EGF-like sequence from No. 462 cysteine to No. 453 cysteine; the nineth EGF-like sequence from No. 498 cysteine to No. 529 cysteine; the 10th EGF-like sequence from No. 536 cysteine to No. 595 cysteine; the 11th EGF-like sequence from No. 602 cysteine to No. 633 cysteine; the 12th EGF-like sequence from No. 640 cysteine to No. 671 cysteine; the 13th EGF-like sequence from No. 678 cysteine to No. 709 cysteine; the 14th EGF-like Sequence from No. 717 cysteine to No. 748 cysteine; the 15th EGF-like sequence from No. 755 cysteine to No. 786 cysteine; and the 16th EGF-like sequence from No. 793 cysteine to No. 824 cysteine. However,the 10th EGF-like sequence has irregular sequence containing 10 residues of cysteine.
A part of sugar chain attached is estimated from amino acid Sequence of the human Serrate-1 may be No. 112, 131, 186, 351, 528, 554, 714, 1014 and 1033 asparagine residue in the sequence listing, SEQ ID NO: 7 as a possible binding site of N-glycoside bonding for N-acetyl-D-glycosamine. O-glycoside bond of N-acetyl-D-galactosamine is estimated to be a serine or threonine residue rich part. Protein bound with sugar chain is generally thought to be stable in vivo and to have strong physiological activity. Consequently,in the amino acid sequence of polypeptide having sequence of the sequence listing, SEQ ID NO: 5, 6 or 7, polypeptides having N-glucoside or O-glucoside bond with sugar chain of N-acetyl-D-glucosamine or N-acetyl-D-galactosamine is included in the present invention.
As a result of studies on binding of Drosophila Notch and its ligand, amino acid region necessary for binding with ligand of Drosophila Notch with the Notch is from N-terminal to DSL sequence of the mature protein, in which signal peptide is removed (Japan. Pat. PCT Unexam. Pub1. No. 7-503121). This fact indicates that a domain necessary for expression of ligand action of human Notch ligand molecule is at least the DSL domain, i.e. a domain containing amino acid sequence of the sequence listing, SEQ ID NO: 1, and a domain at least necessary for expression of ligand action of human Delta-1 is novel amino acid sequence shown in the sequence listing, SEQ ID NO: 2, and further a domain at least necessary for expression of ligand action of human Serrate-1 is novel amino acid sequence shown in the sequence listing, SEQ ID NO: 5.
An mRNA of human Delta-1 can be detected by using DNA coding a part or all of gene sequence in the sequence listing, SEQ ID NO: 8, and an mRNA of human Serrate-1 can be detected by using DNA coding a part or all of gene sequence in the sequence listing, SEQ ID NO: 10. For example, a method for detection of expression of these genes can be achieved by applying with hybridization or PCR by using complementary nucleic acids of above 12 mer or above 16 mer, preferably above 18 mer having nucleic acid sequence of a part of sequence in the sequence listing, SEQ ID NO: 8 or 10, i.e. antisense DNA or antisense RNA, its methylated, methylphosphated. deaminated, or thiophosphated derivatives. By the same method, detection of homologues of the gene of other organisms such as mice or gene cloning can be achieved. Further cloning of genes in the genome including humans can be made. Using these genes cloned by such like methods, further detailed functions of the human Delta-1 or human Serrate-1 of the present invention can be clarified. For example, using the modern gene manipuration techniques, every methods including transgenic mouse, gene targeting mouse or double knockout mouse in which genes relating to the gene of the present invention are inactivated, can be applied. If abnomalities in the genome of the present gene is found, application to gene diagnosis and gene therapy can be made.
A transformant in which vector pUCDL-1F, which contains cDNA coding total amino acid sequence of human Delta-1 of the present invention, is transformed into E. coli JM109, has been deposited in the National Institute of Bioscience and Human-Technology, Agency of Industrial Science and Technology, MITI, of 1-1-3, Higasi, Tsukuba-shi, Ibaragi-ken, Japan, as E. coli: JM109-pUCDL-1F. Date of deposit was Oct. 28, 1996, and deposition No. is FBRM BP-5728. A transformant in which vector pUCSR-1, which contains cDNA coding total amino acid sequence of human Serrate-1 of the present invention, is transformed into E. coli JM109, has been deposited in the National Institute of Bioscience and Human-Technology, Agency of industrial Science and Technology, MITI, of 1-1-3, Higasi, Tsukuba-shi, Ibaragi-ken, Japan, as E. coli: JM109-pUCSR-1. Date of deposit was October 28, 1996, and deposition No. is FBRPM BP-5726.
Exprssion and purification of various forms of human Delta-1 and human Serrate-1 using cDNA coding amino acid sequence of human Delta-1 and human Serrate-1 isolated by the above methods are known in the references (Kriegler, Gene Transfer and Expression- A Laboratory Manual Stockton Press, 1990 and Yokota et al. Biomanual Series 4, Gene transfer and expression and analysis, Yodosha Co., 1994). A cDNA coding the amino acid sequence of the isolated said human Delta-1 and human Serrate-1 is ligated to preferable expression vector and is produced in the host cells of eukaryotic cells such as animal cells and insect cells or prokaryotic cells such as bacteria.
In the expression of human-Delta-1 and human Serrate-1 of the present invention, DNA coding polypeptide of the present invention may have the translation initiation codon in 5xe2x80x2-terminal and translation termination codon in 3xe2x80x2-terminal. These translation initiation codon and translation termination codon can be added by using preferable synthetic DNA adapter. Further for expression of the said DNA, promoter is linkaged in the upstream of the DNA sequence. Examples of vector are plasmid originated from Bacillus, plasmid originated from yeast or bacteriophage such as xcex-phage and animal virus such as retrovirus and vaccinia virus.
Examples of promoters used in the present invention are any promoters preferable for corresponding to the host cells used in gene expression.
In case that the host cell in the transformation is genus Eseherichia, tac-promoter, trp-promoter and lac-promoter are preferable, and in case of host of genus Bacillus, SP01 promoter and SP02 promoter are preferable, and in case of host of yeast, PGK promoter, GAP promoter and ADH promoter are preferable.
In case that the host cell is animal cells, a promoter originated from SV40 such as SRxcex1 promoter as described in Example 5, promoter of retrovirus, metallothionein promoter and heatshock promoter can be applied.
Polypeptide of the present invention can be expressed by using the expression vector having ability to be used by any person skilled in the arts.
Expression of the polypeptide of the present invention can be made by using only DNA coding the amino acid sequence of the sequence listing, SEQ ID NO: 2, 3, 4, 5, 6 or 7. However, the protein added with specific function can be produced by using DNA, to which added cDNA coding the known antigen epitope for easier detection of the produced polypeptide or added cDNA coding the immunoglobulin Fc for forming multimer.
As shown in Example 5, we have prepared expression vectors, which express extracellular proteins of human Delta-1, as follows.
1) DNA coding the amino acids from No. 1 to 520 in amino acid sequence in the sequence listing, SEQ ID NO: 3,
2) DNA coding chimera protein to which added polypeptide having 8 amino acid, i.e. an amino acid sequence consisting of Asp Tyr Lys Asp Asp Asp Asp Lys (hereinafter designates FLAG sequence, the sequence listing, SEQ ID NO: 10), in the C-terminal of the amino acids from No. 1 to 520 in amino acid sequence in the sequence listing, SEQ ID NO: 3, and
3) DNA coding chimera protein to which added Fc sequence below the hinge region of human IgG1 (refer to International Patent Pub1. WO96/11221) in the C-terminal of the amino acids from No. 1 to 520 in amino acid sequence in the sequence listing, SEQ ID NO: 3, and to have dimer structure by disulfide bond in the hinge region,
are ligated individually with the expression vector pMKITNeo (Maruyama et al. Japan Molecular Biology Soc. Meeting Preliminary lecture record, obtainable from Dr. Maruyama in Tokyo Medical and Dental College, containing promoter SRxcex1) to prepare extracellular expression vectors of human Delta-1.
The full-length expression vectors of the human Delta-1 as the expression vectors, which express full-length proteins of the human Delta-1, can be prepared as follows.
4) DNA coding amino acids from No. 1 to 702 in the sequence listing, SEQ ID NO: 4 and
5) DNA coding chimera protein to which added polypeptide having FLAG sequence in the C-terminal of amino acids from No. 1 to 702 in the sequence listing, SEQ ID NO: 4
are ligated individually with the expression vector pMlKITNeo to prepare the full-length expression vectors of human Delta-1. The transformant is prepared by using expression plasmid containing DNA coding the thus constructed said human Delta-1.
As shown in Example 6, we have prepared expression vectors, which express extracellular proteins of human Serrate-1, as follows.
6) DNA coding the amino acids from No. 1 to 1036 in amino acid sequence in the sequence listing, SEQ ID NO: 6,
7) DNA coding chimera protein to which added polypeptide having FLAG sequence in the C-terminal of the amino acids from No. 1 to 1036 in amino acid sequence in the sequence listing, SEQ ID NO: 6, and
8) DNA coding chimera protein to which added said Fc sequence in the C-terminal of the amino acids from No. 1 to 1036 in amino acid sequence in the sequence listing, SEQ ID NO: 6, and to have dimer structure by disulfide bond in the hinge region,
are ligated individually with the expression vector pMKITNeo to prepare extracellular expression vectors of human Serrate-1.
The full-length expression vectors of the human Serrate-1 as the expression vectors,which express full-length proteins of the human Serrate-1, can be prepared as follows.
9) DNA coding amino acids from No. 1 to 1187 in the sequence listing, SEQ ID NO: 7 and
10) DNA coding chimera protein to which added polypeptide having FLAG sequence in the C-terminal of amino acids from No. 1 to 1187 in the sequence listing, SEQ ID NO: 7
are ligated individually with the expression vector pMKITNeo to prepare the full-length expression vectors of human Serrate-1. The transformant is prepared by using expression plasmid containing DNA coding the thus constructed said human Serrate-1.
Examples of the host are genus Escherichia, genus Bacillus, yeast and animal cells. Examples of animal cells are simian cell COS-7 and Vero, Chinese hamster cell CHO and silk worm cell SF9.
As shown in Example 7, the above expression vectors 1)-10) are transduced individually; the human Delta-1 or human Serrate-1 are expressed in COS-7 cell (obtainable from the Institute of Physical and Chemical Research, Cell Development Bank, RCB0539), and the transformants which were transformed by these expression plasmids, can be obtained. Further, human Delta-1 polypeptide and human Serrate-1 polypeptide can be produced by culturing the transformants under preferable culture condition in medium by known culture method.
As shown in Example 8, human Delta-1 polypeptide and human Serrate-1 polypeptide can be isolated and purified from the above cultured mass, in general, by the following methods.
For extraction of the substance from cultured microbial cells or cells, microbial cells or cells are collected by known method such as centrifugation after the cultivation, suspended in preferable buffer solution, disrupted the microbial cells or cells by means of ultrasonication, lysozyme and/or freeze-thawing and collected crude extract by centrifugation or filtration. The buffer solution may contain protein-denaturing agents such as urea and guanidine hydrochloride or surface active agents such as Triton-X. In case of secretion in the cultured solution, the cultured mass is separated by the known method such as centrifugation to separate from microbial cells or cells and the supernatant solution is collected.
The thus obtained human Delta-1 or human Serrate-1, which are contained in the cell extracts or cell supernatants, can be purified by known protein purification methods. During the purification process, for confirmation of existence of the protein, in case of the fused proteins of the above FLAG and human IgGFc, they can be detected by immunoassay using antibody against known antigen epitope and can be purified. In case of not to express as such the fused protein, the antibody in Example 9 can be used for detection.
Antibodies, which specifically recognize human Delta-1 and human Serrate-1, can be prepared as shown in Example 9. Antibodies can be prepared by the methods described in the reference (Antibodies a laboratory manual, E. Harlow et al., Cold Spring Harbor Laboratory) or recombinant antibodies expressed in cells by using immunoglobulin genes isolated by gene cloning method. The thus prepared antibodies can be used for purification of human Delta-1 and human Serrate-1. The human Delta-1 or human Serrate-1 can be detected and assayed by using antibodies which recognize specifically human Delta-1 or human Serrate-1 as shown in Example 9, and can be used for diagnostic agents for diseases accompanied with abnormal differentiation of cells such as malignant tumors.
More useful purification method is the affinity chromatography using antibody. Antibodies used in this case are antibodies described in Example 9. For fused protein, antibodies against FLAG in the case of FLAG, and protein G or protein A in the case of human IgGFc as shown in Example 8.
Any fused protein other than the protein as shown hereinabove can be used. For example, histidine Tag and myc-tag can be mentioned. Any fused proteins can be prepared by using methods of present day genetic engineering techniques other than the known methods, and peptides of the present invention derived from those fused proteins are in the scope of the present invention.
Physiological functions of the thus purified human Delta-1 and human Serrate-1 proteins can be identified by various assay methods, for example, physiological activity assaying methods using cell lines and animals such as mice and rats, assay methods of intracellular signal transduction based on molecular biological means, binding with Notch receptor etc.
We have observed actions for blood undifferentiated cells by using IgG1 chimera proteins of human Delta-1 and human Serrate-1.
As a result, we have found that, as shown in Example 10, in the umbilical cord blood derived blood undifferentiated cells, in which CD34 positive cell fraction is concentrated, polypeptides of the present invention have suppressive action of colony forming action against blood undifferentiated cells, which shows colony formation in the presence of cytokines. The suppressive action is only observed in the presence of SCF. This kind of effect has never been known.
As shown in Example 11, we have found that a maintenance of colony forming cells is significantly extended by addition of IgG1 chimera protein of human Delta-1 or human Serrate-1 in the long term (8 weeks) liquid culture in the presence of cytokines such as SCF, IL-3, IL-6, GM-CSF and Epo. Further we have found that the polypeptides of the present invention had an action not to suppress growth of the colony forming cells. A cytokine, MIP-1 xcex1having migration and differentiation suppressive action of blood cells (Verfaillie et al., J. Exp. Med. 179, 643-649, 1994), has no action for maintaining undifferentiation for blood undifferentiated cells.
Further as shown in Example 12, we have found that as a result of adding IgG1 chimera protein of human Delta-1 or human Serrate-1 to the liquid culture in the presence of cytokines, the human Delta-1 and human Serrate-1 had activities for significantly maintaining LTC-IC (Long-Term Culture-Initiating Cells) number, which is positioned most undifferentiated blood stem cells in the human blood undifferentiated cells.
These results indicate that the human Delta-1 and human Serrate-1 suppress differentiation of blood undifferentiated cells, and these actions spread from blood stem cells to colony forming cells. These physiological actions are essential for in vitro expansion of blood undifferentiated cells. Cells cultured in the medium containing human Delta-1 or human Serrate-1 are efficient in recovery of suppresion of bone marrow after administration of antitumor agents, accordingly in vitro growth of hemopoietic stem cells may be possible if other conditions would be completed. Further pharmaceuticals containing the polypeptide of the present invention have action protection and release of the bone marrow suppressive action, which is observed in adverse effects of antitumor agents.
Suppressive action for differentiation of cells in the undifferentiated cells other than blood cells is expected and stimulating action for tissue regeneration can be expected.
In the pharmaceutical use, polypeptides of the present invention are lyophilized with adding preferable stabilizing agents such as human serum albumin, and is used in dissolved or suspended condition with distilled water for injection when it is in use. For example, preparation for injection or infusion at the concentration of 0.1-1000 xcexcg/ml may be provided. A mixture of the compound of the present invention 1 mg/ml and human serum albumin 1 mg/ml divided in a vial could maintain activity of the said compound for long term. For culturing and activating cells in vitro, lyophilized preparation or liquid preparation of the polypeptide of the present invention are prepared and are added to the medium or immobilized in the vessel for culture. Toxicity of the polypeptide of the present invention was tested. Any polypeptide, 10 mg/kg was administered intraperitoneally in mice, but no death of mice was observed.
In vitro physiological activity of the polypeptide of the present invention can be evaluated by administering to disease model mice or its resembled disease rats or monkeys, and examining recovery of physical and physiological functions and abnormal findings. For example, in case of searching abnormality in relation to hemopoietic cells, bone marrow suppressive model mice are prepared by administering 5-FU series of antitumor agents, and bone marrow cell counts, peripheral blood cell counts and physiological functions are examined in the administered group or the non administered group of mice. Further, in case of searching in vitro cultivation and growth of hemopoietic undifferentiated cells including hemopoietic stem cells, the bone marrow cells of mice are cultured in the groups with or without addition of the compound of the present invention, and the cultured cells are transferred into the lethal dose irradiated mice. Result of recovery is observed with the indications of survival rate and variation of blood counts. These results can be extrapolated to the humans, and accordingly useful effective data for evaluation of the pharmacological activities of the compound of the present invention can be obtained.
Applications of the compound of the present invention for pharmaceuticals include diseases with abnormal differentiation of cells, for example leukemia and malignant tumors. These are cell therapy, which is performed by culturing human derived cells in vitro while maintaining their original functions or adding new functions, and a therapy, which is performed by regenerating without damaging the functions orginally existing of the originally existed in the tissues by administering the compound of the present invention under the regeneration after tissue injury. Amount of administration may differ in the type of preparation and ranges from 10 xcexcg/kg to 10 mg/kg.
Further strong physiological activity can be achieved by expression of forming multimer of the polypeptide of the present invention.
As shown in Example 10, since the suppressive action of human Delta-1 and human Serrate-1 is stronger in the IgG chimera protein having dimer structure, a form of stronger physiological activity is preferably expressed in the form of multimer formation.
Human Delta-1 and human Serrate-1 having multimer structure can be produced by a method of expressing chimera protein with human IgG Fc region as described in the example and expressing the multimer having disulfide bond with hinge region of the antibody, or a method expressing chimera protein, in which antibody recognition region is expressed in the C-terminal or N-terminal, and reacting with the polypeptide containing extracellular part of the thus expressed said human Delta 1 and Human Serrate 1 and the antibody which recognize specifically the antibody recognition region in the C-terminal or N-terminal. In the other methods, a method, in which a fused protein expressed with only the hinge region of the antibody and the dimerized by disulfide bond, can be mentioned. The multimer of human Delta-1 and human Serrate-1 having higher specific activity than the dimer can be obtained. The said multimer is constructed by fused protein which is prepared for expressing the peptide in the C-terminal, N-terminal or other region. The protein is prepared in the form of forming disulfide bond without effecting in any activities of the other human Delta-1 or human Serrate-1. The multimer structure can also be expressed by arranging one or more peptide, which is selected from polypeptides containing amino acids sequence of the sequence listing, SEQ ID NO: 2, 3, 5 or 6, with genetic engineering method in series or in parallel. Other known methods for providing multimer structure having dimer or higher can be applied. Accordingly, the present invention includes any polypeptides containing amino acid sequences described in the sequence listing, SEQ ID NO: 2, 3, 5 or 6 in the form of dimer or higher structure prepared by genetic engineering technique.
Further in the other method, multimerization method using chemical cross-linker can be mentioned. For example, dimethylsuberimidate dihydrochloride for cross-linking lysine residue, N-(xcex3-maleimidebutyryloxy) succinimide for cross-linking thiol group of cysteine residue and glutaraldehyde for cross-linking between amino groups can be mentioned. The multimer with dimer or more can be synthesized by applying these cross-linking reactions. Accordingly, the present invention includes any polypeptides containing amino acid sequences described in the sequence listing, SEQ ID NO: 2, 3, 5 or 6 in the form of dimer or more structure prepared by chemical cross-linking agents.
In application of medical care in which cells are proliferated and activated in vitro and are returned to the body, human Delta-1 or human Serrate-1 of the form hereinabove can be added directly in the medium, but immobilization can also be made. Immobilization method includes applying amino group or carboxyl group in the peptide, using suitable spacers or the above mentioned cross-linkers, and the polypeptide can be covalently bound to the culture vessels. Accordingly, the present invention includes any polypeptides containing amino acid sequences described in the sequence listing, SEQ ID NO: 2, 3, 5 or 6 in the form of existing on the solid surface.
Since the natural human Delta-1 and human Serrate-1 are cell membrane proteins, differentiation suppressive action in Examples can be expressed by cocultivating with cells expressing these molecules and blood undifferentiated cells. Consequently, this invention includes cocultivation method with transformed cells by using DNA coding amino acid sequences in the sequence listing, SEQ ID NO: 2-7 and undifferentiated cells.
Expressed cell may be COS-7 cell as shown in Examples, but cells of human origin are preferable, and further expressed cells may be cell line or any of human in vivo blood cells and somatic cells. Consequently, the polypeptide can be expressed in vivo by integrated into vectors for gene therapy.
As shown in Example 10, FLAG chimera protein of human Delta-1 or human Serrate-1, both of which are low concentrated monomer, shows not a colony formation suppressive action but a colony formation stimulating action. This action may be involved in expressing Notch receptor and Notch ligand in the occasion of cell division of blood undifferentiated cells and acting the polypeptide of the present invention as an antagonist for that action. This suggests that the polypeptide having amino acid sequence of the sequence listing, SEQ ID NO: 1, 2, 4 or 5, shows colony formation stimulation action by controlling the concentration of its action.
This fact suggests that inhibition of binding the polypeptide having amino acid sequence in the sequence listing, SEQ ID NO: 2-7 and these receptors can be used for finding out molecules and compounds for stimulating cell differentiation. The methods include binding experiment using radio isotope, luciferase assay using transcriptional control factors, a down stream molecule of the Notch receptor, and simulation on the computer by X-ray structural analysis. Accordingly, the present invention includes screening method for pharmaceuticals using polypeptide in the sequence listing, SEQ ID NO: 2-7.
As shown in Example 13, specific leukemia cells can be differentiated by using IgG chimera protein of human Delta-1 or human Serrate-1. Consequently, the present invention can be applied for diagnostic reagents for leukemia or isolation of specific blood cells. This result indicates that human Delta-1 or human Serrate-1 molecule binds specifically with its receptor, a Notch receptor molecule. For example, expression of Notch receptor can be detected by using fused protein with the above extracellular region and human IgGFc. Notch is known to involve in some type of leukemia (Ellisen et al., Cell 66, 649-661, 1991). Accordingly, the polypeptide having amino acids sequence in the sequence listing, SEQ ID NO: 2, 3, 5 and 6 can be used for diagnostic reagents for in vitro or in vivo. | {
"pile_set_name": "USPTO Backgrounds"
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In aircraft construction, the use of polymers with strong adhesion to substrates may be required for various reasons, including for forming and/or protecting components of the aircraft, such as the fuselage, wings, and others. Many structures, such as aircraft structures, include a plurality of assemblies that may create gaps, edges, ledges, and other discontinuities where elements of the assemblies interface. Efficient and safe operation of an aircraft, for example, requires that such discontinuities be sealed. Thus, polymers may be used for sealing surface discontinuities, such as encapsulating gaps, edges, ledges and other discontinuities on aircraft structures. When dispensing polymers onto a surface of a substrate, e.g., an aircraft part or aircraft assembly, it is often important to control one or more properties of the polymer, such as its profile or shape. Conventional manufacturing processes that require forming of polymers into complex geometries, are subject to a time-intensive process that include hand-working a high viscosity pre-polymer with the aid of volatile solvents. To increase viscosity, an existing solution is to use fillers within the uncured pre-polymer, which allows for applying the material manually onto the substrate. Yet even such high viscosity polymers require extensive manipulation by skilled mechanics/technicians and high viscosity materials may be difficult to clean, especially when working with substances having short cure times. Additionally, increasing of viscosity in order to allow for manipulation of the polymer into complex shapes results in lower adhesion of such polymers onto the substrates. What is needed in the art, therefore, is a method of forming curable polymers into complex shapes that allows for the use of lower viscosity curable polymers. | {
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This invention relates to an engine control strategy and system and more particularly to an improved control strategy and system for direct cylinder injected, two cycle, internal combustion engines.
The advantages afforded by the simplicity of two cycle engines is well recognized. Also, the ability of these engines to produce greater horsepower per displacement than four cycle engines due to their firing every cycle of rotation is acknowledged. However, because of the overlap in the scavenging and exhaust cycles and other factors, environmental concerns are making the use of two cycle engines more difficult.
One way in which the performance of a two cycle engine can be significantly improved and, at the same time, the fuel economy and exhaust emission control can be improved is through the use of direct cylinder fuel injection. With this type of injection system, fuel is injected directly into the combustion chamber for combustion therein. By utilizing direct cylinder injection, it may be possible to obtain stratification of the charge and, accordingly, exhaust emission and fuel economy improvement.
However, the fact that exhaust port is opened during a portion of the intake or scavenging cycle gives rise to the possibility that injected fuel can be swept out of the exhaust port. Therefore, it has generally been the practice to inject the fuel very late in the compression cycle and oftentimes fuel injection begins immediately after the exhaust port is closed and before the piston has reached its top dead center position. Such a practice will ensure that fuel does not pass out of the exhaust port.
However, this late injection of fuel, particularly under lower speed and load conditions gives rise to a very great difficulty in obtaining proper mixing in the combustion chamber. That is, when the fuel is injected late, there is less turbulence and airflow in the combustion chamber. This result in poor mixing and incomplete combustion.
It is, therefore, a principal object of this invention to provide an improved direct injected two cycle engine and operating strategy.
It is a further object of this invention to provide a fuel control arrangement for a direct injected two cycle engine wherein the timing of the fuel injection is governed so as to ensure that fuel will not pass out of the exhaust port but also so that the fuel is well mixed in the combustion chamber before ignition timing.
To improve the operation of direct injected, two cycle engines, a system has been proposed by us that is described in the co-pending application entitled, "Control for Direct Injected Two Cycle Engine", Ser. No. 09/188,953, Filed Nov. 10, 1998, now U.S. Pat. No. 6,058,908 and assigned to the Assignee hereof. As disclosed therein the injection initiation and duration is controlled so as to minimize the likelihood of fuel escaping from the exhaust port while still obtaining maximum power output. In accordance with that arrangement, the initial fuel injection is begun at a point when the exhaust port is still open but at a time wherein the fuel injected will not reach the exhaust port during the time when the exhaust port is still open. Basically, injection is done while the exhaust port is open rather than delaying it until after it closes as with more conventional methodologies.
In order to achieve this result and still avoid the likelihood that unburned fuel may pass out of the exhaust port, further improvements are believed to be possible. For example, the premise of our aforenoted pending application is based upon injecting so that the duration will end at a time when the first injected fuel will not yet have reached the exhaust port before it has closed. However, it has been discovered that factors may be present in the combustion chamber that can effect the time at which this event occurs.
It is, therefore, a principle object of this invention to provide an improved engine control strategy and system for a direct injected two-cycle engine.
It is a further object of this invention to provide an improved engine control strategy and system for a direct injected two-cycle engine wherein in-cylinder conditions are considered in determining the injection timing.
In conjunction with direct injection in the cylinder, it is also important that the fuel be injected at such a time and for such a duration that it will well mix in the combustion chamber. Unless the fuel is well mixed with the surrounding air, the particles may be too large to completely burn during the combustion cycle.
It is, therefore, a still further object of this invention to provide an improved fuel injection control and method therefor that will improve the efficiency of two-cycle engines while still maintaining good exhaust emission control. | {
"pile_set_name": "USPTO Backgrounds"
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In certain industries it is valuable to characterise particular materials. To do so, sensors can be configured to move with respect to a particular material and signals passed into or through the material. In some cases, the sensors may be moved while the material remains stationary, while in other cases the material may be moved and the sensors remain stationary. In some cases, the sensors may be mechanically touching the material, in other cases, they may not (e.g. acoustic, optical sensors, or the like).
The data output of such sensors is usable to provide a characteristic of the material being measured. This measured characteristic may provide a characteristic image or map of the material itself, or may be useable to reconstruct further data or information encoded with or within the material. The measured characteristic may be representative of the body of the material, and/or the surface or surface region of the material.
Examples of such moving sensors include a tape head usable with magnetic tape, whereby the tape is moved with respect to a stationary, or relatively stationary, tape head, such that the characteristic magnetism of the tape can be measured. This characteristic can then be used to reconstruct audio, video or data. A further example is an image scanner, or facsimile machine. Again the material (i.e. paper, or the like) is moved relative to an optical sensor. The data output of the sensor is usable to provide an image of the paper, or indeed, what is composed on the paper.
By maintaining the relative speed of such sensors to be constant or at least roughly constant, samples can be taken at particular intervals, such as regular intervals, along the material. These samples can then be used to provide a characteristic of the material.
However, because such sensors are being moved (and/or the material is being moved) certain variations in relative speed can arise. In the examples described above, motors used to wind or pull magnetic tape may have an eccentric motion causing a resultant variation in acoustic frequency (i.e. flutter, etc.) when the signal is reconstructed into an audio characteristic. Similarly, the tape itself may have been pulled or stretched, causing an apparent change in speed having the same effect on a reconstructed audio characteristic. In the case of a scanner, paper may jam, or be pulled awkwardly through a machine, resulting in the commonly-seen elongating or contracting of images when data is reconstructed into a copy of images provided on paper.
To compensate for these variations in relative speed, sensors may be used that mechanically interact with the material being characterised. As a result, variations in speed may be caused due to the sensor temporarily sticking or jamming on the material (e.g. as a result of frictional effects). The release of this sticking or jamming may result in a “ping back” effect, whereby the sensor or material accelerates for a time in the other, or opposite, direction. Other effects, such as the variations in roughness or friction of a surface, etc. may also cause variations in speed.
As a result of sensors experiencing these speed variations (e.g. either because the movement of material/sensor cannot be sufficiently controlled or because of sticking/jamming), it can be difficult to provide accurate data derived from such sensors.
An example of an industry that attempts to provide characteristic maps of a material using relatively moving sensors is the oil and gas industry. One such process that uses such techniques is referred to as logging, where boreholes drilled into the ground are characterised by pulling a measurement module, or so-called logging tool, through those holes. In such cases, it can be valuable to measure precisely the characteristics, or formation, of subterranean material through which a borehole passes. This information might be useful when exploring for oil and gas. For example, it can be useful to determine precisely the formation and location of particular strata formations from pilot boreholes: those used to determine the possible location of one or more hydrocarbon reservoirs. By identifying accurately the locations and presence of particular strata, the location of reservoirs can be suggested.
Such logging tools generally comprise a plurality of sensors. Some of these sensors may, in some cases, be displaced in the direction of travel from each other (e.g. the sensors may be configured in rows). As these logging tools are pulled through a borehole, the sensors are configured to touch, or at least communicate with, the wall of the borehole and characterise the associated subterranean material. However, regardless of how carefully the logging tools are pulled, variations in the speed of the tools occur. In addition, each sensor can experience localised variation due to frictional or so-called rumble effects, or the like.
Accelerometers comprised with sensors/tools have been used in order to correct data derived from tools experiencing a deviation in speed that occurred as the logging tool was being drawn through a borehole. However, there are several problems associated with using such accelerometers, which means that the quality of the results is severely limited. Firstly, due to the high forces involved, two or more different accelerometers are needed for each sensor or in order to cover the range of motion (i.e. high and low acceleration). The nature of the mathematical transformations involved when using accelerometers is approximate. Furthermore, the accelerometers can be difficult to calibrate, and in addition, are rarely calibrated when used in real life. Also, due to the harsh environments, the devices are often damaged due to being dropped or knocked, etc.
Correction for speed deviations of sensors/tools based on accelerometer data, or so-called kinematic correction, is not entirely satisfactory. As the resolving power of sensors, such as those provided with logging tools, increases the deficiencies of existing kinematic correction techniques are becoming more noticeable, and thus the information which can be inferred from such data is limited.
This background serves to set a scene to allow a skilled reader to better appreciate the following description. Therefore, none of the above discussion should necessarily be taken as an acknowledgement that that discussion is part of the state of the art or is common general knowledge. One or more aspects/embodiments of the invention may or may not address one or more of the background issues. | {
"pile_set_name": "USPTO Backgrounds"
} |
Many members of the HDAC family require zinc (Zn) to function properly. For instance, the isozyme histone deacetylase 6 (HDAC6) is a zinc-dependent histone deacetylase that possesses histone deacetylase activity. Other family members include HDACs 1-5 and 7-11. (De Ruijter et al, Biochem. J. 2003. 370; 737-749).
HDAC6 is known to deacetylate and associate with α-tubulin, cortactin, heat shock protein 90, ß-catenin, glucose-regulated protein 78 kDa, myosin heavy chain 9, heat shock cognate protein 70, and dnaJ homolog subfamily A member 1 (reviewed in Li et al, FEBS J. 2013, 280: 775-93; Zhang et al, Protein Cell. 2015, 6(1): 42-54). Diseases in which HDAC6 inhibition could have a potential benefit include cancer (reviewed in Aldana-Masangkay et al, J. Biomed. Biotechnol. 2011, 875824), specifically: multiple myeloma (Hideshima et al, Proc. Natl. Acad. Sci. USA 2005, 102(24):8567-8572); lung cancer (Kamemura et al, Biochem. Biophys. Res. Commun. 2008, 374(1):84-89); ovarian cancer (Bazzaro et al, Clin. Cancer Res. 2008, 14(22):7340-7347); breast cancer (Lee et al, Cancer Res. 2008, 68(18):7561-7569; Park et al, Oncol. Rep. 2011, 25: 1677-81; Rey et al, Eur. J. Cell Biol. 2011, 90: 128-35); prostate cancer (Seidel et al, Biochem Pharmacol. 2015 (15)00714-5); pancreatic cancer (Nawrocki et al, Cancer Res. 2006, 66(7):3773-3781); renal cancer (Cha et al, Clin. Cancer Res. 2009, 15(3): 840-850); hepatocellular cancer (Ding et al, FEBS Lett. 2013, 587:880-6; Kanno et al, Oncol. Rep. 2012, 28: 867-73); lymphomas (Ding et al, Cancer Cell Int. 2014, 14:139; Amengual et al, Clin Cancer Res. 2015, 21(20):4663-75); and leukemias such as acute myeloid leukemia (AML) (Fiskus et al, Blood 2008, 112(7):2896-2905) and acute lymphoblastic leukemia (ALL) (Rodriguez-Gonzalez et al, Blood 2008, 1 12(1 1): Abstract 1923)).
Inhibition of HDAC6 may also have a role in cardiovascular disease, including pressure overload, chronic ischemia, and infarction-reperfusion injury (Tannous et al, Circulation 2008, 1 17(24):3070-3078); bacterial infection, including those caused by uropathogenic Escherichia coli (Dhakal and Mulve, J. Biol. Chem. 2008, 284(1):446-454); neurological diseases caused by accumulation of intracellular protein aggregates such as Alzheimer's, Parkinson's and Huntington's disease (reviewed in Simoes-Pires et al, Mol. Neurodegener. 2013, 8: 7) or central nervous system trauma caused by tissue injury, oxidative-stress induced neuronal or axomal degeneration (Rivieccio et al, Proc. Natl. Acad. Sci. USA 2009, 106(46):19599-195604); and inflammation and autoimmune diseases through enhanced T cell-mediated immune tolerance at least in part through effects on regulatory T cells, including rheumatoid arthritis, psoriasis, spondylitis arthritis, psoriatic arthritis, multiple sclerosis, lupus, colitis and graft versus host disease (reviewed in Wang et al, Nat. Rev. Drug Disc. 2009 8(12):969-981; Vishwakarma et al, Int. Immunopharmacol. 2013, 16:72-8; Kalin et al, J. Med Chem. 2012, 55:639-51); and fibrotic disease, including kidney fibrosis (Choi et al, Vascul. Pharmacol. 2015 72:130-140).
