Thin film resonators are deployed in the port ducts of speakers, musical instruments, microphones, and other devices having an important auditory component, to reduce distortion and/or improve other sound qualities. Preferred resonators have a resonator sheet with a first air cavity, and a passageway in an edge of the resonator sheet that opens to the air cavity. The cavity is further defined by a cover sheet, and preferably also a base sheet. The sheets are preferably bonded together by an adhesive. Resonators can be deployed rolled up inside a duct, slightly curved, or laying substantially flat on a surface over which air is flowing. Resonators can be deployed during and/or post manufacturing. Cavities are preferably elliptically shaped, and deployed as substantially mirror image pairs. Openings to the cavities can be positioned on one or more edges of the resonators.

The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
My previous application, Ser. No. 62/548,343, described use of wavy riblets and other surface features within the port of a speaker enclosure, microphone, or musical instrument to reduce turbulence of the air flow within the boundary layer between the mean flow and the surface of the port.
There are, however, additional improvements that can be made to sound devices, using Helmholtz-like resonators. For example, "Separation Control by Flow-Induced Oscillations of a Resonator", Urzynicok, Frank, U. of Berlin, 2003, describes use of paired Helmholtz-like resonators. Additional work was described in "PIV Application to Fluid Dynamics of Bass Reflex Ports, Massimiliano, Rossi et al, Dept of Mechanics, U. Politecnca delle Marche, pages 259-270, Springer Publ, 2008. Yet other work was described in "Numerical study of the aerodynamics of sound sources in a bass-reflex port", Garcia-Alcaide, V. M. et al, Engineering Applications of Computational Fluid Mathematics, 11:1, 210-224, 2017.
The priority application, the '343 application, and all publications referenced herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Despite all the work that has been done in this field, there is still a need for systems and methods that reduce distortion and/or improve other sound qualities of speakers, musical instruments, microphones and other devices having an important auditory component.


A node may include a receiver configured to receive signals transmitted from a gateway and a logic device coupled to the receiver. The node may also include a memory configured to store label information identifying a data packet stored in the node. The logic device may be configured to receive a message from the gateway, where the message includes label information, and access the memory to identify a data packet based on the label information included in the message. The node may also include a transmitter configured to transmit the data packet to the gateway over a channel shared with a number of other nodes.

1. Field of the Invention
The invention relates generally to data communications and, more particularly, to transmitting data over a shared channel.
2. Description of Related Art
Data communications systems often include a number of nodes that transmit data to a destination over a shared channel. Since there may be a large number of nodes in such systems, multiple nodes often transmit data at the same time. As a result, data collisions involving simultaneous transmissions over the shared channel often occur.
When a data collision involving a number of transmitting nodes occurs, the destination device is unable to determine what each node actually transmitted. For example, the destination device may be unable to accurately decode the transmissions from the multiple nodes. In conventional systems, each node may re-send its data one or more times until the data transmission from each node is correctly received at the destination device and an acknowledgement is sent from the destination device to each node that transmitted data. One problem with such conventional systems is that the data throughput is reduced since no agent limits how nodes access the network, resulting in more collisions and subsequent re-transmissions. That is, transmitting data from a node to a destination device, waiting for an acknowledgement from the destination device and then having to re-send the data one or more times is inefficient and results in low data throughput.
In other conventional systems used to resolve data collisions, data packets may be assigned either a high or low priority after a collision occurs. The high priority packets may then be re-sent to the destination. If a collision occurs on this re-transmission or any subsequent re-transmission, the colliding packets may be subdivided again into high and low priority packets until only a single packet is being transmitted. Once high priority packets from a collision are correctly received, the process may be repeated for low priority packets.
One problem with this conventional type of rigid collision resolution system, in which a subset of colliding packets must be received successfully before any others are sent, is apparent in systems with propagation delay. For example, the destination device must wait for information to be received at the destination device regarding past information request(s) before a subsequent request for information is sent to the nodes. As a result of this waiting, channel utilization is decreased and data throughput is reduced when collisions are resolved in this manner.

Systems and methods for facilitating communications over a shared channel


A non-transitory computer-readable recording medium stores a learning program that causes a computer to execute a process including: extracting, from a plurality of data groups, a plurality of first data groups having an order; generating, for each data element corresponding to each of the first data groups, an ordered data matrix in which data elements having same order have value corresponding to relationship among the data elements and data elements having different orders have values corresponding to the different orders; and obtaining input tensor data by performing tensor decomposition with the ordered data matrix, inputting the input tensor data to a neural network at time of performing deep machine learning, performing deep machine learning of the neural network, and learning about method for the tensor decomposition.

In recent years, it has been proposed to apply machine learning in abnormality detection. For example, in the case of performing abnormality detection using a plurality of sensors, it has been proposed to learn about the relationship between the individual value of each sensor and the abnormality using a neural network, and to perform abnormality detection on a sensor-by-sensor basis. Moreover, a graph structure learning technology is known that enables deep machine learning of data of a graph structure (hereinafter, one configuration of the device for performing such graph structure learning is called a "Deep Tensor").
[Patent Literature 1] Japanese Laid-open Patent Publication No. 2014-059754
[Patent Literature 2] Japanese Laid-open Patent Publication No. 2017-068608
[Patent Literature 3] Japanese Laid-open Patent Publication No. 2015-088188
[Patent Literature 4] Japanese Laid-open Patent Publication No. 2016-162437
[Non-patent Literature 1] "Deep Tensor: Eliciting New Insights from Graph Data that Express Relationships between People and Things", written by Koji Maruhashi, Fujitsu Sci. Tech. J., Vol. 53, No. 5, pp. 26-31 (September 2017)
In a Deep Tensor, as a result of using the data of a graph structure, abnormality detection can be performed not only based on the relationship between the individual value of each of a plurality of sensors and the abnormality but also based on the relationship among a plurality of sensors. For example, a coefficient of correlation is calculated using the observation value of each set of sensor information in a predetermined duration, and a graph structure that is formed by connecting the sensors having the correlation equal to or higher than a certain level is input. As a result, it becomes possible to learn a malfunction detection rule, such as "malfunctioning occurs unless there is a strong correlation between sensors A and B".
However, in a Deep Tensor, since the input data is processed as a graph, there is arbitrariness in the node sequence. Hence, it is not possible to handle sequence information such as the anteroposterior relationship of time as it is. For example, regarding a detection rule such as "in a device having a strong correlation between the sensors A and B in the normal state, malfunctioning occurs when that relationship is lost" (if a strong correlation between the sensors A and B is not present even during the normal state, then malfunctioning is not determined to have occurred); unless a measure such as providing a separate feature quantity is taken, it is not possible to perform the learning in a correct manner. As a result, for example, regarding the phenomenon in which the state of not having a correlation between the sensors A and B changes to the state in which there is a strong correlation; there are times when malfunctioning is determined to have occurred regardless of the fact that the anteroposterior relationship of time is reversed. That is, even if the data of a plurality of sensors is input as it is to a Deep Tensor, it becomes difficult to learn about the relationship in which the ordering is called into question.

Computer-readable recording medium, learning method, and learning device


A toy vehicle racing system is disclosed. The toy vehicle racing system comprises a track set including a movable mechanism and a toy vehicle configured to travel along the track set and interact with the movable mechanism. The toy vehicle racing system also includes a remote control in wireless communication with the track set. The remote control is configured to transmit instructions to the track set to move the movable mechanism and also to receive information from the track set regarding the track set and/or toy vehicle.

Children of all ages enjoy watching and racing toy vehicles on track sets. Typically, such toy vehicles have electric motors or external launchers that propel them continuously along the track set. To provide greater play value and enjoyment, the track sets often have different raceway configurations and include various stunt features such as curves, loops, and ramps. Other ways of interacting with the toy vehicles being raced, such as controlling the toy vehicles remotely, provide additional fun and excitement to the child.
However, controlling toy vehicles along a track set at high speeds may be too demanding and difficult for inexperienced users or younger children. Thus, there is a need for a simple yet engaging system for interactively racing toy vehicles. There is also a desire for a toy vehicle racing system that provides augmented reality (AR) features related to the track set and/or toy vehicles for enhanced entertainment and enriched sensory experiences while racing the toy vehicles.

Remote-controlled toy vehicle racing system


A hydraulic brake booster for use in a brake system having a housing with a power piston located in a first bore and a control valve located in a second bore. An input member is connected to the power piston and linked to the control valve by a lever arrangement. The input member is characterized by a cylindrical body with a shaft attached thereto. A bracket with a radial opening is carried by the shaft and urged toward a head on the shaft by a spring. The lever arrangement is characterized by a first lever with a first end pivotally secured in the housing by a first pin and a second end located in the radial opening of the bracket and a second lever pivotally secured at a fulcrum on the first lever by a second pin extending through the first and second levers. A first input force applied to the cylindrical body is transmitted through the spring into the bracket and communicated through the fulcrum point to bring a first end of the second lever into engagement with the control valve and a second end of the second lever into engagement with the power piston. The first input force as applied to the bracket causes the end of the first lever to pivot about the first pin and transmit an actuation force through the fulcrum into the said second pin to move said first end and activate said control valve to meter pressurized fluid into the working chamber to develop a hydraulic force for effecting a brake application. The lever arrangement ratio defined by a first length between the first pin and the second end on the first lever and a second length between the first pin and the second end of the second lever such that axial movement of the cylindrical body and the power piston is defined by this ratio and as a result a hydraulic force produced by the metered pressurized fluid proportional to a manual input force.

