A suction device system comprising a suction tip and a containing unit wherein the containing unit is configured to allow the suction tip to rest within the containing unit such that the suction tip does not contact the containing unit.

1. Field of the Invention
The present invention relates generally to medical and/or health care devices, and in particular to a suction device for clearing of tracheostomy tubes and the like and a sanitary container therefor.
The present invention provides a suction tip and a sanitary container for storing the same such that repeated, efficient clearing of tracheostomy tubes may be accomplished with a single suction tip without allowing substantial bacterial growth between each use thereof.
2. Description of the Related Art
The invention relates generally to a suction device employable for clearing a tracheostomy tube in a patient. A tracheostomy tube is a tube inserted through the outer surface of the body and into the trachea of patients to remedy various conditions. For instance, persons may experience blockage of the upper trachea or upper respiratory tract causing difficulty with, or a complete inability to, breathe and/or respirate. Such blockage may result from a variety of conditions or ailments. The tracheostomy tube is employed to create a bypass of the blockage and allow breathing and/or respiration through the tracheostomy tube. Tracheostomy tubes have also been employed to breakup and remove congestion in the lungs or upper respiratory tract. This may be accomplished by introducing an agent into the congested area through the tracheostomy tube to loosen the congestion. Once loosened, the congesting material may be removed from the lungs or respiratory tract by suction through the tracheostomy tube.
Regardless of the purpose for which a tracheostomy tube is installed into a patient, mucus and other bodily substances typically collect around and in the tracheostomy tube which is positioned inside the trachea of the patient. These bodily substances create difficulty or complete inability to alleviate the problems or ailments for which the tracheostomy tube is intended. It has therefore been found that periodic removal of the bodily substances which collect in and around the tube is necessary.
Removal of bodily substances which collect in and around the tracheostomy tube is preferentially accomplished without removal of the tracheostomy tube from the patient. It has been found that use of suction provides a quick and efficient manner of clearing a tracheostomy tube. However, problems exist with prior equipment for introducing suction to the tracheostomy tube. For various reasons, prior art suction devices are employable for a limited number of uses. For example, the design of many suction devices are inherently weak in construction such that the device breaks after one or two uses. Another problem exists with previous suction devices in that no means is currently available for storing such a suction device between uses which will prevent contamination of the suction device until it is desired for subsequent use. Instead, such devices are set adjacent to the patient in a manner which allows the suction tip to contact a surface on which it is laid. This contact of the suction tip promotes the growth of bacteria on the suction tip, thus promoting infection within the trachea. Therefore, because bacteria on the suction tip renders the suction tip unusable, prior suction devices were relegated to a single use before being disposed.
A tracheostomy suction device which could be used repeatedly for periodic removal of mucus and other bodily matter which collects in and around the tracheostomy tube would present many advantages over prior suction devices. The cost of manufacturing, packaging, inventorying and allocating to patients the additional suction devices required for the multiple tracheostomy tube clearings experienced by many patients would be alleviated. Additionally, the cost required for a health care professional to locate a new suction device, open and attach that device to a suction means, a cost which may become substantial over a number of tracheostomy tube clearings, would be alleviated. Elimination of the time required to locate, open and attach a new suction device also greatly reduces the risk of damage to the health of a patient experiencing a difficulty or inability to breathe. Cost savings are also experienced from a decrease in disposal costs which are ever increasing as the amount of land which can accommodate such disposals decreases.
U.S. Pat. No. 4,673,398 to Turner et al. discloses a prior attempt at a medical suction device designed for clearing of a trachea through the oral cavity by applying suction from a human being. No tracheostomy tube clearing device is taught by Turner et al. Neither does Turner et al. teach a container for storing a suction device between uses such that bacteria and other unwanted substances may attach to the device. Multiple sanitary uses of the Turner et al. device is not therefore taught.
U.S. Pat. No. 4,662,367 to Core, Jr. also discloses a prior attempt at a medical suction device which merely presents a bulbous interface between a suction source and a tracheostomy tube. No sanitary container is employed for storage between uses. Multiple sanitary uses of the Gore, Jr. device is not therefore taught.
Additionally, Children""s Medical Ventures, Inc. produces a product labeled a BBG Nasal Aspirator for clearing of the nasal passages of a patient. No sanitary container is employed to prevent unwanted bacteria from attaching to the device and subsequently being introduced into the patient. Multiple sanitary uses of the BBG Nasal Aspirator device is not therefore taught. Additionally, the BBG Nasal Aspirator requires a health care professional to regulate the amount of suction delivered to the patient by adjusting the coverage of the by-pass hole. As health care professionals typically wear latex gloves over the fingers used to cover the by-pass hole, said latex tends to be suctioned into the by-pass hole even when the health care professional attempts to uncover the by-pass hole. Consequently, problems with control of the BBG Nasal Aspirator are prevalent.
It is therefore an object of the present invention to provide a medical suction device which is of durable construction and designed to allow for multiple uses thereof.
It is a further object of the present invention to provide a medical suction device which may be quickly employed.
It is a further object of the present invention to provide a medical suction device with a means of storing said medical suction device which will keep said medical suction device clean between uses.
It is a further object of the present invention to provide a medical suction device which allows a health care professional proper control over the suction provided to the application.
It is a further object of the present invention to provide a medical suction device which limits the interaction of a health care professional with tracheal secretions of a patient.
It is a further object of the present invention to provide a container that can be easily attached to a patient""s bed or bedside, or placed within a portable suction bag of a patient in the home setting.
It is a further object of the present invention to provide an acutely tapered suction tip to easily grasp tracheal secretions deep within the external protrudence of the tracheostomy tube.
It is a further object of the present invention to provide a vented storage container to avoid bacterial growth within said container.
The above and other objects of the present invention are accomplished by providing a suction device employable for clearing a tracheostomy tube, said suction device comprising a suction tip configured to be inserted into a sanitary adapter which allows for an air tight connection to a suction means. The suction tip is comprised of an elongated tube with a nozzle at an end distal from the sanitary adapter and a lip at the end proximate the sanitary adapter to provide an air tight force fit between the suction tube and the sanitary adapter. The sanitary adapter comprises an adapter tip extending therefrom, which is configured as a tube for accepting the suction tip therein and a suction means there over. In this manner, suction provided by a suction means may be directed through the sanitary adapter to the nozzle of the suction tip.
The suction tip of the present invention is configured to rest in a sanitary container which is covered by a sanitary lid. The sanitary container resembles a jar with a base at a first end thereof and threads at the opposing end thereof to allow securing of the sanitary lid thereon. The sanitary lid comprises threads which complement those of the sanitary container. The sanitary lid further comprises an adapter port to allow the insertion of the suction tip and a portion of the sanitary adapter therein. The sanitary adapter comprises a locator lip and a suspension lip. The locator lip positions the sanitary adapter laterally with respect to said adapter port. The perimeter of the suspension lip is designed to be larger than the perimeter of the adapter port such that the suspension lip stops progression of the sanitary adapter into the adapter port. The top of the threads of the sanitary container are configured at a distance from the base thereof which is greater than the distance from the suspension lip of the sanitary adapter to the nozzle of the suction tip when the suction tip is inserted into the sanitary adapter in the manner required to provide a snug fit. The sanitary lid may also have air holes or vents therein to avoid bacterial growth on the suction tip in the sanitary container which would be fostered by still air therein.
In this configuration, the suction tip of the present invention may be employed to clear the tracheostomy tube of a patient and then placed into the sanitary container through the adapter port of the sanitary lid without the suction tip contacting any objects. Additionally, the present suction tip may be stored without contacting any objects, until the patient again needs clearing of the tracheostomy tube. Because the suction tip contacts no object between uses thereof, the introduction of bacteria to the suction tip, and therefore the patient, is reduced or eliminated.
Numerous other advantages and features of the invention will become readily apparent from the detailed description of the preferred embodiment of the invention, from the claims, and from the accompanying drawings, in which like numerals are employed to designate like parts throughout the same.


A method of pre-loading a camera with film, and specifically a single use camera, is disclosed. According to the disclosed method, the camera is pre-loaded in non-darkroom conditions with the back cover assembled to the camera without exposing any substantial portion of the film to any substantial amounts of light. According to the disclosed embodiment, the camera has a film advance mechanism that employs a manual advance wheel, and the manual advance wheel is rotated in opposing directions to pre-load film from a film cassette in the camera to a film spool compartment and to wind film back into the film cassette from the film spool compartment as exposures are taken. In the disclosed embodiment, the camera is an APS camera, and rotation of the manual advance wheel also opens and closes the APS film cassette's light lock door. In a final assembly step and if the camera employs a battery, the battery is inserted inside the film spool compartment.

