A hair roots coloring kit includes a plurality of kit components carried in a drawstring bag for mixing and applying standard hair coloring materials to the uncolored outgrown roots of a user's hair. One or more measuring devices such as a measuring cup, a syringe, or an eyedropper are used for measuring the hair coloring materials to produce a matching color to previously colored hair shafts of the hair. A reusable mixing bowl or a plurality of disposable mixing bowls hold the measured hair coloring materials. A reusable stirring stick or a plurality of disposable stirring sticks are provided for mixing together the measured hair coloring materials in the mixing bowl. An applicator brush is used for applying the mixed matching color of hair coloring composition to the uncolored hair roots. A pair of protective gloves are provided to protect the user's hands during application of the hair coloring composition to the hair roots. A cleaning brush is used to aid in cleaning the kit components following use.

1. Field
The present invention relates generally to hair coloring tools and methods for mixing hair coloring compositions, and more particularly to a portable hair coloring kit and method for mixing hair coloring compositions to color roots of the user's hair to a matching color to the hair shafts.
2. State of the Art
Hair coloring has been done for hundreds if not thousands of years by women to change and enhance their appearance and to cover graying hair. More recently, men have increasingly colored their hair generally for the same reasons. In the past hair coloring dyes were based on naturally occurring dyes such as those produced by plants or various minerals. In modern times, there are numerous hair coloring products, including coloring shampoos and weekly rinses, semi-permanent hair coloring compositions, and permanent hair coloring compositions.
Many hair coloring products require mixing together of two or more components prior to application to the user's hair, such as a liquid or paste hair coloring composition and a liquid developer or fixing solution. The liquid hair coloring composition may be packaged in a squeeze bottle and the hair coloring paste may be packaged in a squeeze tube. The hair dresser typically mixes the required quantities of hair coloring composition and fixing solution in a bowl or similar container. The mixed coloring composition is applied to the user's hair using one of a number of types of brushes commercially available for the task similar in design to paint brushes.
Coloring may be done of all the user's hair or only to portions of the hair such as in "streaking" the hair. Touch-up coloring is required following full coloring to color the hair roots grown out since the last hair coloring to match the color of the previously colored hair shafts. This may require blending or mixing together of hair coloring compositions of several different colors to match the previously colored hair shafts. Usually a minimum amount of the hair coloring composition is prepared to do the job as the hair coloring materials are quite expensive.
In an effort to more conveniently mix hair coloring compositions of different colors, a hair coloring kit which better enables a user to mix custom colors of hair coloring compositions is disclosed in U.S. Pat. No. 6,440,175 issued to Stanley, III. The kit includes a liquid base composition, a plurality of color concentrates, and a dispenser. The color concentrates provided include the colors green, yellow, blue, red, orange, brown, white, black or any other colors such as purple or any other shades or variations of these colors. The color concentrates can be provided as liquids packaged in respective containers such as vials with a medicine dropper, syringe or eye dropper for transferring the color concentrate from the vials for mixing with the base composition. Alternatively, the vials may each be provided with a cap such that the color concentrates are poured from the respective vials. The color concentrates are mixed with the base composition in the dispenser to form a custom color. The hair coloring composition of the custom color is then sprayed onto the user's hair. The base composition can be a conventional hair spray which also holds the user's hair in place. The base composition could also be a tablet or powder that is mixed with water to form the liquid base composition.
The kit of Stanley, III has several substantial shortcomings. Firstly, the kit cannot be used to mix conventional hair coloring materials which may be quite close to the desired color, requiring only slight tinting. Rather, the basic green, yellow, blue, red, orange, brown, white, black must be mixed to produce the desired color. This can be very difficult to produce the desired color. Likewise, the kit cannot interface with the containers used to package conventional hair coloring materials. Finally, the kit does not provide a sufficient measuring devices for portioning the color concentrates and base composition, provides no mixing device such as a stirring stick, provides no application brush or similar application device, provides no protective gloves, provides no cleaning brush or similar device, and provides no carrying device such as a carrying bag or carrying case.
Therefore, there is a need for a hair coloring kit for use with conventional hair coloring materials which provides a complete set of kit components to conduct the hair coloring process. This might include a container device, one or more measuring devices, a stirring device, protective gloves, an applicator device, and a container in which to store the kit components during periods of non-use. The kit would include cleanable, reusable kit components and/or a plurality of disposable kit components.


Described herein is a push-up exercise apparatus. The push-up exercise apparatus includes a frame having at least a pair of legs and transverse cross braces connecting the legs; a plurality of horizontal platforms coupled to the frame and transverse to the at least pair of the legs; a plurality of horizontal bars coupled the frame and transverse to the at least pair of the legs; and the plurality of horizontal platforms and bars arranged in a stepped configuration such that an upper bar is recessed compared to a lower bar and/or one or more of the plurality of horizontal platforms or bars being slidably coupled to the frame. Methods for performing push-ups are also described.

Field of the Invention
The present invention relates to exercise equipment, more specifically exercise equipment that can be used to perform push-ups.
Description of the Related Art
A push-up (or the British term press-up) is one of the most widely performed free weight exercise. A standard push-up is performed by placing hands and feet on a flat surface with the back and legs maintained in a straight or plank position with arms fully extended. Arms are bent to bring the torso to the ground and then arms are extended to complete the push-up.
The standard push-up is not suitable for all exercise programs. For example, individuals rehabilitating an injury or simply lacking in upper body strength may not be able to perform a standard push-up. Conversely, highly athletic individuals may find that a standard push-up does not sufficiently challenge their muscles.
Various modifications of the standard push-up have been developed to either increase or decrease the physical challenge of the push-up.
Decline push-ups, diamond push-ups, wide-grip push-ups, Maltese push-ups, Chinese or Hindu push-ups, knuckle push-ups, one armed push-ups, guillotine push-ups, backhanded push-ups and walking push-ups are examples of modified push-ups that require increased effort to perform compared to a standard push-up.
Incline push-ups, knee push-ups, and three-phase push-ups are examples of modified push-ups that require less effort to perform compared to a standard push-up.
Furthermore, several push-up exercise devices have been developed with the goal of increasing and/or decreasing the physical challenge of the standard push-up. Examples of such devices are disclosed in U.S. Pat. Nos. 5,033,741; 6,050,926; 7,060,014; 7,318,793; 7,114,352; and 7,588,521. Despite the availability of many such devices, none have achieved popularity in the health club industry.
In commercial gyms the most popular method for achieving a variance of push-ups is to find open space/walls or gym equipment that one can lean into or put their feet up on. This does not always allow for the same stable function, and this improvised method can compromise proper form.
Accordingly, there is a continuing need for devices that allow users to perform a variety of modified push-ups.


The present invention relates to novel thio-aminotetralin compounds of the formula (I)

