A container including a body, a top portion and a bottom portion on the body, a first wall on the body, a material-treating container, a second wall on the material-treating container, a material-treating substance in the material-treating container, a permeable cover on the material-treating container, and the second wall being positioned coextensively within the first wall with the material-treating container in hermetic sealing relationship with the bottom portion of the first wall and with the permeable cover within the body.

Not Applicable
Not Applicable
The present invention relates to an improved container which includes an integral second container containing a material-treating substance and a method of fabrication thereof.
By way of background, certain materials, such as pills, diagnostic test strips and certain granular substances which are packed in containers require the presence of a material-treating substance to either adsorb moisture or absorb oxygen and/or absorb odors in order to preserve the integrity of those materials.
It is one object of the present invention to provide a container having an integral material-treating second container with a material-treating substance therein which is associated with the body of the container in an unique manner.
Another object of the present invention is to provide a container having a second container of a material-treating substance which is assembled with the container after it has been filled so that the material-treating container need not be unduly exposed to the atmosphere prior to and during the filling.
A further object of the present invention is to provide an improved method of fabricating and filling a container which also requires a material-treating substance. Other objects and attendant advantages of the present invention will readily be perceived hereafter.
The present invention relates to a container comprising a body, a top portion and a bottom portion on said body, a first wall on said body, a material-treating container, a second wall on said material-treating container, a material-treating substance in said material-treating container, a permeable cover on said material-treating container, and said second wall being positioned coextensively with said first wall and with said material-treating container in hermetic sealing relationship within said first wall and with said permeable cover within said body.
The present invention also relates to a method of fabricating a container comprising the steps of providing a body having a first wall, providing a material-treating container with a material-treating substance therein and having a second wall and a permeable membrane thereon, and installing said material-treating container in hermetic sealing relationship in said body with said second wall in coextensive engagement with said first wall with said permeable membrane within said body.

Container with integral material-treating container and method of fabrication thereof


A control device for an engine provided with an electromagnetic driven intake valves is provided so that the intake valves may perform a desirous control (for example, early activation of a catalytic converter) in an excellent driving state without having to bring about unfavorable phenomena such as a variety of rotation or serge of the engine. The control device serves to make the given cylinders different in the opening or shutting timing of intake valve from the other cylinders according to the driving state.

The present invention relates to a control device for an engine provided with electromagnetic driven intake valves and more particularly to the control device for an engine provided with an electromagnetic driven intake valves that is constructed to independently control an operation timing of the intake valve in each cylinder.
As a mechanism for controlling a valve operation timing of electromagnetic driven intake valves, conventionally, there has been known a technique disclosed in JP-A-8-200135. This mechanism is constructed to detect an actual operation time of the valve, compare the detected time with a command value given for driving an electromagnetic valve, and detect an abnormality of the electromagnetic valve based on the compared result.
The electromagnetic valve driving technique disclosed in such a prior art has not been constructed to take into consideration a technique of independently controlling the valve timing for each cylinder.
It is therefore an object of the present invention to provide a control device for an engine provided with an electromagnetic driven intake valve which is constructed to focus on the operativity of the electromagnetic driven intake valve, that is, the independent operativity of the intake valve timing of each cylinder in response to an electric command value and secure a desirous control such as activation of a catalytic converter for exhaust emission control, which has conventionally had difficulty in being compossible to drivability, as keeping the excellent drivability, when requested.
In carrying out the foregoing object, the control device for an engine provided with an electromagnetic driven intake valve is constructed to control an electromagnetic driven type intake valve that may drive and control the intake valve for each cylinder and at least one cylinder so that the cylinder has a different crank angle timing of opening or shutting (closing) the intake valve from another cylinder.

Control device for engine provided with electromagnetic driven intake valves


An image processing apparatus that performs image processing on a first image and a second image includes a dividing unit dividing the first image into a plurality of blocks; a first motion-vector calculator calculating first motion vectors representing movements from the blocks of the first image to corresponding regions of the second image; a second motion-vector calculator calculating second motion vectors representing movements of the blocks that occur when the blocks are transformed based on a first positional-relationship parameter representing positional relationship between the first image and the second image; a difference-vector calculator calculating difference vectors representing differences between the first motion vectors and the second motion vectors; and an extracting unit extracting blocks including a moving object or blocks including a non-moving object based on distribution density of end points of the difference vectors.

1. Field of the Invention
The present invention relates to image processing apparatuses and methods, recording media, and programs. Particularly, the present invention relates to an image processing apparatus and method, a recording medium, and a program that allow accurate extraction of, for example, a region including a moving object.
2. Description of the Related Art
When a user captures an image by a camera, such as a digital video camera or a digital still camera, if the user captures an image with the camera held by hands instead of fixing the camera by a tripod, the image captured (hereinafter simply referred to as the image) could look to be shaky, i.e., the effect of camera shake due to movement (shake) of the camera with respect to an object could occur.
In order to alleviate the effect of camera shake on the image, with regard to a plurality of images continuously captured, using an image as a reference image, parameters representing movement of another image as a whole with respect to the reference image are calculated, and the another image is corrected using the parameters (i.e., the position is adjusted with reference to the reference image). This process is referred to, for example, as camera-shake correction.
The parameters representing movement of another image as a whole with respect to the reference image can be considered as parameters representing positional relationship between the reference image and the another image. The reference image is referred to for the purpose of adjusting (correcting) position. Another image whose position is corrected with respect to the reference image will be referred to as a target image.
Image components that occur between a reference image and a target image due to the effect of camera shake can be generally classified into a component of horizontal movement, which occurs when a camera directed to an object shifts horizontally, and a component of rotation centered about an optical axis of a lens, which occurs when the camera rotates clockwise or counterclockwise. More strictly speaking, a component of rotation about an axis that is perpendicular to the optical axis of the camera lens, or an enlarging or reducing component due to movement in the depth direction of the camera also exist.
Positions in the reference image and target image including the effect of camera shake are adjusted, for example, by affine transformation. Thus, as parameters representing positional relationship between the reference image and the target image, for example, affine parameters for affine transformation can be used.
In affine transformation, a position (x, y) in the reference image and a position (x′, y′) in the target image are expressed by expression (1) below.
                              (                                                                      x                  ′                                                                                y                  ′                                                              )                =                                                                                (                                                                    a                                                        b                                                                                c                                                        d                                                              )                                                  (                                                                    x                                                                                y                                                              )                                +                      (                                                            s                                                                              t                                                      )                                              (        1        )
In expression (1), for example, when a=K×cos θ, b=−K×sin θ, c=K×sin θ, and d=K×cos θ, the left-hand side of expression (1) represents affine transformation for rotation by an angle θ, horizontal movement by (s, t), and enlarging or reducing by K with respect to the position (x, y).
In the following description, the matrix (a, b, c, d) of affine transformation and the two-dimensional vector (s, t) in expression (1) will be collectively denoted as affine parameters (a, b, c, d, s, t).
The affine parameters are calculated, for example, by dividing the reference image into a plurality of blocks and detecting motion vectors of the blocks. That is, for example, affine parameters (a, b, c, d, s, t) in expression (1) are determined so as to minimize the sum of square errors between a position (x″, y″) determined by moving the position (x, y) of each pixel of the reference image onto the target image based on the motion vectors of the blocks of the reference image and a position (x′, y′) determined by transforming the position (x, y) to a position on the target image according to expression (1).
However, when a moving object is included in the reference image and the target image, generally, the movement (motion vector) of the moving object in the image differs from movement of the image as a whole caused by camera shake. Thus, when pixels in a region of the moving object are used to calculate the affine parameters (a, b, c, d, s, t), it is difficult to obtain accurate affine parameters (a, b, c, d, s, t) due to the effect of the movement of the moving object.
Thus, when a moving object is included in an image, a region of the moving object is extracted and removed, and affine parameters (a, b, c, d, s, t) representing movement of the image as a whole caused by camera shake are calculated using only the remaining region other than the region of the moving object.
For example, Japanese Unexamined Patent Application Publication No. 07-038800 proposes techniques for removing a region including a moving object to correct the effect of camera shake.
According to Japanese Unexamined Patent Application Publication No. 07-038800, when detecting movement of an image as a whole, the image is divided into a plurality of blocks, and only motion vectors with respect to the horizontal direction and motion vectors with respect to the vertical direction of the respective blocks are considered.
That is, according to Japanese Unexamined Patent Application Publication No. 07-038800, an entire image is divided into four regions, and each of the four regions is further divided into a plurality of blocks. Then, a motion vector V is calculated for each of the blocks of each of the four regions.
Furthermore, in each of the four regions, the sum Σ(|VXi−VXAVR|+|VYi−YYAVR|) for all the blocks of the sum of the absolute value |VXi−VXAVR| of the difference between a value VXi of the motion vector V of each block with respect to the horizontal direction and an average VXAVR of the motion vectors V of all the blocks with respect to the horizontal direction and the absolute value |VYi−VYAVR| of the difference between a value VYi of the motion vector V of each block with respect to the vertical direction and an average VYAVR of the motion vectors V of all the blocks with respect to the vertical direction is calculated as exitance.
Of the respective exitance values of the four regions, two regions with smaller exitance values are selected, and an average of the motion vectors V of the two selected regions is calculated as a motion vector of the image as a whole, i.e., a parameter representing movement of the image as a whole. That is, of the respective exitance values of the four regions, two regions with larger exitance values are considered as regions including a moving object and excluded from calculation of a parameter representing movement of the image as a whole.