Recently, a new type of film cassette has been developed, sometimes called a film safe cassette, which has a light lock door and does not, at the time of purchase, or at the time that the film is first inserted into the camera, have a film leader extending from the cassette to facilitate film loading. One example of film employing such a cassette is KODAK.RTM. brand ADVANTIX.RTM. film. The cameras with which these film cassettes are used are known as Advanced Photo System, or APS, cameras, and the film safe cassettes for use therewith are sometimes also called APS film cassettes. Conventional film cartridges, such as 35 mm film cartridges, have a film leader extending therefrom at the time of purchase, and a brush or similar mechanism at the cartridge's film slot to prevent light from entering the cartridge and exposing film contained therein. In contrast, a film safe cassette does not have a brush or similar mechanism but instead has a light lock door that is automatically opened by the camera after the film has been loaded. Film is loaded into and removed from the camera via a film cassette door disposed on the bottom of the camera. The camera then drives the film out of the cassette and into a film spooling area on the opposite side of the camera from the cassette. Before the cassette can be removed from the camera, the camera rewinds the film back into the cassette, and then closes the light lock door. If the light lock door were permitted to be opened in the presence of light, the film inside the cassette would be exposed. Thus, the light lock door, operating in conjunction with the camera, ensures that film is not inadvertently exposed.
In a conventional camera, such as a conventional 35 mm camera, film is loaded from the back of the camera by opening a back door thereof, dropping the cartridge into the camera, pulling the film leader across the camera, engaging the leader on a take-up spool, then closing the back door. Since opening the light lock door in the presence of light can expose the film in a film safe cassette, conventional methods of loading film cartridges are not suited to loading film safe cassettes into APS cameras. Moreover, because at least re-usable APS cameras employ a small cassette door on the bottom of the camera to load and unload the film cassette, there is no back cover or back door that can be easily opened to practice a conventional loading technique.
So called single use cameras are known in the art. A single use camera is one that is manufactured and sold with the intent of being used only a single time (i.e., with only one roll of pre-loaded film) by the purchaser or end user. Single use cameras are usually made of plastic. Film is pre-loaded into the camera during manufacturing, and the camera is sealed closed. This is done by loading the film into the back of the camera in much the same way as a conventional 35 mm camera is loaded, then securely assembling a back cover to the camera by a locking mechanism, screws, adhesives, thermal bonding, etc., so that the back cover cannot be easily removed. Typically, a package (such as paper, cardboard or even plastic) is placed around the camera body so that the film cannot be removed without destroying at least part of the package, and in some cases, without destroying part of the camera body as well. Additionally, film cannot be easily reloaded into the sealed camera, at least not without removing the back cover and/or partial destruction of the camera body or its packaging. As is known in connection with such cameras, it is intended that the user return the entire camera, intact, to a developing lab for processing after the user is finished taking exposures. The lab removes the exposed film and discards the camera body.
Single use APS cameras are also known in the art. It will be appreciated that loading a film safe cassette into a single use APS camera presents special problems. The light lock door cannot be opened without exposing the film in the cassette, so film loading and final camera assembly must take place in a darkroom. This assembly involves performing the following steps in darkroom conditions: opening the light lock door with a tool or fixture, externally of the camera; driving film from the cassette by rotating the spool inside the cassette either manually, with a tool, or with a fixture, external to the camera; spooling unexposed film into a film spool area of the camera either manually or with a fixture, external to the camera, and loading the film cassette from the back of the camera (i.e., with the back cover removed); then, assembling the back cover to the camera. If the camera requires a battery, then depending on the construction of the camera, the battery may have to be loaded in darkroom conditions. Thus, loading film into a single use APS camera is cumbersome, time consuming, and labor intensive.
Usually, in a single use camera, all of the film is pre-wound into the film spool area (sometimes called "pre-loading"), and, during picture taking, film is withdrawn back into the cassette, one frame at a time. Single use APS cameras usually automatically close the light lock door on the film cassette after all of the film has been rewound back into the cassette. This is usually done by means of a film sensor or other mechanism.
No known single use APS camera has any built-in mechanism for opening the light lock door after the film cassette has been loaded into the camera, much less doing so with the back cover in place on the camera, and thus known single use APS cameras are not presently amenable to a film loading process that can occur in non-darkroom conditions.
Many cameras contain at least one battery, and most all cameras with flashes have at least one battery, such as a size AA or AAA battery. In the prior art, these batteries are usually housed within a specially created and specially allocated space in the camera that defines a battery compartment. Since the battery compartment requires additional space inside the camera (relative to the same camera without a battery compartment), the overall size of a camera with a battery compartment is usually larger when compared to the same camera without a battery compartment. Increasing the camera's overall size may be undesirable, because consumers may desire smaller cameras, and adding a separate battery compartment may increase the cost of production. Moreover, in single use cameras, the battery cannot be easily removed, or can be removed only by destroying a portion of the camera or its packaging, because the battery compartment is sealed within the camera. Further, loading a battery into a single use camera pre-loaded with film may need to be done under darkroom conditions to avoid exposing the pre-loaded film.
It is desirable to provide a method for loading film, and a battery, into a single use APS camera that is simple and relatively labor free, and that does not require film or battery loading in darkroom conditions. It is also desirable to provide a single use APS camera that facilitates a non-darkroom film loading method. It is further desirable to provide a single use camera with a battery compartment that does not significantly increase the overall size of the camera (relative to the same camera without a battery compartment), that permits a battery to be inserted into the camera in non-darkroom conditions, and also facilitates easy removal of the battery. The present invention achieves these and other goals.

Film and battery loading method for a single use camera such as a single use APS camera and a camera loaded according to the same


A method of manipulating a garment on a knitting machine includes the steps of orienting the garment with an opening disposed relative to one end on the knitting machine; and knitting a bridge across the opening of the garment. The bridge is affixed to the garment at a first and second site. The first and second sites are disposed near the opening. The exact positioning of the first and second sites relative to the opening are predetermined in accordance with the orientation of the garment on the knitting machine. The first site opposes the second site. The method of manipulating the garment further includes the step of dividing the bridge forming a first and a second handle. The first and second handle are fixed at the first site and the second handle is affixed at the second site. The first and second handles are useful for further processing the garment.

Manufacturers have sought a method to orientate and manipulate stockings on knitting machines without operator intervention as they automate their operations. The following patents illustrate several approaches:
U.S. Pat. No. 2,926,513 (Tew) discloses a method of closing a toe in a stocking, wherein the machine engaged in continuous circular knitting is converted to reciprocating knitting. It is during the reciprocating knitting that certain of the needles are disengaged while the remaining needles continue the knitting operation. Continuous circular knitting is thereafter resumed as all needles are engaged for the knitting operation and the toe portion is completed. PA1 U.S. Pat. No. 3,800,559 (Fecker) discloses a method for closing the toe of stockings on known circular knitting machines. A toe-closing thread is knit into the toe end of a tubular mesh. The closing thread passes at least once around the entire periphery of the mesh. The mesh is then cast off the needles of a circular knitting machine and the closing thread is pulled or partially drawn out of the mesh, causing the mesh to be constricted thereby closing the toe. The closing thread is then knotted to prevent withdrawal of the thread. PA1 U.S. Pat. No. 4,014,186 (Ferraguti) discloses a method for forming a closed end of a tubular knit sock on a circular knitting machine. After the last row of the tubular fabric is formed by needles slidably assembled in the grooves of the machine cylinder, two annular tubular layers are formed as continuations of the tubular knit fabric at separate stages by needles operating in the same cylinder of the machine. The loops at the free edge of the inner layer are then held on support arranged in a circle and the free edge of the inner layer is then held on support members arranged in a circle. The free edge of the outer layer is held by the needles until a relative rotation of at least 180 degrees between the circle of support members and the cylinder has been effected. The loops held onto the support members are transferred to the needles of the cylinder, and a final few rows are knit before the fabric is removed from the needles. PA1 U.S. Pat. No. 4,958,507 (Allaire et al.) discloses a method for closing the toe of a double-layered sock. A first course knit by needles corresponding to the end of the tip of a first layer is transferred onto a central transfer plate of a machine where the sock is held. Knitting of the first layer continues from the tip to the mock-up edges. Then knitting is continued on the mock-up edges of the second layer to the tip, the knit tubular structure being suspended by one circular end, from the central transfer plate and, by the other circular end from the needle cylinder in the course of work, shaping the two concentric layers within each other. The initial course in standby on the plate is transferred to the needles of the cylinder to join the two layers together, and the toe is joined together by knitting.
While these methods have met with only limited success, none the opening as well as do linking machines.
One reason for this lack of success is the nature of a cylindrical knit garment. Each knit stitch depends upon the previous stitch knit on the same needle for stability and to prevent unraveling.
One proposed solution is to knit the opening of the stocking first. The last stitches at the top of the stocking unravel, even though attempts have been made to prevent this unraveling.
Another proposed solution is to include drawstrings into the stocking to close the opening end. This method works fairly well on ladies hosiery, but is too bulky for applications involving coarser knit fabrics.
Yet another proposed solution involves adapting small linking machines to become knitting machines. The stocking is removed from the needles by a split dial and linked onto the knitting machine. While this provides a satisfactory opening closure without operator intervention, many types of existing equipment are not readily adaptable to this conversion. Also, substantial costs are involved in converting the equipment resulting in additional maintenance. Accordingly, what is needed is a method that will manipulate and orient the stocking, turning and feeding existing opening closing equipment without operator assistance, rather than closing the opening of the stocking on the existing knitting machines.
A device and a method are needed that will enable precision orientation of a knit garment which is useful for either manual or automatic operation for further processing and completion of the garment.


The movable part is constructed from a bridge part 13 with a cantilever structure in which the fixed end is fastened via a leg part 12. The bridge part 13 has two bridge constituent parts 14 and 15 that are connected in series between the fixed end and the free end. The bridge constituent part 14 on the side of the fixed end is a plate spring part. The bridge constituent part 15 on the side of the free end is a rigid part that possesses rigidity. The bridge constituent part 14 is bent toward the opposite side from the substrate 11 in a state in which the bridge part 13 receives no force. The mirror 2 is disposed on the free end side of the bridge constituent part 15. As a result, a microactuator can be obtained which can be operated by a small driving force.