The present invention is related to compounds that exhibit analgesic activity and in particular compounds exhibiting analgesia due to their opioid receptor affinity.
Many natural alkaloids and related analogs bind to specific opioid receptors and elicit an analgesic response similar to classic narcotic opiates. Many different types of opioid receptors have been shown to coexist in higher animals. For example, see W. Martin et al., J. Pharmacol. Exp. Ther 197, p. 517 (1975); and J. Lord et al., Nature (London), 257, p.495 (1977). Three different types of opioid receptors have been identified. The first, xcex4, shows a differentiating affinity for enkephalin-like peptides. The second, xcexc, shows enhanced selectivity for morphine and other polycyclic alkaloids. The third, xcexa, exhibits equal affinity for either group of the above ligands and preferential affinity for dynorphin. In general, the xcexc receptors seem to be more involved with analgesic effects. The xcex4 receptors appear to deal with behavioral effects, although the xcex4 and the xcexa receptors may also mediate analgesia.
Each opioid receptor, when coupled with an opiate, causes a specific biological response unique to that type of receptor. When an opiate activates more than one receptor, the biological response for each receptor is affected, thereby producing side effects. The less specific and selective an opiate may be, the greater the chance of causing increased side effects by the administration of the opiate.
Opiates can cause serious and potentially fatal side effects. Side effects such as respiratory depression, tolerance, physical dependence capacity, and precipitated withdrawal syndrome are caused by nonspecific interactions with central nervous system receptors. See K. Budd,
In International Encyclopedia of Pharmacology and Therapeutics; N. E. Williams and H. Wilkinson, Eds., Pergammon: (Oxford), 112, p.51 (1983). It is therefore an object of the present invention to provide compounds having analgesic effects but having as few side-effects as possible.
In one aspect, the present invention provides novel thio aminotetralin compounds represented by formula (I):
and pharmaceutically acceptable derivatives thereof;
wherein;
Z is S, SO or SO2,
X is selected from anyone of
(i) a bond;
(ii) xe2x80x94CR7R8xe2x80x94 wherein R7 and R8 are independently selected from the group consisting of H, OH, halogen, CN, COOH, CONH2, amino, nitro, SH, C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N; and COORC wherein Rc is C1-6alkyl, C2-6alkenyl or C2-6alkynyl; R7 and R8 can also be connected to form C3-8 cycloalkyl, a C3-8 cycloalkenyl or a saturated heterocycle of from 3 to 8 atoms;
R1 is selected from the group consisting of H, C1-12alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-12alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-12alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C6-12 aryl, C6-12 aralkyl, C6-12 aryloxy, C1-12 acyl, heteroaryl having from 6 to 12 atoms, and phosphoryl;
R2 and R3 are independently selected from the group consisting of C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C6-12 aryl, C6-12 aralkyl, heteroaryl having from 6 to 12 atoms, and H; or
R2 and R3 may together form a saturated heterocycle of from 3 to 8 atoms;
R4 and R5 are independently selected from the group consisting of C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, and H;
R4 and R5 can also be connected to form C3-8 cycloalkyl, a C3-8 cycloalkenyl or a saturated heterocycle of from 3 to 8 atoms;
R6 is hydrogen, OH, C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, C2-6alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, Oxe2x80x94C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, Oxe2x80x94C2-6alkenyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, Oxe2x80x94C2-6alkynyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, halogen, CN, COOH, CONH2, amino, nitro, or SH;
with the provisos that:
1) not both R4 and R5 are H; and
2) at least one of R2 and R3 is H or C1-6 alkyl.
The compounds of the present invention are useful in therapy, in particular as analgesics.
In another aspect, there is provided a method of treating pain in a mammal, comprising administering to said mammal an analgesic amount of a compound or composition of the invention.
Still another aspect of the invention is the use of a compound according to formula (I), for the manufacture of a medicament for the treatment of pain.
In another aspect, there is provided pharmaceutical compositions comprising compounds of the present invention and pharmaceutically acceptable carriers, diluents or adjuvants.
X is preferably xe2x80x94CR7R8xe2x80x94 wherein R7 and R8 are independently selected from the group consisting of OH, halogen, CN, COOH, CONH2, amino, nitro, SH, C1-6 alkyl where one or more of the carbon atoms may optionally be substituted by one or more heteroatoms selected from O, S and N, H, and COORc wherein Rc is C1-6alkyl; R7 and R8 can also be connected to form a C3-8 cycloalkyl.
X is more preferably xe2x80x94CR7R8xe2x80x94 wherein R7 and R8 are independently selected from the group consisting of C1-6 alkyl, and H.
X is most preferably xe2x80x94CH2xe2x80x94.
R1 is preferably selected from the group consisting of H, C1-12alkyl, C6-12 aryl, and C6-12 aralkyl.
R1 is more preferably selected from the group consisting of C1-6alkyl, C6-12 aryl, and C6-12 aralkyl.
R1 is most preferably C1-6 alkyl.
R1 can also be
xe2x80x83wherein n is an integer between 1 to 5, Rx and Rx1 are independently H, C1-6alkyl, C2-6alkenyl or C2-6alkynyl. More preferably, n is 1 or 2 and Rx and Rx1 are C1-6alkyl. Most preferably, Rx and Rx1 are methyl or ethyl.
In an alternative embodiment, R1 is selected from the group consisting of CH3, xe2x80x94(CH2)nxe2x80x94CH3, and xe2x80x94(CH2)nxe2x80x94Oxe2x80x94CH3 wherein n is an integer selected between 1 and 5. In an alternative preferred embodiment R1 is C6-12 aryl or heteroaryl having from 6 to 12 atoms.
In a further preferred embodiment, R1 is selected from the group consisting of
wherein A is selected from the group consisting of C1-6 alkyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Oxe2x80x94C1-6 alkyl, Oxe2x80x94C2-6alkenyl, Oxe2x80x94C2-6alkynyl, Sxe2x80x94C1-6 alkyl, Sxe2x80x94C2-6alkenyl, Sxe2x80x94C2-6alkynyl, Nxe2x80x94C1-6 alkyl, Nxe2x80x94C2-6alkenyl, Nxe2x80x94C2-6alkynyl, CF3, fluoro, chloro, bromo, iodo, OH, SH, CN, nitro, amino, aminoamidino, amidino, guanido, COOH, and COORz wherein Rz is C1-6alkyl, C2-6alkenyl or C2-6alkynyl.
In an alternative embodiment, R1 is C6-12 aralkyl or heteroaryl having from 6 to 12 atoms.
More preferably, R1 is selected from the group consisting of
wherein A is selected from the group consisting of C1-6 alkyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Oxe2x80x94C1-6 alkyl, Oxe2x80x94C2-6alkenyl, Oxe2x80x94C2-6alkynyl, Sxe2x80x94C1-6 alkyl, Sxe2x80x94C2-6alkenyl, Sxe2x80x94C2-6alkynyl, Nxe2x80x94C1-6 alkyl, Nxe2x80x94C2-6alkenyl, Nxe2x80x94C2-6alkynyl, CF3, fluoro, chloro, bromo, iodo, OH, SH, CN, nitro, amino, aminoamidino, amidino, guanido, COOH, and COORz wherein Rz is C1-6alkyl, C2-6alkenyl or C2-6alkynyl and Y is xe2x80x94(CH2)mxe2x80x94wherein m is an integer selected between 1 and 5.
R1 is preferably
wherein A and Y are as defined above.
A is preferably selected from the group consisting of C1-6 alkyl, Oxe2x80x94C1-6 alkyl, Sxe2x80x94C1-6 alkyl, OH, nitro, amino, aminoamidino, amidino, guanido, COOH, and COORa wherein Ra is C1-6alkyl, C2-6alkenyl or C2-6alkynyl. A is more preferably selected from the group consisting of C1-6 alkyl, OH, nitro, amino, aminoamidino, amidino, guanido, and COOH. A is most preferably selected from the group consisting of amidino, guanido, and OH.
R2 and R3 are preferably H.
R4 and R5 are preferably C1-4 alkyl substituted by a hydroxyl.
R4 and R5 are preferably C1-4 alkyl.
In a further preferred embodiment, R4 and R5 are independently selected from the group consisting of methyl, ethyl, isopropyl, propyl, butyl, and isobutyl.
R4 and R5 are preferably ethyl.
R4 and R5 are preferably methyl.
R6 can be substituted at any position on the aromatic ring. More preferably R6 is adjacent to the carbon bearing the OH. In an alternative embodiment, the present invention provides compounds of the formula (II) or (III)
and pharmaceutically acceptable derivative;
wherein each of X, Z, R1, R2, R3, R4, R5, and R6 are defined above.
R6 is preferably, H, methyl, halogen or ORb wherein Rb is C1-6alkyl, C1-6alkenyl or C1-6alkynyl.
R6 is most preferably H.
The compounds of the present invention contains at least 2 chiral centers which are marked by an asterik (*) on the general formula (I). The compounds of formula (I) thus exist in the form of different geometric (i.e. trans and cis) and optical isomers (i.e. (+) or (xe2x88x92) enantiomers). When there is 2 chiral centers at the position marked by the asteriks, the compounds may therefore be in the form of cis isomers or trans isomers. Each cis or trans isomers also exists as a (+) and (xe2x88x92) enantiomer. All such isomers, enantiomers and mixtures thereof including racemic mixtures are included within the scope of the invention.
Preferably the compounds of the present invention are in the form of the trans isomers. More preferably the compounds of the present invention are present in the form of trans (+) and trans (xe2x88x92) enantiomers.
Preferred compounds of the invention include:Trans-7-Amino-8,8-dimethyl-6-methylsulfanyl-5,6,7,8-dihydro-naphthalen-2-ol
(compound #1);Cis-7-Amino-8,8-dimethyl-6-methylsulfanyl-5,6,7,8-dihydro-naphthalen-2-ol
(compound #2); Trans-7-Amino-8,8-diethyl-6-methylsulfanyl-5,6,7,8-dihydro-naphthalen-2-ol
(compound #3);Trans-7-Amino-8,8-dimethyl-6-phenylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (compound #4);
Trans-7-Amino-8,8-dimethyl-6-(pyridin-2-ylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #5);
Trans-7-Amino-8,8-dimethyl-6-(pyrimidin-2-ylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #6);
Trans-7-Amino-6-(3-amino-phenylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #7);
Trans-7-Amino-8,8-dimethyl-6-(4-methylsulfanyl-phenylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #8);
Trans-7-Amino-6-benzenesulfonylmethylsulfanyl-8,8-diethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #9);
Trans-2-(3-Amino-4,4-diethyl-6-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-acetamide (Compound #10);
Trans-(3-Amino-4,4-diethyl-6-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanylmethyl)-phosphonic acid diethyl ester (Compound #11);
Trans-7-Amino-8,8-diethyl-6-(2-hydroxy-ethylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #12);
Trans-7-Amino-6-(5-amino-2H-[1,2,4]triazol-3-ylsulfanyl)-8,8-diethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #13);
Trans-7-Amino-6-(2-amino-ethylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #14);
Trans-7-Amino-6-(5-amino-2H-[1,2,4]triazol-3-ylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #15);
Trans-7-Amino-8,8-dimethyl-6-propylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #16);
Trans-7-Amino-6-isopropylsulfanyl-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #17);
Trans-7-Amino-6-(2-hydroxy-ethylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #18);
Trans-2-(3-Amino-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-acetamide (Compound #19);
Trans-7-Dimethylamino-8,8-dimethyl-6-methylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #20);
8,8-dimethyl-trans-7-methylamino-6methylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #21);
Trans-7-Amino-8,8-diethyl-6-phenylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #22);
8,8-dimethyl-trans-6-phenylsulfanyl-7-propylamino-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #23);
Trans-7-Amino-6-(2-amino-phenylsulfanyl)-8,8-diethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #24;
Trans-7-Amino-8,8-dimethyl-6-(2,2,2-trifluoro-ethylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol Compound #25);
Trans4-(3-Amino-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-butyric acid ethyl ester (Compound #26);
Trans-7-Amino-6-benzenesulfonylmethylsulfanyl-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #27);
Trans-7-Amino-8,8-dimethyl-6-(3-phenyl-allylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #28);
Trans-7-Amino-6-isobutylsulfanyl-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #29);
Trans-7-Amino-8,8-dimethyl-6-(2-phenoxy-ethylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #30);
Trans-7-Amino-8,8-diethyl-6-(2-phenoxy-ethylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #31);
(xe2x88x92)Trans-7-amino-8,8-dimethyl-6-methylsulfanyl-5,66,7,8-tetrahydro-naphthalen-2-ol (Compound #32);
(+)Trans-7-amino-8,8-dimethyl-6-methylsulfanyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #33);Trans-7-amino-6-(4-bromo-phenylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydronaphthalen-2-ol (Compound #34);
Trans-7-amino-8,8-dimethyl-6-(naphthalen-2-ylsulfanyl)-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #35);Trans7-Amino-6-(4-hydroxy-phenylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #36);Trans-7-amino-6-(4amino-phenylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #37);Trans-7-amino-6-(3-hydroxy-phenylsulfanyl)-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ol (Compound #38);Trans-3-(3-Amino-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-propionic acid ethyl ester (Compound #39);Trans-7-amino-8,8-dimethyl-6-phenethylsulfanyl-5,6,7,8-tetrahydronaphthalen-2-ol (Compound #40);Trans-2-(3-amino-6-hydroxy-4,4-dimethyl 1,2,3,4-tetrahydronaphthalen-2-ylsulfanyl)-propionamide (Compound #41);Trans-3-(3-amino-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-propionic acid (Compound #42);Trans-2-[3-(3-Amino-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-ylsulfanyl)-propionylamino]-3-(4-hydroxy-phenyl)-propionamide (Compound #43); 3-trans-(2-ethoxycarbonyl-ethylsulfanyl)-1,1-diethyl-7-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl (Compound #44); 3-trans-(2-carboxy-ethylsulfanyl)-1,1-diethyl-7-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl (Compound #45);
and pharmaceutically acceptable derivatives thereof; wherein said compound is in the form of the (+) enantiomer, the (xe2x88x92) enantiomer and mixture of the (+) and (xe2x88x92) enantiomer including racemic mixture.
More preferably the compound of the present invention is selected from the group consisting of compound#1, compound#3, compound#4, compound#5, compound#9, compound#11, compound#15, compound#31, compound#32, compound#33, compound#36, compound#37, compound#39 compound#41, compound#43, compound#44 and compound #45.
Most preferably the compound of the present invention is selected from the group consisting of compound#1, compound#3, compound#5, compound#32, compound#33, compound#36, compound#44 and compound#45.
As used in the present application the term xe2x80x9cpainxe2x80x9d represents xe2x80x9can unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. The term xe2x80x9cpainxe2x80x9d also includes xe2x80x9cacute painxe2x80x9d and chronic pain.