Image processing apparatus and method, recording medium, and program


Metal films (for instance, gold films or palladium films) to constitute bumps are formed on a metal base by electrolytic plating. Then, a circuit wiring including inner leads is formed by electrolytic plating with a metal so that the inner leads are connected to the respective metal films.

The present invention relates to a lead frame, particularly a lead frame which uses, as a base material, a base having a metal such as a copper-type metal as the main component and which has bumps made of a metal on the surfaces of inner lead tip portions. The invention also relates to a manufacturing method of such a lead frame, a semiconductor device using such a lead frame, an assembling method of the semiconductor device, and an electronic apparatus using the semiconductor device.
Lead frames are indispensable for the techniques of forming leads of respective electrodes of a semiconductor chip, and commonly used in mounting semiconductor chips. Lead frames are generally made of a copper-type material, and bumps are formed on the surfaces of respective inner lead tip portions so as to be bonded to respective electrode pads on a semiconductor chip. Although previously such bumps were using aluminum, in recent years techniques of forming bumps using gold have been developed. The reasons for forming bumps made of gold are that good bonding performance is obtained and that gang bonding is enabled which provides high production efficiency than single point bonding.
In particular, the fact that gang bonding is enabled is very important for the following reason. Electrode pads of a semiconductor chip are made of aluminum. According to the current technology, single point bonding should be used to bond leads of the previous type having aluminum bumps to such aluminum pads. Where bumps are made of gold, gang bonding can be performed and hence the bonding efficiency can greatly be increased.
FIG. 1 illustrates bonding in a case where bumps are made of gold. Respective inner leads made of copper, for instance, have bumps (having a three-layer structure of gold, tin, and aluminum that are provided in this order from the surface) at the tip portions. The bumps are positioned above respective electrode pads (having a three-layer structure of gold, tin, and aluminum that are provided in this order from the surface) of a semiconductor chip and then bonded thereto by ultrasonic bonding by using a bonding tool.
The conventional techniques of forming bumps made of gold will be described below. In a first technique, the bump-forming side of each inner lead made of copper or the like is selectively half-etched so that a bump-forming portion is protruded. Then, the entire lead surface is plated with gold (a nickel plating layer is formed as an undercoat). In a second technique, gold to constitute a bump is transferred to each inner lead surface by a transfer method. In a third method, gold is evaporated on a bump-forming portion of each inner lead. In a fourth method, the entire surface of each inner lead is plated with a gold film with a nickel plating layer formed as an undercoat.
Each of the above conventional techniques of forming bumps made of gold which provide good bonding performance and enable gang bonding has the following problems. The first technique, in which the bump-forming side of each inner lead is selectively half-etched so that a bump-forming portion is protruded and then the entire lead surface is plated with gold, has a problem that because copper that constitutes leads is hard, electrode pads of an IC chip are prone to cracking. Since a nickel plating layer needs to be formed as an undercoat of a gold plating layer, the number of steps is increased. Further, where gold is formed on the entire lead surface, a large amount of gold is used, to increase the material cost, that is, the overall cost.
The second technique, in which gold to constitute a bump is transferred to each inner lead surface by a transfer method, has a problem that it is prone to positional deviations because of low accuracy of the transfer position control.
The third technique, in which gold is evaporated on a bump-forming portion of each inner lead, has problems that it requires a large investment in equipment because evaporation equipment is expensive, that the productivity is low because gold evaporation takes long time, and that the adhesion between a gold evaporation film and a copper lead is insufficient.
In the fourth technique, in which the entire surface of each inner lead is plated with a gold film with a nickel plating layer formed as an undercoat, has a problem that the number of steps is increased because the nickel plating layer needs to be formed as the undercoat of the gold plating layer. Further, where gold is formed on the entire lead surface, a large amount of gold is used, to increase the material cost. In particular, the gold plating film needs to be formed so as to be thick enough to secure good bonding performance. Forming so thick a gold plating film consumes a very large amount of gold, to cause a non-negligible cost increase.
The present invention has been made to solve the above problems in the art, and an object of the invention is therefore to improve the positional accuracy of bump forming positions, enable bumps to be formed even when the inner lead pitch is made finer, form in a relatively short time bumps that are thick enough to secure good bonding performance without using evaporation that is low in productivity and requires a high equipment cost, provides sufficient adhesion between bumps and inner leads, improve the bonding performance while preventing an undue increase in material cost by avoiding useless consumption of a metal, enables gang bonding, and reduce the cost of a metal material of bumps in manufacture of a lead frame which uses, for instance, a metal base as a base material and has bumps made of a metal on the surfaces of inner lead tip portions.
The invention provides a first manufacturing method of a lead frame, comprising the steps of forming metal films to constitute bumps by plating on a base made of a metal; and forming, by plating with a metal, a circuit wiring including inner leads so that the inner leads are connected to the respective metal films.
This manufacturing method of a lead frame can increase the adhesion to the underlying member because of the use of plating rather than evaporation, and can shorten the time required for forming metal films of a necessary thickness because of their high growth rate. Further, the investment in equipment can be reduced because the cost of equipment for plating is lower than that for evaporation.
Since metal films to constitute bumps are formed by plating on a highly rigid base that has not been formed with inner leads yet, the underlying member (base member) is more stable than in a case of forming metal films on the tip portions of the surfaces of inner leads already formed.
Therefore, the bumps are easy to form and the accuracy of their forming positions can be increased.
The metal films may be formed by forming, on the base, a resist film having a negative pattern of a pattern of the intended circuit wiring, and performing the plating in a state that tip portions of the respective inner leads are masked by a mask jig so as to be prevented from being plated. In this case, by securing a proper positional relationship between the resist film and the mask jig, the metal films to constitute bumps can easily be formed with a correct positional relationship with inner leads to be formed next so as to be connected to the metal films.
Further, the circuit wiring including the inner leads may be formed thereafter by performing plating by using only the resist film as a mask in a state that the mask jig is removed. In this case, a desired positional relationship between the bumps and the circuit wiring can be established with high accuracy.
The invention also provides a second manufacturing method of a lead frame, comprising the steps of forming metal firms to constitute bumps by plating on a base having, on a surface thereof, an etching stop layer; forming, by plating with a metal, a circuit wiring including inner leads so that the inner leads are connected to the respective metal films; forming, so as to cover the circuit wiring, an insulating film having openings where the circuit wiring is exposed; forming external electrodes in the respective openings by plating; selectively etching a portion, opposite to the circuit wiring, of the base by using the etching stop layer as a stopper for preventing etching of a portion, on a side of the circuit wiring, of the base; and removing the etching stop layer.
In this manufacturing method of a lead frame, metal films to constitute bumps are formed on a base having an etching stop layer on its surface and a circuit wiring is thereafter formed. This makes it possible to apply the technique of the above-described first manufacturing method of a lead frame for forming metal films as bumps to techniques in which inner leads are formed by using, as a base, a structure in which an etching stop layer is formed on the surface of a relatively thick metal layer made of copper or the like that will become the frame portion of a lead frame, that is, an outer ring, or by using a structure in which a material layer for forming a circuit wiring including inner leads is further formed on the surface of the etching stop layer (refer to Japanese Unexamined Patent Publication Nos. Hei. 8-148530 and Hei. 8-47221).
The invention provides a lead frame comprising an insulating film having openings; a wiring film including inner leads formed on one surface of the insulating film; electrodes as external terminals provided on the other surface of the insulating film so as to be connected to the wiring film through the openings of the insulating film; and bumps made of palladium and connected to the respective inner leads. The invention also provides a semiconductor device using this lead frame.
According to the above lead frame and semiconductor device, since the bumps are made of palladium rather than gold, the material cost is low and gang bonding is still possible. In the case of plating with gold, it is necessary to use a plating liquid containing cyan which is very toxic and dangerous. In the case of plating with aluminum, it is necessary to use an explosive plating liquid. (Aluminum is more frequently formed by evaporation than by plating.) In contrast, in the plating with palladium, it is not necessary to use such problematic plating liquids and hence a merit is obtained that the plating is very safe. An example of palladium plating liquids is paragrite SST of Kojundo Chemical Co. Since palladium plating liquids generally contain a toxic component having an ammonia-type pungent smell, they are not completely free of toxicity. However, gold plating liquids for industrial purposes generally contain cyan compounds, which are such toxic substances that even a very small amount thereof is lethal because cyan compounds produce a hydrogen cyanide gas when reacting with hydrochloric acid HCl or the like. Palladium plating liquids are thus much safer than gold plating liquids.
The invention provides an assembling method of a semiconductor device, comprising the steps of manufacturing a lead frame by any of the above manufacturing methods of a lead frame; and bonding, at the bumps, the inner leads of the lead frame to respective electrode pads of a semiconductor chip by single point bonding or gang bonding.
According to this assembling method of a semiconductor device, since a lead frame manufactured by any of the above manufacturing methods of a lead frame is used, a lead frame formed with bumps that has good bonding performance and enables gang bonding can be used in assembling a semiconductor device. Where the inner leads of such a lead frame are bonded to the respective electrode pads of a semiconductor device by single point bonding, bonding can be performed with much superior performance. Where gang bonding is performed, the productivity can be increased.
Further, the invention provides an electronic apparatus comprising a semiconductor device that uses the above-described lead frame.
By virtue of the use of a semiconductor device that is given the above-mentioned advantages of the lead frame, this electronic apparatus benefits from the same advantages.