As the development of micro-machining techniques has progressed, microactuators have become increasingly important in various fields. For instance, optical switches that switch light paths used in optical communications, etc., may be cited as one example of a field in which microactuators are used. The optical switch disclosed in Japanese Patent Application Kokai No. 2001-142008 may be cited as one example of such an optical switch.
A microactuator comprises a fixed part and a movable part that is movable with respect to the fixed part; there are also microactuators of a type in which the movable part has a cantilever structure. For instance, an example in which the movable part has a cantilever structure is disclosed in FIG. 8 of Japanese Patent Application Kokai No. 2001-142008.
The optical switch disclosed in FIG. 8 of Japanese Patent Application Kokai No. 2001-142008 will be described below. This optical switch comprises an optical waveguide substrate on which optical waveguides are formed in the form of a matrix, and in which grooves into which mirrors can advance are formed at the intersection points of the matrix, and an actuator substrate on which microactuators and mirrors are formed. The mirrors are driven by the microactuators, and when the mirrors advance into the grooves of the optical waveguide substrate, the light is reflected by the mirrors, while when the mirrors are retracted from the grooves, the light advances directly forward, thus switching the light paths.
Furthermore, in the microactuator used in the optical switch disclosed in FIG. 8 of Japanese Patent Application Kokai No. 2001-142008, the movable part is formed only by a uniformly constructed plate spring part. A mirror is fastened to the tip end of this plate spring part. In a case where no driving force is applied, this plate spring part is bent toward the opposite side from the substrate, and when a driving force is applied, the entire surface of the plate spring part on the side of the substrate contacts the surface on the substrate. When the application of the driving force is stopped, the plate spring part returns to a state in which the plate spring part is bent toward the opposite side from the substrate as a result of the spring force (internal stress) of the plate spring part.
As a result of research conducted by the present inventor, it was ascertained that if the movable part is constructed only from a plate spring part that is uniformly constructed and that is bent toward the opposite side from the substrate in a state in which no force is received (as in the conventional microactuator described above) in cases where the movable part has a cantilever structure, it is difficult to operate the microactuator with a small driving force because of the construction of this movable part.
As one example, a case will be described in which a movable electrode is disposed on the tip end of the plate spring part and a fixed electrode is disposed on the substrate in a microactuator that has a movable part structure such as that of the conventional microactuator described above, and the electrostatic force that is generated between the two electrodes by the application of a voltage across the two electrodes is used as a driving force. In this case, in order to reduce the driving force that is required for operation, the distance between the two electrodes in a state in which no voltage is applied across the two electrodes may be shortened, and the length of the plate spring part may be lengthened so that the distance between the fixed end of the plate spring part and the movable electrode is increased. However, since the movable part is constructed only from a plate spring part that is uniformly constructed and that is bent toward the opposite side from the substrate in a state in which no force is received, it is impossible to accomplish both of these design elements at the same time. Specifically, the length of the plate spring part must be unavoidably shortened in order to shorten the distance between the two electrodes in a state in which no voltage is applied across the two electrodes. In this case, furthermore, the movement stroke of the mirrors cannot be sufficiently ensured. On the other hand, if the length of the plate spring part is increased, the distance between the two electrode parts is inevitably lengthened since the plate spring part is bent toward the opposite side from the substrate in a state in which no voltage is applied across the two electrodes. Accordingly, in a microactuator which has a movable part structure such as that of the conventional microactuator described above, it is difficult to operate the microactuator with a small driving force.

Micro actuator and optical switch using the actuator


A semiconductor device is disclosed. In a surface layer of a front surface of an n-type semiconductor substrate, an anode layer is provided in an element activation portion and an annular p-type guard ring and an n-type high-concentration surface region are provided in an annular termination breakdown voltage region which surrounds the outer circumference of the anode layer. The impurity concentration of the n-type high-concentration surface region is higher than that of the semiconductor substrate and is lower than that of the p-type guard ring. The depth of the n-type high-concentration surface region is less than that of the guard ring. The anode layer and the guard ring are formed while the oxygen concentration of the semiconductor substrate is set to be equal to or more than 1×1016/cm3 and equal to or less than 1×1018/cm3.

Power semiconductor devices, such as converters and inverters, require low loss, low power consumption, a high speed, and high efficiency. For example, a power diode or a power IGBT (insulated gate bipolar transistor) with a breakdown voltage of 600 V, or 1200 V or more is used as the power semiconductor device. Therefore, a power diode or a power IGBT which has low loss characteristics when it is turned on or switched has been developed.
Next, the impurity concentration distribution of a device, such as a diode or an IGBT, according to the related art will be described. FIG. 11 is a diagram illustrating the uniform impurity concentration distribution of a general diode according to the related art. FIG. 12 is a diagram illustrating the impurity concentration distribution of a diode with a broad buffer structure according to the related art. FIG. 11(a) schematically illustrates the cross-sectional structure of the general diode. FIG. 12(a) schematically illustrates the cross-sectional structure of the diode with the broad buffer structure (hereinafter, referred to as a BB structure) according to the related art.
As an improvement in the device which has low loss characteristics when it is turned on or switched, a device, such as a power diode or a diode or an IGBT with a BB structure in which a BB region 10 is provided in a drift layer 1 as illustrated in FIG. 12, has been proposed (for example, see the following Patent Document 1). The BB structure has an impurity concentration distribution in which impurity concentration is the maximum in the vicinity of the center of the n− type drift layer 1 in a PIN (P-Intrinsic-N) diode or IGBT and is slowly reduced toward a p anode layer 2 and an n+ cathode layer 3.
The drift layer 1 of the diode with the BB structure illustrated in FIG. 12 is compared with the drift layer (hereinafter, referred to as a drift layer with uniform impurity concentration) 1 with a uniform impurity concentration distribution in the general diode according to the related art illustrated in FIG. 11. The diode illustrated in FIG. 11(a) is configured so as to have the same thickness and breakdown voltage as those in the diode with the BB structure illustrated in FIG. 12. FIG. 11(b) illustrates the impurity concentration distribution taken along the cut line B-B′ of FIG. 11(a). FIG. 11(c) illustrates the impurity concentration distribution taken along the cut line A-A′ of FIG. 11(a).
In FIG. 12(b), the impurity concentration distribution taken along the cut line B-B′ of FIG. 12(a) is represented by a solid line. In FIG. 12(c), the impurity concentration distribution taken along the cut line A-A′ of FIG. 12(a) is represented by a solid line. In FIGS. 12(b) and 12(c), the impurity concentration distribution of the drift layer 1 with uniform impurity concentration in the general diode is represented by a dotted line in order to clarify the difference between the impurity concentration distribution of the drift layer 1 in the diode with the BB structure and the impurity concentration distribution of the drift layer 1 with uniform impurity concentration in the general diode.
As one of the methods of forming the BB region in the drift layer of the device, a method has been proposed which forms the BB region in the drift layer of the device using irradiation with protons (hereinafter, referred to as H+) (for example, see the following Patent Document 2). In the method of forming the BB region disclosed in Patent Document 2, an FZ (Floating Zone) bulk wafer is irradiated with H+ and a heat treatment is performed to partially change the radiated H+ into donors, thereby forming the BB region 10 with a desired impurity concentration distribution illustrated in FIGS. 12(b) and 12(c) in the drift layer 1.
However, the diode or IGBT with the BB structure has the following problems. As illustrated in FIGS. 11 and 12, in the general diode and the diode with the BB structure which have the same breakdown voltage, when the impurity concentration of the drift layer 1 with uniform impurity concentration is compared with the impurity concentration of the drift layer 1 having the BB region 10 provided therein, the maximum value (hereinafter, referred to as maximum impurity concentration) of the impurity concentration of the drift layer 1 having the BB region 10 provided therein is more than the impurity concentration of the drift layer 1 of the general diode. The minimum value of the impurity concentration of the drift layer 1 having the BB region 10 provided therein is less than the impurity concentration of the drift layer 1 of the general diode.
As such, in the drift layer 1 of the diode with the BB structure, the impurity concentration of a surface portion of the semiconductor substrate is less than that in the drift layer 1 with uniform impurity concentration in the general diode which has the same breakdown voltage as the diode with the BB structure. Therefore, it is easy for a depletion layer to extend in a direction (hereinafter, referred to as a surface direction) parallel to the surface of the semiconductor substrate in the surface portion of the semiconductor substrate and it is necessary to increase the area of a termination breakdown voltage region. When the impurity concentration of the surface of the termination breakdown voltage region is low, the device is likely to be affected by external charge. Therefore, the reliability of the breakdown voltage is likely to be reduced. As a method of avoiding the problem of the reliability of the breakdown voltage being reduced, a diode has been proposed in which a surface portion of a termination breakdown voltage region has high impurity concentration (for example, see the following Patent Document 3).

Semiconductor device and method of manufacturing the same


A supply hopper for holding a stack of fanfold paper and guiding such fanfold paper for reliable feeding as it is withdrawn from the supply hopper. The supply hopper comprises a tray for supporting a stack of fanfold paper, the tray including a base member oriented at an angle in the range of between 25.degree.-45.degree. from the horizontal. A stop member is connected to the base member along the lower marginal edge thereof, the stop member and the base member forming an included angle of substantially 90.degree.. Further, a guide member is supported by the tray substantially above a fanfold paper stack supported on the tray at a height sufficient to lift the topmost individual panel of the stack at least partially off the stack when the fanfold paper is threaded over the guide member. A bail assembly is connected to the tray extending away from the base member of the tray on the opposite side of the stop member from the base member. As such, the bail assembly acts as a damper on fanfold paper being withdrawn from the stack of fanfold paper passing from such stack supported on the tray over the guide member and below the bail assembly.