Four HDAC inhibitors are currently approved for the treatment of some cancers. These are suberanilohydroxamic acid (Vorinostat; Zolinza®) for the treatment of cutaneous T cell lymphoma and multiple myeloma; Romidepsin (FK228; FR901228; Istodax®) for the treatment of peripheral T cell lymphoma; Panobinostat (LBH-589; Farydak®) for the treatment of multiple myeloma; and belinostat (PXD101; Beleodaq®) for the treatment of peripheral T cell lymphoma. However, these drugs are of limited effectiveness and can give rise to unwanted side effects. Thus there is a need for drugs with an improved safety-efficacy profile.
Given the complex function of HDAC6 and their potential utility in the treatment of proliferative diseases, neurological diseases, and inflammatory diseases, there is a need for HDAC inhibitors (e.g., HDAC6 inhibitors) with good therapeutic properties. | {
"pile_set_name": "USPTO Backgrounds"
} |
The present invention relates in general to new, improved and more efficient apparatus for producing domestic hot water (hereinafter sometimes "DHW"), and more particularly to an ancillary heat pump (hereinafter sometimes "AHP") system for such purpose.
Experts within the electric utility industry have determined that the 1990 Federal Clean Air Act and other regulatory action may necessitate replacement of resistance electric heat water heating technology, due to the primary energy intensiveness of the operation of such technology. Some public utility commissions have mandated that the electric utilities replace those residential electric hot water heaters utilizing fossil fuel-fired heaters. Thus, the potential loss of the controllable load of over 20,000,000 residential electric hot water heaters has been of major concern for the utilities. In addition, these energy-related factors have presented utility companies with major marketing problems in regard to new residential construction.
The above problems which are principally related to large levels of primary energy consumption have engendered the search for more energy efficient means of producing domestic hot water. Presently available systems for producing domestic hot water, include, inter alia, integrated and combined space conditioning and water heating heat pump apparatus, self-contained heat pump water heaters, desuperheaters and full condensers (some of which are provided as add-ons to condensing units), heat pipe dehumidification apparatus, and similarly related apparatus.
However, each of these presently available prior art methodologies has associated therewith one or more serious application and/or cost effectiveness problems. Some of the problems associated with the prior art are:
1. the necessity for protecting potable water lines from freezing with an add-on reclaim heat exchanger mounted within an outdoor (condensing) unit; PA0 2. the major additional cost of providing a module with the compressor located indoors; PA0 3. field modification of the refrigerant piping system; and PA0 4. installation cost and application problems associated with dedicated heat pump hot water heaters.
In view of the above difficulties, defects and deficiencies with prior art domestic hot water production systems, it is a material object of the present invention to reduce significantly each of the above and other problems associated therewith.
It is a further object of the present invention to provide an ancillary heat pump system for production of domestic hot water wherein a preferably small and self-contained heat pump having a co-axial heat exchanger and compressor is disposed, in one preferred embodiment, with a heat exchanger coil thereof directly in the return air stream of a heat pump or of a heating and air conditioning system.
It is also an object of the present invention to provide means for injecting the associated cooling effect hereof directly into an accompanying heating and air conditioning system, rather than merely "dumping" such associated cooling effect into the space around the heater tank.
It is also a further object of the present invention to provide apparatus wherein there is no necessity to pipe potable water into an outdoor environment, or, as an alternative, to repipe extensively the refrigeration circuit of the condensing unit to an indoor heat exchanger location, but rather to keep the HVAC and hot water system refrigeration circuits totally isolated, so that there is no risk of water contaminating the HVAC refrigeration system in the event of a heat exchanger failure.
It is a yet further object of the present invention to provide hot water efficiently during the heating season regardless of the type of space heating fuel being used.
These and other objects of the ancillary heat pump apparatus for providing domestic hot water of the present invention will become more apparent to those skilled in the art upon review of the following summary of the invention, brief description of the drawing, detailed description of preferred embodiments, appended claims and accompanying drawing. | {
"pile_set_name": "USPTO Backgrounds"
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Transceivers are used in wireless communications to transmit and receive electromagnetic waves in free space. In general, a transceiver comprises three main components: a transmitter, a receiver, and an LO generator or frequency synthesizer. The function of the transmitter is to modulate, upconvert, and amplify signals for transmission into free space. The function of the receiver is to detect signals in the presence of noise and interference, and provide amplification, downconversion and demodulation of the detected the signal such that it can be displayed or used in a data processor. The LO generator provides a reference signal to both the transmitter for upconversion and the receiver for downconversion.
Transceivers have a wide variety of applications ranging from low data rate wireless applications (such as mouse and keyboard) to medium data rate Bluetooth and high data rate wireless LAN 802.11 standards. However, due to the high cost, size and power consumption of currently available transceivers, numerous applications are not being fully commercialized. A simplified architecture would make a transceiver more economically viable for wider applications and integration with other systems. The integration of the transceiver into a single integrated circuit (IC) would be an attractive approach. However, heretofore, the integration of the transceiver into a single IC has been difficult due to process variations and mismatches. Accordingly, there is a need for an innovative transceiver architecture that could be implemented on a single IC, or alternatively, with a minimum number of discrete off-chip components that compensate for process variations and mismatches. | {
"pile_set_name": "USPTO Backgrounds"
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Point-to-Point Protocol over Ethernet (PPPoE), has been widely used as the Internet protocol for ADSL broadband deployment. As providers deploy ADSL service, they often prefer supporting PPP-style authentication and authorization over a large installed base of legacy bridging customer premises (CPE). PPPoE provides the ability to connect a network of hosts over a simple bridging access device to a remote access concentrator or aggregation concentrator. With this model, each host uses its own PPPoE stack, presenting the user with a familiar user interface. Access control, billing, and type of service can be handled on a per user basis, rather than a per site basis.
Internet Protocol (IP) phones have been used to provide Voice over Internet Protocol (VoIP) service to the business enterprise environment. Typically, a VoIP phone set connects to the corporate data network through Ethernet connection and to a voice enabled router in the corporation. Traditionally, the IP parameters for the VoIP phone are statically assigned by the network administrator, or dynamically assigned through DHCP within the corporate network. With increasing attraction of VoIP application in the telecommunication community, the deployment of VoIP phones at a consumer broadband subscriber's location to provide additional phone service has started getting much attention with broadband service providers.
Maintaining Toll Quality of a VoIP service requires detailed planning of the VoIP network. Network delay and network jitter affect voice quality greatly. Several existing consumer VoIP deployments, such as Net2Phone Voice Service and Vonage VoIP Service, utilize the existing broadband access as the transport channel for the VoIP service. The quality of these voice services can be degraded due to network congestion. In the existing deployment model, the device which enables VoIP service in the customer premises relies on other devices on the LAN to initiate a PPPoE session, usually a home gateway or a PC. The particular LAN configuration can also have great impact on the voice quality.
Accordingly, there is a need for an improved VoIP telephone and communication system for communicating VoIP traffic. | {
"pile_set_name": "USPTO Backgrounds"
} |
A TMR sensor otherwise known as a magnetic tunneling junction (MTJ) is a key component in magnetic devices such as Magnetic Random Access Memory (MRAM) and a magnetic recording head. A TMR sensor typically has a stack of layers with a configuration in which two ferromagnetic layers are separated by a thin non-magnetic insulator layer. The sensor stack in a so-called bottom spin valve configuration is generally comprised of a seed (buffer) layer, anti-ferromagnetic (AFM) layer, pinned layer, tunnel barrier layer, free layer, and capping layer that are sequentially formed on a substrate. The free layer serves as a sensing layer that responds to external fields (media field) while the pinned layer is relatively fixed and functions as a reference layer. The electrical resistance through the tunnel barrier layer (insulator layer) varies with the relative orientation of the free layer moment compared with the reference layer moment and thereby converts magnetic signals into electrical signals. In a magnetic read head, the TMR sensor is formed between a bottom shield and a top shield. When a sense current is passed from the top shield to the bottom shield (or top conductor to bottom conductor in a MRAM device) in a direction perpendicular to the planes of the TMR layers (CPP designation), a lower resistance is detected when the magnetization directions of the free and reference layers are in a parallel state (“1” memory state) and a higher resistance is noted when they are in an anti-parallel state or “0” memory state. Alternatively, a TMR sensor may be configured as a current in plane (CIP) structure which indicates the direction of the sense current.
A giant magnetoresistive (GMR) head is another type of memory device. In this design, the insulator layer between the pinned layer and free layer in the TMR stack is replaced by a non-magnetic conductive layer such as copper.
In the TMR stack, the pinned layer may have a synthetic anti-ferromagnetic (SyAF) configuration in which an outer pinned layer is magnetically coupled through a coupling layer to an inner pinned layer that contacts the tunnel barrier. The outer pinned layer has a magnetic moment that is fixed in a certain direction by exchange coupling with the adjacent AFM layer which is magnetized in the same direction. The tunnel barrier layer is so thin that a current through it can be established by quantum mechanical tunneling of conduction electrons.
A TMR sensor is currently the most promising candidate for replacing a GMR sensor in upcoming generations of magnetic recording heads. An advanced TMR sensor may have a cross-sectional area of about 0.1 microns×0.1 microns at the air bearing surface (ABS) plane of the read head. The advantage of a TMR sensor is that a substantially higher MR ratio can be realized than for a GMR sensor. In addition to a high MR ratio, a high performance TMR sensor requires a low areal resistance RA (area×resistance) value, a free layer with low magnetostriction (λ) and low coercivity (Hc), a strong pinned layer, and low interlayer coupling (Hin) through the barrier layer. The MR ratio (also referred to as TMR ratio) is dR/R where R is the minimum resistance of the TMR sensor and dR is the change in resistance observed by changing the magnetic state of the free layer. A higher dR/R improves the readout speed. For high recording density or high frequency applications, RA must be reduced to about 1 to 3 ohm-um2.
A MgO based MTJ is a very promising candidate for high frequency recording applications because its tunneling magnetoresistive (TMR) ratio is significantly higher than for AlOx or TiOx based MTJs as demonstrated by S. Yuasa et al. in “Giant room-temperature magnetoresistance in single crystal Fe/MgO/Fe magnetic tunnel junctions”, Nature Materials, 3, 868-871 (2004), and in “Giant tunneling magnetoresistance up to 410% at room temperature in fully epitaxial Co/MgO/Co magnetic tunnel junctions with bcc Co(001) electrodes”, Appl. Phys. Lett., 89, 042505 (2006), and by S. Parkin et al. in “Giant tunneling magnetoresistance at room temperature with MgO (100) tunnel barriers”, Nature Materials, 3, 862-867 (2004).
CoFeB has been used in the free layer for MgO based MTJs to achieve high MR ratio and a soft magnetic layer. D. Djayaprawira et al. showed that MTJs with a CoFeB/MgO(001)/CoFeB structure made by conventional sputtering can also have a very high MR ratio of 230% with advantages of better flexibility and uniformity in “230% room temperature magnetoresistance in CoFeB/MgO/CoFeB magnetic tunnel junctions”, Physics Letters 86, 092502 (2005).
For a low RA application, the MR ratio of CoFeB/Mg/MgO/CoFeB MTJs can reach 138% at RA=2.4 ohm/μm2 according to K. Tsunekawa et al. in “Giant tunneling magnetoresistance effect in low resistance CoFeB/MgO(001)/CoFeB magnetic tunnel junctions for read head applications”, Applied Physics Letters 87, 072503 (2005). In this case, a DC-sputtered Mg layer was inserted between the CoFeB pinned layer and an RF-sputtered MgO layer, an idea initially proposed by T. Linn et al. in U.S. Pat. No. 6,841,395 to prevent oxidation of the bottom electrode (CoFe) in a CoFe/MgO(reactive sputtering)/NiFe structure. Also, a Ta getter pre-sputtering prior to RF sputtering a MgO layer can achieve 55% TMR with 0.4 ohm/μm2 as reported by Y. Nagamine et al. in “Ultralow resistance-area product of 0.4 ohm/μm2 and high magnetoresistance above 50% in CoFeB/MgO/CoFeB magnetic junctions”, Appl. Phys. Lett., 89, 162507 (2006).
In order to achieve a smaller Hc but still maintain a high TMR ratio, the industry tends to use CoFeB as the free layer in a TMR sensor. Unfortunately, the magnetostriction (λ) of a CoFeB free layer is considerably greater than the maximum acceptable value of about 5×10−6 for high density memory applications. A free layer made of a CoFe/NiFe composite has been employed instead of CoFeB because of its low λ and soft magnetic properties. However, when using a CoFe/NiFe free layer, the TMR ratio will degrade. Another approach is a composite free layer containing CoFeB with a positive λ and a NiFe layer with a negative λ to result in a low λ and magnetic softness for the free layer. However, a CoFeB/NiFe type free layer structure is not usable because direct contact of CoFeB with NiFe will cause a drastic drop in the MR (TMR) ratio. Thus, an improved free layer in a TMR sensor is needed that provides low magnetostriction in combination with a high TMR ratio, low RA value, and low coercivity.
U.S. Pat. No. 7,333,306 and U.S. Patent Application 2007/0047159 show a tri-layered free layer represented by CoFe/CoFeB/NiFe to achieve low coercivity and low magnetostriction for either GMR-CPP or TMR sensors.
In U.S. Patent Application No. 2007/0139827, a free layer is described that includes a sense enhancing layer (Ta) sandwiched between a first ferromagnetic (FM) layer and a second FM layer. The first FM layer has a positive magnetostriction and is made of CoFeB or CoFe based alloys while the second FM layer has negative magnetostriction and is comprised of CoFe, Ni, or NiFe based alloys.
U.S. Patent Application No. 2007/0188942 discloses a free layer comprised of three layers that include a lower NiFe or CoFe layer on the tunnel barrier layer, a Ta, Ru, Cu, or W spacer, and a CoFeB, CoFe, or NiFe upper layer.
U.S. Patent Application No. 2008/0061388 discloses a free layer with a CoFeB/Ru/CoFeTaB configuration.
U.S. Pat. No. 6,982,932 and U.S. Patent Application 2008/0152834 describe free layers that are laminations of NiFe, CoFe, and CoFeB.
A MgO tunnel barrier is formed using a natural oxidation procedure as described in U.S. Patent Application 2007/0111332. | {
"pile_set_name": "USPTO Backgrounds"
} |
It is desirable to remove particles from a fluid for improving cleanliness or safety of an environment, for removing undesirable particles that otherwise may interfere with efficiency or operational life of a device, or for other purposes. It is also important in many applications to remove particles in an efficient and economical way, and to remove particles having a relatively small size.
There are many existing methods for removing particles from a fluid (for example, air). Contact-based methods may be used, such as fiber and other media filters and water or oil scrubbers. Another particle removal method employs electrostatic precipitators. However, such methods often require relatively large quantities of airflow through filtration media so that particles may be captured and removed from the air. Fiber and electrostatic filters, for example, require a medium for making physical contact with the particles to remove them from an air stream. Particles quickly accumulate onto the filtration media, and thus the media is cleaned or replaced frequently, resulting in high maintenance costs. For many dusty environments, such an air cleaning process requires frequent maintenance, including replacement of filters.
Other, non-contact air cleaning devices remove particles from a fluid aerodynamically, rather than by passing the fluid through a filtration media. Certain non-contact devices use centrifugal force to separate particles from a main air stream. These so-called cyclones create spiral airflow at a very high speed to separate particles from the air. The tornado-like particle separation process involves no contact media, and thus does not require frequent cleaning or replacement of a filter media. Additional non-contact devices include louver and baffle types, and settling chambers.
There are two principal types of cyclone air cleaning devices: return flow and uniflow. A return flow cyclone allows air to return, while a uniflow cyclone does not. Due to differences in airflow between these two types of devices, the particle separation processes are quite different.
A large amount of research has been conducted for return flow aerodynamic air cleaning devices, for example, for air sampling purposes, while a relatively smaller amount of research has been conducted for uniflow cyclones. However, though return flow cyclones allow a small particle cutsize (the size of a particle for which collection efficiency is at least 50%), they are energy intensive and have low dust separation efficiency. Furthermore, airflow velocities are very high in conventional cyclones. Accordingly, high turbulence and reentrainment of particles occur, resulting in low particle separation efficiency, especially for small particles.
Traditional cyclone particle separation devices have exhibited great difficulty in separating particles smaller than 10 μm from air. Separation of only larger particle sizes, however, is not particularly useful for conventional air cleaning purposes. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
The present invention relates to a guide wire, particularly to a guide wire used to guide a catheter in a body lumen such as a blood vessel.
2. Description of the Related Art
Guide wires are used to guide a catheter in treatment of sites at which open surgeries are difficult or which require minimally invasiveness to the body, for example, PTCA (Percutaneous Transluminal Coronary Angioplasty), or in examination such as cardio-angiography. A guide wire used in the PTCA procedure is inserted, with the distal end projecting from the distal end of a balloon catheter, into the vicinity of a target angiostenosis portion together with the balloon catheter, and is operated to guide the distal end portion of the balloon catheter to the target angiostenosis portion.
A guide wire used to insert a catheter into a blood vessel complicatedly bent requires appropriate flexibility and restoring performance against bending, pushability and torque transmission performance (generically called “operationality”) for transmitting an operational force from the proximal end portion to the distal side, and kink resistance (often called “resistance against sharp bending”). To obtain appropriate flexibility as one of the above-described performances, there has been known a guide wire configured such that a metal coil having flexibility is provided around a small-sized core member at the distal end of the guide wire, or a guide wire including a core member made from a superelastic material such as an Ni—Ti alloy for improving the flexibility and restoring performance.
Conventional guide wires include a core member that is substantially made from a single material. In particular, to enhance the operationality of the guide wire, a material having a relatively high elastic modulus is used as the material of the core member. The guide wire including such a core member, however, has an inconvenience that the distal end portion of the guide wire becomes lower in flexibility. On the other hand, if a material having a relatively low elastic modulus is used as the material of the core member for increasing the flexibility of the distal end portion of the guide wire, the operationality of the proximal end portion of the guide wire is degraded. In this way, it has been regarded as difficult to satisfy both requirements associated with the flexibility and operationality by using a core member made from a single material.
A guide wire intended to solve such a problem has been disclosed, for example, in U.S. Pat. No. 5,171,383, wherein a Ni—Ti alloy wire is used as a core member, and the distal side and the proximal side of the alloy wire are heat-treated under different conditions in order to enhance the flexibility of the distal end portion of the alloy wire while enhancing the rigidity of the proximal side of the alloy wire. Such a guide wire, however, has a problem that the control of the flexibility of the distal end portion by heat-treatment has a limitation. For example, even if it is successful to obtain a sufficient flexibility of the distal end portion of the alloy wire, it may often fail to obtain a sufficient rigidity on the proximal side of the alloy wire. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
The present invention relates to an exhaust emission control device which controls regeneration of a diesel particulate filter to remove particulate matters contained in exhaust gas of an internal combustion engine and deposited in the filter.
2. Description of Related Art
For the environmental protection, it is necessary to purify exhaust gas outputted from an internal combustion engine of a vehicle. For example, it is necessary to remove particulate matters from exhaust gas of a diesel engine. To remove particulate matters, a diesel particulate filter (hereinafter, called DPF) is disposed in an exhaust pipe through which the exhaust gas outputted from the engine flows. The DPF normally has a filter formed in a honeycomb structure. This honeycomb filter catches and collects a major portion of particulate matters outputted from the engine, so that the exhaust gas is purified.
However, each time a certain quantity of particulate matters are deposited in the DPF, it is necessary to burn the deposited particulate matters for the purpose of regenerating the DPF. As a technique for burning the particulate matters, post injection of fuel is well known. In this post injection, fuel is injected into the engine at a timing retarded from a timing of the normal main injection of fuel.
As the post injection, both multi-post injection and single-post injection are known. In the multi-post injection, a series of fuel injections is performed after the main fuel injection. In the single-post injection, only one fuel injection is performed after the main fuel injection. In case of the multi-post injection, the combustion of fuel is continued in cylinders of the engine to rise the temperature of exhaust gas outputted from the engine. The temperature of the DPF receiving this exhaust gas is risen, so that particulate matters of the DPF are burned. That is, the DPF is purified in response to the temperature rise based on the exhaust gas (hereinafter, called exhaust gas-based temperature rise).
In contrast, in case of the single-post injection, a major portion of fuel injected in the post injection is not burned in the engine, so that unburned hydrocarbons are outputted from the engine and are fed to the DPF. In the DPF, the hydrocarbons are oxidized due to the catalytic reaction caused by catalyst of the DPF, so that the temperature of the DPF is risen by heat generated in the reaction of the hydrocarbons. Therefore, particulate matters of the DPF are burned. That is, the DPF is purified in response to the temperature rise based on hydrocarbons (hereinafter, called hydrocarbon-based temperature rise).
FIG. 1A shows the relationship between the injection valve lift position and the heat release rate in a diesel engine in case of the exhaust gas-based temperature rise, while FIG. 11 shows the relationship between the injection valve lift position and the heat release rate in a diesel engine in case of the hydrocarbon-based temperature rise.
As shown in FIG. 1A and FIG. 1B, main injection is performed at a timing of compression top dead center (TDC). After the main injection, multi-post injection or single-post injection is performed in a period of time between TDC and after top dead center 90 (ATDC90) Heat is generated in an engine in response to the multi-post injection, so that the temperature of exhaust gas is heightened. In contrast, no heat is substantially generated in response to the single-post injection, so that unburned hydrocarbons are outputted from the engine.
When particulate matters are deposited in the DPF, the particulate matters are often deposited in layers on the catalyst held on the front end surface of the DPF. In this case, it is difficult to burn the particulate matters deposited on the front end surface of the DPF by oxidizing unburned hydrocarbons. Therefore, to burn the particulate matters deposited on the front end surface of the DPF, it is required to heighten the temperature of the exhaust gas passing though the DPF.
In the exhaust system holding the catalyst on the upstream side of the DPF, the temperature of the exhaust gas is sometimes risen in response to the oxidation of hydrocarbons based on the catalytic reaction. Therefore, to burn the particulate matters deposited on the front end surface of the DPF, it is not necessary to heighten the temperature of the exhaust gas outputted from the engine. In contrast, in the single DPF system holding no catalyst on the upstream side of the DPF, to burn the particulate matters deposited on the front end surface of the DPF, it is indispensable to heighten the temperature of the exhaust gas outputted from the engine.
In the hydrocarbon-based temperature rise, unburned hydrocarbons not burned in cylinders of the engine are fed to the DPF and are oxidized based on the catalytic reaction, so that the temperature of the DPF is risen. Therefore, the temperature of the exhaust gas outputted from the engine is generally low. In contrast, in the exhaust gas-based temperature rise, fuel injected in the multi-post injection is continuously burned in the engine, so that the temperature of the exhaust gas is heightened. Therefore, the temperature of the exhaust gas outputted from the engine is high. Therefore, for the regeneration of the DPF in the single DPF system, the exhaust gas-based temperature rise is often used.
However, in the exhaust gas-based temperature rise, the heat of the exhaust gas outputted from the engine and flowing through the exhaust pipe is easily dissipated to the outside through the exhaust pipe before the exhaust gas is fed to the DPF. Therefore, to give the dissipated heat and the regeneration heat to the exhaust gas outputted from the engine, it is required to inject a large quantity of fuel in the post injection. In this case, because the temperature of the exhaust gas outputted from the engine is sufficiently heightened to reliably rise the temperature of the DPF, fuel is excessively consumed. Therefore, fuel economy in the vehicle deteriorates.
In contrast, in the combustion of the particulate matters deposited on the front end surface of the DPF, the hydrocarbon-based temperature rise is inferior to the exhaust gas-based temperature rise. However, to rise the temperature of the whole DPF, the hydrocarbon-based temperature rise is superior to the exhaust gas-based temperature rise. That is, in case of the hydrocarbon-based temperature rise, the temperature of the DPF is rapidly risen so as to rapidly regenerate the DPF, so that the deterioration of fuel economy can be suppressed. In the prior art, because only the exhaust gas-based temperature rise is used to regenerate the DPF, the merits of the hydrocarbon-based temperature rise are not obtained.
Assuming that an exhaust emission control device appropriately controls the regeneration of the DPF while considering the merits and demerits in both the exhaust gas-based temperature rise and the hydrocarbon-based temperature rise, the temperature of the DPF is rapidly risen, and fuel consumption in the DPF regeneration is suppressed.
For example, Published Japanese Patent First Publication No. 2007-23961 discloses a fuel injection control device. In this device, to improve the durability of the engine and to lengthen the maintenance interval, the dilution of oil caused by the usage of both the exhaust gas-based temperature rise and the hydrocarbon-based temperature rise is suppressed. More specifically, in response to engine conditions, the post injection for the exhaust gas-based temperature rise is performed for some of cylinders of the engine, and the post injection for the hydrocarbon-based temperature rise is performed for the other cylinders of the engine. That is, the injection mode is set for each cylinder to operate the cylinders according to different injection modes.
However, the prior art including the Publication No. 2007-23961 does not teach or even suggest a technique for alternately selecting the exhaust gas-based temperature rise and the hydrocarbon-based temperature rise to rapidly regenerate the DPF in the single DPF system holding no catalyst on the upstream side of the DPF. | {
"pile_set_name": "USPTO Backgrounds"
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The use of the Internet worldwide is ever increasing with a high growth rate in the developing countries around the world. However, many emerging business centers in regions near the Equator are handicapped by poor connectivity to the Internet. These centers are typically located in countries with limited national high bandwidth network infrastructure, and sometimes surrounded by either hostile neighbors or inhospitable terrain that makes terrestrial and undersea cable connections impractical.
Nevertheless, there is a continuing demand for high bandwidth connectivity to the Internet in these countries. Many of the most rapidly growing markets are both near the Equator and poorly connected via undersea cables. For some of the larger countries, the internal network infrastructure is relatively primitive. Furthermore, natural disasters can also disrupt connections, and the ability to rapidly reconfigure a communication network to reconnect the affected areas can be extremely valuable. In addition to the underserved markets, the major global telecom carriers of significant and growing wholesale bandwidth have needs for backup and replacement bandwidth to maintain Quality of Service agreements.
Geostationary Earth Orbit (GEO) communication satellites have inherently high latency, while other satellite communication networks suffer from some combination of limited worldwide connectivity, low bandwidth, or cost. The GEO satellites offer coverage of a reasonably large fraction of the Earth per satellite but have long communication paths (˜36,000 km) resulting in a signal latency of at least 120 msec per path. Moreover, multiple bounces may be required to provide routing, and connection between ground sites not within footprint of same satellite may require ground connections. Additionally, GEO communication satellites are currently restricted to Radio Frequency (RF) signals, which limit available bandwidth to a range of hundreds of MHz to a few GHz. Furthermore, multiple beams need to be used to provide relatively high total throughput per satellite (72 beams at 48 Mbps is typical, for 3.4 Gbps per satellite).
The “Other 3 Billion” (O3B) program is attempting to serve the same general equatorial region using Radio Frequency (RF) signals. As a result of RF usage, O3B has severe bandwidth restrictions. O3B uses a Medium Earth Orbit (MEO) constellation of 8 to 12 satellites in Equatorial orbit at 8,000 km. Each satellite will have up to 10 RF links that will (eventually) be capable of up to 1.2 Gbps per channel. The constellation is rated at 70 total ground sites at 1.2 Gbps per ground site, or 84 Gbps total, and the satellite network is divided into 7 regions, with a single gateway per region. O3B also has no inter-satellite links, so communicating across regional boundaries requires multiple bounces.
The Iridium™ constellation simply doesn't have the bandwidth to address the same market. Iridium's™ Low Earth Orbit (LEO) constellation has an altitude of about 780 km, which limits access per satellite. Accordingly, a constellation of 66 active satellites is used to provide 24/7 coverage of the entire world. Use of L-band in LEO constellation limits the bandwidth of satellite phones to less than 1 Mbps. Gateway links offer 10 Mbps of bandwidth to a few selected locations. Moreover, inter-satellite links are RF, with substantially limited bandwidth.
Some limited experiments were conducted for free-space optical communication (FSO), also sometimes referred to as laser communication, or lasercom for short, by the National Aeronautics and Space Administration (NASA) around 2005, in the NASA Mars Telecommunication Orbiter program. However, these experiments proved to have limited coverage duration, limited connectivity, and usually limited bandwidth of about 5-10 Gbps of upper limit per link. No commercial viability was the conclusion of the program.
Several attempts have been made to establish a space-based laser communication network. One such network was the Transformational Communication Architecture (TCA), which was designed around a backbone of GEO satellites with inter-satellite links, and laser links to other spacecrafts and to airborne platforms and ground sites. The estimated cost of TCA was so high that it could not survive and was cancelled at its onset.
All prior attempts at lasercom in space have used an optical to electrical to optical (O-E-O) approach, with the incoming optical signal converted to an electrical signal and then converted back to an outgoing optical signal. The approach has the advantage that the signal can undergo a full re-amplification, re-shaping and re-timing (3R) regeneration on-board while it is in the electronic domain, but the size, weight, and especially power of the hardware has been a severe challenge. Much of the work has also concentrated on using satellites in GEO, for which the range is as much as 6 times further than the MEO satellites. | {
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This invention relates to a system for removing odors from motor vehicles.
The problem of controlling odors in motor vehicles is roughly as old as the enclosed passenger compartment. Odors drawn into the passenger compartment from outside are sometimes objectionable. As often, the odors are the result of activities within the automobile, particularly smoking. In modern vehicles, smoke tends to collect in the top liner of the vehicle.
Attempts to remove odors from automobiles, particularly after the odor-causing particles have become lodged in the top liner or other upholstery, have met with only limited success. Materials which merely mask the odor with their own scent are generally objectionable and of limited use. Materials, such as active oxidants, which chemically react with odor-causing particles require treatment of the car when passengers are not in it, are frequently deleterious to some parts of the vehicle, and are not always effective. Recently, solvent-evaporation materials have been used with considerable success in removing serious odors from vehicles. The solvent-evaporation systems include an active ingredient which acts as a highly efficient solvent for most odor-causing particles, and which is capable of evaporation with the odor-causing particles in solution. If the vapor bearing the particles is swept from the passenger compartment before it condenses on a surface in the vehicle, the odor-causing particles, hence the odor, are swept away. The solvent evaporation materials are sprayed into the automobile, particularly around the top liner, the windows of the vehicle are opened, and a large fan is placed in the open trunk of the automobile to draw the vaporized particles out of the passenger compartment. Although this method is effective, it is also time consuming and cumbersome. | {
"pile_set_name": "USPTO Backgrounds"
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Polyphenylene ether has been used in a wide variety of applications because it is excellent in dimensional stability as well as mechanical and electrical properties and heat resistance. However, polyphenylene ether has a significant drawback that it is by itself poor in oil resistance and molding workability. In order to overcome this drawback, there has been proposed a technique to prepare a material in which a polyamide is blended with a polyphenylene ether, and such materials are nowadays used in an extremely wide variety of applications (Patent Document 1).
Recently, polyamide-polyphenylene ether resin compositions have been used in large-size molded products such as automotive fenders. When such molded products are used in combination with metal parts, high temperature environments cause troubles such as dimensional discrepancies and deformation caused by contact with metal parts because the molded products are too larger in linear expansion coefficient than the metal parts. Accordingly, there have been generally adopted such techniques in which an inorganic filler is blended with the resin composition in order to reduce the linear expansion coefficient of the resin composition. However, such blending has resulted in a problem that the impact resistance of the resin composition is remarkably degraded.
As techniques to reduce linear expansion coefficient and to improve Izod impact value, attempts have been made in which a small platy inorganic filler having an average particle size of 8 μm or less, in particular, 5 μm or less is blended with a polyamide-polyphenylene ether resin composition. Disclosed examples of such techniques include: a technique blending talc having an average particle size of 5 μm or less and an aspect ratio of 5 or more (Patent Document 2); a technique blending a platy inorganic filler having an average particle size of 5 μm or less and an aspect ratio of 3 or more (Patent Document 3); a technique blending a platy inorganic filler having an average particle size of 3 μm or less and a specific particle size distribution (Patent Document 4); a technique blending a platy filler having an average particle size of 1.2 to 5 μm and an L/D value of 3 or more and/or a fibrous inorganic filler having a fiber length of 2 μm or more, carbon black, fine fibrous carbon and a hydrogenated block copolymer having a number average molecular weight of 80,000 or less (Patent Document 5); a technique blending talc and carbon (Patent Document 6); a technique blending an inorganic filler having an average particle size of 8 μm or less and a hydrogenated block copolymer having a number average molecular weight of 50,000 to 180,000 (Patent Document 7); and a technique blending small-particle-size talc having an average particle size of 1 to 4 μm and large-particle-size talc having an average particle size of 5 to 10 μm (Patent Document 8).
However, because a platy inorganic filler having a small average particle size has a large surface area, the use of such a filler results in a remarkable degradation of flowability, in particular, a degradation of flowability in a thin mold. Additionally, the above-mentioned conventional techniques do not sufficiently improve tensile elongation.
Recently, application of polyamide-polyphenylene ether resin compositions filled with an inorganic filler and a conductive material to large-size thin-wall molded products such as automotive outer panels has come under review. In particular, the improvement of dart impact strength based on falling weight or the like and flowability in a thin mold, and the impartment of conductivity have come to be demanded.
As affairs now stand, in view of such demands from the market, the above-mentioned conventional techniques are poor in the balance between dart impact strength, tensile elongation and flowability, and have not yet reached a practical application level to be sufficiently satisfactory. Accordingly, resin compositions having excellent balance between dart impact strength, flowability and linear expansion coefficient, and additionally, having conductivity have long been awaited.
Patent Document 1: JP-B-45-997 (corresponding to U.S. Pat. No. 3,379,792)
Patent Document 2: JP-A-2-163158 (corresponding to U.S. Pat. No. 5,086,105)
Patent Document 3: JP-A-6-145499 (corresponding to U.S. Pat. No. 5,475,049)
Patent Document 4: JP-A-2002-194206
Patent Document 5: JP-A-2002-194207
Patent Document 6: JP-A-2003-528941 (corresponding to European Patent EP1,232,218)
Patent Document 7: JP-A-2004-285136
Patent Document 8: JP-A-5-220826 | {
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1. Field of the Invention
The invention relates to an information processing apparatus for performing a setup to control a device, its device setting method, and a memory medium in which a device driver program has been stored. More particularly, the invention relates to an information processing apparatus having means for performing various setups on a device set picture plane which is provided on an information processing apparatus such as a personal computer or the like, its device setting method, and a medium on which its device driver program has been recorded.
