A structure for a hub of a rotor includes a space frame having truss members configured to carry primary torsion, bending, and direct loading. The structure also includes a shell on the space frame configured to stabilize the space frame and carry shear loading.

This invention relates generally to a lightweight hub structure, and more particularly to a hub structure including a space frame with truss members that is particularly suitable for use in wind turbine generators.
Monolithic shell structures with large cutouts are structurally inefficient and wasteful of material to produce. Moreover, large cutouts in monolithic shells result in stress concentrations, which further exacerbate structural inefficiency.
At least one known hub for a wind turbine includes a casting having a weight of approximately 68,000 pounds. This hub requires extensive machining to match multiple component interfaces. One known hub configuration typically has five large cutouts, including three for blade attachments, one for an output shaft, and one for a spinner. The combined weight of the hub plus the interfaced components, including pitch-drive mechanisms, can approach 100,000 pounds. Structural inefficiency equates to excessive weight, and for structures such as wind turbines that are mounted on supporting towers, these supporting towers must be designed with capacity to support the excess weight.


The harness system for identification purposes has several harnesses (101, 111), which are provided with complementary parts (102, 112), which are connected with electrically conducting cables (105, 115), of connecting buttons in order to mechanically connect the harnesses with each other and simultaneously to provide electrical connections via the cables between detectors fastened on the harness system and other electronic components. The connecting buttons are preferably snap fasteners having respectively one head part (102) and one hollow part (112).

The present invention relates to a harness system for identification purposes, having at least two harnesses.
A harness system for combat purposes is known from EP 0 836 069 A1, having a plurality of elements, such as light detectors, a laser transmitter and a control unit. This system comprises several harnesses provided with electric components, which exchange information signals with a central unit by means of ultrasound or radio, and it is the object of the present invention to improve such a system.
This object is attained in an advantageous manner by a harness system in accordance with claim 1.
Further advantageous embodiments of the invention ensue from the further dependent claims.

Harness system for identification purposes


A vehicle electronic key system that may be lent to a third person without having to worry about how the key would be used. The key system includes a portable key and a control unit installed in a vehicle. When the vehicle owner does not want the third person to use a certain accessory, the owner registers a restriction code in the key. The restriction code is registered only when a fingerprint input from an input device matches the owner's fingerprint that is pre-registered in the key. The registration of the restriction code prohibits operation of the accessory.

The present invention relates to an electronic key system for use in a vehicle, and more particularly, to an electronic key system including a portable electronic key for performing wireless communication with a vehicle control unit.
In the prior art, a door lock of a vehicle has a key cylinder having a keyhole in a door. A key is inserted in the keyhole and turned to lock or unlock the door. The key is also used to start the engine and open the trunk or glove compartment. Thus, when a vehicle owner lends the key to a third person, the third person may open the trunk or glove compartment against the owner's will.

Kabushiki Kaisha Tokai Rika Denki Seisakusho


Systems and methods for computer-implemented patient assistance are disclosed. In certain embodiments, the invention contemplates receiving patient data from plurality of sensors at a patient computer, transmitting patient data to a server, monitoring and analyzing the patient data at the server, and outputting recommended actions from the server to a personnel computer. The recommended actions are calculated based on safety considerations, emotional considerations, and/or a patient's treatment plan.

The use of advanced IoT (Internet of Things) devices and medical sensors have had a positive impact on patient care, and shows continuing promise in decreasing preventable injuries, improving healthcare quality, and reducing costs. Such technology allows continuous virtual monitoring and bi-directional virtual communication between the patients and healthcare staff, therefore offering the capabilities of remote diagnosis, treatments and the ability to take proactive actions to prevent injuries and mitigate major, potentially fatal health incidents such as cardiac events, delirium, and falls.
To develop remote monitoring, diagnosis and injury prevention capabilities for patients in hospitals and other healthcare centers, innovative architecture is needed that can effectively utilize the advancements in IoT, wearable sensor technologies, autonomic and cloud computing. The IoT can be viewed as a ubiquitous network that enables monitoring the patient's room and patient's mobility in a HIPAA compliant manner, while respecting patient privacy by collecting and processing de-identified data generated by the deployed sensors. Cloud and autonomic computing will be used to deliver the required innovative AI healthcare services for improving the quality of care.
Sensor medical technologies are important for their impacts on improving the health and treatment of patients, especially in hospitals, rehab centers, home health care, senior living, assisted living, etc. The use of advanced IoT (Internet of Things) devices and medical sensors by patients, promises to decrease preventable injuries, improve the quality of healthcare and reduce costs. Such technology will allow patients to communicate/ alert the healthcare staff about their current situation, if at risk. It will also allow nurses and physicians to continuously monitor patient's health, offering the capabilities of remote diagnosis, treatments and to take proactive actions to prevent injuries and mitigate major health incidents (Cardiac events, delirium, falls, pressure injuries, etc.).
To develop remote monitoring, diagnosis and injury prevention capabilities for patients in hospitals and other healthcare centers, innovative architecture is needed that can effectively utilize the advancements in IoT, wearable sensor technologies, autonomic and cloud computing. The IoT can be viewed as a ubiquitous network that enables monitoring the patient's rooms and patient's mobility in a discrete HIPAA compliant manner, while respecting patient privacy by collecting and processing the deidentified data generated by the deployed sensors. Cloud and autonomic computing will be used to deliver the required innovative AI healthcare services for improving the quality of care.
The Senior's Virtual Assistant ("SeVA") aims to provide these, but to add robustness and meaning to the information and experience provided by using artificial intelligence that is capable of emotional learning and sentiment analysis—technology that has demonstrated value in the fields of consumer and political analytics, and by its processes, also guards against potential programmer/creator bias that may limit its longevity of function.
The technical challenge lies in making this user-friendly to a point that it can be used interactively by patients with limited smartphone technology skills especially older adults. The other challenge is to be able to use this technology in a patient with delirium or altered mentation and be capable of obtaining and conveying adequate meaningful information to clinical teams in order to make timely therapeutic decisions. The simulation scenarios to create this technology will be unique and innumerable, which will constantly need to be updated to meet demands of the healthcare system.
In a manuscript written by Dr. Inouye, a major researcher on Delirium Care, published by Lancet Mar. 8, 2014 edition, supported in part by Grant No. P01AG031720 from the National Institute on Aging: "Delirium affects up to 50% of hospitalized patients, and costs over $164 billion (2011) per year in the United States and over $182 billion (2011) per year in 18 European countries combined. As a preventable condition in 30-40% of cases, delirium holds substantial public health relevance as a target for interventions to prevent its associated burden of downstream complications and costs. Accordingly, delirium is now included on the patient safety agenda, and has been increasingly targeted as an indicator of healthcare quality for seniors."
The present mainstay of therapy for delirium is prevention, early recognition and non-pharmacological management. Currently, there are no specialized technology-based interactive devices to our knowledge that are focused on this task, much less capitalizes and utilizes artificial intelligence that emulates emotional intelligence, and not just basic-level pattern recognition and learning. The SeVA aims to have a more clinically meaningful, seamless therapeutic experience because of this.

Systems and methods for SeVa: senior's virtual assistant

Arizona Board of Regents on Behalf of the University of Arizona


A power transfer system is constituted under a simple construction (a worm gear, transfer rod integrally installed with a worm sector gear, and lower control arm), thereby improving the efficiency of the power transfer of the toe-angle controlling mechanism for vehicle wheels. The worm gear and worm sector gear are closed in a cover part of a housing, acquiring the durability and reliability of the toe-angle controlling mechanism for the vehicle wheels. The toe angle is prevented from being varied according to the exterior force transmitted from the vehicle wheel, by a unique characteristic (no inverse-transfer power) of the worm gear and worm sector gear, thus improving the vehicle stability.

The toe angle of the vehicle wheel typically affects the stability of the vehicle driving. Therefore, a properly aligned toe angle stabilizes the forward driving of the vehicle and precludes an oversteering or excessive understeering during the turning of the vehicle to thereby balance the steering.
Accordingly, if the toe angle of the vehicle wheels is adjusted actively during the vehicle operation, the vehicle stability can be greatly improved.

Mechanism for controlling toe angle of vehicle wheels


A device for emission of laser radiation includes at least one semiconductor laser having a resonator and a pumped active zone disposed within the resonator. The zone is subdivided into at least two spatially separated active zones by free-radiation regions without lateral wave guidance. Preferably, the laser is at least two semiconductor lasers disposed in series, a row, or a line, each having an antireflection coating on at least one side. The lasers have outer mirror elements at an end of the lasers disposed in series and the outer mirror elements form the resonator. A laser configuration includes two opposite semiconductor lasers from which a fundamental mode is in each case imaged into the active zone of the opposite semiconductor laser. The laser configuration has an emerging laser beam with little divergence.

Field of the Invention
The invention relates to a device for emission of laser radiation with one or a plurality of pumped active zones of a semiconductor laser, the zones being disposed within a resonator.
Semiconductor lasers are generally known and are usually produced in two embodiments. In the case of edge-emitting laser diodes, the emission is effected in the direction of extent of the pumped active layer and the laser radiation emerges through the edges of the active layer. This type of laser diodes generally exhibits poor beam quality because the edge-emitting laser does not oscillate in one mode and does not oscillate exclusively in the fundamental mode. Thus, the laser radiation is emitted in a wide angular range. This is a pronounced problem particularly in the case of edge-emitting laser diodes whose active zone has a large extent transversely with respect to the optical axis of the resonator.
In addition to the edge-emitting laser diodes, surface-emitting diodes are also known, in which the laser radiation is emitted at right angles to the pumped active layer. The surface-emitting laser diodes are afflicted, on one hand, with high electrical resistances based on the limited dopability of mirror layers formed on both sides of the active zones. Although the resistances can also be reduced, inter alia, by increasing the diameter of the active zone, this generally has the effect that higher modes start during the operation of the laser, which modes impair the beam quality.