Lead frame, manufacturing method of a lead frame, semiconductor device, assembling method of a semiconductor device, and electronic apparatus


In one implementation, a method includes obtaining a plurality of representations of a digital video asset. The plurality of representations may include a plurality of frames The method also includes generating first data comprising data indicative of temporal dependencies and frame decoding dependencies for the plurality of frames. The frame decoding dependencies may include a plurality of switching points between the plurality of representations of the digital video asset. The method further includes receiving a request for a first representation of the digital video asset from a first computing device and transmitting the first data to the first computing device based on the request. In another implementation, a method includes transmitting a request for a first representation of a plurality of representations of a digital video asset to a first computing device. The plurality of representations may include a plurality of frames. The method also includes receiving first data comprising data indicative of temporal dependencies and frame decoding dependencies for the plurality of frames based on the request. The frame decoding dependencies may include switching points between the plurality of representations of the digital video asset.

Adaptive bit rate (ABR) streaming architectures may dynamically provide different representations (e.g., different bit rates) of a digital video asset (e.g., a movie, a video, etc.) to client devices. For example, a digital video asset may have multiple representations that differ in resolution (e.g., 1080P, 720P, 480P, etc.), encoding quality (e.g., quantization, motion compensation), and/or frame rate, that may result in a range of rendered video quality. The ABR system architecture may divide each version of the streaming video into smaller sized segments (e.g., segments that are 5 seconds long, 1 minute long, etc.). Based on changes in the bandwidth available to a client device, segments from different representations of the digital video asset may be provided to the client device. A client device may initially have low bandwidth and the ABR system architecture may initially provide segments from the low quality representation of the digital video asset to the client device. If the bandwidth of the client device increases, the ABR system architecture may start providing segments from a higher quality representation to the client device. Similarly, if bandwidth decreases, the ABR system architecture may switch to a lower quality representation that may be delivered at the lower bandwidth.

Adaptive bit rate system architectures using named domain networking


A device is described for determining the characteristic configuration of long, towed underwater structures such as tubes or cables. The device is a collar which fits around the structure and has sufficient hydrodynamic drag that it remains essentially stationary relative to the linear configuration of the structure as the structure is drawn through it. The device, however, has relatively low mass and assumes the horizontal and vertical position of the structure as the structure is drawn through it. Instrumentation within the device registers the position assumed by the collar and either records it or transmits it to an external receiving station. This information gives a characteristic profile of the elongated structure as it passes through the water.

The present invention is directed to a system for determining the configuration of long towed underwater cables and for calibrating and determining the characteristics of measuring devices which may be displayed along the cable. The present invention is particularly adapted for determining the vertical and horizontal displacement which characterizes long towed arrays and for determining the response characteristics of hydrophones and depth sensors along the array.
A particularly useful system which has been employed for identifying the presence and location of underwater objects has been the long towed array, which essentially consists of a long oil filled tube having dispersed at regular intervals along its length a series of hydrophone elements which detect the presence and location of underwater objects by receiving acoustic sound waves and communicating a signal back to the vessel which is towing the array. Such arrays, however, which may extend for well over a thousand feet in length, characteristically do not assume a linear configuration when towed by a vessel, but rather extend in such a way that the depth and horizontal displacement along the towed array vary considerably.
Accordingly, in order to assure an accurate interpretation of any signal received from hydrophones along the array indicating the presence of an underwater object, it is necessary to calibrate such towed arrays so that the acoustic signal level is known and the characteristic underwater configuration of each towed array is known and taken into consideration in determining the position and characteristics of the underwater object being detected.
Various techniques have heretofore been employed to calibrate acoustic towed array devices such as the dropping of explosive devices which detonate at predetermined depths and the use of acoustic calibration devices which are lowered in the ocean and which emit a known acoustic signal. These techniques, however, have suffered from the disadvantage of not being particularly accurate and also involving considerable expense.
It is accordingly an object of the present invention to provide a system which permits the inexpensive, expeditious and accurate determination of the characteristic underwater configuration of a towed acoustic array or other elongated towed underwater device.
It is a further object of the present invention to provide a device which will permit determination of the position and functional condition of the respective hydrophone elements in a towed underwater array.
It is still a further object of the invention to provide a system which permits the calibration of depth sensors built into underwater towed arrays and to provide performance tests on each hydrophone element in such underwater towed arrays.

Device for determining the configuration and calibrating long, towed underwater structures


A method is provided for increasing and maintaining the quantity and activity of immune leukocyte effector cells in preparation for lymphokine and cytokine administration before and during treatment for disease pathogens. The method simultaneously up-regulates the expression of high affinity IL-2 receptors on the above mentioned cells, making them receptive to subsequent IL-2 administration, which activates and directs these cells to mediate cytotoxic activity against disease pathogens. The method may also be employed in conjunction with the administration of other lymphokines, cytokines, biological response modifiers and pharmacological compounds whose activity would benefit from an increase in effector cells. The preferred method of administration is by inhalation of a zinc oxide fume or particulate from 15 to 900 mg ZnO/m.sup.3 for one or more exposures per day, one hour or less per exposure.