The present invention relates in general to feeding of fanfold paper, and more particularly, to a supply hopper which in an operative position supports a fanfold paper stack for reliable feeding to a reproduction apparatus, and is readily collapsible to a storage position.
Computer information output is commonly printed on a continuous run of paper. Such paper is typically an elongated web containing perforations along spaced transverse lines for dividing the web into uniform lengths or individual panels in the longitudinal direction. The perforations form weakening lines in the web which facilitate folding of the web into a stack, with alternate lines forming opposing edges of the stack. The elongated web of such perforation-containing construction is commonly referred to as continuous forms or fanfold paper.
In printing computer information output on fanfold paper, the fanfold paper is fed from a stack to a line or page printer, or the like, where the individual panels are imprinted with desired information and then discharged into a receptacle in a manner to reform the stack. Duplicates of selected individual panels of the stack can be made by dividing the fanfold paper into its individual panels by separation along the weakening lines, and thereafter copying the selected individual panels on any well known reproduction apparatus. In order to improve handling of fanfold paper for copying and eliminate the need to separate individual panels for reproduction, feeders have been designed for use with exemplary reproduction apparatus where the entire fanfold paper stack, or any particular portion thereof, can be duplicated by feeding the fanfold paper from the stack, unseparated, by means of a conveyor, to a reproduction apparatus for copying and discharging the fanfold paper into a receptacle in a manner to reform the stack. An example of a fanfold paper feeder associated with a reproduction apparatus for copying fanfold paper is shown and described in VanDongen U.S. Pat. No. 4,087,172, issued May 2, 1978 or Tickner et al. U.S. Pat. No. 4,264,200, issued Apr. 28, 1981.
A supply hopper for a stack of fanfold paper to be conveyed to the reproduction apparatus is shown and described in Leroy U.S. Pat. No. 4,579,449, issued Apr. 1, 1986. The supply hopper of the Leroy patent is collapsible into a compact storage position relative to the reproduction apparatus, and easily erected to support and guide the fanfold paper into operative association with the reproduction apparatus for copying thereof when desired. While the described supply hopper has proven generally reliable, under certain circumstances it fails to permit transport of the fanfold paper by the conveyor in a manner which maintains the fanfold paper stack in the proper orientation without spilling of the stack. Further, it may cause damage to the fanfold paper such as by tearing of individual panels of the stack or stalling of the fanfold paper in the feeder conveyor.


A single control element device provides a user with absolute coordinate information and enables user control of a computer cursor and emulation of mouse clicks. The single control element is user-moved relative to a surface having a dynamic coefficient of friction that reduces false double-clicks. The device may be used by handicapped persons and emulates left mouse clicking and double clicking by recognizing downward force of the single control element into the surface, and recognizes upward movement of the single control element away from the surface as a right mouse click.

Pointing devices for use with computers and other companion electronic equipment are known in the art and include trackballs, joysticks, and variations of the computer "mouse". Typically such devices require that the user move one element to control a cursor on a computer display, and then press or activate separate buttons to accomplish so-called "left-clicks" and "right-clicks". Further it is common that the user must hold such devices in a fairly rigid position during use. While such tasks may not be overly challenging for many users, these tasks can be overwhelming to handicapped users, as will now be described.
A mouse or a trackball typically has a rotatable spherical element that the user moves over a fixed surface such as a desktop to cause movement of a cursor on a computer display. However such pointing devices are not absolutely coordinate devices in the sense that the user cannot tell by looking at the device where on the computer display the cursor may be found. Conventional pointing devices include one or more user-activated buttons, for example one button to left-click (and left double-click) and perhaps a second button to right-click, where the different click functions can cause different menu options to appear on the computer screen, or a program to execute (in the case of a left double-click). A generic mouse weighs perhaps 4 oz. and is perhaps 2″ wide, 5″ long, and 1″ in height. Commonly "left-click" and "right-click" buttons are located on the upper mouse surface, and are pressed, respectively, with the first and second fingers of the user's hand. Using the mouse to move a computer cursor on a display requires that the user move the entire mass of the mouse on the fixed surface such that the spherical element in the bottom of the mouse rotates.
More recently, the so-called optical mouse has found acceptance as a computer input device. An optical mouse often has the form factor of the older rotatable ball device. However instead of user-movement resulting in detectable rotation of a ball, an optical mouse replaces a rotatable ball with an optical emitter that directs light onto the work surface, and an optical sensor that detects light reflected by the work surface. As the user manipulates the mouse across the work surface, the optical sensor can discern relative changes in position by detecting the variation in different regions of the work surface, which variations typically are not apparent to the unaided eye. Exemplary optical mice are described in U.S. Pat. No. 6,281,882 (2001) and U.S. Pat. No. 6,433,780 (2002) to Gordon. However, manipulating an optical mouse requires essentially the same manual dexterity as manipulating a more conventional mouse, which dexterity is often not available to all would be users.
Prior art pointing mechanisms such as digitizer tablets can provide a degree of absolute coordinate information, but only while the digitizer stylus is in contact with the tablet surface. For instance if the stylus is contacting the upper right corner of the tablet, the user knows that the cursor will be in the upper right corner of the associated computer display. However as soon as the stylus is lifted from the digitizer tablet, the user can no longer look at the tablet and discern where on the computer display the cursor will be found. The stylus functions as the user-interface element to manipulate the cursor, and typically can be used to emulate left mouse-clicking.
But many users, especially physically handicapped users, find it difficult if not impossible to use prior art pointing mechanisms. Grasping and moving mice, or grasping and moving trackball devices to manipulate a cursor and then having to move a finger to click buttons may literally be impossible if the user suffers from carpal tunnel syndrome, arthritis, or perhaps has a hand prosthesis. A single user-interface element would be preferably, where the single element could be used to achieve cursor movement, and carry out the various mouse click functions. Even for non-handicapped users, the requirement of maintaining one hand on the device while pressing button(s) with a finger in a repetitive position, day-in, day-out, can result in physical disability, including tendonitis and carpal tunnel syndrome.
Some prior art pointing devices such as pressure or touchpads found on modern laptops, or the so-called TrakPointer™ mechanism found on IBM™ laptops can provide a dual function user-interface element that can be used for cursor movement and for left-clicking. However such devices do not provide absolute coordinate information to the user, do not provide right-clicking, and can be difficult to manoeuver, especially for the handicapped.
U.S. Pat. No. 5,821,921 (1998) and U.S. Pat. No. 6,107,991 (2000) to Osborn (applicant herein), which patents are incorporated herein by reference, disclosed pointing devices that provided the user with absolute coordinate information. The pointer mechanisms disclosed in these two patents included a user-grippable handle-like element that could better enable users, including handicapped users, to control cursor movement on a computer screen. The device described in Osborn '921 includes a peg-like element that a user could grasp to manipulate a cursor, and that could be pushed downward to emulate left mouse-clicking. The undersurface of the element would be moved by the user over a glide surface, and various resistive and/or optical mechanisms would determine the amount of movement in orthogonal x and y axes. Alternate embodiments of the '921 device included additional switches that a non-handicapped user could readily manipulate to emulate left and right mouse clicks. Among the advantages provided by devices according to the Osborn '921 and '991 patents was the substantial decrease in the magnitude of the mass of what the user was required to manipulate. For example rather than move a four ounce mouse, the portion of the device being manipulated weighed less than perhaps one ounce. Understandably for many handicapped users, and indeed for non-handicapped users, it is advantageous if computer control can be achieved while manipulating a smaller mass.
While the Osborn '921 and '991 pointing devices were absolute coordinate devices, there still was room for improvement. It turned out that double-clicking with the devices was difficult, especially for the handicapped. Excessive mechanical movement between the user-mechanism and the glide surface could occur between the movement of the first click and the second click. If the movement exceeds about three pixels on the computer display, the computer software will recognize two discrete and somewhat spaced-apart left mouse clicks, rather than a single left mouse double-click. In essence, while friction between the interface element and the underlying glide surface should be low for ease of user-controlled cursor movement, too low a coefficient of friction makes double-clicking difficult due to interface element movement between the two clicks.
What is needed is a pointing device with a single user-interface element that can be manipulated to move a cursor on a computer screen, while maintaining absolute coordinate information. Preferably the single element should be user-manipulable to emulate single and double left mouse-clicks and also a right mouse click, and should be manipulable even by handicapped users. Preferably the mass of the user-manipulated single-element should be low to reduce user fatigue. Further, the device should include a glide surface having a dynamic coefficient of friction that provides smooth rapid glide movement representing cursor movement, but that exhibits a higher coefficient of friction during mouse clicks to minimize undesired movement between mouse clicks. Preferably the device should sense the single user-interface movement using a mechanism whose form factor allows the device to be fabricated within a computer keyboard, if desired. Regardless of the device is implemented, device output to the companion computer or other equipment should of course be in an industry standard output format. Preferably such device should be implementable with a form factor sufficiently small to fit within a standard computer keyboard, if desired.
The present invention provides such a pointing device.

Absolute coordinate, single user-interface element pointing device


The objective of the present invention is to enable a microfilament that is a nanofilament to be manufactured continuously and consistently from all thermoplastic polymers without requiring a specialized high precision•high performance apparatus and also to present the nanofilament manufactured as described. The present invention comprises a microfilament in a nanofilament region and the manufacturing means thereof wherein a original filament transferred using a filament transfer means is supplied to an orifice under pressure P1 and is heated and drawn using an infrared light beam directly under the orifice under pressure P2 (P1>P2).