An ophthalmic composition comprises active vitamin D as an effective component and is used for preventing deterioration of the optical transparency, occurrence of high intraocular pressure diseases or defective sight, observed after an ophthalmic operation, due to hyperplasia of the anterior ocular cells in the tissues damaged by the ophthalmic operation, which are in course of a healing process, and/or excess production of cellular materials.

The present invention relates to an ophthalmic composition and more specifically to an ophthalmic composition for treating patients suffering from intraocular inflammation, glaucoma and corneal degeneracy and for preventing any occurrence of hyperplasia of anterior ocular cells during the damaged tissue-healing process after operations thereof and/or for preventing, for instance, any reduction in transparency, any change in refractive power and any increase in intraocular pressure.
Rachitis is one of the osteopathy, and it has formerly been believed that the rachitis is closely related to the action of the sunlight. Thereafter, however, it has been found out that a certain vitamin is closely involved in the rachitis. This anti-rachitis vitamin is named vitamin D. Vitamin D2 obtained by purifying vitamin D1 which is a mixture with other isomers as well as vitamin D3 discovered through the subsequent studies have widely been used in the treatments of many patients suffering from osteopathy such as rachitis, osteomalacia, osteoporosis, ostitis fibrous and osteosclerosis, malignant tumors such as breast cancer and carcinoma of large intestine, as well as dermatosis such as psoriasis. Vitamin D is an essential vitamin for the bone modeling and it is prescribed by the Ministry of Public Welfare of Japan that the required amount of this nutrient to be taken with foods is set at 200 IU (5 xcexcg)/day. However, the required amount of the nutrient differs from that prescribed in foreign countries (i.e., 400 IU/day) because of the presence of vitamin D3 which is produced in the skin by the action of ultraviolet light rays through sunbathing. In other words, it is necessary to take excess of vitamin D in case where sufficient sunbathing is not ensured. Vitamins D2 to D7 are classified as vitamins having rachitis-inhibitory activity, but presently used in the treatment of this disease are vitamin D2 and vitamin D3 having high physiological activity.
Vitamin D""s are administered to patients per oral route or by injection. In case of skin diseases, they are also administered in the form of ointments. It has been known that the vitamin D undergoes a change in its molecular structure through the action of ultraviolet rays or in the liver and kidney and that it is thus converted into active vitamin D having high biological activities. It has been recognized that vitamin D""s have not only calcium-regulatory effect, but also other biological activities since the discovery of the active vitamin D3, i.e., calcitriol (1xcex1,25-dihydroxy cholecalciferol) as a derivative of the cholecalciferol. As other derivatives or analogues of the cholecalciferol, there have been known, for instance, alpha-calcidol (1xcex1-monohydroxy cholecalciferol) and calcifedol (25-monohydroxy cholecalciferol). There have recently been known about 16 kinds of cholecalciferol derivatives. In addition, there have been developed several kinds of cholecalciferol analogues such as OCT (2-oxacalcitriol) and calcipotriol. The presence of active vitamin D receptors in cells have been discovered and there have been conducted studies on inhibition of cellular activities because of the ability of the active vitamin D""s to control the production of various cytokines.
In the field of the ophthalmology, it has been known, as the symptoms caused due to vitamin deficiency, for instance, night blindness, Bitot""s spots on conjunctiva, and xerophthalmia due to vitamin A deficiency; beriberi and weak eyesight because of vitamin B1 deficiency; superficial punctate keratitis because of the vitamin B2 deficiency (sometimes associated with retroocular neuropapillitis and optic atrophy); scorbutus due to the vitamin C deficiency (wherein there are often observed bleeding in eyelids, conjunctivae and retinae)
Dr. Ohashi et al. in Osaka University studied the inhibitory effect of vitamin D3 against the expression of MHC class antigens in order to suppress any rejection observed during the keratoplasty and suggest that vitamin D3 may serve to control the rejection of the transplantation of cornea (Bulletin of Ophthalmologic Society in Japan, 1990, Vol. 94, an extra edition, p. 250).
Japanese Un-Examined Patent Publication No. Hei 3-24016 discloses studies of cultivation of human glia cells wherein the ability of active vitamin D3 to inhibit the proliferation of glia cells and also suggests that active vitamin D3 may be applied to the treatment of patients suffering from proliferative retinopathy.
Japanese Examined Patent Publication No. Hei 4-43887 discloses that active vitamin D3 is effective for the treatment of cataract such as congenital cataract, senile cataract, complicated cataract and diabetic cataract.
U.S. Pat. No. 5,254,538 discloses that vitamin D compounds are effective in healing of wounds and healing of a variety of ulcers.
The surgical operation with a scalpel has been employed for the correction of shortsightedness and astigmatisms, but this would adversely affect the visual power. For instance, the operated eye proceeds to the over correction after the operation and the incised site of the cornea becomes turbid or causes irregular reflection, which impair the visual acuity.
As laser device for operating cornea, there have been known an excimer laser and an Ho:YAG laser. The laser operations for cornea are divided into the operations for healing diseases and those for correcting the visual power.
Glaucoma is a disease in which a high intraocular pressure disease is caused due to excess production of the aqueous humor through the posterior chamber gonion or a trouble of flow paths for the aqueous humor in the anterior chamber gonion because of a certain intraocular disease and this leads to the visual field defect. Alternatively, the high intraocular pressure disease may sometimes be caused by a simple mechanical trouble of the flow paths for the aqueous humor in the anterior chamber gonion.
Corneal degeneracy (corneal dystrophy) is a disease in which heterogeneous proteins are mainly deposited on keratocytes due to the dysbolism of the corneal epithelial cells or keratocytes and this in turn leads to corneal haze/opacity. Examples of such corneal degeneracy include granular corneal degeneracy, porphyritic corneal degeneracy, cancellated corneal degeneracy, colloidal guttate corneal degeneracy, Schneider""s corneal degeneracy and Francois"" corneal degeneracy. On the other hand, corneal ulcer is a disease in which a collagenase is excessively produced by the corneal epithelial cells to thus form an ulcer. Accordingly, the corneal degeneracy and the corneal ulcer are quite different from one another in the etiological causes and clinical findings.
In a patient who has been subjected to an operation for incising the cornea using an excimer laser, there is observed, after the operation, the occurrence of hyperplasia of the cells at the inflamed corneal sites during the process for healing the damaged corneal tissues and further there are sometimes observed reduction in the degree of transparency and a change in the refractive power of the cornea due to the presence of cellular materials thus excessively produced. The normal corneal epithelium in general comprises about 5 layers, but when the traumatic injury reaches even the stroma of cornea and it is complicatedly damaged, the corneal epithelial cells covering the stroma may sometimes run up to about 10 layers. The damaged corneal cells undergo hyperplasia and produce metabolites such as collagen and proteins to thus restore the damaged tissue. The multilayered epithelium will return to the normal structure in the future, but the refractive power and the transparency of the cornea are influenced by the transient hyperplasia and the cellular materials produced by the epithelial cells as well as the stroma cells during the damaged tissue-healing process. Moreover, a steroid drug is administered after the operation for cornea using an excimer laser, but it has been known that this is accompanied by steroid glaucoma (high intraocular pressure disease) and steroid cataract as side effects.
In the cataract surgery, there is in general performed the extra capsular cataract extraction and peripheral portions of the anterior lens capsule and the posterior lens capsule are retained. However, lens epithelial cells still remain in the lens capsule and this sometimes leads to proliferation and development of the remaining lens epithelial cells in the lens capsule and the occurrence of lenticular haze/opacity. An intraocular lens is intraocularly transplanted to correct the visual acuity, simultaneous with the cataract surgery. However, lens epithelial cells, fibrin, anterior epithelial cell of iris and phagocytes as inflammatory cells in the aqueous humor are deposited on the transplanted intraocular lens and this may sometimes affect the transparency of the intraocular lens and may result in reduction of the visual acuity of the patient after the operation. It has also been known that the lens epithelial cells are proliferated in the lens capsule over a long time period after the operation, produce cellular materials such as collagen and gradually adversely affects the visual acuity of the patient. It has been believed that the two-rank-reduction in the visual acuity is observed on about 10% of the patients having cataract surgery after one year from the operation and on about 20% of the patients after two years from the operation.
As methods for preventing cornea from becoming turbid after operations, there have conventionally been in course of studies or there have practically been applied, for instance, a method in which the lens epithelial cells are removed mechanically or by a cytotoxin which can specifically affect the epithelial cells; a method for inhibiting the outgrowth of the lens epithelial cells by devising the shape of the intraocular lens to be transplanted; and a method for inhibiting the activity of the lens epithelial cells by administering, for instance, an anti-inflammatory agent or an inhibitory agent for cellular metabolism after the operation. However, there has not yet been developed any safe and effective method.
The foregoing are examples in the field of ophthalmology, which are accompanied by several problems concerning the operation of the anterior ocular region.
Accordingly, a first object of the present invention is to provide an ophthalmic composition for preventing any deterioration, after operation, of the ocular optical transparency due to the hyperplasia of anterior ocular cells in the tissues damaged by an ophthalmic operation, which are in course of a healing process, and/or excess production of cellular materials by the cells.
A second object of the present invention is to provide an ophthalmic composition for controlling any hyperplasia of inflammatory cells and lens epithelial cells present in the aqueous humor during the process for healing the tissues damaged by an intraocular operation for the anterior ocular region and/or any excess production of cellular materials by the cells to thus hold the transparency of the anterior ocular region of the eye ball and the normal intraocular pressure.
A third object of the present invention is to provide an ophthalmic composition for controlling any hyperplasia of corneal epithelial cells and keratocytes during the process for healing the tissues damaged by a corneal operation and/or any excess production of cellular materials by the cells to thus hold the transparency and the normal refractive power of the cornea.