Acute pain is usually immediate and of a short duration. Acute pain can be present further to an injury, short-term illness, or surgical/medical procedure.
Examples of acute pain include a burn, a fracture, an overused muscle, or pain after surgery. Cancer pain may be long-lasting but acute due to ongoing tissue damage.
Some chronic pain is due to damage or injury to nerve fibers themselves (neuropathic pain).
Chronic pain can result from diseases, such as shingles and diabetes, or from trauma, surgery or amputation (phantom pain). It can also occur without a known injury or disease.
The present invention s directed to the treatment of all type of pain, including acute and chronic pain.
As used in this application, the term xe2x80x9calkylxe2x80x9d represents an unsubstituted or substituted (by a halogen, nitro, aminoamidino, amidino, guanido, CONH2, COOH, Oxe2x80x94C1-6 alkyl, Oxe2x80x94C2-6 alkenyl, Oxe2x80x94C2-6 alkynyl, amino, hydroxyl or COOQ, wherein Q is C1-6 alkyl, C2-6 alkenyl, a C2-6 alkynyl) straight chain, branched chain, or cyclic hydrocarbon moiety (e.g. isopropyl, ethyl, flurohexyl or cyclopropyl). The term alkyl is also meant to include alkyls in which one or more hydrogen atoms is replaced by an halogen, more preferably, the halogen is fluoro (e.g., CF3xe2x80x94, or CF3CH2xe2x80x94).
The term xe2x80x9csaturated heterocyclexe2x80x9d represents a carbocyclic ring in which one or more of the from 3 to 8 atoms of the ring are elements other than carbon, such as N, S and O;
The term xe2x80x9carylxe2x80x9d represents an aromatic ring having from 6 to 12 carbon atoms, which may be substituted by a C1-6 alkyl, C2-6 alkenyl, a C2-6 alkynyl, halogen, nitro, aminoamidino, amidino, guanido, CONH2, COOH, Oxe2x80x94C1-6 alkyl, Oxe2x80x94C2-6 alkenyl, Oxe2x80x94C2-6 alkynyl, amino, hydroxyl or COOQ, wherein Q is C1-6 alkyl, C2-6 alkenyl, a C2-6 alkynyl, such as phenyl and naphthyl.
The term xe2x80x9caralkylxe2x80x9d represents an aryl group attached to the adjacent atom by a C1-6alkyl, C1-6alkenyl, or C1-6alkynyl(e.g., benzyl).
The term xe2x80x9caryloxyxe2x80x9d represents an aryl or aralkyl moiety covalently bonded through an oxygen atom (e.g., phenoxy).
The term xe2x80x9cheteroarylxe2x80x9d represents an aromatic ring in which one or more of the from 6 to 12 atoms in the ring are elements other than carbon, such as O, N, and S (e.g pyridine, isoquinoline, or benzothiophene).
The term xe2x80x9cacylxe2x80x9d refers to a radical derived from a carboxylic acid, substituted (by halogen(F, Cl, Br, I), C6-20 aryl or C1-6 alkyl) or unsubstituted, by replacement of the OH group. Like the acid to which it is related, an acyl radical may be aliphatic or aromatic, substituted (by halogen, C1-5 alkoxyalkyl, nitro or OH) or unsubstituted, and whatever the structure of the rest of the molecule may be, the properties of the functional group remain essentially the same (e.g., acetyl, propionyl, isobutanoyl, pivaloyl, hexanoyl, trifluoroacetyl, chloroacetyl, and cyclohexanoyl).
The term xe2x80x9cphosphorylxe2x80x9d represents a radical derived from a phosphono moeity in which the hydrogen atom of at least one of the xe2x80x94OH can be replaced by C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6heteroalkyl, C6-12 aryl, C6-12 aralkyl, and C6-12 heteroaryl(e.g., diethoxyphosphorylmethyl).
The term xe2x80x9chalogenxe2x80x9d encompasses chloro, fluoro, bromo and iodo;
In the present application the following abbreviations are used:
When there is a sulfur atom present, the sulfur atom can be at different oxydation level, S, SO, or SO2. All such oxydation level are within the scope of the present invention.
In yet another aspect of the invention, there is provided a process for preparing compounds of formula (I). The process is described in scheme 1 wherein each of X, R1, R2, R3, R4, R5 and R6 are as defined above and P, P1, P2, and P3 are protecting groups. If desired, the sulfur of the compound of formula Ia can be oxydized to Sxe2x95x90O or SO2 by methods well known in the art.
Step 1
The starting ketone AA was dissolved in a suitable solvent such as DMF, acetonitrile, THF, DME and was treated with sodium hydride or any other base such as potassium t-butoxide, sodium bis(trimethylsilyl)amide. The resulting mixture was then treated with ethyl iodide or any other alkyl halide such as methyl iodide, allyl bromide, diiodobutane to produce the compound A.
Step 2
The compound A was dissolved in a suitable solvent such as pyridine, DMF, ethanol and was treated with hydroxylamine hydrochloride or any other hydroxylamine salt such as hydroxylamine sulfate, hydroxylamine bromide to produce the compound B.
Step 3
The compound B was dissolved in a suitable solvent as THF, dioxane, DME, and was treated with LAH or any other reducing agent such as red-Al in presence of diethylamine or any other amine such as methylbutylamine, dipropylamine. The mixture was then heated to 50xc2x0 C. or at any higher temperature to produce the compound C.
Step 4
The compound C in was dissolved in a suitable solvent as dichloromethane (CH2Cl2) or in any other solvent such as dichloroethane, and was treated with BBr3 or any other demethylating agent such as BCl3, HBr, to produce the compound D.
Step 5
The amino or hydroxyl groups of the compound D were protected with Boc or with any other protecting group, to produce the compound E. Protective groups are described in Protective Groups in Organic Synthesis, 2nd ed., Greene and Wuts, John Wiley and Sons, New York, 1991 which is herein incorparated by reference.
Step 6
The compound E was dissolved in a suitable solvent such as ethanol or in any other alcohol such as methanol, propanol, butanol and was treated with pyridinium p-toluenesulfonate (PPTS) or any other acid or Lewis acid such as HCl, BF3.OEt 2, PTSA, to produce the compound F. Alternatively, a non alcoholic solvent can be used in combination with an appropriate amount of an alcohol and a suitable Lewis acid such as ytterbium triflate see for example Tetrahedron Letters, Vol. 37, No.43, pp7717-7720, 1996 which is herein incorparated by reference.
Step 7
The protecting groups of the compound F were removed under appropriate conditions e.g. with TFA or with any other acid such as HCl, PTSA, to produce the compound Ia.
It will be appreciated that certain substituents require protection during the course of the synthesis and subsequent deprotection. For example, it may be necessary to protect an hydroxyl group by converion to an alkoxy or an ester and subsequently deprotected. Protective groups for other substituents are described in Protective Groups in Organic Synthesis, 2nd ed., Greene and Wuts, John Wiley and Sons, New York, 1991.
In another aspect, there is provided a method of agonizing or activating opioid receptors in a mammal comprising administering to said mammal an opioid receptor agonizing or activating amount of a compound or composition of the invention.
There is also provided pharmaceutically acceptable compositions comprising compounds of the present invention and derivatives thereof, in combination with pharmaceutically acceptable carriers diluents or adjuvants.
By xe2x80x9cpharmaceutically acceptable derivativesxe2x80x9d is meant any pharmaceutically acceptable salt, ester, or salt of such ester, of compounds of formula (I) or (II) or any other compound such as a prodrug which, upon administration to the recipient, is capable of providing (directly or indirectly) compounds of formula (I) or (II) or an active metabolite or residue thereof.
The present invention also provides pharmaceutical compositions which comprise a pharmaceutically effective amount of a compound of the invention, or pharmaceutically acceptable salts thereof, and preferably, a pharmaceutically acceptable carrier, diluent or adjuvant. The term xe2x80x9cpharmaceutically effective amountxe2x80x9d is the amount of compound required upon administration to a mammal in order to induce analgesia. Also, the term xe2x80x9copioid receptor agonizing amountxe2x80x9d refers to the amount of compound administered to a mammal necessary to bind and/or activate opioid receptors in vivo.
Therapeutic methods of this invention comprise the step of treating patients in a pharmaceutically acceptable manner with those compounds or compositions. Such compositions may be in the form of tablets, capsules, caplets, powders, granules, lozenges, suppositories, reconstitutable powders, or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
In order to obtain consistency of administration, it is preferred that a composition of the invention is in the form of a unit dose. The unit dose presentation forms for oral administration may be tablets and capsules and may contain conventional excipients. For example, binding agents, such as acacia, gelatin, sorbitol, or polyvinylpyrolidone; fillers, such as lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricants such as magnesium stearate; disintegrants, such as starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
The compounds may be administered orally in the form of tablets, capsules, or granules containing suitable excipients such as starch, lactose, white sugar and the like. The compounds may be administered orally in the form of solutions which may contain coloring and/or flavoring agents. The compounds may also be administered sublingually in the form of tracheas or lozenges in which each active ingredient is mixed with sugar or corn syrups, flavoring agents and dyes, and then dehydrated sufficiently to make the mixture suitable for pressing into solid form.
The solid oral compositions may be prepared by conventional methods of blending, filling, tableting, or the like. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art. The tablets may be coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
Liquid oral preparations may be in the form of emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may or may not contain conventional additives. For example suspending agents, such as sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, or hydrogenated edible fats; emulsifying agents, such as sorbitan monooleate or acaci; non-aqueous vehicles (which may include edible oils), such as almond oil, fractionated coconut oil, oily esters selected from the group consisting of glycerine, propylene glycol, ethylene glycol, and ethyl alcohol; preservatives, for instance methyl para-hydroxybenzoate, ethyl para-hydroxybenzoate, n-propyl parahydroxybenzoate, or n-butyl parahydroxybenzoate of sorbic acid; and, if desired, conventional flavoring or coloring agents.
The compounds may be injected parenterally; this being intramuscularly, intravenously, or subcutaneously. For parenteral administration, the compound may be used in the form of sterile solutions containing other solutes, for example, sufficient saline or glucose to make the solution isotonic. For parenteral administration, fluid unit dosage forms may be prepared by utilizing the compound and a sterile vehicle, and, depending on the concentration employed, may be either suspended or dissolved in the vehicle. Once in solution, the compound may be injected and filter sterilized before filling a suitable vial or ampoule and subsequently sealing the carrier or storage package. Adjuvants, such as a local anesthetic, a preservative or a buffering agent, may be dissolved in the vehicle prior to use. Stability of the pharmaceutical composition may be enhanced by freezing the composition after filling the vial and removing the water under vacuum, (e.g., freeze drying the composition). Parenteral suspensions may be prepared in substantially the same manner, except that the compound should be suspended in the vehicle rather than being dissolved, and, further, sterilization is not achievable by filtration. The compound may be sterilized, however, by exposing it to ethylene oxide before suspending it in the sterile vehicle. A surfactant or wetting solution may be advantageously included in the composition to facilitate uniform distribution of the compound.
The pharmaceutical compositions of this invention comprise a pharmaceutically effective amount of a compound of this invention and a pharmaceutically acceptable carrier. Typically, they contain from about 0.01% to about 99% by weight, preferably from about 10% to about 60% by weight, of a compound of this invention, depending on which method of administration is employed.
The compounds of the present invention can be administered in combination with one or more further therapeutic agents. Preferably, the one or more further therapeutic agent is selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, narcotics, antidepressants, anticonvulsants, corticosteroid, tramadol, sumatriptan, and capsaicin.
Without limitations, NSAIDs include aspirin (Anacin, Bayer, Bufferin), ibuprofen (Motrin, Advil, Nuprin), naproxen sodium (Aleve) and ketoprofen (Orudis KT)
Without limitations, narcotics include drugs derived from opium (opiates), such as morphine and codeine, and synthetic narcotics (opioids), such as oxycodone, methadone and meperidine (Demerol).
Without limitations, antidepressants include amitriptyline (Elavil), trazodone (Desyrel) and imipramine (Tofranil) may be used with other analgesics. These drugs are especially useful for neuropathic, head and cancer pain.
Without limitations, anticonvulsants include drugs developed for epilepsy, these drugs, such as phonation (Dilantin) and carbamazepine (Tegretol), can also help control chronic nerve pain.
Tramadol (Ultram) is a synthetic analgesic used primarily for chronic pain, but is also prescribed for acute pain.
Sumatriptan (Imitrex), may reduce pain from migraine headache by constricting blood vessels.
Capsaicin (Zostrix), a topical cream made from an extract of red peppers, can help relieve skin sensitivity resulting from shingles. Capsaicin can also be used to treat pain from arthritis, cluster headaches, diabetic neuropathy and pain after mastectomy.
In another aspect of the invention, compounds may be used to identify opioid receptors from non-opioid receptors. For such use, compounds of the invention are radiolabeled e.g. by incorporating 3H or 14C within its structure or by conjugation to 125I. Such radiolabeled forms can be used directly to identify the presence of opioid receptors and in particular p opioid receptors in a receptor population. This can be achieved by incubating membrane preparations with a radiolabeled compound of the invention. The presence and or amount of opioid receptors in the preparation is determined from the difference in membrane-bound radioactivity against a control preparation devoid of opioid receptors. Furthermore, radiolabeled forms of the present compounds can be exploited to screen for more potent opioid ligands, by determining the ability of the test ligand-to displace the radiolabeled compound of the present invention.