This invention relates to an input member and lever arrangement for use in a brake booster having several modes of actuation including a manual mode, a power assist mode, a combined power assist and manual mode and a traction mode in the development of an output force corresponding to a desired brake application.
In hydraulic brake boosters of a type disclosed in U.S. Pat. Nos. 4,281,585; 4,539,892; 4,625,515; and U.S. application Ser. No. 09/894,106 filed Jun. 28,2001, a control valve is located in a first bore and a power piston is located in a second bore of a housing. A lever arrangement is connected to the power piston and the control valve. An input force applied to a brake pedal by an operator acts on the lever arrangement. The lever arrangement pivots on the power piston and communicates an actuation force that moves the control valve to regulate the flow of pressurize fluid from a source to an operational chamber. The regulated pressurized fluid supplied to the operational chamber acts on the power piston to develop an operational force that pressurizes fluid in the first bore that is supplied to wheel brakes to effect a brake application. A reaction force produced by regulated pressurized fluid in the movement of the power piston is transmitted back to the brake pedal to balance the input force such that the operational force supplied to move the power piston in the first bore is a linear function of the input force applied to the brake pedal.
Additional features such as traction control, dynamic operational control and anti-skid control have been added to hydraulic brake booster to provide a total brake system. However, in such brake systems the brake pedal of the hydraulic booster mirrors the movement of the power piston and as a result have not been incorporated in all vehicles. One way to hold a brake pedal stationary during such additional functions is disclosed by the structure in U.S. Pat. No. 6,203,119 wherein a control valve seat moves while the input member remains in a stationary position to meter operational pressurized fluid from a secondary source to effect a brake application.
A primary object of the present invention is to provide an input member and lever arrangement for a hydraulic brake booster in a brake system wherein the lever arrangement includes a first lever that is retained in a housing of the brake booster by a first pivot pin and joined to a second lever by a second pivot pin to communicate an operational force to a control valve whereby pressurized fluid is metered to a working chamber for the development of an operational force that is proportional to an input force applied to a brake pedal by the input member by an operator and communicated to the lever arrangement for effecting a brake application.
According to this invention, the hydraulic brake booster has a housing with a first bore therein separated from a second bore. The first bore retains the power piston while the second bore retains the control valve. The input member is connected to the power piston and linked to the control valve by a lever arrangement. The input member responds to a brake application force applied to the brake pedal by an operator by communicating a first input force to lever arrangement such that the lever arrangement moves and activates the control valve to meter pressurized fluid to a working chamber in the housing. The pressurized fluid in the working chamber acts on the power piston to develop a hydraulic force for pressurizing fluid in the first bore it is this pressurized fluid that is communicated to wheel brakes in the brake system to effect a corresponding brake application. The input member is characterized by a cylindrical body with a shaft attached thereto. The shaft has a head on a first end that is located in an axial slot bore in the power piston and a second end with threads thereon that are mated with threads in the cylindrical body. A bracket that is located on the shaft and is urged toward the head by a first spring such that a radial opening in the bracket is and remains perpendicular to the shaft. The lever arrangement is characterized by a single first lever with a first end pivotally secured to the housing by a first pin and a second end located in the radial opening of the bracket, and parallel first and second member of second lever with each member having a first end and a second end with the first pin passing through a slot in the first end. A second pin extends through the first and second levers to define a fulcrum point for the lever arrangement. A second spring is located between the power piston and the head of the shaft such that a return spring force is applied to the bracket and communicated through the fulcrum point to bring the first end of the parallel first and second members of the second lever into engagement with the control valve and the second end thereof into engagement with the power piston. The first input force is applied to the second end of the first lever through the engagement of the surface surrounding the radial opening in the bracket causing the second end to first lever to pivot about the first pin and transmit an actuation force through the fulcrum into the second lever. The actuation force acts on the second lever causing the first end of the first and second members to move and activate the control valve whereby metered pressurized fluid is communicated into the working chamber for effecting the brake application. The lever arrangement is characterized in that a first length is defined by a distance between the first pin and the second end on the first lever and a second length is defined by a distance between the first pin and the second end of the first and second members of the second lever. The ratio of the first length to the second length corresponds to a difference in axial movement of the cylindrical body and the power piston and corresponds to proportional relationship of the input force applied to the brake pedal and the hydraulic force produced in the working chamber in effecting a brake application. The lever arrangement is also responsive to a force directly applied to the first end of the first and second members of the second lever to effect a brake application under the control of a ECU to provide to independent braking of a vehicle and reduce the speed of the vehicle to a safe operating level as evaluated by input signals transmitted to the ECU relating to current operating condition of the vehicle.
An advantage of this invention resides in a brake booster having a lever arrangement that directs an input force applied to a brake pedal to actuate a control valve such that the linear movement of a power piston is proportional to an input force applied to effect a brake application.
A further advantage of this invention resides in a lever arrangement whereby a first input force corresponding to an operator brake request or a second input force corresponding to a ECU request is communicated through a lever arrangement to meter pressurized fluid that acts on a power piston to pressurize fluid that is communicated to wheel brakes in a vehicle to effect a brake application.


When there exist transmittable cells at the virtual ports communicating with the same physical port, the virtual port delay observing section (140) observes the delay times at the virtual ports, respectively for each physical port. The virtual port delay comparing section (150) compares the observed delay times. The maximum delay virtual port designating section (160) designates the virtual port having the longest delay time, as the maximum delay virtual port, from among the virtual ports corresponding to the physical port designated by the transmission physical port designating section (120). On the other hand, when there exists no transmittable cell at the virtual ports communicating with the same physical port, the first-out virtual port observing section (130) designates the virtual port at which the transmittable cell develops first, as the maximum delay virtual port without comparing the delay times. When the maximum delay virtual port designating section (160) designates one physical port, it is necessary to wait until the load data of all the physical ports have been decided. However, before that, since the virtual port having the longest delay time is designated for each physical port, it is possible to start the processing for discriminating the maximum delay virtual port beginning from an early time.