A fourth object of the present invention is to provide a method for preventing any deterioration of the optical transparency of the human anterior ocular region due to the hyperplasia of the anterior ocular cells, which are in course of the process for healing the damaged tissues, and/or excess production of materials by the cells.
A fifth object of the present invention is to provide an ophthalmic composition for preventing any deterioration of the optical transparency of the intraocular transparent bodies in the human anterior ocular region and the occurrence of high intraocular pressure disorder, due to intraocular inflammation caused by inflammatory diseases including glaucoma.
A sixth object of the present invention is to provide an ophthalmic composition for treating patients suffering from corneal degeneracy.
The inventors of this invention have conducted various studies to accomplish the foregoing objects, have found out that active vitamin D can control the cellular activity of, for instance, corneal epithelial cells, keratocytes, tissues in the anterior ocular region, and inflammatory cells and lens epithelial cells, can maintain the optical transparency, and normal refractive power of the anterior ocular region as well as the normal intraocular pressure and can prevent any reduction in the visual functions and thus have completed the present invention.
The present invention provides an ophthalmic composition for preventing any deterioration, after an ophthalmic operation, of the ocular optical transparency, high intraocular pressure disorders or defective sight caused due to hyperplasia of anterior ocular cells in the tissues damaged by the operation, which are in course of the healing process, and/or excess production of cellular materials by the cells. The composition comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for preventing any deterioration, after an ophthalmic operation, of the optical transparency of the transparent bodies of the human eye or defective sight due to the hyperplasia of the anterior ocular cells, in the tissues damaged by the operation, which are in course of the healing process and/or excess production of cellular materials by the cells. The composition comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for controlling any hyperplasia of inflammatory cells present in the aqueous humor and lens epithelial cells during the process for healing the tissues damaged by an intraocular operation for the anterior ocular region and/or any excess production of cellular materials by the cells to thus hold the transparency of the anterior ocular region of the eyeball as well as the normal intraocular pressure. The composition comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for preventing any deterioration of the optical transparency of the intraocular transparent bodies in the human anterior ocular region and the occurrence of high intraocular pressure disorder, due to intraocular inflammation including glaucoma, caused by inflammatory diseases. The composition comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for treating patients suffering from corneal degeneracy, in particular, human patients suffering from corneal degeneracy. The composition comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for treating patients suffering from glaucoma, which comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for preventing any change in the refractive power of the cornea, which comprises active vitamin D as an effective component.
The present invention provides an ophthalmic composition for treating the inflammation in the anterior ocular region, which comprises active vitamin D as an effective component. Examples of such inflammation of the anterior ocular region of the eyeball include glaucoma, conjunctivitis, scleritis, uveitis, iridocyclitis, choroiditis, amicrobic intraocular inflammation and bacterial endophthalmitis.
The present invention provides a method for preventing any deterioration of the optical transparency of the human anterior ocular region due to the hyperplasia of the cells, which are in course of the process for healing the damaged tissues, and/or excess production of cellular materials by the cells. The method makes use of active vitamin D as an effective component.
The present invention provides an ophthalmic composition for controlling any hyperplasia of inflammatory cells present in the aqueous humor and lens epithelial cells during the process for healing the tissues damaged by an intraocular operation for the anterior ocular region and/or any excess production of cellular materials by the cells to thus ensure the transparency of the anterior ocular region of the eyeball and the normal intraocular pressure and the composition comprises active vitamin D as an effective component. Examples of intraocular operations for anterior ocular regions are operations for glaucoma and cataract and operations for transplantation of intraocular lenses.
The present invention provides an ophthalmic composition for controlling any hyperplasia of corneal epithelial cells and keratocytes during the process for healing the tissues damaged by a corneal operation and/or any excess production of cellular materials by the cells to thus ensure the transparency and the normal refractive power of the cornea and the composition comprises active vitamin D as an effective component. Examples of corneal operations are those which make use of a scalpel and a laser oscillator.
The present invention provides an ophthalmic composition for preventing any deterioration, after an ophthalmic operation, of the optical transparency or defective sight of the transparent bodies of the human eye due to the hyperplasia of the anterior ocular cells which are in course of the healing process of the tissues damaged by the operation and/or excess production of cellular materials by the cells and the composition comprises active vitamin D as an effective component. Examples of ocular transparent bodies are aqueous humor, intraocular lenses, lens capsule and vitreous bodies.
The ophthalmic composition of the present invention comprises active vitamin D as an effective component. Specific examples of active vitamin D""s are ergocalciferol derivatives, ergocalciferol analogues, cholecalciferol derivatives, cholecalciferol analogues and hydrophilic active vitamin D analogues each carrying hydrophilic groups on the side chains. The active vitamin D may be naturally occurring ones or synthetic active vitamin D analogues.
Particularly preferred in the present invention are monohydroxy derivatives of vitamin D each of which carries a hydroxy group on one or both of the Cl position on the sterol A ring and the C25 position on the side chain; and dihydroxy derivatives in which the C1 and C24 positions or C1 and C25 positions are hydroxylated. Preferred examples thereof further include calcitriol (1xcex1,25-dihydroxy vitamin D), 1xcex1,24-dihydroxy vitamin D, alpha-calcidol (1xcex1-monohydroxy vitamin D), calcifedol (25-monohydroxy vitamin D), 1xcex1,24,25-trihydroxy vitamin D, 1xcex1,25,26-trihydroxy vitamin D, 1xcex2,25-dihydroxy vitamin D, 24homo-1xcex1,25-dihydroxy vitamin D, 26-homo-1xcex1,25-dihydroxy vitamin D, OCT (22-oxacalcitriol) and calcipotriol. Among these, a naturally occurring cholecalciferol derivative, i.e., calcitriol (1xcex1,25-dihydroxy vitamin D) is particularly preferred because it is free of any cytotoxicity and is highly active.
It has been recognized that the smaller the molecular weight and the higher the degree of hydrophobicity, the higher the permeability of the drug through the cornea. Calcitriol as a cholecalciferol derivative has a molecular weight of 416.64 dalton, synthetic alpha calcidol has a molecular weight of 400.64 dalton and these active vitamin D""s are excellent in the permeability through cornea.
It has also been known that dihydrotachysterol (DHT) as an active vitamin D analogue shows affinity for active vitamin D receptors present in cells and that it would have an effect similar to that observed for the active vitamin D. Thus the analogue is included in the xe2x80x9cactive vitamin Dxe2x80x9d used in the present invention.
The ophthalmic composition of the present invention is in general used in the form of an eye drop. The active vitamin D used as the effective component in the present invention is oil-soluble and it is preferably converted into an aqueous solution by diluting it with a solvent or diluent such as ethanol and finally diluting with the ophthalmic physiological buffer or converted into the usual ophthalmic solution in oil by dissolving a diluent prepared by diluting active vitamin D with, for instance, ethanol in oils and fats (e.g., sesame oil).
The ophthalmic composition of the present invention may likewise be used in the dosage forms administered per oral or parenteral routes such as injections, powdered drugs, tablets, capsules, powders and aerosols. Alternatively, it is also possible to encapsulate active vitamin D in an ophthalmic drug-delivery system such as liposome, microsphere, gel-like protein, collagen, soft contact lenses for treatment or intraocular lenses or to adhere such vitamin to the drug-delivery system to thus directly administer or deliver active vitamin D to damaged tissues or sites in the form of an ophthalmic treating agent.
The lacrimal fluid is viscous and oil-soluble. Therefore, active vitamin D may preferably be admixed with at least one viscous base or oil base selected from the group consisting of, for instance, polyvinyl alcohol, methyl cellulose, hyaluronic acid, chondroitin sulfuric acid, collagen and oils and fats to thus give a viscous ophthalmic solution which can be used as an eye drop or an agent directly administered into the aqueous humor.
It would be sufficient, in the present invention, that active vitamin D is administered in an amount ranging from 0.1 to 10 ng/dose/day for local administration. This corresponds to 1/5000 to 1/50 time the amount required for the usual administration through oral route and accordingly, there would almost be no systemic side effect.
When orally administering a large amount of the conventional vitamin D-containing pharmaceutical preparation, there is observed hypervitaminosis D in which the calcium and phosphoric acid contents in the blood increase and which is accompanied by the calcification of soft tissues such as kidney, arterial blood vessel, smooth muscles and lung. When the active vitamin D-containing ophthalmic composition of the present invention is administered in the form of an eye drop, it would take effect through local administration even when it is administered in an amount smaller than that conventionally used, for instance, in an amount of not more than 1/50 time that required for the oral administration and there would almost be no side effect unlike the conventional technique even if a certain amount of active vitamin D penetrates into the blood through the ocular mucous membrane.
Oral administration of active vitamin D also shows an effect of preventing the deterioration of the optical transparency of human eyes due to the hyperplasia of cells in damaged tissue-healing process and/or the excess production of cellular materials by the cells. However, active vitamin D must be administered in a large amount in order to achieve the same effect observed when it is locally administered to the eye. For this reason, the ophthalmic composition of the present invention is most preferably administered in the form of an eye drop.
In the present invention, an active vitamin D-containing ophthalmic composition is used for preventing the deterioration of the optical transparency of the human anterior ocular region due to the hyperplasia of cells during damaged tissue-healing process and/or the excess production of cellular materials such as collagen and proteins by the cells.