Abstract: wherein Z, X, R1, R2, R3, R4, R5, and R6 are defined herein. The compounds are useful in pain management.


Techniques are provided that identify near-duplicate items in large collections of items. A list of (value, frequency) pairs is received, and a sample (value, instance) is returned. The value is chosen from the values of the first list, and the instance is a value less than frequency, in such a way that the probability of selecting the same sample from two lists is equal to the similarity of the two lists.

Large collections of documents typically include many documents that are identical or nearly identical to one another. Determining whether two digitally-encoded documents are bit-for-bit identical is easy (using hashing techniques, for example). Quickly identifying documents that are roughly or effectively identical, however, is a more challenging and, in many contexts, a more useful task.
The World Wide Web is an extremely large set of documents. The Web has grown exponentially since its birth, and Web indexes currently include approximately five billion web pages (the static Web being estimated at twenty billion pages), a significant portion of which are duplicates and near-duplicates. Applications such as web crawlers and search engines benefit from the capacity to detect near-duplicates. For example, it may be desirable to have such applications ignore most duplicates and near-duplicates, or to filter the results of a query so that similar documents are grouped together.

Consistent weighted sampling of multisets and distributions


An apparatus and method for conveying information from a signaling trail vehicle to oncoming trail vehicles. The information typically pertains to traffic, environmental or other trail conditions present behind the signaling trail vehicle. The apparatus comprises a signaling device to convey information from the signaling trail vehicle to the oncoming trail vehicles, and an actuation mechanism for operating the signal device. The method comprises the steps of energizing a yellow/amber light to provide a caution to oncoming trail vehicles of a trail hazard and energizing a green light to provide an all-clear signal to indicate that no additional trail vehicles are following the signaling trail vehicle.

