Stromal Derived Factor-1 (SDF-1) is a small, naturally occurring, potent chemokine with inherent angiogenic, neurogenic, anti-apoptotic protein, which is also a potent stem cell chemoattractant, cardiovascular disease, and other metabolic disturbances. The present invention provides methods for treating erectile dysfunction in a male subject comprising administering to the major pelvic ganglion supplying the cavernous nerves subject compositions comprising SDF-1. SDF-1 promotes stem cell activation, to the major pelvic ganglion supplying the cavernous nerves, helps cell preservation, and prevents adverse penile remodeling. It can be administered as a protein or by gene therapy including but not limited to plasmid DNA, viral transduction, or nanoparticle delivery directly to the penis or to the neurovascular bundle or other pelvic nerve structures during the time of surgery, or before injury, or to treat existing erectile dysfunction.

Stromal derived factor 1 (SDF-1) is a small (110 KD), highly conserved chemokine. Discovered in the early 1990's as being important for bone marrow homing and B-cell proliferation. It is also known as chemokine (C—X—C motif) ligand 12″, SDF1, SDF1A, 1B, PBSF, SCYB12, SDF-1a, SDF-1b, TLSF-a, TLSF-b, and TPAR1. A stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C—X—C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. Plerixafor (AMD-3100), used to mobilize hematopoietic stem cells for isolation prior to bone marrow transplantation is an antagonistic inhibitor of CXCR4. SDF-1 is unregulated in many tissues (i.e. heart, brain, muscle) following injury, especially ischemic injury.
Erectile dysfunction is a male sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual intercourse. There are two major causes for erectile dysfunction: psychogenic and organic causes. The psychogenic cause is attributed to the activation of sympathetic nervous system and inhibition of non-adrenergic-non-cholinergic nerve system by psychological or mental effect, which elicits an increase in the smooth muscle tension of corpus cavernosum (erectile tissue of the penis) and resultant erectile dysfunction. The organic erectile dysfunctions are divided into neurogenic, vasculogenic, and endocrine erectile dysfunctions according to the cause.
The vasculogenic erectile dysfunction is known to cause insufficient secretion of relaxation neurotransmitters (e.g., nitric oxide (NO)) from cavernous endothelial cells due to endothelial dysfunction that are caused by hyperlipidemia, diabetes mellitus, high blood pressure, smoking, metabolic syndrome, other vascular risk factors, etc.
Recent researches associated with erectile dysfunction have intensely focused on the organic erectile dysfunction. Phosphodiesterase-5 (PDE-5) inhibitors for oral administration including Viagra (Sildenafil's trade name) are widely utilized as first-line therapy for erectile dysfunction. Oral PDE-5 inhibitors are well known to be effective for the treatment of erectile dysfunction by potentiating the physiologic erectile response to NO and by amplifying the NO-cyclic GMP pathway through competitive inhibition of cyclic GMP degradation.
However, more than 30% of total patients with erectile dysfunction, including diabetic patients, those with spinal cord injuries and those who underwent radical prostatectomy for the treatment for prostatic cancer, etc., do not respond to oral PDE-5 inhibitors.
Prostate surgery results in a temporary neuropraxia resulting in near complete temporary loss of erectile function resulting in decreased penile tissue perfusion. More seriously injured nerves undergo Wallerian degeneration resulting in loss in penile tissue innervation. Morphological tissue changes include smooth muscle apoptosis, decreased density of microvasculature, increased collagen/scar remodeling and replacement of erectile tissues seen both in humans and in animals (using the cavernous nerve crush model). Furthermore, these injuries result in Aberrant molecular signaling including increased RhoA/ROCK activation, decreased nNOS, increased free radical production, decreased growth factor expression.
Moreover, adverse events associated with PDE-5 inhibitor treatment such as headache, facial flushing, indigestion, back pain/myalgia, visual disturbance are not infrequent. In addition, these treatments have also some restrictions in their application. PDE-5 inhibitors are absolutely contraindicated for patients using nitrates and are either not recommended or to be used with caution in men with severe cardiovascular disease such as unstable angina, cardiac failure, recent myocardial infarct, poorly controlled blood pressure, in men who takes ketokonazole, itraconazole, ritonavir, alpha-adrenergic blocker, and in patients with severe hepatic insufficiency or renal insufficiency, etc. Furthermore, PDE5 inhibitors are used as on demand medicines but not effective to cure underlying disease at all, which limits the spontaneity of the sexual activity and causes higher drop out rate of the treatment.

Stromal derived factor 1 and its use in the prevention and treatment of erectile dysfunction


Certain fatty acid amides can be included in plastic skin clad polyurethane formulations to increase adhesion between the plastic skin and the polyurethane. These adhesion improvers can decrease or prevent blister formation in plastic skin clad polyurethanes. Additionally, the adhesion improvers can compatibilize certain extenders with base polyols and improve mold release properties.

The present invention relates to thermoplastic or thermoset skin cladded polyurethanes having an improved surface appearance. The present invention particularly relates to thermoplastic skin cladded polyurethane foams having an improved surface appearance.
Polyurethane based polymers have long been known to be useful in preparing many products. For example, rigid polyurethane foam can be used in products such as pipe insulation, flotation devices and appliance insulation. Flexible polyurethane foam can be use in automotive seat cushions, toys and furniture manufacture. Semi-rigid polyurethane foam can be used to prepare products such as automotive headrests, dashboards and armrests. Reinforced rigid polyurethane foams are increasingly being used to prepare lightweight automotive door panels, seat backs and the like.
Polyurethane surfaces are sometimes neither suitable nor desirable for certain applications. For example, a polyurethane foam surface may not be durable enough or not aesthetically appropriate for an automotive interior application. One means of avoiding this problem while retaining the benefits of using a polyurethane in such applications is by using a plastic skin cladded polyurethane. For example, UK Patent Application 2 148 786 A discloses preparing a bathtub having a preformed acrylic shell and a polyurethane foam reinforcing layer. U.S. Pat. No. 4,784,904 to Wood, et al., discloses preparing an object such as a sink have an acrylic shell and a polyurethane foam reinforcing layer.
Similarly, flexible foams and semi-flexible foams can be prepared with plastic skins. However, preparing cladded polymers, particularly cladded foamed polymers is not always trouble free. One such problem occurs when adhesion between the polymer and the plastic skin fails. Gas can accumulate in the space between the skin and foam and form a raised area on the skin surface commonly called a "blister". Such blisters are serious aesthetic defects and can cause a part to be rejected which increases waste and lost production time. It would therefore be desirable in the art to prepare cladded polyurethane polymers which do not display this blistering phenomena.

Plastic skin cladded polyurethanes having improved surface appearance


A portable showering cabinet for use by non-ambulatory, aged, or other persons unable to use conventional showering and hygienic home care facilities, particularly useful for a private home, hospitality industry, residential schools, general and specialized hospitals, rehabilitation centers, and bedside care in a nursing home. The showering cabinet system provides daily hygienic care for disabled, with or without minimal assistance from a caregiver, eliminating the need for a caregiver to help a disabled person enter a shower stall and eliminating the need for a caregiver to perform the showering of the individual. The portable cabinet includes a water supply system that attaches to existing hot and cold water supply cabinets and a manually movable cabinet that has casters, allowing it to be moved easily and quickly along a floor surface to a bedside, and an improved access auxiliary seat to insure safe entrance by the patient into and out of the enclosure from a seated position on the outside of the cabinet. In one embodiment, a door for user ingress and egress of the cabinet includes a wrap around member that securely and conveniently encloses the cabinet when the door is closed.

1. Field of the Invention
This invention relates generally to a hygienic care system primarily for the non-ambulatory and disabled in the private sector (at home), while a guest at a hotel or residential student, to provide showering and shampooing. Specifically, the invention provides for a portable showering cabinet, adapted for private, personal care, with or without the services of an attendant, and which does not require permanent installation, but uses existing conventional water and draining hardware accessible in the home or other facility, and one which is designed so that the wheelchair user or non-ambulatory patient can safely enter and exit through a side entrance door directly from the wheelchair. The user may also have access from a front door.
2. Description of the Related Art
Bathing cabinets for treating patients in a hospital or other institution are known in the prior art. U.S. Pat. No. 3,562,821 issued Feb. 16, 1971 to Carl J. Queen describes a permanently mounted bathing cabinet that includes interior shower plumbing and a patient access front water shielding door to receive a patient.
Currently there is emphasis on caring for patients in the private home, as opposed to institutional care. Early discharges from the hospital that returns a patient home while requiring the services of a caregiver, the growing population of the aged, the majority of which remain in the home, are contributors to the vital need and demand for a method of providing daily hygienic care with a system designed for the disabled and non ambulatory, while reducing or eliminating potential injury to the patient and the attendant caregiver.
Using the present invention, portable, personalized showering can be obtained for the disabled, the convalescent, the aged, and others who cannot utilize conventional bathtubs and showers. The showering cabinet provides for total body showering, shampooing, perineal cleansing, and may be used for sitz bath treatments. The showering cabinet is completely mobile and does not require costly or elaborate custom plumbing or electrical installation. The showering cabinet also provides for maximum safety in an environment that can be hazardous because of the exposure to slipping and falling by both patient and caregiver into and out of a shower stall or bathtub. With the present invention, a patient can be transferred with safety and comfort, due to the horizontal, side-mounted transfer platform (auxiliary seat) provided and the ability of the shower seat in the housing to align with the auxiliary platform and the wheelchair, which remains in position.
The showering system, being portable, has casters that can be locked into place. The system can be used in numerous environments that include the private home, rehabilitation centers, general and specialized hospitals, adult day care centers, and the acute and critical care units of nursing homes. The 1990 ADA (Americans with Disabilities Act), Title III, states that all public accommodations must provide accessible service and equipment for the disabled. Therefore, hotels and residential schools must offer usable showering facilities for the disabled. The showering system is extremely economical because it is portable, does not require costly renovations for use, and is connected to water and draining hardware already within the home or facility. Should the condition of the patient require assistance in obtaining care, the caregiver stands at the side, always within immediate access to the patient. The patient is always at chair height. The system does not require the use of mechanical lifting and lowering devices. The water entering the cabinet is through a control valve which maintains a selected temperature and shuts down in the event of a variation in the selected temperature.


