Provided is a new 5 V class spinel exhibiting an operating potential of 4.5 V or more (5 V class), which can suppress the amount of gas generation during high temperature cycles. Suggested is a manganese spinel-type lithium transition metal oxide represented by formula: Li[NiyMn2-(a+b)-y-zLiaTibMz]O4 (wherein 0≦z≦0.3, 0.3≦y<0.6, and M=at least one or more metal elements selected from the group consisting of Al, Mg, Fe and Co), in which in the above formula, the following relationships are satisfied: a>0, b>0, and 3≦b/a≦8.

Lithium secondary batteries have features such as high energy density and long service life. Therefore, lithium secondary batteries are widely used as power supplies for electric appliances such as video cameras; portable electronic devices such as laptop computers and mobile telephones, and electric tools such as power tools. Recently, lithium secondary batteries are also applied to large-sized batteries that are mounted in electric vehicles (EV), hybrid electric vehicles (HEV) and the like.
A lithium secondary battery is a secondary battery having a structure in which, at the time of charging, lithium begins to dissolve as ions from a positive electrode and moves to a negative electrode to be stored therein, and at the time of discharging, lithium ions return from the negative electrode to the positive electrode, and it is known that the higher energy density of the lithium secondary battery is attributable to the electric potential of the positive electrode material.
Known examples of this kind of positive electrode active material for lithium secondary batteries include lithium transition metal oxides having a layered structure, such as LiCoO2, LiNiO2, and LiMnO2; and lithium transition metal oxides having a manganese-based spinel structure (Fd-3m), such as LiMn2O4 and LiNi0.5Mn1.5O4 (in the present invention, referred to as "manganese spinel-type lithium transition metal oxides").
Manganese spinel-type lithium transition metal oxides are inexpensive in terms of raw material cost, are non-toxic and highly safe, and have a nature resistant to overcharge. Therefore, attention has been paid to the lithium transition metal oxides as the next-generation positive electrode active materials for large-sized batteries for electric vehicles (EV), hybrid electric vehicles (HEV) and the like. Furthermore, spinel type lithium transition metal oxides (LMO) capable of three-dimensional insertion and extraction of Li ions have superior power output characteristics compared with lithium transition metal oxides having a layered structure, such as LiCoO2. Therefore, it is expected to use the spinel type lithium transition metal oxides in applications where excellent power output characteristics are required, as in batteries for EV, batteries for HEV, and the like.
Among them, it is know that when a portion of Mn sites in LiMn2O4 is substituted with other transition metals (Cr, Co, Ni, Fe or Cu), the lithium transition metal oxide acquires an operating potential at near 5 V. Thus, currently, development of a manganese spinel-type lithium transition metal oxide having an operating potential of 4.5 V or more (5 V class) is in active progress.
For example, Patent Document 1 discloses, as a positive electrode active material for lithium secondary batteries exhibiting an electromotive force of 4.5 V or more (5 V class), a high capacity spinel type lithium manganese composite oxide positive electrode active material obtained by adding chromium as an essential additive component to a spinel type lithium manganese composite oxide, and further adding nickel or cobalt thereto.
Patent Document 2 discloses a crystal having a spinel structure, LiMn2-y-zNiyMzO4 (provided that M: at least one selected from the group consisting of Fe, Co, Ti, V, Mg, Zn, Ga, Nb, Mo and Cu; 0.25≦y≦0.6, and 0≦z≦0.1), with which charging and discharging is conducted against Li metal at a potential of 4.5 V or more.
Patent Document 3 discloses a spinel type lithium manganese composite oxide represented by Lia(MxMn2-x-yAy)O4 (wherein 0.4<x, 0<y, x+y<2, 0<a<1.2; M includes one or more metal elements selected from the group consisting of Ni, Co, Fe, Cr and Cu, and include at least Ni; and A includes at least one metal element selected from Si and Ti, provided that when A includes only Ti, the value of the proportion of A, y, is such that 0.1<y), as a positive electrode material for higher energy density lithium ion secondary batteries having a high voltage of 4.5 V or more against Li.


An improved cup for use on pipeline pigs is formed of a unitary material, such as urethane, the cup having a forward end, a rearward end and a central axis and with an integral flange portion providing means for securing the cup to a pipeline pig, the cup having an intermediate portion extending rearwardly from the flange portion, the intermediate portion having an interior frustro-conical surface and an exterior frustro-conical surface and the cup having a rearward portion, the external surface of the rearward portion curving in an arc to a generally cylindrical configuration. The cup preferably has a plurality of slits formed in the rearward portion, each of the slits being in the plane of the cup central axis and most preferably includes V-shaped grooves in the cup rearward portion external and/or internal surfaces, the grooves being of V-shaped configuration. The provision of the rounded exterior surface of the cup reduces the likelihood of the cup catching on obstructions within the pipeline and the provision of the slits and grooves functioning to increase flexibility of the cup allowing it to more readily deflect inwardly when obstructions in a pipeline interior wall are encountered.

1. Field of the Invention
It is frequently necessary to send mechanical devices through the interior of a pipeline. One reason for using a device that is transmitted through a pipeline, usually referred to as a "pig", is for cleaning the interior surface of the pipeline. Another use for a pipeline pig is for separating one fluid medium from another. Sometimes pipeline pigs are used for pushing out entrapped liquids in a gas transmitting pipeline. Another and very important reason for sending pigs through a pipeline is for gaining information as to the condition of the pipeline. Such pigs are frequently referred to as "instrumentation pigs" and these type of devices can be used to provide information as to the ovality of the pipeline, the interior diameter of various sections of the pipeline, the occurrence of dents, buckles or bulges in the pipeline wall, the detections of bends or changes in direction of the pipeline and the occurrence of corrosion in the pipeline interior or exterior walls.
Pipeline pigs, particularly of the instrumentation type, normally employ cups formed of resilient material, such as urethane. The cups serve two basic functions, that is, (1) they support the body of the pig within the interior of the pipeline and (2) at least one cup for each pig provides a piston-like action so that the flow of the fluid medium, whether liquid or gas, through the pipeline serves to propel the pig within the pipeline.
While the improved cup of this disclosure may be employed on many types of pigs, such as those used for cleaning the interior of a pipeline, the advantages of the improved cup are particularly helpful and important when used on an instrumentation type pig, and the cup will be described as it is particularly applicable for this purpose.
2. The Prior Art
For background information relating to pipeline pigs that employ resilient cups reference may be had to the following U.S. patents:
______________________________________ U.S. Pat. No. Title Inventor Issue Date ______________________________________ 4,984,322 Elastomeric Disc For Cho et al Jan 15, 1991 Use On A Pipeline Pig 4,953,412 Pipeline Caliper Pig Rosenberg Sep 04, 1990 4,930,223 Bend Detector Pig Smith Jun 05, 1990 4,457,073 Pipeline Pig having Payne Jul 03, 1984 Improved Means Of Sensing Changes In The Internal Config- uration Of A Pipeline 4,524,526 Apparatus & Method Levine Jun 25, 1985 For Inertial Measure- ment Of Pipeline Deflection 4,880,028 Completion Machine Osburn et Nov 14, 1989 al 4,522,063 Methods & Apparatus VerNooy Jun 11, 1985 For Indicating Se- lected Physical Par- ameters In A Pipeline 4,457,073 Pipeline Pig Having Payne Jul 03, 1984 Improved Means Of Sensing Changes In The Internal Con- figuration Of A Pipeline 4,413,370 Unitary Pig For Use Payne et Nov 08, 1983 In A Pipeline al 4,365,379 Pipeline Pig Having Neff Dec 28, 1982 Improved end Plate Retention 3,940,855 Pipeline Pig VerNooy Mar 02, 1976 et al 3,887,983 Pipe Pulling Tool Province Jun 10, 1975 3,868,773 Bean Removal Tool Province Mar 04, 1975 3,862,497 Pipeline Pig VerNooy Jan 28, 1975 et al 3,755,908 Pipeline Pig VerNooy Sep 24, 1973 3,732,625 Pipeline Pig VerNooy May 15, 1973 3,704,478 Pipeline Pig VerNooy Dec 05, 1972 3,649,983 Pipeline Pig VerNooy Mar 21, 1972 3,604,041 Pipeline Cleaning VerNooy Sep 14, 1968 Device 3,600,010 Pipeline Coupling Downs et Aug 17, 1971 al 3,576,043 Pipeline Pig With Zongler Apr 27, 1971 Spring-Mounted Scrapers 3,496,588 Pipeline Pig VerNooy Jun 26, 1967 ______________________________________
In addition to the instrumentation type pigs as exemplified by these patents, examples of pigs employing cups that are primarily intended for other purposes, such as cleaning or for fluid separation, are U.S. Pat. Nos. 4,413,370 and 4,365,379.
An object of the present invention is to provide a cup having improvements over cups exemplified by these previously issued patents. The cup to be hereinafter described includes the basic capabilities of the cups illustrated in these patents, that is, for supporting a pipeline pig centrally within a pipeline and for impeding fluid flow therepast so that the pig will be propelled through the pipeline. In addition, the cup to be described has improved strength for supporting a pig body centrally within a pipeline while, at the same time, the cup has greater flexibility. That is, the improved cup of this disclosure more readily flexes inwardly to pass a protrusion in the pipeline wall. In addition, the configuration of the cup is such that it is less likely to catch on or hang up on an object extending within the pipeline wall.


Methods are provided to fabricate semiconductor devices, e.g., FinFET devices, having fin channel structures formed of silicon-germanium alloy layers with uniform thickness. For example, a method includes forming a semiconductor fin structure having sidewalls that define a first width of the semiconductor fins structure, and a hard mask layer disposed on a top surface of the semiconductor fin structure. Portions of the sidewalls are etched to form recessed sidewalls that define a thinned portion, wherein a distance between the recessed sidewalls defines a second width of the thinned portion of the semiconductor fin structure, which is less than the first width. Facetted semiconductor alloy layers are formed on the recessed sidewalls, and then anisotropically etched using the hard mask layer as an etch mask to form planarized semiconductor alloy layers of uniform thickness on the recessed sidewalls of the thinned portion of the semiconductor fin structure.