Fibers with fiber diameters smaller than 1 μm, that is, nanometer sized (from several nanometers to several hundreds of nanometers) fibers have gained attention in recent years as revolutionary materials of the future in a broad range of applications such as IT, bio, environmental and other applications. The nanofibers have typically been prepared using an electro-spinning method (henceforth sometimes abbreviated to "ES method"). (See U.S. Pat. No. 1,975,504; You Y., et al Journal of Applied Polymer Science, Vol. 95, p. 193-200, 2005.) However, the ES method is a complicated manufacturing method since polymer needs to be dissolved in solvent and the solvent must be removed from the product obtained. In addition, molecules lack orientation in the filament obtained, and many quality problems such as the presence of small resin particles, referred to as balls and shots were encountered in the fiber aggregates obtained.
The inventors previously invented a means to obtain microfilaments and non-woven fabrics using a super high draw ratio that exceeded one thousand through molecular orientation conducted according to an infrared method. (See Japanese Patent Publication No 2003-166115 and 2004-107851; International Publication No. WO2005/083165A1; Akihiro Suzuki and one other "Journal of Applied Polymer Science", Vol. 88, p. 3279-3283, 2003; Akihiro Suzuki and one other, "Journal of Applied Polymer Science", Vol. 92, p. 1449-1453, 2004; Akihiro Suzuki and one other, "Journal of Applied Polymer Science", Vol. 92, p. 1534-1539, 2004.) These are simple means, and microfilaments with molecular orientation and non-woven fabrics thereof were obtained. The present invention is a further development of the same theme and relates to a means that allows microfilaments to be manufactured continuously and consistently by enabling filaments to be attenuated into nanofilaments.

Microfilament manufacturing method and manufacturing apparatus therefor


In a trace control method used for machining a workpiece by tracing a model with a tracer head, the path and speed of two axes (X- and Y-axes) are controlled by NC commands, but, three axes (X-, Y- and Z-axes) are controlled to carry out the tracing operation. An NC command speed (F) is changed by an override circuit (2b) so that the NC command speed coincides with the composite speed of the three axes controlled to carry out the tracing operation, and the resultant speed (Fd) is supplied to an interpolator (2a). The direction of movement along the X- and Y-axes is controlled by the NC command and the speed is affected by the tracing operation. Thus the trace control method can control movement as though all three axes are controlled by NC commands.

1. Field of the Invention
The present invention relates to a trace control method for use when machining a metal mold or the like, and more specifically, to a trace control method by which some axes are controlled by an NC command.
2. Description of the Related Art
A control method is used for moving two axes by a numerical control (NC) command and controlling the remaining one axis to carry out a tracing. In this method, for example, the X- and Y-axes are controlled by an NC command and a Z-axis is controlled to carry out a tracing operation. More specifically, the X- and Y-axes are controlled by the NC command and the Z-axis is controlled by the following expression. EQU Vz=(.epsilon.-.epsilon..sub.0).times.G
where, Vz is a tracing speed of the Z-axis, .epsilon. is a composite amount of displacement of the X-, Y- and Z-axes, and .epsilon..sub.0 is a standard amount of displacement.
The above trace control method enables any point or path on an X-Y plane to be traced, and thus is very convenient for partially tracing a complex configuration or the like.
Nevertheless, the above method has a low accuracy and the tracing speed cannot be increased because the tracing is carried out for only one axis, and the indexing and distribution are not carried out for the three axes.
In particular, since the indexing and distribution are not carried out, when a tracer head traces an upward plane in the direction in which the tracer head is moving, the head tends to bite into the surface of the model. Conversely, when the tracer head traces a downward plane, the head tends to move away therefrom. As a result, a problem arises in that, when the tracer head is moved forward and then backward, a step is produced at the position at which the upward tracing movement is changed to a downward tracing movement.


The alpha form of nickel (II) hydroxide is formed by dissolving a compound of nickel (II), such as nickel acetate, in a water miscible dihydric alcohol (diol), such as ethylene glycol, propylene glycol and suitable oligomers, and adding a suitable base such as sodium carbonate. The α-Ni(OH)2 precipitate is separated from the diol-based mother liquor and dried. This stable α-Ni(OH)2 can be calcined at temperatures in the range of about 573K to about 1073K to form nanometer-size particles of NiO having, for example, fibrous shapes. And the small particles of NiO can be reduced with hydrogen to form small, fibrous nickel particles. Both the NiO particles and Ni particles have utility as catalysts and offer utility in applications requiring electronic and/or magnetic properties.

It is desired to make nanometer size particles (5 to 30 nanometers in diameter or largest dimension) of nickel and nickel oxide for applications in catalysis, electronics, and magnetics. Several physical and chemical methods such as metal vapor synthesis, thermal decomposition of a nickel aerosol precursor, and sol-gel methods, can be used to synthesize nanocrystalline NiO. The NiO materials prepared by these methods are generally spherical particles with a size of less than ten nanometers when exposed to a temperature less than 400° C. However, the size of these particles increases to greater than about twenty nanometers when they are heated over 700° C. Moreover, there is little control of the morphology of the spherical particles with such methods.
There is a need for a method of producing nanometer size particles of nickel oxide having high temperature stability. There is also a need for producing new crystalline forms (i.e., other than spherical forms) of thermally stable nanometer size particles of nickel oxide.

Method of making NiO and Ni nanostructures

Dalian Institute of Chemical Physica, Chinese Academy of Sciences


A device for training the muscles used during a golf club swinging motion. The device includes a connector coupled to the head of the golf club and a resilient and extensible tether having a proximal end for connection to the connector and a distal end for connection to a trainee's body. The device is used by causing the trainee to engage in a golf swing motion so that the tether provides resistance to the trainee's muscles in the sequence used to perform the swing.

Extensive practice is required to develop a consistent and proper golf swing. Typical challenges encountered by golfers when improving their golf swing include slicing (hitting the ball so that it curves to the right for a right-handed golfer) and hooking (hitting the ball so that it curves to the left for a right-handed golfer). A variety of devices for improving a golf swing exist. A number of these devices include the use of mechanisms for checking the golfer's body alignment. One such device is disclosed in U.S. Pat. No. 6,805,641 to Pope. This device includes a support section, including an adjustable arm, and an engagement arm for contacting a dorsal surface of a golfer. Such devices are cumbersome to transport and use. They also do not train the muscles used during a golf swing in the sequence they are used.
The use of resilient and extensible tethers for training the muscles used during certain athletic movements is known. For example, a device for training the upper body is described in U.S. Pat. No. 5,518,480 to Frappier, herein incorporated by reference. This device is used to provide resistance to the arms, trunk and shoulders to improve performance in sports such as hockey, basketball, volleyball and baseball/softball. A device for training the lower body is described in U.S. Pat. No. 5,167,601 to Frappier, which is incorporated herein by reference. This device provides resistance to the lower extremities during sprinting and related motions. It is also known to train the muscles used during hockey stick swinging motions by attaching a resilient and extensible tether to a hockey stick and anchoring the tether to a wall.
Therefore, there is a need for an improved golf swing training device for training the muscles used during a golf swing in the sequence they are used. A device of this type that is relatively simple, easy to use, and portable would be especially desirable.

Golf club swing training device and method


A transformer and associated rectifier for supplying low voltage (e.g. 5 volts), high current (e.g. 1,500 amperes) power to a load such as a supercomputer, with a high electrical conversion efficiency and a high volumetric efficiency. The primary winding comprises a number of disc-shaped coils which are spaced apart from each other by coaxial single turn secondary coil elements which are interleaved between the primary coils. A core having E-shaped parts has an inner portion extending through the primary and secondary coils and an outer portion forming two windows with the inner portion, so that the coils extend through the windows. A rectifier assembly is mounted directly to plates which support and act as terminals to the secondary coils.

This invention relates to a transformer for use in high frequency switching power supplies, for supplying regulated low voltage high current power at high energy efficiency, which is especially suitable for, but not limited to, use in power supplies for high performance computers.
Supercomputers and other high performance computers typically require several kilowatts to several hundred or more kilowatts of power to be supplied at one or more low voltages in the range of 1.5 to 6.0 volts D.C.
Each required voltage requires a separate power supply. As power requirements increase, power supply units are operated in parallel, sharing the required load current for each voltage bus.
It is desirable to have these computers occupy as small a volume as possible, and that their power supplies also occupy a small volume (high power density) and have high energy efficiency to minimize heat loss in these power supply units.
Power supplies presently available are capable of meeting these requirements to only a limited extent; a primary limitation being the leakage inductance of the converter transformer. While the high frequency primary voltage may have a duty cycle (on time to total cycle time ratio) of 0.95, the duty cycle for energy transfer from the primary to the secondary winding of the converter transformer is limited by (i) the leakage inductances, (ii) the primary current, which is the load current reduced by the primary to secondary turns ratio, and (iii) the switching frequency. All other things being equal, an increase in switching frequency will further reduce the energy transfer duty cycle.
For a given output power, anything that reduces the energy transfer duty cycle requires a compensating reduction of the primary to secondary turns ratio. This reduction in turns ratio increases the RMS current in the primary circuits, increasing losses and reducing throughput efficiency.
Typical power supplies currently available use two to four or more converter transformers to achieve higher output power in a "single" power supply unit..sup.1 This approach generally requires a higher component count in the power portion of the units, which is likely to reduce reliability. FNT .sup.1 Multiple converter transformer topologies typically are employed for units having an output of two kilowatts or more.
Accordingly, an object of the present invention is to provide an improved high energy efficiency transformer on a single permeable core structure having a low voltage high current secondary winding that will permit the implementation of higher power density, highly efficient power supply units.


A transistor includes a first semiconductor layer associated with a first electrode; a second semiconductor layer associated with a second electrode; and a discontinuous layer between the first and second semiconductor layer. The discontinuous layer has a plurality of openings being formed on a non-uniform organic surface. Applications of the transistor include an inverter that operates at low supply voltage and high frequency.