It is an object to provide a thermal-transfer recording medium and its thermal-transfer recording method whereby it is possible to perform good thermal transfer to a durable transfer medium such as plastic film etc., and the transferred image is excellent in resistance to mechanical abrasion, and whereby color reproducibility is excellent when plural colors of thermal transferred inks are printed in layers. A thermal-transfer ink layer is provided which at least presents the visco-elastic characteristics that tan.delta. is of 1 or more and the complex dynamic viscosity falls within 100 to 40,000 Pa.s in the viscoelasticity measurement with a frequency of 1 Hz in the linear viscoelastic region of temperature from 100 to 150.degree. C. Alternatively, a thermal-transfer ink layer containing a coloring matter and a thermo-fusing resin is provided on a support, and the thermo-fusing resin presents the visco-elastic characteristics that tan.delta. is of 1.7 or more and the complex dynamic viscosity falls within 10 to 20,000 Pa.s in the viscoelasticity measurement with a frequency of 1 Hz in the linear viscoelastic region of temperature from 100 to 150.degree. C.

Thermal-transfer recording methods using thermal heads have become widely used for a variety of utilities such as label printers, ticket venders, word processors etc. As the use has spread, the usage environment of the prints has become more severe than the environment under which they were conventionally used.
Further, as the usage environment of the prints has become more severe, types of transfer media used have diversified from paper as conventionally used to plastic films etc. which have less dependence on the environment. When the transfer material is atypical, conventional ribbons having a thermal-transfer ink composition mainly composed of waxes cannot provide satisfactory transfer of ink or the print tends to easily rub off due to a slight abrasion even after successful transfer, so that the print cannot provide satisfactory mechanical resistance to abrasion.
In particular, in the field of printed matter needing high-quality, posters, billboards etc., there are strict constraints on the reproducibility of colors and color unevenness of the transfer material, and no conventional thermal transfer ribbons can satisfy these requirements.
Further, concerning the conventional thermal transfer ribbons, in the case where color representation is made by repeated transfer operations of thermal-transfer ink layers onto the same transfer medium and when two or more repeated printings are made, the composition of the previously printed transfer ink layer will melt from heat from the thermal head when it makes a repeated printing operation because the viscosity of the conventional thermal transfer ink at the softening point or at the melting point is low. This melting causes color unevenness due to ink mixing and ink repellence, and deficiency in transfer itself in the worst case.
The countermeasures against these problems needed delicate mechanical and electrical controls as being effected by impregnating all the inks which are transferred multiple times into paper as transfer medium so as to produce a mixed state of inks for representation of colors, or by lowering the transfer energy on the printer side depending on the number of repetitions of transfer, i.e., the first, the second and the third, so as to maintain the transferability in a good state.
There has been another attempt in which in accordance with the number of repetitions of transfer and the order of transfer, the softening temperatures of the ink layers to be transferred are differentiated so as to attain both good transfer performance and reproducibility of colors.
These countermeasures are effective in the case where the transfer media is composed of a material such as paper and the like, but cannot exhibit satisfactory effects for materials being less absorptive such as a plastic base etc., during transfer of thermal transfer ink.
As stated above, the environment under which the thermally transferred prints produced by using thermal heads has become more severe than the environment under which the prints were conventionally used. Examples include use under severe room temperatures and use under an environment in which the prints are mechanically abraded.
Because of this tendency, special types of transfer media which are more hard-wearing have been used as already stated. This tendency requires good transfer to the plastic film etc., acquisition of printed matters having the required durability, and solving the problems of ink unevenness due to mixing of inks, repellence of ink, and weak fixing performance due to superimposition of inks when representation of colors is made by repeated transfer of thermal-transfer ink layers onto the same transfer medium.
Therefore, there is an important demand for a thermal-transfer recording medium meeting all the requirements such as being able to perform good transfer to transfer media having durability, such as plastic film, to provide prints having sufficient resistance to mechanical abrasion without causing color unevenness due to ink mixing or ink repellence when representation of colors is made by repeated transfer of thermal-transfer ink layers onto the same transfer medium, and to provide sufficient resistance to abrasion even when inks are layered. The important key to meeting this demand, was considered to reside in the constituents of the thermal-transfer recording medium, that is, the composition of the thermal-transfer ink layers in a so-called ink ribbon. Although the composition of transfer ink constituents has been studied conventionally, no proposal has been made yet which meets the level of the requirements of the invention. The object of the invention is to provide the method to solve this problem.

Thermal-transfer recording medium and thermal transfer recording method


A method for managing read and write data congestion in a system for executing write and read data commands and having a buffer pool of blocks for temporarily storing read and write data is disclosed. Management of the buffer pool and the initiation of read and write commands ensures that free blocks are available to temporarily store read data arriving at a host bus adapter (HBA). If the currently available blocks would be substantially consumed by the total outstanding inbound read data requested, no more write data commands will be initiated. As inbound read data is received into the buffer pool and subsequently transferred out of the buffer pool to the initiator device, the blocks in the buffer pool are freed up. When the read data transfer is completed and sufficient buffer resources have been freed up, read and write data commands may resume.