2. Related Background Art
In a conventional print system, in the case where the system has a plurality of print set picture planes and a preview picture plane to display set contents of the set picture planes, means for changing the setup on the set picture plane is not provided on the preview picture plane or, even if such means is provided, means for changing the setup on the set picture plane is merely provided. Therefore, if the user tries to change the print setup belonging to another set picture plane, it is necessary to switch the print set picture plane by the operation such as button operation, switching of a tab sheet, or the like.
Such conventional processes will now be described with reference to FIGS. 1 and 2.
FIG. 1 shows a user interface picture plane of a print setup in a printer driver of Canon Inc. (registered trademark) corresponding to Windows 95 (registered trademark of Microsoft Corporation in U.S.A.).
In the diagram, reference numeral 101 denotes a set picture plane switching button and a plurality of sheet names for print setup are shown. In FIG. 1, a set picture plane of “page setup” is shown. As shown at 102, a paper size, the number of output copies, a direction of the paper, a page layout, a stamp function, and the like can be set. Reference numeral 103 denotes a preview picture plane. A print preview is displayed in accordance with the set items set on the set picture plane 102 which is opened at present. In the preview picture plane 103 in FIG. 1, preview set items of “A4”, “portrait”, and “1 page per sheet” are displayed.
In the recent printer driver, there are a variety of print purposes and there is a printer driver having a complicated print setup. To provide a wide degree of freedom for the print setup, a plurality of set picture planes (set sheets) are needed.
To change each set item, the user selects “page setup” by the set picture plane switching button 101 by using a pointing device such as a mouse or the like and switches the set picture plane to the “page setup” set picture plane. The change of the set items can be realized by selecting desired set items as shown at 102 after the switching. For example, when the setup of “page layout” is changed from “1 page per sheet (standard)” to “4 pages per sheet”, an example of the print set picture plane just after the setup of “page layout” was changed is as shown in FIG. 2. The preview picture plane 103 and a print set item 201 show the contents of “4 pages per sheet”.
In the conventional print system, however, in the case where a setup is performed on a certain set picture plane, if the user tries to change the setup of another set picture plane, it is necessary to switch the print set picture plane itself including the preview picture plane as mentioned above. Therefore, since the user cannot simultaneously see the setup on the set picture plane before switching and the setup on the set picture plane after the switching, a use efficiency is not good for the user who changes a plurality of setups. It is also necessary to often switch the picture plane in order to confirm the set contents, and the like. There is a problem such that it is difficult for the user to understand the setup changing operation. | {
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Densitometers can measure the passage of light through a transparent or semitransparent material. The measured density of a measurable substance is typically determined by measuring a decrease in the amount of light which passes through the measurable substance, the measurement may be related to the absorption of light of the measurable substance.
Most densitometers include a light source, often a laser, aimed at a photoelectric cell, with the measurable substance between the light source and the photoelectric cell. The densitometer determines the density of the measurable substance by analyzing the attenuation of light from the light source that has passed through the substance, and comparing that value with a known reference value.
Densitometers can be either transmission densitometers or reflection densitometers. Transmission densitometry instruments typically measure how transparent a substance is to visible light or other electromagnetic radiation. Reflection densitometry devices measure the amount of reflected signal, typically light or other electromagnetic radiation, of a sample. Densitometers are used in many industries as tools to measure the optical density of materials, i.e., liquids, and to provide quality assurances of a particular liquid, including foodstuffs, medications, or ink for printers.
It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. | {
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Herein, related art may be discussed to put the invention in context. Related art labeled “prior art” is admitted prior art; related art not labeled “prior art” is not admitted prior art.
Regardless of the amount of pre-release testing, computer software is rarely flawless when it is released. Security issues, compatibility issues, and other problems may be discovered post release. Accordingly, software developers can release patches to update the software. In the case of some operating systems, hundreds or thousands of patches may be available, so that users often rely on the operating system developer for recommendations regarding which patches to install.
While it might seem advantageous to simply install the latest version of all patches, there are many situations in which this is not done. New patches can introduce new problems, and may not be tested on some system configurations. Some “restrictive” users do not want to “disturb” their systems any more than necessary; such users tend to address only actual problems or important security issues. Other users may be may be reluctant to install patches that have not been extensively vetted in the field.
Accordingly, a solution provider typically takes into account both the configuration of the system being patched and the user's preferences regarding patching in general. When a particular problem or security issue is identified, the solution provider can determine the configuration of the user system and determine what patches address the problem or issue. The user preferences can help select among the solution patches.
When a large number of patches are involved, some patches require other patches be installed with them. When a patch is selected to address a user issue, the patch space has to be analyzed to determine its dependencies so they can be induded in the solution. This analysis can be quite complex and must often be repeated for users with multiple systems with different configurations. The present invention addresses the problem of having to perform intensive dependency analyses every time a patch solution is required. This and other problems addressed by the invention are apparent from the description below with reference to the following FIGURE. | {
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Vanillin, whose chemical name is 4-hydroxy-3-methoxybenzaldehyde, is one of the most important aromatic flavor compound used in food, beverages, fragrances and phaimaceuticals. Vanillin was historically extracted from Vanilla planifolia, Vanilla tahitiensis and Vanilla pompona pods. Today, as a result of constantly rising demand, less than 5% of worldwide vanillin production comes from vanilla orchid. Currently, chemical synthesis is the most important process for producing vanillin. However, there is a growing interest in other sources of vanillin and in particular in bio-based routes using bioconversion processes from natural raw material. The use of microbial cells and their enzymes as biocatalysts for the synthesis of chemicals and flavor compounds has attracted much attention lately. Advantageously, the products of such bioconversions are considered as ‘natural products’ by the European Community Legislation.
Bioconversion processes are based on the following substrates: lignin, phenolic stilbenes, isoeugenol, eugenol, ferulic acid, sugars, aromatic amino acids and waste residues containing these precursors. A recent review (Kaur B, Chakraborty D. “Biotechnological and molecular approaches for vanillin production: a review” Appl Biochem Biotechnol. 2013 February; 169(4):1353-72) lists several biosynthetic pathways and appropriate microorganisms used for biosynthesis of vanilloids.
Strains of the genus Amycolatopsis have been identified as being able to synthetize vanillin from ferulic acid, a natural cell wall component of higher plants (U.S. Pat. No. 6,133,003). Among the strains from this genus, the strain accessible under number ATCC 39116 has been selected as being capable of synthetizing large amounts of vanillin, due to its high resistance to vanillin toxicity.
The metabolic pathway of conversion of ferulic acid into vanillin is shown in FIG. 1. In wild-type Amycolatopsis strains, the produced vanillin is then converted into both vanillic acid and vanillic alcohol, as shown in FIG. 2. This unwanted consumption of vanillin by endogenous enzymes is a major obstacle for using microorganisms of the Actinomycetales order in an industrialized process for producing vanillin.
In order to prevent the oxidation of vanillin into vanillic acid, the gene coding for the enzyme responsible of this oxidation reaction entitled vanillin dehydrogenase has been recently investigated in Amycolatopsis sp. strain ATCC39116. A putative vdh gene was identified, characterized and a vdh deletion mutant was generated. Fermentation of this mutant strain enables the obtaining of a 2.3-fold higher vanillin concentration, compared to fermentation of the wild-type strain, and a substantially reduced amount of vanillic acid was observed (Fleige C, Hansen G, Kroll J and Steinbüchel A, Investigation of the Amycolatopsis sp. strain ATCC 39116 vanillin dehydrogenase and its impact on the biotechnical production of vanillin, Appl. Environ. Microbial. 2013, vol. 79, 81; patent application WO 2012/172108). The vdh gene is accessible in NCBI database, under accession number AFY98904.
The conversion of vanillin into vanillic alcohol is catalysed by an enzyme having vanillin reductase activity. However, this enzyme has not been identified yet in a strain of Amycolatopsis sp. neither in any strain of the order of Actinomycetales. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The present invention relates to a profile clamp and a method for manufacturing the profile clamp. More specifically, the present invention relates to a profile clamp, having conical side walls that are bent radially inwardly, for connecting components that have flanges at their respective ends.
2. Discussion of the Related Art
Profile clamps, per sxc3xa9, are known, for example, from German Reference DE 30 38 491 C2, U.S. Pat. Nos. 3,498,649, 3,964,773, French Reference No. 1,016,629 and from the brochures xe2x80x9cNORMA Conical Flange Jointsxe2x80x9d, (copyright) 1979 and 1988, xe2x80x9cNORMA Profile Clamp with Conical Flangexe2x80x9d,(copyright) November 1996. These known profile clamps are made of ferritic or pure austenitic steel. They are manufactured by pure cold forming, with subsequent welding. These steel profile clamps are not stable at relatively high temperatures. Alternatively, they have too high of a coefficient of thermal expansion [18xc3x9710xe2x88x926 to 22xc3x9710xe2x88x926 m/mxc2x0 C. (for austenitic, creep-resistant steels)], which causes loss of elasticity at high temperatures and, thus, leakages in the joint.
The housings of turbochargers for large diesel engines or gas turbines are currently made of ferritic casting materials which, in the range of 20xc2x0 C. to 600xc2x0 C., have a coefficient of thermal expansion that ranges from 10xc3x9710xe2x88x926 to 14xc3x9710xe2x88x926 m/mxc2x0 C. as the temperature changes. Thus, the known profile clamps, which are made of ferritic or pure austenitic steel, are not suited to join the housing or other components of turbo chargers because the joint would leak at temperatures up to 750xc2x0 due to the excessively high coefficients of thermal expansion of the conventional clamp material. Leaking joints will, among other things, lead to a substantial loss of output from the turbochargers.
In addition, a leaking or loosening connection constitutes a security risk, because turbochargers that have been assembled with these clamps could burst as a result of the loose connection, thereby increasing the risk of injury.
It is an object of the present invention to provide a profile clamp and a method for manufacturing the profile clamp that may be used to reliably secure ferritic, pearlitic casting materials of components through which hot gas flows while meeting the desired requirements of tightness and stability in a temperature range up to 750xc2x0 C.
These and other objects are achieved with a profile clamp made of a martensitic steel, which, at an ambient temperature of 20xc2x0 C. to 750xc2x0 C., has a coefficient of thermal expansion that is at least 0.3xc3x9710xe2x88x926 m/mxc2x0 C. lower than that of a ferritic casting material.
Martensitic steel has a high degree of hardness at very high temperatures and, therefore, withstands high forces that are exerted on the point of junction without being deformed. Furthermore, as a result of the selection of the coefficient of thermal expansion, the profile clamp expands slightly less than the components that are being joined, which are made of a ferritic casting material. The clamping force exerted by the profile clamp on the flanges of the components to be joined increases as the temperature of the joint rises, thereby ensuring that the components will be held together not only due to the lower deformability of the profile clamp, but also because the clamping force increases with rising temperature. Thus, in use, the profile clamp according to the present invention not only avoids the dangers described above, but also avoids the costly manner that is currently used to bolt known profile clamps, which may include the use of additional clamping rings that are fitted with holes for the insertion of screws to further secure the joint.
The profile clamp is made of a steel that is comprised of iron as its main constituent. The remaining constituents, in percentage by weight, are as follows: up to 0.45% C, up to 2.0% Si, up to 2.0% Mn, up to 0.04% P, up to 0.04% S, 15 to 20% Cr, from 1 to 8% Ni, up to 2.5% Mo, up to 0.5% V, up to 0.1% Al, up to 0.1% Co, up to 0.4% Cu, up to 0.4% Pb, up to 0.1% Se,up to 0.1% Te, up to 0.5% Ti, up to 0.1% W, up to 0.05% Zr, up to 0.01% O, up to 0.01% N, up to 0.1% Bi, up to 0.001% B, up to 0.05% Nb.
In a currently preferred exemplary embodiment, the maximum amount of C is 0.4%, of Si is 0.5%, of Mn is 0.8% and of Mo is 2.0%, and the minimum amount of Ni is 1.0%, of Mo is 0.3% and of V is 0.25%.
The profile clamp in one exemplary embodiment of the present invention has at least one clamping band with its end sections being bent radially outwardly and back to form loops. The ends of the end sections are welded to the clamping band. A bolt is disposed in each loop. Each loop has a slit that extends around a major portion of the bolt. The bolts in adjacent loops are connected by a headed clamping bolt. The clamping bolt shaft extends through the slits in the loops. At least one circular ring segment is welded to a radial inner surface of the clamping band. The circular ring segment has conical side walls so that, in axial cross-section, the ring segment is approximately hat-shaped. The conical side walls are fitted with a plurality of reinforcements. One of the bolts disposed within the loops has, in axial cross-section, an approximately tear drop shape with its sides enclosing a right angle. One of the sides of the tear drop shaped bolt extends radially outwardly away from the clamp circumference and the other side extends approximately in the circumferential direction of the clamp. The loop enveloping the tear drop shaped bolt has a matching cross sectional shape. The clamping bolt head is supported on the side of this matching loop that extends radially outwardly and away from the clamp circumference. The profile clamp according to this embodiment withstands, on the basis of its shape alone, very high axial forces, such as may occur in profile clamps with diameters of up to 500 mm and higher. Nevertheless, the clamping band is sufficiently flexible to adapt perfectly to the diameter of the flanges of the components to be joined together because of the separate construction of the semi-circular profiled ring segments and their connection to the clamping band in a circumferential direction. Because the clamping bolt head is supported on the side of the loop, the width of the slit formed in this loop is smaller than in known profile clamps where the clamping bolt head is supported directly on the bolt disposed within the loop. Thus, the clamp according to the present invention has a slit width in the loop that is approximately equal to the diameter of the clamping bolt shaft so that the loop can withstand higher tension forces. Additionally, the clamping bolt head is supported on a large surface on an approximately radially extending side of the loop, without putting stress on the loop with the edge of the clamping bolt head.
In accordance with an alternate exemplary embodiment of the profile clamp according to the present invention, the clamp has at least one circular ring segment having end sections that are bent radially outwardly and back to form loops at each end section. The end sections are welded to the circular ring segment. A bolt is disposed within each of the loops. Each loop has a slit extending around a major portion of the bolt. The bolts in adjacent loops are connected by a headed clamping bolt. The clamping bolt shaft extends through the slits in the loops. The circular ring segment includes conical side walls so that, in axial cross-section, the ring segment is approximately hat-shaped. The conical side walls have a plurality of reinforcements. One of the bolts in the adjacent loops has, in axial cross-section, an approximately tear drop shape with its sides enclosing a right angle. One of the sides of the bolt extends approximately radially outwardly away from the clamp circumference and the other side extends in the circumferential direction of the clamp. The loop surrounding the tear drop shaped bolt has a matching cross-sectional shape. The clamping bolt head is supported on a side of the matching shape loop that extends radially outwardly away from the clamp circumference. In this embodiment, one circular ring segment may be used, as opposed to two, if slightly lower joining forces can be applied by the profile clamp on the components to be joined.
The reinforcements are preferably made of sheet metal and are welded to the conical side walls. These sheet metal reinforcements ensure that the side walls have a very high flexural strength.
A plain washer, having a diameter larger than that of the head of the headed clamping bolt, is disposed between the head of the headed clamping bolt and the loop. Such a plain washer facilitates not only the tightening of the clamp bolt, but also reduces the surface pressure between the clamping bolt head and the side of the loop.
The method for manufacturing the profile clamp according to the present invention includes the material being prequenched and tempered while in the form of a strip. Thereafter, the clamping band is shaped and welded. The welds are subject to an induction tempering treatment for structural homogenization of the profile clamp. By prequenching and tempering, optimal technological properties are obtained in the steel. The induction tempering, which preferably occurs after controlled cooling of the welds, avoids or at least reduces the risk of crack formation in the area of the welds.
The induction tempering treatment is preferably a short-term spheroidization that takes place for less than 5 minutes. The spheroidization preferably occurs in the range of the Ac1 temperature, which results in optimal structural formation in the welding zones. | {
"pile_set_name": "USPTO Backgrounds"
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I. Technical Field
The present invention relates to a wireless communication and reception quality reporting method, and particularly relates to a wireless communication apparatus and reception quality reporting method for performing high-speed packet communication using adaptive modulation and scheduling.
II. Related Art and Other Considerations
In a conventional art, in HSDPA (High-Speed Downlink Packet Access) of 3GPP, adaptive modulation where the modulation scheme is adaptively controlled according to propagation path conditions and scheduling for transmitting a user signal for which propagation path conditions are comparatively superior have been employed in downlink high-speed packet transmission.
In multi-carrier transmission such as OFDM and MC-CDMA (for example, Hara, Kawabata, Duan and Sekiguchi, “MC-CDM System for Packet Communications Using Frequency Scheduling”, TECHNICAL REPORT OF IEICE, RCS2002-129, July 2002, refer to pp. 61-66) being examined as transmission schemes for beyond 3G mobile communication systems, high speed transmission is implemented using a large number of sub-carriers.
In this kind of transmission scheme, performing adaptive modulation and scheduling every sub-carrier is examined.
With this kind of adaptive modulation and scheduling system, it is necessary for the mobile station to give reporting of channel quality information (CQI (Channel Quality Indicator)) of each sub-carrier instantaneously at a base station.
The mobile station reports individual CQIs on every sub-carrier for all sub-carriers to the base station.
A base station then determines the sub-carrier, modulation scheme and encoding rate to be used at each mobile station in accordance with a predetermined scheduling algorithm taking into consideration the CQIs from each mobile station.
Typically, sub-carriers with comparatively good propagation path conditions are allocated to each mobile station, and a modulation scheme and encoding rate satisfying a predetermined packet error rate are employed for these propagation conditions.
In the event that a base station transmits to a plurality of mobile stations at the same time, frequency scheduling is carried out using CQIs of all of the sub-carriers from all of the users.
In other words, if there are 64 sub-carriers, it is necessary for each mobile station to give reporting of 64 CQIs.
In this event, when a CQI is expressed using five bits, it is necessary to transmit a total of 64×5=3 20 bits per one user in each wireless frame.
However, with wireless communication apparatus of the conventional art, the quantity of signal required for CQI reporting is enormous. This means that interference incurred by other data channels and other cells is large, and the quantity of data that can be transmitted is therefore substantially reduced.
Further, as the quantity of signal for giving CQI reporting is enormous, power consumption of the mobile station is increased and a battery life is shortened. | {
"pile_set_name": "USPTO Backgrounds"
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The invention relates to catalysts and methods for the conversion of carbon dioxide to valuable products. More particularly, the invention relates to carbide catalysts, in particular metal carbide catalysts, for the production of hydrocarbons from carbon dioxide or carbon monoxide.
According to the United States Environmental Protection Agency carbon dioxide is the primary greenhouse gas emitted by humans, accounting for greater than 80% of all greenhouse gases. Therefore, decreasing the emission of carbon dioxide is a priority to reduce and/or avoid the adverse effects of global climate change. One approach to reducing carbon dioxide emissions is electrochemically converting it to fuels and other valuable products. Electrochemical conversion could also provide a method for making renewable biomass fuels (ethanol and biodiesel) and fossil fuels carbon neutral, reducing fossil fuel demand and carbon dioxide emissions. Another option is to transition to renewable energy sources, such as hydro, wind, geothermal, solar, etc. Unfortunately, renewable sources tend to be intermittent and lack portability requiring large scale energy storage to meet energy demands. Conversion of carbon dioxide to fuels could be used with or as an alternative to the energy storage requirements.
A key technological challenge to industrial application of electrochemical conversion of carbon dioxide to useful fuels and other products is the development of catalysts to make the process cost effective. Efficient catalysts enable electrochemical conversions at low overpotential and reasonable current densities. Due to the low reactivity and high stability of carbon dioxide, identification of efficient catalysts to convert carbon dioxide to hydrocarbons has been challenging. For example, copper, a commonly used catalyst for carbon dioxide reduction to hydrocarbons, requires an overpotential on the order of 1 V.
According to the United States Department of Energy, “[t]he major obstacle preventing the efficient conversion of carbon dioxide into energy-bearing products is lack of catalysts” with satisfactory activity at low overpotentials and high electron conversion (US Dept. of Energy, Basic Research Needs: Catalysts for Energy, Report PNNL17712, 2008). Overpotential is related to the loss of energy during the process, so efficient conversion requires low overpotentials. Therefore, it is necessary to find catalytic materials having lower overpotentials to produce hydrocarbons from carbon dioxide more efficiently. | {
"pile_set_name": "USPTO Backgrounds"
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This invention relates, in general, to an apparatus and method for transporting products, for example, for use with a conveying and processing system.
Most transporting systems currently available include a plurality of grippers, such as suction heads, that are moved simultaneously with a frame to which the grippers are connected. The grippers are often lowered onto the products to be picked up and raised with the products and moved to another location. In such systems, the spacing of the grippers is matched to the spacing of the products to assure proper operation. An apparatus for allowing the spacing between the products to be reduced or increased would be desired.
In light of the shortcomings described above, it is desirable to provide an apparatus and system for transporting products that facilitates reducing or increasing the spacing of products being transported. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The invention relates to a microbiological process for the production of 6-hydroxypicolinic acid, starting from picolinic acid and/or its salts.
2. Background Art
Several methods for the production of 6-hydroxypicolinic acid by organic syntheses are known. From picolinic acid, for example, the 6-hydroxypicolinic acid can be obtained by reaction with potassium hydroxide [Tetrahedron Letters, Vol. 29, (1988), pages 4389 to 4392]. A drawback of such process is that the 6-hydroxypicolinic acid is obtained only in moderate yield (51 percent).
It is also known that microorganisms of genus Bacillus hydroxylate picolinic acid to 6-hydroxypicolinic acid [O. Shukla and S. M. Kaul, Indian J. of Biochemistry and Biophysics, Vol. 10, (1973), pages 176 to 178; O. Shukla et al., Indian J. of Biochemistry and Biophysics, Vol. 14, (1977), pages 292 to 295]. A great drawback of such process is that the further metabolization of the 6-hydroxypicolinic acid can be stopped only with the inhibitor sodium arsenite, and thus the growth of the microorganisms also is inhibited. Another drawback consists in that 6-hydroxypicolinic acid is not exclusively formed, but instead a mixture of 3,6-dihydroxypicolinic acid and 6-hydroxypicolinic acid is formed.
R. L. Tate and J. C. Ensign, Can. J. Microbiol., Vol. 20, (1974), pages 695 to 702, describes the hydroxylation of picolinic acid with microorganisms of genus Arthrobacter. Drawbacks of such process are that these microorganisms cannot exclusively use picolinic acid as a carbon, nitrogen and energy source, but in the hydroxylation, a yeast extract has to be present, which can lead to undesirable impurities of the product. Another drawback lies in the fact that the 6-hydroxypicolinic acid is formed only in the case of low oxygen content, and the microorganisms are not present in the growth phase, and thus little product is formed. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
This invention relates to a washing process in which the concentration of the wash liquor is determined by analysis.
2. Discussion of Related Art
In the machine washing of laundry, it is desirable, above all in the institutional sector, completely or partly to automate dosage of the detergent in the preparation or regeneration of the wash liquor. To control dosage according to requirements, it has proved to be useful to employ not only external parameters, but also the actual concentration of washing-active substance in the liquor as a guide for subsequent dosage of the detergent. The necessary dosage is thus the difference between the required concentration and actual concentration of washing-active substance. Control methods such as these are today mainly used in batch washing machines, the fact that the total conductivity of the liquor increases with increasing concentration being used to determine the content of washing-active substance in the liquor. The connection between conductivity and concentration of washing-active substances has to be empirically determined for each new composition of a detergent. With this system, difficulties arise out of the highly variable input of electrolytes with the soiled washing which leads to inaccurate analysis results and hence to incorrect dosage. In addition, DE-OS 29 49 254 describes a process in which the concentration of wash liquors and cleaning solutions is photometrically determined through the content of fluorescent dyes. The disadvantage of this process lies in the tendency of all dyes to be adsorbed onto textile fibers from solution so that the wash liquor loses these dyes more quickly than the other active substances. Since, in addition, dye adsorption also depends on the quality of the fibre material, the concentration of washing-active substances cannot be reliably determined in this way. Accordingly, for more reliable dosage of the detergent, efforts have long been made to find a process which would not be affected by such factors. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
This invention relates to a mirror position control device for automobiles that adjusts the viewing angle of a mirror automatically to accomodate a driver's individual preferences.
2. Description of the Prior Art
The optimum angle of a rear view mirror of an automobile varies depending upon the driver's individual characteristics, such as size, posture, driving habits, etc. The automobile is sometimes shared by members of a family, office, etc. and the optimum position and/or angle of the rear view mirror differs from driver to driver; thus, the angle of the rear view mirror must be adjusted each time a different driver enters the automobile. This adjustment is troublesome, and if a new person drives the automobile without adjusting the angle of the mirror, either because they forget or they do not want to go through the bother of adjusting the mirrors in the vehicle, then the danger of an accident being caused due to improper mirror positioning increases. | {
"pile_set_name": "USPTO Backgrounds"
} |
The present invention relates to a unique solenoid operated valve structure and a method of making the same and more particularly to a solenoid valve structure which is hermetically sealed and which includes a valve housing that can be manufactured and assembled in a straight forward, economical manner from a comparatively inexpensive sheet like material with a minimum of fluid leakage.
Hermetically sealed, solenoid operated valve structure in the prior art, particularly in the refrigeration industry, has been comparatively difficult, requiring valve housing structure which includes costly body parts, which are milled and machined from solid metal, thus necessitating several take-apart, bolted or screwed gasket seals to provide a leak-free housing assembly which has occasioned frequent maintenance or replacement in order to minimize fluid leakage.
The present invention, recognizing the associated disadvantages of prior art solenoid operated valve structures which have required comparatively expensive operating parts including milled and machined valve body parts and numerous take-apart gasket members to reduce fluid leakage, provides a uniquely modified, solenoid operated valve which is straightforward and economical in manufacture and assembly, utilizing a minimum of parts, eliminating most, if not all of previously required gasket seals and yet substantially reducing fluid leakage, the unique hermetically sealed, solenoid structure of the present invention allowing ready, straightforward connection and replacement disconnection in a hermetically sealed fluid system with a minimum of operating steps. In addition, the valve structure of the present includes a novel valve stem and seat arrangement which minimizes valve wear, maximizes valve life and, at the same time, can be effectively utilized with various valve sizes and fluid capacities. Further, the present invention provides a long enduring arrangement which provides tighter sealing, reduces requirements for special valve seat parts, utilizing required conduit extremities for such purposes. Various other features of the present invention will become obvious to one skilled in the art upon reading the disclosure set forth herein. | {
"pile_set_name": "USPTO Backgrounds"
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The present invention relates to networked financial interfaces and more particularly to conducting trade finance business operations including account settlements.
In international sales of goods, the buyer and seller may not know each other, or may not be familiar with the other""s legal system. Thus, one of the major difficulties in international trade is to assure payment, particularly when the buyer or the seller is a small or medium sized business which expects difficulties in obtaining payment should a problem arise. Conventionally, a letter of credit is used in international trade to shift transaction risks to parties better able to manage these risks, specifically, to shift payment risks from unknown entities, such as a distant buyer, to known entities, such as a local bank.
A letter of credit (L/C) is usually an irrevocable undertaking by a bank to pay the beneficiary of the letter, for example, a seller of goods, specified sums of money when certain conditions are fulfilled, to be charged to the account of the person, for example, the buyer of the goods, who causes the bank to issue the letter of credit. Generally, after a buyer and seller have made an agreement for the sale of goods, the buyer instructs its bank to open an L/C in favor of the seller. The buyer""s bank advises the seller""s bank that an L/C has been opened in favor of the seller, and the seller""s bank accepts the buyer""s bank""s guarantee to pay. The seller""s bank advises the seller that an L/C has been opened in its favor, and the conditions which must be fulfilled for payment to occur. Usually, the seller""s bank makes an irrevocable promise to pay the seller upon presentation of appropriate documents. The L/C document is considered an asset of the seller, and can be sold or assigned by the seller.
Documentation which the seller usually must present to obtain payment includes a bill of lading from its shipper, an invoice identifying the purchase, an appropriate insurance certificate, a certificate of inspection from an inspection firm confirming that the required goods are being shipped, export licenses and/or health inspection certificates, and certificates of origin used by customs personnel. After the correct documents are presented, the seller""s bank pays the seller, then collects payment from the buyer""s bank and delivers the presented documents to the buyer""s bank. In turn, the buyer""s bank obtains payment from the buyer.
Meanwhile, the shipper, via a carrier, transports the goods to the buyer""s location. The carrier requires presentation of the bill of lading, which was delivered to the seller, before transferring possession of the goods to the buyer.
The buyer obtains the bill of lading from its bank after payment, and then the buyer and its broker arrange for presentation of the bill of lading to the carrier and delivery of the goods to the buyer""s location. Often, the carrier delivers the goods to the buyer""s broker at the customs entry point of the buyer""s country.
During an international trade using a conventional letter of credit, the buyer and seller are assumed to be located in countries B and S, respectively. The issuing bank is a bank in country B which has agreed with the buyer to issue a letter of credit in favor of the seller. The paying bank is a bank in country S known to the seller which has guaranteed the letter of credit to the seller. The intermediary bank, which may be in country B, country S or a third country, is a bank trusted by both the issuing bank and the paying bank.
To begin, the buyer issues a purchase order based on an agreement previously concluded between the buyer and the seller. Then, the buyer approaches its chosen issuing bank and instructs the issuing bank to open a letter of credit in favor of the seller confirmed on its chosen paying bank. The letter of credit may be confirmed, unconfirmed or standby. In a standby letter of credit, if the transaction proceeds properly, the standby L/C expires, but if the transaction does not proceed properly, the damaged party draws on the standby L/C.
The issuing bank is assumed in this example to have no direct relationship with the paying bank, so the issuing bank approaches an intermediary bank which accepts the guarantee to pay of the issuing bank. The intermediary bank then approaches the paying bank, which accepts the guarantee to pay of the intermediary bank.
The paying bank then advises the seller that an L/C has been opened in its favor and that upon presentation of appropriate confirming documentation, including the Bill of Lading from a Shipper, the paying bank will pay the seller. In this scenario, that is, assuming a confirmed L/C, the paying bank must pay without recourse upon presentation of appropriate documentation. In other cases, the paying bank has recourse, that is, the paying bank passes the documentation to the issuing bank and obtains payment therefrom before paying the seller.
The seller finishes producing the goods and arranges for shipment with a shipper. Goods are passed to the shipper. The shipper transports the goods to a port of entry in the buyer""s country.
Upon receipt of goods, the shipper provides the seller with a bill of lading. The seller presents the bill of lading and other confirming documentation to its paying bank in order to collect against the L/C. After verifying that the documentation is in order, the paying bank pays the seller.
The paying bank presents the documentation and its proof of payment to the intermediary bank, which pays the paying bank. The intermediary bank in turn presents the documentation and its proof of payment to the issuing bank, which pays the intermediary bank. The issuing bank then obtains payment from the buyer and gives the buyer the confirming documentation including the bill of lading.
The buyer gives its agent, such as a broker, the bill of lading and other necessary documentation. The buyer""s agent obtains the goods from the shipper, clears the goods through customs in country B and arranges for delivery of the goods to the buyer. The international trade is now completed.
An L/C shields the seller from the risk of non-payment by the buyer and reduces the risk to the buyer that the buyer will pay for goods not received. With the L/C, the risk of non-payment is assumed substantially by the buyer""s bank, which is assumed to be able to evaluate the risk of non-payment by the buyer. The seller""s bank assumes the risk of non-payment by the buyer""s bank, which the seller""s bank is assumed to be able to evaluate. The banks require fees to compensate them for their risks and the expenses they incur in connection with the L/C. Typically the buyer""s bank also requires that the buyer pledge collateral such as cash or marketable securities against the L/C or otherwise reduces its exposure in the event of non-payment by the buyer. These bank fees and requirements are a burden on trade, particularly on the buyer. Also, the delay involved in establishing an L/C for each transaction is a burden on trade.
Problems multiply because the L/C mechanism separates the transaction into substantially independent contracts, namely, the contract for the sale of goods from buyer to seller, the bill of lading, and the letter of credit.
One fertile source of difficulties for the seller is that its bank usually requires that all the documents called for in the L/C exactly correspond with the terms of the L/C, and withholds payment to the seller even due to typographical errors and minor misspellings. This has caused an enormous amount of frustration to sellers seeking payment.
Another problem is that the L/C holder can obtain payment with the correct documents, even if shipment has not actually occurred.
Yet another problem is that the L/C document itself has value, so there are expenses associated with its custody and in assuring that it is genuine.
A bank incurs roughly the same expenses in connection with an L/C, independent of the value of the goods to which the L/C pertains. The bank""s fee is sometimes expressed as a percentage of the amount of the L/C, such as 1%. Assuming, for example, that the bank""s expenses are $10,000, it will be appreciated that the bank is reluctant to open an L/C for transactions involving less than $1,000,000 of goods, as this business is not profitable for the bank. Thus, it is difficult for parties wishing to participate in international trade to use the L/C mechanism when the value of the goods involved in a transaction is small enough that the expense of an L/C becomes significant.
A system, method and article of manufacture are provided for account settlement utilizing a network. First, a buyer is allowed to select from a group of options in order to settle an account utilizing a network. The options include settling a minimum balance, partially settling, settling a full balance, and applying for an import loan on payment due date. The selected option is then received utilizing the network. Finance interest may then be booked against the buyer for an unpaid portion of the account if the selected option includes either settling a minimum balance or partially settling. If the selected option includes settling a full balance, the account may be reconciled. On the other hand, if the selected option includes applying for an import loan on payment due date, an import loan may be booked and a credit line may be transferred to a trade loan line.
In one embodiment of the present invention, ownership of goods may be released to the buyer by transferring title thereto if the selected option includes either settling a minimum balance or partially settling. As an option, a consolidated card statement may be sent to the buyer utilizing the network.
In another embodiment of the present invention, a third party who reconciles the account may be engaged if the selected option includes settling a full balance. | {
"pile_set_name": "USPTO Backgrounds"
} |
Today's consumer is inundated with advertising. In fact, advertising is so ubiquitous it is often times ignored. What is more, many people lack the belief that companies tell the truth in advertisements. As a result, word of mouth marketing and advertising has become increasingly important with respect to the sales of certain products. Word of mouth refers to the passing of information, especially recommendations, but also general information. In the context of advertising and marketing, the use of word of mouth may mean passing information between consumers or other entities, including manufacturers, experts, retailers, etc. to convey aspects or merits of a product or service, or the experience one person has related to that product or service, or related products or services.
The emergence of the importance of word of mouth marketing and advertising has coincided with the use of the Internet for researching, shopping and purchasing of products. Thus, online marketing and advertising has also become increasingly important. The use of word of mouth marketing in an online setting may therefore be an effective method for such online advertising, as consumer recommendations allow word of mouth advertising to be disseminated either online or offline.