1. Field of the Invention
The present invention relates to a method and an apparatus for controlling the flow rate of cells at one or plural physical ports in packet communications, in particular in asynchronous transfer mode (referred to as ATM, hereinafter) communication system.
2. Description of the Prior Art
In a packet communication system, in particular in an ATM communication system, communications are executed in transfer unit called "cell". In this case, shaping control for controlling cell flow rate is executed in order to suppress the fluctuations of the flow rate of communications. Here, the shaping control is one of usage parameter controls. In this control method, cell flow rate is always monitored at each virtual transmission port, and whenever the flow rate exceeds a predetermined value, the cell transmission is delayed for shaping so that the cell flow rate does not exceed the predetermined value.
A prior art shaping control method will be explained hereinbelow with reference to FIG. 9. In FIG. 9, there are a plurality of virtual ports 231 to 232, 233 to 234, . . . , 235 to 236 in correspondence to a plurality of physical ports 201, 202, . . . , 203, respectively. The virtual ports 231 to 232, 233 to 234, . . . , 235 to 236 communicate with the physical ports 201, 202, . . . , 203, respectively under control of a shaper 220 and a plurality of schedulers 211, 212, . . . , 213.
When a cell is inputted to a queue of a buffer provided for each of the virtual ports 231 to 232, the intervals at which the cells are transmitted to the shaper 220 are managed so as to be smoothed. In addition, the schedulers 211 to 213 each provided for each of the physical ports 201 to 203 schedule both the cell of the queue shaped by the shaper 220 and the cell of the queue not shaped by the shaper 220. In general, the scheduling is executed in such a way that the queue to be shaped has a priority.
Further, a single scheduler 241 is provided as a whole, to select one physical port which transmits the cell, for each cell period, from among all the physical ports 201 to 203. This is because the physical port which can transmit cell for each cell period is only one. When there exist a cell shaped by the shaper 220, the scheduler 241 schedules the cell transmission in such a way that the corresponding cell can be transmitted to the selected physical port.
The above-mentioned prior art shaper 220 smooths the cell transmission intervals in accordance with the following procedure: The shaper 220 monitors the time elapsed after the preceding cell is transmitted for each of the virtual ports 231 to 236. For instance, as shown in FIG. 10, when the preceding cell is transmitted at a time point t1, at a time point t2 at which the predetermined time T1 has elapsed for shaping after the time point t1, the present cell can be transmitted. Therefore, a time elapsed after this time point t2 is a transmission delay time T2.
Further, when the cell transmission from the physical ports 201 to 203 to the rear stage apparatus stagnates, as when the cell transmission exceeds a predetermined transfer flow rate at the physical ports 201 to 203, there exists such a case that the cell transmission is still kept restricted even after the predetermined time T1 has elapsed. In this case, the shaper 220 monitors the transmission delay time T2 at each of the virtual ports 231 to 236, and when the load at the physical port is reduced below an allowable limit, the cell transmission is executed again, beginning from the maximum delay virtual port at which the transmission delay time T2 is maximum.
In the above-mentioned prior art flow rate control method, however, there exist the following problems: Since the maximum delay virtual ports must be discriminated, it is necessary to monitor and further compare all the cell transmission delay times T2 for each of all the virtual ports 231 to 236. Therefore, when the number of the virtual ports increases, the comparison processing of the transmission delay times is complicated more and more.
In addition, the processing of comparing the transmission delay times T2 must be executed within one cell period, after the load data (indicative of whether the load exceeds an allowable limit or not) have been decided at all the physical ports 201 to 203. In other words, the processing of discriminating the maximum delay virtual port must be perfectly completed, after the preceding cell has been transmitted at the time point t1, but between a time point when all the load data at all the physical ports 201 to 203 have been decided and a time point when the present cell must be transmitted. In general, however, it takes a relatively long time to decide the load data at all the physical ports. Therefore, the time interval between when all the load data are decided and when the present cell is transmitted is relatively short, so that it has been difficult to complete the discrimination processing of the maximum delay virtual port.
Further, in the case where there exist no transmittable cells stored in queues in the virtual ports 231 to 236 communicating with a physical port, there exists such a case that queues storing transmittable cells develop concentratively in a time shorter than a single cell period. Further, there exists such the case where the delay virtual ports develop concentratively within the same cell period at a plurality of the physical ports. In these cases, it is substantially impossible to discriminate the virtual port through which the cell is to be transmitted within a short time.
To overcome these problems, in the prior art flow rate control method, a plurality of buffer stages are provided at the front stage of the physical ports, to delay the timing at which the cell is transmitted to such an extent as to correspond to the number of the buffer stages. In this method, it is possible to obtain a time interval margin from when the load data are decided at all the physical ports to when the virtual port used to transmit the cell is discriminated. In this method, however, since the buffers are provided at the front stage of the physical ports, the cell transmission time itself is delayed, with the result that there exists a problem in that the throughput is lowered.
Further, in the case when a plurality of the physical ports are used and further demuitiplex communications are executed, the shaping must be executed at a plurality of physical ports, so that it is necessary to discriminate the maximum delay virtual port from among all the virtual ports. In this case, however, in the case where there exist a plurality of physical ports, the load data exist for each physical port and in addition the load data vary with the lapse of time. In the shaping at the physical ports, it is necessary to delay the transmission of the cell to the physical port having a large load and to transmit the cell to the physical port having no load. Therefore, it is necessary to select the maximum delay virtual port from among the virtual ports communicating with the physical port having no load. In this case, however, since the sequence of the queues at the virtual ports is not decided until the load data are decided, it is impossible to previously discriminate the maximum delay virtual port.

Method and apparatus for controlling physical port flow rate in packet communications


A light scanning unit includes a light source unit to emit a plurality of light beams, a light deflector to deflect the plurality of light beams emitted from the light source unit in a sub-scanning direction, an incident optical system to allow the plurality of light beams emitted from the light source unit to be incident on different reflection surfaces of the light deflector, and an imaging optical system that allows a plurality of light beams that are deflected by the light deflector, to be imaged on different scanning surfaces, wherein the incident optical system includes at least one incident light path changing member that folds light paths of the plurality of light beams between the light source unit and the light deflector.

1. Field of the Invention
The present general inventive concepts relates to a light scanning unit and electrophotographic image forming apparatuses using the light scanning unit, and more particularly, to a light scanning unit simultaneously scanning a plurality of light beams and electrophotographic image forming apparatuses using the light scanning unit.
2. Description of the Related Art
Light scanning units scan a laser beam onto a photoconductor to form an electrostatic latent image in an electrophotographic image forming apparatus such as a laser printer. The light scanning units include a light deflector that deflects a light beam emitted from a light source and scans the same onto a photoconductor, and an imaging optical system that is placed between the light deflector and the photoconductor and forms the deflected light beam as an image on the photo conductor.
In an electrophotographic image forming apparatus, when a light scanning unit scans a light beam onto a photoconductor such as a photosensitive drum, an electrostatic latent image is formed on the photoconductor by main-scanning by the light scanning unit and sub-scanning by movement of the photoconductor. The electrostatic latent image is developed to form a development image by using a development agent such as a toner, and the development image is transferred onto a printing medium.
Recently, technologies for reducing the size of an image forming apparatus such as a color laser printer and reducing the manufacturing costs thereof are being developed, and one such development tendency involves developing techniques for reducing the size of the light scanning unit and the manufacturing costs thereof.

Light scanning unit and electrophotographic image forming apparatus using the same


A method of controlling access to playable content. The disclosed method includes receiving a request to access playable content having a plurality of associated access criteria, receiving a plurality of credentials, performing a matching process to compare the credentials to the access criteria, and allowing access to the playable content is permitted if the access criteria are met by a logical combination of the plurality of credentials.

A great deal of information in the form of multimedia files, hereinafter referred to as "content" is available over the Internet. Such content may, for example, comprise images, audio or video files, HTML pages, text, or any other appropriate form of information as desired. The content may comprise streamed material, such as streamed audio or video information.
It is often desirable to control access to content, such that, for example, the content cannot be accessed by people younger than a particular age, or in a particular geographical location or otherwise as desired. It is known to provide password-protected Internet sites, where a password must be supplied by the user to access restricted pages of the site. However, in this situation the user must first provide personal details to the Internet site provider in order to be issued with a password, with corresponding privacy concerns. To prevent children obtaining access to websites with adult content, age verification schemes are known whereby a user supplies information, such as credit card information and other personal information if requested, to a third party credential provider. The third party credential provider verifies the information, in particular the age of the user, and issues a password or credential to enable the user to access those websites which recognise the password supplied by the third party. A similar system of providing a credential to authenticate a user's identity to allow the user to access a client system without reference by the client system to the credential provider is known, for example the Kerberos authentication scheme. The credential effectively acts as a password to a site and in the case of commercial or adult verification credentials, the user may be reported back to the third part credential provider for billing purposes.
An aim of the invention is to provide a new or improved method of controlling access to playable content.

Hewlett-Packard Development Company, L.P.


A snap-together universal-jointed electrical device comprised of an essentially spherical plug and socket that can rotate and swivel with respect to each other, the plug and/or socket portions being comprised of elastic material that resiliently deforms to permit the plug to be pushed and snapped into, and pulled and snapped out of, the socket, the plug being connected to a bulb with filament and means provided for linking together multiple socket/plug units.

1. Field of the Invention
This invention relates to electrical devices and, more particularly, to devices having universally jointed electrical connections of the snap-apart type.
2. Description of the Prior Art
The prior art reveals several approaches to electrical swivel connectors and, more particularly, to universally-jointed electrical connection devices. Some of the prior art relating to universally-jointed electrical connectors only provides for one electric path through the joint. Such is the case with Berger, U.S. Pat. No. 3,012,798; Cass, U.S. Pat. No. 2,673,965; and Blasdell, U.S. Pat. No. 2,564,520. It is an object of the present invention to provide a universally-jointed electrical connection device that will conduct electricity on up to three separate paths.
Some of the prior art of universally-jointed electrical connection devices, in order to make provision for more than one path of electricity specifies the use of more than one spherical plug and socket joint. This is the case with Morris, U.S. Pat. No. 1,953,864, and Soleau, U.S. Pat. No. 4,746,297. It is an object of the present invention to provide for up to three paths of electricity through one joint utilizing one spherical plug located in one spherical socket.
Some of the prior art of universally connected electrical connectors provides for a limitation of the rotation of the plug within the socket such that the permitted rotation is less than 360.degree.. Such is the case with Jines, U.S. Pat. No. 3,116,940, and Brown, U.S. Pat. No. 3,328,741. It is the intent of the present invention to provide for unlimited rotation of the plug within the socket, as well as for significant swivel.
The prior art directed to universally-jointed, fully rotating electrical connector devices that provides for conducting electricity on at least two paths through a single joint, has been found to provide for the use of a plurality of spherical plug elements and/or spherical socket elements within the one joint. This prior art is illustrated by Goldrick, U.S. Pat. No. 1,650,014; Jones, U.S. Pat. No. 1,957,714; Sheward, U.S. Pat. No. 2,007,617; Rouault, U.S. Pat. No. 2,519,933; and Christner, U.S. Pat. No. 2,652,546. In Goldrick, in particular in FIG. 5, it can be seen that the socket is comprised of two spherical shell elements that make contact with two spherical portions of the plug. Likewise, Jones' socket, as illustrated in FIG. 1, is comprised of two spherical shell elements that make contact with two spherical portions of Jones' plug. Also in Sheward, FIG. 2, it can be seen that Sheward's plug is comprised of an interior spherical portion and an exterior hemispherical portion. Sheward's socket offers two concentric spherical portions that relate to the spherical portions of the plug. In Rouault, the spherical plug clearly offers two concentric spherical portions that relate to spherical surfaces of the socket. In Christner, although the socket is comprised of one spherical portion, the plug offers an interior spherical element and an exterior spherical element. It is an object of the present invention to disclose a universally-jointed, fully rotatable electrical connecting device comprised of only one substantially spherical plug and one substantially spherical socket where different portions of those spherical surfaces are utilized to conduct electricity on up to three paths. Such a device achieves a simplicity of design and makes possible the further snap-apart, snap-together feature.
As a further feature, the present invention teaches a "snap-apart and snap-together" electrical connection device. None of the prior art reviewed teaches such a means of connection. In the prior art reviewed, the plug is either designed to be permanently situated within the socket or significant mechanical labor is involved in attaching the plug to the socket and detaching the same. The present invention teaches electrical connectors in which the plug can be easily connected to and disconnected from the socket, substantially independently of the plug's orientation, by a snap-together and snap-apart means, the connectors further providing the features that the plug can rotate fully and freely within the socket and swivel to a significant degree and the connection carries electricity on up to three paths.
The snap-together universally-jointed electrical connection device taught by the present invention is applicable to a wide array of devices, providing a variety of advantages for convenience and comfort. The snap-apart connection provides the advantage of quick and easy connect and disconnect, substantially independent of the orientation of the plug. The snap-apart, snap-together means for connection enjoys a positive mechanical advantage against accidental or partial dislocation. The universal joint in which the plug can rotate fully within the socket and swivel to a significant degree is especially useful in operation with electric service cords. Such a universal joint prevents the cord from becoming twisted and knotted and permits it to diverge at a sharp angle from the socket without undergoing a constant weakening bend.
A further advantage of the snap-apart universally-jointed electrical connector is that the adjustable plug could be directly associated with a light bulb. The direction of light could be adjusted by swiveling and rotating the plug while the snap in and out feature would facilitate the replacement of the bulb. Bulbs could be designed associated not only with plugs, but also with a socket to link into a further bulb. Alternately, multiple socket units could be devised permitting the attachment of a plug and bulb at a plurality of locations. Toys, games, or models could profit from this snap-apart universal connection. The invention makes possible the easy snap-apart and snap-together of a composite of units that can rotate and swivel with respect to each other while at the same time conducting electricity therethrough. The path of the connection of the units to form the composite could be illuminated. Alternately, motorized movement of the parts could be effected.