The medical and scientific community has been intrigued at the potential for harnessing the immune system to combat disease pathogens. Scientists have learned that the immune system relies on a symphony of elevated, unique types of cells in the blood and tissues, governed by hormones, in particular, the interleukins. It is a continuing pursuit of medical research to direct the power of the immune system toward control of disease pathogens such as cancer cells, tumor cells, viral infection and infectious diseases. See Smith, Scientific American, 50-57 (March 1990).
The lymphokine Interleukin-2 (IL-2) has a wide scope of activity and plays a key role in immune regulation. In clinical trials, IL-2 alone has produced tumor responses in approximately 15 to 20% of the patients with renal cell carcinoma and metastatic melanoma. Although IL-2 alone can mediate an anti-tumor response, it has limitations and is accompanied by severe toxicities in most current modalities. See Smith, op. cit.; Sznol, Seminars in Oncology 20:1, 80-93 1993); Cetus Oncology Div & Chiron Corp, IL-2 Brochure, 3-48 (1992); Devita, Hellman & Rosenberg, Cancer Principles and Practice of Oncology 1, 332-341 (1989); Haskell, Cancer Treatment, 3rd ed., 102-119, (1990); Stein & Dalgleish, European Journal of Cancer 30A:3, 400-404 (1994); Rosenberg & Yang et al., JAMA 271:12, 907-913 (1994).
In order to improve and potentiate the effect of IL-2 and lessen the toxicities associated with IL-2 treatment, effector cell transfer and expansion techniques have been developed. In a procedure known as adoptive cellular immunotherapy, effector lymphocytes are taken from the patient ("rescued") and expanded in in vitro cultures with IL-2. These lymphokine-activated killer (LAK) cells are then re-infused into the patient in conjunction with IL-2. Essentially these LAK cells are additional effector cells which are reinfused into the patient. This combination of additional effector (LAK) cells and IL-2 results in more effective therapy than IL-2 alone.
Although the addition of these effector cells resulted in a trend toward more long term survivors, the results were further improved upon by the continuing development of adoptive immunotherapy. Improved cell transfer and expansion techniques made possible the rescue, removal and expansion in vitro of more tumor specific effector cells from patients with cancer, which in animal tumor models were 100 times as potent as previously used LAK cells on a per cell basis. See Devita, Hellman & Rosenberg, op. cit.; Rosenberg et al, Journal of the National Cancer Institute 86:15, 1159-1166 (1994); Haskell, op. cit.; Stein, op. cit.; Rosenberg & Yang, JAMA, op. cit. These improved effector cell transfer and expansion techniques involve the growth of tumor-infiltrating lymphocytes (TILS) by first extracting bits of tumor from the patient (rescue), then expanding the effector cells therein in vitro, followed by re-infusing the expanded effector cells into the patient. Initial treatments may be followed by further growing of more effector TILS for a second and third course of treatment.
However, there are substantial limitations to this present state of the art technique. The limitations are that it is very expensive in terms of time, equipment and consumables. Further, the original effector TIL cells can only be rescued from a fraction of cancer patients and many tumor sites are inaccessible to this approach. Even if original effector TILS are rescued from a tumor site, only approximately 50 to 70% can be expanded in vitro to provide a suitable dose for treatment. In addition, the actual growing of these TILS is very complex and difficult. Each cancer patient's cells react differently to in vitro effector cell transfer techniques. Even after the first set of TILS are rescued and expanded in vitro, the second or third set for future treatment may not grow. Also, the very invasiveness of extracting tumor from a patient (rescue) could have a tendency to spread tumor cells in the blood system, thus possibly promoting and spreading tumor growth.
Moreover, because the time and labor required to grow these cells for the majority of patients is 20 to 60 days, it is burdensome and time consuming for the medical team. Since each patient's effector TILS grow differently, the rate of growth of each patient's effector cells affects the anti-tumor activity of the cells. Namely, the slower growing TILS have less anti-tumor activity than the more quickly growing effector TILS. Furthermore, the actual administration of the effector TIL cells, in two to four separate bags, separated by several hours, is burdensome and invasive to the patient and requires massive amounts of IL-2 for further activation. The procedure is associated with a grade 3 or 4 toxicity, which means admittance to Intensive Care Unit (ICU) (see Rosenberg, JNCI, op. cit.).
In sum, although the addition of these TIL effector cells is more potent than IL-2 alone or IL-2 with LAK effector cells, this technology, with its complexity, cost, invasiveness, time and other aforementioned aspects, does not lend itself to the American Community Hospitals. Also, the addition of TILS is only one type of effector cell, it does not address other potent effector cells such as NK cells, macrophages, B cells, Neutrophils (PMNs) and others, which are all responsive to and activated by the lymphokine IL-2 to mediate an anti-tumor response. For instance, IL-2 treated patients demonstrate a T cell and macrophage inflammatory infiltrate at tumor sites. The immune system operates as a symphony with myriad complexity and interactions with a multitude of effector cells. This effector TIL technique does not address this.
The lymphokine IL-2 exerts its effects through a specific saturable receptor system, located primarily on T cells, B cells, NK cells and LAK cells. The bulk of the IL-2 dependent activity occurs via the high affinity receptor. The effector cell transfer and expansion TIL technique does not address or direct its activity toward the high affinity IL-2 receptor. Therefore, even if these TIL effector cells are re-infused in the patient, these same effector TIL cells would not be any more receptive to IL-2 because nothing has been done to up-regulate their high affinity IL-2 receptors.
Currently under investigation is the utilization of monoclonal antibodies to stimulate and/or enhance host immune effector mechanisms along with several other techniques. See Nakajima et al., Proc. Natl. Acad. Sci. USA 91, 7889-7893 (1994). Another technique currently being investigated is the insertion of the gene for the high affinity IL-2 receptor in effector TILS. This technique is exceedingly complex, expensive, difficult and does not appear to work in sufficient amount of cells to be clinically relevant at this time. The grade 3 and/or 4 toxicity associated with IL-2 and effector TILS treatment is a severe detriment to this method of increasing effector cells and potentiating lymphokine IL-2 activity.
In a study of IL-2 and TILS, effector TILS were characterized extensively. See Rosenberg et al., op. cit. These TILS, which were rescued from a tumor site, expanded in vitro, and re-infused in the patient were primarily CD-3+, CD-4+, CD-8+ and CD-56. The sole advantage of effector TIL rescue, expansion and re-infusion is that patients treated with IL-2 alone demonstrated a 17% response rate; whereas the addition of effector TILS increased the response rate to 34%, indicating that the addition of effector cells adds therapeutic benefit. See Cetus, op. cit.; Devita, Hellman & Rosenberg, op. cit.; Rosenberg et al., JNCI, op. cit. Further evidence that the addition of effector cells, such as TILS, adds therapeutic benefit to lymphokine administration is that some patients who have failed lymphokine, for instance, IL-2, administration alone, respond to a subsequent course of IL-2 plus effector cells. These results suggest that the addition of effector cells to lymphokine administration adds therapeutic benefit.
The present invention is directed to a method for adding and maintaining effector cells prior to and during treatment to potentiate and increase therapeutic benefit derived from the administration of a lymphokine, such as IL-2, or IL-12, a cytokine, biological response modifier and/or pharmacological agents directed toward disease pathogens. The present invention appears to cause a broad based leukocytosis, lymphocytosis and increase of effector cells in vivo, and to increase the same sub-population of lymphocytes as the aforementioned effector TILS in vivo and in an apparently essentially non-toxic to minimally toxic manner.
It is generally believed that the larger the population of effector cells, the better the chance for a favorable resolution for many disease states, including cancer, and viral, bacterial and protozoa infection. Historically and currently this increase in effector cells is known as an active non-specific response. Examples of agents which have been used in this modality are: Bacille Calmette-Geurin--methanol extractable residue (BCG-MER), Coryne bacterium parvum, levamisole, thymosines, and Coleys mixed toxins. Results of studies of these agents show little value and a checkered history because it apparently is inadequate to simply expand the quantity of effector cells alone without administering a lymphokine, cytokine and/or biological response modifier in order to activate and turn these effector cells on to elicit a cytotoxic anti-pathogen response from these cells.
These methods of increasing effector cells have substantial shortcomings. Among the most serious are production of antibodies and tolerance. See Devita, Hellman & Rosenberg, Ch 17, op. cit.; Haskell, op. cit. The aforementioned agents all engender the creation of specific antibodies and the patient subsequently develops irreversible tolerance to these agents. Therefore, administration of these agents will apparently not elevate effector cells after a series of administrations. Furthermore, since antibody is created, the bulk of increase of effector cells with little activity is directed toward the reaction to these agents and only the excess immune cells (by-standers) are available to fight the disease pathogen or be stimulated by subsequent lymphokine/cytokine administration. These agents also produce their own unique toxicities. For instance, BCG is known to have substantial toxicities associated with its use. See Devita, Hellman & Rosenberg, Ch 17, op. cit.; Haskell, op. cit.
None of the aforementioned methods, including adoptive immunotherapy, are known to induce the expression of the high affinity IL-2 receptor on effector lymphocytes. Tanaka et al. (Scand. J. Immuno. 31, 547-552 1990), have shown that the specific culturing in vitro of human peripheral blood mononuclear cells with high concentrations of zinc induces the expression of high affinity IL-2 receptors on effector lymphocytes. The present invention raises the intracellular concentration of zinc in whole blood thus producing in vivo, the in vitro conditions reported by Tanaka. It is believed that this induces the expression of high affinity IL-2 receptors on lymphocytes. See Hamdi, Brit. J. Indust. Med. 26, 126-134 (1969).
The effect of zinc exposure by ingestion, inhalation or other means on human health and safety has been extensively studied. Zinc oxide fume inhalation, in every reference to it from pre-christian times onwards, is considered a nuisance, occupational disease and an industrial toxicological problem. See NIOSH, criteria document. There does not appear to be any suggestion of possible or potential medical usefulness in the historical reports to date.
The present invention involves administration of zinc by zinc oxide fume inhalation. It is believed that effects equivalent to the present invention are not achievable by other forms of administration of zinc, including ingestion of up to and including toxic levels in humans, since sufficient elevation of intracellular zinc levels and symptomology of zinc metal fume fever including expansion of effector cells is not thereby attained. Studies have shown that up to 300 mg of zinc, 10 fold more than is administered by inhalation by the present invention, administered orally does not elevate the intracellular level of zinc or expand effector cells. Study suggests that excess ingested zinc is stored in the plasma without expansion of effector cells. See Chandra, JAMA 252:11, 1443-1446 (1984).
The safety of zinc oxide fume inhalation has been ascertained by agencies of the United States Government and by published case reports and experimental studies. See Blanc, Annals of Internal Medicine 114, 930-936, 1991; Drinker et al., Journal of Industrial Hygiene 9:8, 88-97, 98-108, 331-345, 1927; NIOSH, Recommended Standard, US Dept. of Hlth, Educ, & Welfare, 657-645/220, 1976; NIOSH, National Institute for Occupational Safety, Criteria Document PB-246-693, 1-52 1975; Occupational Hlth Guideline for Zinc Oxide Fume, US Dept of Hlth & Human Svc--US Dept of Labor, Sept 1978; National Safety Council, Data Sheet 1-267-Rev 86. As an example of the lack of toxicity of the present invention, Hamdi (op. cit.) reports on page 127, that the 12 workers, working 8 hours a day, 6 days a week with heavy exposure to zinc oxide fume, exposed several times a day from 4 to 21 years, with the average duration of exposure of 11 years, demonstrated no apparent toxicity.
Zinc oxide fume inhalation according to the present invention is directly useful in potentiating existing and emerging treatments in cancer medicine, AIDS and AIDS-related complex (ARC) where the patient would benefit in an increase in effector cells and up-regulation of lymphokine IL-2 receptors on these same cells in preparation for lymphokine and cytokine administration. AIDS is characterized by progressive destruction of CD-4 lymphocytes. In addition it has been discovered that CD-8 lymphocytes are very useful in combating HIV disease and holding the virus in check. The present invention would expand effector CD-4 and effector CD-8 populations in afflicted patients and up-regulate the IL-2 receptor on these same cells in preparation for administration of cytokines, such as the lymphokine IL-2.
Moreover, IL-12, a potent lymphokine, activates natural killer cells. Natural killer cells have been shown in vitro, in the presence of IL-12, to correct some of the immunological deficiencies of blood taken from HIV patients and to kill the AIDS virus in vitro. See Stein, op. cit.; Cancer Research Institute 1:2, 1-8, 1994; J. of Experimental Medicine, May 1992, Science, Dec. 10, 1993, Science, Oct. 8, 1993.
In cancer and HIV medicine, the expansion and up-regulation of all these distinct populations of effector cells which respond to IL-2, IL-12 or other lymphokines or cytokines is directly useful in increasing existing therapeutic response and extending indications for the usefulness of lymphokines and cytokines.
The agent itself, in addition to expanding effector cells and up-regulating high affinity IL-2 receptors, synergizes with lymphokines and cytokines, such as IL-2 and potentiates the effect of IL-2. See Tanaka, op. cit. The present invention addresses the shortcomings and of the current adoptive immunotherapy modality used in preparation for administration of lymphokines, including IL-2 and IL-12, and cytokines, including the interferons. See Stein et al., op. cit.; Nakajima et al., op. cit.
Among the advantages of the present invention are that it does not appear to produce tolerance other than tachyphylaxis. Thus no tolerance is developed to successive treatments. Accordingly, long term and short term treatment is feasible without chronic or acute toxicity. See Niosh, criteria doc; Occupational Health Guideline, op. cit.
It is thus an object of the present invention to provide a relatively simple, nontoxic and nonspecific method of increasing and maintaining immune effector cells in vivo and up-regulating high affinity IL-2 receptors on such cells.
In particular, it is an object of the present invention to provide a method of increasing the quantity and quality of effector cells and IL-2 receptors in patients afflicted with cancer, or viral, bacterial, or other infectious diseases or pathogens, before and during treatment with lymphokines, including IL-2, or other cytokines, biological response modifiers or pharmacological immunomodulators.
Further, it is an object of the present invention to provide a method of increasing the quantity and quality of immune effector cells in patients afflicted with cancer, viral, bacterial, or other infectious diseases or pathogens, in preparation and maintenance of such effector cells before and during treatment with lymphokines, including IL-2 and IL-12, cytokines, biological response modifiers and other pharmacological immunomodulators. Such immune effector cells include T cells (T-11), B cells (B-1), mature t cells (T-3), T helper/inducer (T-4), T suppressor/cyto (T-8), natural killer (NK), macrophages, neutrophils (PMNs) and other leukocytes.