The vitamin D orally taken is converted into active vitamin D in the liver and/or kidney. It is known that, in the skin, 7-dehydrocholesterol is converted into previtamin D by the irradiation with ultraviolet rays in the sunlight and thereafter converted into active vitamin D in the liver and/or kidney .
The ophthalmic composition of the present invention is, for instance, used in the following manner.
When the transparency of the anterior ocular region of the human eyeball is impaired due to proliferation of, for instance, corneal epithelial cells, keratocytes, and inflammatory cells present in the aqueous humor and lens epithelial cells for the healing of damaged tissues and/or the production of cellular materials by the cells, the active vitamin D-containing ophthalmic solution of the present invention can be administered in the form of an eye drop to control the activity of these anterior ocular cells and to thus hold or ensure the desired transparency, normal refractive power and normal intraocular pressure.
Moreover, the active vitamin D-containing eye drop of the present invention is administered to a patient who has been subjected to a cataract operation immediately after the operation so that active vitamin D can permeate even into the posterior chamber from the anterior ocular region of the eye to control the activity of the lens epithelial cells and to thus prevent any reduction of the visual acuity due to the opacification of the lens capsule. Moreover, the administration of the active vitamin D-containing composition of the present invention permits the inhibition of the opacification of the transplanted intraocular lens surface due to the deposition of phagocytes present in the aqueous humor on the surface of the lens. The cataract surgery may sometimes be accompanied by accidental breakage of the capsule and inflammatory cells are penetrate into the vitreous body from the posterior chamber after the operation to thus cause opacification of the vitreous body. If administering, after the operation, the active vitamin D-containing composition of the present invention in the form of an eye drop, however, any such opacification of the vitreous body can be prevented.
In addition, the active vitamin D-containing eye drop of the present invention is administered to a patient who has been subjected to operation for glaucoma immediately after the operation so that active vitamin D can permeate even into the tissues of the anterior chamber gonion to control the cellular activity of tissues such as the Schlemm""s canal of the anterior chamber gonion, to thus suppress the hyperplasia of the anterior chamber gonion near the operated site and/or excess production of cellular materials and to prevent the recurrence of glaucoma.
The active vitamin D-containing eye drop of the present invention would show more higher cell activity-inhibitory effect if the eye drop is administered to a patient several days before the ophthalmic operation.
Furthermore, the active vitamin D-containing ophthalmic composition of the present invention can likewise be used for the treatment of the corneal degeneracy. Active vitamin D may correct any abnormal metabolism of the keratocytes to thus allow the keratocytes to synthesize proteins normally and to thus allow the keratocytes to undergo normal differentiation-induction.
The active vitamin D-containing ophthalmic composition of the present invention can be administered to a patient who has been subjected to an operation for cornea with a scalpel or a laser in the form of an eye drop to inhibit the hyperplasia of the corneal epithelial cells and keratocytes and any excess production of cellular materials such as collagen, to control the tugging of the wound due to the scaring, to prevent any change of the refractive power of the cornea and any turbidity of the cornea and to thus prevent any reduction of the visual acuity. The administration of the active vitamin D-containing ophthalmic solution of the present invention can control the cellular activity during the process for healing the damaged tissues and can likewise prevent any deterioration of the transparency of the human anterior ocular region due to the hyperplasia of the intraocular cells during the damaged tissue-healing process and the excess production of cellular materials.
In the patient who has been subjected to the keratectomy using an excimer laser, corneal epithelial cells are regenerated on the stroma after the keratectomy and the regeneration is completed within several days. The epithelial cells are thus regenerated, but there are observed epithelial hyperplasia and rise in epithelium and keratocyte cell activity at the periphery of the site from which the cornea is removed by the operation with an excimer laser and at sites from which the keratocytes are complicatedly removed. Reduction of visual acuity may be caused at these sites because of a corneal refractive power change and turbidity thereof due to cellular materials of the epithelial cells and keratocytes. A steroid drug has mainly been used to prevent the occurrence of these phenomena, but the administration thereof may cause, as side effects, steroid-induced glaucoma and steroid-induced cataract and accordingly, there has been a tendency of avoiding the use of any steroid-containing drug. Thus, if administering the ophthalmic composition of the present invention to a patient who has been subjected to keratectomy with an excimer laser in the form of an eye drop, the active vitamin D as the effective component thereof can inhibit the hyperplasia of the epithelial cells and the activity of the keratocytes and can in turn prevent the reduction of visual acuity due to any refractive power change and turbidity of the cornea.
As has been discussed above, Dr. Ohashi et al. in Osaka University studied the inhibitory effect of vitamin D3 against the expression of MHC class antigens in order to suppress any rejection observed during the keratoplasty and suggest that vitamin D3 may serve to control the rejection of the transplantation of cornea. However, the present invention is completely independent of the rejection observed during the keratoplasty and is based on such a finding that active vitamin D can maintain the transparency of the cornea and/or stabilize the refractive power thereof.
Japanese Un-Examined Patent Publication No. Hei 3-24016 discloses that active vitamin D3 is effective for the treatment of the proliferative retinopathy. However, the present invention is independent of the proliferative retinopathy of the eyeground and is based on such a finding that active vitamin D3 has an anti-inflammatory effect on the inflammatory cells in the anterior intraocular region and can maintain the optical transparency of the anterior ocular region during the process for healing damaged tissues after the ophthalmic operations and/or can stabilize the refractive power thereof.
Japanese Examined Patent Publication No. Hei 4-43887 discloses that active vitamin D3 is effective for the treatment of cataract while making use of the hypercalcemic action of active vitamin D3. However, the present invention is independent of the treatment of patients suffering from cataract while making use of the hypercalcemic action of active vitamin D3 and is based on such a finding that active vitamin D3 has an anti-inflammatory effect on the inflammatory cells in the anterior intraocular region and can maintain the optical transparency of the anterior ocular region during the process for healing damaged tissues after the ophthalmic operations and/or can stabilize the refractive power thereof.
The ophthalmic composition of the present invention is effective for inhibiting or suppressing the intraocular inflammation of patients and the activity of cells in course of the healing process of damaged tissues after operations.
The present invention is based on such a finding that the local administration of active vitamin D to the eye permits the maintenance of desired transparency, normal refractive power and normal intraocular pressure. On the other hand, it has been known that the vitamin D taken from foods is converted into active vitamin D in the kidney and liver. For this reason, the oral administration of non-active form of vitamin D may have the same ocular transparency-maintaining effect observed for active vitamin D. However, sufficient conversion of non-active form of vitamin D into active vitamin D cannot be expected in patients who also suffer from kidney and/or liver deficiencies and therefore, the administration of active vitamin D is effective for achieving the ocular transparency-maintaining effect.
According to the method of locally administering the ophthalmic solution of the present invention to the eye, it would be recognized that the active vitamin D binds to the vitamin D receptor to form a complex and that the complex is incorporated into cell nuclei to affect the DNA and to thus control the activity of the cells, but active vitamin D does not adversely affect the normal ocular cells unless it is administered in an extremely excess amount since it does not show any cytotoxicity.
The vitamin C deficiency results in reduction in the number of vitamin D receptors and thus adversely affects the incorporation of active vitamin D into the nuclei. Accordingly, the presence of vitamin C is quite important and in particular, patients desirably take a sufficient amount of vitamin C when using the ophthalmic composition of the present invention. Therefore, the ophthalmic composition of the present invention which is further admixed with vitamin C would show further improved effect of active vitamin D and thus the use thereof is preferred. Vitamin C is preferably incorporated into the composition in an amount ranging from about 1 to 100 mg/ml.
It would be difficult to deliver active vitamin D even to the eyeground according to the method for administering the ophthalmic composition of the present invention in the form of an eye drop and thus it would be more effective to use the method simultaneously with the oral administration of vitamin D when the posterior ocular region of a patient is to be treated with active vitamin D.
The composition of the present invention may be administered, in the form of an eye drop, to a patient, whose anterior ocular region has been operated, over a long period of time after the operation, but as has been discussed above, it is also possible to encapsulate active vitamin D in an ophthalmic drug-delivery system such as liposome, microsphere, gel-like protein, collagen, soft contact lenses for an ophthalmic treatment or intraocular lenses or to adhere such vitamin to the drug-delivery system to thus directly administer active vitamin D to damaged tissues or sites in the form of an agent for ophthalmic treatments, which may have a sustained release effect of the drug.
Moreover, active vitamin D is inactivated when it is oxidized and therefore, it would be desirable to use a container for storage or an antioxidant when storing it in the form of an ophthalmic solution or when administering it while expecting the sustained release effect thereof.
As has been described above, the usual vitamin D is converted into active vitamin D in liver and kidney and accordingly, the intended effect of the present invention cannot be achieved even if the usual vitamin D is locally administered to the eye.
In respect of safety of active vitamin D, Enjyo et al. carried out toxicity tests and irritability tests for a synthetic 1xcex1,24-dihydroxycholecalciferol-containing ointment using the skin and ocular mucous membrane of rabbit to thus confirm the safety thereof (xe2x80x9cToxicity Investigation of TY-02xe2x80x9d in YAKURI TO CHIRYO (Pharmacological Action and Treatment), Vol. 17, No. 10, October, 1989).