Snap-apart universal jointed electrical device


Enabling automated provisioning on a data processing network includes providing the network with access to an automated provisioning controller. The controller enables a user to specify resource allocation priorities and uses the user-specified priorities, in conjunction with a resource stabilization policy, to resolve conflicting resource requests. The resource allocation priorities include priorities for demand-based resource requests and maintenance-based resource requests. The stabilization policy includes a policy for constraining allocation of a resource based on forecasted demand and a policy for constraining allocation of a resource based on a scheduled maintenance task.

1. Field of the Present Invention
The present invention is in the field of data processing networks and, more particularly, data processing networks in which resources from a pool of available resources are dynamically allocated as needed.
2. History of Related Art
In the field of information technology (IT), provisioning is an increasingly important concept. Provisioning, as the term is used in this disclosure, refers to functionality that enables an environment such as a data center to allocate IT resources as they are needed. In a fully automated provisioning implementation, a data center may respond to variations in load by allocating and deallocating servers to a particular server cluster.
A web server cluster, for example, may require more servers during peak demand periods (such as when consumers are likely to be accessing the cluster) while a database server cluster may be configured to execute the bulk of its tasks at other times. In this scenario, provisioning may include allocating servers from a pool of available server resources to the web server cluster during normal business hours, deallocating some servers from the web server cluster after hours, and allocating server resources to the database server cluster during off hours.
This simple example illustrates a primary benefit of provisioning, namely, dynamic allocation of resources to conserve the amount of total resources required. Instead of configuring the database server cluster with sufficient server resources to handle the peak database workload and the web server cluster with sufficient server resources to handle the peak web server workload, the total resources required are reduced by using server capacity more efficiently. In addition, automated provisioning reduces the amount of time and human effort required to configure resources for a particular task and thereby reduces management overhead.
While automated data provisioning is a theoretically desirable goal, customers are justifiably wary of automated provisioning implementations. Regardless of the level of automation, customers tend to desire a mechanism by which they can monitor or control the manner in which the automation is deployed. It would be desirable, therefore, to implement an automated provisioning environment and user interface that enabled an administrator to monitor and control automated provisioning activity.
Provisioning as it has generally been implemented to date, is devoted more or less exclusively to core provisioning tasks, namely, allocation of resources in response to fluctuating demand or loading. IT administrators recognize, however, that other activities such as maintenance tasks and reservation requests (for developmental testing as an example), must be accommodated and that these activities have generally been handled through ad hoc and manual resource re-allocation. It would be desirable, therefore, if the implemented automated provisioning solution encompassed not only the traditional provisioning tasks, but also resource-consuming activity that has not been previously considered together with core resource provisioning activity.
In addition, a concern with automated provisioning implementations involves the concept of stabilization. Stabilization, as it suggests, refers to the stability of a particular resource allocation state. Illustrating with a simple example, stabilization concerns would advise against allocating a currently available server to a particular customer application when it is known that the server is scheduled for mandatory maintenance. Similarly, stabilization policies might prevent re-allocation of a resource from a first application to a second application when it can be predicted from historical data that the first application will soon experience a demand surge. In the absence of at least some stabilization policies, automated provisioning may result in provision "thrashing" in which resources are being allocated and re-allocated frequently and the provisioning overhead associated with each re-allocation tends to mitigate, if not entirely negate, any benefit provided. Whereas, conventional automated provisioning systems do not adequately recognize or accommodate provisioning policies, it would be desirable to implement an automated provision system that fully embraced provisioning concerns and enabled the integration of provisioning policies into the provisioning domain.

This patent is subject to a terminal disclaimer.

Enabling user control over automated provisioning environment

International Business Machines Corporation


The invention provides a bone screw for use in an implant assembly having a member including a hole through which the screw extends. The member preferably includes a socket in an anchor that receives a rounded bottom portion of the screw head in order to form a ball and socket connection. The screw has a necked area below the rounded bottom portion which projects through the hole and below that on the longitudinal axis of the screw. The screw includes a knurled collar that is sized so as to allow the anchor to be inserted onto the screw but which subsequently restrains the anchor from falling downward onto the threaded area of the screw.