FinFET technology is an emerging semiconductor technology that is being developed to provide effective scaling solutions for field effect transistor (FET) fabrication at, and below, the 22 nanometer (nm) node. FinFET structures include one or more narrow semiconductor fin structures, wherein each semiconductor fin structure is gated on at least two sides thereof. FinFET structures may be formed using silicon-on-insulator (SOI) substrates, as SOI technology provides low source/drain diffusion, low substrate capacitance, and ease of electrical isolation by use of shallow trench isolation structures. FinFETs may be also formed on bulk substrates to reduce wafer cost and/or enable formation of certain devices in the bulk substrate.
The implementation of silicon-germanium channels with high-percentage Ge concentration in FinFET devices is a primary choice for future technology nodes. Indeed, SiGe channels are desirable for state-of-the-art planar and trigate CMOS technologies because, e.g., a p-metal-gate results in a higher than desired threshold voltage. For advanced technology nodes such as 10 nm and beyond, FinFET devices having channel fin heights of 50 nm or greater are being developed to achieve enhanced performance. It is problematic and non-trivial, however, to form SiGe channel fin structures at heights of 50 nm or greater.
For example, while semiconductor fins can be formed by depositing a SiGe layer on a substrate and patterning the SiGe layer to form SiGe fin structures, the ability to deposit a high Ge-percentage (˜50%-75%) SiGe film with a thickness of 30-60 nm is limited and not practically feasible due to the low critical thickness of high-Ge percentage SiGe alloys. Indeed, the formation of a thick SiGe layer results in high density of defects in the SiGe layer, such as stacking faults, due to high lattice mismatch. Moreover, while thin SiGe layers can be grown on the sidewalls of silicon fin structures (with active fin heights greater than 30 nm), such growth results in non-uniform or facetted growth of SiGe layers on the fin sidewalls (110 surfaces). This can result in variation of device performance due to the non-uniform thickness of the SiGe channel layer along the fin width.

FinFET devices having silicon germanium channel fin structures with uniform thickness

International Business Machines Corporation


A detachable retainer for optical fibers, in particular optical fiber ribbons, is intended to be used in welding operations. The retainer generally has the structure of a rectangular block having lids that can be swung up and down and are arranged at the top side of the block for clamping the optical fibers. On the underside of the retainer a cylindrical recess is provided, along the transversal diameter of which a more shallow groove is provided which extends up to the longitudinal sides of the retainer. The corresponding flat surface, where the retainer is to be placed, has a cylindrical, short projection or boss having an upper edge with a large bevel and a transversal pin or transversal rib. The pin or rib has a close or tight fit to the corresponding groove in the underside of the retainer whereas the boss and the cylindrical recess have a fit with a considerable play. This results in that the retainer can be easily placed at its position by the boss and the cylindrical recess guiding the retainer to an approximate position and then a more accurate position in the longitudinal direction is obtained, when the pin or the is rib enters the groove. A limited movability is obtained in the lateral direction, which can be required in the case where the optical fibers are to be fitted into stationary V-grooves.

When handling optical fibers intended for telecommunication in connection with splicing the fibers movable retainers are used, which generally have the shape of low rectangular blocks including lids, which securely clamps the fiber or fibers. The retainer including inserted fibers is placed in a more or less accurate way in the machines or devices used, such as in a fiber welding machine on movable blocks, see for example Swedish patent application 9300578-3, which discloses a fiber welding device for fiber ribbons, such as when removing a protective sleeve and cutting optical fibers, see Swedish patent application 9103492-6, which discloses a combined stripping and cutting device for optical fibers, and when simultaneously handling a plurality of individual optical fibers placed in parallel, see Swedish patent application 9401421-4, which discloses a fiber organizer to be used when welding a plurality of optical fibers to for example the fibers of a fiber ribbon.
An optical fiber ribbon comprises a plurality of optical fibers placed at each other, isolated from each other and from the surroundings, but in some way secured in parallel at each other, e.g. by a polymer sleeve. The number of fibers, which in this way are mounted in parallel to each other, is arbitrary but fiber ribbons comprising 4 parallel fibers, so called 4 fiber ribbons, and 6, 8 fiber and 12 fiber ribbons comprising 6, 8 or 12 parallel optical fibers respectively which are retained at each other are commercially used.
In the prior art typically a loose or movable fiber retainer can be attached in a somewhat more or less definite position on a movable block, which is moved in all three coordinate directions for alignment in the welding operation. V-grooves and other devices having surfaces located in angles to each other can alternatively be used in order to accurately position the ends of the optical fibers in lateral and/or height directions and then also high requirements are posed on an accurate rigid positioning of the fiber retainer in height and lateral directions.
However, such alignment can without large problems be achieved for simple fibers owing to the fact that optical standard fibers usually have the same exterior diameter of about 250 .mu.m. In the published British patent application No. 2 303 223 for example a device is disclosed for welding optical PM fibers having stationary surfaces which are intended for a fine-positioning and are located in right angles to each other, in which device a retainer is placed accurately in height and lateral directions by bringing it, by means of magnetic forces, to engage with a fixed longitudinal projecting rib on a horizontal base surface.
However, the width of fiber ribbons present variations and differ between different brands, whereas the height from the bottom side of the fiber ribbon to the centre axis of the optical fibers included in the fiber ribbon only present insignificant variations. A loose retainer intended to be capable of being used when welding different types of fiber ribbons must therefore be capable of being displaced laterally on a fixed base surface in order that the ends of the optical fibers, which has been rid of primary and secondary protective enclosures, i.e. from the individual polymer sleeves, which surround and isolate each fiber individually, and the material or the sleeve respectively, which keeps the fibers coated with a primary coating together to form a fiber ribbon, will be capable of extending, as straight as possible, from the retainer to and through the fixedly arranged V-grooves or in any case without any bending laterally and most preferably always without any S-shaped bending in this region.
A simple small bending upwards, so that the fiber ends are still always located in a vertical plane extending from the retainer to the V-grooves, in order that the fibers by their own elasticity will remain in the V-grooves can be allowed, see the above-cited Swedish patent application 9300578-3. It must also be possible to adjust the position of the retainer by a parallel displacement, i.e. so that the retainer maintains the same angular position during the displacement and thus is not rotated, neither around a horizontal or a vertical axis.
Furthermore, it should for this case also be possible to secure such a retainer laterally in a suitable selected position, after having placed the optical fibers included in the fiber ribbon as straight as possible from the retainer to the fine alignment means having the shape of the V-grooves. The fiber ribbon must be firmly retained in the selected position laterally during the fine positioning in the longitudinal direction of the fiber ribbon, which is always necessary in order that the end surfaces of the individual opposite fibers will come in contact with each other and which is made by the displacing the blocks, on which the retainers are secured, in this direction, see the cited Swedish patent application 9300578-3.
The Japanese patent application No. 1-129 208 discloses a loose fiber retainer or jig 1, which can be placed in a fiber welding device and be clamped in it by means of clamping means 2. The German patent document No. 40 18 226 discloses a device for positioning optical fibers in connection with a welding operation. The published German patent application No. 40 06 799 is concerned with welding two groups of optical fibers to each other and discloses a retainer means and its attachment to a base. The published German patent application No. 40 25 351 also deals with welding two groups of optical fibers using a retainer.


Improvements in a compliant upright drink insulator attachment device that is works with a standard drink insulator. The attachment device uses two parts where one part mates with the second part to slip through a standard insulated drink holder. These insulated drink holders are commonly called coolies or koozies and are manufactured with a central hole to allow for draining. A clip connects a compliant cord to one or both of the two parts. The compliant cord is configured as a coiled cord. A weight is connected to the free end of the compliant cord to keep the insulated drink holder in an upright orientation in the water. The compliant cord allows the weight to move semi independent from the insulated drink holder, and further allows the weight to be stored within the insulated drink holder for storage when it is not being used.

1. Field of the Invention
This invention relates to improvements in a beverage flotation device. More particularly the improvement relates to an attachment for a beverage cooler that retains the beverage in an upright orientation.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Several products and patents have been filed an issued on drink insulators and retaining devices for beverages that are consumed while a person is in the water. Depending upon the amount of wakes that are encountered while on the water and the amount of natural or artificial topography that exists in the body of water the beverage can tip over. Some of these devices operate as stand-alone flotation devices or utilize existing beverage coolers coolies or koozies. Exemplary examples of patents covering these products are disclosed herein.
U.S. Pat. No. 4,571,194 issued Feb. 18, 1986 to James M. Kiss et al., and U.S. Pat. No. 6,607,090 issued Aug. 19, 2003 to Stephen Doerr disclose floating beverage holders that a user blows air into the inflate the float. The user can then open to filling valve to deflate the float when it is not being used. While this patent provides for a floatation device the amount of thermal insulation to the beverage is limited. The physical size of these devices is also significant because the floatation area must be significantly large to create enough width to make the float stable in the water.
U.S. Pat. No. D440,469 issued Apr. 17, 2001 to John J. Krist et al discloses a Floatation Holder For a Beverage Container. This design patent is a for a molded or formed beverage holder with an enlarged base that provides for a floatation device. This device requires a wide base for floatation. When a full soda container is placed within the container it is top heavy and can tip over with a large wave.
U.S. Pat. No. 5,447,764 issued Sep. 5, 1995 to Mark H. Langford and U.S. Pat. No. 6,616,493 issued Sep. 9, 2003 both disclose an essentially thick flat foam float that slides around the cylindrical side of the soda can. This is a simple version of a floatation device, but it provides minimal insulation to the beverage can and the location of the floatation device on the soda can is variable based upon placement by the user. If the floatation device is not placed properly on the can the can is more susceptible to tipping over.
U.S. Pat. No. 6,991,505 issued Jan. 31, 2006 to Robert Ray Wells discloses a Buoyant Apparatus for Attachment to Beverage Insulators Holding Beverage Containers. The device works with a standard beverage container insulator. The bottom of the beverage container insulator must be modified to allow the attachment to fit through the bottom of the insulator. The bottom of the buoyant apparatus is rigid and can tip over if the weighted end comes in contact with a rock or the ground.
What is needed is a compliant upright drink insulator attachment that works with an existing drink insulator. The bottom of the attachment device needs to be compliant to move with the waves of the water and compliant enough to still keep the drink in an upright orientation around rocks and shallow water.