Method of preparing and maintaining the immune system for lymphokine, cytokine and biological response modifier administration


A circulation channel circularly supplying air heated by a burner is connected to a drying chamber into which a painted workpiece is supplied. The circulation channel includes a flame holding cylinder surrounding a flame of the burner and a casing surrounding the flame holding cylinder from outside and protrudes further than the flame holding cylinder toward a front end side, opposite to a side of the burner, of the flame holding cylinder. The casing includes a low temperature air inlet port that introduces low temperature air from outside into the casing, an exhaust port that exhausts high temperature air heated by the burner and the low temperature air to the circulation channel, and a mixing mechanism that is formed in the casing and mixes the high temperature air and the low temperature air before the high temperature air and the low temperature air are exhausted from the exhaust port.

Conventionally, as this type of a paint drying oven, a drying oven is known in which air heated by a burner is circularly supplied into a drying chamber into which a workpiece is to be supplied (for example, see Patent Literature 1). Further, in recent years, there has been proposed a configuration that includes a flame holding cylinder surrounding a flame of a burner and a burning cylinder covering the flame holding cylinder from outside, where low temperature air is supplied into the burning cylinder from outside.


A self-operated mini therapeutic device for venous thrombus prophylaxis, including plural “Z” shape air passages and plural magnets defined in an air cushion, a mouth of the respective air passages connected to diverting valve via pipes, the diverting valve connected to an inflating and extracting mechanism via the pipes, so as to form air paths for inflation and extraction of the respective air passages in the air cushion, a control circuit employed to control the diverting valve. The self-operated mini therapeutic device can use pressure wave and magnetic stimulation to prevent and treat venous thrombus.

1. Field of the Invention
The present invention relates to a therapeutic device, and more particularly to a self-operated mini therapeutic device that can use pressure wave and magnetic stimulation to prevent and treat venous thrombus.
2. Description of the Prior Arts
According to clinical observation, the peoples after operation, anesthesia, long time bedridden or the disabilities, such as the patients suffering from paraplegia, out of conscious, or the healthy peoples after long time of sitting or standing, they are susceptible to so-called deep venous thrombus which happens in the deep vein at the patients' thigh or buttocks. The thigh muscles lack of exercise or the partial blood vessels are injured or the blood viscosity of the lower part of the body is too high, all these factors will engender the venous thrombus. Clinics show that if a blood clot moves from deep vein to lung, which can lead to sudden death by lung clot, or it will interfere the cardiovascular blood circulation that also endangers the life of the patient.
Humen are susceptible to varicose veins of lower limbs because we walk on two legs, which results in valve failure and stagnant blood. The pregnant women are also susceptible to varicose veins of lower limbs due to the increment of the progestational hormone and hypervolemia.
The solution of eliminating or preventing the above-mentioned symptoms is to improve the blood circulation and make it flow smoothly. The blood circulation depends not only on the cardiac contraction but also on the muscle contraction. Since over half of the muscles are located in lower limbs, the legs play the role of a "second heart".
In clinical practices or in particular environments, besides medicines can be used to improve the blood circulation, it is also very important to take some auxiliary measures to prevent, control or treat such kind of deceases.
Conventional method is to apply intermittent compression to patient's legs so as to improve the blood circulation. According to a thesis of "External Pneumatic Intermittent Compression on Fibrinolysis in Man" by Allenby et al published in "The Lancet" of Dec. 22, 1973, which discloses that the Fibrinolysis in patient's body will be inhibited after operation, and the pneumatic intermittent compression in the thighs will encourage the fibrinolysis. The author further discloses that the best way of preventing the after-operation venous thrombus is to apply pneumatic intermittent compression to the patent's shank in or after operation.
Furthermore, from hemorheological point of view, the blood viscosity can be decreased only when subjected to enough shearing stresses, especially the blood in the deep vein of the legs needs more high shearing stresses then the blood circulation can be activated and improved. Since the veins have venous valves, the axial shearing stresses in the veins should be maintained in a higher level then the blood circulation runs smoothly.
However, due to the structural limitation of the air sacs of the conventional portable pneumatic therapeutic device for treatment of venous thrombus, which only uses the vertical compression of the air sacs to the body surface. As disclosed in U.S. Pat. No. 6,290,662 of Sep. 18, 2001, wherein a portable self-operated device for deep venous thrombus prophylaxis only has vertical compression on the patient's body so that the viscose blood in the deep and shallow veins will only reciprocate between two or several venous valves, and the blood circulation cannot be improved. Moreover, since the air sac is too big, it needs long time to inflate the air to a desired pressure.
In addition, many documents have disclosed that magnetic stimulation has positive effect on muscle nerves, e.g. Wen-Hau Lin disclosed in U.S. Pat. No. 6,213,933 of Apr. 10, 2001, that magnetic stimulation could stimulate fibrinolysis. However, so far the magnetic stimulation device of prior arts is not portable, let alone a mini therapeutic device with functions of pneumatic compression and magnetic stimulation.
So far, all the devices with the similar functions, whatever portable or not, they have very limited treatment effect due to the strength and the acting level are inappropriate which cannot satisfy the demands of the physiological pulsation of the deep veins and the peripheral nerves and muscle tissues. The way the devices operate is monotonic and some effects are even unsuitable. And the portability of the so-called "portable" is also limited due to the air sacs should be big enough for maintaining useful effect.
The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional therapeutic device.

Self-operated mini therapeutic device for venous thrombus prophylaxis


An apparatus for evaluating arteriosclerosis of a living subject, including a blood-pressure measuring device which measures at least one blood-pressure value of the subject, a pulse-wave detecting device which detects a pulse wave from a portion of the subject, a relationship determining device for determining a relationship between pulse-wave magnitude and blood pressure, based on at least one magnitude of the pulse wave detected by the pulse-wave detecting device and said at least one blood-pressure value measured by the blood-pressure measuring device, an incident-wave-peak determining device for determining a magnitude of a peak point of an incident-wave component which is contained in the pulse wave detected by the pulse-wave detecting device, a reflected-wave-occurrence-time determining device for determining a time of occurrence of a peak point of a reflected-wave component which is contained in the pulse wave, a pressure-difference determining device for determining, according to the relationship between pulse-wave magnitude and blood pressure, a pressure difference corresponding to a magnitude difference between a magnitude of the pulse wave at the time of occurrence of the peak point of the reflected-wave component, and the magnitude of the peak point of the incident-wave component, and a display device which displays the pressure difference determined by the pressure-difference determining device.