1. Field of the Invention
The present invention relates, generally, to the management of memory required to facilitate the execution of read/write commands in host bus adapter (HBA) cards and, in one embodiment, to an apparatus and method for managing read/write command data congestion at the application layer to improve performance and reduce the occurrence of resource exhaustion that results in lost packet data at the transport layer.
2. Description of Related Art
HBAs are input/output (I/O) adapters that connect a host computer's bus and an outside network such as the Internet or a Fibre Channel loop. HBAs manage the transfer of information between the bus and the outside network. HBAs are typically implemented in circuit cards that can be plugged into the backplane of the host computer. For example, as illustrated in FIG. 1, a HBA 100 can be inserted into a connector 102 which interfaces to the Peripheral Component Interconnect (PCI) bus 104 of a host computer 106 to enable devices connected to the PCI bus 104 to communicate with devices in a storage area network (SAN) 108 using, for example, fibre channel or Internet Small Computer System Interface (iSCSI) protocols.
Within the host computer 106 is a SCSI driver 110 which, upon initialization, enumerates all SCSI devices attached to the PCI bus 104. If the HBA 100 is an iSCSI HBA, then the HBA 100 will appear to be a SCSI device in the list of one or more SCSI devices enumerated by the SCSI driver 110. The HBA contains components such as a microprocessor 114, memory 116, and firmware 118. Also within the host computer 106 is an iSCSI driver 112 that locates SCSI devices in the SAN 108. The located SCSI devices are presented to the PCI bus 104 through the HBA 100 as if they were locally attached to the PCI bus 104.
Once initialization and identification of the SCSI devices is complete, iSCSI commands, formatted into protocol data units (PDUs), may be communicated between devices connected to the PCI bus 104 and SCSI devices in the SAN 108. iSCSI commands, as defined herein, are Transmission Control Protocol/Internet Protocol (TCP/IP) packets traveling in both directions containing SCSI data and commands encapsulated in a TCP/IP frame, but may also include iSCSI logging sequences (control) and asynchronous control messages between an initiator device and a target device. Examples of iSCSI commands that would be included in a packet are a request to enumerate the devices that a particular target is controlling, a request to abort a command in progress, or a logoff request.
As noted above, in order to facilitate the communication of iSCSI protocols over the SAN 108, the iSCSI commands must be encapsulated into TCP/IP packets. For example, when an iSCSI command tagged with a particular target SCSI device is presented to the HBA 100, the iSCSI command is first encoded into TCP/IP packets, which are then sent to the target device. The target will extract the SCSI information out of the TCP/IP packets and reconstruct the PDUs. The target SCSI device may also send a response back to the HBA 100 which will be encapsulated into TCP/IP packets. The HBA 100 will extract the SCSI information out of the TCP/IP packets and send it back to the initiator device on the local PCI bus 104.
FIG. 2 illustrates a protocol stack 202 in HBA 200 according to the Open Systems Interconnection (OSI) model for networking. Firmware in the HBA may control the functions of the protocol stack. There are a total of seven layers in the OSI model. The bottom physical layer or Media Access Control (MAC) layer 204 communicates with a similar protocol stack 206 in a device 208 in a SAN. Above the MAC 204 is the link layer 210. The top layer is the application layer 212, which uses an interface to the stack called a socket, and thus it can be considered a socket layer. Data or commands can be sent or received through the application layer 212. For example, a write command and its associated data can be sent using a socket call, which (conceptually) filters down through the stack 202, over a wire or other link 216 to a similar stack 206 in a target device 208. The target device 208 can also send a response socket call back to the initiator which travels across the wire 216 and back up through the stack 202 to the application layer 212, which communicates with the PCI bus.
If an iSCSI write command is to be communicated to a target device, a SCSI driver first formats the write command. As illustrated in FIG. 3, within the formatted write command is a scatter gather list 300, which is comprised of a list of scatter gather elements 302, each of which includes an address field for identifying the location of data to be written, a length field indicating the amount of data at that location, and an optional pointer to another scatter gather element. The scatter gather list 300 enables write data for a particular write command to be stored in separate locations.
Referring now to FIG. 4, when a write command is processed, the write data from the initiator device is retrieved using the address fields in the scatter gather list and stored into one or more buffers or blocks within a limited-size buffer pool 412, which is part of the memory of the HBA. The limited-size buffer pool may be a fixed-size buffer pool, or it may be of a configurable size but nevertheless not easily expandable as memory needs dictate. The buffer pool 412 is comprised of a number of buffers or blocks (e.g. 4 kB) that are typically of fixed size. The buffer pool 412 is managed by the stack (see FIG. 2), and is accessible from the stack.
When write data is stored in blocks in the buffer pool 412, pointers to those blocks called local descriptors 404 are stored in sequence in a transmit (Tx) list 400. Each local descriptor points to only one block, and a link in the descriptor identifies how much of that block is filled with valid data. At the end of the Tx list is a "stop" marker, which indicates the end of the Tx list. Thus, the number of local descriptors and the links in the Tx list are an indication of how much of the buffer pool is occupied by write data.
When the write command is ready to be transmitted to the target, the local descriptors 404 in the Tx list 400 are asynchronously processed in sequence. As each local descriptor 404 is processed, the data stored in the block identified by the local descriptor 404 is formatted into TCP/IP packets. The target address information must also be placed into the TCP/IP wrapper so that the target device will recognize itself as the intended target. The formatted write data is then sent into the protocol stack and out over the network, and the local descriptor that pointed to the block of write data is removed from the Tx list 400. When the last descriptor is reached, this process is stopped. When the write operation is complete, the target device will send an acknowledgement response back to the initiator device, indicating that the write command has been completed.
If an iSCSI read command is to be communicated to a target device, an SCSI driver first formats the read command. The read command includes a scatter gather list, whose address fields identify locations in the initiator device at which the read data will be stored. When a read command is received at the HBA, the read command is encapsulated into TCP/IP packets, which then conceptually filter down through the stack and are transmitted across a wire to the target. The target then locates the data, encapsulates it, and send it back to the HBA.
When read data is received from the target, the HBA uses the Rx list 402 to determine where to store the read data. The Rx list 402 contains local descriptors 406 that normally point to free blocks in the buffer pool 412. As the read data is received into the HBA, the read data is stored into free blocks in the buffer pool 412 identified by the local descriptors 406 in the Rx list 402, and the status of the local descriptors is changed to indicate that the local descriptors are now pointing to filled blocks.
In some implementations, once all the read data has been stored in the buffer pool 412, the read data can be transferred to memory using direct memory addressing (DMA) in accordance with the address locations in the read command scatter gather list. As read data is transferred out of the buffer pool 412, the buffers in the buffer pool are freed up and the local descriptors in the Rx list 402 that previously pointed to the read data are now re-designated as pointing to free blocks. Alternatively, as read data arrives and is stored in the buffer pool 412, look-ahead DMA may be performed to move the data to destinations specified by the scatter gather list in advance of the receipt of all read data.
Note, however, that if the reading of data from the target is initiated but there are insufficient local descriptors in the Rx list pointing to free blocks to accommodate the read data, the MAC will discard any inbound read data.
In general, the movement of read or write data between host computer memory and the buffer pool may occur using DMA under the control of a specialized DMA processor that can take control of the PCI bus and move data across the PCI bus in the background without the participation of the host computer's main processor. In addition, multiple reads and writes may occur at the same time.
It should be understood that the Tx list 400 and the Rx list 402 may contain a fixed maximum number of entries (descriptors), e.g. 256. Because there may be more total blocks in the buffer pool 412 (e.g. 5000) than are identified in the entries in the Rx and Tx lists, a "free" list of descriptors 414 is also maintained within the HBA memory that keeps track of free blocks not identified in the Tx and Rx lists.
As illustrated in FIG. 4, the MAC manages two lists, a transmit (Tx) list 400 and a receive (Rx) list 402. In one example, 32 MB of memory may be available in the HBA, and of those 32 MB, 19 MB may available for the buffer pool. The other 13 MB are reserved for other functions, including the Tx and Rx lists. Firmware in the HBA controls the Rx and Tx lists and the buffer pool. In general, the SCSI driver makes read or write commands available on the PCI bus and signals the HBA, which then controls the Tx and Rx lists and the filling and emptying of the buffers while the host computer is passive.
In the conventional architecture described above, if a large portion of the buffer pool in the HBA was utilized to temporarily store outbound write data and received read data, and there were insufficient free blocks to store further incoming read data, inbound data packets would have been dropped. Furthermore, because TCP/IP provides a mechanism for counting packet headers received from the target during the transmission of command or data packets, if the target detected that the count did not conform to expectations then a retransmission would be initiated, which would create further slowdowns. Moreover, if certain packets in a sequence were not transmitted, the entire transmission may be delayed until the missing packet is successfully retransmitted. The loss of inbound read data packets therefore results in time-outs and retransmissions by the target device, which can severely degrade throughput performance.
In addition, if the above-described shortage of blocks in the buffer pool occurs, causing read data congestion and the incomplete processing of read commands, and nevertheless the HBA continues to receive and initiate new write commands, any remaining free blocks in the buffer pool could be consumed by write data. However, because the pending read commands do not have sufficient buffers for completion, they cannot be completed. Without completion of the pending read commands, the new write commands cannot be processed. In such a situation, the remaining free blocks in the buffer pool are being used for write commands that couldn't possibly succeed. If this should happen, then subsequent retransmissions of read data by the target would also be doomed to failure, because there would be no free blocks available to receive it. This lockup condition would persist until the target terminated its retransmissions, closed the connection, and started over. Therefore, a performance problem (degradation) could turn into a functional problem (lockup) if the bottleneck became severe enough.
To overcome these problems and minimize the chance of performance degradation or lockup, in some previous designs the buffer pool is split in half, with one half of the buffer pool reserved for transmit (write) data, and the other for receive (read) data. This structure is easier to manage, but more wasteful and inefficient, especially if the buffer pool usages are unequal. With split buffer pools, if the transmit path, for example, needed more memory, it couldn't use the memory for the receive path, even if that memory were unused.
Thus, a need exists for an apparatus and method that manages read/write command data congestion at the application layer to improve performance and reduce the resource exhaustion that results in lost packet data at the transport layer.

Read/write command buffer pool resource management using read-path prediction of future resources

Emulex Design & Manufacturing Corporation


The invention relates to a novel memory cell structure and process to fabricate chalcogenide phase change memory. More particularly, it produces a small cross-sectional area of a chalcogenide-electrode contact part of the phase change memory, which affects the current/power requirement of the chalcogenide memory. Particular aspects of the present invention are described in the claims, specification and drawings.

1. Field of Invention
The invention relates to a novel memory cell structure and process to fabricate chalcogenide phase change memory. More particularly, it produces a small cross-sectional area of a chalcogenide-electrode contact part of the phase change memory, which affects the current/power requirement of the chalcogenide memory.
2. Background
Chalcogenides have been utilized in the formation of memory cells for integrated circuit memory devices. Representative prior art patents in this field include Reinberg, U.S. Pat. No. 5,789,758; Harshfield, U.S. Pat. No. 6,077,729; Wolstenholme, et al., U.S. Pat. No. 6,153,890, Ovshinsky, U.S. Reissue Pat. No. RE37,259 (Reissue of U.S. Pat. No. 5,687,112), and many others.
Chalcogenides used for integrated circuit memory devices are materials characterized by more than one solid-state phase, and which can be switched between such phases using the application of heat caused for example by electrical current or optical pulses. Memory cells which include a chalcogenide element are arranged in an array which can be addressed using conventional word lines/bit line addressing schemes common in integrated circuit memories. The state of the memory cell is determined by the bulk resistance of the chalcogenide element. Because the different solid-state phases of the chalcogenide have different resistivity, the bulk resistance of the chalcogenide element indicates the amount of the chalcogenide element in a selected phase state.
The problem of applying current at sufficient current densities to cause the phase change in the chalcogenide element is reflected in the design of the memory cells. Typically, relatively complex structures are utilized to form small pores in the current path that is coupled to the chalcogenide element. Current is concentrated through the small pores to induce a locally high current density in the chalcogenide element.
The complex structures utilized to form the pores, and other aspects of chalcogenide based memory cells, have required relatively large cell sizes to implement. Furthermore, complex structures can affect the reliability of the memory devices. Large cell sizes limit the density of the memory device, and increase its cost. Likewise, reliability in manufacturing is critical to successful commercial application of memory devices. High-density, self aligned memory cells have been manufactured for other types of storage technologies, such as the vertically stacked, non-volatile memory described in Johnson et al., U.S. Pat. No. 6,185,122.
One approach to producing higher density cells is proposed by Wicker, U.S. Pat. No. 6,597,009, entitled "Reduced Contact Area of Sidewall Conductor". In Wicker's design, a trench 250 is the size of or narrower than a phase change material plug 290. The phase change material plug is aligned over one of two sidewall conductors 260 that are electrically coupled. Plugs of phase change material 290 are discontinuous and separated by an insulator.
Accordingly, it is desirable to provide phase change memory cell structures and devices with smaller sizes and power requirements. Furthermore, it is desirable to provide methods for manufacturing such devices, which are efficient and result in reliable structures.

Self-aligned small contact phase-change memory method and device


Novel transgenic plants having the ability to express a functional 2-5A system, i.e., a 2-5A synthetase which produces 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) in response to double stranded RNA (dsRNA), and a 2-5A-dependent (RNase L), are disclosed. The novel transgenic plants expressing the functional 2-5A system, such as novel transgenic tobacco plants, are immune to and resistant against viral infection. When the novel transgenic tobacco plants are exposed to three different types of plant viruses, i.e., TMV, TEV and AIMV, such viral exposure leads to necrotic local lesions in such transgenic tobacco plants instead of typical systemic infections.