The invention relates generally to screws for use in a spinal implant system. The particular screw is a fixation screw that can be locked at a variable angle in a stabilizer anchor assembly. The screw includes restraining means that maintains the level of the anchor relative to the longitudinal axis of the screw.
Spinal implant systems have been developed for use in addressing certain spinal problems. These systems generally include an elongate stabilizer which is a rod, plate, or cable that is secured to a bone in a stabilizer anchor by means of a fixation member, in this case a screw. In some of these systems, the stabilizer anchor is a separate component from the screw in order to provide for a variable angle of the stabilizer fixation means relative to the angle of fixation. Often for such a system, the components are assembled prior to surgery. The present invention has application for such a system.
These implants have been developed over time to constitute very elegant constructs. The function dictates that the components are relatively easy to assemble and to manipulate and to surgically implant. The design requires minimization of size and invasion into the biological environment, while meeting the structural requirements to achieve the desired function of spinal alignment and stabilization depending on the medical indication. In addition, the construct has to be flexible in its use to account for differences in individuals, or for problems that may arise during the course of surgery. Spine surgery is by its nature intense and long surgery which requires great precision. It is critical that the implements that are developed for use by the surgeon are, given the design considerations, as efficient and easy to use as possible in order to facilitate the surgery.
In a preferred embodiment, the variable angle anchor of the present system can include a concave socket having a central opening through which the screw extends and which captures the convex head of the screw, and transverse to that opening, the anchor includes a channel for the stabilizer which resides above the screw head. Thus, the anchor and the head form a limited ball and socket joint to allow the anchor to have a variable angle on the screw. There can be means to lock the angle at a desired angle. Finally, the system can include means to secure the stabilizer in the anchor. In one particularly elegant design, the securing means can comprise compression means which locks the stabilizer in the anchor and which also locks the position of the anchor relative to the screw. The compression means illustrated with the assembly of the present invention is a nut which is screwed downwardly on external threads of the anchor. When screwed in place, the nut bears down on the stabilizer which in turn compresses the screw head in the anchor to form a locking interface and to lock the angular and radial position of the screw in the anchor. The bottom of the screw includes a machined, high friction surface which improves locking of the screw head in the socket. Of course, it should be understood that other locking or compression means could be used, for example, a locking disc, or a set screw, or other means which use internal threads or flanges on the anchor member.
The particular screw of the present invention is assembled into a cooperation with the stabilizer anchor to permit a variable angle of the anchor with respect to the screw which can subsequently be locked into position at a desired angle as previously discussed. However, the screw presents an advantage over the prior art insofar as the screw includes a restraining means which permits relatively easy assembly of the screw and anchor, but which inhibits the anchor from dropping on the screw to a position which may be difficult for the surgeon to access. The present invention also presents an advantage to variable angle spinal systems which maintain the freedom of movement between the anchor and the screw.
In a preferred embodiment, the restraining means is an annular collar having diamond point knurls which are sized to permit insertion of the screw and collar through the central opening of the anchor member, but where the collar will act to inhibit the anchor from slipping downward on the screw. The anchor actually floats on the screw and moves fairly freely, except the downward play is limited by the interaction of the annular shoulder of the central opening of the anchor and the restraining collar. Preferably at least a relevant portion of the screw head forms a ball and socket type interaction with the anchor opening. Thus, the screw head may include an generally outwardly rounded surface that forms an interface with an inwardly rounded surface of the anchor screw opening. In addition, there is preferably a mating interface between the screw and the anchor in order to ensure a locking cooperation between these two components. This mating interface may for example, be a high friction surface that may be formed as a result of the nature of the mating contoured surfaces, i.e., one surface may be slightly under specification, or alternatively, one or both of the mating surfaces may include a surface which has been worked to render it high friction, such as for example as is the case of the mating diamond point knurls that are shown. Other means of forming this mating locking interface are also contemplated, and include, for example, the use of a locking or pressure disc to effectively increase the frictional fit of the screw head in the socket of the anchor opening.
In the most preferred embodiment, the collar forms an annular barrier below a smooth inwardly rounding portion of the screw head which forms a neck between the screw head and the screw threads. The collar includes two rows of knurls which have a depth of the magnitude of about 0.01 inch and where the collar has a point to point diameter that is approximately the same magnitude larger than the opening in the anchor (or plate) through which it is inserted. This allows the knurls to asymmetrically deform during insertion so as to permit insertion but to inhibit the anchor from slipping below the collar. In the absence of the restraining means, it might be possible for the anchor to slip downward on the screw to a position where it is difficult for the surgeon to reach. This situation could arise for example, where a vertebrae is mis-aligned in the anterior direction, and the screw might not be screwed fully into position. In this instance, the bone surface doesn""t act to hold the anchor close to the head of the screw.
It is an object of the invention to provide a bone screw that can be used with a stabilizer including but not limited to a rod or plate or other construct component that is secured to the bone by the screw where the screw includes a restraining collar below the head of the screw in a necked area upward of the screw threads.
It is a further object of the invention to provide a spinal screw that is used in conjunction with a stabilizer anchor where the screw is inserted through an opening in the anchor along the longitudinal axis of the screw, where the screw includes means to inhibit the anchor from slipping longitudinally downward along the screw. In a preferred embodiment, the means to inhibit the downward motion comprises a collar having deformable projections that are collectively close to or slightly larger than the size of the opening in the anchor for the screw to be inserted through. For example, these projections can be diamond point knurls that allow for the screw to be inserted through the opening to the necked portion of the screw, but which maintain the anchor above the collar notwithstanding the fact that the knurls were deformed slightly during assembly with the anchor. Of course, other deformable configurations, such as spiral ridges or splines, or threads could also be used with the collar as the restraining means. Alternately, an asymmetrical opening or key could be used with a corresponding keyway on the collar (or anchor respectively.)

Variable locking spinal screw having a knurled collar


An electronic device and method for fabricating the same are disclosed herein. In one example the electronic device includes a substrate, a first die stack, and a second die stack. The first die stack includes a first functional die and a first dummy die. The first functional die is mounted to the substrate. The second stack includes a plurality of serially stacked second functional dies mounted to the substrate. The first dummy die is stacked on the first functional die. The first dummy die has a top surface that is substantially coplanar with a top surface of the second die stack. In one particular example, the first die stack includes a logic die and the second die stack includes a plurality of serially stacked memory dies.

Electronic devices, such as tablets, computers, server, in-door telecom, out-door telecom, industrial computers, high performance computing data centers, copiers, digital cameras, smart phones, control systems and automated teller machines, among others, often employ electronic components which leverage chip packages for increased functionality and higher component density. Conventional chip packages include one or more stacked components such as integrated circuit (IC) dies, through-silicon-via (TSV) interposer, and a package substrate, with the chip package itself stacked on a printed circuit board (PCB). The IC dies may include memory, logic, MEMS, RF or other IC device.
In many chip packages, providing adequate thermal management has become increasingly challenging. Failure to provide adequate cooling often results in diminished service life and even device failure. Thermal management is particularly problematic in applications where high bandwidth memory (HBM) stacks and logic die, such as field programmable gate arrays (FPGA), are integrated in a single package. In such applications, the height differential between the HBM stack and logic die may result in inefficient cooling due to excessive use of thermal interface material or overmolding to compensate for the height mismatch. Failure to adequately regulate the temperature of the chip package may also result in diminished performance, device failure or system shutdowns. Furthermore, a large height differential between the HBM stack and logic die also creates a variety of assembly and factory automation problems, which undesirably contribute to poor production yields and longer, and thus more costly, fabrication times.
Therefore, a need exists for an improved chip package for co-packaged logic and memory applications.


A communication sheet structure for transmitting electromagnetic waves, and thereby performing communication, is characterized in that the communication sheet structure includes a planar base material with a relative dielectric constant at a frequency of from 800 MHz to 10 GHz of from 1.0 to 15.0, and one side of the base material includes conductor A existing portion and non-existing portion, and the other side of the base material includes a conductor B existing over 90% or more thereof. The communication sheet structure enables communication in two dimensions, and the communication sheet structure is extremely excellent in communication performances.

In recent years, use of computer communication networks or information networks represented by the Internet, has come into wide and popular use, and has been increasing without distinction among ordinary households, enterprises, and the like. The most common use form is such that personal computers and the like are directly connected with LAN cables, or connected by way of wireless to establish a LAN (Local Area Network), which allows access from the computers in the LAN to a network such as the Internet. In such circumstances, when a LAN cable is used, the cable is routed in a house or an office, causing an obstruction to walking or an appearance problem. Whereas, when wireless LAN is used, communication is performed using radiation of electric waves, which causes security problems such as information leakage and an unauthorized access.
Under such circumstances, the fact that these problems can be solved by making communication means two-dimensional, and using a two-dimensional communication medium is shown in Patent Document 1 (JP-A-2004-7448) and Patent Document 2 (JP-A-2006-19979).
Whereas, in recent years, office security has received attention, so that information networks of an office environment have been upgraded. In a conference room or a discussion space, prevention of information leakage has become valued, creating a demand for space with high security in an office. On the other hand, a free-address office also has attracted great attention. One can hold one's access environment even upon moving, which enables control of the individual ID, and acquisition/control/display of the positional information.
In such circumstances, setting of a communication sheet structure on a top of a desk in a conference room or one's own room in an office is largely useful for construction of an office network.
Other than these, there are ideas in which RFID tags and this communication sheet structure are combined to perform inventory control and physical distribution management; and in which this communication medium is set over the entire wall surface or the entire floor surface for use as a sensor sheet.
Such ideas of use in combination with RFID tags, and use in the form with a larger area such as the wall entire surface or the floor entire surface require further enhancement of the transmission efficiency of the communication medium, and improvement of the communication performances. Further, there is a demand for a communication medium with higher durability from the viewpoint of practical utility.
On the other hand, for the foregoing uses, being handy to carry is desirable in consideration of the convenience of a constructor and a user. Particularly, the communication medium to be set over the entire wall surface or the entire floor surface increases in area as described above. Therefore, it is required to be carried or stored in the rolled form. However, with the conventionally proposed communication media, no specific proposals have not been made on this point at all. The inventors attempted to form communication media with various materials. However, they found that there were problems such as difficulty in winding this in a roll form, becoming wrinkled upon attempting to forcedly wind this in a roll form, and reduction of communication performances.
[Patent Document 1] JP-A-2004-7448
[Patent Document 2] JP-A-2006-19979


A pharmaceutical composition for dermal use, wherein the composition has a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue, and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1. The composition can also have at least one solvent component C, where component C is compounds of the general formula R3 (OCH2C(R1)H)xOR2 (I), wherein x is in the range of 2-60, R1 in each of the x units independently is H or CH3, R2 is straight chain or branched C1-20alkyl or benzoyl, and R3 is H or phenylcarbonyloxy; di-(straight or branched)-C4-10alkyl esters of C4-C8dicarboxylic acids; straight or branched C12-18-alkyl benzoates; straight or branched C2-4-alkyl esters of straight or branched C10-18-alkanoic or -alkenoic acids; propylenglycol diesters with C8-14-alkanoic acids; and branched primary C18-24alkanols.