Ophthalmic composition containing active vitamin D

Abstract: The ophthalmic composition can be dropped in the eye after operations such as those for cataract, for transplantation of intraocular lenses and for cornea to maintain the intraocular transparency of the anterior ocular region, to control the hyperplasia of the anterior ocular cells in the tissues damaged by the ophthalmic operation, which are in course of a healing process, and/or excess production of cellular materials and to thus prevent any reduction of visual acuity.


A sensor is provided which is sensitive to a particular property of a medium and which is thermally activated when in contact with the property containing medium. The sensor is externally mounted on the undersurface of a silicon wafer, the upper surface of which contains a well in which a vibratile bridge element is located. The top of the well is closed off so that the vibratile bridge element is within a chamber. Excitation energy from a source is delivered to the vibratile bridge element to establish vibratory motion which is monitored and detected by a circuit. Presence of the particular property in the medium causes a thermal change in the wafer resulting in a change in the resonance frequency of the vibratory motion of the vibratile bridge element. The frequency shift is a measure of the particular property.

A known form of apparatus for assessing a property of a fluid comprises an optical fiber coated near its tip with an enzyme or antibody. When the coated tip is contacted with the fluid, enzyme-catalyzed reactions create localized heating and expansion of the fiber and the rate of expansion, ana hence the rate of reaction, is measured by comparing the fiber length with that of an adjacent reference fiber using interferometry. The known apparatus is not temperature stable and operation depends on the expansion of an optical fiber which is a disadvantage where space is limited.

Apparatus for assessing a particular property in a medium


A display including a display panel, a circuit board and a tape carrier package structure is provided. The circuit board is disposed at the display panel. The tape carrier package structure includes a substrate having an opening, a plurality of leads, a chip, and a blocking bar. The substrate is between the display panel and the circuit board. A plurality of leads, each having an inner lead and outer lead, are disposed around the opening on the substrate. A portion of the outer leads is electrically connected to the display panel, and another portion is electrically connected to the circuit board. The chip has a plurality of contact points, and is disposed at the opening of the substrate. The contact points are electrically connected to the inner leads. Moreover, the blocking bar is disposed on the substrate between the chip and the display panel.

1. Field of the Invention
The present invention generally relates to a display. More particularly, the present invention relates to a display with a tape carrier package (TCP) structure or with a package structure of chip on flexible printed circuit board (chip on FPC, COF).
2. Description of Related Art
As the video technology advances drastically, a variety of display devices has been developed. In general, a conventional display includes a display panel for displaying image. The display panel is controlled by a circuit board. The chip on the circuit board computes and provides digital signals in order to control the pixels of the display panel for displaying image and to generate a frame of image. In general, a package structure has to be electrically connected between the circuit board and the display panel.
A conventional tape carrier package (TCP) structure or a chip on flexible printed circuit board (chip-on-FPC, COF) package structure is a design for packaging the semiconductor chip to a small size unit. The technology is broadly used to package the liquid crystal display driving integrated chip (LDI).
FIG. 1 is a schematic top view of a display using a conventional tape carrier package structure. Referring to FIG. 1, a display 100 includes a display panel 110, at least a circuit board 120 and at least a tape carrier package structure 130. The circuit board 120 is disposed at a side of the display panel 110, and the tape carrier package structure 130 is electrically connected between the display panel 110 and the circuit board 120.
FIG. 2 is a schematic cross-sectional view of the tape carrier package structure along line A-A′ of FIG. 1. Referring to FIG. 1 and FIG. 2, the tape carrier package structure 130 includes a substrate 132, a plurality of leads 134 and a chip 136. The substrate 132 has an opening 132a. The leads 134 are disposed around the opening 132a of the substrate 132, and each lead 134 has an inner lead 134a and an outer lead 134b. A portion of the outer lead 134b is electrically connected to the display panel 110 and another portion of the outer lead 134b is electrically connected to the corresponding circuit board 120 by using anisotropic conductive film (ACF) 140. The chip 136 is disposed close to the opening 132a of the substrate 132. In addition, the chip 136 has a plurality of contact points 136a electrically connected to the inner lead 134a. Moreover, a sealing material 150 covers the chip 136 of the tape carrier package structure 130.
However, in the package process of the display panel 110 and the circuit board 120 using the tape carrier package structure 130, the influence of particles on the yield of the package process should be considered.
FIG. 3 is a schematic cross-sectional side view of the tape carrier package structure, a portion of the display panel and a portion of the circuit board along line B-B′ of FIG. 1. Referring to FIG. 3, a conventional tape carrier package structure 130 is electrically connected to the display panel 110 and the circuit board 120 by using the anisotropic conductive film 140. However, a bevel region 112 is generally designed on the display panel 110. Since variation may occur when bonding the package structure and the display panel 110, in general, the anisotropic conductive film 140 is moved towards the inner side of the display panel 110 for adhesion so that the anisotropic conductive film 140 may be far away from the bevel region 112.
However, as described above, a larger space is formed in the bonding region of the display panel 110 and the anisotropic conductive film 140. Consequently, particles 160 are easily to fall in the space. Accordingly, abnormal short circuit or open circuit may be occurred between the package structure 130 and the display panel 110.

Display and tape carrier package structure


A system and method for storing and providing media objects in a navigable environment implemented on at least one computer executing computer readable program code stored in a tangible memory medium. The at least one computer is configured to access a plurality of media objects comprising a media recording and metadata. The at least one computer is further configured to generate an index of said plurality of media objects based on said metadata.

1. Field of the Invention
Embodiments of the invention described herein pertain to the field of computer systems. More particularly, but not by way of limitation, one or more embodiments of the invention enable a system and method for creating and providing media objects in a navigable environment.
2. Description of the Related Art
Advancements in networking technologies have facilitated the self-publication of user-created content. Average computer users are able to publish digital media over a network, such as the Internet. Available systems, such as the system accessible at youtube.com, provide a platform for users to self-publish media. Such media includes audio recordings, video recordings, audio-video recordings, and other digital media recordings or recordings convertible to a digital format.
In addition, advancements in digital recording technologies have brought about the ability for the average consumer to produce publishable materials. These digital recording technologies include photo cameras, video recorders, audio recorders, audio-video recording devices, and other device capable of recording live media. These recording devices are easy to use, portable, and offer network connectivity which in turn facilitates the creation of media and the publication of user-created media over a network, such as the Internet.
Currently, published media is created, stored and provided with limited context. Published media is typically created, stored and presented as a continuous stream. Authors are not given an incentive to portray a small set of events, entities, thoughts, ideas or concepts in each piece of published media. Because authors are not given incentive to portray such concepts in their recorded media, the recorded media resembles streams of media content rather than media objects.
Furthermore, authors using text to provide context about the stream of media content are limited only to words describing the content. Additional information such as viewership statistics and/or feedback information is sometimes used to provide more information about the context of the media content. Streams of content are harder to describe using concrete terms, which generally facilitates organizing the media by context and relationship.
Published media is also currently provided to viewers with limited context and is not presented in a flexible, navigable environment which provides context about the published media. Rather, published media is searchable based on the limited context information accompanying the published media.
To overcome the problems and limitations described in conjunction with current systems there is a need for a system and method for creating and providing media objects in a navigable environment.

System and method for creating and providing media objects in a navigable environment


A solid-state imaging device includes: a first photodiode made up of a first first-electroconductive-type semiconductor region formed on a first principal face side of a semiconductor substrate, and a first second-electroconductive-type semiconductor region formed within the semiconductor substrate adjacent to the first first-electroconductive-type semiconductor region; a second photodiode made up of a second first-electroconductive-type semiconductor region formed on a second principal face side of the semiconductor substrate, and a second second-electroconductive-type semiconductor region formed within the semiconductor substrate adjacent to the second first-electroconductive-type semiconductor region; and a gate electrode formed on the first principal face side of the semiconductor substrate; with impurity concentration of a connection face between the second first-electroconductive-type semiconductor region and the second second-electroconductive-type semiconductor region being equal to or greater than impurity concentration of a connection face of an opposite layer of the second first-electroconductive-type semiconductor region of the second second-electroconductive-type semiconductor region.

The present technology relates to a solid-state imaging device, a solid-state imaging device manufacturing method, and an electronic device employing this solid-state imaging device.
With solid-state imaging devices having a photoelectric conversion region, there is a solid-state imaging device having a configuration wherein multiple photoelectric conversion regions are disposed in the depth direction of a semiconductor substrate. With such a solid-state imaging device, a trench is formed in proximity to a photoelectric conversion region disposed in a depth position of the semiconductor substrate, and a readout gate is disposed within this trench via a gate insulating film.
With the solid-state imaging device thus configured, a channel is formed in a position along the gate insulating film between the depth position where the photoelectric conversion region is disposed and a floating diffusion within the semiconductor substrate. Signal charges accumulated in the photoelectric conversion region are read out to the floating diffusion via this channel by applying voltage to a readout gate embedded in the trench (see Japanese Unexamined Patent Application Publication No. 2009-295937).
Also, a configuration has been disclosed wherein a semiconductor substrate region where a channel between a photoelectric conversion region having an n-type impurity region disposed in a depth position of a semiconductor substrate and a floating diffusion made up of an n-type impurity region is formed is taken as an n-type impurity region having low concentration. With such a configuration, the photoelectric conversion region is completely depleted by adjusting the n-type impurity concentration, whereby all of the signal charges can be transferred (see Japanese Unexamined Patent Application Publication No. 2010-114322).
Also, with regard to rear face irradiation type solid-state imaging devices, improvement in saturation charge amount, and high sensitivity have been demanded.
As a configuration for increasing saturation charge amount, a solid-state imaging device has been proposed wherein multiple photodiodes are formed in the depth direction within a substrate (see Japanese Unexamined Patent Application Publication No. 2010-114274). With this configuration, saturation charge amount is increased by laminating three photodiodes (PD1, PD2, and PD3) formed with PN junction between an n-type semiconductor region and a p-type semiconductor region on the n-type semiconductor region in the depth direction. Additionally, a vertical-type gate electrode embedded in the depth direction from the surface of the substrate is provided as a transfer transistor (Tr). Electric charges are transferred to the floating diffusion (FD) from a photodiode PD formed in a depth position of the substrate using this vertical-type Tr.
Also, as for a configuration for enabling high sensitivity, a solid-state imaging device has been proposed wherein a second photodiode PD2 is provided on the light incident side (substrate rear face), and a first photodiode PD1 is provided on the opposite face (substrate front face) on the light incident side (see Japanese Unexamined Patent Application Publication No. 2010-192483).
With this solid-state imaging device, the first photodiode PD1 and floating diffusion (FD) and so forth are formed by injecting ions into the surface of the semiconductor substrate. Further, after forming a gate electrode, a wiring layer, or the like on the semiconductor substrate, the semiconductor substrate is reversed, and the rear face of the semiconductor substrate is ground.
Next, ions are injected from the rear face side of the semiconductor substrate to perform activation of impurities by heat treatment of 1000° C. such as laser annealing or the like for example to form a second photodiode PD2 and so forth.