Control of RNA degradation is a critical cell function, and gene expression is often regulated at the level of RNA stability. See, e.g., Sha, G. and Kamen R., Cell, 46:659-667 (1986). Nevertheless, relatively little is known about the biochemical pathways that mediate RNA degradation in mammalian or plant systems. For instance, most if not all of the ribonucleases responsible for mRNA turnover in mammalian or plant cells remain unidentified. This was reviewed in Brawerman, G., Cell, 57:9-10 (1989).
Presently, the 2-5A system is believed to be the only well-characterized RNA degradation pathway from higher animals including man. See FIG. 1. See also, e.g., Kerr, I. M. and Brown, R. E., Prod. Natl. Acad. Sci. USA, 75:256-260 (1978) and Cayley, P. J. et al.: Biophys Res. Commun., 108:1243-1250 (1982); reviewed in Sen, G. C. and Lengyel, P., J. Biol. Chem., 267:5017-5020 (1992). The activity of the 2-5A system is believed to be mediated by an endoribonuclease known as 2-5A-dependent RNase. See Clemens, M. J. and Williams, B. R. G., Cell, 13:565-572 (1978). 2-5A-dependent RNase is a unique enzyme in that it requires 2-5A, unusual oligoadenylates with 2',5' phosphodiester linkages, p.sub.n (A2'p).sub.n A, for ribonuclease activity. See Kerr, I. M. and Brown, R. E., Prod. Natl. Acad. Sci. USA, 75:256-260 (1978). 2-5A is produced from ATP by a family of synthetases in reactions requiring double-stranded RNA (dsRNA). See FIG. 1. See also Hovanessian, A. G. et al., Nature, 256:537-539 (1977); Marie, I. and Hovanessian, A. G., J. Bio. Chem., 267:9933-9939 (1992). 2-5A is unstable in cells and in cell-free systems due to the combined action of 2',5'-phosphodiesterase and 5'-phosphatase. See Williams, B. R. G. et al.; Eur. J. Biochem., 92:455-562 (1978); and Johnson, M. I. and Hearl, W. G., J. Biol. Chem., 262:8377-8382 (1987). The interaction of 2-5A-dependent RNase and 2-5A(K.sub.d =4.times.10.sup.-11 M), Silverman, R. H. et al., Biol. Chem., 263:7336-7341 (1988), is highly specific. See Knight, M. et al., Nature, 288:189-192 (1980). 2-5A-dependent RNase is believed to have no detectable RNase activity until it is converted to its active state by binding to 2-5A. See Silverman, R. H., Anal. Biochem., 144:450-460 (1985). Activated 2-5A-dependent RNase cleaves single-stranded regions of RNA 3' of UpNp, with preference for UU and UA sequences. See Wreschner, D. H. et al., Nature, 289:414-417 (1981a); and Floyd-Smith, G. et al., Science, 212:1020-1032 (1981). Analysis of inactive 2-5A-dependent RNase from mouse liver revealed it to be a single polypeptide of approximately 80 kDa. See Silverman, R. H. et al., Biol. Chem., 263:7336-7341 (1988).
Although full scope and biological significance of the 2-5A system remains unknown, studies on the molecular mechanisms of interferon action have provided at least some of the functions. Interferons .alpha., or Y are believed to induce the accumulation of both 2-5A-dependent RNase, Jacobsen, H. et al., Virology, 125:496-501 (1983A) and Floyd-Smith, G., J. Cellular Biochem., 38:12-21 (1988), and 2-5A synthetases, Hovanessian, A. G. et al., Nature, 268:537-539 (1977), reviewed in Sen, G. C. and Lengyel, P., J. Biol. Chem., 267:5017-5020 (1992). Furthermore, several investigations have implicated the 2-5A system in the mechanism by which interferon inhibits the replication of picornaviruses. Indeed, 2-5A per se and highly specific 2-5A mediated rRNA cleavage products were induced in interferon-treated, encephalomyocarditis virus (EMCV)-infected cells. See Williams, B. R. G., Nature, 282:582-586 (1979); Wreschner, D. H. et al., Nucleic Acids Res., 9:1571-1581 (1981b); and Silverman, R. H. et al., Eur. J. Biochem., 124:131-138 (1982a). In addition, expression of 2-5A synthetase cDNA inhibited the replication of picornaviruses, Chebath, J., Nature, 330:587-588 (1987) and Rysiecki, E. F. et al., J. Interferon Res., 9:649-657 (1989), and the introduction of a 2-5A analogue inhibitor of 2-5A-dependent RNase into cells reduced the interferon-mediated inhibition of EMCV replication. See Watling, D. et al., EMBO J., 4:431-436 (1985). Further, 2-5A-dependent RNase levels were correlated with the anti-EMCV activity of interferon, Kumar, R. et al., J. Virol., 62:3175-3181 (1988), and EMCV-derived dsRNA both bound to and activated 2-5A synthetase in interferon-treated, infected cells. See Bribaudo, G. et al., J. Virol., 65:1948-1757 (1991).
The 2-5A system, however, almost certainly provides functions beyond the antipicornavirus activity of interferons. For instance, introduction of 2-5A into cells, Hovanessian, A. G. and Wood, J. N., Virology, 101:81-90 (1980), or expression of 2-5A synthetase cDNA, Rysiecki, G. et al., J. Interferon Res., 9:649-657 (1989), inhibits cell growth rates. Moreover, 2-5A-dependent RNase levels are elevated in growth arrested cells, Jacobsen, H. et al., Proc. Natl. Acad. Sci. USA, 80:4954-4958 (1983b), and 2-5A synthetase, Stark, G. et al., Nature, 278:471-473 (1979), and 2-5A-dependent RNase levels are induced during cell differentiation. See, e.g., Krause, D. et al., Eur. J. Biochem., 146:611-618 (1985). Therefore, interesting correlations exist between 2-5A-dependent RNase and the fundamental control of cell growth and differentiation suggesting that the 2-5A system may function in general RNA metabolism. The ubiquitous presence of the 2-5A system in reptiles, avians and mammalians certainly supports a wider role for the pathway. See, for example, Cayley, P. J. et al., Biochem. Biophys. Res. Commun., 108:1243-1250 (1982).
While it is presently believed that the 2-5A system is the only well-characterized RNA degradation pathway from higher animals, the dsRNA-dependent protein kinase enzyme, known as PKR, is also thought to have antiviral effects in higher animals. Like the 2-5A synthetase enzyme, it is believed that PKR is stimulated by dsRNA. It is believed that activated PKR phosphorylates the alpha subunit of translation factor eIF.sub.2 -alpha, which indirectly inhibits protein synthesis initiation. It is believed that interferons .alpha., and Y induce the accumulation of PKR. See Hovanessian et al.: J. Interferon Res., 9:641-647 (1989).
Like the 2-5A system, the PKR system is also likely to provide functions beyond the antipicornavirus activity of interferons. See Meurs, E. F. et al.: J. Virology, 66:5805-5814 (1992). For example, expression of mutant forms of PKR in NIH 3T3 cells resulted in tumor formation when injected into nude mice. See Meurs, E. F. et al.: Proc. Natl. Acad. Sci USA, 90:232-236 (1993).
In short, the 2-5A system and the PKR system inhibit viral protein synthesis. This is believed to be accomplished by the 2-5A system by degrading mRNA and rRNA whereas the PKR system is believed to accomplish this by indirectly inhibiting protein synthesis initiation.
Viral plant diseases are pandemic and their severity varies from mild symptoms to plant death. The majority of plant viruses are believed to have single stranded RNA genomes. Moreover, it is currently believed that plants are void of the three enzymes discussed above, i.e., PKR, 2-5A synthetase and 2-5A-dependent RNase. See Cayley, P. J. et al.: Biochem. Biophys. Res. Commun., 108:1243-1250 (1982) and Devach, Y. et al.: Biochemistry, 24:593-599 (1985); but see Crum, C. et al.: J. Biol. Chem., 263:13440-13443 (1988); Hiddinga, H. J. et al.: Science, 241:451-453 (1988); Sela, I.: TIBS, pp. 31-33 (February 1981); and Devach, Y. et al.: Science, 216:1415-1416.
The interferon family of cytokines are believed to induce an antiviral state in cells of higher vertebrates. J. Vilcek, G. C. Sen, In Virology, B. Fields, ed. (Raven, New York, 1995). Virus infected cells produce and secrete interferons .alpha. and .beta., which are believed to signal uninfected cells that a virus infection has occurred. Interferons are thought to bind to specific cell surface receptors, activating Jak-STAT signal transduction pathways which induce interferon-stimulated genes. Darnell, J. E. et al.: Science, 264:1415 (1994). The proteins encoded by these genes are believed to be responsible for the biological effects of interferons, including the antiviral responses. The 2-5A system, see Kerr, I. M. et al.: Proc. Natl. Acad. Sci. USA, 75:256 (1978), is one such interferon-induced, antiviral pathway present in cells of reptiles, avians and mammals. Cayley et al.: Biochem. Biophys. Res. Commun., 108:1243 (1982). Two types of enzymes are believed to be essential for a functional 2-5A system: 1) any one of several 2-5A synthetases, which require dsRNA to produce 2-5A, a series of 5'-phosphorylated, 2',5'-linked oligoadenylates, A. G. Hovanessian, A. G. et al.: Nature, 268:537 (1977), and Marie, I. et al.: J. Biol. Chem., 267:9933 (1992); and 2) the 2-5A-dependent Rnase L. Clemens, M. J. et al.: Cell, 13:565 (1978), Slattery et al.: Proc. Natl. Acad. Sci. USA, 76:4778 (1978), and Zhou, A. et al.: Cell, 72:753 (1993). 2-5A is thought to activate Rnase L which cleaves viral and cellular single-stranded RNAs, predominantly after UpNp sequences. Floyd-Smith, G. E. et al.: Science, 212:1020 (1981); and Wreschner, D. H. et al.: Nature, 289:414 (1981). Because virus-infected cells often contain dsRNA activators of 2-5A synthetase, see, e.g., Gribaudo G. et al.: J. Virol., 65:1748 (1991), for instance as replicative intermediates of RNA viruses, RNA degradation by Rnase L is believed to frequently occur in interferon-treated, virus-infected cells. See Wreschner, D. H. et al.: Nucleic Acids Res., 9:1571 (1981); and Silverman, R. H. et al.: Eur. J. Biochem., 124:131 (1982). It is believed that the 2-5A system inhibits replication of the picornaviruses, encephalomyocarditis virus and mengo virus in interferon-treated mammalian cells. Chebath, J. et al.: Nature, 330:587 (1987); Rysiecki, G. et al.: J. Interferon Res., 9:649 (1989); Coccia, E. M. et al., Virology, 179:228 (1990); and Hassel, B. A. et al.: EMBO J., 12:3297 (1993).
RNase L, assayed by 2-5A binding activity, was not detected in tobacco, Nicotiana glutinosa and N. tabacum. See Cayley et al.: Biochem. Biophys. Res. Commun., 108:1243 (1982). Furthermore, 2-5A synthetase was not detected in such plants, and 2-5A synthetase was not detected in control, tobacco mosaic virus (TMV)-infected, interferon-treated or poly (I):poly (C)-treated plants. Plants therefore appear to lack a 2-5A system or an equivalent of the mammalian 2-5A system.
Previously, expression in potato of rat 2-5A synthetase mRNA, without co-expression of RNase L., was correlated with possible partial resistance to potato virus X (PVX) in some, but not all transgenic plants. See Truve, E. et al.: Bio/Technology, 11:1048 (1993). The biochemical basis for both this perceived effect and for a possible anti-TMV effect of 2',5'-oligoadenylate in non-transgenic N. glutinosa leaf disks has not been established. See Y. Devash, et al.: Science 216: 1415-1416 (1982). Although plant oligoadenylates are believed to exist, they appear to differ from 2-5A, see, e.g., Y. Devash et al.: Biochem., 24:593 (1985). It is therefore presently believed that plants do not produce or express 2-5A synthesis and RNase L.
Notwithstanding the importance of 2-5A-dependant RNase to the 2-5A system, 2-5A-dependent RNase enzymes having ribonuclease function have not been isolated, purified or sequenced heretofore. Consequently, there is a demand for isolated, active 2-5A-dependent RNases and their complete amino acid sequences, as well as a demand for encoding sequences for active 2-5A-dependent RNases. There is also a demand for transgenic plants which are immune or resistant to viruses, such as transgenic tobacco plants that are immune or resistant to viruses such as the picornaviruses, tobacco mosaic virus (TMV), tobacco etch virus (TEV) and alfalfa mosaic virus (AIMV).