In fact, according to a 2007 global Nielsen survey, consumer recommendations are the most credible form of advertising, as cited by 78% of the study's respondents. When businesses enable customers, or other types of users, to write reviews, ask or answer questions from the community, or share experiences, they create content that become powerful forms of marketing, and in particular, as discussed above, word of mouth marketing.
This view has been widely reinforced by many retailers (retailers will be used herein to refer to any type of seller of product or service, for example both online and brick and mortar) who report that products with relatively more reviews sell better and are returned less often. Thus, user-generated content (comprising any information such as text, audio, video, or other information carrying medium generated by a user who is a consumer (of goods, a product, website, service, purchaser of the product, etc.)) may be extremely important to manufacturers, retailers or other sellers of a product or service (collectively referred to herein as a product) as user-generated content may allow products to be differentiated and sales of products increased.
As this user-generated content may include such things as user reviews, user stories, ratings, comments, problems, issues, question/answers, or other type of content which, for example, a user is allowed to compose or submit through any medium, there may be many methods and locations (for example, online or offline) where a user may be allowed to generate content and the user content generated may be provided in a wide variety of mediums or formats the distribution of this user-generated content may be difficult. In fact, in many cases user-generated content may be more effectively generated or gathered at one location and more effectively utilized at a different location. Thus, the effective collection and distribution of user-generated content may be important to both manufacturers and retailers of products, as utilization of such user-generated content may increase sales of these products.
Accordingly, improved systems and methods for the collection and distribution of user-generated content are desired. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
This invention is concerned with certain aryl amidoxime ethers of 3-phenoxybenzyl alcohol, which have insecticidal activity.
2. Description of the Prior Art
In Japanese Pat. No. 154,426, there are disclosed pyrethroid alcohol esters of substituted phenyl-.alpha.-dimethylaminoacetic acid having insecticidal activity. Insofar as is now known, the amidoxime ethers of this invention have not been proposed. | {
"pile_set_name": "USPTO Backgrounds"
} |
Non-invasive molecular imaging plays a key role in detection of disease by characterizing and measuring biological processes at the molecular level. A number of medical diagnostic procedures, including PET and SPECT utilize radiolabeled compounds. PET and SPECT are very sensitive techniques and require small quantities of radiolabeled compounds, called tracers. The labeled compounds are transported, accumulated and converted in vivo in exactly the same way as the corresponding non-radioactively compound. Tracers or probes, can be radiolabeled with a radionuclide useful for PET imaging. Such radionuclide may include 11C, 13N, 15O, 18F, 61Cu, 62Cu, 64Cu, 67Cu, 68Ga, 124I, 125I and 131I, or with a radionuclide useful for SPECT imaging, such as 99Tc, 75Br, 61Cu, 153Gd, 125I, 131I and 32P.
PET creates images based on the distribution of molecular imaging tracers carrying positron-emitting isotopes in the tissue of the patient. The PET method has the potential to detect malfunctions on a cellular level in the investigated tissues or organs. PET has been used in clinical oncology, for the imaging of tumors and metastases, and has been used for diagnosis of certain brain diseases, as well as for mapping brain and heart function. Similarly, SPECT can be used to complement any gamma imaging study, where a true 3D representation can be helpful, for example, imaging tumor, infection (leukocyte), thyroid or bones.
The formation of new blood vessels sprouting from existing blood vessels, is a fundamental process, known as angiogenesis, associated with tumor progression. Angiogenesis is regulated by a balance between pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and anti-angiogenic molecules, such as angiostatin and endostatin. Most tumors begin growing as avascular dormant nodules until they reach steady-state populations of proliferating and apoptosing cells. Angiogenesis starts with perivascular detachment and vessel dilation, followed by angiogenic sprouting, new vessel formation, maturation, and the recruitment of perivascular cells. Blood vessel formation continues as the tumor grows, feeding on hypoxic and necrotic areas of the tumor for essential nutrients and oxygen. This multi-step process offers several targets for the development of tumor angiogenic and metastatic diagnostics.
Integrins, are largely responsible for cell-cell and cell-matrix interactions, and are one of the main classes of receptors regulating tumor metastasis and angiogenesis. In addition to having adhesive functions, integrins transduce messages via various signaling pathways influencing proliferation and apoptosis of both tumor cells, and activated endothelial cells. Research has shown that integrins are a family of adhesion molecules consisting of two noncovalently bound transmembrane subunits (α and β). Both subunits are type I membrane proteins with large extracellular segments that pair to create heterodimers with distinct adhesive capabilities. In mammals, 18α and 8β subunits assemble into 24 different receptors. One prominent member of this receptor class is the integrin αvβ3 receptor. The special role of integrin αvβ3 in tumor invasion and metastasis arises from its ability to recruit and activate matrix metalloproteinases 2 (MMP-2) and plasmin, which degrade components of the basement membrane and interstitial matrix. It has been demonstrated that tumor expression of integrin αvβ3 correlates well with tumor progression in several malignancies such as melanoma, glioma, breast cancer, and ovarian cancer. The receptor αvβ3 is not readily detectable in quiescent vessels but becomes highly expressed in angiogenic vessels, serving as an excellent molecular marker for tumor metastasis and angiogenesis imaging. Thus, the ability to noninvasively visualize and quantify integrin αvβ3 expression level will provide new opportunities to document tumor integrin expression, to properly select patients for anti-integrin treatment, and to monitor treatment efficacy in integrin-positive patients.
Based on the findings that several extracellular matrix proteins, such as vitronectin, fibrinogen, and thrombospondin interact with integrins via the amino acid sequence arginine-glycine-aspartic acid (RGD). Linear and cyclic peptides containing the RGD sequence have been extensively explored and tested. Kessler and co-workers [1] developed the pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) (“c(RGDfV)”) which showed both high affinity and selectivity for integrin αvβ3. To date, most integrin αvβ3 targeted PET studies have utilized the radiolabeling of c(RGDfV)-based antagonists due to their high binding affinities which range from nanomolar to subnanomolar range for monomeric and multimeric c(RGDfV) respectively. In particular, most efforts [2-4] are focused on the modification of the linkage connecting cyclic RGD peptide to the radionuclide. Currently, [18F]Galacto-RGD [5-7] represents the most promising integrin marker in the clinical trial arena. Despite its successful translation into clinical trials, several key issues remain to be resolved. As a monomeric RGD peptide tracer, it has a relatively low tumor targeting efficacy. In addition, its clinical utility is severely limited because of its relatively low integrin binding affinity, modest tumor standard uptake values, and unfavorable pharmacokinetic behavior. Therefore, tumors with low integrin expression levels may not be detectable. In addition, prominent tracer accumulation in the liver, kidneys, spleen, and intestines was observed in both preclinical models and human studies resulting in difficult visualization of abdomen lesions. To add to its imaging drawbacks, the synthetic preparation of the tracer is labor intensive, time consuming and inefficient, thereby limiting its widespread availability to clinicians.
Recently, a library of RGD-containing pseudopeptides has been synthesized [8]. These compounds are characterized by the replacement of the D-Phe-Val or the D-Phe-[NMe]Val dipeptide with a 6,5- and 7,5-fused bicyclic lactam. In comparison with D-Phe-Val or D-Phe-[NMe]Val dipeptide, bicyclic lactams show different reverse-turn mimetic properties that constrain the RGD sequence into different conformations and provide the required integrin activity and selectivity. While these cyclic peptides validate the use of conformationally constrained RGD peptides as integrin ligands, they cannot be used directly for PET imaging due to their difficult synthesis. | {
"pile_set_name": "USPTO Backgrounds"
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The popularity of the World Wide Web, the Java™ programming language, and relational database systems have jointly enabled user applications to be economically developed, distributed, and maintained anywhere throughout the world. FIG. 5 illustrates one configuration of a web-based application, whose execution is distributed between a client system 500 and a server system 510 interconnected by an Internet Protocol (IP) network. In this configuration, a web browser 501 executing at the client system 500 is responsible for presenting the application's user-interface to a user and enabling communications with a web server 511 executing on the server system 510 in accordance with the Hypertext Transfer Protocol (HTTP). The web browser 501 can also download from the web server 511 executable code 503 such as bytecodes compiled from a program developed in the Java programming language. The downloaded Java code 503 can be executed from within the web browser 501 to implement the application logic of the web-based application.
The server system 510 may also host a relational database 515, which organizes information into tables of rows and columns. A relational database server 513 is provided to receive database commands and statements that request data, e.g. in the Structured Query Language (SQL) and fetch the requested data from the tables in the relational database 515.
One source of complexity in this model is that the web-based application uses downloaded Java code 503, which is written in an object-oriented programming language, but the relational database server 513 is responsive to SQL commands, statements, and queries, which are expressed in a fourth generation language (4GL). Although it is possible to code a Java application to manipulate SQL statements directly, it is more convenient at the application programming level to let a library do all this processing and simply let the application programmer to work with Java objects.
Accordingly, an Application Program Interface (API) 505 is provided to furnish the Java code 503 with an object-oriented interface to the functionality of the relational database server 513. Calls to the API 505 from the Java code 503 use objects and methods as in Java and are processed by routines in a Java Database Connectivity (JDBC) driver 507 to form appropriate SQL statements. For example, the JDBC driver 507 is responsible for opening a connection over the network to the database server 513, formulating SQL statements for submission to the database server 513, and returning result sets back to the application executing the Java code 503.
Although the JDBC driver 507 presents a convenient interface to the relational database server 513 from a programming perspective, the JDBC driver 507 nevertheless imposes a performance penalty by its overhead in creating Java objects and in round-trip network communications. Because performance is vital to users, there is a need for improving the performance of web-based database applications without losing the convenience provided by encapsulating the manipulation of relational database statements in a driver. | {
"pile_set_name": "USPTO Backgrounds"
} |
Alzheimer's disease (AD) is a degenerative brain disorder characterized clinically by progressive loss of memory, temporal and local orientation, cognition, reasoning, judgment and emotionally stability. AD is a common cause of progressive dementia in humans and is one of the major causes of death in the United States. AD has been observed in all races and ethnic groups worldwide, and is a major present and future health problem. No treatment that effectively prevents AD or reverses the clinical symptoms and underlying pathophysiology is currently available (for review see Dennis J. Selkoe; Cell Biology of the amyloid (beta)-protein precursor and the mechanism of Alzheimer's disease, Annu Rev Cell Biol, 1994, 10: 373-403).
Histopathological examination of brain tissue derived upon autopsy or from neurosurgical specimens in effected individuals revealed the occurrence of amyloid plaques and neurofibrillar tangles in the cerebral cortex of such patients. Similar alterations were observed in patients with Trisomy 21 (Down's syndrome), and hereditary cerebral hemorrhage with amyloidosis of the Dutch-type. Neurofibrillar tangles are nonmembrane-bound bundles of abnormal proteinaceous filaments and biochemical and immunochemical studies led to the conclusion that their principle protein subunit is an altered phosphorylated form of the tau protein (reviewed in Selkoe, 1994).
Biochemical and immunological studies revealed that the dominant proteinaceous component of the amyloid plaque is an approximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acids. This protein was designated Aβ, β-amyloid peptide, and sometimes β/A4; referred to herein as Aβ. In addition to its deposition in amyloid plaques, Aβ is also found in the walls of meningeal and parenchymal arterioles, small arteries, capillaries, and sometimes, venules. Aβ was first purified and a partial amino acid reported in 1984 (Glenner and Wong, Biochem. Biophys. Res. Commun. 120: 885-890). The isolation and sequence data for the first 28 amino acids are described in U.S. Pat. No. 4,666,829.
Compelling evidence accumulated during the last decade revealed that Aβ is an internal polypeptide derived from a type 1 integral membrane protein, termed β amyloid precursor protein (APP). β APP is normally produced by many cells both in vivo and in cultured cells, derived from various animals and humans. Aβ is derived from cleavage of β APP by as yet unknown enzyme (protease) system(s), collectively termed secretases.
The existence of at least four proteolytic activities has been postulated. They include β secretase(s), generating the N-terminus of Aβ, a secretase(s) cleaving around the 16/17 peptide bond in Aβ, and γ secretases, generating C-terminal Aβ fragments ending at position 38, 39, 40, 42, and 43 or generating C-terminal extended precursors which are subsequently truncated to the above polypeptides.
Several lines of evidence suggest that abnormal accumulation of Aβ plays a key role in the pathogenesis of AD. Firstly, Aβ is the major protein found in amyloid plaques. Secondly, Aβ is neurotoxic and may be causally related to neuronal death observed in Aβ patients. Thirdly, missense DNA mutations at position 717 in the 770 isoform of β APP can be found in effected members but not unaffected members of several families with a genetically determined (familiar) form of AD. In addition, several other β APP mutations have been described in familiar forms of AD. Fourthly, similar neuropathological changes have been observed in transgenic animals overexpressing mutant forms of human β APP. Fifthly, individuals with Down's syndrome have an increased gene dosage of β APP and develop early-onset AD. Taken together, these observations strongly suggest that Aβ depositions may be causally related to the AD.
It is hypothesized that inhibiting the production of Aβ will prevent and reduce neurological degeneration, by controlling the formation of amyloid plaques, reducing neurotoxicity and, generally, mediating the pathology associated with Aβ production. One method of treatment methods would therefore be based on drugs that inhibit the formation of Aβ in vivo. Methods of treatment could target the formation of Aβ through the enzymes involved in the proteolytic processing of β amyloid precursor protein. Compounds that inhibit β or γsecretase activity, either directly or indirectly, could control the production of Aβ. Advantageously, compounds that specifically target γ secretases, could control the production of A{tilde over (β)} Such inhibition of β or γ secretases could thereby reduce production of Aβ which, thereby, could reduce or prevent the neurological disorders associated with Aβ protein.
PCT publication number WO 96/29313 discloses the general formula:
covering metalloprotease inhibiting compounds useful for the treatment of diseases associated with excess and/or unwanted matrix metalloprotease activity, particularly collagenase and or stromelysin activity.
Compounds of general formula:
are disclosed in PCT publication number WO 95/22966 relating to matrix metalloprotease inhibitors. The compounds of the invention are useful for the treatment of conditions associated with the destruction of cartilage, including corneal ulceration, osteoporosis, periodontitis and cancer. European Patent Application number EP 0652009A1 relates to the general formula:
and discloses compounds that are protease inhibitors that inhibit Aβ production. U.S. Pat. No. 5,703,129 discloses the general formula:
which covers 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives that inhibit Aβ production and are useful in the treatment of Alzheimer's disease.
Copending, commonly assigned U.S. patent application Ser. No. 09/370,089 filed Aug. 7, 1999 (equivalent to international application PCT US99/17717) discloses lactams of general formula:
wherein the lactam ring B is substituted by succinamide and a carbocyclic, aryl, or heteroaryl group. These compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein.
None of the above references teaches or suggests the compounds of the present invention which are described in detail below. | {
"pile_set_name": "USPTO Backgrounds"
} |
The present invention relates to data processing, and more specifically, to a coherent proxy for an attached processor.
A conventional distributed shared memory computer system, such as a server computer system, includes multiple processing units all coupled to a system interconnect, which typically comprises one or more address, data and control buses. Coupled to the system interconnect is a system memory, which represents the lowest level of volatile memory in the multiprocessor computer system and generally is accessible for read and write access by all processing units. In order to reduce access latency to instructions and data residing in the system memory, each processing unit is typically further supported by a respective multi-level cache hierarchy, the lower level(s) of which may be shared by one or more processor cores.
Because multiple processor cores may request write access to a same memory block (e.g., cache line or sector) and because cached memory blocks that are modified are not immediately synchronized with system memory, the cache hierarchies of multiprocessor computer systems typically implement a cache coherency protocol to ensure at least a minimum required level of coherence among the various processor core's “views” of the contents of system memory. The minimum required level of coherence is determined by the selected memory consistency model, which defines rules for the apparent ordering and visibility of updates to the distributed shared memory. In all memory consistency models in the continuum between weak consistency models and strong consistency models, cache coherency requires, at a minimum, that after a processing unit accesses a copy of a memory block and subsequently accesses an updated copy of the memory block, the processing unit cannot again access the old (“stale”) copy of the memory block.
A cache coherency protocol typically defines a set of cache states stored in association with cached copies of memory blocks, as well as the events triggering transitions between the cache states and the cache states to which transitions are made. Coherency protocols can generally be classified as directory-based or snoop-based protocols. In directory-based protocols, a common central directory maintains coherence by controlling accesses to memory blocks by the caches and by updating or invalidating copies of the memory blocks held in the various caches. Snoop-based protocols, on the other hand, implement a distributed design paradigm in which each cache maintains a private directory of its contents, monitors (“snoops”) the system interconnect for memory access requests targeting memory blocks held in the cache, and responds to the memory access requests by updating its private directory, and if required, by transmitting coherency message(s) and/or its copy of the memory block.
The cache states of the coherency protocol can include, for example, those of the well-known MESI (Modified, Exclusive, Shared, Invalid) protocol or a variant thereof. The MESI protocol allows a cache line of data to be tagged with one of four states: “M” (Modified), “E” (Exclusive), “S” (Shared), or “I” (Invalid). The Modified state indicates that a memory block is valid only in the cache holding the Modified memory block and that the memory block is not consistent with system memory. The Exclusive state indicates that the associated memory block is consistent with system memory and that the associated cache is the only cache in the data processing system that holds the associated memory block. The Shared state indicates that the associated memory block is resident in the associated cache and possibly one or more other caches and that all of the copies of the memory block are consistent with system memory. Finally, the Invalid state indicates that the data and address tag associated with a coherency granule are both invalid. | {
"pile_set_name": "USPTO Backgrounds"
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This invention relates to ventilators for use in assisting patients to breathe, and, more particularly, to the triggering of such ventilators responsive to the breathing of the patient.
The condition of a patient who suffers from respiratory difficulties or other health problems can often be remarkably improved simply by ensuring a regular air supply that permits the energy of the patient to be directed elsewhere than obtaining sufficient oxygen. Many ill persons are therefore placed onto a program of breathing assistance with a device called a "ventilator". In simplest terms, the ventilator either forces pressurized gas into the lungs (e.g., a positive-pressure ventilator) or expands the chest cavity to draw gas into the lungs (e.g., a negative-pressure ventilator such as an iron lung) under a selectable schedule of gas composition, pressure, and flow pattern.
Although negative-pressure ventilators enjoyed a degree of popularity in the past, their use has been largely replaced by positive-pressure ventilators. The positive-pressure ventilator is a mechanical device external to the patient, which creates an external pressure and thereby forces gas into the patient's lungs through a tube termed the "airway". The gas may be air, pure oxygen, air enriched with additional oxygen, or some other oxygen-containing mixture.
Where the patient is attempting to breathe on his or her own, termed a "spontaneous breath", under some modes of breathing assistance the operation of the ventilator is synchronized to the spontaneous breathing of the patient so that the ventilator is not forcing gas into the lungs at the same time that the patient is attempting to breathe out. If the operation of the ventilator is not properly synchronized to the breathing of the patient, the ventilator actually works against the spontaneous breathing of the patient. In the absence of proper synchronization, the power of the ventilator can overcome breathing efforts of infants or weakened adults, and can do more harm than good.
To accomplish synchronization of the ventilator to the spontaneous breathing of the patient, a sensor is provided to sense the initiation of a spontaneous breath. The sensor output is used to generate a trigger signal for the ventilator, which then operates to reinforce the spontaneous breath. There is a lag time between the initiation of a spontaneous breath by the patient and the actual flow of gas from the ventilator to the airway, for several reasons. It is therefore important to provide a trigger signal that is as early in time, but after the patient initiates the spontaneous breath, as possible. That is, the sensor should sense the initiation of a spontaneous breath as quickly as possible after the breath is initiated.
Various sensor approaches have been used in the past. One is a pressure or flow sensor placed into the airway of the ventilator. Another type of sensor is a pneumatic sensor placed on the chest of the patient over the diaphragm, so as to sense the first movement of the diaphragm at the start of a spontaneous breath. Electrical sensing of diaphragm and muscle activity have also been used. Studies show that the trigger signal of the airway sensor lags the initiation of a spontaneous breath by a significant period of time. The trigger signals of the pneumatic or electrical diaphragm and muscle sensors lag the initiation of a spontaneous breath by a shorter, but still significant, period of time. Although these types of sensors can provide satisfactory results in some cases, there is an ongoing search for better types of sensors and breathing assistance methods to aid in synchronizing the ventilator to the spontaneous breathing of the patient.
There exists a need for a better approach to the synchronization of a ventilator to a patient's own breathing. Such an improved apparatus would significantly improve the potential for respiratory care of the patients. The present invention fulfills this need, and further provides related advantages. | {
"pile_set_name": "USPTO Backgrounds"
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Genetic markers represent (mark the location of) specific loci in the genome of a species or closely related species. A sampling of different genotypes at these marker loci reveals genetic variation. The genetic variation at marker loci can then be described and applied to marker assisted selection, genetic studies, commercial breeding, diagnostics, cladistic analysis of variance, genotyping of samples, forensic analysis and the like.
Genetic markers have the greatest utility when they are highly heritable, multi-allelic, and numerous. Most genetic markers are highly heritable because their alleles are determined by the nucleotide sequence of DNA, which is highly conserved from one generation to the next, and the detection of their alleles is unaffected by the natural environment. Markers have multiple alleles because, in the evolutionary process, rare, genetically-stable mutations in DNA sequences defining marker loci arose and were disseminated through the generations along with other existing alleles. The highly conserved nature of DNA combined with the rare occurrence of stable mutations allows genetic markers to be both predictable and discerning of different genotypes.
DNA fingerprinting is a broad term used to designate methods for assessing sequence differences in DNA isolated from various sources, e.g., by comparing the presence of marker DNA in samples of isolated DNA. Typically, DNA fingerprinting is used to analyze and compare DNA from different species of organisms or DNA from different individuals of the same species. DNA sequence differences detected by fingerprinting are referred to as DNA polymorphisms. The presence of a DNA polymorphism in an organism""s DNA can serve to indicate that the genetic origin of such an organism is different from the genetic origin of organisms whose DNA does not have the polymorphism. Such polymorphisms can result, e.g., from insertion, deletion, and/or mutation events in the genome.
Many genetic-marker technologies are adaptable to fingerprinting, including restriction-fragment-length polymorphism (RFLP) Bostein et al (1980) Am J Hum Genet 32:314-331; single strand conformation polymorphism (SSCP) Fischer et al. (1983) Proc Natl Acad Sci USA 80:1579-1583, Orita et al. (1989) Genomics 5:874-879; amplified fragment-length polymorphism (AFLP) Vos et al. (1995) Nucleic Acids Res 23:4407-4414; microsatillite or single-sequence repeat (SSR) Weber JL and May PE (1989) Am J Hum Genet 44:388-396; rapid-amplified polymorphic DNA (RAPD) Williams et al (1990) Nucleic Acids Res 18:6531-6535; sequence tagged site (STS) Olson et al. (1989) Science 245:1434-1435; genetic-bit analysis (GBA) Nikiforov et al (1994) Nucleic Acids Res 22:4167-4175; allele-specific polymerase chain reaction (ASPCR) Gibbs et al. (1989) Nucleic Acids Res 17:2437-2448, Newton et al. (1989) Nucleic Acids Res 17:2503-2516; nick-translation PCR (e.g., TaqMan(trademark)) Lee et al. (1993) Nucleic Acids Res 21:3761-3766; and allele-specific hybridization (ASH) Wallace et al. (1979) Nucleic Acids Res 6:3543-3557, (Sheldon et al. (1993) Clinical Chemistry 39(4):718-719) among others. Kits for RAPD and AFLP analyses are commercially available, e.g., from Perkin Elmer Applied Biosystems (Foster City, Calif.). For example, the restriction fragment length polymorphism (RFLP) technique employs restriction enzyme digestion of DNA, followed by size separation of the digested DNA by gel electrophoresis, and hybridization of the size-separated DNA with a specific polynucleotide fragment. Differences in the size of the restriction fragments to which the polynucleotide probe binds reflect sequence differences in DNA samples, or DNA polymorphisms. See Tanksley, Biotechnology 7:257-264 (1988).
PCR-based fingerprinting methods result in the generation of a large number of reproducible DNA fragments of specific size that can be separated, typically by gel electrophoresis. These fragments are visualized to produce a xe2x80x9cfingerprintxe2x80x9d of the amplified DNA. Visualization of the size-separated fragments is effected either by direct visualization, e.g., with a fluorescent dye, by hybridization with a polynucleotide probe, or by labeling the amplification products during PCR (radioactively or flourescently) followed by detection of the labeled products in the gel. These fingerprints have a variety of uses: parentage analysis, linkage analysis of specific traits, analysis of the degree of generic relationship between individuals within a species and analysis of phylogenetic relationships between species. This has considerable commercial use in agriculture for marker assisted selection of genetic traits specific to particular genotypes (e.g., in crops or animals), identification and mapping of quantitative trait loci (QTLs) and the like.
A problem common to all DNA fingerprinting techniques in the prior art stems from the low throughput of the techniques. There exists a need to simplify and speed the DNA fingerprint analysis. The RFLP technique attempts to solve this problem by producing a limited number of DNA fragments by selective use of restriction enzymes, size separating DNA fragments using gel electrophoresis and employing specific polynucleotide probes to visualize a small number of DNA fragments at any one time. The RAPD and SSR techniques selectively amplify only one or a few fragments at a time and this small array of fragments is separated by gel electrophoresis and visualized. The AFLP technique also selectively amplifies certain restriction fragments, followed by size separation using acrylamide ,sequencing gels. DNA fragments are visualized by autoradiography or detection of fluorescence of labeled DNA molecules which were produced using labeled primers during the amplification procedure.
Each prior art fingerprinting technique is of limited usefulness because each fingerprint is generated by size separation using gel electrophoresis of each DNA sample analyzed. No meaningful data is generated without electrophoresis of the DNA samples to be analyzed. Both polyacrylamide and agarose gel electrophoresis are time consuming. Each DNA fingerprint using prior art methods requires running a gel, visualizing the DNA fragments on the gel, and analyzing the DNA fragment pattern. Thus, the number of DNA polymorphisms that can be analyzed at one time is limited by the time and cost of preparing and analyzing a gel electrophoresis fingerprint. Data density is limited by the resolution of the gels and capability of image analysis systems to reproducibly record the sizes of the separated fragments. In addition, the utility of existing methods is limited because the identity of each band amplified or hybridized is normally by size rather than sequence, making it difficult or impossible to precisely correlate bands on gels and alleles.
Therefore, it would be very useful to have a method for DNA fingerprinting that does not rely on gel electrophoresis for the generation of fingerprint information. Such a method would not require analysis of the complex data in a gel fingerprint and would allow the production of more DNA polymorphism data in less time and at a lower cost compared to levels currently achievable using prior art methods. In addition, a method which uses polynucleotide probes of known sequence has the advantage of being able to specifically associate DNA markers with alleles. This invention fulfills these and other needs.
The invention provides compositions, probes, methods of fingerprinting and genotyping, new marker assisted selection methods, methods of making probes, integrated systems for performing high-throughput assays, and other features which will be apparent upon reading this disclosure.
The fingerprinting methods herein do not rely on the rate-limiting step of gel electrophoresis for the generation of DNA fingerprints and can, therefore, produce a large number of DNA fingerprints in a short time. In one preferred embodiment, AFLP is used to identify differentially amplified nueleic acids, which are then converted into polynucleotide probes which map to polymorphisms. The differentially amplified AFLP DNAs are converted into polynucleotide probes by isolating individual polymorphic AFLP fragments from a mixture of fragments in an AFLP amplification product, followed by using these isolated fragments (dr clones or subclones thereof) as polynucleotide probes in hybridizations with immobilized DNA amplification mixtures (e.g., AFLP products). To generate a DNA fingerprint, a polynucleotide probe made according to the method of the invention is hybridized to a mixture of AFLP amplified DNA restriction fragments from DNA samples, generating a xe2x80x9cpositivexe2x80x9d or xe2x80x9cnegativexe2x80x9d hybridization result. Many unique DNA samples (typically in the thousands) can be analyzed together in a single hybridization. A series of hybridizations yields a unique fingerprint of each DNA sample in the analysis set of samples. This method is an improvement over the gel-based AFLP technique, which relies on gel electrophoresis for the production of every DNA fingerprint, significantly lowering the number of samples that can be analyzed easily. Gel-based AFLP techniques also suffer from the lack of a precise method for distinguishing AFLP fragments that have different sequences but have the same length. The hybridization-based assays of the invention can easily distinguish fragments with different sequences. Hybridization improves the genotyping capability of the AFLP technique in both sample throughput and specificity.
The techniques of the invention are adaptable to characterization of any biological nucleic acid (RNA, cDNA, genomic DNA, synthetic DNA or the like). In one aspect, a probe which hybridizes to a marker in linkage disequilibrium with a polymorphism is provided. The probe can be provided, e.g., by isolating, cloning, sub-cloning or synthesizing a nucleic acid corresponding to (the same as or hybridizing to) a marker such as a differentially amplified AFLP fragment. An exemplar probe is an oligonucleotide between about 8 and about 100 nucleotides in length corresponding to a polymorphic nucleotide marker nucleic acid. The probe is hybridized to a mixture of amplified biological DNA which includes a target nucleic acid which has the polymorphism as a subsequence. The amplified DNA can be amplified, e.g., by cloning, PCR, LCR, TAS, 3SR, NASBA, Qxcex2 amplification or the like. The DNA is optionally heterogenous by either size or sequence, or both. Typically, the amplified DNA is genomic DNA (including cellular genomic DNA, and DNA from an organelle such as a mitochondria, chloroplast or the like), or cDNA. In a preferred assay format, the amplified DNA mixture or the probe is fixed to a solid support.
The invention further provides methods of mapping polymorphic genetic markers. In the methods, a mixture of restriction enzyme-digested nucleic acids from biological samples is provided. The mixture is amplified, thereby identifying a set of differentially amplified nucleic acids in the mixture, and at least one of the differentially amplified nucleic acids is mapped to a unique genetic polymorphism, thereby providing a marker for the polymorphism. Typically, more than one differentially amplified nucleic acid is mapped, thereby providing a set of markers. The set can be of any size, although more information is provided by larger sets. Typical set sizes are from about 1-100 markers, often 10-50 markers, generally about 10-30 markers. In one typical format, the method includes hybridizing a probe nucleic acid to a mixture of DNA amplified from a biological source of DNA comprising the polymorphism, thereby identifying the polymorphism in the biological source of DNA. In this format, the probe nucleic acid hybridizes under stringent conditions to a target nucleic acid comprising the polymorphism. This information is typically used to genotype a biological sample, e.g., for marker assisted selection.
In several embodiments, the invention comprises detection of target nucleic acids in an amplified mixture of DNA, by hybridizing a probe to the amplified mixture. Depending on the available equipment and intended application, many hybridization formats are desirable. For example, either the amplified mixture or the probe can be fixed to the solid support. Typically, the solid phase of the assay will be in an array format, with either selected probes or selected amplified mixtures being fixed to predetermined locations of the array, facilitating consideration of hybridization signal information. The assays may be performed in serial or in parallel formats, i.e., by simultaneously or serially measuring hybridization results of probe-amplification mixture hybridization. Many other variations will be apparent upon full review of this disclosure.
The invention also provides probes, compositions and methods of making probes. For example, the invention provides compositions having a marker nucleic acid which specifically hybridizes to a nucleotide polymorphism and an amplified mixture of DNA isolated from a biological source.
Probes used in the above assays can be made by providing first and second samples of amplified DNA, comparing the first and second samples of amplified DNA to identify differentially amplified DNAs, isolating the differentially amplified DNA, thereby providing isolated differentially amplified DNAs and genetically mapping the isolated differentially amplified DNA, thereby providing a genetically mapped isolated DNA, which hybridizes to a unique polymorphic nucleic acid. Typically, at least a portion of the genetically mapped isolated DNA is sequenced to identify associated polymorphisms. Oligonucleotides comprising a portion of the sequenced region are also provided. Preferred probes uniquely map to single sites in a haploid genomic DNA of a plant or animal, or to cDNA.
Any of the assays or compositions provided herein are optionally provided or practiced in kit form. Kits optionally have one or more component selected from the components consisting of a container, instructional materials, one or more control nucleic acids complementary to the markers, and recombinant cells comprising one or more target nucleic acids. | {
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This invention relates to arthroscopic surgery of the temporomandibular joint (TMJ) and methods and devices for incision, excision, repositioning, recontouring, and replacement of joint fluids and soft and hard tissues by "less invasive surgery" technique.
The temporomandibular joint (TMJ) is the freely movable articulation between the condyle of the mandible and the squamous portion of the temporal bone. While having much in common with other synovial joints of the body, there are several anatomic and functional characteristics that distinguish the TMJ from most other synovial joints. These distinctions are as follows:
(a) The articulating surfaces of the bones are covered by an avascular fibrous connective tissue that may contain a variable number of cartilage cells and thus can be designated fibrocartilage.
(b) The two articulating complexes of bone carry teeth, whose shape and position influence the movements of the joint. It is the only joint with a rigid end-point of closure.
(c) It has a bilateral articulation with the cranium, so the right and left temporomandibular articulations must function together.
(d) The TMJ is a complex joint because each joint has an articular disc (meniscus) interposed between the condyle and the temporal bone.
The TMJ is a combined hinge-glide articulation of the mandibular condyle with the mandibular fossa and articular eminence of the temporal bone. The muscles of mastication and the suprahyoid muscles act bilaterally to produce three types fo movement: rotation, translation, and a combination of rotation and translation movement of the condyles. Rotation and some slight translation take place in the lower joint space between the condyle and the articular disc. Translation of the condyle-disc complex takes place in the upper joint space.
Changes in the disc-condyle relationship often produces pain and/or functional disturbances in the masticatory system. The disc is most commonly displaced anteromedially and, in the last few years, the term "internal derangements of the TMJ" connotes any disturbance between the articulating components within the joint proper.
Little is known about the prevalence of displacement. Some authors (W. L. McCarty, Jr. and W. Farrar: Surgery for Internal Derangements of the Temporomandibular Joint. J. Prosthet Dent 42:2 79) maintain that it is extremely common, whereas others believe it is rare. In a recent autopsy study of young adults, (W. Solberg, T. Hanson, B. Nordstrom: Morphologic Evaluation of Young Adult TMJs at Autopsy, abstracted J. Dent Res 63:228 1984), found disc displacement in 11.6% of the TMJs and noted it to be present more commonly in women. In other study of adult cadavers by PL. Westesson and M. Rohlin, Internal Derangement Related to Osteoarthrosis in Temporomandibular Joint Autopsy Specimens, Oral Surg 57:17, 1984, disc placement was found in 56% of the TMJs. Thus, the prevalance of disc displacement appears to increase with age.