Solid state imaging device having impurity concentration on light receiving surface being greater or equal to that on opposing surface


An improved depositor apparatus for depositing material from a material source. The depositor apparatus including first and second dispensing assemblies having spaced-apart outlets. The first and second dispensing assemblies are reciprocally operated to alternately dispense material. A feed device is coupled to the first and second dispensing assemblies for supplying material from the material source to the first and second dispensing assemblies for discharge.

The present invention relates to a depositor apparatus for dispensing measured units of material. In particular, the present invention relates to a depositor apparatus which dispenses material from spaced dispensers.
Depositors are known which meter and dispense material to a moving conveyor system. Typically, material from a hopper or feed reservoir is filled into a dispensing chamber for discharge. The dispensing chamber typically includes a reciprocating dispensing plunger operable within said chamber to force material from the chamber to dispense the material from the depositor. While the dispensing chamber is being filled with material from a hopper or feed reservoir, the dispensing plunger remains in a retracted position, such that no material is expunged from the depositor while the dispensing chamber is being filled. After the dispensing chamber is filled, then the dispensing plunger can operate to dispense a metered unit of material. Thus, the depositor must complete the metering and filling cycle prior to commencing the dispensing cycle. Thus, the rate at which measured units of material can be dispensed is limited by the rate at which the metering and filling cycles can take place and the dispensing rate.
There is a continuing effort to increase production rates of product; and, thus, there is an effort to increase the rate for depositing measured units of material onto a conveyor system. A system incorporating coordinated dual dispensing chambers where material is metered into a first dispensing chamber while other material is dispensed from a second separate dispensing chamber is disclosed in U.S. Pat. No. 3,342,145 to Brunson. Brunson discloses dual dispensing chambers coupled to a single discharge chamber having a discharge opening. A valve assembly rotates between the dual dispensing chambers to selectively connect a filled dispensing chamber with the single discharge chamber and discharge opening. Due to limitations in the operation of the valve assembly, time delays exist between the connection of respective dispensing chambers to the single discharge chamber thus limiting the rate at which material may be filled into the dispensing chamber and dispensed. In Brunson, the valve assembly essentially selectively forms a portion of the dispensing chamber when coupled to the discharge chamber and forms a portion of the filling chamber when the dispensing chamber is coupled to a filling chamber and thus pressure is exerted to the valve assembly tending to decrease operating efficiency of the valve assembly. Thus, it is desirable to provide an improved depositor assembly with increased speed, capacity and/or efficiency for metering and dispensing product.


A pitch actuation system restraint (PASR) device that provides, inter alia, protection for the pitch actuation system of a helicopter having a main rotor assembly configured for main rotor blade folding operations. The PASR device includes permanent adapter brackets that are permanently mounted in combination with the rotor hub arms of the main rotor assembly. The PASR device further includes a temporary adapter bracket and quick release pins for each main rotor blade to be folded. Prior to implementing blade folding operations, a temporary adapter bracket is temporarily secured in combination with the pitch control horn of each main rotor blade to be folded and the permanent adapter bracket of the adjacent rotor hub arm by means of the quick release pins. Each temporary adapter bracket and permanent adapter bracket as temporarily secured in combination functions as a rigid structural interconnection between the corresponding pitch control horn and the main rotor hub assembly that effectively locks the pitch control horn in position during blade folding operations such that displacements induced in the main rotor blade during blade folding operations cannot be coupled into the pitch actuation system.

While the flight capabilities of helicopters makes them effective vehicles for a wide variety of flight missions, the utility of helicopters in certain circumstances may be limited by the overall structural envelopes thereof. To provide the power required to support the flight capabilities of helicopters, the main rotor assemblies of helicopters incorporate a plurality of main rotor blades having large radial dimensions. The large radial dimensions of helicopter rotor assemblies results in helicopters having large structural envelopes that occupy an inordinate amount of space. The large structural envelopes of helicopters may limit their utility in some circumstances.
For example, helicopters utilized for maritime flight operations may be required to conduct operations from ships for extended periods of time. Shipboard space is generally at a premium, and the large structural envelopes of helicopters means that stowage of helicopters during periods of non-use requires a large allocation of such limited space. The same concern arises for helicopters operating from oceanic oil rigs wherein helicopters are stowed during periods of non-use. In addition to space limitations arising from the structural envelopes of helicopters due to the main rotor assemblies, the main rotor assemblies of stowed helicopters that are exposed to the environment are vulnerable to wind gusts. Furthermore, strategic and tactical considerations in the military utilization of helicopters has led to a requirement for helicopters having main rotor assemblies that may be readily reconfigured for rapid deployment, routine transport, and/or stowage through reduction in the structural envelopes of the helicopters.
Several options are available to reduce the structural envelopes of helicopters to facilitate rapid deployment, routine transport, stowage, and/or to reduce the vulnerability thereof to environmental conditions. One option is to design the main rotor assemblies of helicopters so that the main rotor blades may be removed from the rotor hub assembly. While this is a viable solution in some circumstances, it should be appreciated that such main rotor blade assemblies may be unnecessarily complex. In addition, it should be appreciated that removal of the main rotor blades tends to be time consuming and labor intensive. Moreover, these same time constraints and labor requirements exist when the helicopter is reconfigured for subsequent flight operations. Therefore, reduction of the structural envelope of helicopters by removal of the main rotor blades may not be the most viable option under some circumstances.
Another option available to reduce the structural envelopes of helicopters is to design the main rotor assemblies thereof so that the main rotor blades may be folded about the main rotor hub assembly. Main rotor blade folding operations may be implemented either automatically via hydraulic systems or manually. Automatically controlled blade folding operations require relatively extensive modifications to the main rotor assembly to incorporate the necessary mechanical apparatus to effectuate automatic blade folding. In addition, specialized software must be incorporated in the automatic flight control system to regulate automatic blade folding operations. Representative examples of such mechanical apparatus and specialized software are illustrated in U.S. Pat. Nos. 4,354,234, 4,284,387, and 3,743,441. Such mechanical apparatus unnecessarily increase the complexity of the main rotor assembly. In addition, such mechanical apparatus and software increases the overall system cost of the helicopter.
Manual blade folding operations, in contrast, generally require minimal mechanical modifications to the main rotor assembly, and do not generally require specialized software. In light of the minimal mechanical modifications required to incorporate blade folding capabilities in helicopter main rotor assemblies, this option represents a viable approach in a number of circumstances. For example, for maritime operations and oil rig use, manual blade folding operations may be effected with minimal manpower in a short period of time to reduce the overall structural envelope of helicopters. The modifications to the main rotor assembly required to accommodate manual blade folding operations result in only an incremental increase in the complexity of the main rotor assembly and the overall systems costs of the helicopter.
However, manual blade folding operations do pose a concern in terms of the pitch actuation system of the helicopter. The helicopter pitch actuation system is a relatively complex hydromechanical system comprised of a large number of precisely aligned, structurally and functionally interrelated components. Such components include the pilot's input (collective; cyclic), interconnecting mechanical linkages, hydraulic servo systems, a swashplate assembly (stationary; rotating), pitch control rods, and pitch control horns. It goes without saying that proper operation of the pitch actuation system is vital to safe and efficient helicopter flight operations. Proper operation of the pitch actuation system, in turn, requires precise alignment and functional interactions among the various elements of the hydromechanical system. Pilot inputs via the collective and cyclic controls must be accurately and systematically converted to repeatable pitch inputs to the main rotor blades via the pitch actuation system.
During blade folding operations, however, displacements may be induced into the main rotor blades being folded by wind gusts, loss of physical blade control, etc. Such displacements may be coupled into the pitch actuation system by means of the respective pitch control horns. Such coupled displacements may damage or degrade the pitch actuation system by disrupting the precise alignment and/or functional interactions among the various components of the hydromechanical pitch actuation system, thereby negatively impacting the accuracy and repeatability of the pitch actuation system. Increasing the concern vis-a-vis damage or degradation of the flight actuation system is the fact that such damage or degradation may occur to components of the hydromechanical system that are located within the helicopter fuselage, and as such, not readily visible during preflight checks prior to commencing flight operations.
Therefore, a need exists to protect the pitch actuation system of a helicopter during manual blade folding operations. The protective apparatus should preclude main rotor blade displacements incurred during blade folding operations from being coupled into the helicopter pitch actuation system. The protective apparatus should be simple in design and readily fabricated so as to not significantly increase the overall complexity of the main rotor assembly or the overall systems costs of the helicopter. The protective apparatus should also be easy to install and remove, and installation/removal should not effect the precise alignment and/or functional interaction among the hydromechanical components of the pitch actuation system.