Transgenic plants co-expressing a functional human 2-5A system


Techniques for sharing data among a plurality of networked devices, also referred to network nodes, are discussed. To best use an available uploading bandwidth of a device sharing data with a receiving device, a portion of the data is uploaded within the available uploading bandwidth, and another portion of the data is uploaded from another device locally caching the same data. To satisfy the minimum transmission rate of the data to the receiving device, both portions of the data are concurrently uploaded from the two devices to the receiving device. In reference to a predetermined minimum uploading bandwidth and the available uploading bandwidth, the two portions of data are interleaved and must be reassembled to recover the data for consumption in the receiving device. A size of the first portion of the data is determined by a server in view of the available uploading bandwidth a designated supplying box has.

1. Technical Field
The present invention is generally related to multimedia data delivery over the Internet. Particularly, the present invention is related to techniques for sharing media files among network nodes.
2. Description of the Related Art
It is common to share files among computing devices across a network. However, when data to be shared is of huge size and the network bandwidth between two devices sharing the data is limited, the utility or application of the data could suffer. For example, one device is supplying data pertaining to a movie to another device over a network with a limited bandwidth. If the data does not arrive at a required transmission rate, the playback of the movie at the receiving device could demonstrate annoying jittery effects.
One possible solution to resolve jittery effects is to design a lower transmission rate. However, there are applications that require a minimum transmission rate, otherwise the applications could not perform or be conducted as expected.
There, thus, is a great need for techniques that maximize the use of available bandwidths whiling sharing data among computing devices across one or more networks.

Method and apparatus for sharing media files among network nodes


An intelligent switch and method are described herein which help to effectively retransmit a lost packet that is associated with a television broadcast stream to one or more set-top boxes.

1. Field of the Invention
The present invention is related to an intelligent switch and a method for retransmitting a lost packet that is associated with a television broadcast stream to one or more decoders (set-top boxes).
2. Description of Related Art
The following abbreviations are herewith defined, at least some of which are referred to in the ensuing description of the prior art and the present invention.
BTVBroadcast TelevisionCOCentral OfficeDSLDigital Subscriber LineDSLAMDigital Subscriber Line Access MultiplexerGbpsGiga-bits-per-secondICCInstant Channel ChangeSAIService Area InterfaceSHESuper HeadendSTBSet-Top BoxTVTelevisionVHOVideo Hub OfficeVODVideo-On-Demand
Referring to FIG. 1 (PRIOR ART), there is a block diagram that illustrates the basic components of an exemplary transport network 100 which can provide broadcast TV channels to homes via DSL phone lines. The exemplary transport network 100 shown includes two super head-ends 102, a backbone network 104, multiple VHOs 106, multiple IOs 108, multiple COs 110, multiple SAIs 112 and multiple STBs 114. In operation, each super head-end 102 (which includes a router 116) receives international TV feeds and supplies those international TV feeds via the backbone network 104 to each VHO 106. Then, each VHO 106 (which includes a router 118, intelligent switch 120, VoD server 122 and BTV server 124) receives local TV feeds and multicasts all of the TV feeds to their respective IOs 108. And, each IO 108 (which includes a router 126) then multicasts all of the TV feeds to their respective COs 110. Then, each CO 110 (which includes an intelligent switch 128) multicasts all of the TV feeds to their respective SAIs 112. And, each SAI 112 (which includes a DSLAM 130) then multicasts all of the TV feeds to their respective STBs 114. In this way, users can interface with their STB 114 and select one of the multicast TV channels to watch on their TV (not shown). The transport network 100 in addition to providing broadcast TV can also provide voice (telecommunications) and data (Internet) to the homes via DSL phone lines.
Each VHO 106 contains a BTV server 124 (multiple BTV servers 124 are possible) whose main purpose is to provide a rapid TV channel change functionality. This functionality is used when a user changes a TV channel and their STB 114 sends an ICC request/fast channel change request) to the BTV server 124 (e.g., delivery server 124). In response, the BTV server 124 unicasts the newly requested TV channel directly to that STB 114 so it can be displayed in a timely manner on the user's TV. Thus, the user will not have to experience an undesirable delay waiting for the new TV channel to be displayed on their TV.
The BTV server 124 also has a secondary purpose in which it is responsible for retransmitting a copy of a lost packet to STBs 114. This functionality is used when a STB 114 is tuned to a TV channel and it detects that there is a lost packet associated with a video stream of that TV channel. In this situation, the STB 114 sends a retransmission request for the lost packet back to the BTV server 124. And, the BTV server 124 then retransmits a copy of the packet back to that particular STB 114 using a unicast session. For example, assume a packet 132 is lost between one of the COs 110′ and one of it's corresponding SAIs 112′. Then, each downstream STB 114′ (only two shown) which happened to be tuned to the TV channel that is associated with the lost packet 132 sends a retransmission request 134 back to the BTV server 124. The BTV server 124 then retransmits (unicasts) two individual lost packets 132′ directly back to the two requesting STBs 114′. It is fairly easy to see how the reception of multiple retransmission requests 134 for the same lost packet 132 and then the retransmission of multiple lost packets 132′ back to the requesting STBs 114′ can lead to a congestion problem. A second example is provided below to better illustrate this point.
In the second example, assume a packet 136 is lost between one of the IOs 108″ and one of it's corresponding COs 110″. Then, each downstream STB 114″ (only four shown) which happened to be tuned to the TV channel that is associated with the lost packet 136 sends a retransmission request 138 back to the BTV server 124. The BTV server 124 then retransmits (unicasts) four individual packets 136′ directly back to the four requesting STBs 114″. Thus, depending on the location of the packet loss and the number of viewers (e.g., STBs 114′ and 114″) that happen to be affected by the packet loss it is possible to overload the BTV server 124. In fact, the BTV server 124 can receive an avalanche of retransmission requests 134 and 138 so it has to individually retransmit a large number of lost packets 132′ and 136′ directly back to the STBs 114′ and 114″. This can lead to two problems:
1. I/O Congestion at BTV server 124: The BTV server 124 has a limited output capacity (e.g., 2 Gbps) to serve both retransmission requests 134 and 138 and ICC requests from STBs 114. Therefore, the mentioned avalanche of retransmission requests 134 and 138 would likely create a congestion problem at the BTV server 124. FIG. 2 (PRIOR ART) is a graph which illustrates the estimated I/O bandwidth requirements in the future on a BTV server 124. As can be seen, this I/O problem is only going to get worse with the passage of time.
2. Transaction Congestion at BTV server 124: The BTV server 124 has to respond to retransmission requests 134 and 138 by locating the requested lost packets 132 and 136 in its buffer, establishing a unicast session, and retransmitting the lost packets 132′ and 136′ back to STBs 114′ and 114″. In addition, the BTV server 124 is responsible for handling ICC requests. Therefore, the mentioned avalanche would likely create an overload at the BTV server 124. FIG. 3 (PRIOR ART) is a graph which illustrates the estimated number of retransmission requests and ICC requests in the future that may be sent to the BTV server 124. As can be seen, this processing/transaction overload is only going to get worse with the passage of time.
Accordingly, there is a need for a new procedure to handle retransmission requests and the retransmissions of lost packets such that the BTV server 124 does not suffer from problems like I/O congestion and/or transaction congestion. This need and other needs are satisfied by the intelligent switch and method of present invention.