Cooleebob compliant upright drink insulator attachment


A water-resistant porcelain enamel coating and method of making the same is provided. The porcelain enamel coating is prepared using a borosilicate glass frit, and mill additions of silica and a zirconia compound. The mixture is applied to a metal substrate and fired, resulting in a water-resistant coating that resists cracking and crazing. The coating is particularly useful in water heaters. In one embodiment, the coating comprises a fine zirconia compound having a median particle size of less than 10 microns.

Porcelain enamel is subject to corrosion and dissolution by hot water. This can cause difficulties in applications such as hot water heaters. In a water heater, once the porcelain enamel coating protecting a metal substrate is dissolved through to the substrate, then the substrate corrodes rapidly and is perforated through. At this point the water heater must be replaced.
Attempts to improve the corrosion resistance of porcelain enamel have resulted in the use of various mill additions. However, mill additions that improve corrosion resistance tend to result in porcelain enamels that are subject to fish scaling or crazing.
Therefore, it would be desirable to have an improved porcelain enamel coating which is not only highly water-resistant, but also resists crazing or cracking.

Water-resistant porcelain enamel coatings and method of manufacturing same


If first another communication device and second another communication device are wirelessly connected with one another on the basis of information acquired from a captured image, a communication device as a slave station connects with a wireless network constructed by the second another communication device as a base station, and makes communication for sharing a communication parameter with the second another communication device.

In recent years, a case increases in which an electronic device, such as a digital camera, a printer, a cell phone, or a smartphone, has a wireless communication function and is connected to a wireless network for use. In particular, a case increases in which communication is made between devices by using a wireless local area network (LAN) as a wireless communication function.
To connect the electronic device to the wireless network, it is required to set at least one of various communication parameters, such as an encryption method, an encryption key, an authentication method, and an authentication key. As a technology to make setting of such a communication parameter easy, there is a technology disclosed in PTL 1.
In PTL 1, an electronic device displays a Quick Response code (QR code, registered trademark, this note will be omitted hereinafter) indicative of a communication parameter. A cell phone reads the QR code by capturing the image of the QR code, and sets the read communication parameter at an access point.
Also, there is a technology in which ability information and identification information on an electronic device are included in a QR code, and processing for determining a role whether to operate as a base station or to operate as a slave station is simplified in Wi-Fi Direct (registered trademark, this note will be omitted hereinafter) (see PTL 2).
As described in PTL 1 and PTL 2, by setting a communication parameter upon capturing of an image of code information such as a two-dimensional code that can code much information, troublesome input by a user can be reduced. If a communication parameter is set through three devices like PTL 1, the device that executes image capturing causes the other devices to connect with one another, and thereafter the own device may no longer need to communicate with the other devices. In this case, if the technology for determining the role whether the base station or the slave station of Wi-Fi Direct is used like PTL 2, a connection network may be unnecessarily constructed unless the role of the device being an intermediary that wirelessly connects the other devices with one another is properly defined.
For example, if a first device being an intermediary wirelessly connects a second device and a third device with one another, first, the first device is connected with the second device, and transmits information required for wireless connection between the second device and the third device, to the second device. In this case, if information on the third device is transmitted to the second device in a wireless network constructed by the first device serving as a base station, the first device is no longer required to communicate with the second device or the third device. Hence, since the first device does not make communication by itself, the first device is no longer required to keep the formed wireless network.
In this way, after the first device being the intermediary operates as the base station and transmits the information required for the wireless communication between the second and third devices to the second device, the first device is no longer required to keep the formed wireless network, and therefore the first device may possibly terminate the wireless network. When the first device being the intermediary terminates the wireless network, the second device or the third device is required to execute processing of newly forming a wireless network for communication between the second and third devices.

Communication device, control method of communication device, and program


A method and apparatus are provided for locating a object based on a reference to the object. An application determines whether the reference has previously been used to locate the object. If the reference has previously been used to locate the object, then a data structure referred to as a "tombstone" that has been associated with the object is located based on a first virtual memory address that is stored in the reference. Once the tombstone has been located, a first pseudo-timestamp that is stored in the reference is compared to a second pseudo-timestamp that is stored in the tombstone. If the first pseudo-timestamp matches the second pseudo-timestamp, then the object is located based on a second virtual memory address that is stored in the tombstone. If the first pseudo-timestamp does not match the second pseudo-timestamp or if the reference has not been previously used to locate the object, then the object is located based on the identifier stored in the reference. During the process of locating the object based on the object identifier, the virtual address of the tombstone associated with the object is stored in the reference, and the pseudo-timestamp stored in the tombstone is stored in the reference. When tombstones are reused, the pseudo-timestamp within the tombstone is incremented.

Many computer programs model problems as sets of inter-related objects. During execution, such programs perform operations on objects that are stored as data structures in the memory of the computer system. Objects may have numerous attributes, including attributes that represent relationships to other objects. When a first object has an attribute that represents a relationship to a second object, the first object is referred to as the source object and the second object is referred to as the target object.
The information used to represent an attribute that represents a relationship with a target object is referred to as a "reference". A reference to a target object is stored in the data structure that represents the source object. For many applications, the most common operation in processing objects is to locate the target object based on the reference to the target object contained in the source object. This operation is known as reference traversal.
Many programs use a data type called a "pointer" as a reference to a target object. A pointer indicates the memory location of the data structure that corresponds to the target object. To allow a program to access more objects than can fit in the available dynamic memory, pointers typically indicate the virtual memory address of the target object rather than the actual physical address of the dynamic memory location at which the target object resides. When a program uses the virtual memory address as the representation of the reference, the program relies on the underlying virtual memory mechanism of the computer operating system and hardware for looking up the physical memory addresses of target objects.
When an object is in dynamic memory, the virtual memory address of the object is the optimal representation for a reference to the object because most computers have a built-in hardware lookup mechanism and high-speed memory for an address translation table that maps virtual memory addresses to physical memory addresses. In addition, operating systems typically provide very efficient memory caching support based on virtual memory access. By employing the built-in address translation and memory caching mechanisms, the use of virtual memory addresses as references to target objects results in a highly efficient reference traversal.
Unfortunately, virtual memory addresses are dynamically allocated and are thus only valid within and during a particular program execution. Therefore, a virtual memory address used for a target object during one execution of a program may not be the same for the same target object during a subsequent execution of the same program. Similarly, the virtual memory address of any given target object may not be the same for two concurrently executing programs. Therefore, virtual memory addresses cannot be used as the sole representation of references to target objects in environments where objects are shared across different executions of the same program, or across different concurrently-executing programs.
In a database management system (DBMS), the information used for references must correctly identify objects across all program executions. Therefore, a unique object identifier (OID) is assigned to each object. Unlike virtual memory addresses, the OID of an object uniquely identifies the object across all program executions. However, if the OID is used as a reference to an object stored in dynamic memory, each traversal operation requires mapping the OID to the virtual memory address of the target object, and then mapping the virtual memory address to the physical memory address of the target object. The process of mapping an OID to a virtual memory address consumes significantly more processing time than mapping a virtual memory address to a physical address.
Various attempts have been made to achieve the efficiency of reference traversals with virtual memory addresses while still being able to share objects between multiple programs and multiple executions of the same program. Typically, these approaches use OIDs as references to objects that are not currently loaded into dynamic memory, and virtual memory addresses as references to objects that have been loaded into dynamic memory. Therefore, references to an object must be converted from one form to another when the object is transferred between static memory and dynamic memory. The process of converting references between an external form and an internal form is referred to as reference swizzling.
According to one prior art reference swizzling technique, when an object is loaded from disk into main memory, all of the references contained within the object are converted into virtual memory addresses. Since the target objects of those references may not be in main memory, virtual memory addresses must be pre-allocated for the target objects as if they were already in main memory.
When a reference to a target object that is not in main memory is traversed, the DBMS loads the target object into main memory. To detect such reference traversal operations, the DBMS relies on the computer operating system by setting all pre-allocated virtual memory addresses in access-protected mode. When an access-protected virtual memory address is accessed, the computer operating system detects a memory access protection violation and raises an exception. The DBMS handles the exception by loading the desired target object into main memory and changing the virtual memory address to a mode that allows access.
While the use of protected mode allows for fast reference swizzling, it relies on special operating system supports, such as the memory access control, detection, and exception handling functions of the operating system. Unfortunately, these supports may deviate from platform to platform, and may even be unavailable in some platforms. Therefore, this approach is not practical for DBMS systems that are intended for use on multiple platforms. Further, because memory has been pre-allocated for all of the objects, the memory cannot be reused for other purposes. Therefore, applications that use a large number of objects may run out of memory.
According to an alternative approach, each reference is a data structure that contains a discriminant field and a variant field. The value in the discriminant field indicates whether the variant is an object identifier or the virtual memory address of the target object. Each object in main memory has a "surrogate" that is a data structure containing a reference count, the object identifier of the target object, and the virtual memory address of the target object. When the DBMS loads an object from disk into main memory, the value of the discriminant of each reference contained in the object is initially set to indicate that the corresponding variant is the object identifier of the target object.
When an application traverses the reference, the DBMS determines whether the discriminant of the reference indicates that the variant is an object identifier or a virtual memory address. If the variant is a virtual memory address, then the virtual memory address is used to locate the surrogate. The virtual memory address stored in the surrogate is then used to locate the target object.
If the variant is an object identifier, then the DBMS looks up the virtual memory address of the surrogate. If the surrogate exists, then the variant of the reference is set to the virtual memory address of the surrogate. The discriminant of the reference is set to indicate that the variant is the virtual memory address of the surrogate. The reference count of the surrogate is then incremented by one.
If the surrogate does not exist, then the target object is loaded from disk into main memory, a surrogate is allocated for the target object, the object identifier and the virtual memory address in the surrogate are set to those of the target object and the reference count of the surrogate is set to zero. Then, the DBMS performs the steps of setting the variant, setting the discriminant, and incrementing the reference count, as described above.
When an object is saved to disk, the DBMS decrements the reference count of all of the surrogates pointed to by the references in the object. Therefore, at any given time, the reference count of a surrogate indicates how many references are currently pointing to the surrogate. Only when the reference count of a surrogate is zero may the object pointed to by the surrogate be swapped to disk and the surrogate deallocated.
One disadvantage of the surrogate technique is that the DBMS cannot swap an object to disk to free up memory as long as an object that has a traversed reference to the object remains in memory. Consequently, the DBMS may become significantly limited with respect to how it may free up memory to load newly referenced objects. In addition, the process of decrementing surrogates adds overhead to the process of storing objects to disk.
Based on the foregoing, it is clearly desirable to provide a mechanism for and method for swizzling references to objects that increases the reference traversal speed over using OIDs as the representation for references. It is further desirable to provide a mechanism for swizzling references that does not rely on support from specific platforms.