The present invention concerns pharmaceutical compositions for dermal use which contain at least one vitamin D or vitamin D analogue and at least one corticosteroid. More specifically, the invention relates to pharmaceutical compositions containing two or more pharmacologically active compounds which have low compatibility with respect to the pH value of optimum stability, preferably, said pharmacologically active compounds are at least one vitamin D analogue and at least one corticosteroid.
In the treatment of a number of conditions using dermal application, e.g. in the art treatment of psoriasis, it is often indicated to employ a combination treatment incorporating two or even more different pharmacologically active compounds. Thus, in the treatment of e.g. psoriasis, it is common to use a combination treatment involving a steroid compound, such as a corticosteroid compound, and a vitamin D analogue such as calcipotriol, and where each of the active compounds are formulated in separate preparations.
Until now a topical pharmaceutical composition comprising a combination of a vitamin D analogue and a topical steroid has not been described. Moreover, these two types of compounds often have optimum stability values of pH that differ significantly from one another making it non-obvious to attempt to prepare a topical pharmaceutical preparation containing a steroid compound together with a vitamin D analogue. U.S. Pat. No. 5,565,462 relates to topical pharmaceutical compositions containing certain xanthine compounds, and where said compositions may additionally contain active compounds, such as steroids and vitamin D and its derivatives. However, there is no disclosure of a topical composition containing both a steroid and a vitamin D or vitamin D analogue or derivative, nor is there any description of a method of preparing such a composition.
The following example describes the difficulties encountered when the skilled person wishes to prepare a combination composition for topical use comprising both a vitamin D or a vitamin D analogue or derivative and a topical steroid: The vitamin D analogue calcipotriol, as well as other examples of vitamin D analogues, requires a pH value above 8 for maximum stability, whereas corticosteroids such as Betamethasone (9-fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione) require pH values in the range of 4-6 for maximum stability. Since the base auxiliary materials and additives traditionally used in preparing topical formulations, such as creams and/or ointments, involve having some kind of acid or alkaline nature or reaction ability, it has therefore hitherto not been possible to combine the two active compounds in one single formulation while maintaining good stability of the active compounds.
Consequently, physicians have had to resort to letting patients under this type of two-component regimen perform sequential application of two creams/ointments, each containing one of the compounds formulated at its maximum stability pH. This may lead to incompatibility of the preparations so that patients must, e.g., apply one cream/ointment in the morning and the other in the evening. Needless to say, patient compliance as well as correct administration dosage is a problem under such circumstances. Richards, H. L. et al. report in J Am Acad Dermatol 1999 October; 41(4):581-3 on a study of patients with psoriasis and their compliance with medication. They report that poor compliance with treatment advice in chronic conditions, such as psoriasis, represents a major challenge to health care professionals: Thirty-nine percent of participants reported that they did not comply with the treatment regimen recommended. The noncompliant group had a higher self-rated severity of psoriasis, were younger, and had a younger age at onset than those who were compliant. The noncompliant group reported that psoriasis had a greater impact on daily life.
It is therefore an object of the present invention to provide a pharmaceutical composition for dermal use where said composition alleviates the inconveniences of a two-component or multi-component regimen for the treatment of psoriasis and other inflammatory skin diseases including nail diseases. The provision of said composition will result in a substantial improvement in quality of life for a large population of psoriasis patients, especially the noncompliant group having a higher self-rated severity of psoriasis, being younger, and having a younger age at onset than those who are compliant.
In order to solve the above mentioned problems, the invention provides a pharmaceutical composition for dermal use, said composition comprising a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue and a second pharmacologically active component B consisting of at least one corticosteroid.
As a first pharmacologically active component A it is preferred to use a compound selected from the group consisting of seocalcitol; calcipotriol; calcitriol; tacalcitol, maxacalcitol; paricalcitol; falecalcitriol; 1xcex1, 24S-dihydroxy-vitamin D2; and 1(S),3(R)-dihydroxy-20(R)-[((3-(2-hydroxy-2-propyl)-phenyl)-methoxy)-methyl]-9,10-seco-pregna-5(Z),7(E),10(19)-triene, as well as mixtures thereof.
More preferred are vitamin D analogues selected from the group consisting of calcipotriol, calcitriol, tacalcitol, maxacalcitol, and 1(S),3(R)-dihydroxy-20(R)-[((3(2-hydroxy-2-propyl)-phenyl)-methoxy)-methyl]-9,10-seco-pregna-5(Z),7(E),10(19)-triene as well as mixtures thereof. Synthetic vitamin D analogues are more preferred in the compositions according to the invention than naturally occurring vitamin D""s or vitamin D derivatives, since the therapeutic effects of the latter may be less selective for the treatment of skin diseases, such as psoriasis.
Further non-limiting examples of vitamin D compounds constituting the first pharmacologically active component A are:
alphacalcidol;
1xcex1-hydroxy-vitamin D2;
1xcex1-hydroxy-vitamin D5;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-5-hydroxy-1-heptyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6-hydroxy-6-methyl-1-heptyl)-9,10-secopregna-5(2),7(E)-10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6-hydroxy-6-methylhept-1(E)-ene-1-yl-9,10)-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6-ethyl-6hydroxy-1-octyl)-9,10)-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(7-hydroxy-7-methyl-1-octyl)-9,10)-secopregna-5(2),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(7-hydroxy-7-methyloct-1(E)-en-1-yl-9,10)-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6xe2x80x2-methyl-1xe2x80x2-heptyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-(5xe2x80x2-hydroxy-5xe2x80x2-methyl-1xe2x80x2-hexyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4xe2x80x2-hydroxy-4xe2x80x2ethyl-1xe2x80x2-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6xe2x80x2-hydroxy-1xe2x80x2-hexyloxy-9,10-seco-pregna-5(Z),7(E),10(19 )-triene;
1(S),3(R)-Dihydroxy-20(R)-(5xe2x80x2-hydroxy-5xe2x80x2-ethyl-1xe2x80x2-heptyloxy)-9,10-seco-pregna-5(,7(E),10,19-triene;
1(S),3(R)-Dihydroxy-20(R)-(5xe2x80x2-hydroxy-5xe2x80x2-methyl-1xe2x80x2-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(5xe2x80x2-methyl-1xe2x80x2-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4xe2x80x2-hydroxy4xe2x80x2-(1 xe2x80x3-propyl)-1xe2x80x2-heptyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4xe2x80x2-hydroxy-4xe2x80x2-methyl-1xe2x80x2-pentyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3xe2x80x2-hydroxy-3xe2x80x2-methyl-1xe2x80x2-butyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-(4-hydroxy-4-methyl-1-pentyl)-9,10-secopregna-(5Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-(5-ethyl-5-hydroxy-1-hept-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-(5-ethyl-5-hydroxy-hept-1(E)-en-1-yl),9,10-secopregna-5(2),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-(5xe2x80x2-hydroxy-1xe2x80x2-methyl-hexa-1xe2x80x2(E),3xe2x80x2(E)-dien-1xe2x80x2-yl)-9,10-secopregna-5(2),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-(5xe2x80x2-ethyl-5xe2x80x2hydroxy-hepta-1xe2x80x2(E),3xe2x80x2(E)-dien-1xe2x80x2-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-(6xe2x80x2-hydroxy-hexa-1xe2x80x2(E),3xe2x80x2(E)-dien-1xe2x80x2-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-(5xe2x80x2-cyclopropyl-5xe2x80x2-hydroxy-penta-1xe2x80x2(E),3xe2x80x2(E)-dien-1xe2x80x2-yl)-9,10-secopregna-5(Z)-7(E),10,19-triene (5xe2x80x2(R) and 5xe2x80x2(S) isomers);
1(S),3(R)-Dihydroxy-20-(6xe2x80x2-hydroxy-6xe2x80x2-methyl-hepta-1xe2x80x2(E),3xe2x80x3(E)-dien-1xe2x80x2-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-(2-hydroxy-2-pentyl)-phenylmethoxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-(3hydroxy-3-propyl)-phenylmethoxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-hydroxy-4-methyl-1-pentyloxymethyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-hydroxy-4-methyl-1-pent-2-ynyloxymethyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-hydroxy-4-trifluoromethyl-5,5,5-trifluoro-1-pent-2-ynyloxymethyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-[3-(2-hydroxy-2-propyl)-phenoxymethyl]-9,10seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-hydroxy-3ethyl-1-pentylthiomethyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-hydroxy-3-ethyl-1-pentylsulphonylmethyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-((1-hydroxy-1-methyl)ethyl)phenylthiomethyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3,3-difluoro-4-hydroxy-4-methyl-1-pentyloxymethyl)-9,10-seco-pregna-5(Z)-7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(6xe2x80x2-ethyl-6xe2x80x2-hydroxy-oct-1xe2x80x2-yn-1xe2x80x2-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(7xe2x80x2-ethyl-7xe2x80x2-hydroxy-non-1xe2x80x2-yn-1xe2x80x2-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(1,5-dihydroxy-5-ethyl-2-heptyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-5-hydroxy-1-methoxy-2-heptyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20(R)-(1-ethoxy-5-ethyl-5-hydroxy-2-heptyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20(R)-(1-methoxy-4-hydroxy-4-ethyl-2-hexyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20(R)-(1-ethoxy-4-hydroxy-4-ethyl-2-hexyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20-(4-ethyl-4-hydroxy1-hexyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19)17(20)(Z)-tetraene;
1(S),3(R)-Dihydroxy-20-(5-ethyl-5-hydroxy-1-heptyn-1-yl)-9,10-seco-pregna-5(Z),7(E)-10(19),17(20)(Z)-tetraene;
1(S),3(R)-Dihydroxy-20-(6-ethyl-6-hydroxy-1-octyn-1-yl)-9,10-seco-pregna-5(Z),7(E),10(19),17(20)(Z)-tetraene;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-4,4-difluoro-5-hydroxy-heptyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S)3(R)-Dihydroxy-20(R)-(4,4-dichloro-5-hydroxy-5-methyl-hexyloxy)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4,4-difluoro-5-hydroxy-5-methyl-hexyloxy)-9,10-seco-pregna-5(Z),7(E)-10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-fluoro-4-methyl-pentyl-oxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-ethyl-4-fluoro-hexyl-oxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(5-fluoro-5methyl-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R),20(S)-Trihydroxy-20-(4-ethyl-4-hydroxy-1-hexyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-methoxy-20-(4-ethyl-4-hydroxy-1-hexyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(S)-ethoxy-20-(4-ethyl-4-hydroxy-1-hexyl)-9,10-secopregna-5(Z),7(E),10(19)-triene;
1 (S),3(R)-Dihydroxy-20(S)-[3-(2-hydroxy-2-methyl-1-propoxy)-prop-1E-en-1-yl]-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(4-ethyl-4-hydroxy-1-hexylthio)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-[5-methyl-5-hydroxy-1-hexylthio]-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-[3-(1-methyl-1-hydroxyethyl)benzylthio]-9,10-seco-pregna-5(Z),7E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(3-methyl-3-hydroxy-1 butylthio)-9,10-seco-pregna-5(Z)-7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-5-hydroxy-hept-1(E)-en-3-yn-1-yl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
24-oxo-1(S),3(R),25-Trihydroxy-20(S)-9,10-seco-cholesta-5(Z),7(E),10,19-triene;
1(S),3(R) -Dihydroxy-20(R)-(3-oxo-4-hydroxy-4-ethyl-1-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-methyl-18-(5-methyl-5-hydroxy-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-methyl-18-(4-ethyl-4-hydroxy-hexyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-methyl-18-(4-ethyl-4-hydroxy-hex-2-ynyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-methyl-18-(4-hydroxy-4-methylpentyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20-methyl-18-(4-hydroxy-4-methylpent)-2-yn-1-yloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S)3(R)-Dihydroxy-20-methyl-18-(3,1-hydroxy-1-methylethyl)phenylmethyloxy)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R)-Dihydroxy-20(R)-(1-methoxy-4-hydroxy-4-methyl-1-pentyl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene; isomer A;
1(S),3(R)-Dihydroxy-20(R)-(1-ethoxy4-hydroxy-4-methyl-1-pentyl) -9,10-seco-pregna-5(Z),7(E),10(19)-triene; isomer A;
1(S),3(R),25-Trihydroxy-(20(S)-9,10-seco-cholesta-5(Z),7(E),10(19),23(E)-tetraene;
1(S),3(R)-Dihydroxy-(20(S)-(6xe2x80x2-hydroxy-6xe2x80x2-methyl-4xe2x80x2(E)-hepten-1xe2x80x2yl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene;
1(S),3(R),22(S),25-Tetrahydroxy-20(R),9,10-seco-cholesta-5(Z),7(E),10(19),23(E)-tetraene;
22(S)-Ethoxy-1(S)-3(R),25-trihydroxy-10(R)-,9,10-seco-cholesta-5(Z),7(E),10(1,23(E),-tetraene;
1(S),3(R)-Dihydroxy-20(S)-(3-(1-hydroxy-1-methylethyl)phenoxymethyl)-9,10-secopregna-5(Z),7(E),10(19),16-tetraene or the corresponding 20(R) isomer;
1(S),3(R)-Dihydroxy-20(S)-(3(1-hydroxy-1-methylethyl)phenylthiomethyl)-9,10-secopregna-5(Z),7(E),10(19),16-tetraene or the corresponding 20(R) isomer;
1(S),3(R)-Dihydroxy-20(S)-(4-hydroxy-4-methylpent-1-yl)-9,10-secopregna-5(Z),7(E),10(19), 16-tetraene;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-5-hydroxyhept-1-yl)-9,10-secopregna-5(Z),7(E),10(19),16-tetraene or the corresponding 20(S) isomer;
1(S),3(R)-Dihydroxy-20(R)-(5-ethyl-5-hydroxyhepta-1(E),3(E)-dien-1-yl)-9,10-secopregna-5(Z),7(E),10(19),16-tetraene or the corresponding 20(S) isomer;
1(S),3(R)-Dihydroxy-20(R)-(3cyclopropyl-3-hydroxyprop-1(E)-en-1-yl)-9,10-secopregna-5(Z),7(E),10(19),16-tetraene (24(S) isomer) or the corresponding 24(R) isomer; and
1(S),3(R)-Dihydroxy-20(1,5-dihydroxy-5-ethyl-2-heptyn-1-yl)-9,10-secopregna-5(Z),7(E),10(19),17(20)Z-tetraene, both 22-isomers.
As a second pharmacologically active component B it is preferred to use a group I, II or III topical steroid, more preferably a medium to weak acting steroid (groups I and II). Component B is preferably selected from the group consisting of Betamethasone (9-fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione) and esters thereof such as the 21-acetate, 17-adamantoate; 17-benzoate, 17-valerate, and 17,21-dipropionate; Alclomethasone and esters thereof such as the dipropionate; Clobetasole and esters thereof such as the propionate; Clobetasone and esters thereof such as the 17-butyrate; Desoximetasone; Diflucortolon and esters thereof, Diflorasone and esters thereof such as the diacetate; Fluocinonid; Flumetasone and esters thereof such as the pivalate; Fluocinolon and ethers and esters thereof such as the acetonide; Fluticasone and esters thereof such as the propionate; Fluprednidene and esters thereof such as the acetate; Halcinonide; Hydrocortisone and esters thereof such as the -17-butyrate; Mometasone and esters thereof such as the furoate; and Triamcinolon and ethers and esters thereof such as the acetonide; as well as mixtures thereof. More preferred examples of the corticosteroids are Betamethasone or esters thereof such as the 17-valerate or the 17,21-dipropionate, Clobetasole or esters thereof such as the propionate, Triamcinolon or ethers and/or thereof such as the acetonide or the acetonide-21-N-benzoyl-2-methyl-xcex2-alaninate or the acetonide-21-(3,3-dimethylbutyrate), or Hydrocortisone or esters thereof such as the 17-butyrate.
Moreover, the invention relates to a pharmaceutical compositions for dermal use which contain at least one vitamin D or vitamin D analogue and at least one corticosteroid and which exhibits a higher efficacy in the treatment of psoriasis and other inflammatory skin diseases in humans and other mammals than any of the pharmacologically active components used alone. Said efficacy is preferably measured as percentage change in PASI score in psoriasis and related skin diseases, such as sebo-psoriasis and seborrhoic dermatitis.
PASI (Psoriasis Area and Severity Index) score assesses the extent and severity of the patient""s psoriasis. The following formulae are used to calculate the PASI score:
Arms 0.2(R+T+S)E=X
Trunk 0.3(R+T+S)E=Y
Legs 0.4(R+T+S)E=Z
Where R=score for redness, T=score for thickness, S=score for scaliness, and E=score for extent where the score is assessed according to a scale from 0 to 4 as follows:
0=no involvement, 1= less than 10%, 2=10-29and, 3=30-49%, and 4=50-69%. The sum of X+Y+Z gives the total PASI score which can range from 0 to 64.8.