Intelligent switch and method for retransmitting a lost packet to decoder(s)


Techniques are described for providing alternative media content to a client device along with primary media content.

Live media content includes channels or feeds of live broadcasts (e.g., sporting events, news, etc.). Unlike video-on-demand (VOD) content, live content may not have a distinct end point and may continue indefinitely. In addition, VOD content may be buffered or otherwise stored in client devices well in advance of the client playhead (i.e., the content fragment currently being rendered by the client). This is typically not the case for live content because of the fact that the delay between the live playhead (i.e., the latest content fragment available) and the client playhead may be only a few seconds, as well as the fact that the live content is often generated in real time and therefore may not yet exist.

This patent is subject to a terminal disclaimer.

Providing alternative live media content


Methods and systems for automatically locating and identifying labware using radio-frequency identification (RFID) tags are described herein. The methods and systems include a plurality of RFID tags (pre-programmed with unique data codes) that are associated with labware (or labware holders). For example, the RFID tags can be embedded within the locating pegs of the labware (or labware holders). The methods and systems also include a plurality of RFID tag readers that mount near known locations of an instrument deck which receives the labware. The RFID tag readers automatically scan for the presence of RFID tags such that when a piece of labware is added to the instrument deck, and then report to a processing device the specific known location on deck where each tag was found, as well as the unique data code of each tag. Using this information, the methods and systems determine one or more of the location, orientation, and identity of the received labware.

1. Technical Field
The present disclosure relates to the use of radio-frequency identification (RFID) techniques for locating and identifying labware used in biochemical and chemical processing as well as in the analysis of samples in laboratories and the like.
2. Description of Related Art
Automated liquid handling and chemical analysis instruments have been developed for biochemical and chemical processing and analysis of samples. These instruments generally use different types of labware to process the samples. These labware items can be containers in which samples are held (e.g., test tubes, micro-titer plates), holders for the sample containers (e.g., a test tube rack), holders for accessories (e.g., a disposable pipette rack), processing items (e.g., heaters, chillers, washbowls), or various other accessories. Such labware is available from a number of sources including PerkinElmer Life & Analytical Sciences.
Labware placed onto an instrument, workstation, work area, instrument deck, and the like, is typically identified manually. It is also known in the art to identify the labware semi-automatically by applying a bar code identifying label to the labware and using a bar code wand or reader to recover labware identification information.
Another prior art system describes the use of RFID tags that are attached to sample vials so that the vials may be identified when stored or transferred.
Other prior art systems attempt to automate labware identification using optical means.

Methods and systems for locating and identifying labware using radio-frequency identification tags


A method is provided for ligating a segment of a biological vessel having a proximal end and a distal end. According to the method, the distal end of the vessel segment to be ligated is accessed; an inner fluid delivery catheter is attached to the distal end of the vessel segment; fluid is infused into the biological vessel; the vessel segment is advanced within a lumen of an outer catheter, the outer catheter including a cautery-sectioning system; tributaries extending from the vessel segment are cauterized and sectioned with the cautery-sectioning system as the vessel segment is advanced within the outer catheter; and the vessel segment proximal end is ligated.

1. Field of the Invention
The invention relates to a device for harvesting a segment of a biological vessel and a method by which the device is used to harvest the biological vessel segment.
2. Description of Related Art
A variety of surgical applications require the harvesting of a segment of a biological vessel, such as a vein or artery, in one location of a patient's body for use in a surgical application in a second location of the body. The most common example is the harvesting of the saphenous vein for use in multiple vessel coronary artery bypass surgery. For this application, it is necessary to provide a section of vein that is approximately the size of the coronary arteries in a condition in which the intimal lining is in a healthy native condition. At the present time, this is accomplished by making an incision in the skin, identifying the saphenous vein in the leg, separating the vein from adjacent adventitial tissues, ligating or cauterizing tributary veins and delivering the vein. Subsequently, the vein is divided into segments of appropriate length for the purpose of creating anastomotic channels from the aorta to an occluded coronary artery(s) distal to an area of occlusion. This procedure is laborious, time consuming and results in considerable discomfort in the calf region of the leg and is a significant part of the general morbidity following coronary bypass surgery. This effect is not trivial since there are approximately 500,000 such operations annually in the United States alone.
A need currently exists for a minimally invasive biological vessel harvesting device which can be used to harvest segments of biological vessels for later use in surgical procedures while causing a minimal degree of trauma to the patient. A further need exists for a biological vessel harvesting device which can be rapidly and effectively used, thereby reducing the surgeon time and operating room costs associated with harvesting a segment of a biological vessel.

Minimally invasive biological vessel harvesting method


An optical pickup transducer senses vibrations of string instruments transducing the vibrations into an electrical signal with fidelity, high signal-to-noise ratio and with exclusion of extraneous effects such as noise. The transducer includes a housing with an upper deck that holds one or more light emitters, and a lower deck that holds light sensors in a one-to-one arrangement with the emitters so that each sensor is physically in opposition to each emitter. For application to the string instruments, each string is conducted through the light beam between an emitter and a sensor. The sensors may be photodiodes, so that their electrical output is related to the amount of incident light and therefore varies with the movement of the string, that is, the string modulates the incident light on the photodiode. This electrical output is then amplified to drive a loudspeaker.

1. Field of the Present Disclosure
This disclosure relates generally to vibration pickups for stringed instruments and particularly to an optical pickup with transduction circuit for stringed instruments.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Kawabata et al U.S. Pat. No. 3,472,943 discloses a circuit using two coils as pickup elements influenced by string vibrations. The circuit simulates movement of the pickup elements for changing tone. Rowe U.S. Pat. No. 4,061,934 discloses a pickup using a piezoelectric element in contact with the strings of the instrument. Underwood U.S. Pat. No. 4,147,084 discloses a bridge with an integral transducer element. Melvin CA 2053118 discloses an electromagnetic pickup for an instrument with steel strings or strings with a metallic coating. Nakamura U.S. Pat. No. 5,189,241 discloses a pickup having a differential amplifier for eliminating noise. Hoshino U.S. Pat. No. 5,539,147 discloses a guitar pickup structure which includes pickup elements located below the guitar string's saddle to pickup vibrations of the saddle. Yamada U.S. Pat. No. 5,945,622 discloses a piezoelectric pickup inserted between the bridge and the body of the instrument. Hoshino U.S. Pat. No. 6,198,036 discloses an electric guitar tremolo bridge which holds the instrument's strings in contact with a piezoelectric pickup.
The related art described above discloses electric induction, electromagnetic and piezoelectric transducer pickups for musical instruments, e.g., stringed instruments. However, the prior art fails to disclose optical transducer methods. The present disclosure distinguishes over the prior art providing heretofore unknown novel and non-obvious optical transduction approaches with advantages as described in the following summary.

Light beam shaping in an optical pick up for a musical instrument


A memory device has an SRAM that stores a logic state. A first MTJ has two terminals. A second one of the terminals is coupled to a storing node. A first terminal of a second MTJ is coupled to the storing node. The first and second MTJs are programmed to a first resistance by flowing current from the first second terminals and to a second resistance by flowing current from the second to first terminal. A storing circuit is coupled to the storing node, the SRAM cell, and a non-volatile word line. The storing circuit couples the logic state of the SRAM cell to the storing node during a store mode. The logic state of the SRAM cell is stored in the first and second MTJs by applying a storing voltage between the first terminal of the first MTJ and the second terminal of the second MTJ of a first polarity then a second polarity.

Field
This disclosure relates generally to semiconductor memory devices, and more specifically, to static random access memory (SRAM) with backup non-volatile memory that includes magnetic tunneling junction (MTJ) resistive elements.
Related Art
Memories with resistive storage elements under development across the semiconductor industry are geared to replace conventional random access memory (RAM) and non-volatile memory devices. The resistive memory devices include magnetoresistive random access memory (MRAM), Resistive random-access memory (RRAM or ReRAM), and phase-change memory (PCM), among others. Most of the resistive memory devices are implemented in one transistor/one resistive element or one diode/one resistive element memory cell configurations, which require minimal cell area but exhibit relatively slow read and write performance (e.g., approximately 30 nanoseconds or more per operation). Thus, resistive memory devices are not a viable substitute for much of the static RAM in a higher performance system where read/write operations occur within a few clock cycles. It is also difficult to produce a reliable one transistor/one resistive element or one diode/one resistive element memory.
Memory cells with one transistor and one resistive element may eventually replace embedded flash on future SoCs, but it is desirable to use these same elements to replace the static random access memory (SRAM) as well. Potentially, less flash would be needed, or the system could use a more efficient architecture, if the 'fast' memory such as SRAM was also compact and non-volatile.

Systems and methods for SRAM with backup non-volatile memory that includes MTJ resistive elements


A throttle control device for a hand held tool, such as a chain saw, is provided. The tool is provided with a forwardly extending wire for transmitting a motion from a throttle control lever turnably arranged about a first axis to a throttle valve. One end of the wire is secured to a wire arm that is turnably arranged about a second axis. The wire arm is provided with one or several teeth cooperating with the throttle control lever and the second axis is arranged behind the first axis.