1. Field of the Invention
The present invention relates to an arteriosclerosis evaluating apparatus which evaluates arteriosclerosis of a living subject based on afterload acting on the subject's heart.
2. Related Art Statement
Pulse-wave propagation velocity or pulse-wave augmentation index is known as an index used to evaluate arteriosclerosis of a living person. Pulse-wave propagation velocity is a velocity at which a pulse wave propagates between two portions of a person, and it increases as the person's arteriosclerosis advances. Pulse-wave augmentation index, known as AI, is generally determined as a percentage of a value obtained by dividing a magnitude difference between a magnitude of a pulse wave at the time of occurrence of a reflected-wave component of the pulse wave and a magnitude of a peak point of an incident-wave component of the pulse wave, by a pulse pressure of the pulse wave, and there is a tendency that this index increases as arteriosclerosis advances.
In addition, cardiac afterload, i.e., afterload acting on person's heart changes in relation with arteriosclerosis. The cardiac afterload is known as a load that is exerted to the heart by the resistance of peripheral blood vessels, such as aorta and arterioles. The reason why cardiac afterload relates to arteriosclerosis is that the harder the arteries are, the greater the resistance of the blood vessels is and accordingly the harder the arteries are, the greater the load acting on the heart at the time of ejecting blood is.
Cardiac afterload provides different information about evaluation of arteriosclerosis, than the information provided by the conventional arteriosclerosis-evaluation indexes such as pulse-wave propagation velocity or pulse-wave augmentation index. Thus, it is expected that if cardiac afterload is used either solely or in combination with one or more conventional arteriosclerosis-evaluation indexes such as pulse-wave propagation velocity or pulse-wave augmentation index, arteriosclerosis can be evaluated with higher accuracy.
However, as described above, cardiac afterload is a load exerted to person's heart by resistance of peripheral blood vessels, and accordingly it is difficult to directly measure it. Thus, there has not been practiced to measure cardiac afterload and evaluate arteriosclerosis based on the measured afterload.


A method for fitting a cochlear prosthesis to a cochlea having residual acoustic hearing capability, in order to exploit the residual acoustic hearing capability to the extent possible. A portion of the cochlea having residual acoustic hearing capability is determined by measuring the neural response to acoustic and/or electrical stimulations. Electrical stimulations are applied only to the portions of the cochlea lacking acoustic hearing capability, or possessing only partial acoustic hearing capability. Surgical implantation depth may be optimised by the method, and/or a patient map may be suitably defined to implement the method.

1. Field of the Invention
The present invention relates to fitting of cochlear implants, and in particular to an electrode array fitting which allows the auditory nerve to be stimulated by both acoustic and electrical stimuli.
2. Related Art
Cochlear implants have been developed to assist people who are profoundly deaf or severely hearing impaired, by enabling them to experience a hearing sensation representative of the natural hearing sensation. For most such individuals the hair cells in the cochlea, which normally function to transduce acoustic signals into nerve impulses which are interpreted by the brain as sound, are absent or have been partially or completely destroyed. The cochlear implant therefore bypasses the hair cells to directly deliver electrical stimulation to the auditory nerve with this electrical stimulation being representative of the sound.
Cochlear implants have traditionally consisted of two parts, an external speech processor unit and an implanted receiver/stimulator unit. The external speech processor unit has been worn on the body of the user and its main purpose has been to detect the external sound using a microphone and convert the detected sound into a coded signal through an appropriate speech processing strategy.
This coded signal is then sent to the receiver/stimulator unit which is implanted in the mastoid bone of the user, via a transcutaneous link. The receiver/stimulator unit processes the coded signal into a series of stimulation sequences which are then applied directly to the auditory nerve via a series or an array of electrodes positioned within the cochlea, proximal to the modiolus of the cochlea. One such cochlear implant is set out in U.S. Pat. No. 4,532,930, the contents of which are incorporated herein by reference.
With improvements in technology it is possible that the external speech processor and implanted stimulator unit may be combined to produce a totally implantable cochlear implant unit that is capable of operating, at least for a period of time, without the need for any external device. In such a device, a microphone would be implanted within the body of the user, for example in the ear canal or within the stimulator unit, and sounds would be detected and directly processed by a speech processor within the stimulator unit, with the subsequent stimulation signals delivered without the need for any transcutaneous transmission of signals. Such a device would, however, still have the capability to communicate with an external device when necessary, particularly for program upgrades and/or implant interrogation, and if the operating parameters of the device required alteration.
Much effort has gone into developing stimulation strategies to provide for device customisation in order to produce the best available percepts for the prosthesis recipient. Nevertheless it is acknowledged in the cochlear implant field that the percepts produced by pulsatile electrical stimulation often sound unnatural and somewhat harsh. Although many patients adapt to this sound and, after some time, even find it natural, this is not always the case and some patients may experience difficulties. In some instances in the past, for potential implant recipients having some amount of residual natural hearing, the expectation of harsh and/or unnatural sounding percepts produced by cochlear implants has been less attractive than simply persisting with unassisted residual hearing.
Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.
Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.


A computer-assisted method, computer system, and program product provide the functionality of a portal for persons to find, based on a topic of interest, the nearest relevant in-person gathering of other persons interested in the topic as well. The system provides for the automated creation of groups and for their automatic sustainment through automatic scheduling of periodic gatherings. Strangers in geographic proximity are automatically brought together into chapters formed around the topic of interest. Chapters may be led by organizers, and gatherings may have hosts. Automatic functions for venue selection, venue voting, cancellation, and feedback are provided.

Field of the Invention
A system and a method consistent with the present invention broadly relates to organizing real-world gatherings. More particularly, the present invention is consistent with providing an automated, computer-assisted system and a method for organizing a real-world gathering for a particular topic of interest.
Description of the Related Art
The Internet now is one of the most popular sources for obtaining and sharing information. One popular activity associated with the Internet is communication between people, and notably people who may be separated by vast distances. Some familiar technologies that facilitate communication and involve the Internet include email, bulletin boards, virtual chat rooms, blogs, and instant message systems. This set of technologies, and those that are similar, are characterized by being substantially solely on-line.
In other words, the foregoing set of well-known Internet related applications support geographically distributed communications, and do not have as their objective anything more.
In spite of the increased ability to communicate on-line, however, many people still are interested in meeting together in person with other people who are interested in the same topic. What is needed is a way to harness the formidable communications capabilities of the Internet to help support and facilitate such in-person topic-related gatherings (herein, 'gatherings' and 'meetings' shall be interchangeably used, and shall unless otherwise noted refer to in-person gatherings).
The challenges of organizing real-world gatherings are much different from those of organizing online meetings. For example, to engage in online chat, there is no question of physical location, distance from home, availability of venue, or the like. All of the foregoing considerations and more, including intangibles such as social dynamics, make organizing real-world gatherings a more difficult and complex task.
Known Internet communication tools are insufficient for the task. In particular, email alone is inadequate because a person in one area has no organized way of approaching the problem of finding the identities and addresses of others in his area who are interested in a given topic and also interested in a topic-related meeting. Instant messaging and chat rooms alone are likewise inadequate for the same reasons.
Message boards and blogs are insufficient by themselves because these tools are not designed to allow a person to begin with a topic of interest, find an associated message board or blog that is relevant to the topic, and identify participants of the board or blog who are in a person's area and who are interested in an in-person topic-related meeting.
Internet dating and introduction services are related to the idea of in-person meetings, but only on a one-to-one model, and all of these services are agnostic with respect to a particular topic of interest; instead, such services focus on compatibility with the idea of forming a relationship and not on meeting in a group setting to discuss a given topic of mutual interest. In effect, these services facilitate only one-off (non-recurring) gatherings in only a single geographical locale.
Internet newsgroups are topic related, but provide no support to a person who wants to attend a topic-related meeting in person in his own geographic area.
Additionally, so-called 'social networking' services, such as SixDegrees, provide a system for users to be introduced to friends of friends via website communication and/or email, but again provide no support to a person who wants to attend a topic-related gathering in person in a selected geographic area.
Internet invitation services likewise are inadequate to fulfill the above-identified need. Such services, of which Evite is an example, allow users to enter the email addresses of invitees to private events. Automated invitations are sent by the service, and each invitee may accept or decline the invitation. Separately, users may browse or search the Evite website directory of public events, but all the events are one-off, non-recurring events, and all the events must be submitted by individual users choosing to publicize already existing events. It is impossible for persons who are not already acquainted to use the system to self-organize into groups, and to attend topic-related in-person gatherings with others in a given locale. Evite thus does not provide an automated method for strangers with a common interest to self-organize into real-world, local groups.
General information postings, such as ads or articles in print media and signs posted around town, are well known. This approach starts with a meeting at a date and time certain, and then advertises the meeting. Posting such notices in common locations such as a town square or popular bulletin board is now possible online as well. One such example of this approach is a 'craigslist' type website (see, e.g., dc.craigslist.com), where people wishing to advertise meetings can easily make such a posting. Such posting approaches, however, are limited in that they begin with a predetermined meeting location, date, and time, and require a group already to be formed. No self-formation of groups takes place, and the location of the posted meeting cannot be determined by those Interested in attending. Furthermore, the posted events are typically one-off, non-recurring events. Any group continuity depends on the efforts of the person doing the posting, and no support along these lines is provided by the website.

This patent is subject to a terminal disclaimer.

System and a method for organizing real-world group gatherings around a topic of interest


An integrated circuit device which implements a plurality of programmable digital logic functions derived from a number of digital logic inputs and further includes an on-chip digital-to-analog converter providing an analog output current signal responsive to the programmable logic functions derived from the digital inputs is provided. The means for implementing the programmable logic functions may include a programmable logic circuit having a programmable AND array comprising a plurality of AND gates, each with a plurality of inputs and at least one output. The AND gate inputs are selectively programmable with the input terms to generate an output signal to the AND gate outputs. The device further includes an OR gate array having a plurality of OR gates, each of the OR gates including a plurality of inputs and an output, thereby providing a plurality of OR gate array outputs generating a plurality of digital logic signals. The digital-to-analog converter includes a plurality of inputs coupled to a subset of the plurality of OR gate array outputs for converting the digital signals present on the OR gate array outputs into a variable amplitude output signal. In one embodiment, an 8-to-8 encoder providing the outputs of the subset of OR gate array outputs to the inputs of the digital-to-analog converter is also included.