1. Field of the Invention
The present invention relates, generally, to vehicle operation signaling apparatus and methods. More particularly, the invention relates to an apparatus and method for signaling and conveying certain predefined information between operators of two or more trail vehicles such as snowmobiles. Most particularly, the invention relates to an apparatus and method for signaling and conveying information from the operator of a trail vehicle traveling in a first direction on a trail or route to the operator or operators of one or more oncoming trail vehicles traveling in a second, opposite direction on the trail or route, the information pertaining to traffic, environmental or other predefined trail conditions.
2. Background Information
The figures illustrate the apparatus and method of the present invention used in conjunction with snowmobiles. However, the present invention can be used with all types of trail vehicles. Therefore, for the purposes of this specification and the claims, the term "trail vehicle" incorporates all transportation means on a recreational trail, including but not limited to snowmobiles, all-terrain vehicles, cyclists, skaters, and skiers. Additionally, reasonable analogies can be extended from the descriptions associated with the term "snowmobile" to other types of trail vehicles.
The general use of recreational trails is currently popular and is growing in popularity both in the United States of America and internationally. In particular, the number of snowmobiles and riders has increased significantly over the past few years. Snowmobile riders often take extended trips on groomed trails and often travel in groups for both safety and social reasons. An affect of the increase in popularity of snowmobile riding is that snowmobile trails have become crowded with more and larger groups comprising both experienced and inexperienced riders. Well-groomed, scenic, and therefore popular trails are often rather narrow due to land ownership constraints, the topography of the land, and aesthetic considerations. These crowded, narrow, winding trail corridors within a forested area increase the hazard level for riders because the limited line of sight reduces the amount of time to react to hazards and reduces the amount of room to maneuver around hazards. A hazard of a particular concern is groups of snowmobiles passing in opposite directions, especially during extended rides when the riders are more subject to physical and mental fatigue.
The state of the art in snowmobile trail riding includes a loosely followed method or convention for signaling group size information from the operator of a snowmobile traveling in a first direction on a designated, confined snowmobile trail to the operator or operators of one or more oncoming snowmobiles traveling in a second, opposite direction on the trail. According to the current convention practiced by some typically more experienced riders, riders traveling in the first direction and riders traveling in the second direction signal the number of snowmobiles traveling behind them within their group by raising that number of fingers on one hand. The last rider in a group signals his or her status as the last rider by raising a closed fist.
This convention, as well as other signaling or warning methods used on recreational trails, are believed to have significant limitations and shortcomings. These limitations and shortcomings include the following:
(1) There is a lack of a standardized, common signaling apparatus for conveying group information or other pertinent traffic or safety information. PA0 (2) Manual signaling does not have a universally understood and practiced signaling convention. Rather, these hand gestures are frequently confused with a greeting hand wave. PA0 (3) Manual signaling, when understood and practiced, is dependent upon the mental diligence of the individual and is therefore subject to lapses and failures when the trail user becomes physically or mentally fatigued. PA0 (4) Manual signaling is difficult to view and process in inclement weather, at higher speeds, and in low light or nighttime conditions. PA0 (5) The manual signaling of a group number with a gloved, and particularly a mittened, hand is difficult to view and will often become an ambiguous hand gesture that conveys little or no information. PA0 (6) Manual signaling of group size is limited by the number of fingers on one hand. PA0 (7) Manual signaling may require the removal of one hand from the handle bars or steering system of the trail vehicle at a particularly hazardous time when trail vehicles are approaching and control is paramount. PA0 (1) A standardized, common apparatus for signaling. PA0 (2) An intuitive signaling method analogous to automobile traffic signals which could develop into a universal signaling convention used and recognized by most trail users. PA0 (3) A signal that is easily recognized and easily set or reset while traveling on the trail. The signal is less subject to lapses and failures of fatigued trail users. PA0 (4) A light or illumination-based signal that is viewable in inclement weather, at greater distances and speeds, and in low light or nighttime conditions. PA0 (5) A clear, definite, and unambiguous signal. PA0 (6) A signal regarding group configuration that is not limited by the number of fingers on one hand. PA0 (7) A signal that can be actuated while maintaining complete control of the steering system of the trail vehicle. In the case of a snowmobile or a bicycle for example, a hand does not have to be removed from the handle bars to actuate the signal.
The present invention provides a signaling apparatus and method which are believed to overcome at least some of the limitations and shortcomings of the known art to increase trail safety by providing:

Signaling apparatus and method for trail vehicles


A remote start controller is mounted on a vehicle, which includes a keyless entry device for controlling a locking action of doors of the vehicle in response to a user's operation with respect to a lock button of a transmitter. The remote start controller includes a CPU. Upon detecting that the lock button of the transmitter is operated in a first predetermined way, the CPU causes an engine of the vehicle to start.

1. Field of the Invention
This invention relates to a remote start controller for a vehicle, which is used to start the engine of the vehicle parked at a location distant from a user, such as a parking lot.
2. Description of the Related Art
In a vehicle such as an automobile, a starter motor is actuated using a battery installed in a vehicle body as a power supply and an engine is cranked by the rotation force of the motor, to start the engine. To actuate the starter motor, a driver inserts an ignition key into the key hole of an ignition switch and turns the ignition key at a predetermined angle, thereby turning on the ignition switch and a starter switch. These days, a device for starting an engine by remote operation of a driver who does not ride in a vehicle has been often used for starting an air conditioner before starting the vehicle in winter or summer.
Such a remote start controller of a vehicle includes a transmitter carried with a driver, a receiver and a controller attached to the vehicle. When the receiver receives a start signal from the transmitter and the controller controls starting of the engine, only if safety conditions are satisfied, the controller generates and outputs pseudo signals to each line of the ignition switch and starter switch to drive the starter motor for starting the engine.
On the other hand, these days, a keyless entry device for controlling a locking action of doors of a vehicle by remote operation of a transmitter has also become widespread and has been installed in a large number of vehicles. The remote start controller and the keyless entry device each require a transmitter. Therefore, users must carry two transmitters; this is cumbersome. The same goes for the case where an antitheft apparatus for setting a security function for a vehicle by remote operation and the remote start controller are installed.
Thus, it is desirable that it should be made possible to control these apparatuses with a common transmitter; hitherto the keyless entry device and the antitheft apparatus have been controlled with a common transmitter. For example, a lock button and an arming button of security are provided as one button and an unlock button and a disarming button of security are provided as one button. When the lock button is operated, security is set in conjunction with the door locking. When the unlock button is operated, security is disarmed in conjunction with door unlocking. However, with the remote start controller, if operation is associated with the lock button or the unlock button, since the driver does not always want to start or stop the engine when locking or unlocking the doors, it would be inconvenient to the user.
On the other hand, to make it possible to control the keyless entry device and the remote start controller with a common transmitter, JP Hei. 9-303020 has proposed that a transmitter is provided with two switches and one of the switches is used as a mode change switch. Specifically, the transmitter is usually operated in a keyless entry mode. In the keyless entry mode mode, a lock command and an unlock command are transmitted by operating the two switches. If a user keeps operating one switch for a predetermined time, the mode is switched from the keyless entry mode to an engine control mode. In the engine control mode, an engine start command and an engine stop command are transmitted by operating the two switches.
Likewise, to make it possible to control the keyless entry device and the remote start controller with a common transmitter, JP Hei. 9-322265 A has proposed that a position of an antenna of a transmitter is changed manually between keyless entry operation and remote start operation and that the transmitter selectively transmits a door lock command or an engine start command in response to the position of the antenna when the user operates the common switch.
Further, to make it possible to control a security apparatus and the remote start controller with a common transmitter, JP 2002-130034 A has proposed that the transmitter is provided with an engine start switch and a security switch.


Ring protector made from an elastic material and including a safety mesh. Ring protectors made according to principles of this invention protect rings from damage while at the same time keeping them on the wearers finger and avoiding slippage during active endeavors such as swimming.

Typically, an individual's most valuable piece of jewelry (both in terms of sentimental and monetary value) is a ring. Like most jewelry of significant monetary or sentimental value, rings are kept throughout a person's life and are often worn during active conduct. Rings are typically sized to fit a person's finger at the time of purchase or at the time of other acquisition. Throughout the course of a person's life, ring size for a particular finger may change for a variety of reasons. A ring may be incorrectly sized for the wearer's finger or it may become incorrectly sized due to natural changes in finger size.
Some forms of active conduct, including swimming in cold water, may cause a finger to be reduced in size. Further, some individuals may experience weight loss after being sized for a ring. Weight loss may cause a smaller ring size. When a ring is sized too large for the wearer's finger, there exists substantial risk for the ring to become lost, especially during active conduct. Further, when a ring is sized too large for a wearer's finger, there exists substantial risk that the ring could oscillate or move upon the finger in a way that could cause injury.
Rings often include gems that protrude away from the body of the ring. In many cases, gems make up the most valuable portion of the ring, both in terms of sentimental and monetary value. A protruding gem is typically affixed to the body of the ring through conventional mechanical means known to skilled jewelers. The quality or nature of the workmanship used to mount a gem may place it at risk of becoming lost. Poorly mounted gems could become dislodged from even minimal impact. If the wearer of a ring with a gem engages in active conduct, the gem is at further risk of becoming dislodged. Further, if the ring is poorly fit to the wearer's finger, the gem may move about during active conduct, causing risk of injury to the wearer or others.
In view of the foregoing, there exists a need for a ring protector that may be worn by an individual in order to protect the ring and gem from being lost, especially during active conduct. Further, there exists a need for a ring protector that can be used to reduce movement of the ring on the wearer's finger and consequently reduce the risk of injury to the wearer or others during active conduct.