In conventional combustion engines that are provided with carburetors the carburetor comprises one or several throttle valves with associated return springs that are connected to a throttle control lever via a bowden cable. The spring or springs are designed such that they safely can pull the throttle valve back also under bad conditions such as when the motion is influenced by dirt and freezing temperatures. For this reason the springs have to be rather strong which means the force transmitted to the control lever increases considerably. Since a finger acting on the throttle control lever is very sensitive for these type of forces such forces causes discomfort and might lead to injuries for the operator.
It is also previously known, see U.S. Pat. No. 6,182,524, to use a toothed transmission gear linked to a separate cable/pulley arrangement in order to transmit the forces from the throttle control lever to the throttle valve. This arrangement is however rather complicated and space demanding.

Throttle control device for a hand held tool


Techniques for hosting adding and warming a host are described. In some instances, a method of determining that at least one group of hosts is to be increased by adding an additional host to the group of hosts; sending a request to the group of hosts for a list of machine learning models loaded per host of the group of hosts; receiving, from each host, the list of loaded machine learning models; loading at least a proper subset of list of loaded machine learning models into random access memory of the at least one group; receiving a request to perform an inference; routing the request to the additional host of the group of hosts; performing an inference using the additional host of the group of hosts; and providing a result of the inference to an external entity is described.

Loading a machine learning model (e.g., retrieving the model from disk, storing it in memory, and instantiating it) on-the-fly in a hosted environment in response to a request from a user is typically not feasible because of the relatively high latency for the loading operations. Further, memory sizes for a single host typically do not allow for all models to be cached, or for all models to be cached economically.

Pre-warming scheme to load machine learning models


A computer card mounted in a computer, which has at least one other card having a similar functionality to the card, with the cards being connected to a common bus. Both cards also have overlapping memory, I/O, and interrupt selections assigned by a plug-and-play device. The card comprises a unique handle that is latched to the card by the plug-and-play device. If a card comparator detects a match between the unique handle and the selection data, a selector enables the card. If the comparator does not detect a match between the unique handle and the selection data, the selector disables the card.

Open platform computers allow the addition of hardware cards to a computer bus in a computer which provides additional functionality to the computer. These cards can take the form of a video card, a LAN interface card, a telephony interface card, etc. Most common buses use address space as the mechanism to distinguish when a particular computer card is being selected. For example, when computer software requires some video function to be performed, the software is connected to the video card through a specific address range. Typically, each board is assigned a unique address space, usually to a traditional address location, such as the traditional location for video cards or the traditional location for disk drive interface cards.
Usually, the computer bus does not allow for multiple cards of the same type, i.e. multiple disk drive cards or multiple LAN cards. If multiple card capability were supported, individual address blocks for each card would be required, such that if a particular video card requires a 16 k address block, and there were four such video cards, then a 4.times.16 k block of address space would be utilized. Most computers are limited in their total available address space, and may not have sequential or linear address blocks available. This can complicate the board design which is intended to be installed in a computer having multiple copies of the same card. The addressable range may have to be broken into smaller pieces so that it can fit into the address space available on the computer. This not only increases the cost of the board design, but also requires increased complexity in the software which controls the communication with these cards. The existing system makes it difficult, if not impossible, to install more than a few cards of the same type in a computer with the limited address space.
Therefore, there exists a need in the art for a mechanism to allow multiple cards of the same type or different types in combination to be installed in large numbers on common computer buses.
Furthermore, there is a need in the art for a system which has quick and efficient mechanisms to select these cards to avoid unnecessary machine operations and software instructions to select and communicate with the cards.
There is a also a need in the art for a system which will allow multiple cards of the same type to be utilized at the same time without fragmenting the memory and without having the card address memory scattered at various places throughout the memory space.

Assigning and utilizing overlapping address space for multiple cards on a common computer bus


Methods, apparatuses, and systems directed to reliably providing emergency services to wireless clients. In one embodiment, a wireless client determines if an attempt to transmit an emergency message exists. If so, the wireless client determines if one or more wireless access points support expedited bandwidth capabilities. If so, the wireless client notifies one of the wireless access points that the wireless client has an expedited bandwidth request.

Market adoption of wireless LAN (WLAN) technology has exploded, as users from a wide range of backgrounds and vertical industries have brought this technology into their homes, offices, and increasingly into the public air space. This inflection point has highlighted not only the limitations of earlier-generation systems, but also the changing role that WLAN technology now plays in people's work and lifestyles, across the globe. Indeed, WLANs are rapidly changing from convenience networks to business-critical networks. Increasingly users are depending on WLANs to improve the timeliness and productivity of their communications and applications, and in doing so, require greater visibility, security, management, and performance from their networks.
Admission control is a technique used in bandwidth-constrained networks or over bandwidth-allocated links to manage the effects of congestion. In wireless local area networks (WLANs), wireless clients may request bandwidth for Quality of Service (QoS) services via a traffic specification (TSPEC) request according to the IEEE 802.11e specification or the Wi-Fi Alliance's Wi-Fi Multimedia (WMM) specification. In response to this request, a wireless access point will attempt to admit the QoS flow if over-the-air (OTA) bandwidth is available. A policy configured by a system administrator permits this operation. One characteristic of admission control is that a wireless access point will continue to accept and admit new QoS flows, but only until the OTA bandwidth is used up or until the OTA usage reaches a pre-defined threshold set by the system administrator. Once this occurs, subsequent requests for OTA bandwidth are denied.

Expedited bandwidth request for emergency services for wireless clients


A system for displaying a performance dashboard comprises an input interface, a processor, and an output interface. The input interface is configured to receive log data. The log data comprises a set of process log entries. The processor is configured to determine one or more daemon response times and to determine dashboard information. The dashboard information is based at least in part on the log data and the one or more daemon response times. The output interface is configured to provide the dashboard information.

An enterprise backup software system comprises many backup clients to protect backup data. An enterprise software system additionally comprises many backup server systems to store backup copies of the data in case an older version needs to be accessed. An enterprise software system administrator maintains the enterprise software system and determines the cause of any system problems. Some software systems problems can be very difficult to understand because of the large number of systems interacting with one another.

System and method of smart framework for troubleshooting performance issues


Systems and methods are disclosed for planning demand of a product, such as a configurable product. In one embodiment, a method is provided for planning demand for a configurable product in a managed supply chain. The method may comprise the steps of storing data relating to the possible combinations of characteristics defining configurable products, wherein product dependent characteristic data and product independent characteristic data are stored dependently with respect to one another, and converting a planning demand for a configurable product into a planning demand for an actual combination of characteristics defining a configured product.

I. Field of the Invention
The present invention generally relates to computerized planning systems and methods and to such systems and methods for planning demand for products. More particularly, the invention relates to planning systems and methods for planning demand for a configurable product in a managed supply chain.
II. Background Information
Demand planning is used to forecast the demand for products, such as configurable products. A configurable product is a product having one or more product dependent characteristics. Demand planning works with characteristics-based forecasting. For example, a configurable products such as a car has certain attributes (also referred to as product dependent characteristics) such as color, model and engine. Conventional demand planning identifies certain primary attributes, such as model, and other secondary attributes, which are typically less important, such as battery type.
In the conventional demand planning, in order to reduce the volume of data to be processed in demand planning, only the possible combinations of primary attributes are stored independently. One problem with this approach to demand planning is that planned characteristics can only be used for planning configurable products, and not for configured finished products and assemblies. Another problem with conventional demand planning is that it is not possible to generate configured orders (e.g., CDP and IBASE orders) for the explosion of the Production Process Model (PPM) and Integrated Product and Process Engineering (iPPE). An additional problem with conventional demand planning is that configured sales orders do not take into account configured forecasts.
In view of the foregoing, it is an object of the present invention to address these and other problems encountered in conventional demand planning systems and methods.

Systems and methods for planning demand for configurable products


Described is system and method for robust ground-plane homography estimation using adaptive feature selection. The system determines feature correspondences of an image that correspond with at least one moving object in each image in a set of images. Additionally, feature correspondences of the image that correspond with at least one above-ground object are determined in each image. Feature correspondences that correspond with each moving object in each image are excluded, and feature correspondences that correspond with each above-ground object in each image are excluded. Each image is divided into a plurality of sub-regions comprising features correspondences. The number of feature correspondences in each sub-region is limited to a predetermined threshold to ensure that feature correspondences are evenly distributed over each image. Finally, a ground-plane homography estimation between the set of images is generated.