This invention relates to organic transistors and inverters.
Organic thin-film transistors (OTFTs) have several advantages over traditional transistors, including, for example, low cost, low processing temperature, mechanical flexibility, and large area coverage. Applications of OTFTs in consumer electronics and optoelectronics include flat-panel display drivers, radio-frequency identification (RFID) tags, smart cards, and sensors.
Conventional OTFTs are designed using the architecture of a typical inorganic metal-oxide-semiconductor field-effect transistor, in which a source terminal and a drain terminal are usually formed on the same plane above or below the transistor's semiconductor layer. The performance of conventional OTFTs is generally influenced by two design parameters: channel length (L) and field-effect mobility (μFE). One characterization of the performance is the source-drain response time tSD, which can be determined by the following equation: tSD=L2/(μFE×VDD), where VDD is the supply voltage.
With conventional OTFTs, it is difficult to reduce this source-drain response time tSD to achieve high operation frequency. One difficulty, for example, is the low field-effect mobility μFE of organic semiconductors used in OTFTs. Another difficulty relates to the channel length of the OTFT, which cannot be easily shortened using nano-lithographic techniques. In cases where the channel length of an OTFT can be reduced to the order of sub-micrometers, the contact resistance between its semiconductor layer and electrodes becomes another factor that can affect the performance of this organic device.


A method of separating air in which a compressed air stream is divided into first and second subsidiary streams. The first subsidiary air stream is cooled by heat exchange to a temperature suitable for its separation by rectification and introduced into the higher pressure stage of a double rectification column. The second subsidiary air stream is further compressed and then at least part of it is cooled by heat exchange to a first intermediate temperature below ambient temperature but above those temperatures at which the double rectification column operates. The thus cooled second subsidiary air stream is expanded in a first expansion turbine and is withdrawn therefrom at a second intermediate temperature below the first intermediate temperature but above those temperatures at which the double rectification column operates. After withdrawal, the second subsidiary air stream is introduced into a second expansion turbine where it is further expanded. After the further expansion, the second subsidiary air stream is introduced into the lower pressure rectification stage of the double rectification column. Air is separated in the double rectification column into oxygen and nitrogen. Oxygen and nitrogen streams are withdrawn from the said lower pressure stage and a part of at least one of the oxygen and nitrogen is produced as a liquid product.

This invention relates to air separation.
Modern chemical and metallurgical processes including an oxidation step call for ever larger quantities of oxygen. Oxygen can be produced in quantities in excess of 2,000 tonnes per day by an air separation process which comprises compressing an air stream, purifying the air stream by removing therefrom components of relatively low volatility such as water vapour and carbon dioxide, cooling the thus purified air stream to a temperature suitable for its separation by fractional distillation or rectification, and then performing that separation so as to produce oxygen product of desired purity. The purification is preferably performed by beds of adsorbent which adsorb the components of low volatility such as water vapour and carbon dioxide. The fractional distillation or rectification of the air is preferably performed in a double rectification column comprising a higher pressure stage and a lower pressure stage that typically share a heat exchanger effective to condense nitrogen at the top of a higher pressure column and reboil oxygen-rich liquid at the bottom of the lower pressure column. Some of the thus formed liquid nitrogen is used as reflux in the higher pressure column while the remainder is typically removed from the higher pressure column, is sub-cooled, and is passed through an expansion valve into the top of the lower pressure column so as to provide reflux for that column, the air being introduced into the higher pressure column. Oxygen-enriched liquid air is withdrawn from the bottom of the higher pressure column and is passed to the lower pressure column where it it typically separated into substantially pure oxygen and nitrogen products. These products may be withdrawn from the lower pressure column in the gaseous state and warmed to ambient temperature in countercurrent heat exchange with the incoming air, thereby effecting the cooling of the incoming air. Since such a process operates at cryogenic temperatures, refrigeration has to be generated. This is typically done either by expanding a part of the incoming air in a turbine or by taking a stream of nitrogen from the higher pressure column and passing it through an expansion turbine.
In DE-A-2 854 508 there is disclosed a process in which all the air exiting the turbine is introduced into the lower pressure column. Such a process offers the advantage that introduction of the turbine-expanded air into the lower pressure column helps to enhance the thermodynamic efficiency with which rectification takes place when there is not a requirement to produce either a liquid oxygen or a liquid nitrogen product. The process is however limited in that it is generally not suitable for use when it is desired to produce liquid oxygen and/or liquid nitrogen products (in addition to a gaseous oxygen and/or gaseous nitrogen product) in a total amount of more than 5% of the gaseous oxygen product.
It is also known to provide refrigeration for an air separation process by arranging for an air expansion turbine to exhaust into a higher pressure column. Such a process therefore entails compressing the air to a higher pressure than those at which the double rectification column operates. Such a process is disclosed in U.S. Pat. No. 2,779,174. By arranging for the expansion turbine to exhaust into the higher pressure column, it is possible to obtain a greater yield of liquid oxygen or liquid nitrogen than in the process described in DE-A-2 854 508. Our analysis shows however that the process is relatively inefficient thermodynamically, especially when the liquid production is in the range of 10 to 50% of the plant output.
A large number of proposals also exist in the art for using two expansion turbines in parallel with one another to generate refrigeration for the process and to enable any desired proportion of the oxygen and nitrogen products to be produced in liquid state. An example of such a proposal is given in U.S. Pat. No. 4,883,518. In general, in comparison with single turbine systems, additional passes are required through the heat exchanger in which the air is cooled. Moreover, such processes employing two turbines in parallel require a large proportion of the turbine-expanded air to be directed other than to the lower pressure column.
EP-A-0 420 725 discloses an air separation cycle in which a part of a main compressed air stream is withdrawn from a main heat exchanger at a first intermediate location; is expanded in a first turbine; is returned through the heat exchanger from its cold end to a second intermediate location at a higher temperature than the first intermediate location; is withdrawn from the second intermediate location is expanded in a second turbine, which therefore operates at higher temperatures than the first turbine; and is then mixed with an impure nitrogen stream flowing through the main heat exchanger from its cold end to its warm end. The entire air stream is compressed to a relatively high pressure in the order of 30 bar and all the oxygen product is produced as liquid.


The present invention relates to anti-PD-L1 antibodies, bispecific antibodies containing one domain with specificity to PD-L1, and to immunocytokines comprising an anti-PD-L1 antibody fused to a cytokine, such as IL-2. The present invention also provides methods of treatment, uses and pharmaceutical compositions comprising the antibodies, bispecific antibodies and immunocytokines.