Pitch actuation system restraint device for a helicopter blade folding system


Disclosed is an improved arrangement for allowing more accurate automatic calibration for a system in which blood pressure pulses are derived for remote sites from a calibrated measurement and a waveform measurement, when these are made at different sites. Where a calibrated measurement is made, say, at the brachial artery (11), and a waveform recorded at the radial artery (12), a waveform is derived for the calibrated site using a known transfer function, this drived waveform is then calibrated by the measurements already made, and the calibrated waveform for any remote site, for example the ascending aorta (14), can be derived using a known transfer function.

A technique for utilising peripheral pressure pulses to determine the pulse waveform at other body sites, particularly the ascending aortic waveform, is disclosed in U.S. Pat. No. 5,265,011 by Michael F. O'Rourke. The books "The Arterial Pulse" by O'Rourke, Kelly and Avolio published by Lea Febiger, Philadelphia USA 1992 and "Arterial Vasodilation", by O'Rourke, Saffer, and Dzau, published by Arnold, London 1993 disclose the use of a measured peripheral waveform to determine the waveform at another site, using an empirically determined transfer function. The derived waveform can be calibrated, as it is derived from the peripheral waveform which itself is calibrated. In these documents, it is assumed that the brachial cuff sphygmomanometer measurement can be used to directly calibrate waveforms measured at the radial artery. It is assumed that relatively little change occurs in the parameters between the brachial artery and the radial artery. Whilst this is a reasonable working assumption, it is not strictly accurate.
It is an object of the present invention to provide an improved calibration procedure, such that derived waveforms are able to be more accurately calibrated.


A spinal implant is inserted between adjacent vertebrae to function as an disk prosthesis. The prosthesis has two plates fastened to adjacent vertebrae facing each other. The facing sides of the plates each have a depending skirt formed as concentric arcs of about 90 degrees. The skirts are either bowed or tapered in the axial direction. A protrusion is centrally located between the arcs on one plate and a depression is centrally located between the arcs of the other plate. The plates are oriented to each other with the concentric arcs of each interrupted skirt at 90 degrees and the protrusion is engaged in the depression. The plates are then rotated about 90 degrees and the opposed arcs of one plate interlock with the opposed arcs of the other plate to prevent separation in the axial direction.

Several attempts have been made to design a spinal prosthesis for replacement of missing or excised disk material that replicates the functions of the missing tissue. U.S. Pat. No. 4,759,769 to Hedman et al discloses a two piece artificial disk device in which two plates are attached to the adjacent vertebrae by bone screws inserted through flanges on the plates. A spring biasing mechanism is captured between the plates to simulate the actions of the natural disk material. U.S. Pat. No. 5,246,458 to Graham and U.S. Pat. No. 6,228,118 to Gordon disclose other intervertebral implants with arcuate flanges used to connect the device to adjacent vertebra.
The patents to Marnay, U.S. Pat. No. 5,314,477, Buttner-Janz et al, U.S. Pat. No. 5,401,269, Yuan et al, U.S. Pat. No. 5,676,701, and Shelokov, U.S. Pat. No. 6,039,763, all are directed to the design of the opposing faces of the adjacent plates of an implant to provide a limited universal joint to simulate the natural movement of the spine.
U.S. Pat. No. 5,683,465 to Shinn et al teaches two plates with bow shaped skirts which are interlocked.
What is needed in the art is a disk prosthesis that has limited universal motion yet is securely interlocked to prevent dislocation or separation.

This patent is subject to a terminal disclaimer.


A midlength balanced rotor comprises a rotor assembly for rotation about an axis of rotation defining at least one of an axially extended, radially concentric, centerline borehole; an array of radially or tangentially distributed, axially extended pockets; and a series of radially or tangentially distributed, axially extended slots. At least one balance weight is positioned within at least one of the axially extended, radially concentric, centerline borehole, the array of radially or tangentially distributed, axially extended pockets, or the radially or tangentially distributed, axially extended slots to balance the rotor assembly. Alternatively, at least one balance correcting mass is removed from at least one of the axially extended, radially concentric, centerline borehole, the array of radially or tangentially distributed, axially extended pockets, or the radially or tangentially distributed, axially extended slots to balance the rotor assembly. In addition, a method of midlength balancing a rotor comprises the steps of providing a rotor assembly with at least one of an axially extended, radially concentric, centerline borehole; an array of radially or tangentially distributed, axially extended pockets; and a series of radially or tangentially distributed, axially extended slots; rotating the rotor shaft about an axis of rotation; determining unbalance of the rotor shaft; and adding or removing weight to at least one of said an axially extended, radially concentric, centerline borehole; array of radially or tangentially distributed, axially extended pockets; or series of radially or tangentially distributed, axially extended slots, to balance the rotor shaft.

The invention relates generally to methods and apparatus for balancing a rotor and more specifically to methods and apparatus for midlength balancing of a rotor.
A rotating body will not exert any variable disturbing force on its supports when the axis of rotation coincides with one of the principal axes of inertia of the body. This condition is quite difficult to achieve in the normal process of manufacturing since due to errors in geometrical dimensions and non-homogeneity of the material, some irregularities in the mass distribution are always present.
As a result of the above, variable disturbing forces occur which produce vibrations. To remove these vibrations and establish safe and quiet operation, balancing becomes necessary. The importance of balancing becomes especially great in the case of high-speed machines, for example a turbine rotor or electric machinery that operates at speeds typical of turbomachinery. In such cases the slightest unbalance may produce a very large disturbing force.
The proper balancing of certain rotors, particularly for high-speed applications, requires unbalance correction not just in the end regions of the rotor but also in the midlength of the rotor body. Common rotor architectures, especially in high-speed applications, make use of an outer shell of material that is highly stressed. This highly stressed material cannot tolerate the stress concentrations caused by weight-addition or weight-removal features typically used for balancing. Accordingly, the only locations available for balancing rotors of this configuration have traditionally been in the end regions of the rotor where the materials are not as highly stressed. With correction planes available only in the end regions, the speed range over which a rotor can be successfully operated in without rotor dynamic instability is limited.
The typical solution is to design a rotor with high enough stiffness such that the residual unbalance of the unit can be corrected in locations on either end of the rotor body. This effectively restricts the size and speed that a rotor can operate. If a design must operate in a regime where mid-length rotor balancing is required, then sub-component and sub-assembly balancing techniques can be employed to limit the potential unbalance of the full assembly. This approach has limited effectiveness, as it does not address the unbalance caused during the assembly process. The ability to correct the rotor balance at axial locations between the end regions after it is assembled can enable the rotor to operate at higher speeds without experiencing instability issues.
The process by which a typical high-speed rotor is balanced requires access to the balance correction locations. For a traditional balancing scheme, correction masses are added or removed from available end regions. Access to these regions is often restricted by the rotor support structure and the non-rotating machine components. Because of access restrictions, the balancing operations are often conducted before the rotor is assembled to the machine. Future balance correction for machines of this nature require significant disassembly to gain access to the balance correction locations. End-wise access to balance correction locations can enable rotor balancing on a machine that is nearly fully assembled, ideally requiring access to only one end of the rotor. Future balance correction can be enabled in this way without significant machine disassembly.
Accordingly, there is a need for an improved rotor balancing method and apparatus, especially for midlength rotor balancing.

Method and apparatus for balancing a rotor


Novell IL-8 compounds and methods of using them are provided.