Persistent (chronic) "closed locking" of the temporomandibular joint has been attributed to internal derangement due to anterior disc displacement without reduction. Anatomic, arthrographic, clinical, and surgical studies have supported this concept. Among such studies is C. H. Wilkes: Structural and Functional Alterations of the Temporomandibular Joint. Northwest Dent 57:287, 1978 and C. H. Wilkes: Arthrography of the Temporomandibular Joint in Patients With the TMJ Pain-Dysfunction Syndrome. Minn Med 61:645, 1978.
The natural history of internal derangement leading to persistent "closed lock" has been described by V. E. Ireland: The problem of "The Clicking Jaw". Proc. R. Soc. Med. 44:191, 1951 and M. F. Dolwick, R. W. Katzberg, C. A. Helms: Internal Derangement of the Temporomandibular Joint: Fact or Fiction? J Prosthet Dent 49:415, 1983. Trauma to the mandible has been reported to be a common etiologic factor leading to the development of internal derangement with closed lock. The traumatic event may result not only in disc displacement, but also intracapsular microbleeding and effusion. Subsequent adhesions may form. These adhesions are most commonly seen in the superior compartment. Additionally, morphological changes occur in the TMJ including synovitis and synovial hyperplasia.
Treatment of acute closed locking of the TMJ may include mandibular manipulation, splint therapy, and other non-surgical therapy. These modalities are intended to "recapture" the displaced disc. If "non-invasive therapy" is not successful, a persistent (chronic) closed lock may occur.
A plethora of evidence exists demonstrating the reality of disc displacement. This evidence includes clinical, anatomic, radiographic, and surgical findings. It has been shown that the TMJ disc is displaced anteromedially and that the displaced disc can mechanically interfere with jaw movement.
P. L. Westesson and M. Rohlin: Internal Derangement Related to Osteoarthrosis in Temporomandibular Joint Autopsy Specimens, Oral Surg 57:17, 1984, studying adult cadaver TMJs, have shown a progression of internal derangements that includes not only changes in disc position but also in disc configuration. A progression from oblique disc position with biconcave disc or disc of even thickness to complete displacement with biconvex disc configuration was shown. The most advanced form of internal derangement showed perforation of the disc and/or its attachment tissues. The occurrence of osteoarthrosis was observed to increase with more advanced disc displacement and changes in disc configuration. Discs of even thickness were associated with osteoarthrosis in 50% compared to 90% for biconvex discs.
The disclosures of the foregoing references are hereby incorporated by this reference.
Temporomandibular joint surgery via arthrotomy (open surgical approach) has been widely advocated for treatment of internal derangements with closed lock when non-surgical therapy has failed. Preauricular, endaural, and postauricular approaches have been employed by various clinicians. Disc repositioning, arthroplasty, meniscectomy with implant, and other procedures have been described to treat internal derangement.
However, one of the principal disadvantages of open surgical approach is that a relatively large incision is necessary to perform two basic procedures: disc repositioning and disc removal. Typically, a curvalinear incision of 6 to 7 centimeters is made and extended through skin and subcutaneous tissues to the depth of the temporalis fascia. The superior part of the flap is extended anteriorly by blunt dissection with a periosteal elevator. The flap is developed inferiorally adjacent to the external auditary cartilage. Usually, a vein crosses the lateral aspect of the articular fossa. This vein while identifying the correct depth of the capsule, is generally dissected out, clamped, divided, and ligated or cauterized.
An oblique incision, parallel to the temporal branches of the facial nerve, is typically made through the superficial layer of the temporal fascia. The incision may extend to bone over the lateral part of the fossa. Its inferior aspect generally should be no farther than 8 millimeters in front of the tragus of the ear. As before, the lateral aspect of the fossa is exposed by blunt dissection with a periosteal elevator.
This type of surgical procedure can lead to a relatively high complication rate, among other disadvantages. For instance, the serious dangers associated with TMJ surgery via arthrotomy include facial nerve paralysis with inability to close eyelid on the affected side, and inability to wrinkle the forehead, post-operative infection, resultant malocclusion (incorrect bite) and limited opening, lack of improvement or worsening of pain and jaw dysfunction; and further degenerative changes with the TMJ.
Accordingly, those skilled in the art have recognized a significant need for TMJ arthroscopic surgical treatment which affords the clinical advantages of using relatively small incision techniques, yet possesses the requirements thereby providing a safer and more convenient surgical procedure and more comfortable therapy for the patient. | {
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In a data recording device, such as a hard disk drive, data is written to circular tracks formed on a disk which is a magnetic recording medium. Therefore, in order to write or read the data, positioning control is necessary for moving a magnetic head to a position on the track. In such a head-positioning mechanism, there are various kinds of measures taken against periodic disturbance caused by various factors.
However, the above disturbance includes, for instance, vibration given to the magnetic disk device whose frequency is hard to specify in advance or the one whose frequency changes with the passage of time. On the other hand, the follow-up control for maintaining the position of the magnetic head relative to a target track is designed to suppress the disturbance in a wide range. As a result, there may be a case where its ability is not enough to suppress disturbance of a specific frequency component.
In recent years, data recording devices such as a hard disk drive have come to be used in various fields including those of portable computers, cellular phones, car-navigation systems, etc. Therefore, a technique to fully suppress the influence of external vibration is desirable.
Japanese Patent Publication No. 2003-109335 (“Patent Document 1”) discloses a method wherein a resonant filter to remove a signal having a specific frequency component is used, and the resonant frequency of the resonant filter is repetitively updated to be gradually close to the frequency of the disturbance so as to remove the disturbance. Moreover, “Frequency Chasing Peak Filter”, M. Kisaka, IEE of Japan Technical Meeting Record, No. IIC-04-70, pg. 19-23 (2004) (“Non-patent document 1”) discloses a technique wherein, when the repetitive updating is performed, such an update-width is determined as the one whose minimum value is set to the square of the position error.
According to the method disclosed by Non-patent document 1, while a convergence rate is increased, a resonant frequency of the resonant filter can be made closer to a target frequency as compared to a case where the update-width is fixed, improving the capability of suppressing disturbance. According to the method disclosed in Non-patent document 1, however, depending on a frequency band to which the resonant frequency belongs, the convergence rate becomes excessively high, resulting in a conversion of the resonant frequency on a frequency away from the target frequency, etc., and desired performance may not be achieved. | {
"pile_set_name": "USPTO Backgrounds"
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Enterprises handle a large number of customer transactions on a daily basis. New methods of conducting transactions become available as technology advances. For some customers, it may be desirable to conduct transactions using a mobile device, such as a smart phone device. However, if a malicious user gains access to a customer's mobile device, the malicious user may be able to conduct transactions. | {
"pile_set_name": "USPTO Backgrounds"
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TDP-43 (TAR DNA-Binding Protein 43) was identified as a protein that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs and represses transcription of viral RNA (Ou, S., J Virol., 69(6):3584-96, 1995). TDP-43 was also identified as a splicing regulator that binds to the (UG)m-repeated polymorphic region near the 3′ splice site of CFTR exon 9 and down-regulates its recognition by the splicing machinery (Buratti, E. and Baralle F E, J Biol Chem., 276(39):36337-43, 2001 and references therein). Notably, exon 9 skipping produces a nonfunctional CFTR protein and is associated with some forms of cystic fibrosis. It was also observed that TDP-43 recognizes (UG) repeats in other contexts.
Hyperphosphorylated, ubiquitinated, C-terminal fragments of TDP-43 have been recovered from the central nervous system (e.g., hippocampus, neocortex, and spinal cord) from patients with frontotemporal lobar degeneration (FTLD) with ubiquitin-positive inclusions and amyotrophic lateral sclerosis (ALS) and is believed to be the hallmark pathological feature of FTLD and ALS (Neumann et al. Science, 314(5796):130-3. 2006). The presence or amount of abnormal aggregation of phosphorylated and ubiquitinated TDP-43 is believed to define a novel class of neurodegenerative diseases referred to as “TDP-43 proteinopathies” (Cairns et al. (2007) The American Journal of Pathology 171(1):227). | {
"pile_set_name": "USPTO Backgrounds"
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In some instances a document, such as an essay or a memorandum, may be thought of as a single individually readable block of data or “story”. In the context of an essay or memorandum the story generally flows in a linear fashion from the front or beginning of the document to the back or end of the document. In other instances, a document may contain more than one story. In some such cases the stories may be arranged in a consecutive manner, such that an entirety of a first story is presented and then an entirety of a second story is presented. In other instances, such as in a newspaper or magazine scenario, the stories may be presented as interposed fragments of stories or story fragments.
Modern documents are often defined using a markup language such as XML or HTML and described as markup documents. Modern documents may also be classified as fixed layout documents or adaptive documents. Adaptive documents re-layout the contents of the document based on the desired overall size of the content, such as a single sheet of paper or the size of a display window. Fixed layout documents describe where each discrete unit of a page's content, such as an image or a single run of text, is positioned on the page. Fixed layout documents are also frequently markup documents. The XML Paper Specification (XPS) describes one such document format (the XPS Document format) that is a fixed layout document and also a markup document.
Fixed layout markup document formats, such as the XPS Document format, define a document as a set of markup elements. Individual markup elements define portions of document content and a location where the content should be displayed within the document. Fixed layout markup document formats do not natively handle structural information relating to the document's markup; such as to recognize that a particular portion of the markup relates to a particular story. Accordingly, fixed document formats do not readily distinguish between multiple stories within a document. | {
"pile_set_name": "USPTO Backgrounds"
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Transparent electrical conductors are widely used in the flat-panel display industry to form electrodes that are used to electrically switch light-emitting or light-transmitting properties of a display pixel, for example in liquid crystal or organic light-emitting diode displays. Transparent conductive electrodes are also used in touch screens in conjunction with displays. In such applications, the transparency and conductivity of the transparent electrodes are important attributes. In general, it is desired that transparent conductors have a high transparency (for example, greater than 90% in the visible spectrum) and a low electrical resistivity (for example, less than 10 ohms/square).
Transparent conductive metal oxides are well known in the display and touch-screen industries and have a number of disadvantages, including limited transparency and conductivity and a tendency to crack under mechanical or environmental stress. Typical prior-art conductive electrode materials include conductive metal oxides such as indium tin oxide (ITO) or very thin layers of metal, for example silver or aluminum or metal alloys including silver or aluminum. These materials are coated, for example, by sputtering or vapor deposition, and are patterned on display or touch-screen substrates, such as glass. For example, the use of transparent conductive oxides to form arrays of touch sensors on one side of a substrate is taught in U.S. Patent Publication 2011/0099805 entitled “Method of Fabricating Capacitive Touch-Screen Panel”.
Transparent conductive metal oxides are increasingly expensive and relatively costly to deposit and pattern. Moreover, the substrate materials are limited by the electrode material deposition process (e.g. sputtering) and the current-carrying capacity of such electrodes is limited, thereby limiting the amount of power that can be supplied to the pixel elements. Although thicker layers of metal oxides or metals increase conductivity, they also reduce the transparency of the electrodes.
Transparent electrodes including very fine patterns of conductive elements, such as metal wires or conductive traces are known. For example, U.S. Patent Publication No. 2011/0007011 teaches a capacitive touch screen with a mesh electrode, as do U.S. Patent Publication No. 2010/0026664, U.S. Patent Publication No. 2010/0328248, and U.S. Pat. No. 8,179,381, which are hereby incorporated in their entirety by reference. As disclosed in U.S. Pat. No. 8,179,381, fine conductor patterns are made by one of several processes, including laser-cured masking, inkjet printing, gravure printing, micro-replication, and micro-contact printing. In particular, micro-replication is used to form micro-conductors formed in micro-replicated channels. The transparent micro-wire electrodes include micro-wires between 0.5μ and 4μ wide and a transparency of between approximately 86% and 96%.
Conductive micro-wires can be formed in micro-channels embossed in a substrate, for example as taught in CN102063951, which is hereby incorporated by reference in its entirety. As discussed in CN102063951, a pattern of micro-channels is formed in a substrate using an embossing technique. Embossing methods are generally known in the prior art and typically include coating a curable liquid, such as a polymer, onto a rigid substrate. A pattern of micro-channels is imprinted (impressed or embossed) onto the polymer layer by a master having an inverted pattern of structures formed on its surface. The polymer is then cured. A conductive ink is coated over the substrate and into the micro-channels, the excess conductive ink between micro-channels is removed, for example by mechanical buffing, patterned chemical electrolysis, or patterned chemical corrosion. The conductive ink in the micro-channels is cured, for example by heating. In an alternative method described in CN102063951, a photosensitive layer, chemical plating, or sputtering is used to pattern conductors, for example, using patterned radiation exposure or physical masks. Unwanted material (e.g. photosensitive resist) is removed, followed by electro-deposition of metallic ions in a bath.
Conductive micro-wires are used to form a touch switch, for example, as illustrated in U.S. Patent Publication 2011/0102370. In this example, a capacitive touch switch includes a first substrate on which is formed a first mesh-like electrode and a second substrate on which is formed a second mesh-like electrode. The first and second substrates are integrally bonded via an adhesive layer in such a manner that the first and second mesh-like electrodes face each other. Such a design requires the use of two substrates that are aligned and bonded together.
Multi-level masks are used with photo-lithography to form thin-film devices, for example as disclosed in U.S. Pat. No. 7,202,179. An imprinted 3D template structure is provided over multiple thin films formed on a substrate. The multiple levels of the template structure are used as masks for etching the thin films. This approach requires the use of a mask and multiple photo-lithographic steps.
The use of integrated circuits with electrical circuitry is well known. Various methods for providing integrated circuits on a substrate and electrically connecting them are also known. Integrated circuits can have a variety of sizes and packages. In one technique, Matsumura et al., in U.S. Patent Publication No. 2006/0055864, describes crystalline silicon substrates used for driving LCD displays. The application describes a method for selectively transferring and affixing pixel-control devices made from first semiconductor substrates onto a second planar display substrate. Wiring interconnections within the pixel-control device and connections from busses and control electrodes to the pixel-control device are shown.
Printed circuit boards are well known for electrically interconnecting integrated circuits and often include multiple layers of conductors with vias for electrically connecting conductors in different layers. Circuit boards are often made by etching conductive layers deposited on laminated fiberglass substrates. | {
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When actuated, irreversible displays undergo permanent changes in appearance. Initially obscured or otherwise hidden information is revealed by the changes of appearance.
Changes that take place in irreversible displays generally involve the revelation of indicia, which can range from a patch of color to text and pictures. The indicia can be revealed by chemical or physical agents that change themselves or that produce other changes in the displays. For example, opaque coloring agents can be rendered transparent to reveal underlying indicia, or similar agents can change from one color to another to indicate a change.
Chemical transformations in irreversible displays are sometimes used for security purposes to provide evidence of tampering or counterfeiting. U.S. Pat. No. 4,488,646 to McCorkle hides a warning message behind a solvent-sensitive blush coating to provide evidence of solvent tampering with letters, tickets, and other information-bearing constructions. Upon exposure to a wide range of aromatic or aliphatic solvents, the blush coating is transformed into a transparent state revealing the message. U.S. Pat. No. 4,903,991 to Wright discloses a document security system in which a latent image is developed by rupturing photoactive microcapsules to verify authenticity.
Mechanical transformations are more often used for interactive game pieces. The most common are scratch-off games in which an opaque coating is removed by abrasion to reveal a hidden indicium. Chang et al. in U.S. Pat. No. 5,431,452 separately position a latent image and a removable image-developing device on different portions of a substrate. The image-developing device contains a chromogenic composition that converts the latent image into a visible image.
Our irreversible displays exploit features of thin metal films, especially vapor deposited films, for such purposes as temporarily obscuring predetermined indicia from view and subsequently reacting with chemical clearing agents to reveal the predetermined indicia. The thin metal films can be cleared away to reveal underlying indicia, or the indicia can also be formed by clearing the films in predetermined patterns. The clearing process is visually engaging as a preferably lustrous metal progressively disappears.
One example of our irreversible display includes a metal layer having a surface that overlies an indicium, such as a contrasting color, a pattern, or a message. A substrate supports the metal layer and the indicium. A chemical clearing agent is supported on the substrate out of contact with the surface of the metal layer that overlies the indicium. The clearing agent is relatively movable into contact with the surface of the metal layer for inducing a chemical reaction that clears the metal layer and reveals the underlying indicium. The metal layer, which can be formed from a variety of metals including aluminum, zinc, or silver, is preferably thick enough to completely obscure the indicium but thin enough to rapidly disappear when placed in contact with the clearing agent. Thicknesses between 100 and 1000 Angstroms are preferred for these purposes.
The clearing agent can be drawn from a variety of materials including electrolytes, acids, bases, and other agents that participate in localized reactions for corroding or otherwise clearing the metal layer. Among the choices are many safe and environmentally friendly materials including edibles such as juices, carbonated beverages, and even condiments. The reactions that clear the metal layer include localized electrochemical reactions that oxidize the metal layer. In contrast to galvanic or electrolytic electrochemical reactions, the localized electrochemical reactions between the clearing agent and the metal layer produce a mixed electropotential and do not require a net flow of current through the metal layer.
Preferably, the substrate is one of a pair of top and bottom substrates between which the clearing agent is confined within a reservoir out of contact with the surface of the metal layer. The top substrate preferably includes a transparent portion (i.e., a window) that overlies the metal layer and the indicium. A gated pathway between the substrates can be used to direct the clearing agent from the reservoir into contact with the surface of the metal layer.
The reservoir can be arranged adjacent to or even surrounding the surface of the metal layer that overlies the indicium. Squeezing the reservoir forces some of the clearing agent along one or more of the gated pathways into contact with the surface of the metal layer from one or more directions. Alternatively, the clearing agent can be arranged to overlie the metal film at an initial separation set by a spacer. An opening through the spacer allows the clearing agent to be relatively moved into contact with the metal layer. The clearing agent of this overlapping arrangement can be an adhesive for maintaining contact with the surface of the metal layer after being relatively moved through the spacer opening.
Another example of our irreversible display includes a metal film, a display window aligned with the metal film, and an indicium that is aligned with the display window but obscured by the metal film. The window provides access to the metal film for exposing the metal film to a chemical clearing agent that clears a portion of the metal film and reveals the indicium. A separate access opening can also be provided along with a transport medium (e.g., a wick) to transport the clearing agent from the opening to the metal film.
The exemplary display can be activated by adding the clearing agent through the display window or other access opening. Contact between the clearing agent and the metal film produces a localized electrochemical reaction between the clearing agent and the metal film without generating an electromotive force beyond the clearing agent. The localized electrochemical reaction clears the metal film (in an apparent gnawing action) and reveals the indicium within the display window through an opening cleared in the metal film by the reaction with the clearing agent.
Other exemplary approaches for controlling contact between a clearing agent and a metal film include forming a breakable barrier layer and microencapsulating the clearing agent. Mechanical action such as squeezing or bending can be used to breach the barrier layer or release the clearing agent from microencapsulation. Adhesive clearing agents can be separately mounted and temporarily protected by a release liner. Upon removal of the release liner, the adhesive clearing agent can be moved in contact with the metal layer through an opening in the top substrate.
Instead of clearing the metal film to reveal an underlying indicium, the metal film can be cleared in a pattern (e.g., a stencil) that forms its own indicium. For example, a protective layer could be laid out in a pattern on the metal film. Exposing a portion of the metal film that is not covered by the protective layer to a clearing agent changes the exposed metal film from opaque to clear. The remaining portion of the metal film that is covered by the protective layer is sheltered from similar exposure to the clearing agent. The two portions of the metal film are arranged for producing a predetermined pattern upon exposure of the first portion of the metal film to the clearing agent.
Our irreversible displays can be manufactured by an in-line press. All of the layers including substrates, metal films, clearing agents, graphics, adhesives, and spacers can be formed from individual webs or from layers applied to the individual webs. The result is a succession of thin flexible displays that can be manufactured quickly at low cost and integrated if desired with other press-produced or otherwise compatible articles. | {
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1. Field of Invention
This invention pertains to a method and an apparatus for shaping an elongated hollow or solid article, and more particularly to a method and apparatus for performing consistent, accurate spatial dimensional shaping of an elongated extruded product.
2. Description of the Art
There are a considerable number of operating parameters and conditions present in various metal forming methods which cause finished products to exhibit dimensional variability. In certain processes the dimensional variability is acceptable, while in other processes the dimensional variability is unacceptable and requires subsequent metal finishing operations.
In the extrusion process, for example, a heated ingot or billet is forced to flow under pressure through a die opening to form an elongated article such as a channel, a tube or an angle. In a typical aluminum extrusion process the extruded product is forced through the die at forces in the 500 to 15,000 ton range. The extrusion exits the die of an extrusion press at elevated temperatures on the order of 300.degree. to 1200.degree. F. It is common to solution heat treat and quench the extruded product in an in-line solution heat treating process or by a separate solution heat treatment process. Such extruded product may be made to various lengths, including lengths in excess of 150 feet, and may be of diverse cross-sectional configuration.
Considering the operating parameters of the extrusion process including pressures, temperatures, die condition and product length, and considering the effects of subsequent heat treatment and quenching, it is understandable that extruded metal products may exhibit considerable dimensional variation about the cross-section and over the length of the product. It is also understandable that such dimensional variation may be present from product cycle to product cycle and from extrusion run to extrusion run. It is therefore often necessary to perform subsequent metal finishing operations to bring the product within acceptable dimensional tolerance. There are some dimensional variations on extruded metal products which are not readily correctable by conventional metal finishing operations, including bending, roll straightening and hammering. In such conventional metal finishing operations, springback is a major concern. Such springback may be so extreme, especially in products with substantial dimensional variation, that such conventional metal finishing operations are inadequate.
Prior shaping methods and apparatus have provided methods to finish the shape of articles, such as extrusions. The tolerances currently permissible for such products, as published by the Aluminum Association, particularly for thin walled extrusions, are so broad that the products may be precluded from certain critical applications. If the dimensional deviation could be reduced, the products may be applicable in an increased number of applications where dimension is important. Furthermore, the dimensional quality of the product in existing applications could be dramatically increased.
Despite prior art attempts to improve the dimensional tolerance and minimize dimensional variation in a finishing operation, there is a need for further improvement. Accordingly, a stretch shaping method and apparatus are desired which results in finish shaping an elongated article, such as an extrusion, to minimize cross-sectional and longitudinal dimensional deviations from nominal value. | {
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With recent developments in digital technology, electronic devices available for communication and personal data processing on the move, such as mobile communication terminals, personal digital assistants (PDAs), electronic organizers, smart phones, and tablet personal computers (PCs), are being diversely released. Such electronic devices may not stay in their own traditional specific areas and can attain a mobile convergence stage in which they embrace the areas of other terminals.
Typically, an electronic device may include a call function such as a voice call or a video call function, a message transmission function such as a short message service (SMS)/multimedia message service (MMS) and an e-mail function, an electronic organizer function, a recording function, a TV playback function, a video playback function, a music playback function, an Internet function, a messenger function, and a social networking service (SNS) function. The electronic device may download an application corresponding to the above function from a server device and may install the downloaded application.
The electronic device can provide a function for interlocking with a peripheral device. Here, the peripheral device may include an output device for outputting audio data or a display device for outputting video data according to the execution of a function in an electronic device.
Moreover, a conventional peripheral device can be manufactured below a predetermined size according to a specific purpose such as portability or mounting. For example, a conventional peripheral device may limit the size of a mounted battery or may present difficulties in mounting a specific communication module. Accordingly, the conventional peripheral device may have difficulties in receiving information relating to a specific function through direct market access due to a power issue or difficulty in establishing a communication channel. | {
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Storytelling, as an art, has evolved over centuries from being verbally communicated to electronically communicated. Likewise, within the field of electronic communications, methods and systems for storytelling have progressed.
However, even with such progress, there still exists a need for a platform via which storytelling with tangents and side thoughts can be communicated in an efficient and elegant manner. Further, there exists a need for a platform via which a user or storyteller can check and search on specific topics or subjects within the story and/or tangential story. | {
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1. Technical Field
Embodiments of the present disclosure relate generally to delay line circuits, and more specifically to a delay locked loop with delay programmability.
2. Related Art
A delay locked loop (DLL) refers to a closed-loop feedback circuit that adjusts the phase of its output to achieve a desired phase difference between the output and an input signal. The adjustment is typically done based on an error signal generated as a comparison result of the phases of the output and the input signal. The input signal is typically a clock signal, a data stream or other periodic signal, while the output is typically a clock signal.
The phase difference between the output of a DLL and the input signal is termed as the ‘delay’ provided by the DLL. Delay programmability refers to a capability by which the delay provided by the DLL can be specified as an input value or otherwise be set in the DLL. The input specifying the delay may be provided, for example, as a “delay value” by an external device (e.g., by a processor external to the DLL). Alternatively, the desired delay may be obtained by activating one or more control signals provided as inputs to the DLL. | {
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Wireless data usage has experienced, and continues to experience, significant growth. Some estimates provide for growth in data usage exceeding one thousand times current usage in the near future. Contributing factors to this growth include higher data usage on mobile devices such as smartphones or tablets, as well as the use of data in other emerging areas such as machine-to-machine, device-to-device, or other traffic types.
Currently, significant data is provided by network operators. For example, data may be provided over cellular networks, such as those described by the Third Generation Partnership Project (3GPP) standards. Such mobile technologies include, but are not limited to, Second Generation networks such as the Global System for Mobile Communications (GSM) and Code Division Multiple Access (CDMA), Third Generation networks such as the Universal Mobile Telecommunications System (UMTS), and Fourth Generation networks such as Long Term Evolution (LTE). Also, Fifth Generation (5G) networks are starting to be developed. Utilizing the technologies in these standards, network operators provide a user equipment (UE) with data services.
Wireless data is also provided in other ways, for example, The Institute of Electrical and Electronic Engineers (IEEE) 802.11 standards for wireless local area networks (WLAN).
However, wireless spectrum is heavily utilized in many situations by network operators and in order to accommodate a significant data increase, various options including the use of unlicensed spectrum for 5G communications is being explored. | {
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1. Field of the Invention
The present invention relates to a catalyst for purifying the contents of exhaust gas from an internal combustion engine, and metal oxide particles suitable as a carrier for an exhaust gas purifying catalyst and a method for preparing this.
2. Description of the Related Art
Exhaust gas from an internal combusting engine such as an automobile engine comprises nitrogen oxide (NOx), carbon monoxide (CO), hydrocarbon (HC) and etc. These contents of the exhaust gas can be purified by the use of an exhaust gas purifying catalyst which oxidizes CO and HC while reduce NOx. A representative exhaust gas purifying catalyst includes a three way catalyst which comprises porous metal oxide carrier such as γ-alumina and a noble metal such as platinum (Pt), Rhodium (Rh) and/or Palladium (Pd) carried thereon.
It is necessary that an internal combustion engine is driven at stoichiometric air/fuel ratio (stoichiometry) in order for the three way catalyst to achieve effective oxidation of CO and HC as well as reduction of NOx. In the case that the internal combustion engine is driven at excess oxygen atmosphere (lean) or at excess fuel atmosphere (rich), the three-way catalyst cannot demonstrate its purification ability as the oxygen concentration in the exhaust gas becomes outside the range of the optimum oxygen concentration for the three-way catalyst.
It is well known that a material having an oxygen storage capacity (OSC) is used with an exhaust gas purifying catalyst. OSC means a capacity enabling storing oxygen at the high oxygen concentration and releasing oxygen at the low oxygen concentration. OSC is useful to buffer the change of oxygen concentration in exhaust gas and thereby enhances the exhaust gas purifying ability of the three way catalyst. A representative material having OSC is ceria (CeO2). Ceria has not only OSC but also large affinity with noble metal carried thereon. Therefore, the ceria is also useful to prevent particle growth (sintering) of the noble metal carried thereon. Methods for preparing mixed metal oxide of ceria and zirconia have been developed to provide materials having high heat resistivity as ceria has small specific surface area and low heat resistivity. Regarding the prior arts, refer to Japanese Unexamined Patent Publication No. 8-103650, 8-109020, 8-109021, 2000-319019, 2001-89143 and etc.
According to the prior arts, as both ceria and zirconia exist on the surface of the mixed metal oxide comprising uniformly mixed ceria and zirconia, a noble metal carried by the mixed metal oxide randomly deposits on both ceria and zirconia surface. Therefore, in the prior arts, there is a problem that an affinity between the mixed metal oxide and noble metal is lowered, the noble metal is sintered and, then, the catalyst loses its ability to purify exhaust gas.
That is, the previous catalysts comprising a cerium-zirconium mixed metal oxide lose OSC, and an ability to purify exhaust gas, by the sintering of noble metal on their surface, particularly when they are exposed to a high temperature of 1000° C. or more for a long time.
Therefore, there remains a need for an exhaust gas purifying catalyst which maintains a heat resistivity of mixed metal oxide, has high affinity to a noble metal to maintain OSC, and only slightly lose its ability to purify exhaust gas after being exposed to a high temperature. Further, there remains a need for a method for preparing a metal oxide suitable for the exhaust gas purifying catalyst. | {
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The device of this invention resides in the area of cartridges having nozzles and foil seals located at the bottom of such nozzles, such cartridges containing a variety of filler materials such as a caulking material, adhesive and the like, such cartridges, after the top of the nozzle has been opened and the foil seal broken, to be inserted into a gun for the application of its contents through the nozzle when the gun""s plunger is advanced by action of its trigger, and more particularly relates to an improved nozzle having built-in means for piercing the foil seal.
Cartridges containing a wide variety of flowable material, such as caulking material and adhesives, are well known in the industry. Such cylindrical cartridges have nozzles at their top end and, after opening, such cartridges are inserted into guns wherein a plunger is advanced therein by action of squeezing a trigger, causing material in the cartridge to flow out through the nozzle to the area where it is to be applied. Some cartridges have a foil seal under the nozzle against which seal the material can be positioned. Some materials, if exposed to air, will harden, so that by providing such a seal, air contact with the materials before the cartridge is opened is minimized. To open a cartridge having a foil seal, one must first snip off the tip of the plastic nozzle and then insert an object down the nozzle to puncture the foil seal located at the bottom of the nozzle to allow the passage of the filler material out of the cartridge. It is sometimes difficult to locate a narrow enough instrument to insert down the open nozzle tip to puncture the foil seal. Further, if one snips off the nozzle tip to leave a small diameter opening to achieve a fine application bead of material and one does not have an instrument narrow enough to pass down through the opening in the nozzle to puncture the foil seal, one can undesirably stretch the nozzle tip by using a larger object, making it difficult to apply a narrow bead of material as the now-wider opening in the nozzle tip will allow a wider-than-desired bead of material to pass out the nozzle.
Cartridges filled with a variety of filler materials are commonly sold. The tops of such cartridges including their nozzles are formed of plastic. The top is spun within the barrel to effect a heat seal with the sides of the barrel. Nozzle tops are also made in two parts wherein plastic nozzle top is press fit into a metal crimpable end cap, forming a nozzle top which can be crimped onto a paperboard barrel. The foil seal of a cartridge is located beneath the central bore of the nozzle which foil seal prevents the premature escape of the filler material when the cartridge is loaded in the gun and also prevents such material from drying out and hardening within the cartridge. The tip of the cartridge nozzle is often initially sealed and must be snipped off at a desired point along the tapered nozzle to effect the desired shape of opening to create the size of the bead of material which will be applied by the user.
My own patent, granted to Paul D. Jackman, U.S. Pat. No. 6,029,856, issued on Feb. 29, 2000, hereafter referred to as xe2x80x9cmy prior patentxe2x80x9d describes a self-puncturing cartridge nozzle. The devise of my prior patent requires that the user manually bend the nozzle laterally in relation to nozzle base which motion causes a sharpened edge located at the inside of the base of the nozzle to cut through the foil seal.
Normally cartridge nozzles are opened by first snipping the tip off at a certain distance from the tapered end to achieve a specific bead width. A disadvantage of my prior patent is that the user is also required to bend the nozzle to a specific point whereby the foil seal is punctured. This manual opening procedure related to the foil seal must be communicated to the user in writing on the cartridge body of specific instructions regarding it. The above describes a two step opening procedure.
Disadvantages of my prior patent:
(a) Two separate steps are required to open the cartridge.
(b) A user may inadvertently bend the nozzle too far and possibly fracture plastic at base of nozzle.
(c) A user may not bend the nozzle far enough to sufficiently puncture the foil seal.
(d) A cartridge may be dropped accidentally causing nozzle to bend and puncture foil seal before it was intended to be opened possibly causing contents to leak or dry out.
(e) Softer, pliable plastic compounds required to allow nozzle to be flexible may be too weak for requirements in shipping, handling, vertical stacking, and other manufacturing procedure.
(f) Foil seals could be punctured by persons tampering with cartridges at retail locations which could cause filler material to dry out.
It is the object of this invention to provide a cartridge for containing various filler materials having a nozzle tip and a foil seal thereunder with self contained means to puncture foil seal by pressurizing filler material to allow the passage through the nozzle of the contents of the cartridge.
To accomplish this result, the plastic nozzle top of the cartridge is formed with a downwardly extending sharp edge disposed above the foil seal. When the contents of the cartridge is pressurized, the foil seal is forced by such pressure into the sharp edge at the base of the nozzle causing the foil seal to puncture and thereby allow the contents of the cartridge to pass through the opened tip of the nozzle for application.
It is yet a further object of this invention to provide an improved nozzle to a cartridge barrel which is molded of plastic which can be easily substituted for prior art nozzle tops during the manufacture of cartridges without any other changes to the product required and which can be entirely molded of one piece of plastic.
It is yet a further object of this invention to provide an improved nozzle top to a cartridge which can be press fit into a crimpable metal end cap. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The present invention relates to a lubricant heating system for use with an internal combustion engine.
2. Description of the Prior Art
It takes a warming-up time of several minutes for an internal combustion engine of an automobile or the like to have its lubricant temperature raised to a sufficient level for its normal operation after it has been started. Moreover, the unevaporated fuel, which may steal into the air-fuel mixture sucked into a combustion chamber during the operation of the engine, may flow down a piston through a clearance, which is formed between the facing ends of a piston ring, during the compression stroke of the piston until it steals into the lubricant below a crankcase. This tendency is increased when the internal combustion engine is run at a cold place or when an alcohol fuel is used. Moreover, the lubricant, which has been mixed with the fuel, has its viscosity lowered to invite a disadvantage that its lubricating performance is degraded. | {
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Within the conventional technology, an implementation of a B+ tree data structure can be used for creating some type of indices. For example, a larger virtual address space can be mapped to a relatively smaller physical address space. In this case, the key-value pairs in the B+ tree data structure are virtual to physical address mappings (or translations). In addition, these translations are stored in B+ tree format in order to obtain search efficiency and to keep metadata (translations) size proportional to the physical storage. There is a requirement that such B+ tree data structures should satisfy ACID (atomicity, consistency, isolation, durability) properties.