Method and apparatus for locating a first set of data using a global identifier and a virtual addressing data structure


The present invention is a massage tool comprised of a flexible mitt-shaped sheet, made of plastic or rubber, which has a separate thumb portion and numerous projections that are specially shaped and spaced to ensure flexibility while massaging, allowing comfortable pushing, patting and pinching throughout the surface of the flexible sheet, and a fastening device on the back that can be easily cleaned, attached or removed.

The present invention relates to a massage tool that is comprised of a flexible mitt-shaped sheet, made of plastic or rubber, which has a separate thumb portion and numerous projections on its front surface, and a fastening device on the back.
Massage tools having many projections have been used for body massage, excluding the scalp. A massage tool designed for the scalp was therefore sought.
For scalp massage, some conventional massage tools, which are in the form of gloves, mittens and the like, are impracticable for the following reasons:
1) The length of the projections are too short and cannot reach the scalp.
2) The diameter of the projections are too thick and the shape of the projection tips are too flat, resulting in the hair being caught between the scalp and projections.
3) The length/diameter ratio of the projections are too large; thus projections do not possess sufficient rigidity to grip the scalp.
4) The projections are spaced too closely together meaning that the flexible sheet cannot easily follow the hand""s movements.
Cleaning, attaching or removing these massage tools are cumbersome in that some conventional massage tools have a suction portion that collects rubbish, the opening of which is often too narrow to insert one""s hand or finger.
For massage of a wide area of the scalp in a short time some conventional massage tools do not possess sufficient flexibility to follow comfortably the hand""s movements or the shape of the head, and the area of projections is insufficient to cover the scalp.
The invention was created to improve upon such drawbacks contained in conventionally used massage tools.
The present invention is a massage tool comprised of a flexible mitt-shaped sheet, made of plastic or rubber, which has a separate thumb portion and numerous projections, which are specially shaped and spaced to ensure flexibility while massaging, allowing comfortable pushing, patting and pinching throughout the surface of the flexible sheet, and the fastening device on the rear can be easily cleaned, attached or removed.


Embodiments herein describe DRAM that includes storage circuitry coupled between complementary bit lines which are in turn coupled to the same sense amplifier. The storage circuitry includes a transistor and a storage capacitor coupled in series. The gate of the transistor is coupled to a word line which selectively couples the storage capacitor to one of the complementary bit lines. Because the capacitor is coupled to both of the bit lines, when reading the data stored on the capacitor, the charge on the capacitor causes current to flow from one of the bit lines into the other bit line which causes a voltage difference between the complementary bit lines. Put differently, both ends of the capacitor are electrically coupled to bit lines thereby generating a larger voltage difference between the bit lines when reading data from the storage capacitors.

Embodiments presented herein generally relate to integrated circuit (IC) memory devices, and more specifically, to dynamic random access memory (DRAM) with differential sensing.
DRAM is a type of random access memory which utilizes separate capacitors to store each bit of data based upon the voltage stored in the capacitors. A memory circuit is formed from an array of DRAM cells where all of the cells in a given column of the array are coupled to a single bit line. Similarly, a single word line may serve all the cells in a given row. In this manner, data stored in one of the DRAM cells in the memory circuit can be read from the cell's capacitor through its respective bit line in response to the word line activating the cell.
DRAM cells and circuits may be produced using semiconductor lithography. Modern trends in DRAM production scale DRAMs to ever smaller lithography sizes. As sizes are reduced, it becomes more difficult to maintain reliability and performance as lithography error rates increase.

Random access memory with pseudo-differential sensing

INTERNATIONAL BUSINESS MACHINES CORPORATION


Disclosed is a simple and highly efficient method for introducing a gene into a target cell using a retrovirus vector. The method comprises the steps of (a) placing a liquor containing a retrovirus vector having a foreign gene carried thereon into a bag for cell culture on which a retrovirus-binding substance has been immobilized, and incubating the liquor at a temperature lower than 25° C. for 8-48 hours, thereby producing a culture bag having the retrovirus vector bound thereto, (b) adding a target cell to the culture bag that has been produced in step (a) and incubating the culture bag for 8 hours or less, and (c) flipping the culture bag upside down and incubating the culture bag. The gene introduction method is useful particularly in medicine, cell technology, gene technology, and embryologic technology.

Recently, gene therapies for treating severe genetic diseases, cancers and the like have been developed. Most of the gene therapies which have been examined for clinical application to humans heretofore involve gene transfer into cells using recombinant retroviral vectors. The retroviral vector can stably integrate a foreign gene of interest into chromosomal DNA of target cells. Therefore, gene transfer by the retroviral vector is a preferable means of gene transfer particularly for the gene therapy in which long-term gene expression is desired.
It has been reported that the efficiency of gene transfer using a retroviral vector is increased by use of a cell adhesive substance that binds to retroviruses, such as fibronectin or a fibronectin fragment CH-296 [RETRONECTIN® (recombinant human fibronectin fragment)] (e.g., Patent Literature 1). Also, it has been reported that the gene transfer efficiency is further increased by a method comprising adding a solution containing a retroviral vector to a vessel coated with RETRONECTIN® (recombinant human fibronectin fragment) followed by incubation for a certain period of time to allow only the viral vector to bind onto RETRONECTIN® (recombinant human fibronectin fragment), removing a supernatant containing an inhibitory substances against infection, and then adding target cells (RETRONECTIN® Bound Virus Infection Method: RBV method) (Patent Literature 2, Non-Patent Literature 1).
The binding of the viral vector to RETRONECTIN® (recombinant human fibronectin fragment) in the RBV method can be enhanced by utilizing centrifugal force (centrifugal RBV method). However, the centrifugal RBV method requires a vessel that can bear centrifugal force and an expensive apparatus for a centrifugal operation, and the operation includes multi-steps. In addition, there is also a problem that it is difficult to scale up the processing capacity when gene transfer into a large amount of cells is required.

This patent is subject to a terminal disclaimer.


In accordance with the present invention there is provided a biopsy device and method for the collection of at least one tissue sample from a surgical patient. The device includes a frame and an elongated piercing element attached to the distal end of the frame. The piercing element has distal end, a proximal end and a lumen extending at least partially therethrough. The piercing element has a sharpened member at its distal end for piercing tissue, and a port proximal thereto which exposes the lumen. The device further includes an elongated cutter and tissue remover disposed coaxially and slidably within the lumen of the piercing element for harvesting a tissue mass disposed within the port of the piercing element and depositing the tissue mass proximal to the port for retrieval. Lastly, the device includes a mechanism for automatically axially rotating the piercing element after severing a sample so multiple samples can be harvested about a longitudinal axis of the piercing element without manually rotating the piercing element.