A new Lobelia plant named ‘Tech Hepdab,’ particularly distinguished by deep blue flowers with distinct white eyes, deep green foliage, initially upright stems, semi-upright, medium vigor, and about medium sized, mounding plant habit with long inflorescences above the foliage, and relatively good heat tolerance.

The present invention comprises a new and distinct cultivar of Lobelia, botanically known as Lobelia erinus and hereinafter referred to by the cultivar name 'Tech Hepdab'.
'Tech Hepdab' is a product of a planned breeding program. The new cultivar originated from a hybridization made in June 2005 in Andijk, Netherlands.
The female parent was an unpatented proprietary Lobelia plant designated 'LOB04-315-2' with dark blue flowers. 'LOB04-315-2' has larger leaves and has a less upright plant habit than 'Tech Hepdab'.
The male parent of 'Tech Hepdab' was an unpatented proprietary Lobelia plant designated 'LOB04-307-4' having blue flowers with white eyes. 'LOB04-307-4' has a larger plant habit with longer stems than 'Tech Hepdab'.
The resulting seeds were sown in October 2005. 'Tech Hepdab' was selected as one flowering plant within the progeny of the stated cross in January 2006 in a controlled environment in Andijk, Netherlands.
The first act of asexual reproduction of 'Tech Hepdab' was accomplished when vegetative cuttings were taken from the initial selection in the spring of 2006 in a controlled environment in Andijk, Netherlands.
Horticultural examination of plants grown from cuttings of the plant initiated in the spring of 2007 in Andijk, Netherlands, and in Hillscheid, Germany, and continuing thereafter, has demonstrated that the combination of characteristics as herein disclosed for 'Tech Hepdab' are firmly fixed and are retained through successive generations of asexual reproduction.
'Tech Hepdab' has not been observed under all possible environmental conditions. The phenotype may vary significantly with variations in environment such as temperature, light intensity and day length.
A Plant Breeders' Right for this cultivar was applied for with the European Union on Jul. 21, 2008. 'Tech Hepdab' has not been made publicly available more than one year prior to the filing of this application.


A system and method that identifies delayed infusion programs at an infusion pump or with a first computer and an infusion pump. The first computer receives an infusion auto-program from a remote source, transmits the infusion auto-program to the infusion pump, and sends a stale auto-program to the infusion pump. The infusion pump receives a manual infusion program, saves and executes the manual infusion program, and compares the stale auto-program to the manual infusion program to identify potential matches between the stale auto-program and the manual infusion program. The infusion pump evaluates the potential matches and determines if the potential matches are within a predefined tolerance, continues to execute the at least one manual infusion program on the infusion pump if the potential matches are within the predefined tolerance, and remotely saves differences in the manual infusion program and the at stale auto-program in a remote server for later analysis.

Field of the Invention
The present disclosure relates to infusion pump programming analysis. Specifically, disclosed is a system and method that matches delayed infusion auto-programs with manually entered infusion programs and analyzes differences therein. At least one embodiment optionally displays an error message at the infusion pump if the manual or auto-program request is inconsistent with a drug library. At least one embodiment analyzes the differences in the manual program and the stale auto-program and saves the results of the analysis locally in the pump or remotely in a remote server for subsequent review and/or data mining.
Description of the Related Art
Infusion pumps are commonplace among medical devices in modern hospitals. The pumps serve as a useful tool for delivering medication to patients, and are particularly beneficial for their great accuracy in delivering medication at a specific rate and dose. Moreover, medical facilities have enabled hospital caregivers, such as nurses, to deliver medication to patients using auto-programming features available for the infusion pump. Although auto-programming features may reduce errors made manually by hospital caregivers, medical facilities still struggle with identifying and responding to errors made when using an infusion pump. In a conventional auto-programmable pump, error codes and messages may be sent surreptitiously from the pump to other areas of the medical network, but are not immediately accessible to a hospital caregiver submitting an auto-program request at the infusion pump. Furthermore, these error codes often do not specifically describe the error to the caregiver at the pump so that the caregiver may immediately respond to the error.
In addition, known systems do not analyze potential acceptable events if the manual program entered by the caregiver while waiting for an auto-program to arrive at the infusion pump is acceptable. Known systems do not store or analyze the differences between the manual program and the auto-program to determine response times, quality of data entry by the caregiver, and do not learn from caregivers that are at the point of care and thus may purposefully enter a different infusion rate or volume. Thus, there is a need for system and method that matches delayed infusion auto-programs with manually entered infusion programs and analyzes differences therein.

System and method that matches delayed infusion auto-programs with manually entered infusion programs and analyzes differences therein


An apparatus to facilitate the handling of multi-wall bags containing powdered or particular material or product, more specifically but not limited to the emptying of ex factory bags containing milk powder for further processing in a sterile manner. The apparatus includes an outer bag slitting station, an outer and inner bag separating device and an inner bag slitting station incorporating a tilting table to convey the slit inner bag to a powder receiving hopper.

Milk powder ex factory is most often packed in multiwall bags ranging from 10-30 kg, but typically 25 kg in weight that have a multilayer brown (Kraft) paper outer bag for handling strength and a plastic inner liner for powder containment. The bags are sealed using a heat sealer that acts through the paper bag to seal the inner plastic liner. The paper bag is sealed by folding its protruding flap over and re-heating hot melt glue on the underside of the flap. A line of cuts/perforation is scored along the inside of the plastic liner bag to assist separation of the plastic liner from the outer paper bag when this is required. When the bags are constructed, small traces of hot-melt glue are used to fix the inner plastic liner to the outer paper bag in order to assist filling the bag with powder in an automated process.
In order to comply with hygiene requirements, hygienic recovery of the bag contents is required before the product can be further processed into for example infant formula, retail packs or the like. The outer bag which may be contaminated must be removed in a way that maintains the cleanliness of the inner plastic liner bag.

Apparatus for the handling of multiwall bags containing powdered or particulate material


A device is presented comprising a multi-layer structure with a plurality of metal islands on the surface of a solid transparent substrate. The islands are coated by an ultrathin sol-gel derived silica film via self-assembled monolayer.

The following references are considered to be pertinent for the purpose of understanding the background of the present invention:
(1) Hutter, E.; Fendler, J. H. Exploitation of localized surface plasmon resonance, Adv. Mater. 2004, 16, 1685.
(2) Kalyuzhny, G.; Vaskevich, A.; Schneeweiss, M. A.; Rubinstein, I. Transmission surface-plasmon resonance (T-SPR) measurements for monitoring adsorption on ultrathin gold island films, Chem.-Eur. J. 2002, 8, 3850.
(3) Doron-Mor, I.; Barkay, Z.; Filip-Granit, N.; Vaskevich, A.; Rubinstein, I. Ultrathin Gold Island Films on Silanized Glass. Morphology and Optical Properties., Chem. Mater. 2004, 16, 3476.
(4) Doron-Mor, I.; Cohen, H.; Barkay, Z.; Shanzer, A.; Vaskevich, A.; Rubinstein, I. Sensitivity of transmission surface plasmon resonance (T-SPR) spectroscopy: Self-assembled multilayers on evaporated gold island films, Chem.-Eur. J. 2005, 11, 5555.
(5) Wanunu, M.; Vaskevich, A.; Cohen, S. R.; Cohen, H.; Arad-Yellin, R.; Shanzer, A.; Rubinstein, I. Branched Coordination Multilayers on Gold, J. Am. Chem. Soc. 2005, 127, 17877.
(6) Liz-Marzan, L. M.; Giersig, M.; Mulvaney, P. Synthesis of nanosized gold-silica core-shell particles, Langmuir 1996, 12, 4329.
Various sensors making use of surface plasmon resonance such as biosensors, gas sensors, concentration sensors and ion sensors have been proposed in recent years.
The coupling of electromagnetic radiation to metal island films results, under certain condition, in enhanced extinction due to localized surface plasmon resonance (LSPR) scattering. Ultrathin gold films, prepared by evaporation of sub-percolation layers (typically up to 10 nm nominal thickness) onto transparent substrates followed by optional annealing, form arrays of well-defined metal islands with tunable wavelength of surface plasmon (SP) absorption band. As the SP band intensity and position are sensitive to the film morphology (island shape and inter-island separation) and the effective dielectric constant of the surrounding medium, such systems can be used for chemical and biological sensing in the transmission localized surface plasmon resonance (T-LSPR) mode. The localized SP coupling observed in dense assemblies of nanoparticles (NPs), either in solution or immobilized on solid substrates, introduces an additional factor which may strongly influences the conditions of the SP resonance.
Sensors based on localized SP resonance can be divided into two broad groups, namely, sensors based on monitoring changes in the dielectric constant of the immediate environment, and sensors based on changes in SP coupling. A combination of these effects was also exploited in localized SP sensing [1].
Changes in the localized SP band of discontinuous Au or Ag films upon analyte binding can be conveniently monitored using standard spectrophotometric equipment in the transmission mode, presenting a notable advantage in sensing applications. This method of transduction was termed transmission localized surface plasmon resonance (T-LSPR) spectroscopy [1, 2].
Some earlier works of the inventors have shown that ultrathin (typically not exceeding 10 nm nominal thickness) Au island films vapor-deposited onto transparent substrates display a SP extinction peak at 550-800 nm. The shape, intensity and position of the peak depend on the island morphology, determined by the evaporation conditions and post-deposition treatment [3]. Changes in the SP extinction band (intensity and wavelength of maximum absorbance) resulting from binding of various molecules to the Au islands were measured in the transmission mode [2]. A linear relationship existing between the surface coverage by adsorbing molecules, either bound directly to the Au or through a receptor layer, and the change in the SP intensity and wavelength [2], is useful for quantitative sensing. The T-LSPR spectroscopy was shown to be widely applicable, with a sensitivity which depends on the film preparation conditions [4].
WO 2002/068943, assigned to the assignee of the present application, discloses chemical detection and quantification methods and apparatus employing optical properties of ultra-thin metallic films. According to this technique, detecting changes in surface plasmon intensity of an ultra-thin metallic film provides a quantitative indication of an adsorbed or non-adsorbed chemical substance.