More specifically, in order to guarantee ACID properties, an implementation of the B+ tree data structure requires updates to the tree to go through a transaction mechanism. For example, the transaction mechanism involves writing to a transaction log and then replaying the transaction log. However, the transactions are costly to performance in terms of the number of inputs and outputs (I/Os) and contention that they cause for the transaction log area. | {
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A device provided with a shutter-type optical power attenuator and an optical power monitor is known (for example, see patent literature 1). In this device, incident light from an optical fiber on an input side is attenuated by the shutter-type optical power attenuator and the attenuated light is output from an optical fiber on an output side. Moreover, a light quantity thereof is detected by the optical power monitor. | {
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The variety of applications available for devices like laptops, mobile phones, tablets, netbooks, and other computing devices have not only increased demand for such devices but have also made them a necessity. In addition to basic communication/computing capability of the devices, the applications installed on the devices may allow users to perform varied functions like access information, improve interactivity with customers, work from remote locations, contact administrative departments, access multimedia content, etc. Generally, there may be two types of applications, namely, native applications, which may be developed using native technologies and tend to work on devices for which they are developed using closed compiled code; and web-based applications, which may be developed using a language readable by everyone, for example, a markup language (for example, hypertext markup language 5 (HTML5)) or JavaScript.
Application developers may develop an application using a language that is widely acceptable as it becomes easier for them to release versions of the application for all platforms. However, as the code may be accessible (for example, in clear text), it may give rise to code protection problems. For instance, competitors may steal the code and reuse it for their own applications, therefore, saving upon the initial investments (for example, time and cost) needed to produce an equivalent code; or there may be pirated versions of the code that may be leaked onto the web. These versions may be accessed by users who may be able to install and execute the code without buying it.
A number of techniques have been employed to counter this problem. For example, before the code is transmitted, it is encrypted using a random key or a hash key. At the client (for example, a mobile phone or a laptop) or the computing device, the encrypted code is decrypted by using the random key or hash key transmitted by the server. However, once the code is decrypted, it can be captured and installed on any other client. Therefore, there is a need for a mechanism that solves the above problems and provides for a protection mechanism for web-based applications. | {
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1. Field of the Invention
The invention pertains to an improvement in the art of the toy or sporting device generally referred to as a skateboard.
2. Description of the Prior Art
Skateboards, as presently produced, evolved from a separation of a roller skate in two parts and the attachment of the front and rear wheel assemblies to a board. In recent years, fiberglass and plastics have been used for construction of the platforms and well designed and highly efficient wheels, bearings and associated structure mounted on pivotally flexible mounts have been developed. The area of improvement incorporated in this invention generally pertains to a torsion bar interconnecting the front wheel assemblies and the rear wheel assemblies. To the best knowledge of your applicant no similar structure has heretofore been employed in skateboards. A somewhat related structure appears in U.S Pat. Nos. 1,377,948 to Wacker; 3,667,777 to Enriquez; and 3,891,225 to Sessa. | {
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1. Field of Art
The present invention generally relates to the field of digital video, and more specifically, to methods of identifying real-world objects present within a video.
2. Background of the Invention
Currently, automated recognition within a digital video of images of real-world objects of interest to a user, such as people, animals, automobiles, consumer products, buildings, and the like, is a difficult problem. Conventional systems, to the extent that they allow for such recognition at all, typically use supervised learning which requires training sets of images that have been manually labeled as representing particular objects. Thus, such conventional systems rely on direct human input to provide object exemplars explicitly labeled as representing the object, such as a set of images known to include, for example, dogs, based on prior human examination. However, such human input is expensive, time-consuming, and cannot scale up to handle very large data sets comprising hundreds of thousands of objects and millions of images. This is particularly a problem in the context of video hosting systems, such as Google Video or YouTube, in which users submit millions of videos, each containing numerous distinct visual objects over the length of the video. The use of unsupervised learning techniques, in which the explicit input of human operators is not required to learn to recognize objects, has not yet been achieved for large-scale image recognition systems. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The present invention relates to a semiconductor integrated circuit device and more particularly to a technology effectively utilized, for example, for a preprocessing LSI (AFE: Analog Front End) for a camera provided with Pipelined A-D conversion circuit.
2. Description of Related Art
Pipeline A-D conversion circuits are disclosed, for example, in Japanese Unexamined Patent Publication No. Hei 08 (1996)-337989 and in Japanese Unexamined Patent Publication No. 2000-013232.
[Patent Document 1] Japanese Unexamined Patent Publication No. Hei 08 (1996)-337989
[Patent Document 2] Japanese Unexamined Patent Publication No. 2000-013232 | {
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} |
The goal of the invention is to replace or reduce personal auto, bus, and taxi use and thereby reduce traffic congestion in urban areas, with an “Energy Neutral” (i.e.: “zero emissions/zero fossil fuel use”) “single person mover” vehicle, which as an alternative vehicle, creates a smaller “urban footprint” as compared to a personal automobile, bus, or taxi.
Prior to this invention, all other personal mobility transport devices have failed to provide solutions to the need for a complementary commuter vehicle for the “first mile trip” (i.e. from home to train station or bus stop) and for the “last mile trip” (i.e: leaving a train station or bus stop to any destination not within ones desired walking distance), that are small enough to be accepted with regular usage of public transit, such, but not limited to, train, bus and subway. While other attempts have been made to create viable complementary commuter devices, such devices have been too heavy to be portable and too large to be accepted in public transport vehicles during rush hours.
In the case of some more recent devices where some portability is allowed, these devices (known as “single wheel electric unicycles” or “single or dual wheel light SEGWAY”) are more portable and may be accepted on certain public transport vehicles, but all require more advanced balancing skills than most consumers have. Further, all of the more recent devices rely on gyroscopic sensors to control these devices. These devices many times cause a multitude of accidents and serious injuries to those who use these devices. For example, James Heselden, a former owner of the SEGWAY company died in 2010 after losing control of such a device. | {
"pile_set_name": "USPTO Backgrounds"
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The present invention relates to a device for removing a film-like image forming substance from a recording medium for thereby regenerating the medium.
Recent office automation has brought about the consumption of a great amount of printer sheets and copier sheets and, therefore, a great amount of waste sheets in offices. Most of the waste sheets are simply disposed of. The disposal of the waste sheets not only needs an extra cost, but also deteriorates the local environment due to the processing of the sheets. Moreover, it deteriorates the environment in the global scale due to excessive lumbering.
It has been customary to recycle the sheets by removing ink therefrom, immersing them in a liquid, and then making new sheets. Today, an advanced kind of sheets are under development which can be recycled for copying and printing purposes if text images formed thereon are removed by cleaning. For example, Japanese Patent Laid-Open Publication 4-670043 discloses a sheet having a substrate whose surfaces, particularly one surface, is treated to have a parting ability. The substrate with the parting ability is provided with a mark to be distinguished from ordinary sheets. However, this kind of sheet is special and not feasible for a copier because an image cannot be stably fixed thereon. Japanese Patent Laid-Open publication Nos. 1-101576 and 1-101577 each teaches a method of removing an image from a sheet by treating the sheet with ultrasonic waves in an organic solvent, which dissolves a film-like image forming substance (toner) on the substrate of the sheet. The organic solvent, however, brings about environmental pollution as well as hazards due to its inflammability and toxicity. Hence, this kind of scheme is not feasible for offices and homes. Japanese Patent Laid-Open publication No. 1-297294 proposes a cleaning method practicable with a substrate made of plastic, metal, paper low in infiltration, ceramic or similar material. The method heats, with the intermediary of a thermally soluble separating body, an image formed on such a kind of substrate. However, this approach is not practicable without resorting to a special sheet whose surfaces are provided with a parting ability.
On the other hand, Japanese Patent Laid-Open Publication No. 4-255916 teaches a method and device for removing a film-like image forming substance from a recording medium having a layer which swells when brought into contact with a liquid. The swelling layer is formed at least on the side of the medium where an image is to be formed. The device includes supplying means for supplying to the medium a water-containing liquid (removal accelerating liquid) which causes the swelling layer to swell more than the substance provided on the medium. Separating means presses, after the liquid has been supplied to the medium, a separating member against the medium with or without heating to thereby transfer the substance from the medium to the separating member. It was experimentally determined that this method is capable of removing only the film-like image forming substance from the medium without damaging the texture of the medium to a noticeable degree, thereby restoring the medium to a reusable condition. It should be noted that the word "film-like" refers not only to a condition wherein the entire image forms a single film, but also to a condition wherein the substance is not infiltrated deep into the medium, and a condition wherein the substance is not adsorbed by the medium almost at the molecule level. This kind of adsorption occurs with water ink containing a dye. | {
"pile_set_name": "USPTO Backgrounds"
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Obesity is a major health problem in developed countries. In the United States, the complications of obesity affect nearly one in five individuals at an annual cost of approximately $40 billion. Except for rare pathological conditions, weight gain is often directly correlated to overeating.
One strategy for controlling the individual's food intake is via the use of intragastric volume-occupying devices. Such devices are placed in the stomach and occupy a portion of its interior. Properly placed and sized, the intragastric volumes provide the patient with a feeling of satiety after having eaten only a smaller amount of food. Typically, the individual's caloric intake is thus diminished due to the subjective feeling of fullness. There are a number of available volume-occupying devices. Many must be introduced using surgical or other complex gastric procedures.
Intragastric balloons have been in clinical use for several years. Their success in the treatment of certain individuals with morbid obesity is well accepted.
Published U.S. Patent Application No. 2004/0186502, U.S. Pat. No. 6,981,980, and published PCT application WO/2006/020929, to Sampson et al, each disclose inflatable, intragastric volume-occupying balloons including a valve that provides fluid communication into the balloon from outside the body. The '502 application further discloses a method for occupying some amount of stomach volume comprising the step of inserting the deflated balloon into the stomach through the esophagus, inflating the balloon by introducing an activating liquid through the self-sealing valve. Each document describes selection of polymers allowing gastric erosion of the balloon and causing its subsequent deflation.
Published PCT Application WO/2006/044640, to Baker et al, shows an implant used as a bariatric device situated along certain walls of the stomach to induce a feeling of satiation.
Published U.S. Patent Application 2004/0192582, to Burnett et al, shows a composition and a device that expands in the stomach after swallowing and provide a temporary, erodible volume and consequent diminution of gastric volume in the stomach.
U.S. Pat. Nos. 6,271,278 and 5,750,585, each to Park et al, show compositions of swellable, superabsorbant-hydrogel composites that may be used in gastric retention treatments for obesity.
U.S. Pat. No. 4,607,618, to Angelchik, discloses an intragastric device made up of semi-rigid skeleton members, collapsible to a shape, and having dimensions suitable for endoscopic insertion into the stomach through the esophagus.
U.S. Pat. No. 5,129,915, to Cantenys, relates to an intragastric balloon that is intended to be swallowed and that inflates automatically under the effect of temperature. The Cantenys patent lists three ways that an intragastric balloon might be inflated by a change in temperature. First, a composition of a solid acid and of a non-toxic carbonate or bicarbonate is temporarily kept from the fluid in the stomach by a coating of chocolate, cocoa paste, or cocoa butter. The chocolate coating is selected to melt at body temperature. Secondly, a citric acid and alkaline bicarbonate composition coated a coating of non-toxic vegetable or animal fat melting at body temperature may be used. When in the presence of water, the composition is said to produce the same result as does the earlier-discussed composition. Third, the solid acid and non-toxic carbonate or bicarbonate composition may be temporarily isolated from water by an isolation pouch of a low-strength synthetic material which is to break immediately upon swallowing. Breaking the isolation pouches causes the acid, carbonate or bicarbonate, and water to mix and to react, thereby inflating the balloon. The balloon itself is said to be made up of a modestly porous, but non-digestible material that allows slow deflation.
WO/2005/039458 shows a gastric constriction device that is to be mounted exterior to the stomach and cause feelings of satiation due to pressure on the vigil nerves of the stomach.
WO/2005/101983, to Dharmadhikari, shows an expandable composition that may be used as a gastric retention system, with or without the presence of ancillary drugs.
U.S. Pat. No. 5,783,212, to Fasihi et al, shows an expandable, erodible polymeric composition that may be used in drug delivery systems.
U.S. Pat. No. 6,733,512, to McGhan, describes an intragastric balloon having erodible patches that allow self-deflation of the balloon after a chosen period of residence in the stomach.
None of the cited documents discloses the bioerodible intragastric implant deliverable to the stomach by conventional oral administration that is described below. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The present invention relates to a method of producing a fiber containing carbon as a major component, a method of producing an electron-emitting device using the fiber, a method of producing an electron source having a plurality of the electron emitting devices arranged in an array configuration, and a method of producing an image display device comprising the electron source.
2. Description of the Related Art
One type of cold cathode device which has been given attention is the field-emission type (FE type) of electron emitting device which emits electrons from the surface of a material utilizing the known tunnel effect. As an example of the FE type cold cathode, at least one having a cone or quardrangular pyramid shape such as the FE cold cathode disclosed in the publication entitled “physical properties of thin-film field emission cathodes with molybdenum cones”, J. Appl. Phys., 47, 5248 (1976), by Spindt, or the like, has been known (hereinafter, referred to as the Spindt type).
In recent years, much attention also has been given to FE type cold cathodes using carbon nanotubes as emitter materials thereof. With regard to methods of producing electron emission devices using carbon nanotubes, a method of placing previously-produced carbon nanotubes into a paste material or the like, and arranging them into predetermined positions in array configuration is known (see Japanese Patent Laid-Open No. 2001-043792; hereinafter, this method is referred to as an indirect arraying method), as is a method of arranging a metallic catalyst in desired positions in an array on a substrate, and selectively growing carbon nanofibers in areas having the metallic catalyst arrayed therein by a chemical vapor deposition method (see Japanese Patent Laid-Open No. 2000-057934; hereinafter, this method is referred to as a direct arraying method). | {
"pile_set_name": "USPTO Backgrounds"
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Drive mechanisms are known in the art. They generally include a motor, a controller connected to the motor to control its operation and various sensors including limit switches, proximity sensors and the like, connected to the controller to supply data thereto in view of improving the usability and the safety of the drive mechanism.
The use of such sensors is detrimental since they are prone to failure and increase the cost of the drive mechanism. Furthermore, failure of safety sensors may lead, in some case, to material damage and potentially to human injury. | {
"pile_set_name": "USPTO Backgrounds"
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1. Technical Field
The present invention relates to an acceleration switch and an electronic device including the acceleration switch.
2. Background Art
As a conventional acceleration switch, an omnidirectional acceleration switch in which a counter electrode is provided inside amass body and the mass body is supported by a plurality of beams is described with reference to FIG. 19. FIG. 19 is a top view of the conventional acceleration switch. This acceleration switch 100 includes a peripheral portion 101, four beams 102 to 105, a mass body (weight) 106, and a counter electrode 107. One end of the mass body is supported by the four beams, which are fixed to the peripheral portion. In accordance with acceleration applied to the acceleration switch, the mass body and the counter electrode disposed inside the mass body are brought into contact with each other. In this manner, an external device connected to the acceleration switch detects vibration. This acceleration switch has various advantages such as being available as a normally-off and omnidirectional switch and being relatively compact and mass-producible because monocrystalline silicon can be used as abase for production with the use of semiconductor manufacturing technology.
If the acceleration switch is mounted in, for example, a portable device which can incorporate only a small capacity battery to save power, the device can stop its operation when a human vibration is not detected, that is, when the device is not used, and the device can automatically start its operation upon detection of vibration, that is, when the device is used. Thus, it is possible to realize an electronic device in which the wasted use of a battery is avoided.
On the other hand, in an acceleration switch which detects vibration based on applied acceleration and turns ON and OFF the device, it is desired to uniformly detect vibration in any direction, and hence an omnidirectional switch is advantageous. Accordingly, as described in Patent Literature 1, it is desired to support a weight (mass body) by a plurality of beams so that the vibration of the weight may not be one-sided depending on the acceleration.
Such acceleration switch to be mounted on a portable device is highly required to be more compact, and hence a smaller external dimension of the acceleration switch is more advantageous. Cost of the acceleration switch is also highly required to be lower, and it is therefore further advantageous to use the semiconductor manufacturing technology to reduce the external dimension of the acceleration switch and thereby produce a large number of acceleration switches on a single wafer. | {
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The present invention generally relates to an apparatus for manually transporting and supporting a work tool at a desired location at a work site. More specifically, the present invention relates to a convertible apparatus that can transport a work tool in a horizontal, transport position and can be manipulated to support the work tool in an upright, working position.
Power tools, such as miter saws, sanders, table saws and grinders, are often needed to perform work operations in more than one location on a construction or work site. Since large power tools, such as those described above, are oftentimes large and cumbersome and have uneven weight distribution, transporting these work tools from one location at a work site to another, or from a vehicle to the work site, can be difficult. Often moving such work tools requires more than one worker or the use of a hand truck. When an upright hand truck is employed, the work tool is frequently supported on the toe plate of the hand truck in an unsecured manner, creating the potential for damage to the work tool if the work tool falls from the toe plate.
Once the work tool has been transported to the desired location at the work site, the work tool must be positioned in a convenient location for proper use. For example, it is desirable to have a work tool such as a miter saw or table saw positioned at least at waist height in order to ensure the ease of operation of the work tool. Proper support of the work tool can require that the work tool be placed on a level surface or be securely fastened to a table or machine stand. However, depending on the particular work site, these conditions may not be available and something less than ideal might have to be settled for. In either event, a worker must lift the work tool off of the hand truck and into the operating position, creating a risk of injury to the worker. The potential for injury is further increased if the work tool must be operated in a position that is less than ideal, as described above.
In addition to the problems associated with moving a work tool to the desired location at a work site, once the tool is no longer needed at the work site, the tool must be loaded into a work truck. Since the work tool is oftentimes heavy and cumbersome, more than one worker is again required to load the work tool onto the truck or other transportation device.
Therefore, it is an object of the present invention to provide a convertible transporting and supporting apparatus for use with a work tool. It is an additional object of the present invention to provide such an apparatus that is convertible between a working position and a transport position such that the apparatus and attached work tool can be both easily transported and functional in presenting the work tool at an acceptable operating height once at the work site. Further, it is an object of the present invention to provide a convertible apparatus that includes a removable handle member that allows the handle to be used when the convertible apparatus is in both the horizontal, transport position and the vertical working position.
The present invention is a convertible apparatus that can be used to transport a work tool around a work site and can be converted into an upright, working position to support and position the work tool at a desired, usable height. The convertible apparatus includes a back, support frame that includes a pair of spaced support tubes each of which extend parallel to a longitudinal axis. The support frame of the convertible apparatus extends between a first end and a second end and forms the backbone of the apparatus.
The convertible apparatus includes a base member that extends from the first end of the support frame in a direction perpendicular to the longitudinal axis of the support frame. The base member contacts the ground to stabilize the convertible apparatus when the convertible apparatus is in its upright, working position. A pair of lower braces extend from opposite sides of the base member and are each attached to one of the support tubes of the support frame. The base members strengthen the perpendicular connection between the support frame and the base member such that the apparatus can support the weight of the work tool when the apparatus is in its upright, working position. A primary wheel assembly is mounted to the first end of the support frame opposite the mounting connection between the support frame and the base member. The primary wheel assembly aids in supporting the apparatus in the upright, working position and also allows the convertible apparatus to be transported for short distances when in the upright, working position.
The convertible apparatus includes a work platform that is mounted to a mounting platform secured to the support frame. The work platform is pivotally mounted to the mounting platform and is movable between an extended position and a collapsed position. When the convertible apparatus is in its upright, working position, the work platform can be extended such that the work tool secured to the work platform is presented in the proper orientation for use by a worker.
The convertible apparatus includes a pair of braces that are connected to the work platform to support the work platform when the work platform is in its extended position. Each of the braces extend from one side of the work platform and are each received within a locking device mounted to the support frame. The locking devices include a locking handle that can be tightened to secure the brace within a stationary position. When the work platform is moved to its extended position, the locking device is tightened such that the braces can no longer move through the locking device. In this manner, the pair of braces are used to support and stabilize the work platform in its extended position.
When the convertible apparatus is to be moved around the work site, the locking devices are loosened and the work platform is moved from its extended position to its collapsed position. When the work platform moves to the collapsed position, a securing pin passes through a hole in the work platform to retain the work platform in its collapsed position. Once the work platform has been stabilized, the support frame is moved from the upright, working position to a horizontal, transport position. When the convertible apparatus is in the horizontal, transport position, a secondary wheel assembly attached to the second end of the support frame supports the apparatus on the ground along with the primary wheel assembly.
The secondary wheel assembly includes a pair of wheel tubes that extend perpendicular to the longitudinal axis of the support frame. Each of the wheel tubes is attached to one of the support tubes of the support frame by an angle bracket.
The convertible apparatus includes a removable handle that is attachable to the support frame in both a first position and a second position. When the handle is in the first position, the handle is received within the spaced support tubes of the support frame and extends parallel to the longitudinal axis of the support frame. When the handle is in the second position, the handle is received within the wheel tubes and thus extends perpendicular to the longitudinal axis of the support frame. The movement of the handle between the first position and the second position allows the handle to be used to move the apparatus when the apparatus is in both the upright, working position and the horizontal, transport position.
Various other features, objects and advantages of the invention will be made apparent from the following description taken together with the drawings. | {
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The invention relates generally to data storage systems, and in particular, to job scheduling for I/O requests directed to devices in data storage systems.
In typical data storage systems, a storage controller serves as an interface between external host computers and the physical storage devices of the data storage system, and thus controls all back-end (or device-side) operations. The back-end operations can include services for read misses, as well as write destaging, read prefetching, RAID, data copy and other types of background operations. The scheduling of these types of operations has a major effect on the performance of the data storage system as a whole.
In prior art data storage systems, the storage controller typically strives to provide the lowest response time possible for host-waiting type operations (e.g., read misses) at the expense of its background duties. Favoring the host requests in this manner tends to starve the background operations. Moreover, when there are no pending host requests, the storage controller schedules a background operation for a logical device and decisions regarding the logical device selection are made entirely at the logical level.
Such an approach can have a detrimental impact on daa storage system performance. For instance, the execution of pending background operations requests that have accumulated in significant number while higher priority host requests were serviced can create a bottleneck for back-end operations. Also, the scheduling of jobs at the logical level can result in an uneven workload distribution at the physical level. That is, some physical resources (e.g., buses, physical storage devices, etc.) may be over-utilized while other physical resources are under-utilized.
This invention relates to a job scheduler that considers the loading of physical resources in a data storage system in selecting a logical volume for new job generation.
In an aspect of the invention, scheduling I/O requests directed to logical volumes that are associated with physical resources of a data storage system includes determining a job workload for each of the physical resources, choosing at least one of the physical resources based on the job workload and selecting one of the logical volumes associated with the chosen at least one physical resource. Once a logical volume has been selected, an I/O request directed to the selected one of the logical volumes is selected.
Embodiments of the invention may include one or more of the following features.
The physical resources can include Direct Memory Access (DMA) paths or xe2x80x9cpipesxe2x80x9d having at least one I/O bus for accessing physical devices. The workload determination can include determining the number of pending jobs associated with each of the pipes. Choosing one of the physical resources can include selecting one of the pipes based on the determined number of pending jobs associated with the pipes. The chosen one of the pipes is associated with a lowest number of pending jobs. The chosen one of the pipes can also be associated with a lowest number of pending jobs not in excess of a predetermined maximum pipe threshold number. If at least two of the pipes have a lowest number of pending jobs, then choosing at least one of the physical resources can include determining which of the at least two of the pipes is idle and, if more than one of the at least two of the pipes is idle, selecting from more than one of the at least two of the pipes. Selecting from more than one of the at least two of the physical devices is performed in a round robin manner. If only one of the at least two of the pipes is idle, the idle one of the at least two of the pipes is selected. Alternatively, if only one of the at least two of the pipes is idle, then the idle one of the at least two of the pipes is selected if the number of pending jobs is not in excess of the predetermined maximum pipe threshold number.
The physical resources can further include physical devices connected to the at least one I/O bus of each of the pipes. Choosing at least one physical resource can include determining the number of active jobs associated with each of the physical devices and selecting one of the physical devices based on the determined number of pending jobs associated with each of the physical devices. The selected one of the physical devices can be associated with a lowest number of pending jobs. Alternatively, the selected one of the physical devices can be associated with a lowest number of pending jobs not in excess of a predetermined maximum physical device threshold number. If at least two of the physical devices have a lowest number of pending jobs, then choosing the at least one of the physical resources can include selecting the one physical device having a next higher number of pending jobs than a most recently selected one of the physical devices. Alternatively, if at least two of the physical devices have a lowest number of pending jobs, choosing at least one of the physical resources includes selecting one of the physical devices having a next higher number of pending jobs than a most recently selected one of the physical devices not in excess of the predetermined maximum physical device threshold number.
Selecting one of the logical volumes can include determining a least recently selected one of those of the logical volumes associated with the selected one of the physical devices and selecting the least recently selected one.
The I/O scheduling can further include determining if any of the I/O requests are host I/O requests and, if any of the I/O requests are determined to be host I/O requests, deciding whether or not the host I/O requests are to be considered for scheduling. Deciding whether or not the host I/O requests are to be considered for scheduling can include using a parameter corresponding to the probability that the host I/O requests will be considered for scheduling if one or more of the I/O requests are not host I/O requests. One of any of the I/O requests determined to be host requests is selected if it is decided that the host I/O requests are to be considered for scheduling.
Among the advantages of the scheduling mechanism of the invention are the following. The scheduling mechanism provides the lowest response time possible for host requests while still performing its background duties in a timely manner. Additionally, because it uses a xe2x80x9cbottom-upxe2x80x9d approach to the selection of logical volumes, that is, it selects a pipe, then a physical device on that pipe, and then a logical volume on the selected physical device, overall system performance is much improved. Such an approach considers physical load balancing during the scheduling of background operations. Also, the total number of supported logical volumes is far greater than the number of physical resources, so considering the fewer physical resources for job scheduling purposes is more efficient. | {
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This invention relates to a container having an opening, or mouth, covered with a flexible sheet of material, and an outer closure lid disposed above the flexible sheet. Such containers are generally used in the food packaging industry and embody various sizes, shapes and forms for packaging various food products, particularly of the flowable type.
Cottage cheese, butter, yogurt and similar foot-stuffs are commonly packaged and marketed in a container that is generally wax-coated or wax-impregnated paper or plastic. The container has a receptacle portion, consisting of a base and upwardly extending sidewall, and an outer closure lid which is pressed onto the sidewall top peripheral opening, or mouth, as snuggly as possible so as to minimize the entry of air or the escape of food-stuff from the closed container. Outer closure lids for such containers are either the plain disc-like lids which engage a peripherally extending bead located below the mouth rim on the container on the interior surface of the sidewalls, or so-called flush-type lids which fit across the opening of the container and have a depending skirt or snap-on engagement with an exterior portion of a beaded rim of the container, or so-called plug-type lids which project into the interior of the container adjacent the inner surface of the upwardly extending sidewall and engage the sidewall opening in snap-on relation.
Conventionally, with containers of this type, it is relatively easy for the consumer, or other person, to remove the outer lid as well as the underlying flexible sheet closure. Because of the relative ease with which the flexible sheet closure and the outer closure lid may be removed from the top of the container, innocent, or willful and malicious tampering with the container's internal contents is possible. After removing the outer lid closure, a potential consumer may lift up a portion of the flexible sheet closure from engagement with the top of the container. With such containers, it is possible to determine if the flexible sheet closure has been loosened from the top of the container, but only by lifting the outer closure lid from the container and performing a close inspection.
In known containers which include a flexible sheet inner closure underneath the lid, such as those disclosed in U.S. Pat. Nos. 3,301,464; 3,338,027 and 3,471,992, a thin film or sheet of flexible material is disposed across the opening of the top of the container and is in contact with, and supported by, the top peripheral surfaces of the rim of the container. With those containers employing plug-type lids, the plug-type lid presents a substantially vertical and peripherally-extending wall area, which will lie adjacent to the interior surface of the container sidewall immediately below the top edge of the rim of the container when the lid is placed thereon. This vertically disposed peripheral wall area of the plug-type lid will engage a portion of the flexible sheet film and press it against the interior surface of the sidewall of the container. In some conventional containers, the flexible sheet closure is heat-sealed to the portion of the container sidewall adjacent the vertical and peripherally-extending wall area of the plug-type lid. In other containers, the flexible sheet closure material may be heat-sealed across the upper surface of the rim of the container. Further, instead of heat-sealing, adhesive means can be employed.
While such double-seal containers have functioned generally satisfactorily, several problems have been encountered, both in manufacture and in ultimate use. With respect to manufacturing, in accordance with known techniques, it is necessary to cut the sheet closure to a relatively precise size and shape corresponding to the size and shape of the container lid and the mouth of the container. And, it is necessary to maintain the sheet in relatively precise registry with the lid and to secure the sheet to the lid prior to insertion of the lid into the mouth of the container. The strength of the attachment between the lid and sheet must be accurately controlled to prevent the lid from tearing the sheet when the lid is removed, as for example, to check the tamper-proof integrity of the container. And, since the sheet does conform in size and shape to the lid and mouth of the container, there are no readily graspable tabs to facilitate removal of the sheet when it is desired to get access to the contents of the container.
Owing to the possibility and ease of opening of the flexible sheet closure, as a result of inadvertent shipping and handling activities or as a result of innocent potential consumer curiosity or malicious tampering, it is desirable to be able to more easily determine if the flexible sheet closure has been opened. Further, it is desirable that a tamper-indicating construction be employed with such flexible sheet closures that will allow the closure to be used with many types of lids and containers now in use. Advantageously, such a tamper-indicating construction of a flexible sheet closure should be effective regardless of the manner of engagement of the closure with the upper rim of the container. That is, the tamper-indicating flexible sheet closure construction should be effective regardless of whether or not the flexible sheet closure is heat-sealed or adhesively secured to the top rim of the container or just non-sealingly supported thereon. Further, it is desirable that the tamper-indicating construction of the flexible sheet closure not require visual inspection through complicated, relatively more expensive, transparent windows in the outer closure lid when such outer closure lid is used. The taper-indicating flexible sheet closure construction should also work with a large variety of different types of flexible sheet materials that may be used. | {
"pile_set_name": "USPTO Backgrounds"
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According to prior art, a digital content stream, such as an audio or a video stream possibly comprising audio, delivered to a receiver in the context of content-on-demand such as video-on-demand (VoD) is delivered through a one-to-one connection with a VoD server, for example by using IP (Internet Protocol) unicast distribution. This one-to-one distribution model is opposed to a one-to-many distribution model, where a same content source is received at the same time by many receivers.
The one-to-one distribution model allows a receiver to intervene on the unrolling of the content by issuing so-called trick mode commands. Trick mode commands comprise actions such as play, stop, pause, fast reverse, fast forward and go to chapter. In this distribution model, it is the receiver that commands the streaming of a content stream through a one-to-one connection with a content streaming server. While this distribution model allows trick mode commands, the model does not allow more than one receiver to receive the same content stream and allow more than one receiver to issue trick mode commands on the same stream.
In the one-to-many distribution model, it is the distribution server that commands the streaming. The one-to-many distribution model is used to distribute a same content stream to a large audience, for example to distribute TV or radio programs. With this distribution model, trick mode commands are not allowed, or only allowed for one receiver.
The above described distribution models are convenient for Video-on-Demand applications and television or radio broadcasting. However, the above described distribution models do not allow combining a one-to-many distribution with the support of trick mode commands from several receivers.
One of the problems that need to be solved when trick mode commands from several receivers are to be supported in a one-to-many stream distribution model is the management of the flow of trick mode commands that the streaming server must handle.
According to prior art, rendering of a content over multiple receivers with support of trick mode commands is applied in the context of, for example, e-learning applications, where students each have a receiver and can issue trick mode commands to intervene on the unrolling of a course. According to prior art, the course is distributed through prior downloading of the course content on the receiver of each student, and each student can issue trick mode commands. However, current state of the art does not allow management for handling the flow of trick mode commands. | {
"pile_set_name": "USPTO Backgrounds"
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1 Field of the Invention
This invention relates to antenna constructions and more particularly to a wire carrier clip for providing an improved method and means for attaching lead wires to the antenna.
2 Description of the Prior Art
Most antenna installations in the home TVRO industry have no means of attaching the receiving cables to the antenna. It is largely left up to the imagination of the installer as how best to attach the antenna lead wires. Most installers use plastic tie wraps to secure the lead wires, drilling holes in the antenna mesh or antenna ribs for attachment.
Tie wraps usually don't last long in the weather conditions of an outside installation. Consequently, important wires are caused to dangle and are left unattached. | {
"pile_set_name": "USPTO Backgrounds"
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Many computing applications such as computer games, multimedia applications, office applications or the like use controls to allow users to manipulate game characters or other aspects of an application. Typically such controls are input using, for example, controllers, remotes, keyboards, mice, or the like. Unfortunately, such controls can be difficult to learn, thus creating a barrier between a user and such games and applications. Furthermore, such controls may be different than actual game actions or other application actions for which the controls are used. For example, a game control that causes a game character to swing a baseball bat may not correspond to an actual motion of swinging the baseball bat. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
The present invention relates to an image pick-up apparatus, image pick-up method, and image pick-up system, and particularly to an image pick-up apparatus, image pick-up method, and image pick-up system preferably applied to X-ray image pick-up devices using two-dimensional solid sensors.
2. Description of Related Art
Generally, a method widely used in actual practice for industrial non-destructive testing and medical diagnosis involves exposure an object with radiation, and measuring the intensity distribution of the radiation which has transmitted the object, thus obtaining a radiograph. One generally used such image pick-up method for obtaining a radiograph involves combining silver halide film with intensifying screen or a phosphor which exhibits fluorescence under the presence of radiation, changing the radiation which has transmitted the object into visible light on the phosphor and forming a latent image on the silver halide film, following which the silver halide film is subjected to chemical processing so as to obtain a visible image. The analog radiograph obtained by this radiography method is used for diagnosis, inspection, and so forth.
On the other hand, progress in digital technology in recent years has led to obtaining high-quality radiographs with high diagnosis capabilities, by means of converting the radiograph into electrical signals (image signals) and subjecting the electrical signals to image processing, and then displaying on a CRT or the like as a visible image.
Also used are computed radiography apparatuses (CR apparatuses) which use an imaging plate coated with accelerated phosphoresce material serving as the fluorescent material. This method employs; the fact that when an imaging plate which has been subjected to primary excitation by radiation irradiation is subjected to secondary excitation by visible light such as red laser light or the like, the accelerated phosphoresce material emits light. The CR apparatus extracts a radiograph by detecting this photo-emission with a photo-sensor such as a photo-multiplier or the like, and outputs a visible image to the photography photosensitive material, CRT, or the like, based on this image data.
Further, more recently, technology has; been developed wherein a digital image is obtained by using image-receiving means comprised of a photo-electric converting device formed of picture elements of minute photo-electric converters and switching devices arrayed in a lattice-work. Such radiography apparatuses wherein fluorescent material is layered upon a CCD or amorphous silicone two-dimensional photo-electric converting device are disclosed in U.S. Pat. Nos. 5,418,377, 5,396,072, 5,381,014, 5,132,539, 4,810,881, etc.