A method and system for fabricating an energy assisted magnetic recording (EAMR) transducer is described. The EAMR transducer has an air-bearing surface (ABS) and a waveguide. The method includes providing a planarized near field transducer (NFT) for the waveguide and forming a sloped surface on the planarized NFT. The sloped surface has a front edge separated from the ABS by a distance. The method and system also include providing a write pole on the sloped surface.

FIG. 1 depicts a portion of a conventional energy assisted magnetic recording (EAMR) transducer 10. The conventional EAMR transducer 10 is used in writing to recording media 30. To do so, the conventional EAMR transducer 10 receives light, or energy, from a conventional laser (not shown in FIG. 1). Also shown is grating 20. The conventional EAMR transducer 10 includes a conventional waveguide 12, conventional pole 14, and a conventional near-field transducer (NFT) 16. Also shown is a laser spot 22 on the gratings 20. Other components that may be part of the conventional EAMR transducer 10 are not shown.
In operation, the light from the spot 22 on the grating 20 is coupled to the conventional waveguide 12. The conventional waveguide 12 guides the light to the conventional NFT 16 near the air-bearing surface (ABS). The conventional NFT 16 focuses the energy from the waveguide 12 to an optical spot 32 on the media 30. A small region of the conventional media 30 is heated by the spot 32. This region becomes more magnetically soft. The conventional EAMR transducer 10 magnetically writes data to the heated region of the recording media by energizing the conventional pole 14.
Although the conventional EAMR transducer 10 may function, there are drawbacks. In order to reduce the track size, and thus increase density, the spot 32 size is decreased to prevent heating of adjacent tracks. Thus, the size of the conventional NFT 16 is desired to be small in order to limit the size of the spot 32. Further, the distances between the pole 14 and the conventional NFT 16 and between the conventional NFT 16 and the media 30 are desired to be carefully controlled. In addition, care must be taken in ensuring that the conventional pole 14 and conventional waveguide 12 are sufficiently separated that the magnetic field of the conventional pole 14 does not adversely affect the optical performance of the conventional waveguide 12. Fabrication of a conventional EAMR transducer 10 that takes these factors into consideration may be problematic.
Accordingly, what is needed is a system and method for improving the fabrication of an EAMR transducer.