1. Field of the Invention
The invention relates to integrated circuit devices incorporating programmable logic to provide user programmable output functions, and specifically, devices which provide analog signal outputs.
2. Description of the Related Art
Programmable logic devices (PLD), including the programmable array logic (PAL) device and the programmable gate array, are integrated circuits which can be configured by the user to perform logic functions on digital inputs. PLDs offer digital designers a flexible and cost-effective implementation for complex logic circuits and the best alternative amongst a spectrum of products ranging from fully customized integrated circuits to standard, dedicated-purpose devices.
A typical PAL includes a programmable array of AND gates, and a fixed array of OR gates. In other programmable logic devices, both the AND and the OR arrays are programmable. The outputs of such combinatorial logic arrays used in programmable logic circuits may be coupled directly to an I/O pin, or input to clockable registers. In many devices, the combinatorial logic array outputs are registered and are fed back to the inputs of the combinatorial array. Some programmable logic circuits also include a clockable input synchronizing register located between an input pin and one of the inputs to the combinatorial array. PAL is a trademark of Advanced Micro Devices, Inc. See, Advanced Micro Devices, Inc. PAL.RTM. Device Handbook, (1988).
The programmable logic device has thus given the digital designer a means for reducing circuit size through higher integration, ease of design and documentation by software specification, and the security of keeping one's own design proprietary.
It is desirable to provide a single integrated circuit which has both analog and digital functional components working together to provide an analog output signal responsive to digital inputs which are acted upon by programmable logic functions. Such a device allows great flexibility and programmability by allowing analog outputs to be derived from programmable digital solutions.
One simple solution to this objective is presented in the X9MME E.sup.2 POT Digitally Controlled Potentiometer by Xicor Corporation, Milpitas, Calif., which provides ninety-nine (99) increment, resistor ladder controlled by a digitally decoded counter which includes the capability of storing the count value in non-volatile memory on power down. In addition, several types of digital-to-analog converters are well known in the art, including the "weighted resistor" and the "ladder network" types of DACS. However, to the best of applicants' knowledge, no devices have been provided which provide programmable logic circuitry and a digital-to-analog converter in a integrated circuit device.

Programmable logic device incorporating digital-to-analog converter


A handheld power tool is disclosed. The handheld power tool has a drive oscillating along a working axis and a vibration damper. The vibration damper has a mass element suspended in a spring mechanism. The spring mechanism acts with a first spring stiffness and acts with a second spring stiffness. The first spring stiffness is different from the second spring stiffness.

The present invention relates to a handheld power tool.
The inventive handheld power tool has a drive oscillating along a working axis and has a vibration damper. The vibration damper has a mass element suspended in a spring mechanism. The spring mechanism acts in a first direction parallel to the working axis with a first spring stiffness and it acts with a second spring stiffness in a second direction opposite the first direction. The first spring stiffness is different from the second spring stiffness.
The handheld power tool, for example, a handheld power tool having a pneumatic striking mechanism, exerts a return blow periodically on the user. The amplitude thereof may be diminished by the vibration damper, but a vibration damper having an asymmetrical design can produce a greater damping effect with the handheld power tool. The spring stiffness may have a discontinuity or a very drastic change relative to the basic position. The discontinuity leads to a highly non-harmonious movement of the mass element and non-harmonious forces, which may be more suitable for damping the machine housing.
According to one embodiment, the first spring stiffness amounts to between five and ten times the second spring stiffness. The ratio of the spring stiffness values may be used to adjust the damping of the vibration damper to the rebound behavior of the handheld power tool. The greater the ratio, the shorter and greater is the acceleration of the mass element by the stiffer side.
According to one embodiment, the mass element in the basic position is in contact with the spring. In the basic position the mass element may be arranged between two prestressed springs. According to one embodiment, the two prestressed springs are fixedly connected to the mass element. Because of the fixed connection, this results in low losses in the springs due to plastic deformation or due to friction.
According to one embodiment, the mass element is attached to a bending spring which is arranged at an inclination to the working direction. The bending spring is relaxed when the mass element is in the basic position.
The following description illustrates the invention on the basis of exemplary embodiments and figures.


A handheld device for the location and identification of a radiation source, including: a radiation transparent housing; a radiation locator device disposed within the radiation transparent housing operable for determining the location of the radiation source, wherein the radiation locator device includes a plurality of gamma detection crystals arranged in a geometric pattern and separated by a gamma shielding material, a plurality of detectors coupled to the plurality of gamma detection crystals, and a processor module coupled to the plurality of detectors; one or more of a neutron detection crystal and a gamma spectroscopy crystal disposed within the radiation transparent housing adjacent to the radiation locator device; and one or more detectors coupled to the one or more of the neutron detection crystal and the gamma spectroscopy crystal and the processor module; wherein the one or more of the neutron detection crystal and the gamma spectroscopy crystal, the one or more detectors, and the processor module are collectively operable for identifying the radiation source.

In general, it is difficult to locate and identify unknown sources of radiation. Often, complex and bulky devices utilizing many radiation detection crystals are necessary.
For example, U.S. Pat. No. 7,626,178 provides an integrated neutron-gamma radiation detector with an adaptively selected gamma threshold. An integrated radiation detector having a pulse-mode operating photosensor optically coupled to a gamma sensing element and a neutron sensing element is disclosed. The detector includes a pulse shape and processing electronics package that uses an analog to digital converter (ADC) and a charge to digital converter (QDC) to determine scintillation decay times and classify radiation interactions by radiation type. The pulse shape and processing electronics package determines a maximum gamma energy from the spectrum associated with gamma rays detected by the gamma sensing element to adaptively select a gamma threshold for the neutron sensing element. A light pulse attributed to the neutron sensing element is a valid neutron event when the amplitude of the light pulse is above the gamma threshold. However, this does not provide 4pi triangulation and does not solve the high gamma interference problem.
U.S. Pat. No. 7,335,891 provides a gamma and neutron radiation detector. A sensing element or detector activated by radiation includes a first scintillator activated by gamma radiation; and a neutron sensing layer including a second scintillator activated by neutron radiation. Again, this does not provide 4pi triangulation and does not solve the high gamma interference problem.
U.S. Pat. No. 8,232,530 provides a solid state neutron detector. A neutron detector for the detection of neutrons in fields with significant gamma or beta radiation includes a neutron sensitive scintillator crystal, providing a neutron capture signal being larger than the capture signal of 3 MeV gamma radiation, a semiconductor based photo detector being optically coupled to the scintillator crystal, where the scintillator crystal and the semiconductor based photo detector are selected so that the total charge collection time for scintillator signals in the semiconductor based photo detector is larger than the total charge collection time for signals generated by direct detection of ionizing radiation in the semiconductor based photo detector, the neutron detector further including a device for sampling the detector signals, a digital signal processing device, means which distinguish direct signals from the semiconductor based photo detector, caused by γ or β-radiation and being at least partially absorbed in the semiconductor based photo detector, from light signals entering the semiconductor based photo detector, after being emitted from the scintillator crystal after capturing at least one neutron, by means of pulse shape discrimination, utilizing a difference between the total charge collection time for scintillator signals from the total charge collection time for signals generated by direct detection of ionizing radiation in the semiconductor based photo detector, and means which distinguish neutron induced signals from γ-radiation induced signals in the scintillator crystal by discriminating the different signals via their pulse height, making use of the difference between the number of photons generated by neutron and γ-radiation in the field of interest. However, this does not provide for the location or identification of radiation sources.
U.S. Pat. No. 8,389,941 provides a composite gamma-neutron detection system, including a gamma-neutron detector based on mixtures of thermal neutron absorbers that produce heavy-particle emission following thermal capture. The detector consists of one or more thin screens embedded in transparent hydrogenous light guides, which also serve as a neutron moderator. However, this is not portable and does not provide for the location of a radiation source.
Finally, US 20160041273 provides a combined thermal neutron detector and gamma-ray spectrometer system, including: a first detection medium including a lithium chalcopyrite crystal operable for detecting neutrons; a gamma ray shielding material disposed adjacent to the first detection medium; a second detection medium including one of a doped metal halide, an elpasolite, and a high Z semiconductor scintillator crystal operable for detecting gamma rays; a neutron shielding material disposed adjacent to the second detection medium; and a photodetector coupled to the second detection medium also operable for detecting the gamma rays; wherein the first detection medium and the second detection medium do not overlap in an orthogonal plane to a radiation flux. Optionally, the first detection medium includes a 6LiInSe2 crystal. Optionally, the second detection medium includes a SrI2(Eu) scintillation crystal. However, this does not provide for the location of a radiation source.
Thus, what is still needed in the art is a simple and compact device and method, such as a handheld device and method, for both locating and identifying a radiation source.