Generally, radiography used for medical diagnosis requires reducing the amount of exposure to a minimal amount, while obtaining high-quality radiographs having maximum diagnosis capabilities. With the photography method using silver halide film/fluorescent plate or intensifying screen, the dynamic range of the radiation detecting device comprised of silver halide film/fluorescent plate or intensifying screen as to the amount of radiation is narrow, so in the event that the amount of radiation entering the silver halide film/fluorescent plate or intensifying screen is not appropriate, the resultant radiograph is either diagnosis. However, by means of using CR apparatuses and photo-electric converting devices, the image can be directly obtained as digital data, so ease of image processing is facilitated, and easy correction of inappropriate photography conditions and image enhancement of the range of concern is enabled.
Various types of large-area solid sensors have been commercially produced in recent years to served as photo-electric converting devices, such as described above. On the other hand, large-scale facilities are necessary for manufacturing such large-area solid sensors, so it is difficult to manufacture different types of sensors for each film size, and accordingly, a method generally employed involves manufacturing only one type of large-scale solid sensor which encompasses all film sizes, and digitally clipping the necessary image following imaging so as to meet the film size which differs for each member.
However, even though such general photography digital diagnostic apparatuses using such photo-electric converting devices (large-area solid sensors) have been developed for the purpose of realizing a film-less diagnosis environment, in many cases, final output to film is required. However, although laser printers having a digital interface are generally used for film output at the present, there are few such printers which can handle all film sizes, and the most common printers can only deal with one, or a few of the following film sizes: 35 cmxc3x9743 cm, 35 cmxc3x9735 cm, 11xe2x80x3xc3x9714xe2x80x3, 8xe2x80x3xc3x9710xe2x80x3, and 10xe2x80x3xc3x9712xe2x80x3.
Also, the image obtained by diagnosis apparatuses using large-area solid image pick-up devices are digital images, so it is easy to generate images of a desired size, but the output film size is limited, so there is a problem in that the user has to set the valid range for the digital diagnosis apparatus while taking into concern the usable film size for each shot.
On the other hand, in the event of indirect photography with the known photography system using film, the user desires that diagnostic images of the front and side views be simultaneously output onto the film. Regarding such requests, diagnosis apparatuses using large-area solid image pick-up devices are capable of taking a plurality of photographed images into a workstation, synthesizing the images as necessary, and outputting to the printer. However, there is a problem with this arrangement, in that the user must perform final output synthesizing, and thus is troublesome.
Also, in the event that digital image data is obtained using the above-described photo-electric converting devices or CR devices, performing communication of the obtained digital data between radiography apparatuses using a recently-developed standard protocol DICOM for transferring medical-use image information. However, with such arrangements, a great number of image generating apparatuses and image output devices are connected to a single network, so registration of the name and network address of the transfer destination must be regularly performed for each apparatus, making for troublesome work for the user and service personnel and taking excessive time.
Accordingly, it is an object of the present intention to solve the problems of known photography apparatuses and system such as described above.
It is another object of the present invention to improve operability for the user of an image pick-up system using image pick-up means with a large screen.
With consideration to these objects, an image pick-up apparatus according to an embodiment of the present invention comprises: image pick-up means; detecting means for detecting the state of one or more image output devices connected to the apparatus via a network; and control means for controlling the exposure area defined by the image pick-up means, according the detection output of the detecting means.
Also, an image pick-up apparatus according to another embodiment of the present invention comprises: a sensor for forming image signals from X-ray signals transmitting an object; detecting means for detecting the state of one or more image output devices connected to the apparatus via a network; and display means for displaying the exposure range of the sensor according to the size detected by the detecting means.
It is yet another object of the present invention to provide an image pick-up apparatus and system which is capable of automatically achieving optimal image output without troubling the operator.
With consideration to these objects, an image pick-up apparatus according to yet another embodiment of the present invention comprises: image pick-up means; a plurality of image output devices connected to the apparatus via a network; detecting means for detecting the state of the plurality of image output devices; and setting means for setting the output device for outputting the image signals exposed by the image pick-up means, according the detection output of the detecting means.
Other objects and characteristics of the present invention will be more clearly understood from the following detailed description of the invention. | {
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1. Field of the Invention
The present invention relates generally to electromagnetic methods of and an apparatus for stimulating healing of living tissue and more specifically to a method and apparatus for electromagnetic therapy to promote healing of tissue, e.g., electromagnetically stimulating osteogenesis, i.e., bone growth.
2. Discussion of the Prior Art
The process of healing diseased or damaged tissue including bone involves a variety of biochemical, cellular and tissue events, including changes in nuclear material (DNA), protein synthesis, membrane transport, progenitor-mesenchymal cell differentiation and migration, mitosis, etc.
It has long been recognized that properly applied electro-therapy signals can stimulate bone growth in the vicinity of fresh fractures and non-union fractures, and apparently do so by initiating or stimulating the requisite biochemical changes. That is, it has been thought that the stimulation of these cellular growth processes is related to the changing electrical and/or electro chemical environment of the cells present in bone. This electrical change, in turn, causes an alteration in cell behavior resulting in the synthesis of molecules produced by these cells necessary to effect bone healing. The mechanism underlying these events is thought to be an alteration of the interaction of charged species at the cell surface caused by the electrical signal. Because of the uncertainty regarding the most effective modality of electro-therapeutic treatment, including the nature of the electrical signal, and methods for applying the signal to the site of treatment, a substantial amount of research has been undertaken over quite a number of years to determine the most effective parameters.
Extensive research has been conducted in both experimental animal studies and human clinical trials utilizing various specific waveform formats for such treatment, including invasively-coupled, direct-current devices; capacitively-coupled, symmetric and asymmetric waveforms, and electro-magnetically coupled asymmetric waveforms.
There is a substantial body of prior art detailing the materials and methods used to effect electrotherapeutic bone healing, and many of these are described in the Annals of the New York Academy of Sciences, Vol. 238, October 1974, in an article entitled "Electrically Mediated Growth Mechanisms in Living Systems" (Editors, A. R. Liboff and R. A. Rinaldi). Excellent technical reviews of this field are J. A. Spadaro's "Bioelectric Stimulations of Bone Formation: Methods, Models and Mechanisms," in the Journal of Bioelectricity, Volume 1 (1), p. 99, 1982; and the Orthopedic Clinics of North America Symposium on Electrically Induced Osteogenesis, W. B. Saunders Corp. 1984. These reports detail variations in waveform formats for semi-invasive direct current devices, capacitively-coupled symmetric and asymmetric waveforms and inductively-coupled asymmetric waveforms.
All currently used electro-therapy techniques have one or more limitations. For example, invasive or semi-invasive techniques require at least one electrode to be inserted through the patient's skin in the vicinity of the fracture site. As with any surgical technique this will increase the risk of infection and may limit patient mobility and require subsequent operative procedures. The capacitively-coupled systems operate with a low impedance electrical connection but require that the capacitive plates be located adjacent the skin and require that they be gel-coated daily. Obviously this requires consistent patient compliance to be effective and can be annoying to the patient. The electromagnetic inductively-coupled methods and apparatuses require high power consumption waveform generation devices and bulky coil configurations which also limit the mobility of a patient to function normally outside the clinical environment.
The uncertainty regarding the most effective electrotherapeutic parameters that affect treatment is reflected in numerous patents. For instance, U.S. Pat. No. 4,467,808 (Brighton and Pollack) utilizes a 20-100 KHz signal generated by an alternating current power supply for the treatment of osteoporosis in bone. Unidirectional low voltage pulses are provided to the injury site in a non-invasive method described in U.S. Pat. Nos. 4,266,532 (Ryaby) and 4,461,663 (Delgado). A non-invasive capacitively coupled signal is disclosed in U.S. Pat. No. 4,535,775 (Brighton and Pollack). Other patents pertinent to the electro-therapy area are U.S. Pat. Nos. 3,890,953 (Kraus and Viehbach), 3,893,462 (Manning), 3,952,751 (Yanger) and 4,667,809 (Brighton).
Although the above references are primarily directed towards bone growth stimulation, there are also benefits with respect to the electromagnetic stimulation of soft tissues. These benefits are discussed in Black, "Electrical Stimulation of Hard and Soft Tissues in Animal Models," Clinics in Plastic Surgery, 12 (April, 1985) and Frank et al "A Review of Electro-magnetically Enhanced Soft Tissue Healing," IEEE Eng. in Medicine and Biol, (Dec., 1983).
It may be explained here that it generally takes bone fractures, particularly non-union fractures, many weeks or months to heal, and this is true even with the aid of electro-therapy where it has been tried as an adjunct treatment in an experimental setting. Because the presently utilized electro-therapy devices are, with a few exceptions, not truly portable, if the patient is to benefit from electro-therapy, he must have ready access to a source of electric power to effect treatment. Considering the time required for a bone to heal, this constraint is particularly annoying on a day to day basis, and requires that a patient constantly interrupt his daily routine for treatment, which may in turn cause failure of the patient to comply with the required protocol. Also, in most non-union fracture cases it is desirable for the patient to bear weight on the fracture site while maintaining the electromagnetic stimulation. A non-portable device requires the patient to remain limited in movement to the vicinity of the electromagnetic stimulator device.
Therefore, it is apparent that it is desirable to produce a device having the effective features of the devices currently in use but lacking their undesirable features, particularly their power wasting aspects. By creating a more power-efficient electro-therapy device it is possible to considerably reduce the size of the electro-therapy machines, hence permitting the construction of a completely portable device that allows the user to go about his daily routine without being tethered to a source of electric power.
A few inventors have appreciated the practical advantages of having a portable electro-therapy device. It is important to note that portability in the art is taken to mean a device readily carried by the patient without cumbersome support aids, and particularly connotes devices less than two pounds in weight, preferably less than one pound, and no larger than a small pocket camera inasmuch as portable is a relative term. U.S. Pat. No. 4,432,361 (Christensen and Mizoguchi) describes a portable device that has self monitoring features thereby allowing the patient to ascertain its operational status without having to have it checked by a physician, or another person skilled in the use of the device. This invention is an improvement over that described in U.S. Pat. No. 3,842,841 (Brighton and Freidenberg) which does not have the desirable self-monitoring features. Another portable electrotherapy device is described in U.S. Pat. No. 4,574,809 (Talish et al). It shows a device suitable for integration into an orthopedic cast with a signal generator removably mounted in the cast.
It is evident from the foregoing that there is a need for an effective electrotherapeutic method that is not limited by the currently used devices, but rather which employs a truly portable device. | {
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A method for the construction of a rein-girth bridge is known (DE-AS No. 27 54 213) in which first the stiffening girder is produced by a cycle-pushing method and then brought into its final position. Subsequently the pylon is built and the reins are attached for the final guying. In such a system, a bridge having larger spans requires temporary supports underneath the stiffening girder until the guying is completed and anchored and capable of taking over the support function assigned to it.
In the cycle-pushing method, it is known to use a temporary guying in form of an additional support (DE-OS No. 27 03 822). In such a setup, with the displacement of the stiffening beam, the cantilevering part of the bridge is stayed by means of a temporary pylon which is set upon the stiffening beam. In this manner the cantilevering bridge part is held during its advancement, so that less temporary supports are required. The auxiliary pylon and the temporary guying are then removed after the completion of the bridge. | {
"pile_set_name": "USPTO Backgrounds"
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1. Field of the Invention
The present invention relates to a semiconductor package and a method of fabricating same and, more particularly, to a TCP (tape carrier package) structure and a method of fabricating same.
2. Description of the Related Art
As the density of ICs increases, there is also a tendency for the number of wires in the semiconductor package to increase. Accordingly, there is a great demand for thinner and smaller semiconductor packages. Currently, the TAB (tape automated bonding) structure, which allows a semiconductor package to be made thinner than a flat package, is being developed and used in order to attempt the increased IC density on the substrate. A TAB-created package is known as a TCP, and permits high-density surface mounting. The TAB structure is adopted in an LCD (Liquid Crystal Display), for example.
However, there are limits in establishing high-density metal wiring even when the TCP is employed.
Single-layer wiring structures are also faced by wiring design (I/O terminal design) restrictions. | {
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The present invention relates generally to electromagnetic energy collection and more particularly to devices useful in the collection and utilization of radiant energy from solar and other sources.
The prior art has proposed numerous devices for detection of electromagnetic energy (e.g., infrared scanners, detectors of light from high energy particles, and the like) and for collection of such energy (e.g., microwave antennas, solar collectors, and the like) and is particularly rich in suggestions of systems for collection and utilization of solar energy.
Notwithstanding the voluminous proposals of the art, among the basic, and as yet inadequately resolved, problems inherent in the efficient utilization of solar energy are avoidance of energy loss through re-radiation (i.e., energy conservation) and avoidance of intricate, and hence costly, apparatus for tracking the sun in its apparent daily motion through the celestial sphere.
A typical attempt to solve solar energy conservation problems involves providing selective coatings on energy absorbing surfaces as well as elaborate insulation of the particular "trap" employed for the utilization of collected energy. U.S. Pat. No. 3,277,884, for example, illustrates such a scheme.
Another common manner of dealing with energy conservation involves including in the collection scheme reflective or refractive concentration apparatus to permit collection of solar energy impinging upon a relatively large area and focusing of collected energy toward a relatively small area of utilization. Typical schemes proposing use of reflector concentrators are illustrated in U.S. Pat. Nos. 1,814,897, 3,200,820 and 3,217,702, for example. ("Shadowing" effects encountered in disposing an energy utilization body in path of sunlight impinging upon reflectors are to some extent avoided through use of off-axis reflectors, as in U.S. Pat. Nos. 3,052,229, 3,613,659 and Tabor, "Stationary Mirror Systems for Solar Collectors" Solar Energy, Vol. II, No. 3-4, pp. 27 et seq. (1958)). Typical lens systems for solar concentration are illustrated in U.S. Pat. No. 3,125,091 and Meinel et al., "Physics Looks at Solar Energy" Physics Today, Vol. 25, pp. 684 et seq. (1972). All of the mirroring and lens systems proposed above are basically imaging systems wherein solar energy is reflected or refracted to a system focal point at which the "concentrated" energy is utilized for heating or power generation.
Among the solutions proposed for avoidance of diurnal solar tracking is the provision of huge, but marginally efficient, mirrored surfaces such as shown in U.S. Pat. No. 3,179,105.
None of the prior art systems has adequately solved the problems of energy conservation and solar tracking and, to a degree, solution of one problem often tends to enlarge the difficulties posed by the other. This is to say that systems permitting solar concentration by large factors generally will require the most careful and frequent diurnal adjustments for solar tracking. Conversely, systems requiring little or no diurnal adjustment generally provide lowest factors of concentration. Thus, Tabor, infra concludes that the maximum concentration available in a stationary system (i.e., one requiring only seasonal tracking) is on the order of 3 or 4.
Non-imaging light funnels having utility in collection of light from high energy particles and having a greater concentration capacity than imaging systems have been proposed by the inventor and his collaborators in earlier publications, i.e., Review of Scientific Instruments, Vol. 37, No. 8, pp. 1094-5 (1966), ibid., Vol. 39, No. 3, pp. 419-20 (1968), ibid., Vol. 39, No. 8, pp. 1217-8 (1968), and J. Opt. Soc. Am., Vol. 60, No. 2, pp. 245-7 (1970). The inventor also noted the similarity between such funnels and the geometry of retinal cones in J. Opt. Soc. Am., Vol. 61, No. 8, pp. 1120-1 (1971). Basically, the above publications dealt with proposals for "ideal", conical-shaped, light collectors which approach an f number equal to 0.5, a physically unrealizable limit for lens systems. The field of acceptance of conical collectors therein proposed may be represented by a right circular cone having a gradually diminishing (over about 1.degree.) external boundary cut-off. | {
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Electronic equipment is routinely used in an operational environment by mounting the equipment in one or more cabinets. It is becoming more and more common to use commercial off-the-shelf (COTS) electronic equipment whenever possible since COTS equipment is typically less expensive and more readily available than specialized equipment. However, in rugged environments such as various commercial or military applications, electronic equipment could be subjected to severe shocks or vibrations. Unfortunately, standard COTS equipment is usually not designed to operate in rugged environments where severe shocks or vibrations are present. If not mitigated, these shocks or vibrations could damage or destroy the electronic equipment or even cause the electronic equipment to be forcibly ejected from a cabinet. | {
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Endothelin is an endothelial cell-derived peptide hormone capable of acting on various cells and tissues through its receptors. For example, endothelin is known to cause a rise in intracellular calcium concentration in vascular smooth muscle cells and other cells (Non-Patent Literature 1).
In recent years, it is reported that endothelin promotes a rise in intracellular calcium concentration in epidermal melanocytes (melanin cells) to facilitate cell growth through the intracellular signal transduction system, and to enhance the activity of tyrosinase which is a rate determining enzyme in melanin synthesis (see Non-Patent Literature 2). It is also reported that endothelin is a melanocyte activating factor produced by epidermal keratinocytes (Non-Patent Literature 3) and that endothelin is an important factor in ultraviolet light-induced pigmentation or senile lentigines (Non-Patent Literatures 4 and 5).
Such biological actions of endothelin may well suggest that materials capable of suppressing endothelin action can be useful for reducing or preventing melanin production, pigmentation, or the like.
Whiteworm lichen (scientific name: Thamnolia vermicularis or Thamnolia subuliformis) is a lichen species growing in highlands of China and other areas. Whiteworm lichen is said to be effective in breaking down fat or in dieting, and also in Japan, it is often drunk in the form of tea or the like. | {
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Non-volatile memory devices, such as universal serial bus (USB) flash memory drives and removable storage cards, provide increased portability of data and software applications. Such devices may copy data from a source location in memory to a destination location in the memory using error detection and correction techniques to remove errors in the copied data. Alternatively, such devices may copy data from the source location to the destination location without using error detection and correction during the copy operation. Copying data without using error detection and correction reduces copy latency but increases a risk that the data becomes unrecoverable due to too many errors accumulating in the data. Therefore, it would be beneficial to improve an average speed of data copying within a non-volatile memory device while maintaining an acceptably low risk that the data becomes unrecoverable due to accumulated errors. | {
"pile_set_name": "USPTO Backgrounds"
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1. The Field of the Invention
The present invention is generally directed to agricultural irrigation systems, and more particularly, it is directed to novel apparatus for controlling irrigation valves.
2. The Prior Art
Since it became a desirable and generally accepted practice to transport various liquid and gaseous materials by pipeline, methods have been required for controlling the flow of those products within the pipeline system. Pipelines of various types are, of course, widely used in a variety of fields. For example, energy pipelines of various types are found in every region of the country and carry such products as natural gas, oil and natural gas liquids from their point of production to the point of end use. In addition, in attempts to increase the amount of farmable land surface, water has become another product which is commonly carried by a pipeline.
In arid and semi-arid environments, such as those existing generally in the western United States, production of various crops depends upon the ability to transport water to those crops. Rain fall in these areas is relatively sparse, commonly not exceeding approximately 10 inches per year. As a result, in order to grow most agricultural crops it is clear that water must be transported to the farm from a remote location.
Since the colonization of the western United States in the late 19th century, it has been a common practice to use irrigation as a method of supporting agricultural production. Irrigation systems began as a simple series of canals and ditches which were capable of taking water from springs or streams and transporting it to the field. Since that time irrigation systems have become much more sophisticated.
Many irrigation systems are currently comprised of complex systems of pipes which are able to carry water from a central source to the field. For example, a typical irrigation system may include a large main water line of up to 12 inches in diameter. Such main lines may easily carry 1,000 gallons of water per minute or more. These main lines are then fed into various smaller branch lines until finally the water reaches a small distributor line, possibly accompanied by a sprinkler at the terminal end. These smaller lines may typically carry approximately 150 gallons of water per minute.
It will be appreciated that it is critical to control the flow of water through the system. The farmer must have efficient equipment and methods to direct needed water to particular areas of his farm and to stop the water flow to areas which have sufficient irrigation water.
It is not uncommon for a farm, particularly in the western United States, to be comprised of several hundred or even several thousand acres. As a result, it will be appreciated that the task of irrigating such a farm is substantial. As a result, various valve systems have been developed which help to mechanize the task of irrigating crops by controlling the flow of water through the irrigation system.
It is now common practice to use electrically controlled valves on the various water pipelines used in irrigation systems. This allows a farmer to irrigate his crops automatically through an electrical system which controls the various valves. The farmer is provided with the ability to remotely, and even automatically, direct a predetermined quantity of water to a predetermined location on his farm.
While such systems have many advantages, when valves are operated remotely by an electrical control means, it is clear that the farmer is not able to check the condition of each valve as it is operated. Thus, dirt and other contaminants may enter the valve and associated motor without detection. The motor and valve may thus be operated while the contaminants are in contact with the mechanism. As a result, the potential for damage to the valves and associated motor assemblies is great.
It is the current practice in most conventional irrigation systems to employ a valve which is controlled by a small electric motor. The motor is connected to the main electrical control system so that the valve can be opened and closed remotely. The typical motor which is now in wide use is a 1/8th horsepower electric motor. The gears associated with the motor are generally made of a type of plastic such as nylon or teflon. Unfortunately, the motors used in the prior art are not currently equipped with adequate safety shut-off control mechanism. As a result, if dirt or other types of obstructions enter the gears or the associated valve, the small motor will continue to turn until either the motor is damaged or the gears are rendered unusable.
A significant problem with such motor and valve assemblies is that they do not employ conventional replaceable parts. Thus, when a gear or motor is damaged, it is not practical to attempt to replace the damaged part; as a result, the entire motor and assembly must be removed and replaced with a new motor and assembly. It will be appreciated, therefore, that the use of such a motor and assembly rapidly becomes very expensive.
It is apparent that what is currently needed in the art is a more durable and reliable valve control mechanism than those which have been available in the past. It would be an advancement in the art to provide a valve control mechanism which could remotely control a valve, yet had safety features built in which would protect the valve and control mechanism from damage. It would be a further advancement in the art to provide such a valve control mechanism which employed conventional and inexpensive parts which could be easily replaced if necessary.
It would also be an advancement in the art if such a valve control mechanism had a conventional manual method of turning the valve on and off. And, mentioned above, it would be a significant advancement in the art to provide a valve shut-off mechanism which included a safety feature which would prevent damage to the mechanism in the event any part of the mechanism became jammed or clogged. Such an apparatus is disclosed and claimed herein. | {
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Introducers, or introducer sheaths, are used for minimally invasive placement of medical devices, such as catheters, into the vasculature. Introducers typically include a tube that is inserted percutaneously into a vascular structure and a valve, including a sealing member, positioned at a proximal end of the tube. The valve, which is positioned outside the body of the patient, may be a hemostasis valve for reducing blood loss at the valve. Delivery catheters are used for a variety of diagnostic and/or therapeutic purposes and may be introduced into the vascular structure through the hemostatic valve of the introducer. The introducer thus provides access for a delivery catheter, or other similar medical device, and protects walls of the vascular structure from damage during insertion of the delivery catheter.
According to some percutaneous vascular procedures, the delivery catheter may require repositioning, including insertion and withdrawal, relative to the introducer. For example, during a medical device placement procedure, a portion of the delivery catheter may require retraction relative to the introducer, to deploy the medical device. During this proximal retraction, or withdrawal, it may be necessary to maintain a stationary position of both another portion of the delivery catheter and the introducer, particularly in light of the friction between the sealing member of the valve and the delivery catheter. This maneuvering can be difficult, particularly since precise positioning and movement of the respective components is important for proper medical device placement.
U.S. Pat. No. 8,114,057 to Gerdts et al. (hereinafter “Gerdts”) discloses a stent delivery system including an adaptor having a valve, a coaxial catheter assembly configured to extend through the valve, and a telescoping sleeve including a plurality of telescoping tubes. The first tube of the plurality of telescoping tubes may be secured to the adapter using the valve and, when the coaxial catheter assembly is positioned through the adaptor, the first tube may be positioned between the catheter assembly and the adaptor. The telescoping sleeve may be proximally extended to abut a distal portion of a handle of the catheter assembly. As such, the portion of the catheter assembly between the adaptor and the handle may be inhibited from bowing or arching outward using the extended telescoping sleeves. In addition, the friction between the tubes of the telescoping sleeve may help inhibit the handle from moving distally relative to the adaptor during stent deployment using the coaxial catheter. Although the system of Gerdts may be useful for some applications, it should be appreciated that there is a continuing need for efficient and effective catheter systems.
The present disclosure is directed toward one or more of the problems or issues set forth above. | {
"pile_set_name": "USPTO Backgrounds"
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The present disclosure is directed to accessories for toy figures, including battery-powered accessories for toy figures, and play kits including toy figures and accessories for toy figures.
Examples of accessories, including accessories for toy figures are found in U.S. Pat. Nos. 6,824,442; 6,071,166; 5,730,638; 5,364,107; 5,147,237; 5,092,810; 5,073,140; 4,902,262; 4,874,343; 4,723,931; 4,637,007; 4,626,222; 4,185,412; 4,060,929; 3,925,924; 3,911,613; 3,808,736; 3,911,613; 3,614,110; 3,127,176; 2,211,105; and D437,012; U.S. Patent Application Publication Nos. US 2005/0096111 and US 2004/0212148; European Patent Application No. 0482887; PCT Application Publication No. WO 98/50126; and United Kingdom Patent Application Nos. 2,180,768 and 1,549,964, the entire disclosures of the above patents and patent applications are herein incorporated by reference for all purposes. | {
"pile_set_name": "USPTO Backgrounds"
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The present invention relates to platinum catalyzed SiH-olefin silicone compositions utilizing an addition cure reaction and more specifically it relates to an improved process for formulating such silicone rubber products. The present invention allows a silicone formulator or fabricator to selectively control the rheological properties of the silicone products and process. Additionally, the present invention provides a silicone rubber product which utilizes an effective level of inhibitor which is lower than that which was previously available in the art.
In U.S. Pat. No. 4,061,609, issued Dec. 6, 1977, Bobear demonstrated a silicone rubber composition which has been shown to be useful, commercially successful, and which has met with wide acceptance in the silicone industry. This patent is hereby incorporated by reference.
Bobear recognized that several major disadvantages of prior art silicone rubber compositions could be eliminated entirely with the use of a proper inhibitor for the platinum catalyzed cure reaction. SiH-olefin platinum catalyzed compositions had been well-known in the art. Such compositions generally comprise a vinyl-containing polysiloxane base material having a treated or untreated filler therein and a hydrogen-containing polysiloxane along with a platinum catalyst which could be solid platinum metal deposited on a solid carrier such as gamma alumina or it could be a solubilized platinum complex. Normal procedure was to package the vinyl polysiloxane, the filler and the platinum catalyst in one package and to provide a second package containing the hydrogen-containing polysiloxane. The fabricator or other user of the material produced a cured silicone elastomer by mixing the two packages according to specified proportions whereupon the composition could be fabricated to a desired shape and allowed to cure either at room temperature over a period of time or at elevated temperatures in relatively very short periods of time.
The above-described compositions which were sold in the two component or package format are usually referred to as room temperature vulcanizable silicone rubber compositions and more specifically, SiH-olefin platinum catalyzed room temperature vulcanizable silicone rubber compositions. It is to be understood that these types of compositions could be cured at varying rates depending upon the temperature. For example, at room temperature the composition might take 1 hour to 12 hours to cure but at elevated temperatures such as 100.degree. to 200.degree. C. the composition might cure in seconds or minutes.
Such compositions start curing as soon as the two components are mixed together and will usually cure or at least set in approximately 1 hour even at room temperature. Therefore, it was desirable to incorporate into the prior art compositions inhibitors which would retard the curing of the composition for at least 12 hours when the two components were mixed together in order to allow the composition to be fabricated to the desired shape before such composition sets. After the two components have been mixed together but prior to their having set such that they cannot be molded further, it is desirable to have as long a work-life as possible. The function of the inhibitor is to increase the work-life of the composition prior to curing at an elevated temperature. The inhibitor must provide suitable work-life yet not impede or any way detract from the final cure and properties of the composition of the silicone elastomer.
Among the prominent prior art inhibitors were acetylenic-functional organic polymers and monomers as shown by Kookootsedes in U.S. Pat. No. 3,445,420.
These inhibitors were ultimately undesirable insofar as the acetylenic radical-containing compounds had to be sealed in air tight containers because exposure or leaks to the atmosphere will cause the acetylenic compound to evaporate thereby decreasing its inhibiting properties. This was a further disadvantage insofar as ordinarily SiH-olefin platinum catalyzed compositions did not otherwise have to be packaged in air tight containers.
Accordingly, Bobear recognized a very effective class of inhibitors utilizing hydroperoxy radicals which were quite effective and overcame many of the prior art disadvantages. As mentioned above, Bobear's rubber composition met with success in the market place and served to provide useful silicone rubber fabricated silicone rubber products. Not only did Bobear avoid the use of explosive acetylenic compounds which require careful manufacturing procedures for their preparation and use but he was able to provide inhibitors having a higher effective rate of inhibition.
Prior SiH-olefin platinum catalyzed compositions usually consisted of polysiloxane polymers having a viscosity of approximately 1000 to 500,000 centipoise at 25.degree. C. so that such polymers could be manipulated or worked at a rate which is more efficient than possible with higher viscosity polymers. In other words, the lower viscosity polymers serve the additional purpose of assisting in providing additional work-life.
Since Bobear utilized extremely effective inhibitors he was able to provide high viscosity SiH-olefin platinum catalyzed compositions wherein viscosity could range anywhere from one million to 200 million centipoise at 25.degree. C. Not only did these compositions remain workable, the final products exhibited very satisfactory higher tensile strengths. These compositions opened up entirely new markets and uses for these SiH-olefin platinum catalyzed silicone rubber compositions.
The difficulty in developing such high viscosity SiH-olefin platinum catalyzed compositions arose because they normally had to be worked on a mill or other apparatus after the two ingredients were mixed together thereby requiring extended work-life of at least 12 hours. In the past when such high viscosity materials were used, portions of the material would cure right on the mill upon contact and mixing of the two components. This made it exceedingly difficult to fabricate products. Bobear provided compositions which avoided many of these problems.
Fabricators and formulators in the silicone industry immediately recognized the significance of Bobear's contribution. It has become an industry standard to utilize Bobear's rubber composition in a two-package format at a 1:1 or 50:50 mixture ratio. This system works quite well as evidenced by the success in the market but there are several disadvantages which have now been overcome by the present invention.
The present invention provides a system for packaging and formulating silicone rubber products which lowers the cost to the formulator, especially inventory costs since large quantities of two different packages are no longer required. The process of the present invention also allows more reproducible results and products since formulators have previously been well accustomed to utilizing an approximately 99:1 system.
Furthermore, the present invention offers flexibility to the fabricator who may now vary the cure rate of the system thereby facilitating various types of fabrication such as extrusion through a hot air tunnel or a steam autoclave as well as molding via compression, tranfer or injection devices.
The flexibility afforded by the opportunity of varying the cure rates, as provided by the present invention can be demonstrated by considering various silicone rubber fabricating techniques. When the catalyzed composition is manipulated through an extrusion device and directed to a hot air vulcanization tunnel or zone, it is desirable that there be a relatively quick cure of the material. That is to say, best results are obtained if the composition begins to cure immediately upon exposure to the HAV zone.
However, if a hot mold technique is utilized such as compression or injection molding, a slower cure is necessary in order that the rubber first obtain the configuration of the molding device before the cure reaction is initiated.
A two-package, 50:50 mixture effectively fixes the ratio of catalyst and inhibitor and thereby limits a fabricator flexibility. Not only does the three-package system of the present invention provide such flexibility through the selective use of cure agents and cure modifiers, it does so at effective inhibitor levels which are lower than those previously provided by the art.
It is therefore a primary object of the present invention to provide a system for formulating silicone rubber products.
It is another object to provide silicone rubber compositions utilizing lower effective levels of inhibitors.
It is another object to provide a system for modifying the cure rate and rheological properties of a silicone rubber composition during the fabrication of such composition.
These and other objects will become apparent to those skilled in the art upon careful consideration of the following specification, examples and claims. | {
"pile_set_name": "USPTO Backgrounds"
} |
a) Field of the Invention
The invention is directed to a fluorescence turret for inverted microscopes which contains fluorescence cubes. These fluorescence cubes can be brought into operative position selectively in order to carry out different examinations in fluorescence microscopy.
b) Description of the Related Art
As is known, these fluorescence cubes comprise exciter filters in the direction of the light source, dichroic splitter mirrors and blocking filters in the observation direction. Turrets of this kind are known from DE 2316386, for example. | {
"pile_set_name": "USPTO Backgrounds"
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The present invention relates to a method of appending a dataset onto a dataset already written to a tape medium, and an apparatus such as a magnetic tape device (also referred to as a tape drive below) or portion thereof employing the method.
A large tape drive, such as IBM TS1120, and a tape drive compliant with linear tape open (LTO) sequentially write data to a tape medium in fixed length units called datasets (DS). In response to a reading instruction issued by a host, the tape drive sequentially reads DSs written to the tape. In a tape drive, a tape cartridge is repeatedly used by appending a new DS onto an old DS, instead of deleting the DS written to the tape medium.
FIG. 1 shows a state in which multiple DSs are sequentially written to a tape medium. To “append” a new DS onto a DS already recorded to a tape refers to overwriting the DS recorded to a tape by the new DS. First of all, a tape drive sequentially writes data in DS units to the tape medium while sequentially assigning DS numbers (DS #) to the pieces of data. In the case of appending a DS onto a DS recorded to a tape, it is preferable that the old DS be left on the tape medium and a new DS having the same DS # as the old DS is substantially overwritten thereon.
The lower view in FIG. 1 shows a state in which DSs #1 to #5 are appended. Two types of identification marks including the DS # and a so-called write pass (WP) are assigned to each DS written to the tape. As for writing data, every time the tape drive writes a DS to the tape, the tape drive increments the DS # by one. The WP of each DS indicates the number of times of writing operations. Here, the number of times is increased every time a retry is executed at the occurrence of a write error. When failing to write a DS of DS #X (X being an arbitrary number), the tape drive assigns, to the following DS, a value obtained by increasing the WP, as the WP therefor.
The upper view in FIG. 1 shows a current state of the tape in which each DS is successfully written to the tape, in the initial stage. In the current state, each DS is written only once, and thus the same value (WP 1) is assigned to each of the DSs. In the lower view in FIG. 1, for differentiation, the DSs #1 to #5 used to be appended onto the original DSs #1 to #5 are each assigned a WP 2 obtained by incrementing the WP 1 of each of the original DSs #1 to #5. By using the WP, the tape drive distinguishes a new DS from an old DS among the DSs having the same DS #, appended on a tape, and thus reads the new DS.
For the sake of data integrity (DI), it is preferable that an old DS be completely overwritten by a new DS of the same DS # at the appending operation. However, part of the front and rear ends of an old DS written to a tape remains thereon, due to occurrence of a slight error in writing control of the tape drive. Accordingly, multiple appending operations result in multiple DSs of the same DS # remaining on the tape. When sequentially reading multiple DSs of the same DS #, the tape drive forwards the DS assigned the maximum WP as the newest DS to the host, and assures data integrity (DI).