Method and system for providing a magnetic recording transducer having a planarized near-field transducer and a sloped pole


Methods of treatment of benign prostatic hyperplasia and reduction of the level of the prostate specific antigen (PSA) of benign prostate conditions are disclosed. The treatment method includes an initial treatment of patients with orally administration of an initial dosage of about 40 mg 13 cis-retinoic acid daily for a period from about ten days to about twenty days, and followed by a sustaining treatment of the patients with orally administration of a sustaining dosage of about 40 mg 13 cis-retinoic acid about every five to seven days in a sustaining period.

The present invention relates to methods for treating benign prostate hyperplasia and reducing the level of prostate specific antigen of benign prostate conditions. More specifically, the methods utilize 13 cis-retinoic acid to effectively treat benign prostate hyperplasia, and to reduce the level of prostate specific antigen of the patients with benign prostate conditions.
The three most common prostate health problems facing men and their families today are benign prostatic hyperplasia (BPH), prostate cancer, and prostatitis. Each of these conditions affects the prostate differently. Benign prostate hyperplasia is the most common benign neoplasm (non cancerous enlargement of the prostate gland) in men, and has a high prevalence that increases with age. The increase in size of the prostate inside its capsule exerts pressure on the urethra, which passes through the capsule, resulting in obstruction to urine flow. Half of all men have BPH identifiable histologically at age 60 years, and by 85 years the prevalence is about 90%. In the United States about 25% of men will be treated for BPH by age 80, and over 300,000 surgical procedures are performed each year for BPH (mostly transurethral resection of the prostate, TURP). This makes TURP the second most common surgical procedure, second only to cataract surgeryxe2x80x94at a cost estimated at $2 billion per year. Experts do not yet know what causes BPH, but the condition may be related to the hormone testosterone and its relationship to other hormones that change during the aging process.
There are a number of treatment options for BPH. These include watchful waiting, medical therapy such as alpha blocker therapy and finasteride therapy, balloon dilatation and various surgical procedures such as transurethral incision of the prostate (TUIP), transurethral resection of the prostate (TURP), and open prostatectomy. Few treatments are without any adverse consequences, and this is particularly so with treatments with BPH, where there is a delicate balancing act between the benefits and demerits of the treatments available. The adverse events following treatment for BPH include impotence (for various surgical procedures ranging from about 4% to 40%, the incidence of impotence is also increased after some medical treatments), incontinence (stress incontinence about 3% after surgery, with total urinary incontinence approaching 1%), and the need for re-treatment. Combined analysis of published data estimated that the mean probability for perioperative mortality (death within 90 days of a procedure) was 1.5% for TURP. For open surgery it was 2.4% and for balloon dilation it was 3.5%.
It is well known that prostate specific antigen (PSA), a protein produced by prostate cells, is frequently present at elevated levels in the blood of men who have prostate cancer. The U.S. Food and Drug Administration has approved a PSA test for use in conjunction with a digital rectal exam to help detect prostate cancer in men age 50 or older and for monitoring prostate cancer patients after treatment. However, much remains unknown about the interpretation of PSA levels, the test""s ability to discriminate cancer from benign prostate conditions, and the best course of action following a finding of elevated PSA. Furthermore, clinically it is known that BPH and prostatitis can cause elevated PSA.
13-cis retinoic acid, more generally known as retinoic acid, also referred to as isotretinoin, and sold under the Roche trademark Accutane, has long been known as a topical and oral dermatologic agent used in the treatment of acne vulgrais and several other skin diseases. 13-cis retinoic acid inhibits sebaceous gland function and keratinization. The exact mechanism of action of Accutane in treating acne is unknown. Since retinoic acid is a teratogneic drug and, because of the mutagenic effects associated with such drugs, it has only gradually entered the mainstream of medicine.
Experimentation in non-dermatologic applications of retinoic acid appeared in the literature in 1992 in an investigation at the University of California School of Medicine (Department of Urology), in San Francisco, this with reference to the effect of 13-cis-retinoic acid upon human prostate cancer cells. Since 1992, the research group at the University of California, headed by Dr. Dahiya, established the effect of retinoic acid in the downregulation of saturated fatty acids coupled with the upregulation of unsaturated fatty acids in human prostate cancer cells. As such, saturated fatty acids, which are believed to play a significant role in prostate cancer, were inhibited while unsaturated fatty acids, which are believed to act in a protective way relative to such cancers, were increased in cell lines.
However, isotretinoin or retinoic acid has not been used for treating benign prostate hyperplasia, or for reducing the level of prostate specific antigen of benign prostate conditions.
In one embodiment, the present invention relates to a method of treating benign prostatic hyperplasia. The method comprises the steps of (a) orally administering about 40 mg of 13-cis-retinoic acid daily for an initial treatment period from about ten days to about twenty days; and (b) thereafter orally administering about 40 mg of 13-cis-retinoic acid in about every five to seven days in a sustaining period.
In a further embodiment, the present invention relates to a method of reducing the level of prostate specific antigen (PSA) of patients. The method comprises the steps of (a) orally administering about 40 mg of 13-cis-retinoic acid daily for an initial treatment period from about ten days to about twenty days; and (b) thereafter orally administering about 40 mg of 13-cis-retinoic acid in about every five to seven days in a sustaining period.
It is accordingly an object of the present invention to provide a method of treating benign prostatic hyperplasia and related symptoms such as reduced or constricted urine stream and urinary retention.
It is another object to provide a method of reduction of the level of the prostate specific antigen of benign prostate conditions.
The above and yet other objects and advantages of the present invention will become apparent from the hereinafter set forth Detailed Description of the Invention and Claims appended herewith.
The instant invention derived from the observation that the human prostate comprises a modified sebaceous gland and that, given the many years of usage of successful Accutane/isotretinoic/retinoic acid in the treatment of acne, this through the shrinking of sebaceous glands within the face and neck, that a similar action might occur upon the prostate gland if Accutane were taken as an oral medication.
Operating with the informed consent of approximately twelve patients exhibiting either or both an elevated PSA, that is, patients with a PSA of greater than 4 ng/ml and/or with exhibiting benign prostatic hyperplasia, the patients were treated with Accutane manufactured by Roche.
The treatment method involves essentially two periods: an initial treatment, and a sustaining treatment. First, in the initial treatment the patients orally administrate an initial dosage about 40 mg of 13-cis-retinoic acid daily for a period from about ten days to about twenty days. Thereafter, the patients orally administrate a sustaining dosage about 40 mg of 13-cis-retinoic acid about every five to seven days in a sustaining period. Typically, the sustaining period is about one year. However, it can be extended longer if extended maintenance is needed. Preferably, the initial treatment period is about fourteen days, because beyond fourteen days side effects of the medicine, such as tenderness at sites of old injuries to the fibro-musculo-skeletal system, dry skin, chapped lips, dry eyes, and dry nose, tend to occur. If these side effects occur during the initial treatment period, they normally subside after the sustaining dosage is instituted.
In the initial treatment, 40 mg of 13-cis-retinoic acid can be administrated in a single dose, or divided doses. Commercially, Accutane has three available doses, 10 mg, 20 mg, and 40 mg soft gelatin capsules. The patients can either take one 40 mg capsule, or take two 20 mg capsules daily. The same applies to the dosage in the sustaining treatment. For convenience, the patients can take one 40 mg dose every five to seven days.
The initial dosage of about 40 mg 13-cis-retinoic acid daily is determined based on average men""s body weight of about 160 lbs, i.e. at about 0.25 mg/lb of body weight. For patients who weigh substantially above or less than the average body weight, the dosage described above can be adjusted accordingly. The same principle applies to the sustaining dosage.
The 13-cis-retinoic acid used for the purpose of the present invention can be in various forms, such as powders, pills, capsules, tablets, and liquids. The liquids comprise 13-cis-retinoic acid in a suitable pharmaceutical media, such as water, glycols, oils, alcohols, and syrups.
This treatment method resulted in subjective as well as objective amelioration of benign prostatic hyperplasia and symptoms thereof, and a measurable reduction in the prostate specific antigen (PSA). In particular, through examination of these patients and through their own anecdotal comments, a reduction in prostate enlargement was confirmed. Furthermore, the blood test results showed that PSA levels had been dramatically reduced to levels in a range of b 0 to 2 ng/ml among these patients.
Example 1 to 4 illustrate clinical effectiveness of the above described treatment method. It was found that none of the conditions of these patients worsened either in terms of PSA or hyperplasia, and none progressed into any form of diagnosable malignancy. Further, no serious adverse side effects or contra-indications of any kind were observed among the patients in the informal trials.

Method of treating benign prostatic hyperplasia and other benign prostate conditions