The diagnosis and treatment of patients with cancerous tumors, pre-malignant conditions, and other disorders has long been an area of intense investigation. Non-invasive methods for examining tissue are palpation, X-ray, MRI, CT, and ultrasound imaging. When the physician suspects that a tissue may contain cancerous cells, a biopsy may be done either in an open procedure or in a percutaneous procedure. For an open procedure, a scalpel is used by the surgeon to create a large incision in the tissue in order to provide direct viewing and access to the tissue mass of interest. Removal of the entire mass (excisional biopsy) or a part of the mass (incisional biopsy) is done. For a percutaneous biopsy, a needle-like instrument is used through a very small incision to access the tissue mass of interest and to obtain a tissue sample for later examination and analysis. The advantages of the percutaneous method as compared to the open method are significant: less recovery time for the patient, less pain, less surgical time, lower cost, less risk of injury to adjacent bodily tissues such as nerves, and less disfigurement of the patient's anatomy. Use of the percutaneous method in combination with artificial imaging devices such as X-ray and ultrasound has resulted in highly reliable diagnoses and treatments.
Generally there are two ways to obtain percutaneously a portion of tissue from within the body, by aspiration or by core sampling. Aspiration of the tissue through a fine needle requires the tissue to be fragmented into small enough pieces to be withdrawn in a fluid medium. The method is less intrusive than other known sampling techniques, but one can only examine cells in the liquid (cytology) and not the cells and the structure (pathology). In core sampling, a core or fragment of tissue is obtained for histologic examination which may be done via a frozen or paraffin section. The type of biopsy used depends mainly on various factors present in the patient, and no single procedure is ideal for all cases. However, core biopsies seem to be more widely used by physicians.
Recently, core biopsy devices have been combined with imaging technology to better target the lesion. A number of these devices have been commercialized. One such instrument type is the BIOPTY gun, trademark of C.R. Bard, Inc. and described in U.S. Pat. Nos. 4,699,154 and 4,944,308 as well as in U.S. Reissued Pat. No. Re. 34,056. The BIOPTY device is spring-powered, and each time a sample is to be taken the breast or organ must be punctured again upon re-insertion of the device. Another product is the TRU-CUT needle, trademark of C.R. Bard, Inc. The TRU-CUT needle collects a single core of tissue using a pointed stiletto with a side-facing notch to receive tissue near its distal end and an outer, sharpened sliding cannula.
To overcome operator error associated with these devices, and to enable multiple sampling of the tissue without having to re-puncture the tissue for each sample there was a desire for an automated device which took multiple samples with a single puncture. One such commercially available product is marketed under the trademark name MAMMOTOME, Ethicon Endo-Surgery, Inc. An embodiment of such a device is described in U.S. Pat. No. 5,526,822 issued to Burbank, et al, on Jun. 18, 1996, and is hereby incorporated herein by reference.
As seen from that reference, the MAMMOTOME instrument is a type of image-guided, percutaneous, coring, breast biopsy instrument. It is vacuum-assisted, and some of the steps for retrieving the tissue samples have been automated. The physician uses this device to capture "actively" (using the vacuum) the tissue prior to severing it from the body. This allows for sampling tissues of varying hardness. The device can also be used to collect multiple samples in numerous positions about its longitudinal axis, and without needing to remove the device from the body. These features allow for substantial sampling of large lesions and complete removal of small ones.
Co-pending application 60/240,877 filed Oct. 13, 2000 which is hereby incorporated herein by reference, describes other features and potential improvements to the MAMMOTOME device including a molded tissue cassette housing permitting the handling and viewing of multiple tissue samples without physical contact by the instrument operator. Another described therein is the interconnection of the housing to the piercing needle using a thumbwheel, to permit the needle to rotate relative to the housing, and preventing the vacuum tube from wrapping about the housing. During use, the thumbwheel is rotated so that the device rotates within the lesion, and samples can be taken at different points within the lesion.
In actual clinical use for breast biopsy the MAMMOTOME instrument (probe and driver assembly) is mounted to the three axis positioning head of an x-ray imaging machine. The three axis positioning head is located in the area between the x-ray source and the image plate. The x-ray machines are outfitted with a computerized system which requires two x-ray images of the breast be taken with the x-ray source at two different positions in order for the computer to calculate the x, y and z axis location of the suspect abnormality. In order to take the stereo x-ray images the x-ray source must be conveniently movable. The x-ray source therefore is typically mounted to an arm which, at the end opposite the x-ray source, is pivotally mounted to the frame of the machine in the region of the image plate.
The mounting of the device to an X-Ray machine has caused some difficulty in operating the thumbwheel. During a breast biopsy procedure, the operator has limited space to work in and it can be difficult for the operator to grasp and manually rotate the thumbwheel. Additionally, for the upright X-ray applications the operation of the thumbwheel causes the operator to be close to the patient's face. This can be awkward or difficult to manage, and can be uncomfortable for the patient. Lastly, the operator's hands can come in contact with bodily fluids and tissue during the biopsy procedure and these contaminants may be passed on to the surface of the thumbwheel.
Therefore, there has been a need for a biopsy device of the type described above, similar to the MAMMOTOME, which has a thumbwheel that automatically rotates after each sample is obtained. If such a device were to utilize existing rotational components for the additional task of rotating the needle aperture, the need for an extra shaft or gear is eliminated. Therefore the size of the device is reduced, creating more space for the manual rotation, but moreover it offers the operator the option of automatic rotation.

Surgical biopsy device having automatic rotation of the probe for taking multiple samples


A motor control apparatus is combined with an internal combustion engine and an electric motor to form a vehicle-propelling system. The motor is connected to a crank shaft of the engine and has both driving and power-generating functions. The motor control apparatus includes an automatic start-up/stop control device having automatic start-up control and automatic stop control sections. When the vehicle is started with a key, the automatic start-up control section uses the starter motor and always gains assistance from the electric motor in starting the vehicle. Only the automatic start-up control section controls start up of the electric motor, which prevents a noise occurring when a ring gear is engaged with a starter motor gear. This operation improves the quietness of the engine. This arrangement enhances discharge of exhaust gas.

This invention relates to a motor control apparatus combined with an engine, particularly to a motor control apparatus combined with an engine having an automatic start-up/stop control means for start-up, which is disposed in a vehicle having the engine and an electric motor disposed therein as a vehicle-propelling system. The motor is combined with a crank shaft of the engine, and has both driving and power-generating functions.
Some motor vehicles are of a type commonly called a hybrid vehicle having an internal combustion engine and an electric motor (referred to as xe2x80x9cmotorxe2x80x9d throughout the specification) disposed therein as the power sources of a propulsion system. The motor disposed in the hybrid vehicle is combined with the engine, and the hybrid vehicle further includes an engine control means for controlling a running state of the engine and a motor control means for controlling an operating state of the motor. The engine control means and the motor control means detect respective operating states of the engine and the motor when the vehicle is traveling, and then exchange such detected data regarding the running states. As a result, the respective operating states of the engine and the motor are controlled in association with one another. Such a control system attains a high level of required performance (such as fuel efficiency, lower values of detrimental components in exhaust gases, and power performance).
One such example of a control apparatus for a motor combined with an engine is disclosed in published Japanese Application Laid-Open No. 8-93517. The hybrid electric powered vehicle includes a power generating apparatus driven by an engine and a battery for powering the vehicle. The vehicle includes a motor that can receive electric power supplied from the battery, or the power generating apparatus can supply electric power to the battery. An electronic control apparatus for controlling the motor is powered by a sub-battery. The electronic control apparatus includes a means for determining that the engine is started, a means for prohibiting driving of the starter by electric power from the sub-battery during control of the motor after the engine is determined to have started and a means for determining whether a terminal voltage of the sub-battery is less than a predetermined voltage. As a result, the control means prevents a false movement of an electronically controlled apparatus due to a drop in voltage of the sub-battery during a restart operation for the engine.
Published Japanese Patent Application Laid-Open No. 10-136508 discloses a hybrid vehicle that has an engine operated by combustion energy of fuel and an electric motor operating by electric power from a power source in the vehicle. The vehicle has a starter for start up, and usually is started by cranking an engine with the electric motor. But, the hybrid vehicle has an engine start-up control means to start cranking the engine with the starter when a start-up by the electric motor is determined to be impossible. Then engine start-up control means has an additional function to assist in cranking the engine when the hybrid vehicle starts cranking an engine with the starter. In this way, the hybrid vehicle suitably starts up the engine by using the small and cheap starter.
In published Japanese Patent Application Laid-Open No. 6-257484, the engine automatic start-up/stop apparatus controls start up of an engine when a predetermined start-up condition is satisfied after the engine disposed in a vehicle is stopped, and also stops the engine when a predetermined stopping condition is satisfied during running of the engine. In the engine automatic start-up/stop apparatus, when a predetermined time condition passes while a stop mode is continued after the engine is started up by an operation of an engine-key, and a following stopping condition when the vehicle moves, satisfying a condition, then the engine is automatically stopped. The automatic start-up/stop apparatus makes automatic shutoff of an engine possible when the temperature is low, and improves mileage when a driving time is comparatively short.
Published Japanese Patent Laid-Open No. 10-47104 discloses an engine automatic start-up/stop apparatus which is controlled so as to automatically stop when a predetermined automatic stop condition is satisfied during running of an engine disposed in a vehicle, and is controlled to automatically start up when a predetermined automatic start-up condition occurs after being automatically stopped. The engine automatic start-up/stop apparatus determines whether the vehicle is started up by the engine-key when the engine is started up, and whether the vehicle is started up after automatically being stopped, and can change the initial value of a revision quantity of an idle air flow quantity at a key start-up mode and the initial value at an automatic start mode.
The engine automatic start-up/stop apparatus prevents an unnecessary rise of an idle speed in automatically starting-up the vehicle after automatically being stopped, and improves the mileage.
A control means of a motor combined with an engine is used for a so-called idle-stop vehicle. The idle-stop vehicle is restarted by a starter motor after the engine is stopped.
If using the starter motor to restart, when the starter motor is engaged with a ring gear, an inconvenience occurs from a noisy sound. There is also inconvenience in that the durability of a starter motor is decreased.
When the engine is restarted, a starting-up compensation acts, and it can become unnecessarily rich in fuel to maintain a rise of engine speed. As a result, there is inconvenience in that more fuel is used than needed. Further, an exhaust gas containing harmful ingredients in unnecessary abundance is exhausted. When a restart of an engine occurs for a fixed time, additional fuel is desirable for a certain mileage distance and a proper output dispersion of exhaust gas from the engine continues.
In the apparatus disclosed in published Japanese Patent Application Laid-Open No. 10-136508, when cranking by a motor is impossible, then the cranking may be done by a starter. When the cranking is done by the starter, then the motor assists in cranking the engine according to need. In operation of the above-mentioned published Japanese Patent Application Laid-Open No. 10-136508, inconvenience occurs from noisy sound when a starter gear is engaged.
In order to obviate the above problems, the present invention provides a motor control apparatus combined with an engine and an electric motor in a vehicle-propelling system. The motor is connected to a crank shaft of the engine and has both driving and power-generating functions. An automatic start-up/stop control means includes automatic start-up control and automatic stop control sections. The start-up control section starts the vehicle using the starter motor while always receiving assistance from the motor when the vehicle is started with a key. The automatic start-up control section automatically starts up the motor, which cancels noisy sounds occurring when a ring gear engages a starter motor gear. This improves quietness, which characteristic is advantageous in practical use. Further, improved characteristics for discharge of exhaust gas result.
According to the present invention as previously described, at automatic start-up, the control means controls a vehicle start up automatically using only the motor and cancels noisy sounds occurring when a ring gear engages with a starter motor gear. As a result, the quietness is improved, better dispersion of the exhaust gas is expected, and a simplification of the system results.