Device and method for the location and identification of a radiation source


The invention relates to methods for treating or preventing abnormal skin conditions in a human in need thereof, comprising administering a cell culture composition comprising a living culture of bacteria comprising at least one engineered strain that produces a recombinant polypeptide for therapeutic treatment of the abnormal skin condition. The invention also relates to pharmaceutical compositions containing, as the active principle, engineered microorganisms expressing non-vaccinogenic pharmacologically active recombinant therapeutic polypeptides in order to treat or prevent abnormal skin conditions.

The advent of compounds that are generated using recombinant DNA technology has facilitated development of a vast array of therapeutic agents having the potential to treat a great variety of disease states in animals, in particular in humans. These agents are primarily protein in nature.
The epidermis, the squamous stratified epithelium of the skin, consists of multiple sublayers and is one of the most important barriers of the body against the outside world. The stratum corneum is the outermost layer of the epidermis and develops as a result of the final anucleated step in keratinocyte differentiation from the cells in nucleated epidermal layers. Although the stratum corneum is recognized as the most important physical barrier, the nucleated epidermal layers are also significant in barrier function (Proksch. Brandner et al. 2008). Together, the skin barrier protects against extensive water loss in one direction (inside-outside barrier) and against the invasion of harmful substances from the environment (outside-inside barrier) (Proksch, Brandner et al. 2008). The maintenance of the barrier is also important for balanced proliferation in the basal layer and preservation of the calcium ion gradient and thus proper epidermal differentiation (Lee, Jeong et al. 2006).
Recent work suggests that skin commensal microorganisms are essential to maintaining healthy skin and maintaining the skin barrier. Commensal microorganisms are ones that are beneficial to their subject. e.g., human, hosts. Studies also suggest that certain skin diseases (such as acne vulgaris and atopic dermatitis) can be associated with disruptions to the normal microflora (Lin, Wang et al. 2007). Therefore, the idea that the skin microflora can be modulated using specific skin commensals to promote health or inhibit disease has received some attention (Muizzuddin, Maher et al. 2012). Many skin commensal bacteria are not considered pathogenic, therefore, these bacteria can potentially be used topically if they have therapeutic value (Nakatsuji and Gallo 2014). So far the limited amount of research in this area suggests that conventional probiotic bacteria can be of significant value when used on the skin. For example, topical application of a Bifidobacterium longum lysate has been shown to induce clinical improvement of "reactive skin" (Gueniche, Bastien et al. 2010). This is skin that is more sensitive to physical changes such as atmospheric temperature, and to chemical changes such as seen with topically applied products (Gueniche, Bastien et al. 2010). Application of the B. longum lysate to the skin of volunteers was shown to decrease sensitivity and decrease transepidermal water loss (TEWL) after tape stripping. Additionally, application of the lysate to ex vivo skin was shown to decrease signs of inflammation such as vasodilation, edema and TNF-α release (Gueniche, Bastien et al. 2010, Nakatsuji and Gallo 2014, Volz, Skabytska et al. 2014). Topical application of Lactobacillus plantarum has also been demonstrated to improve tissue repair in a burned mouse model and prevent infection in chronic leg ulcers and burns in humans (Peral. Martinez et al. 2009, Peral, Rachid et al. 2010, Brachkova, Marques et al. 2011).
A number of current limitations exist in the treatment of skin, however. Many treatments, such as topical corticosteroids or expensive biologics, do not treat the underlying issues of deficient intrinsic protein in the epidermis or imbalances in the microbial diversity in the skin. While recombinant proteins represent a promising group of therapeutic agents in the treatment of skin disease, several problems accompany their use in the context. Traditional methods employ the use of purification of recombinant proteins that are extracted from bacterial systems, purified, concentrated, and incorporated into a delivery system. The purification of recombinant proteins is often a very costly method of obtaining protein. Moreover, a number of issues accompany this, including proteolytic degradation, inefficient delivery, and the need for repeated application overtime to achieve therapeutic effect.
Our method, in contrast, addresses these issues by allowing bacteria to colonize the skin and continually secrete therapeutic polypeptides of benefit to the skin. This approach reduces need for multiple topical applications by creating a sustainable delivery system for therapeutic proteins.
Most of the microorganisms until now used for the production of recombinant proteins cannot be in safely administered to humans and animals, not being usual components of the physiological flora or being devoid of any pathogenic risk. This is particularly true for Escherichia coli, which is considered pathogenic in many cases. However, here, we describe methods of production of recombinant proteins using microorganisms that can be safety administered to humans and animals, particularly Staphylococcus epidermidis.
Other species, already used for the production of recombinant proteins, can also be used provided they meet the requisites of non-pathogenicity and ability to colonize human or animal mucosae. For example, Bacillus subtilis has been widely used as a cloning vector for producing a large number of eukaryotic proteins in view of its recognized advantageous properties (Simonen and Palva 1993). The present invention allows therefore, by suitably selecting and adapting the microorganism, the polypeptide to be expressed and the expression vectors, previously used for the production in laboratory or industrial environment, to address specific skin diseases (see FIG. 1). The present invention concerns therefore the therapeutic use of said engineered microorganisms and compositions containing the same, thereby satisfying a long felt need in the area of therapeutic delivery of drugs to treat skin conditions in humans.
Atopic dermatitis (AD), which is also known as eczema, is a chronic inflammatory skin disease that usually involves a defect in the stratum corneum of the skin, which is the protective layer comprising the outermost part of the skin. This defect is caused by a confluence of genetic, environmental, and immunological factors and is associated with an overgrowth of Staphylococcus aureus. The genetic basis of AD appears to involve a defect in the filaggrin gene (FLG), seen in approximately 50% of AD patients (McAleer 2013). The prevalence of atopic dermatitis is increasing, and affects 0.1-1% of the population worldwide, with higher rates in developed countries. AD is more common in children, affecting as many as 20% of children (McAleer 2013). Of these children, 25% never recover and continue to suffer from atopic dermatitis into adulthood. In many cases, AD can lead to more severe allergic conditions, including asthma, through a process known as the "atopic march."
The pathogenesis of AD is not completely understood, but defects in filaggrin expression are attributed to most cases of atopic dermatitis, and the pathogenesis is related to an immune response. It has been shown that AD can be caused by a combination of dry skin, skin that is prone to itching more than the average person, infections caused by bacteria, viruses, fungi, etc., and emotional and environmental factors. Filaggrin is encoded by the FLG gene on the 1q21 epidermal differentiation complex. Filaggrin is a protein produced by differentiating keratinocytes, and functions to aggregate keratin filaments into a cytoskeleton that, in combination with other components, comprises the cornified cell envelope (Brown & McLean 2012). Filaggrin loss of function mutations (R501X and 2282del4) cause ichthyosis vulgaris, the most common inherited disorder of keratinization. The same mutations also are associated with other skin and allergic conditions including AD, irritant contact dermatitis, asthma, and food allergy. Several studies have shown that increasing filaggrin on the skin helps to mitigate the AD phenotype (e.g. Stout et al. 2014, Otsuka et al. 2014).
Currently, the major therapies for AD include topical corticosteroids and antibiotics, both of which have limited efficacy in more severe cases of AD. Major drawbacks of antibiotics include issues of antibiotic resistance and dysregulation of the microbiome ecology. The microbiome is the aggregate of microorganisms present in a particular environment. The microbiome mentioned herein, is the totality of the microorganisms present on the largest human organ, the skin. Topical corticosteroids provide respite from symptoms for mild AD patients, but do not address the needs of those with chronic or severe disease. While some targeted therapies for AD treatment are under development, the competitive landscape in this market is characterized by a largely unmet need for an effective, targeted therapy for AD. One biologic therapy, Dupilumab, is an anti-IL4/13-receptor monoclonal antibody that is under Phase II clinical trial for AD, being developed by Regeneron Pharmaceuticals and Sanofi. This drug has shown promising efficacy, and is expected to reach markets in the next five years. Other similar biologic therapeutics for immunomodulation of AD are under development. However, these drugs are expected to cost tens of thousands of dollars for consumers due to high production and R&D costs, and insurance companies may not necessarily cover these costs. While these drugs attenuate the immune response, they do not have direct effects on re-establishing the skin barrier and normalizing the microbial ecology to prevent S. aureus infections. Thus, new compositions and methods for the effective treatment and prevention of abnormal skin conditions such as AD, while minimizing unwanted side effects are required.

Therapeutic treatment of skin disease with recombinant commensal skin microorganisms


The present disclosure relates generally to a modular angled light engine. In one embodiment, the modular angled light engine includes a center portion comprising an interlocking feature to connect to a second modular angled light engine and at least one housing coupled to the center portion. The at least one housing includes a heat sink coupled to a first side of the at least one housing, at least one light emitting diode (LED) coupled to an interior volume of the at least one housing and a lens covering the at least one LED and coupled to a second side of the at least one housing.

Present street light fixtures designs are inefficient and suffer a large amount of light loss. For example, street lighting requires light to be bent at high angles to achieve uniformity and higher pole spacing. The light fixture suffers with increased Fresnel reflection losses when light transmits through the flat lens at high angles. As a result, the current street light fixtures suffer from increased Fresnel reflection losses when it transmits light through the lens.