Device and method for optical localized plasmon sensing

YEDA RESEARCH AND DEVELOPMENT COMPANY LTD. AT THE WEIZMANN INSTITUTE OF SCIENCE


In a semiconductor package including at least one plate-like mount, a semiconductor chip has at least one electrode formed on a top surface thereof, and is mounted on the plate-like mount such that a bottom surface of the semiconductor chip is in contact with the plate-like mount. The semiconductor package also includes at least one lead element having an outer portion arranged to be flush with the plate-like mount, and an inner portion deformed and shaped to overhang the semiconductor chip such that an inner end of the lead element is spaced apart from the top surface of the semiconductor chip. The semiconductor package further includes a bonding-wire element bonded at ends thereof to the electrode of the semiconductor chip and the inner end of the lead element, an enveloper sealing and encapsulating the plate-like mount, the semiconductor chip, the inner portion of the lead element, and the bonding-wire element.

1. Field of the Invention
The present invention relates to a semiconductor package including a plate-like mount, a semiconductor chip mounted on the plate-like mount, a plurality of leads electrically connected to the semiconductor chip, and an enveloper sealing and encapsulating the plate-like mount, semiconductor chip, and inner portions of the leads.
Also, the present invention relates to a production process for manufacturing such a semiconductor package.
2. Description of the Related Art
For example, as disclosed in Japanese Patent Publication No. 2714037 corresponding to Japanese Laid-Open Patent Publication (KOKAI) No. HEI-01-087535, a lead frame is used to manufacture an electronic package having a plurality of leads.
In particular, the lead frame includes an outer frame section, a plurality of islands or plate-like mounts, and a set of lead sections associated with each plate-like mount, and the plate-like mounts and lead sections are suitably supported by the outer frame section. A semiconductor chip is mounted on each plate-like mount, and is electrically connected to inner end portions of the lead sections in each set through the intermediary of bonding-wires.
Then, each plate-like mount, the semiconductor chip mounted thereon, and the inner end portions of the lead sections are sealed and encapsulated in a mold resin or enveloper, resulting in production of a plurality of electronic packages on the lead frame. Thereafter, the individual electric packages are cut and separated from the lead frame, using a punching machine.
In this type electronic package, especially a MOSFET package, there is a demand for miniaturization of the electronic package, whereas there is a demand for use of a large-sized semiconductor chip in the electronic package to thereby obtain a high power performance. To deal with these contradictory demands, it is proposed that the inner ends of the lead sections are directly and electrically connected to the semiconductor chip, as disclosed in Japanese Laid-Open Patent Publication (KOKAI) No. HEI-11-354702, and Japanese Patent Publication No. 3240292 corresponding to Japanese Laid-Open Patent Publication (KOKAI) No. 2000-114445.
Namely, it is possible to compactly arrange the lead sections with respect to the semiconductor chip mounted on the plate-like mount, due to the direct connection between the semiconductor chip and the inner ends of the lead sections. However, this arrangement of the lead sections fails to obtain a sufficiently high power performance in the electronic package, as discussed in detail hereinafter.
In short, conventionally, there are no proposals for successively dealing with the aforesaid contradictory demands.

Semiconductor package having encapsulated chip attached to a mounting plate


An illumination system having a refractive optical element that compensates for dependence in irradiance of images of objects captured by a photosensor is provided. The refractive optical element may structure the light such that similar objects in the same spherical surface in the field of view of the camera have the same irradiance on the camera photosensor. The illumination system may have an image sensor, a light source, and a refractive optical element. The image sensor has a photosensor that captures images of objects in a field of view. The irradiance of images of objects having a given exitance that are captured by the photosensor may depend on angular displacement from an optical axis of the image sensor. The refractive optical structures light from the light source to illuminate the field of view to compensate for the dependence of irradiance on angular displacement from the optical axis.

The amount of electromagnetic radiation (e.g., light) that a camera photosensor collects and images may depend on the location of objects in the field of view (FOV) of the camera. Briefly, an object that is on the camera's optical axis may appear brighter to the camera's photosensor than an object that is off-axis, other factors being equal. The term "irradiance" generally refers to the electromagnetic radiation that is incident on a surface, such as a photosensor. The terms "radiant exitance" or "radiant emittance" generally refer to electromagnetic radiation that emerges (e.g., reflects) from an object. Irradiance, as well as exitance may be measured per second per unit area. For an object having an angular displacement "θ" relative to the camera's optical axis, the irradiance may, in general, decrease as cos4 θ.
For various applications, it can be advantageous for objects in a scene imaged by a camera to have substantially the same irradiance on the camera photosensor independent of the angular displacement θ. For example, a time of flight (TOF) three-dimensional (3D) camera determines distances to objects in a scene that the camera images by timing how long it takes for light transmitted by the camera to travel to the objects and back to the camera. For some systems, an illumination system transmits the light to the object in very short light pulses. The camera images light that is reflected by the objects and is collected by the photosensor to determine round trip travel times for light. Accurate distance measurement depends on the irradiance associated with the image of the object captured by the photosensor. Moreover, accuracy may improve with increase in the irradiance.

Illuminator with refractive optical element


A mortar cartridge generates effective white or colored smoke obscuration with reduced adverse environmental impact and collateral damage and provides an improved drag assembly that reduces drift during projectile descent and improves targeting.

Presently, the only 120 mm cartridge in the U.S. arsenal that produces white smoke is the White Phosphorus (WP) cartridge. While the WP cartridge provides effective smoke obscuration for combat missions it has limited use in training and in peacekeeping missions. White phosphorus has a detrimental environmental impact on wetland areas in addition to other undesirable side effects such as producing secondary fires, and metal fragments. In particular, unburned phosphorous can cause a hazard to friendly forces. Also, the smoke generated from WP cartridges includes acid fumes that are produced from phosphorus oxidation reactions. While a variety of other smoke producing compositions provide effective smoke obscuration they are likewise known to be toxic and irritating. If such cartridges are used for training they require additional safety measures and still have the potential for causing injury to personnel and/or the environment. Thus, there is a need for a reliable, low-toxicity, environmentally friendly smoke producing mortar cartridge.
These and other problems are solved, at least in part, by embodiments of a smoke producing mortar cartridge in accordance with the present invention.

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


A system and method for diagnosis of living tissue diseases is described. The system includes a computer device for controlling its operation. An operator control device is coupled to the computer device. A viewing screen is coupled to the computer device for displaying digitized images of the living tissue. The operator, using the control device, selects desired portions of the digitized image for further image enhancement according to a desired image enhancement feature selectable from a plurality of image enhancement features. The image enhancement features include any combination of grey scale stretching, contrast enhancement based on logarithmic histogram equalization, spot enhancement and magnification. The system further includes means for visualization and quantification of micro-calcifications, and means for visualization and quantification of mass spiculations.

Breast cancer affects a major segment of the female population over the age of 40. To reduce the mortality from this disease, it is vital to diagnose it as early as possible. If breast cancer is detected early enough, chances of a cure are markedly higher. Accordingly, breast cancer screening projects designed for early detection of breast cancer have proven to dramatically reduce the mortality from the disease. Because breast cancer is such a major public health problem, many health authorities worldwide recommend that women undergo routine breast examination.
Today, the standard methods for detecting breast cancer are 1) self examination; 2) clinical examination; and 3) radiography of the breast, known as mammography. Routine mammography screening can reduce mortality from breast cancer. The American Cancer Society recommends that a baseline mammogram be taken between the ages of 35 and 39, every one to two years between the ages of 40-49 and annually on women aged 50 years and older.
The main objective of screening mammography is to detect breast cancer early, before it is palpable. The standard mammographic procedure is to take two views of each breast with specially designed mammography equipment. The breast is optimally positioned so that as much tissue as possible can be examined. The radiologist visually examines the mammographic images on a light box. Using a magnifying glass, the radiologist examines each image in detail. If the radiologist detects any suspicious findings on mammographic examination, he or she may suggest a biopsy of the suspicious area. Suspicious findings include any abnormalities in the breast tissue. Abnormalities may be either malignant or benign, and many times the radiologist cannot diagnose precisely the type of abnormality from the image. Additionally, it has been established that 10-30% of women who indeed have breast cancer have negative mammograms.
There are four possible outcomes in screening mammography:
1) True positive: Earlier detection, treatment and better prognosis; PA0 2) True negative: Reassurance of no cancer; PA0 3) False positive: Anxiety and time, cost and risks of more tests; and PA0 4) False negative: Delay in diagnosis and treatment. Worse prognosis.
The technical interpretive expertise of the radiologist is a crucial factor in effective breast cancer detection. A standard non-invasive procedure does not exist to diagnose a patient after a finding has been detected by mammography. When there is a suspicious finding, a biopsy is frequently performed. Because the information on the mammogram many times is ambiguous, in order not to miss the diagnosis of cancers, many biopsies are performed for mammographic abnormalities. Approximately 70% of these biopsies turn out to be benign.
Although there have been many improvements in the mammographic equipment over the last 10 years, technical impediments limit the ability of mammography to display the finest or most subtle details in good contrast. In order to achieve specific diagnoses, the radiologist needs to visualize the infrastructure of the mammographic abnormality.
Currently, cancers imbedded in dense breast tissue are found at later stages than those in breasts with high fat percentage of tissue. These cancers in dense breasts, in particular, need an earlier detection method. Although radiologists specializing in mammography have stated that the constraints of conventional mammography can be overcome by digital image processing, an effective digital diagnostic assistance approach has not yet been available.