Motor control apparatus combined to engine


A method of obtaining high affinity human monoclonal antibodies having a Kd of .ltoreq.2.times.10.sup.-9 molar in SCID mice is provided.

Respiratory syncytial virus (RSV) is a Parmixovirus of the Pneumovirus genus which commonly infects the upper and lower respiratory tract. It is so contagious that by age two, a large percentage of children have been infected by it. Moreover, by age four, virtually all humans have an immunity to RSV.
Typically, RSV infections are mild, remaining localized in the upper respiratory tract and causing symptoms similar to a common cold which require no extensive treatment. However, in some subjects, e.g., immunosuppressed individuals such as infants, elderly persons or patients with underlying cardiopulmonary diseases, the virus may penetrate to the lower respiratory tract requiring hospitalization and breathing support. In some of these cases, RSV infection may cause permanent lung damage or even be life threatening. In the United States alone, RSV results in about 90,000 hospitalizations each year, and results in about 4500 deaths.
RSV appears in two major strain subgroups, A and B, primarily based on serological differences associated with the attachment glycoprotein, G. The major surface glycoprotein, i.e., the 90 kD G protein, can differ up to 50% at the amino acid level between isolates Johnson et al, Proc. Natl. Acad. Sci. (1987), 84, 5625-5629. By contrast, a potential therapeutic target, the 70 kD fusion (F) protein, is highly conserved across different RSV strains, about i.e., 89% on the amino acid level Johnson et al, J. Gen. Virol.(1988), 69, 2623-2628, Johnson et al, J. Virol. (1987), 10, 3163-3166, P. L. Collins. Plenum Press. NY (1991), 103-162. Moreover, it is known that antibodies elicited against F-protein of a given type are cross-reactive with the other type.
The F-protein is a heterodimer, generated from a linear precursor, consisting of disulfide-linked fragments of 48 and 23 kD respectively Walsh et al, J. Gen. Virol, (1985), 66, 401-415. Inhibition of syncytia formation by polyclonal antibodies is associated with significant reaction to the 23 kD fragrment.
As noted, while RSV infections are usually mild, in some individuals RSV infections may be life threatening. Currently, severe RSV infection is treated by administration of the antiviral agent Ribavarin. However, while Ribavarin exhibits some efficacy in controlling RSV infection, its use is disfavored for several reasons. For example, it is highly expensive and may be administered only in hospitals. Other known RSV treatments only treat the symptoms of RSV infection and include the use of aerosolized bronchodilators in patients with bronchiolitis and corticosteroid therapy in patients with bronchiolitis and RSV pneumonia.
To date, RSV vaccines intended to boost antiviral protective antibodies have been largely unsuccessful. For example, a vaccine based on formalin-inactivated RSV that was tested approximately 25 years ago, induced antibodies that were deficient in fusion inhibiting activity Murphy et al, Clinical Microbiology (1988), 26, 1595-1597, and sometimes even exacerbated the disease. This may potentially be explained to the inability of the formalin inactivated virus to induce protective antibodies. While high antibody titers were measured in vaccine recipients, specific protective titers were lower than in the control population. This may be because formalin inactivated RSV does not display the necessary conformational epitopes required to elicit protective antibodies.
While there is no known effective RSV vaccine to date, there exists some clinical evidence that antibody therapy may confer protection against RSV infection in susceptible individuals, and may even clear an existing RSV infection. For example, it has been reported that newborn infants show a low incidence of severe bronchiolitis, which is hypothesized to be attributable to the presence of protective maternal antibodies Ogilvie et al, J. Med Virol (1981), 7, 263-271. Also, children who are immune to reinfection exhibit statistically higher anti-F-protein titers than those who are reinfected. Moreover, intravenous immune globulin (IVIG) prepared from high titer RSV-immune donors reduces nasal RSV shedding and improves oxygenation Hemming et al, Anti. Viral Azents and Chemotherapy (1987), 31, 1882-1886. Also, recent studies have suggested that the virus can be fought and lung damage prevented by administering RSV-enriched immune globulin (RSVIG Groothuis et al. The New England J. Med. (1993), 329, 1524-1530, K. McIntosh The New England J. Med. (1993), 329, 1572-1573, J. R. Groothuis. Antiviral Research, (1994), 23, 1-10, Siber et al. J. Infectious Diseases (1994), 169, 368-1373, Siber et al, J. Infectious Diseases (1992), 165:456-463.
Similarly, some animal studies suggest that antibody therapy with virus neutralizing antibodies may confer protection against RSV or even clear an existing RSV infection. For example, in vitro neutralizing mouse monoclonal antibodies have been reported to protect mice against infection and also to clear established RSV infections Tavlor et al, J.Immunology, (1984), 52, 137-142, Stott et al, "Immune Responses, Virus Infections and Disease, I.R.L. Press, London (1989), 85-104. Also, monoclonal antibodies to the F-protein of RSV have shown high efficacy in both in vitro and in vivo RSV models Tempest et al, Bio/Technology, (1991), 9, 266-271, Crowe et al, Proc. Natl. Acad. Sci. (1994), 91, 1386-1390, Walsh et al, Infection and Immunity, (1984), 43, 756-758, Barbas III, et al, Proc. Natl. Acad. Sci. (1992), 89, 10164-10168, Walsh. et al, J. Gen. Virol. (1986), 67, 505-513. Antibody concentrations as low as 520-2000 .mu.g/kg body weight have been reported to result in almost instant recovery in animal studies Crowe et al, Proc. Natl. Acad. Sci. (1994), 91, 1386-1390. Moreover, these monoclonal antibodies have been disclosed to neutralize both A and B strains, including laboratory strains and wildtype strains. These antibodies were administered either by injection Groothuis et al, The New England J. Med. (1993), 329, 1524-1530, Siber et al, J. Infectious Diseases (1994), 169, 1368-1373 or by aerosol Crowe et al, Proc. Natl. Acad. Sci. (1994), 91, 1386-1390.
Two different types of potentially therapeutic monoclonal antibodies to the RSV F-protein have been previously described in the literature, humanized murine antibodies Tempest et al, Biol. Technology, (1991) 9, 266-271, or true human antibodies (Fab fragments) Barbas III, et al, Proc. Natl. Acad. Sci. (1992), 89, 10164-10168. Humanized murine antibodies were generated by CDR grafting a cross-strain neutralizing murine anti-F-protein antibody onto a generic human Fc, as well as structural areas of the variable part. The human Fab fragments were produced by combinatorial library technology using human bone marrow cells obtained from an HIV positive donor (immunocompromised). The therapeutic in vivo titers of the humanized and human RSV antibodies were 5 and 2 mg/kg body weight, respectively. It is noted, however, that the humanized antibodies were tested in a syncytia inhibition assay, whereas the human anti-RSV Fab fragments were assayed to determine their virus neutralization activity. Therefore, the results reported with the humanized and human anti-RSV antibodies are not directly comparable.
The Fab fragment generated by the combinatorial library technology were disclosed to be efficient in aerosol. This is probably because of the relatively small size of the molecule. These results are highly encouraging because a major target population for an RSV vaccine is infants. Therefore, aerosol is a particularly desirable mode of administration.
However, notwithstanding the previous published reports of humanized and Fab fragments specific to RSV, there still exists a significant need for improved anti-RSV antibodies having improved therapeutic potential, in particular anti-RSV antibodies which possess high affinity and specificity for the RSV F-protein which effectively neutralize and prevent RSV infection.
Antibody therapy can be subdivided into two principally different activities: (i) passive immunotherapy using intact non-labeled antibodies or labeled antibodies and (ii) active immunotherapy using anti-idiotypes for re-establishment of network balance in autoimmunity.
In passive immunotherapy, naked antibodies are administered to neutralize an antigen or to direct effector functions to targeted membrane associated antigens. Neutralization would be of a lymphokine, a hormone, or an anaphylatoxin, .e., C5a. Effector finctions include complement fixation, macrophage activation and recruitment, and antibody dependent cell mediated cytotoxicity (ADCC). Naked antibodies have been used to treat leukemia Ritz et al, S.F. Blood. (1981), 58, 141-152 and antibodies to GD2 have been used in treatments of neuroblastomas Schulz et al. Cancer Res. (1984), 44:5914 and melanomas Irie et al., Proc. Natl. Acad. Sci., (1986, 83:8694. Also, intravenous immune gamma globulin (IVIG) antibodies with high anti-RSV titers recently were used in experimental trials to treat respiratory distress caused by RSV infection Hemming et al, Anti. Viral Agents and Chemotherapy, (1987), 31, 1882-1886, Groothuis et al., The New England J. Med. (1993), 329, 1524-1530, K. McIntosh, The New Enyland J. Med. (1993), 329, 1572-1573, J. R. Groothuis, Antiviral Research, (1994), 23, 1-10, Siber et al, J. Infectious Diseases (1994), 169, 1368-1373.
The therapeutic efficacy of a monoclonal antibody depends on factors including, e.g., the amount, reactivity, specificity and class of the antibody bound to the antigen. Also, the in vivo half-life of the antibody is a significant therapeutic factor.
Still another factor which may significantly affect the therapeutic potential of antibodies is their species of origin. Currently, monoclonal antibodies used or immunotherapy are almost exclusively of rodent origin Schulz et al, Cancer Res. (1984), 44:5914, Miller et al, Blood (1981), 58, 78-86, Lanzavecchia et al,J. Edp. Med. (1988), 167, 345-352, Sikora et al, Br. Med. Bull. (1984), 40:240, Tsujisaki et al, Cancer Research (1991), 51:2599, largely because the generation of rodent monoclonal antibodies uses well characterized and highly efficient technique Kohler et al, Nature, (1975), 256:495, Galfre et al, Nature, (1977), 266:550. However, while rodent monoclonal antibodies possess therapeutic efficacy, they can present restrictions and disadvantages relative to human antibodies. For example, they often induce sub-optimal stimulation of host effector functions (CDCC, ADCC, etc.). Also, murine antibodies may induce human anti-murine antibody (HAMA) responses Schroff et al, Can. Res. (1985, 45:879-885, Shawler et al, J. Immunol. (1985), 135:1530-1535. This may result in shortened antibody half-life Dillman et al, Mod. (1986), 5, 73-84, Miller et al, Blood, (1983), 62:988-995 and in some instances may cause toxic side effects such as serum sickness and anaphylaxis.
In some subjects, e.g., heavily immunosuppressed subjects (e.g., patients subjected to heavy chemical or radiation mediated cancer therapy Irie et al, Proc. Natl. Acad. Sci. (1986), 83:8694, Dillman et al, Mod. (1986), 5, 73-84, Koprowski et al, Proc. Natl. Acad. Sci. (1984), 81:216-219), use of murine monoclonal antibodies causes limited negative side effects. By contrast, in patients with normal or hyperactive immune systems, murine antibodies, at least for some disease conditions may exhibit limited efficacy.
In an effort to obviate limitations of murine monoclonal antibodies, recombinant DNA techniques have been applied to produce chimeric antibodies Morrison et al, Proc. Natl. Acad. Sci. (1984), 81:216-219, Boulianne et al, Nature, (1984), 312, 644-646, humanized antibodies by "CDR grafting" Riechmann et al, Nature (1984), 332, 323-327 and "veneered" antibodies by substitution of specific surface residues with other amino acids to alleviate or eliminate antigenicity.
However, although such antibodies have been used successfully clinically Gillis et al, J. Immunol. Meth (1989), 25:191, they have proven cumbersome to produce. This is because the understanding of the requirements for optimal antigen recognition and affinity is not yet fully understood. Also, the human framework and the mouse CDR regions often interact sterically with a negative effect on antibody activity. Moreover, such antibodies sometimes still induce strong HAMA responses in patients.
Human antibodies present major advantages over their murine counterparts; they induce optional effector functions, they do not induce HAMA response and host antigen-specific antibodies may lead to identification of epitopes of therapeutic value that may be too subtle to be recognized by a xenogeneic immune system Lennox et al, "Monoclonal Antibodies in Clinical Medicine." London: Academic Press (1982).