Immunocytokines (antibody-cytokine fusion proteins) were first reported in the literature in the early 1990s and consisted of whole antibody fusions with cytokines such as lymphotoxin (TNF-α) or interleukin 2 (IL-2). Subsequent studies in GD2-expressing tumour models in mice indicated that the ch14.18 antibody and ch14.18-IL2 immunocytokine both had anti-tumour activity but that the immunocytokine was far more potent than the antibody, even when combined with free IL-2, (see Sabzevari H et al., Proc. Natl. Acad. Sci. USA, 1994, 91:9626-30; Pancook J D, et al., Cancer Immunol. Immunother., 1996, 42:88-92; Becker J C, et al., Proc. Natl. Acad. Sci. USA, 1996, 93:2702-7). In addition, immune-competent mice treated with the immunocytokine, but not the antibody plus IL-2, developed an adaptive immune response dependent on CD8+ T-cells that prevented subsequent tumour challenge (Becker J C, et al., J. Exp. Med., 1996, 183:2361-6; Becker J C, et al., Proc. Natl. Acad. Sci. USA, 1996, 93:7826-31). Thus, the targeting of IL-2 to the tumour microenvironment induces an anti-tumour vaccine effect that is not possible with the antibody, either alone or together with the free cytokine. A related humanized immunocytokine, hu 14.18-IL2, achieved clinical proof of concept in relapsed non-bulky neuroblastoma as monotherapy where it induced a significant number of complete responses in patients with no other treatment options (see Shusterman et al., Journal of Clinical Oncology, 2010, 28(33), 4969-4975). A number of publications describe the ability of this molecule to activate several components of the immune system to kill tumour cells (particularly NK cells and CD8+ T-cells), and develop T-cell memory in order to resist subsequent tumour challenge (Yamane et al. 2009; Expert Opi, Investig. Drugs, 18(7): 991-1000; Neal et al., 2004, Clin. Cancer Res., 1010, 4839-4847).
As IL-2 based immunocytokines can have significant side effects, recent efforts have focused on the reduction of toxicity whilst maintaining efficacy. One example is Selectikine (EMD 521873), which has a substitution of aspartic acid for threonine at position 20 of IL-2, a key residue in the binding of IL-2Rβ (Gillies et al., Clinical Cancer Research, 2011, 17(11), 3673-3685). Selectikine, which binds necrotic tissue, has been shown to have good anti-tumour activity, despite its selectivity for the high affinity IL-2R, over the intermediate IL-2R and good tolerability in Phase I studies (Laurent et al., Journal of Translational Medicine, 2013, 11(1), 5. Available on the World Wide Web at doi.org/10.1186/1479-5876-11-5)
WO2012/178137 (Gillies) describes light chain immunocytokine fusions with tumour targeting antibodies.
An adaptive immune response involves activation, selection, and clonal proliferation of two major classes of lymphocytes termed T-cells and B-cells. After encountering an antigen, T-cells proliferate and differentiate into antigen-specific effector cells, while B-cells proliferate and differentiate into antibody-secreting cells. T-cell activation is a multi-step process requiring several signalling events between the T-cell and an antigen-presenting cell (APC). For T-cell activation to occur, two types of signals must be delivered to a resting T-cell. The first type is mediated by the antigen-specific T-cell receptor (TcR), and confers specificity to the immune response. The second signal, a costimulatory type signal, regulates the magnitude of the response and is delivered through accessory receptors on the T-cell.
A primary costimulatory signal is delivered through the activating CD28 receptor upon engagement of its ligands B7-1 or B7-2. In contrast, engagement of the inhibitory CTLA-4 receptor by the same B7-1 or B7-2 ligands results in attenuation of a T cell response. Thus, CTLA-4 signals antagonize costimulation mediated by CD28. At high antigen concentrations, CD28 costimulation overrides the CTLA-4 inhibitory effect. Temporal regulation of the CD28 and CTLA-4 expression maintains a balance between activating and inhibitory signals and ensures the development of an effective immune response, while safeguarding against the development of autoimmunity.
Programmed death-1 (PD-1) is a 50-55 kDa type I transmembrane receptor that is a member of the CD28 family. PD-1 is involved in the regulation of T-cell activation and is expressed on T cells, B cells, and myeloid cells. Two ligands for PD-1, PD ligand 1 (PD-L1) and ligand 2 (PD-L2) have been identified and have co-stimulatory features.
Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation (CD274) or B7 homolog 1 (B7-H1), is a member of the B7 family that modulates activation or inhibition of the PD-1 receptor. The open reading frame of PD-L1 encodes a putative type 1 transmembrane protein of 290 amino acids, which includes two extracellular Ig domains (a N-terminal V-like domain and a Ig C-like domain), a hydrophobic transmembrane domain and a cytoplasmic tail of 30 amino acids. The 30 amino acid intracellular (cytoplasmic) domain contains no obvious signalling motifs, but does have a potential site for protein kinase C phosphorylation.
The complete amino acid sequence for PD-L1 can be found in NCBI Reference Sequence: NP_054862.1 (SEQ ID NO: 1), which refers to many journal articles, including, for example, Dong, H., et al. (1999), "PD-L1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion," Nat. Med. 5 (12), 1365-1369. The PD-L1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish. The murine form of PD-L1 bears 69% amino acid identity with the human form of PD-L1, and also shares a conserved structure.
In humans, PD-L1 is expressed on a number of immune cell types including activated and anergic/exhausted T-cells, on naive and activated B-cells, as well as on myeloid dendritic cells (DC), monocytes and mast cells. It is also expressed on non-immune cells including islets of the pancreas, Kupffer cells of the liver, vascular endothelium and selected epithelia, for example airway epithelia and renal tubule epithelia, where its expression is enhanced during inflammatory episodes. PD-L1 expression is also found at increased levels on a number of tumours including, but not limited to breast (including but not limited to triple negative breast cancer), ovarian, cervical, colon, colorectal, lung, including non-small cell lung cancer, renal, including renal cell carcinoma, gastric, oesophageal, bladder, hepatocellular cancer, squamous cell carcinoma of the head and neck (SCCHN) and pancreatic cancer, melanoma and uveal melanoma.
PD-1/PD-L1 signalling is believed to serve a critical non-redundant function within the immune system by negatively regulating T cell responses. This regulation is involved in T cell development in the thymus, in regulation of chronic inflammatory responses and in maintenance of both peripheral tolerance and immune privilege. It appears that upregulation of PD-L1 may allow cancers to evade the host immune system and, in many cancers, the expression of PD-L1 is associated with reduced survival and an unfavourable prognosis. Therapeutic monoclonal antibodies that are able to block the PD-1/PD-L1 pathway may enhance anti-tumoural immune responses in patients with cancer. Published clinical data suggest a correlation between clinical responses with tumoural membranous expression of PD-L1 (Brahmer et al., Journal of Clinical Oncology, 2010, Topalian et al., NEJM, 2012) and a stronger correlation between lack of clinical responses and a lack of PD-L1 protein localized to the membrane (Brahmer et al., Journal of Clinical Oncology, 2010, Topalian et al., NEJM, 2012). Thus, PD-L1 expression in tumours or tumour-infiltrating leukocytes (Herbst R S, et al., "Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients", Nature, 2014, Nov. 27, 515(7528)563-7, doi: 10.1038/nature14011) is a candidate molecular marker for use in selecting patients for immunotherapy, for example, immunotherapy using anti-PD-L1 antibodies. Patient enrichment based on surface expression of PD-L1 may significantly enhance the clinical success of treatment with drugs targeting the PD-1/PD-L1 pathway.
Further evidence of PD-L1 expression and correlation to disease will emerge from the numerous ongoing clinical trials. Atezolizumab is the most advanced, and recent data from Phase II trials shows therapeutic effects in metastatic urothelial carcinoma and NSCLC, particularly in patients with PD-L1+ immune cells in the tumour microenvironment (see Fehrenbacher et al., 2016, The Lancet, http://doi.org/10.1016/S0140-6736(16)00587-0; Rosenberg et al., 2016, The Lancet, http://doi.org/10.1016/S0140-6736(16)00561-4).


A side wall surface of a carriage is disclosed with two first projection parts and a second projection part that define the inclination of a reflective optical sensor in its vertical direction. The two first projection parts are arranged at the same height position with a detection surface as a reference, and the second projection part is arranged at a position higher than the first projection parts with the detection surface as the reference. The second projection part has a first part higher in position from the side wall surface of the carriage than the first projection parts and has a second part lower in position than the first part. The second part has a screw hole into which a clamping member for fixing the reflective optical sensor to the second part is tightened.

1. Field of the Invention
The present invention generally relates to image forming apparatuses and carriages and, in particular, to a carriage in which an image forming section is installed and an image forming apparatus having the carriage.
2. Description of the Related Art
As an image forming apparatus such as a printer, a facsimile machine, a copier, and a multi-task machine having plural such functions, there is employed, e.g., a liquid ejection apparatus including a recording head composed of liquid ejection heads (liquid droplet ejection heads) that eject the liquid droplets of recording liquid (liquid) so as to perform image formation. During image formation (used synonymously with recording, printing, and imaging), this liquid ejection apparatus causes liquid (hereinafter referred to as ink) to adhere to a medium, while transferring the medium (hereinafter referred also to as a sheet, but it does not limit the material; also it is used synonymously with a medium to be recorded, a recording medium, a transfer member, a recording paper, etc.).
Note that in the present invention, the "image forming apparatus" refers to an apparatus that ejects liquid onto a medium such as a paper, a thread, a fiber, a fabric, leather, metal, a plastic, glass, wood, and a ceramic so as to perform the image formation. Furthermore, the "image formation" refers to forming on the medium not only meaningful images such as characters and graphics, but also meaningless images such as patterns (i.e., liquid droplets are just ejected and shot). That is, the image forming apparatus refers also to a textile printing apparatus or an apparatus that forms a metal wiring. Furthermore, the "ink" is not particularly limited so long as it is capable of performing the image formation.
When the image forming apparatus of such a liquid droplet ejection type causes a carriage, on which the recording heads that eject liquid droplets are mounted, to reciprocate so as to print the images of ruled lines bi-directionally, the deviation of the ruled lines is likely to occur in forward and backward directions. Furthermore, when printed images in different colors are superposed one on another, slurring is likely to occur.
Generally, in an ink jet recording apparatus or the like, a test chart for adjusting the deviation of shooting positions is output so that users select and input an optimum value. Accordingly, ejection timing is adjusted based on the input results. However, users have their own way of viewing the test chart and are unaccustomed to the operations. Therefore, they are likely to erroneously input data. As a result, an adjustment problem may be adversely incurred.
In view of the above problem, Patent Document 1 describes an image forming apparatus that prints test patterns on a holding and conveying member, such as a conveying belt and a medium, and scans the test patterns with an optical sensor provided in a carriage to correct the deviation of shooting positions.
Patent Document 1: JP-A-2006-264194
Note that examples of image forming apparatuses including an electrophotographic type using the optical sensor are as follows.
Patent Document 2: JP-A-9-226198
Patent Document 3: JP-B2-3397441
Patent Document 4: JP-A-2007-121952
However, when the test patterns formed on the conveying belt are scanned by the optical sensor provided in the carriage, it is difficult to scan the test patterns accurately because their color difference is small depending, for example, on the combination of the color of the conveying belt and that of the ink. In this case, it is necessary to provide a configuration such as a light source whose wavelength is varied for each color so as to detect the colors accurately. In practical sense, however, the test patterns formed on the conveying belt cannot be accurately scanned.
If there is employed, as the conveying belt, an electrostatic one composed of an insulating layer on its front surface and an intermediate resistive layer on its rear surface and incorporating carbon to provide the intermediate resistive layer with a conductive property, the color of the electrostatic belt is black in appearance. Therefore, when the test patterns are detected only by the reflection of the colors, it is difficult to distinguish black ink from the electrostatic belt. As a result, the patterns cannot be detected.
Thus, the present inventor has proposed a method for dealing with the above problem. According to this method, patterns composed of independent ink droplets are formed on the surface of the conveying belt in advance. Then, short-wavelength light is applied to the ink droplets. Taking advantage of the characteristics in which the ink droplets are formed into a semispherical shape, the attenuated amount of regular reflection light is detected according to the formed patterns. As a result, the positions of the patterns and positional deviation can be accurately detected.
Typically, when the conveying surface (called a "detection surface") of a medium to be recorded, such as the front surface of the medium to be recorded and the conveying belt, is detected using a reflective optical sensor, it turns out that light-receiving sensitivity when the reflective optical sensor is arranged to be slightly inclined is greater than that when the optical sensor applies injection light in a direction perpendicular to the detection surface and receives its reflection light.
On the other hand, the carriage is generally fabricated by injection molding using resin. However, in consideration of the cutting out of the carriage, the injection molding is performed so that a cutting-out direction is perpendicular to the carriage. Therefore, it is necessary to provide a simple structure for mounting and arranging the optical sensor on the side wall surface of the carriage.