FIG. 2 illustrates a retry of writing a DS in a position shifted in the tape movement direction (forward), from a position on the tape where an error has occurred in writing an initial DS. Assume a case where there is a scratch, dust or the like on the tape. Here, it is difficult to continuously write DSs on this point of the tape medium by minimizing the spaces between the DSs and giving preference to data recording density. The LTO standards allow the writing position to be shifted for a maximum of 4 m, for instance, to carry out a retry (refer to Ultrium Generation 3 16-Channel Format Specification Document U-316, Revision B, Sep. 7, 2004, which is hereinafter referred to as Non-patent document 1). Here, a WP is incremented for each retry operation. Conventional tape drives employ the technique of carrying out a retry in writing, when an error occurs in writing data to a tape (see Japanese Patent Application Publication No. Hei 8-45200 and Japanese Patent No. 3436206).
By applying the technique of carrying out a retry with position shifting to perform appending, localized dust attachment and scratches due to deterioration with age can be avoided. Hence, permanent errors can be reduced. In the case where an error occurs in appending a DS onto a DS originally recorded to a tape, the appending is retried in a position shifted forward from the posit-on of the original DS. This appending operation is referred to as suspended appending (see Non-patent Document 1). In order to retain existing data while assuring to append a DS onto a DS of the DS # to be changed in one tape cartridge only, it is preferable that the number of permanent errors be reduced at the time of appending. This is because frequent occurrences of permanent errors in appending require needless exchange of tape cartridges and work of backup copy operation for the data (cost and time).
However, assume a case of carrying out a retry by shifting a long distance, that is, to shift from a position of the original DS while jumping over succeeding multiple DSs. Here, in order to assure DI, time is required to identify an old DS from a new DS positioned ahead, having the same DS #. In order to assure DI, a sequential access device (tape drive) is required to first read an old DS of the same DS # and a DS of a succeeding DS #, and then to read an appended DS to identify the newest DS by the WP. Thus, the reading performance of the device is affected.
In the coming years, tape drives may be required to carry out suspended appending in which a dataset is appended onto an existing dataset by shifting the writing position from the position where an error has occurred. Accordingly, it would be desirable to have a method and system for retrying appending so that the reading performance of the device would not be largely influenced even if a DS that was subjected to suspended appending is included. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
This invention relates to a novel production process capable of substantially producing optically active 3-hydroxy-xcex3-butyrolactone useful as a synthetic intermediate for pharmaceutical preparations and agrochemicals and as a functional material.
2. Description of the Related Art
The conventional process for producing optically active 3-hydroxy-xcex3-butyrolactone includes e.g. (1) a process for producing the same in 7 steps from D-isoascorbic acid and L-ascorbic acid as the starting materials (Synthesis, pp. 570-573, 1987), (2) a process for producing the same by reducing L-malic acid diester with a dimethyl sulfide/borane reagent and then subjecting the resultant diol ester to cyclization reaction with trifluoroacetic acid (Chemistry Letters, pp. 1389-1392, 1984), and (3) a process for producing the same by forming ethyl 4-tert-butoxy-3-hydroxybutyrate in 2 steps from ethyl 4-chloro-3-oxobutyrate and then cyclizing it in trifluoroacetic acid (Synthesis, pp. 37-40, 1986).
However, the process (1) is conducted through plural steps as many as 7 to make the procedure complicated, and this process is not desirable in respect of yield too. The process (2) has a problem that the dimethyl sulfide/borane reagent used in the production is expensive and difficult to handle. In the process (3), the product is produced in relatively short steps, but corrosive and toxic trifluoroacetic acid serving not only as a reagent but also as a solvent is used in a large amount, and low-temperature reaction is required, so this process cannot be said to be an industrial process.
Further, 3-hydroxy-xcex3-butyrolactone is water-soluble, and in any processes (1) to (3), washing with water is necessary at the stage of post-treatment after the reaction is finished, thus making the procedure troublesome and often lowering the yield, and therefore these cannot be said to be efficient processes.
Accordingly, it cannot be said from an economical viewpoint and in respect of efficiency that the prior art processes are industrially suitable production processes, and there is demand for development of an industrially suitable process for producing optically active 3-hydroxy-xcex3-butyrolactone.
The object of this invention is to provide a novel process for producing optically active 3-hydroxy-xcex3-butyrolactone in a short step, which is superior economically and in efficiency and industrially suitable by using a starting material which is inexpensive and easily available and reagents easy to handle.
Under these circumstances, the present inventors made an extensive study for solving the object described above. As a result, they found that an optically active 4-substituted oxy-3-hydroxybutyrate obtained by asymmetrically hydrogenating an easily available 4-substituted oxy-3-oxobutyrate is hydrogenated in the presence of a heterogeneous hydrogenation catalyst and an acidic substance followed by deprotection and simultaneous ring closure thereof, whereby optically active 3-hydroxy-xcex3-butyrolactone of high optical purity can be obtained in high yield, and this invention was thereby completed.
That is, this invention relates to a process for producing optically active 3-hydroxy-xcex3-butyrolactone represented by formula I:
wherein the symbol * means an asymmetric carbon atom, which comprises hydrogenating an optically active 4-substituted oxy-3-hydroxybutyrate represented by formula II:
wherein R1 represents a C1-4 lower alkyl group, R2 represents a protective group for a hydroxyl group deprotected by hydrogenation with a heterogeneous hydrogenation catalyst, and the symbol * has the same meaning as defined above, in the presence of a heterogeneous hydrogenation catalyst and an acidic substance followed by deprotection and simultaneous ring closure thereof.
Further, this invention relates to the process for producing optically active 3-hydroxy-xcex3-butyrolactone, wherein the optically active 4-substituted oxy-3-hydroxybutyrate represented by the general formula II above is obtained by asymmetrically hydrogenating a 4-substituted oxy-3-oxobutyrate represented by the general formula III:
wherein R1 and R2 have the same meanings as defined above, in the presence of a ruthenium complex comprising an optically active phosphine compound as a ligand.
Further, this invention relates to the process for producing optically active 3-hydroxy-xcex3-butyrolactone, wherein R 2is an optionally substituted benzyl group, more preferably a benzyl group.
Further, this invention relates to the process for producing optically active 3-hydroxy-xcex3-butyrolactone, wherein the metal catalyst is a heterogeneous catalyst of palladium, iridium, rhodium, ruthenium, nickel, osmium or platinum.
Further, this invention relates to the process for producing optically active 3-hydroxy-xcex3-butyrolactone, wherein the acidic substance is p-toluenesulfonic acid, methanesulfonic acid, camphor sulfonic acid, sulfuric acid, trifluoroacetic acid, ferric chloride, zinc chloride or stannic chloride.
Hereinafter, this reaction is described in more detail.
The process for producing optically active 3-hydroxy-xcex3-butyrolactone according to this invention is conducted according to the following reaction scheme:
wherein R1 represents a C1-4 lower alkyl group, R2 represents a protective group for a hydroxyl group deprotected by hydrogenation with a heterogeneous hydrogenation catalyst, and the symbol * means an asymmetric carbon atom.
That is, the optically active 4-substituted oxy-3-hydroxybutyrate (II) is hydrogenated in the presence of a heterogeneous hydrogenation catalyst and an acidic substance followed by deprotection and simultaneous ring closure thereof, whereby optically active 3-hydroxy-xcex3-butyrolactone (I) is formed. The optically active 4-substituted oxy-3-hydroxybutyrate (II) used as the starting material in this process can be produced by asymmetrically hydrogenating preferably a 4-substituted oxy-3-oxobutyrate (III) in the presence of a ruthenium complex comprising an optically active phosphine compound as a ligand.
The reaction scheme described above shows a series of these reactions.
In this invention, R1 in the optically active 4-substituted oxy-3-hydroxybutyrate (II) may be a group capable of cleavage with its adjacent oxygen atom by participating in the reaction under the reaction conditions used, and the type of this group is not important, but the group is preferably a lower alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group or tert-butyl group, more preferably a C1-4 lower alkyl group.
In this invention, R2 in the optically active 4-substituted oxy-3-hydroxybutyrate (II) may be a hydroxyl-protecting group capable of cleavage upon deprotection under the reaction conditions for producing optically active 3-hydroxy-xcex3-butyrolactone (I), and the protective group for a hydroxyl group deprotected by hydrogenation with the heterogeneous hydrogenation catalyst is preferably a benzyl group which may have one or more substituent groups thereon. The substituent groups on the benzyl group are not particularly limited insofar as the benzyl group can act as a protective group capable of deprotection, and preferable examples thereof include a lower alkyl group such as methyl group and ethyl group, a lower alkoxy group such as methoxy group, an aryl group such as phenyl group, p-methoxyphenyl group and naphthyl group, a halogen atom such as fluorine atom and chlorine atom, and a nitro group. The benzyl group may be substituted with these substituent groups on either its phenyl ring or its methylene group.
Examples of R2 include a benzyl group, p-methyl phenyl methyl group, p-ethyl phenyl methyl group, p-methoxy phenyl methyl group, 3,5-dimethyl phenyl methyl group, 3,5-dimethoxy phenyl methyl group, p-fluorophenyl methyl group, p-chlorophenyl methyl group, 2,6-dichlorophenyl methyl group, xcex1-phenyl ethyl group, o-nitrophenyl methyl group, p-nitrophenyl methyl group, p-cyanophenyl methyl group, diphenyl methyl group, triphenyl methyl group, naphthyl methyl group, naphthyl diphenyl methyl group and p-methoxy phenyl diphenyl methyl group. More preferable examples of R2 include a benzyl group, p-methyl phenyl methyl group, p-ethyl phenyl methyl group, p-methoxy phenyl methyl group, 3,5-dimethyl phenyl methyl group, 3,5-dimethoxy phenyl methyl group, p-fluorophenyl methyl group, p-chlorophenyl methyl group and xcex1-phenyl ethyl group. R2 is most preferably a benzyl group.
The optically active 4-substituted oxy-3-hydroxybutyrate (II) as the starting material in this invention is a known compound and can be produced by various methods, preferably by asymmetric hydrogenation of the 4-substituted oxy-3-oxobutyrate (III) in the presence of a ruthenium complex comprising an optically active phosphine compound as a ligand.
The substituent groups R1 and R2 on the 4-substituted oxy-3-oxobutyrate (III) are defined as being identical with, but may be different from, R1 and R2 on the compound represented by formula II above. R1 and R2 in formula II are groups to be eliminated under the reaction conditions, while R1 and R2 in formula III are groups acting as protective groups under the reaction conditions used. Accordingly, R1 and R2 in production of the starting material may be different from R1 and R2 in the conversion of the starting material into lactone, but the substituent groups R1 and R2 in the former step are preferably identical with R1 and R2 in the latter step in order to eliminate exchange the substituent groups with other ones.
Examples of the 4-substituted oxy-3-oxobutyrate (III) include methyl 4-benzyloxy-3-oxobutyrate, ethyl 4-benzyloxy-3-oxobutyrate, propyl 4-benzyloxy-3-oxobutyrate, isopropyl 4-benzyloxy-3-oxobutyrate, n-butyl 4-benzyloxy-3-oxobutyrate, tert-butyl 4-benzyloxy-3-oxobutyrate, methyl 4-(p-methylphenyl)methyloxy-3-oxobutyrate, ethyl 4-(p-methylphenyl)methyloxy-3-oxobutyrate, methyl 4-(p-ethylphenyl)methyloxy-3-oxobutyrate, ethyl 4-(p-ethylphenyl)methyloxy-3-oxobutyrate, methyl 4-(p-methoxyphenyl)methyloxy-3-oxobutyrate, ethyl 4-(p-methoxyphenyl)methyloxy-3-oxobutyrate, methyl 4-(xcex1-phenylethyl)oxy-3-oxobutyrate, ethyl 4-(xcex1-phenylethyl)oxy-3-oxobutyrate etc.
More preferably, methyl 4-benzyloxy-3-oxobutyrate and ethyl 4-benzyloxy-3-oxobutyrate can be mentioned.
In a preferable aspect of this invention, the 4-substituted oxy-3-oxobutyrate represented by the general formula III is asymmetrically hydrogenated in the presence of a ruthenium complex comprising an optically active phosphine compound as a ligand, whereby the optically active 4-substituted oxy-3-hydroxybutyrate (II) is produced.
The optically active phosphine compound used for asymmetrically hydrogenating the 4-substituted oxy-3-oxobutyrate used in this process is an optically active phosphine compound represented by the general formula IV:
wherein R3 represents an optionally substituted aryl group or a C3-8 cycloalkyl group.
In the general formula IV, R3 is preferably an optionally substituted phenyl group, an optionally substituted naphthyl group, or a C3-8 cycloalkyl group.
The substituent group which may be present thereon includes e.g. a C1-4 lower alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl and isobutyl; a halogen atom such as fluorine, chlorine and bromine; a C1-4 lower alkoxy group such as methoxy, ethoxy, propoxy and butoxy; and a halogenated lower alkyl group such as trifluoromethyl and trichloromethyl, or an benzyloxy group.
Preferable examples of R3 include a phenyl group, 4-tolyl group, 3-tolyl group, 4-methoxyphenyl group, 3,5-xylyl group, 3,5-di-tert-butyl phenyl group, 4-methoxy-3,5-dimethyl phenyl group, 4-methoxy-3,5-di-tert-butyl phenyl group, naphthyl group, cyclohexyl group and cyclopentyl group.
Preferably used optically active phosphine compounds of the general formula IV are for example tertiary phosphine compounds described in e.g. Japanese Patent Laid-Open Nos. 63690/1986 and 265293/1987, and specifically mention can be made of:
2,2xe2x80x2-bis(diphenylphosphino)-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cBINAPxe2x80x9d),
2,2xe2x80x2-bis[di(p-tolyl)phosphino]-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cp-Tol-BINAPxe2x80x9d),
2,2xe2x80x2-bis[di(3,5-xylyl)phosphino]-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cDM-BINAPxe2x80x9d),
2,2xe2x80x2-bis[di(3,5-di-tert-butylphenyl)phosphino]-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9ct-Bu-2-BINAPxe2x80x9d),
2,2xe2x80x2-bis[di(4-methoxy-3,5-dimethylphenyl)phosphino]-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cDMM-BINAPxe2x80x9d),
2,2xe2x80x2-bis(dicyclohexylphosphino)-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cCy-BINAPxe2x80x9d), and
2,2xe2x80x2-bis(dicyclopentylphosphino)-1,1xe2x80x2-binaphthyl (abbreviated hereinafter to xe2x80x9cCp-BINAPxe2x80x9d).
Other optically active phosphine compounds used in asymmetric hydrogenation include optically active phosphine compounds represented by the general formula V:
wherein R3 represents an optionally substituted aryl group or a C3-8 cycloalkyl group.
R3 in the general formula V includes the groups enumerated above.
Preferably used optically active phosphine compounds of the general formula V are for example tertiary phosphine compounds described in e.g. Japanese Patent Laid-Open No. 139140/1992, and specifically mention can be made of:
2,2xe2x80x2-bis{diphenylphosphino}-5,5xe2x80x2,6,6xe2x80x2,7,7xe2x80x2,8,8xe2x80x2-octahydrobinaphthyl (abbreviated hereinafter to xe2x80x9cH8-BINAPxe2x80x9d),
2,2xe2x80x2-bis{di-p-tolylphosphino}-5,5xe2x80x2,6,6xe2x80x2,7,7xe2x80x2,8,8xe2x80x2-octahydrobinaphthyl (abbreviated hereinafter to xe2x80x9cp-Tol-H8-BINAPxe2x80x9d),
2,2xe2x80x2-bis{di-(3,5-xylyl)phosphino}-5,5xe2x80x2,6,6xe2x80x2,7,7xe2x80x2,8,8xe2x80x2-octahydrobinaphthyl (abbreviated hereinafter to xe2x80x9cDM-H8-BINAPxe2x80x9d), and
2,2xe2x80x2-bis{di-(4-methoxy-3,5-dimethylphenyl)phosphino} -5,5xe2x80x2,6,6xe2x80x2,7,7xe2x80x2,8,8xe2x80x2-octahydrobinaphthyl (abbreviated hereinafter to xe2x80x9cDMM-H8-BINAPxe2x80x9d).
Other optically active phosphine compounds used in asymmetric hydrogenation include optically active phosphine compounds represented by the general formula VI:
wherein R3 represents an optionally substituted aryl group or a C3-8 cycloalkyl group, R4 represents a hydrogen atom or a C1-4 lower alkyl group, R5 represents a hydrogen atom, methyl group, methoxy group or halogen atom, and R6 represents a methyl group or methoxy group, or R5 and R6 may be combined to form a methylene dioxy group.
R3 in the general formula VI includes the groups enumerated above.
Preferably used optically active phosphine compounds of the general formula VI are for example optionally active tertiary phosphine compounds described in e.g. Japanese Patent Laid-Open Nos. 182678/1998, 269185/1999 and 16997/2000, and specifically mention can be made of:
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(diphenyl phosphine) (abbreviated hereinafter to xe2x80x9cSEGPHOSxe2x80x9d),
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(di-p-tolyl phosphine) (abbreviated hereinafter to xe2x80x9cp-Tol-SEGPHOSxe2x80x9d),
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(di-3,5-xylyl phosphine) (abbreviated hereinafter to xe2x80x9cDM-SEGPHOSxe2x80x9d),
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(di-4-methoxy-3,5-dimethylphenyl phosphine) (abbreviated hereinafter to xe2x80x9cDMM-SEGPHOSxe2x80x9d),
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(di-4-methoxy-3,5-di-tert-butylphenyl phosphine) (abbreviated hereinafter to xe2x80x9cDTBM-SEGPHOSxe2x80x9d), and
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(dicyclohexyl phosphine) (abbreviated hereinafter to xe2x80x9cCy-SEGPHOSxe2x80x9d).
Other compounds represented by the general formula VI include the following optically active phosphines:
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(diphenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cBIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-p-tolyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cp-Tol-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-3,5-xylyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDM-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-4-methoxy-3,5-dimethylphenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDMM-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-4-t-butoxy-3,5-dimethylphenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDTBM-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-6,6xe2x80x2-bis(dicyclohexyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cCy-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(diphenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cMeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(di-p-tolyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cp-Tol-MeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(di-3,5-xylyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDM-MeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(di-4-methoxy-3,5-dimethyl phenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDMM-MeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(di-4-t-butoxy-3,5-dimethyl phenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDTBM-MeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethoxy-6,6xe2x80x2-bis(dicyclohexyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cCy-MeO-BIPHEPxe2x80x9d),
2,2xe2x80x2-dimethyl-3,3xe2x80x2-dichloro-4,4xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-p-tolyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cp-Tol-CM-BIPHEMPxe2x80x9d),
2,2xe2x80x2-dimethyl-3,3xe2x80x2-dichloro-4,4xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-3,5-xylyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDM-CM-BIPHEMPxe2x80x9d), and
2,2xe2x80x2-dimethyl-3,3xe2x80x2-dichloro-4,4xe2x80x2-dimethyl-6,6xe2x80x2-bis(di-4-methoxy-3,5-dimethyl phenyl phosphino)-1,1xe2x80x2-biphenyl (abbreviated hereinafter to xe2x80x9cDMM-CM-BIPHEMPxe2x80x9d).
In the above-described process of this invention, the 4-benzyloxy-3-oxobutyrate (III) is hydrogenated by a complex comprising ruthenium and at least one member selected from the optically active phosphine compounds represented by the general formulae IV, V and VI.
Because these optically active phosphine compounds occur with (R)- and (S)-configurations, one configuration may be selected depending on the absolute configuration of the desired optically active 4-benzyloxy-3-hydroxybutyrate. That is, the optically active phosphine compound of (S)-configuration may be used to prepare the product of (3R)-configuration, while the optically active phosphine compound of (R)-configuration may be used to prepare the product of (3S)-configuration.
The ruthenium complex used in this hydrogenation reaction can be prepared by heating [Ru(p-cymene)X2]2 (X is a chlorine atom, bromine atom or iodine atom) and L (L is an optically active phosphine compound) in methylene chloride and ethanol under stirring in accordance with a method described in a literature (K. Mashima, K. Kusano, T. Ohta, R. Noyori, H. Takaya, J. Chem. Soc., Chem. Commun., 1208 (1989)). Examples of the ruthenium complex include:
[RuCl(benzene) (L)]Cl,
[RuBr(benzene) (L)]Br,
[RuI(benzene) (L)]I,
[RuCl(p-cymene)(L)]Cl,
[RuBr(p-cymene)(L)]Br,
[RuI(p-cymene)(L)]I,
[RuCl(mesitylene)(L)]Cl,
[RuBr(mesitylene)(L)]Br,
[RuI(mesitylene)(L)]I,
[RuCl(hexamethylbenzene)(L)]Cl,
[RuBr(hexamethylbenzene)(L)]Br,
[RuI(hexamethylbenzene)(L)]I,
[{RuCl(L)}2(xcexcL-Cl)3][NR2Me2],
[{RuCl(L)}2(xcexc-Cl)3][NH2Et2],
[{RuCl(L)}2(xcexc-Cl)3][NH2Pr2], and
[{RuCl(L)}2(xcexc-Cl)3][NH2i-Pr2].
Preferable examples of the ruthenium complex comprising the optically active phosphine complex of this invention as a ligand include the following ruthenium complexes using ((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy) biphenyl-2,2xe2x80x2-diyl)bis(biphenyl phosphine) (abbreviated into SEGPHOSs) as the optically active phosphine compounds:
[RuCl(benzene)]{(R)- or (S)-SEGPHOSs}]Cl,
[RuBr(benzene)]{(R)- or (S)-SEGPHOSs}]Br,
[RuI(benzene)]{(R)- or (S)-SEGPHOSs}]I,
[RuCl(p-cymene)]{(R)- or (S)-SEGPHOSs}]Cl,
[RuBr(p-cymene)]{(R)- or (S)-SEGPHOSs}]Br,
[RuI(p-cymene)]{(R)- or (S)-SEGPHOSs}]I,
[RuCl(mesitylene)]{(R)- or (S)-SEGPHOSs}]Cl,
[RuBr(mesitylene)]{(R)- or (S)-SEGPHOSs}]Br,
[RuI(mesitylene)]{(R)- or (S)-SEGPHOSs}]I,
[RuCl(hexamethylbenzene)]{(R)- or (S)-SEGPHOSs}]Cl,
[RuBr(hexamethylbenzene)]{(R)- or (S)-SEGPHOSs}]Br,
[RuI(hexamethylbenzene)]{(R)- or (S)-SEGPHOSs}]I,
[{RuCl {(R)- or (S)-SEGPHOSs}}2(xcexc-Cl)3][NH2Me2],
[{RuCl {(R)- or (S)-SEGPHOSs}}2(xcexc-Cl)3][NH2Et2],
[{RuCl {(R)- or (S)-SEGPHOSs}}2(xcexc-Cl)3][NH2Pr2], and
[{RuCl {(R)- or (S)-SEGPHOSs}}2(xcexc-Cl)3][NH2i-Pr2].
The asymmetric hydrogenation in this invention can be carried out by subjecting the 4-benzyloxy-3-oxobutyrate represented by the general formula III to asymmetric hydrogenation reaction in the presence of the ruthenium complex comprising an optically active phosphine compound as a ligand.
This reaction can be carried out in an organic solvent. The organic solvent includes e.g. aromatic hydrocarbons such as toluene, benzene and chlorobenzene, aliphatic esters such as ethyl acetate, propyl acetate and butyl acetate, ethers such as diethyl ether, diisopropyl ether and tetrahydrofuran, halogenated hydrocarbons such as dichloromethane and dichloroethane, and alcohols such as methanol, ethanol and isopropanol. These can be used alone or as a mixture of two or more solvents. The solvent is preferably an alcohol, more preferably methanol or ethanol.
The ratio by volume of the solvent to the starting compound (substrate) is in the range of about 0.1 to 10, preferably about 0.5 to 3.
The ruthenium complex used in the asymmetric hydrogenation reaction in this invention is used in an amount of about 1/20000 to 1/10 mole, preferably about 1/10000 to 1/100 mole, per mole of the starting compound (substrate).
The hydrogen pressure is in the range of about 0.5 to 10 MPa, preferably about 1 to 5 MPa.
The reaction temperature used is in the range of about 30 to 100xc2x0 C., preferably about 60 to 90xc2x0 C., and while the temperature is kept in this range, the reaction is carried out for about 1 to 100 hours, preferably 1 to 24 hours, whereby the asymmetric hydrogenation reaction can proceed smoothly.
The reaction solution obtained in the above reaction can be purified by known techniques such as solvent extraction, transfer to another solvent, distillation, crystallization, re-crystallization and chromatography to give the compound (II).
In the process of this invention, the optically active 4-substituted oxy-3-hydroxybutyrate represented by the general formula II, preferably the optically active 4-substituted oxy-3-hydroxybutyrate represented by the general formula II obtained by the method described above, is hydrogenated in the presence of a heterogeneous hydrogenation catalyst and an acidic substance followed by deprotection and simultaneous ring closure thereof to produce optically active 3-hydroxy-xcex3-butyrolactone (I).
As the heterogeneous hydrogenation catalyst used in the hydrogenation of the optically active 4-substituted oxy-3-hydroxybutyrate used in this invention, a conventionally used heterogeneous hydrogenation catalyst is used.
The heterogeneous hydrogenation catalyst includes e.g. Raney nickel, platinum oxide, platinum black, palladium black, rhodium black, palladium carbon, iridium carbon, rhodium carbon, ruthenium carbon, osmium carbon, palladium alumina, palladium silica and palladium silica alumina. The catalyst is preferably Raney nickel, platinum black, palladium black, palladium carbon, palladium alumina, palladium silica or palladium silica alumina. Among these, Raney nickel, palladium black and palladium carbon are more preferable because of high selectivity and yield in the reaction and usability for various purposes.
As the acidic substance used in the process of this invention, various acidic substances such as Lewis acid can be used. Examples of such acidic substances include sulfonic acids such as benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, camphor sulfonic acid and sulfuric acid; perhalogenoacetic acids such as trifluoroacetic acid and trichloroacetic acid, and Lewis acids such as ferric chloride, zinc chloride and stannic chloride. Preferable acidic substances include e.g. p-toluenesulfonic acid, methanesulfonic acid and camphor sulfonic acid. Among these, p-toluenesulfonic acid and methanesulfonic acid are more preferable because of usability for various purposes and high selectivity and yield in the reaction. These acidic substances can be used singly or in combination thereof, but is used preferably singly.
This reaction can be carried out in an organic solvent. The organic solvent includes e.g. aromatic hydrocarbons such as toluene, benzene and chlorobenzene, aliphatic esters such as ethyl acetate, propyl acetate and butyl acetate, ethers such as diethyl ether, diisopropyl ether and tetrahydrofuran, halogenated hydrocarbons such as dichloromethane and dichloroethane, and alcohols such as methanol, ethanol and isopropanol. These can be used singly or as a mixture of two or more solvents. The solvent is preferably an alcohol, particularly methanol, ethanol, isopropanol and toluene. Among these alcohols, methanol, ethanol and isopropanol are more preferable because of usability for various purposes and high selectivity and yield in the reaction.
The amount of the solvent is not particularly limited, but the ratio by volume of the solvent to the starting compound (substrate) is in the range of about 0.1 to 10, preferably about 0.5 to 3.
The heterogeneous hydrogenation catalyst in this invention is used in the range of preferably about 0.02 to 20% by weight, more preferably about 0.1 to 5% by weight, relative to 1% by weight of the starting compound (substrate), but this range is not restrictive.
The acidic substance in this reaction is used in the range of preferably about 0.1 to 10% by weight, more preferably about 0.5 to 5% by weight, relative to 1% by weight of the starting compound (substrate), but this range is not restrictive.
The hydrogen pressure is preferably in the range of about 0.05 to 10 MPa, more preferably about 0.1 to 3 MPa, but this range is not restrictive.
The reaction temperature used is in the range of about 20 to 100xc2x0 C., preferably about 30 to 60xc2x0 C., and while the temperature is kept in this range, the reaction is carried out for about 1 to 50 hours, preferably 1 to 10 hours, whereby the hydrogenation reaction can proceed smoothly.
After the reaction is finished, the heterogeneous hydrogenation catalyst is removed by filtration from the reaction solution obtained in the above reaction, and the solvent is distilled away under reduced pressure. The resultant residues are distilled under reduced pressure, whereby optically active 3-hydroxy-xcex3-butyrolactone as the desired compound of this invention can be obtained with high purity and in high yield.
That is, the process of this invention is an efficient process because the process neither requires conventional techniques such as solvent extraction and transfer to another solvent, nor requires treatment in an aqueous solution in the reaction system or in post-treatment steps (isolation, purification etc.) to isolate and purify 3-hydroxy-xcex3-butyrolactone, thus eliminating necessity for extraction from the aqueous system to make the procedure simple and eliminate a loss in the aqueous system. | {
"pile_set_name": "USPTO Backgrounds"
} |
Vehicles may be powered by an engine and/or one or more batteries. For example, the engine may provide motive power for the vehicle and/or charge the batteries. The batteries, in turn, may provide power for starting the engine, and/or may provide motive power for the vehicle.
Both engines and batteries may produce a large quantity of waste heat, i.e., excess thermal energy, and close to half of the waste heat is typically dissipated into the atmosphere as an exhaust stream. Despite improvements in engine and combustion technology, nearly one-quarter of fuel energy may be expelled as waste heat in the exhaust stream. Therefore, significant gains in vehicle fuel economy may be realized if waste heat is converted into usable mechanical and/or electrical energy. | {
"pile_set_name": "USPTO Backgrounds"
} |
Solution condensation polymerizations of esterified, but unprotected, carbohydrate diacids (aldaric acids) with alkylenediamines to give polyhydroxypolyamides were first reported by Ogata and coworkers1-8 who utilized diesters of acyclic L-tartaric acid1,2 and galactaric (mucic)acid3,4 as diacid monomers. D-glucaric,9-14 meso-xylaric,9,10,15,16 and D-mannaric acid11,14 based polyhydroxypolyamides (PHPAs) were described more recently by others. The primary structural differences between those polymers having alkylendiamine units in common, originate from the variable stereochemistry and number of carbon atoms in the diacid monomer units.
The patent of Kiely and Lin10 describes the preparation of polyhydroxypolyamides from several esterified aldaric acids (carbohydrate diacids) with a number of alkylenediamines, polymerization being carried out without concern for controlling the stereochemical alignment of the diacids, all of which contain chiral carbons. The report of Kiely, Chen and Lin12 describes PHPAs derived only from D-glucaric acid, but with a variety of diamines, including alkylenediamines, diamines with heteroatoms (heterodiamines) in place of one or more carbons in the diamine chain, and arylalkyldiamines. In all of the above preparations of PHPAs, no control of stoichiometry is indicated, and the diacid and diamine monomers are not in an exact 1:1 (molar) stoichiometric relationship in the reaction mixtures. Having a 1:1 molar ratio between reacting monomers is a requirement for forming high molecular weight polymers (17, pp 274-275) by a condensation polymerization process. Consequently, the reported number average molecular weights (Mn) of the PHPAs derived from alkylenediamines as above are typically relatively low and below 3,000. The polyamides have low solubility in methanol, the reported solvent of choice for polymerization, a condition which limits their molecular weights. The report of Morton and Kiely18 describes PHPAs from D-glucaric acid and D-galactaric acid with a number of diamines that also contain a heteroatom or heteroatoms in place of diamine carbon atoms. The resulting polyamides have higher methanol solubility than do those derived from alkylenediamines, which results in significantly higher molecular weights for the PHPAs that precipitate from solution. What these literature sources tell us is: a) that higher molecular weight PHPAs, particularly those with low methanol solubility, are likely to be only achieved by strict control of stoichiometry between the diamine and aldaric acid units, but does not explicitly indicate how this stoichiometry can be achieved in a practical manner; b) enhanced solubilization of the growing polymer is imperative if significantly higher molecular weights are to be achieved.
All patents, patent applications, provisional patent application and publications referred to or cited herein, or from which a claim for benefit of priority has been made, are incorporated by reference in their entirety to the extent they are not inconsistent with the explicit teachings of the specification. | {
"pile_set_name": "USPTO Backgrounds"
} |
1. Field of the Invention
The present invention relates to a device and a method for adjusting, by a desired magnification, the number of pixels of image data which is displayed or printed using a data processing device.
2. Description of the Prior Art
In personal computers, printers and various other data processing devices, when transferring image data between applications having different image data resolutions, an image data adjusting process is carried out for a resolution adjustment by increasing or decreasing the number of pixels of the image data. Further, when storing image data having a large number of pixels into a memory, a process is performed to decrease the number of pixels of the image data for reducing a storage capacity of the memory. The number of the pixels of the image data may also be reduced upon transmitting the image data via a communication line for reducing a transmission time.
When, for example, increasing the number of pixels of image data by integer times (integral magnifications) in width and height directions (X- and Y-directions), respectively, each pixel is copied as many times as represented by the magnifications in the X- and Y-directions. Accordingly, for example, each pixel is copied N times in the X-direction and M times in the Y-direction so that image data having N.times.M times pixels can be obtained.
On the other hand, when increasing the number of pixels of image data by a magnification of a real number not an integer, such as 1.5 times or 2.5 times, in either direction, the pixels to be copied and the pixels not to be copied are mixed to achieve such a magnification.
For increasing the number of pixels, it is the simplest to add a pixel of the same pixel value at a subsequent position. However, in case of an image expressing the halftone, unnatural shade is generated to deteriorate the quality of the image when displayed or printed. This is particularly significant when adjusting the number of pixels of image data by a non-integral magnification.
Accordingly, for achieving smooth change in pixel values of pixels in an output image which are increased by copying, a proper calculation is carried out by referring to a plurality of peripheral pixels. This is called a resampling process, wherein the method of first degree interpolation or the like is used for calculating pixel values of the respective pixels.
However, the foregoing conventional technique has the following problem:
For calculating pixel values of output pixels in an output image using the method of first degree interpolation or the like, it is necessary to provide in advance pixel values of input pixels disposed around each of the output pixels whose pixel values are to be derived. Accordingly, it is necessary that, for example, substantially one-page image data or the like be stored in advance in a buffer memory and then read out in turn to be subjected to a given process.
Thus, the conventional technique can not achieve the effective use of the memory and prolongs an image data processing time. | {
"pile_set_name": "USPTO Backgrounds"
} |
Screen printing is a very old process and produces extremely good results. However, an apparatus for screen process printing is quite expensive and complicated for large procedures, and generally homemade for light service. It is known to produce screens for printing with light sensitive emulsions, opaque positives and light exposure; however, this manufacturing process usually requires a dark room, complicated equipment, or is done with great difficulty. | {
"pile_set_name": "USPTO Backgrounds"
} |
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