While human antibodies are highly desirable, their production is complicated by various factors including ethical considerations, and the fact that conventional methods for producing human antibodies are often inefficient. For example, human subjects cannot generally be adequately immunized with most antigens because of ethical and safety considerations. Consequently, reports of isolation of human monoclonal antibodies with useful affinities, >10.sup.8 molar to specific antigens are few McCabe et al, Cancer Research, (1988), 48, 4348-4353. Also, isolation of anti-viral human monoclonal antibodies from donor primed cells has proved to be unwieldy. For example, Gorny reported that only 7 of 14,329 EBV transformed cultures of peripheral blood mononuclear cells (PMBC's) from HIV positive donors resulted in stable, specific anti-HIV antibody producing cell lines Gorny et al, Proc. Natl. Acad. Sci. (1989), 86:1624-1628.
To date, most human anti-tumor antibodies have been generated from peripheral blood lymphocytes (PBLs) Irie et al, Br. J. Cancer, (1981), 44:262 or tumor draining lymph node lymphocytes Schlom et al, Proc. Natl. Acad. Sci. (1980), 77:6841-6845, Cote et al, Proc. Natl. Acad. Sci. (1983), 80:2026-2030 from cancer patients. However, such antibodies often react with intracellular, and thus therapeutically useless antigens Ho et al, In Hybridoma Technology, Amsterdam (1988), 37-57 or are of the IgM class McCabe et al, Cancer Research (1988), 48, 4348-4353, a class of antibodies with lesser ability to penetrate solid tumors than IgGs. Few of these human antibodies have moved to clinical trials Drobyski et al, R.C. Transplantation (1991), 51, 1190-1196, suggesting that the rescued antibodies may possess sub-optimal qualities. Moreover, since these approaches exploit the testing donor primed B cells, it is clear that these cells are not an optimal source for rescue of useful monoclonal antibodies.
Recently, generation of human antibodies from primed donors has been improved by stimulation with CD40 resulting in expansion of human B cells Banchereau et al, F. Science (1991), 251:70, Zhana et al, J. Immunol. (1990), 144, 2955-2960, Tohma et al, J. Immunol. (1991), 146:2544-2552 or by an extra in vitro booster step primer to immortalization Chaudhuri et al, Cancer Supplement (1994), 73, 1098-1104. This principle has been exploited to generate human monoclonal antibodies to Cytomegalovirus, Epstein-Barr Virus (EBV) and Hemophilus influenza with cells from primed donors Steenbakkers et al., Hum. Antibod. Hybridomas (1993), 4:166-173, Ferraro et al., Human Antibod. Hybridomas (1993), 4:80-85, Kwekkeboom et al., Immunological Methods (1993), 160:117-127, with a significantly higher yield than obtained with other methods Gorny et al., Proc. Natl. Acad. Sci. (1989), 86:1624-1628.
Moreover, to address the limitations of donor priming, immunization and cultivation ex vivo of lymphocytes from healthy donors has been reported. Some success in generating human monoclonal antibodies using ex homine boosting of PBL cells from primed donors has been reported Maeda et al, Hybridoma (1986), 5:33-41, Kozbor et al, J. Immunol. (1984), 14:23, Duchosal et al, Nature (1992, 355:258-262. The feasibility of immunizing in vitro was first demonstrated in 1967 by Mishell and Dutton Mishell et al, J. Exp. Med (1967), 126:423-442 using murine lymphocytes. In 1973, Hoffman successfully immunized human lymphocytes Hoffman et al, Nature (1973), 243:408-410. Also, successful primary immunizations have been reported with lymphocytes from peripheral blood Luzzati et al, J. Exp. Med. (1975) 144:573:585, Misiti et al, J. Exp. Med. (1981), 154:1069-1084, Komatsu et al, Int. Archs. Allergy Appl. Immunol. (1986), 80:431-434, Ohlin et al, C.A.K. Immunology (1989), 68:325 (1989) tonsils Strike et al, J. Immunol. (1978), 132:1789-1803 and spleens, the latter obtained from trauma Ho et al, In Hybridoma Technology, Amsterdam (1988), 37-57, Boerner et al, J. Immunol. (1991), 147:86-95, Ho et al, J. Immunol. (1985), 135:3831-3838, Wasserman et al, J. Immunol. Meth. (1986), 93:275-283, Wasserman et al, J. Immunol. Meth. (1986), 93:275-283, Brams et al, Hum. Antibod. Hybridomas (1993), 4, 47-56, Brams et al, Hum. Antibod. Hybridomas (1993), 4, 57-65 and idiopathic thrombocytopenia purpura (ITP) patients Boerner et al, J. Immunol. (1991), 147:86-95, Brams et al, Hum. Antibod. Hybridomas (1993) 4, 47-56, Brams et al, Hum. Antibod. Hybridomas (1993), 4, 57-65, McRoberts et al, "In Vitro Immunization in Hybridoma Technology". Elsevier, Amsterdam (1988), 267-275, Lu et al, P. Hybridoma (1993), 12, 381-389.
In vitro immunization offers considerable advantages, e.g., easily reproducible immunizations, lends itself easily to manipulation of antibody class by means of appropriate cultivation and manipulation techniques Chaudhuri et al, Cancer Supplement (1994), 73, 1098-1104. Also, there is evidence that the in vivo tolerance to self-antigens is not prevalent during IVI Boerner et al, J. Immunol. (199), 147:86-95, Brams et al, J. Immunol. Methods (1987), 98:11. Therefore, this technique is potentially applicable for production of antibodies to self-anigens, e.g., tumor markers and receptors involved in autoimmunity.
Several groups have reported the generation of responses to a variety of antigens challenged only in vitro, e.g., tumor associated antigens (TAAs) Boerner et al, J. Immunol. (1991), 147:86-95, Borrebaeck et al, Proc. Natl. Acad. Sci. (1988), 85:3995. However, unfortunately, the resulting antibodies were typically of the IgM and not the IgG subclass McCabe et al, Cancer Research (1988), 48, 4348-4353, Koda et al, Hum. Antibod. Hybridomas, (1990), 1:15 and secondary (IgG) responses have only been reported with protocols using lymphocytes from immunized donors. Therefore, it would appear that these protocols only succeed in inducing a primary immune response but require donor immunized cells for generation of recall responses.
Also, research has been conducted to systematically analyze cultivation and immunization variables to develop a general protocol for effectively inducing human monoclonal antibodies in vitro Boerner, J. Inmunol. (1991) 147:86-95, Brams et al, Hum. Antibod. Hybridomas (1993), 4, 47-56, Lu et al, Hybridoma (1993), 12, 381-389. This has resulted in the isolation of human monoclonal antibodies specific for ferritin Boerner et al, J. Immunol. (1991), 147:86-95, induced by IVI of naive human spleen cells. Also, this research has resulted in a protocol by which de novo secondary (IgG) responses may be induced entirely in vitro Brams et al, Hum. Antibod. Hybridomas (1993), 4, 57-65.
However, despite the great potential advantages of IVI, the efficiency of such methods are severely restricted because of the fact that immune cells grow in monolayers in culture vessels. By contrast, in vivo germinal centers possessing a three-dimensional structure are found in the spleen during the active phases of an immune response. These three-diimensional structures comprise activated T- and B-cells surrounded by antigen-presenting cells which are believed by the majority of immunologists to compare the site of antigen-specific activation of B-cells.
An alternative to the natural splenic environment is to "recreate" or mimic splenic conditions in an immunocompromised animal host, such as the "Severe Combined Immune Deficient" (SCID) mouse. Human lymphocytes are readily adopted by the SCID mouse (hu-SCID) and produce high levels of immunoglobulins Mosier et al, Nature (1988), 335:256, McCune et al, L. Science (1988), 241, 1632-1639. Moreover, if the donor used for reconstitution has been exposed to a particular antigen, a strong secondary response to the same antigen can be elicited in such mice. For example, Duchosal et al, Duchosal et al. Nature (1992), 355:258-262 reported that human peripheral blood B-cells from a donor vaccinated with tetanus toxoid 17 years prior could be restimulated in the SCID environment to produce high serum levels, i.e., around 10.sup.4. They further disclosed cloning and expression of the genes of two human anti-TT antibodies using the lambda and the M13 phage combinatorial library approach Huse et al, R.A. Science (1989), 246:1275 from the extrated human cells. The reported antigen affinities of the antibodies were in the 10.sup.8 -10.sup.9 /M range. However, this protocol required donor primed cells and the yield was very low, only 2 clones were obtained from a library of 370,000 clones.
Therefore, previously the hu-SPL-SCID mouse has only been utilized for producing human monoclonal antibodies to antigens wherein the donor has either been efficiently primed naturally or by vaccination Stahli et al, Methods in Enzymology (1983), 92, 26-36, which in most cases involves exposure to viral or bacterial antigens. Also, the reported serum titer levels using the hu-SCID animal model are significantly lower than what is typically achieved by immunization of normal mice.
Additionally, two protocols have been described by which induction of primary antibody responses can be followed by induction of secondary antibody responses in hu-SCID mice using naive human lymphocytes. However, use of both of these protocols are substantially restricted. In the first protocol, primary responses are induced in hu-SCID mice into which human fetal liver, thymus and lymph nodes have been surgically implanted. However, this method is severely restricted by the limited availability of fetal tissue, as well as the complicated surgical methodology of the protocol McCune et al, L. Science (1988), 241, 1632-1639. In the second protocol, lethally irradiated normal mice were reconstituted with T- and B-cell depicted human bone marrow and SCID mouse bone marrow cells Lubin et al, Science, (1991), 252:427. However, this method is disadvantageous because it requires a four month incubation period. Moreover, both protocols result in very low antibody titers, i.e., below 10.sup.4.
Also, Carlson et al. Carlson et al, J. Immunol. (1992), 148:1065-1071 described in 1992 an approach using PBMCs from an antigen (tetanus toxoid) primed donor. The cells were first depleted of macrophages and NK cells before being subjected to a brief in vitro cultivation and priming period prior to transfer into a SCID mouse. The hu-SPL-SCID mouse was then boosted with antigen. This method was reported to result in average TT specific human IgG titers of .apprxeq.10.sup.4 in the hu-SPL-SCID serum, with up to 5.times.10.sup.5 reported.
Production of human monoclonal antibodies further typically requires the production of immortalized B-cells, in order to obtain cells which secrete a constant, ideally permanent supply of the desired human monoclonal antibodies. Immortalization of B-cells is generally effected by one of four approaches: (i) transformation with EBV, (ii) mouse-human heterofusion, (iii) EBV transformation followed by heterofusion, and (iv) combinatorial immunoglobulin gene library techniques.
EBV transformation has been used successfully in a number of reports, mainly for the generation of anti-HIV antibodies Gorny. et al, Proc. Natl. Acad. Sci. (1989), 86:1624-1628, Posner, et al, J. Immunol. (1991), 146:4325-32. The main advantage is that approximately one of every 200 B-cells becomes transformed. However, EBV transformed cells are typically unstable, produce low amounts of mainly IgM antibody, clone poorly and cease making antibody after several months of culturing. Heterofusion Carrol, et al, J. Immunol. Meth. (1986), 89:61-72 is typically favored for producing hybridomas which secrete high levels of IgG antibody. Hybridomas are also easy to clone by limiting dilution. However, a disadvantage is the poor yield, i.e., .ltoreq.1 hybridomas per 20,000 lymphocytes Boerner. et al, J. Immunol. (1991), 147:86-95, Ohlin, et al, C.A.K. Immunology (1989), 68:325, Xiu-mei et . al, Hum. Antibod. Hybridomas (1990), 1:42, Borrebaeck C.A.K. Abstract at the "Second International Conference" on "Human Antibodies and Hybridomas." Apr. 26-28, 1992, Cambridge, England. Combining EBV transformation followed by heterofusion offers two advantages: (i) human B-cells fuse more readily to the fusion partner after EBV transformation, and (ii) result in more stable, higher producing hybridomas Ohlin, et al, Immunology (1989), 68:325, Xiu-mei. et al, Hum. Antibod. Hybridomas (1990), 1:42, Borrebaeck C.A.K. Absract at the "Second International Conference" on "Human Antibodies and Hybridomas." Apr. 26-28, 1992, Cambridge, England. The advantage of the final technique, i.e., combinatorial immunoglobulin gene library technique is the fact that very large libraries can be screened by means of M13 Fab expression technology Huse. et al, Science (1989), 246:1275, William Huse, Antibody Engineering: A Practical Guide. Borrebaeck C.A.K., ed. 5:103-120 and that the genes can easily be transferred to a production cell line. However, the yield is typically extremely low, on the order of 1 per 370,000 clones Duchosal. et al, Nature (1992), 355:258-262.
Thus, based on the foregoing, it is apparent that more efficient methods for producing human monoclonal antibodies, in particular antibodies specific to RSV, would be highly advantageous. Moreover, it is also apparent that human antibodies specific to the RSV F-protein having superior binding affinity, specificity and effector functions than those currently available would also be highly desirable.

Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof


A closing unit for a shaping machine includes mutually moveable mold mounting plates suitable for carrying mold tool portions, a first hydraulic cylinder adapted to apply a closing force to the mold mounting plates, a second hydraulic cylinder, and a pressure storage device connected to the first hydraulic cylinder and adapted to store a pressure prevailing in the first hydraulic cylinder upon pressure relief at a storage device pressure. A hydraulic interconnection of the pressure storage device with the second hydraulic cylinder allows the storage pressure stored in the pressure storage device to be used for locking and/or unlocking the locking device.

The present invention concerns a closing unit for a shaping machine.
Shaping machines can be understood to be injection molding machines, injection presses, presses and the like. Hereinafter, the state of the art is outlined by reference to the example of injection molding machines. Similar problems and corresponding details however also apply in regard to other shaping machines.
Hydraulic closing units of the general kind set forth have at least one first hydraulic cylinder which serves to apply a closing force to mutually moveable mold mounting plates. As a result, tool portions which are to be mounted to the mold mounting plates are pressed against each other. After the closing force has been built up, a shaping process is carried out. For example, a plasticized plastic can be injected into the mold which is subjected to the action of the closing force (injection molding process). Alternatively, for example, a reactive mixture can be introduced into the mold and cured therein.
There are various kinds of structure for common closing units, including for example two-plate closing units having four bars or a central push rod. Three-plate machines with four bars are, however, also known.
As the first hydraulic cylinder in many cases has to generate a considerable force (power stroke), in many cases there is a separate fast stroke in order to be able to move the mold mounting plates relative to each other at a higher speed. That makes it necessary at the same time for the first hydraulic cylinder and/or one of the mold mounting plates to be locked relative to at least one pull or push rod so that, after the fast stroke movement has been performed, the closing force can be built up. At least one locking device can be actuated by at least one second hydraulic cylinder which, for example, moves halves of a split nut relative to each other. In a closed position, an internal profile of the split nut then engages into an external profile on the pull or push rod.
The closing force can be reduced after the shaping process has been carried out so that the closing unit can be opened and the molding can subsequently be removed.
It is known from DE 10 2012 104 251 to load a hydraulic storage device upon pressure relief to reduce the closing force. The energy stored in that way is used in the next shaping cycle for again building up the closing force. By virtue of the high pressures which have to be achieved when applying the closing force in the first hydraulic cylinder, and by virtue of the pressure loss which inevitably occurs upon storage of the energy in the hydraulic storage device, the amount of energy which is actually re-used is however relatively slight in comparison with that which is used for applying the closing force.
DE 10 2007 011 442 A1 discloses a closing unit with a hydraulic power stroke and electrically driven fast stroke. In that case, it is proposed that the energy which is recovered from an electrically driven fast stroke movement is stored hydraulically and used for applying the closing force or for further fast stroke movements. In that respect, there is naturally the disadvantage that the energy involved in applying the closing force is not re-used at all, and further use of the energy from the fast stroke for applying the closing force is quite inefficient.


In one embodiment, a fluid ejection device is configured to receive a signal and ejecting fluid in response thereto, including an ink ejecting nozzle layer having a substrate with first and second surfaces joined along an edge, an insulating feature located on the first surface adjacent the edge and a flexible lead that bends around the edge and lies flush against the insulating feature.

Fluid ejection devices, such as those based on piezo-electric or thermal technologies, typically have a firing element which activates in response to a firing signal to emit a small droplet of fluid from a firing chamber through a nozzle. The firing elements, firing chambers and nozzles may be constructed as a die using various photo-etching ("photolithography") techniques, such as those used to construct integrated circuits.
The firing signals are typically received from a controller which is electrically coupled to the firing elements by electrical conductors, often including flexible leads which are coupled to the die. Earlier systems of routing and protecting these leads over a side edge of the die resulted in the flexible leads projecting well above the exit surface of the nozzles, disadvantageously increasing the distance from the nozzle to the target surface which received the fluid droplets.
This increased nozzle-to-target distance decreases the trajectory accuracy, so the droplets are less likely to land where intended. If the fluid ejection device is used for depositing drops of ink onto a medium to print an image, the quality of the resulting printed image can be degraded as the trajectory accuracy is decreased. For these and other reasons, there is a need for the present invention.

Fluid ejection device with insulating feature

Hewlett-Packard Development Company, L.P.