Antibodies, or antigen-binding fragment thereof, which bind to a CCR7 receptor are capable of selectively killing, impairing migration and/or blocking dissemination of tumor cells expressing a CCR7 receptor. Use of said antibodies for killing or for inducing apoptosis of said tumor is disclosed, thus providing an alternative therapy for treatment of cancer which tumor cells express a CCR7 receptor.

Cancer is a group of diseases characterized by uncontrolled cell division (or by an increase of survival or apoptosis resistance) and by the ability of said cells to invade other neighbouring tissues (invasion) and spread to other areas of the body where the cells are not normally located (metastasis) through the lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body. Depending on whether or not they can spread by invasion and metastasis, tumours are classified as being either benign or malignant: benign tumours are tumours that cannot spread by invasion or metastasis, i.e., they only grow locally; whereas malignant tumours are tumours that are capable of spreading by invasion and metastasis.
There are several types of cancers that can be classified by the type of cell in which it originates and by the location of the cell, i.e., carcinomas, which arise from the cells that cover external and internal body surface, e.g. skin, digestive tract or gland; leukaemia, which starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter into the bloodstream; Lymphoma, which is a cancer originating in lymph nodes and tissues of the body's immune system; melanoma, which arises in melanocytes; sarcoma, which begins in the connective tissue of bone or muscle; and teratoma, which begins within germ cells.
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy or other methods. The choice of therapy depends upon the location and grade of the tumour and the stage of the disease.
A significant problem to address in tumour treatment regimens is the desire for a "total cell kill". This means that the more effective treatment regimens come closer to a total cell kill of all so-called "clonogenic" malignant cells, i.e., cells that have the ability to grow uncontrolled and lead to tumour mass formation that might be removed by the therapy.
Another tumour treatment strategy is the use of an "immunotoxin", in which an anti-tumour cell antibody is used to deliver a toxin to the tumour cells. However, in common with the chemotherapeutic approaches described above, immunotoxin therapy also suffers from significant drawbacks. For example, antigen-negative or antigen-deficient cells can survive and repopulate the tumour or lead to further metastases. Even if a primary cancer is completely eliminated, a malignant tumour will often be metastatic. The formation of metastases of malignant tumours, initiated from a primary tumour at more or less remote locations of the body, is one of the most serious effects of cancer and one for which a satisfactory treatment protocol is currently unavailable. The currently available methods of cancer therapy have either been of limited success in preventing metastasis or give rise to serious and undesirable side effects.
Although the specific delivery of therapeutic agents, such as anti-cellular agents, toxins and coagulation factors, to tumour mass represents a significant advance in cancer treatment protocols, there is still room for additional or even alternative therapies. The identification of additional targets to allow specific tumour destruction in vivo would naturally be of benefit in expanding the number of targeting options.
The novel therapeutic strategies for treating cancer are now moving towards the use of specific treatments, including monoclonal antibodies (mAbs) against different antigens expressed by tumour cells, which may hopefully cure the disease.
Antigen selection in immunotherapy must take into account either the tumour specificity of the antigen, the antigenic density in the surface of the tumour cells and the antigen modulation or the internalization of the antigen-antibody complex, which can reduce the ability to produce cell death. In most cases, complement-dependent cell lysis (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) are believed to be responsible for the clinical utility of the unconjugated mAbs, although the induction of apoptosis or cell cycle arrest could also play a substantial role in other cases.
Cancer cells may express certain molecular receptors. Different studies show that CC chemokine receptor 7 (CCR7) is expressed in different tumour cells, e.g., B-cell chronic lymphocytic leukaemia, non-Hodgkin lymphomas, breast cancer cells, malignant breast tumours, etc. Moreover, it appears that CCR7 receptor plays a role in lymph node metastasis of different cancers, e.g., gastric carcinoma, melanoma, non-small cell lung cancers, T-cell leukaemia cells, etc. Thus, said chemokine receptor (CCR7) can be selected as a possible target for mAb therapy in cancer.
CCR7 is a seven transmembrane-spanning domain G protein coupled receptor (GPCR). The family of G-protein coupled receptors (GPCRs) includes receptors for hormones, neurotransmitters, growth factors, and viruses [Yoshie O, Imai T, Nomiyama H. Novel lymphocyte-specific CC chemokines and their receptors. J Leukoc Biol. 1997; 62:634-644; Kim C H, Pelus L M, White J R, Applebaum E, Johanson K, Broxmeyer H E. CK beta-11/macrophage inflammatory protein-3 beta/EBI1-ligand chemokine is an efficacious chemoattractant for T and B cells. J Immunol. 1998; 160:2418-2424; Dieu M C, Vanbervliet B, Vicari A, et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med. 1998; 188:373-386; Willimann K, Legler D F, Loetscher M, et al. The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7. Eur J Immunol. 1998; 28:2025-2034; Yoshida R, Nagira M, Imai T, et al. EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC. Int Immunol. 1998; 10:901-910; Sallusto F, Schaerli P, Loetscher P, et al. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol. 1998; 28:2760-2769].
A particular case of a leukaemia which tumour cells express a CCR7 receptor is chronic lymphocytic leukaemia (CLL), the most common type of human adult leukaemia. Said leukaemia is a B cell leukaemia characterized by accumulation of a single clone of CD5+ B cells with a great resistance to undergo apoptosis due to deregulation of extracellular or intracellular signalling events implicated in programmed cell death. Despite its very low proliferation index, peripheral blood lymphocyte count reaches values greater than 5×103/μL and leukaemic cells demonstrate a marked tendency to invade lymph nodes, spleen and bone marrow.
The treatment of CLL is based in the use of purine analogues, particularly fludarabine, alone or in association, as frontline regimen. To date, the only therapeutic combination resulting in a higher complete remission rate than that obtained with fludarabine, has been the use of rituximab, an anti-CD20 monoclonal antibody, in association with either fludarabine or fludarabine plus cyclophosphamide. Moreover, molecular remissions in bone marrow aspirates were achieved in CLL patients with the above combinations, raising the possibility that CLL may be potentially curable without stem cell transplantation. Obtaining the best initial response together with the elimination of CLL cells in the inoculum of the patients undergoing autologous transplantation constitute some of the main therapeutic challenges in CLL.
Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma. The cells are characterized as CD20+ CD5+ CD23− with a t(11;14) and cyclin D1 overexpression. Patients are usually treated with either rituximab-CHOP (cyclophosphamida, hydroxyl daunorubicin, oncovin and prednisone) followed by stem cell transplantation or rituximab-HyperCVAD (cyclophosphamide, vincristine, adriamycin, and dexamethasone). However, MCL remains without cure in most cases, indicating a clear need for new treatment approaches.
It has been recently demonstrated that CLL patients presenting clinical lymphadenopathy have a higher in vitro migratory response of CLL cells to the ligands of CCR7, the homeostatic chemokines CCL19 (MIP3-β) and CCL21 (6Ckine). Therefore, blocking the entry of the CLL cells into secondary lymphoid tissue with anti-CCR7 mAbs could be another advantage. Also, in this sense, non-lymphoid tumours expressing ectopic CCR7 have the ability to metastasize into secondary lymphoid organs, whereas tumours lacking this molecule or other chemokine receptors involved in the homing to secondary lymphoid organs, present a minimal nodal dissemination.
Therefore, there is a need for additional cancer therapies, in particular, cancer and tumour cells expressing a CCR7 receptor. Advantageously, said therapy should allow specific tumour destruction in vivo by, for example, killing tumour cells, impairing migration and/or blocking dissemination of tumour cells.

Anti-CCR7 receptor antibodies for the treatment of cancer


A novel multi-slug bullet or round is provided that, through the use of flat-faced abutting end walls of successive cylindrical slugs, tightly packed above the powder charge in the cartridge casing, and appropriate fast-burning powder charge tailored to the weight of the multiple slugs, achieves multiple-hit stopping power within self-defense ranges and the like with greatly reduced penetration and thus minimal chance of lethality or collateral damage. With a single firing, multiple hits over a controlled area are achieved, materially lessening the requirement for precise aiming, reducing the amount of ammunition and the number of firings required in use, and reducing recoil, while eliminating ricochet effects.

The art is replete with many types of ammunition designed for a wide variety of uses and effects, ranging in the case of hand-held guns, from hard lead pointed penetration projectiles to multiple bursting projectiles such as shot gun pellets on the one hand, and so-called "Glaser" rounds for penetration and the tearing of lethal holes in the recipient, on the other hand. In all such devices, the approach is to employ a rather slow-burning powder to create the required gas expulsion pressure in the cartridge or shell casing to generate muzzle velocity necessary to launch and carry the hard lead projectile(s), packed in the cartridge, to the target for the intended penetration and, most often, lethal effects.
Emphasis in both police and military applications has been also upon developing aiming expertise, with the particular end in view of hitting a precise spot behind which lies an organ or other body part that the bullet is to enter or where the projectile(s) should burst in order to kill the assailant. Multiple firings of successive rounds is provided for in revolvers and semi-automatic and automatic weaponry to insure the ultimate result if the first projectile fails to achieve its goal. Such conditions are described, for example, in an article entitled "Accurately Predicting Stopping Power" appearing in Guns Magazine, 1992.
There are occasions and circumstances, however, including personal or home self-defense, as well as police, military and other uses, where society generally deems it preferable to achieve the stopping or disabling of an attacker or other threatening individual, without inflicting a likely lethal result, and otherwise with low inflicted collateral damage, and most desirably with greatly reduced ricochet potential.
It is to such applications that the present invention is in large measure primarily directed, having also the concomitant synergistic effects of reducing both the required aiming skills and the number of bullets that must be carried in the weapon and potentially fired.

Incapacitating non-lethal multiple projectile ballistic round