This invention relates to novel sulfonamide substituted diphenyl urea compounds, pharmaceutical compositions, processes for their preparation, and use thereof in treating IL-8, GROxcex1, GROxcex2, GROxcex3, NAP-2 and ENA-78 mediated diseases.
Many different names have been applied to Interleukin-8 (IL-8), such as neutrophil attractant/activation protein-1 (NAP-1), monocyte derived neutrophil chemotactic factor (MDNCF), neutrophil activating factor (NAF), and T-cell lymphocyte chemotactic factor. Interleukin-8 is a chemoattractant for neutrophils, basophils, and a subset of T-cells. It is produced by a majority of nucleated cells including macrophages, fibroblasts, endothelial and epithelial cells exposed to TNF, IL-1xcex1, IL-1xcex2or LPS, and by neutrophils themselves when exposed to LPS or chemotactic factors such as FMLP. M. Baggiolini et al., J. Clin. Invest. 84, 1045 (1989): J. Schroder et al, J. Immunol. 139, 3474 (1987) and J. Immunol. 144, 2223 (1990); Strieter, et al., Science 243, 1467 (1989) and J. Biol. Chem. 264, 10621 (1989); Cassatella et al., J. Immunol. 148, 3216 (1992).
GROxcex1, GROxcex2, GROxcex3and NAP-2 also belong to the chemokine family. Like IL-8 these chemokines have also been referred to by different names. For instance GROxcex1, xcex2, xcex3 have been referred to as MGSAxcex1, xcex2 and xcex3 respectively (Melanoma Growth Stimulating Activity), see Richmond et al., J. Cell Physiology 129, 375 (1986) and Chang et al., J. Immunol 148, 451 (1992). All of the chemokines of the xcex1-family which possess the ELR motif directly preceding the CXC motif bind to the IL-8 B receptor (CXCR2). IL-8, GROxcex1, GROxcex2, GROxcex3, NAP-2, and ENA-78 stimulate a number of functions in vitro. They have all been shown to have chemoattractant properties for neutrophils, while IL-8 and GROxcex1 have demonstrated T-lymphocytes, and basophilic chemotactic activity. In addition IL-8 can induce histamine release from basophils from both normal and atopic individuals. GRO-xcex1 and IL-8 can in addition, induce lysozomal enzyme release and respiratory burst from neutrophils. IL-8 has also been shown to increase the surface expression of Mac-1 (CD11b/CD18) on neutrophils without de novo protein synthesis. This may contribute to increased adhesion of the neutrophils to vascular endothelial cells. Many known diseases are characterized by massive neutrophil infiltration. As IL-8, GROxcex1, GROxcex2, GROxcex3and NAP-2 promote the accumulation and activation of neutrophils, these chemokines have been implicated in a wide range of acute and chronic inflammatory disorders including psoriasis and rheumatoid arthritis, Baggiolini et al., FEBS Lett. 307, 97 (1992); Miller et al., Crit. Rev. Immunol. 12, 17 (1992); Oppenheim et al., Annu. Rev. Immunol. 9, 617 (1991); Seitz et al., J. Clin. Invest. 87, 463 (1991); Miller et al., Am. Rev. Respir. Dis. 146, 427 (1992); Donnely et al., Lancet 341, 643 (1993). In addition the ELR chemokines (those containing the amino acids ELR motif just prior to the CXC motif) have also been implicated in angiostasis, Strieter et al., Science 258, 1798 (1992).
In vitro, IL-8, GROxcex1, GROxcex2, GROxcex3 and NAP-2 induce neutrophil shape change, chemotaxis, granule release, and respiratory burst, by binding to and activating receptors of the seven-transmembrane, G-protein-linked family, in particular by binding to IL-8 receptors, most notably the IL-85xcex2receptor (CXCR2). Thomas et al., J. Biol. Chem. 266, 14839 (1991); and Holmes et al., Science 253, 1278 (1991). The development of non-peptide small molecule antagonists for members of this receptor family has precedent. For a review see R. Freidinger in: Progress in Drug Research, Vol. 40, pp. 33-98, Birkhauser Verlag, Basel 1993. Hence, the IL-8 receptor represents a promising target for the development of novel anti-inflammatory agents.
Two high affinity human IL-8 receptors (77% homology) have been characterized: IL-8Rxcex1, which binds only IL-8 with high affinity, and IL-8Rxcex2, which has high affinity for IL-8 as well as for GROxcex1, GROxcex2, GROxcex3 and NAP-2. See Holmes et al., supra; Murphy et al., Science 253, 1280 (1991); Lee et al., J. Biol. Chem. 267, 16283 (1992); LaRosa et al., J. Biol. Chem. 267, 25402 (1992); and Gayle et al., J. Biol. Chem. 268, 7283 (1993).
There remains a need for treatment, in this field, for compounds, which are capable of binding to the IL-8xcex1 or xcex2 receptor. Therefore, conditions associated with an increase in IL-8 production (which is responsible for chemotaxis of neutrophil and T-cells subsets into the inflammatory site) would benefit by compounds, which are inhibitors of IL-8 receptor binding.
This invention provides for a method of treating a chemokine mediated disease, wherein the chemokine is one which binds to an IL-8a or b receptor and which method comprises administering an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In particular the chemokine is IL-8.
This invention also relates to a method of inhibiting the binding of IL-8 to its receptors in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula (I).
The present invention also provides for the novel compounds of Formula (I), and pharmaceutical compositions comprising a compound of Formula (I), and a pharmaceutical carrier or diluent.
Compounds of Formula (I) useful in the present invention are represented by the structure:
wherein
Rb is independently hydrogen, NR6R7, OH, ORa, C1-5alkyl, aryl, arylC1-4alkyl, aryl C2-4alkenyl; cycloalkyl, cycloalkyl C1-5alkyl, heteroaryl, heteroarylC1-4alkyl, heteroarylC2-4alkenyl, heterocyclic, heterocyclic C1-4alkyl, or a heterocyclic C2-4alkenyl moiety, all of which moieties may be optionally substituted one to three times independently by halogen; nitro; halosubstituted C1-4alkyl; C1-4 alkyl; amino, mono or di-C1-4alkyl substituted amine; ORa; C(O)Ra; NRaC(O)ORa; OC(O)NR6R7; hydroxy; NR9C(O)Ra; S(O)m, Ra; C(O)NR6R7; C(O)OH; C(O)ORa; S(O)tNR6R7; NHS(O)tRa. Alternatively, the two Rb substituents can join to form a 3-10 membered ring, optionally substituted and containing, in addition to optionally substituted C1-4alkyl, independently, 1 to 3 NRa, O, S, SO, or S2 moities which can be optionally unsaturated;
Rais an alkyl, aryl, arylC1-4alkyl, heteroaryl, heteroaryl C1-4alkyl, heterocyclic, COORaxe2x80x2, or a heterocyclic C1-4alkyl moiety, all of which moieties may be optionally substituted;
Raxe2x80x2 is an alkyl, aryl, arylC1-4alkyl, heteroaryl, heteroaryl C1-4alkyl, heterocyclic or a heterocyclic C1-4alkyl moiety, all of which moieties may be optionally substituted;
m is an integer having a value of 1 to 3;
mxe2x80x2 is 0, or an integer having a value of 1 or 2;
n is an integer having a value of 1 to 3;
q is 0, or an integer having a value of 1 to 10;
t is 0, or an integer having a value of 1 or 2;
s is an integer having a value of 1 to 3;
R1 is independently selected from hydrogen, halogen, nitro, cyano, C1-10 alkyl, halosubstituted C1-10alkyl, C2-10alkenyl, C1-10alkoxy, halosubstituted C1-10alkoxy, azide, S(O)tR4, (CR8R8)q S(O)tR4, hydroxy, hydroxy substituted C1-4alkyl, aryl, aryl C1-4alkyl, aryl C2-10alkenyl, aryloxy, aryl C1-4 alkyloxy, heteroaryl, heteroarylalkyl, heteroaryl C2-10 alkenyl, heteroaryl C1-4 alkyloxy, heterocyclic, heterocyclic C1-4alkyl, heterocyclicC1-4alkyloxy, heterocyclicC2-10 alkenyl, (CR8R8)q NR4R5, (CR8R8)qC(O)NR4R5, C2-10 alkenyl C(O)NR4R5, (CR8R8)q C(O)NR4R10, S(O)3R8, (CR8R8)q C(O)R11, C2-10 alkenyl C(O)R11, C2-10alkenyl C(O)OR11, (CR8R8)q C(O)OR11, (CR8R8)q OC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q C(NR4)NR4R5, (CR8R8)q NR4C(NR5)R11, (CR8R8)q NHS(O)tR13, (CR8R8)q S(O)tNR4R5, or two R1 moieties together may form Oxe2x80x94(CH2)sO or a 5 to 6 membered saturated or unsaturated ring, and wherein the alkyl, aryl, arylalkyl, heteroaryl, heterocyclic moieties may be optionally substituted;
R4 and R5 are independently hydrogen, optionally substituted C1-4alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C1-4alkyl, heterocyclic, heterocyclicC1-4alkyl, or R4 and R5 together with the nitrogen to which they are attached form a 5 to 7 member ring which may optionally comprise an additional heteroatom selected from O, N and S;
R6 and R7 are independently hydrogen, or a C1-4 alkyl, heteroaryl, aryl, aklyl aryl, alkyl C1-4heteroalkyl, which may all be optionally substituted or R6 and R7 together with the nitrogen to which they are attached form a 5 to 7 member ring which ring may optionally contain an additional heteroatom is selected from oxygen, nitrogen or sulfur, and which ring may be optionally substituted;
Y is hydrogen, halogen, nitro, cyano, halosubstituted C1-10 alkyl, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxy, halosubstituted C1-10 alkoxy, azide, (CR8R8)qS(O)tRa, (CR8R8)ORa, hydroxy, hydroxy substituted C1-4alkyl, aryl; aryl C1-4 alkyl, aryloxy, arylC1-4alkyloxy, arylC2-10 alkenyl, heteroaryl, heteroarylalkyl, heteroaryl C1-4 alkyloxy, heteroaryl C2-10 alkenyl, heterocyclic, heterocyclic C1-4alkyl, heterocyclicC2-10 alkenyl, (CR8R8)qNR4R5, C2-10 alkenyl C(O)NR4R5, (CR8R8)qC(O)NR4R5, (CR8R8)q C(O)NR4R10, S(O )3R8, (CR8R8)qC(O)R11, C2-10alkenylC(O)R11, (CR8R8)qC(O)OR11, C2-10alkenylC(O)OR11, (CR8R8)qOC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q NHS(O)tR13, (CR8R8)q S(O)tNR4R5, (CR8R8)qC(NR4)NR4R5, (CR8R8)q NR4C(NR5)R11, or two Y moieties together may form Oxe2x80x94(CH2)sxe2x80x94O or a 5 to 6 membered saturated or unsaturated ring, and wherein the alkyl, aryl, arylalkyl, heteroaryl, heteroaryl alkyl, heterocyclic, heterocyclicalkyl groups may be optionally substituted;
R8 is hydrogen or C1-4 alkyl;
R9 is hydrogen or a C1-4alkyl;
R10 is C1-10 alkyl C(O )2R8;
R11 is hydrogen, optionally substituted C1-4 alkyl, optionally substituted aryl, optionally substituted aryl C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroarylC1-4alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclicC1-4alkyl;
R13 is suitably C1-4 alkyl, aryl, aryl C1-4alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclic, or heterocyclicC1-4alkyl; or a pharmaceutically acceptable salt thereof.

Hydroxy diphenyl urea sulfonamides as IL-8 receptor antagonists