System and method for diagnosis of living tissue diseases


Circuit designs and operating techniques for a storage device that includes, in one implementation, a memory device including a plurality of memory blocks, each memory block including a plurality of memory cells coupled to a plurality of corresponding word lines; and a memory controller configured to store data in memory cells included in a main area coupled to a selected word line of the plurality of word lines, and store word-line information in a spare area coupled to the selected word line to indicate that a program operation has been performed on the main area.

A storage device is a device that is capable of storing data in a storage medium. Such a storage device is used by computing devices such as a personal computer, a smartphone, or a tablet computer to store and retrieve data. The storage device can be classified based on the type of storage medium. For example, a hard disk drive (HDD) uses a magnetic disk as the storage medium, and a solid state drive (SSD) or a memory card uses a semiconductor memory, such as a nonvolatile memory, as the storage medium.
The storage device implemented using semiconductor memories may include a plurality of memory devices and a memory controller configured to control the memory device to store and retrieve data in and from the memory device. The memory device may be classified into a volatile memory and a nonvolatile memory. Representative examples of the nonvolatile memory include a read only memory (ROM), a programmable ROM (PROM), an electrically programmable ROM (EPROM), an electrically erasable programmable ROM (EEPROM), a flash memory, a phase-change random access memory (PRAM), a magnetic RAM (MRAM), a resistive RAM (RRAM), a ferroelectric RAM (FRAM), etc.

Storage device and method of operating the same for detecting last programmed page


In a throttle device for a pressure control apparatus, the return line inside a pressure control valve or in the line course outside it is provided with a cross-sectional constriction that throttles the flow. This cross-sectional constriction is variable automatically, as a function of the flow rate and hence of the prevailing pressure, in such a way that at a low flow rate a small flow cross section and at a high flow rate a large flow cross section results. It is thus possible to design the return line pressure as high as possible over a wide range of the flow rate and to keep the pressure difference between the inflow line and return line slight and thereby to minimize the noise production in the pressure control valve.

The invention is based on a throttle device for a pressure control apparatus.
To regulate the pressure in a fuel supply system of an internal combustion engine, a pressure control apparatus that contains a pressure control valve is typically used. This valve is located on the compression side of a fuel pump that communicates with a tank. Some of the fuel pumped by the fuel pump is delivered to the engine via injection valves. In many internal combustion engines, one injection valve per cylinder is provided. The need is for the injection valves to inject the precise correct fuel quantity at any given moment, with only a very slight allowable deviation among the injection valves. The excess fuel quantity not needed by the engine is returned in the return line to the fuel tank via the pressure control valve. The pressure control valve regulates the pressure on the compression side of the fuel pump. In different motor vehicles, components are inserted into the return line leading back from the pressure control valve to the tank, in order to influence the return pressure. These components may for instance be a jet pump and/or a control valve. As such components, throttle devices which effect a throttling action by cross-sectional constriction have also already been proposed. This is in recognition of the fact that the noise produced by the pressure control valve and caused by the expansion of the fuel of the valve seat can be reduced by increasing the pressure in the return line. This reduces the pressure difference between the inflow line and the return line and thus reduces the noise produced. In known throttle devices, the throttling is achieved by means of a cross-sectional constriction in the return line. The flow cross section must be large enough that the return line pressure, if the flow rate is high, does not reach the inflow line pressure, in which case the control function would be lost. As a result, with a lesser flow rate there is a lesser return line pressure and hence a large pressure difference between the inflow and return lines. Because of a varying pressure difference between the inflow and return lines, a reduction in noise produced by the pressure control valve is hardly achievable.

Throttle device for a pressure control apparatus


There is provided a piping structure of a front work machine which prevents an increase in total with of the front work machine caused by hydraulic piping extended from the main machine side, and enables the piping following a structure of the front work machine turning vertically, by which a burden on the hydraulic piping accompanying the turning of the front work machine can be reduced to improve the durability.

Conventionally, in a work vehicle such as a tractor and a back hoe loader, a front work machine such as a loader is mounted on a front portion of a main machine (vehicle) thereof. Some of these front work machines are constituted such that a base portion(s) (rear end portions) is supported by one side or both right and left sides of a bonnet provided in the front portion of the main machine. That is, the constitution is such that on each of the right and left sides or one side of the bonnet, a turnably-supporting part made of a bracket or the like is provided in a body frame or the like on the main machine, and that the base portion of the front work machine is supported by this turnably-supporting part. This allows the front work machine to be supported so as to turn vertically with respect to the main machine (e.g., refer to Patent Document 1).
In the front work machines as described above, some are constituted so as to have a bucket constituted openably and closably by a hydraulic cylinder, a hydraulically-driven auger or the like as a work part, and to require hydraulic oil for operation. In such a constitution, hydraulic piping is extended from the main machine side, and the hydraulic oil is supplied through this hydraulic piping.
In this manner, when the hydraulic oil is supplied to the work part and the like of the front work machine by the hydraulic piping extended from the main machine side, the following problems arise due to the constitution of the front work machine.
As described before, in the case where the front work machine is constituted so as to be supported on the side(s) of the bonnet, the arrangement of the hydraulic piping between the bonnet and the front work machine requires sufficient space between the bonnet and the front work machine. Providing such space for piping causes an increase in total width of the front work machine, and thus, causes an increase in total width of the work vehicle including the main machine.
Moreover, since the front work machine turns vertically with respect to the main machine as described before, the hydraulic piping needs to follow the movement of the front work machine by this turning. That is, the front work machine is a moving side, while the main machine is a non-moving side, and thus, a necessary length of the hydraulic piping connecting the front work machine and the main machine may vary, and also, it can be considered that the turning of the front work machine puts a burden on the hydraulic piping, thereby decreasing its durability, which makes it necessary that the hydraulic piping follows the front work machine.
Consequently, there has been desired a piping structure of the front work machine which prevents an increase in total width of the front work machine due to the hydraulic piping extended from the main machine side, and enables the piping following the structure of the front work machine turning vertically, by which the burden on the hydraulic piping accompanying the turning of the front work machine can be decreased to increase the durability.
[Patent Document 1] Japanese Patent Application Laid-Open No. 2002-308157


A system capable of automatically generating an answer in response to a query or an instruction such as a letter writing instruction input to the system in the form of a natural language. The system understands the goal of the natural language input and retrieves information from knowledge bases to formulate a plan and an action for achieving the goal.

1. Field of the Invention
The present invention relates to a knowledge information processing system such as, for example, an expert system. More particularly, the invention relates to an information processing system which, upon receipt of information, for example, describing a daily living problem expressed in a natural language ordinarily used by human beings, provides knowledge or information concerning a skill which is useful in overcoming the problem. Still more particularly, the invention is concerned with a system capable of performing knowledge information processing in which information such as an instruction given by a human being, expressed by a natural language, can be formed into a sentence or text stating the content of the instruction with minimal human aid.
2. Description of the Prior Art
Daily living problems encountered in daily life, such as problems concerning child care, cooking, laundry and so forth, are overcome by knowledge derived from, for example, books, telephone counseling, data retrieval by a computer and so forth. The best way of obtaining a solution, however, is to ask an expert or someone who has abundant experience.
Information derived from various sources has its own shortcomings. Books or the like include too much information so that it is difficult to pick out the desired information. Telephone counseling involves the problem or the risk of invasion of privacy. In addition, the reply often fails to address the point in which the consulter is interested. It is therefore not overstating the case to say that a practical limit exists in obtaining information through manual labor.
On the other hand, in mechanical processing, i.e., retrieval by a computer, one encounters difficulty in selecting effective keywords from a thesaurus and, hence, is not suitable for ordinary users.
Thus, problems encounters in human daily living are intricate and involve much ambiguity. It is therefore difficult to cope with such problems.
One of the tasks that is difficult for a machine to perform is writing a text. Users are generally obliged to input most portions of the sentence to be output. In some cases, terms and phrases which are used frequently are registered and called up as required to reduce the load on the user who inputs the sentence.
Constructing a text, however, requires much labor and is quite time-consuming. The use of registered terms or phrases cannot significantly reduce the load on the user because the construction of the whole text in which these terms and phrases are to be incorporated still requires manual processing to be conducted by the user. In addition, sentences tends to become stiff due to use of the fixed terms and phrases, failing to meet a demand for adaptability to a variety of situations.