(1) Field of Invention
The present invention relates to a system for ground-plane homography estimation and, more particularly, to a system for ground-plane homography estimation using adaptive feature selection.
(2) Description of Related Art
In the field of computer vision and computer graphics, any two images of the same planar surface in space are related by a homography (assuming a pinhole camera model). Homography is a concept in the mathematical science of geometry. A homography is an invertible transformation from a projective space (e.g., the real projective plane) to itself that maps straight lines to straight lines. Through homography mapping, the image coordinate in image A of a physical planar surface point can be mapped to the coordinate in image B of the same point. This has many practical applications, such as image rectification, image registration, or computation of camera motion (rotation and translation) between two images. Once camera rotation and translation have been extracted from an estimated homography matrix, this information may be used for navigation, or to insert models of three-dimensional (3D) objects into an image or video, so that they are rendered with the correct perspective and appear to have been part of the original scene, as in augmented reality.
Conventional homography estimation methods in the prior art use random sample consensus (RANSAC) to find the homography function between two images of the same scene, such as two consecutive images taken by an airborne platform looking down to the wound. RANSAC picks random samples of the given correspondences between them, fits the homography function, and then evaluates the function to all possible correspondences. Evaluation of the fitted homography is a process to find a function that has a maximum number of inliers among all the correspondences. Thus, the conventional ground-plane homography estimation methods assume that the correspondences lie on the planar surface (i.e., the ground plane). If a significant amount of the feature correspondences is from either moving or above-ground objects, the estimated homography may contains errors and inaccuracies, since those outlier correspondences do not hold the ground-homography transform.
The moving object detection and tracking algorithm described by Bhattacharya et al. in "Moving Object Detection and Tracking in Infra-red Aerial Imagery," Machine Vision Beyond Visible Specturm, Augmented Vision and Reality, Volume 1, 2011 (which is hereby incorporated by reference as though fully set forth herein) performs pound-plane homography estimation in forward looking infrared aerial imagery. It uses speeded up robust features (SURF) and Kanade-Lucas-Tomasi (KLT) features to regulate cumulative homography drift, but the algorithm still has the problem of non-planar outlier features.
The locally optimized RANSAC approach described by Chum et al. in Locally Optimized RANSAC," Pattern Recognition (2003), pp. 236-243 (which is hereby incorporated by reference as though fully set forth herein) modified RANSAC so that it simultaneously improves the speed of the algorithm and the quality of the solution by introduction of two local optimization methods, but it didn't actively exclude outlier features for quality improvement.
Each of the prior methods described above exhibit limitations that make them incomplete. Thus, a continuing need exists for a method for robust ground-plane homography estimation using adaptive feature selection, which includes feature exclusion from moving or above-ground objects and a sub-region feature correspondence limitation

Robust ground-plane homography estimation using adaptive feature selection


A catalyst supporting honeycomb including a pillar-shaped honeycomb structure having a plurality of cells formed in parallel with one another in a longitudinal direction with a cell wall interposed therebetween, and catalyst particles supported on the honeycomb structure. The catalyst particles include an oxide catalyst, an average particle diameter of which is at least about 0.05 μm and at most about 1.00 μm.

1. Field of the Invention
The present invention relates to a catalyst supporting honeycomb and a method of manufacturing the same.
2. Discussion of the Background
There has been known a catalyst supporting honeycomb which converts exhaust gases by allowing the exhaust gases to contact with a catalyst supported on cell walls of a honeycomb structure which is mainly made of inorganic fibers. With regard to a catalyst supporting honeycomb disclosed in WO 2007/10643 A1, a catalyst is supported on a honeycomb structure by impregnating the honeycomb structure in a catalyst solution in a slurry state, and then heating the honeycomb structure.
The contents of WO 2007/10643 A1 are incorporated herein by reference in their entirety.

Catalyst supporting honeycomb and method of manufacturing the same


Apparatuses and methods for providing data from stacked memory are described. The stacked memory may include multiple die. In some examples, a master die may receive data from one or more slave die. The master die may provide data from the master die and the data from the one or more slave die to a plurality of output terminals. Different ones of the output terminals may provide data from a different die of the stacked memory. In some examples, the data may be retrieved from the multiple die concurrently.

In recent years, three-dimensional (3D) memory devices have been introduced. Some 3D memory devices are formed by stacking die vertically and coupling the die using through-silicon (or through-substrate) vias (TSVs) and/or wire bonds. Thus, 3D memory may also be referred to as "stacked memory." 3D memory may provide greater memory capacity and/or higher bandwidth with less increase in area than non-3D memory. Example 3D memory devices include Hybrid Memory Cube (HMC), High Bandwidth Memory (HBM), and Master-Slave Memory (MSM).
MSM may include multiple dynamic random access memory (DRAM) die coupled to one another in a stack. One die may serve as a master die and the remaining die may serve as slave die. The master die may control memory operations of the slave die. In some MSM, the master die and slave die may be identical with either a hardwired or programmable designation as to which die serves as the master die. In other MSM, the master die may have a different design than the slave die. The master die may be the only die of the MSM to directly interface with a component external to the memory (e.g., a substrate, a memory controller). Having only one die directly coupled to a component external to the MSM in a device including the MSM (e.g., a memory module including multiple MSMs, a computing device) may reduce loading on the device. However, this advantage may require that all data from the slave die is transmitted through the master die, which may limit bandwidth and/or speed of the MSM.

Apparatuses and methods for different IO widths for stacked die


Various aspects of the subject technology related to systems and methods for providing secure end-to-end data encryption between devices. In one aspect, a method includes encrypting data for a sending device using an encryption key. The encryption key is not stored on a server. The method includes decrypting the encrypted data transmitted from the sending device to a receiving device using a decryption key. The decryption key is also not stored on a server.

A messaging application using end-to-end encryption attempts to transmit messages between a sender and receiver such that the sender and the receiver, rather than an unauthorized third party, can access the contents of the messages. However, end-to-end encryption does not eliminate the risk of an unauthorized third party accessing the contents of the messages.

Providing secure end-to-end data encryption between devices


The invention relates to an attenuated non-segmented negative-sense RNA virus characterized by at least one mutation in the L gene wherein the mutation reduces viral replication, the methods of manufacturing and methods of use.

Vesicular stomatitis virus (VSV), the prototypic Rhabdovirus, has a non-segmented negative-sense (ns NS or NNS) RNA genome of 11,161 nucleotides comprising a 50-nucleotide 3′ leader region (Le); five genes that encode the viral nucleocapsid (N) protein, phosphoprotein (P), matrix (M) protein, attachment glycoprotein (G) and large polymerase subunit (L), and a 59-nucleotide trailer region (Tr), arranged in the order 3′-Le-N-P-M-G-L-Tr 5′ (1, 3, 4). The viral genomic RNA is encapsidated by N protein to form a ribonuclease-resistant ribonucleoprotein (RNP) complex that acts as template for the RNA-dependent RNA polymerase (RdRP). The viral components of the RdRP are a monomer of the 241-kDa L protein and a trimer of the 29-kDa P protein (19). During RNA synthesis, the RdRP uses the encapsidated genomic RNA as template in two distinct reactions: (i) transcription of five messenger RNAs that encode the N, P, M, G and L proteins; and (ii) replication to yield full length antigenomic and then genomic strands (reviewed in ref. 66).
During transcription the RdRP sequentially synthesizes five capped and polyadenylated mRNAs (1, 3, 4). These mRNAs are not produced in equimolar amounts; rather, their abundance decreases with distance from the 3′ end of the template such that N>P>M>G>L (63). This polarity gradient reflects a localized transcriptional attenuation at each gene junction, where 30% of RdRP molecules fail to transcribe the downstream gene (34). The widely accepted model for mRNA synthesis is the stop-start model of sequential transcription. In the original version of this model, polymerase initiates at a single site on the genome yielding a leader RNA and, by sequential reinitiation, the 5 viral mRNA's. Access of polymerase to downstream genes is, therefore, entirely dependent upon termination of transcription of the upstream gene (hence stop-start). Recent experiments with VSV indicate that the polymerase molecule that transcribes the leader region does not proceed to transcribe the N mRNA (12, 46, 67). Other than this refinement, the stop-start model is well supported by much experimental evidence (reviewed in 66).
The cap structure of ns NS viral mRNAs is formed by a mechanism that appears unique. For VSV (2), respiratory syncytial virus (7) and spring viremia of carp virus (26), the two italicized phosphates of the 5′Gppp5′NpNpN triphosphate bridge have been shown to be derived from a GDP donor. By contrast, cellular and all other known viral capping reactions involve GMP transfer (reviewed in 24). This difference, combined with the cytoplasmic location of viral RNA synthesis suggested that a viral protein, possibly the L protein subunit of polymerase, possesses guanylyltransferase activity, though direct evidence for this is lacking. Following capping, the 5′ terminus of the nascent transcript is methylated by [guanine-N-7] and [ribose-2′-O] methyltransferases (30, 35, 40, 41, 48-50, 62). These activities have been mapped to the L gene (30). Recent work has shown that alteration of amino acid residue D1671 which resides within a predicted s-adenosyl methionine (SAM) binding region of L protein inhibited mRNA cap methylation (25). However, the catalytic residues within the polymerase, the substrate requirements for the reactions and the order in which the mRNA processing reactions occur, remain poorly understood.
The nucleotide sequence of 39 ns NS RNA virus genomes have been determined. See "The Viral Genomes Resources" Homepage at NCBI. Amino acid sequence alignments between the L proteins of representative members of each family identified 6 conserved domains numbered I-VI (45). X-ray crystal structures of representative members of each class of template-dependent polynucleotide polymerase have been determined. Each contains a catalytic core resembling a cupped right hand. Within the palm region are motifs A-B-C-D found in all polymerases and motif E, found in RdRPs and reverse transcriptase. Domain III of the ns NS virus L proteins contains these A-B-C-D motifs. Consistent with this, domain III of VSV L was shown to be critical for polymerase activity (58). Functions have yet to be assigned to the other conserved domains, although sequence comparisons to FtsJ/RrmJ (FIG. 1), a heat shock methyltransferase of Escherichia coli, suggest that a region spanning domain VI might function as a [ribose-2′-O]-methyltransferase (9, 22).
A comprehensive genetic and biochemical analysis of the conserved domains of the VSV L protein has not been performed. However, studies with the paramyxovirus, Sendai (SeV), showed that genetic alterations introduced throughout each of the conserved domains of L protein revealed multiple defects in a reconstituted RNA synthesis assay (11, 20, 21, 32, 59, 60). These studies did not permit the assignment of specific functions to conserved domains of L protein. Rather, these experiments indicated that the global architecture of the SeV L protein was essential for all polymerase functions. More recently, domains V and VI of the SeV L protein were expressed independently and shown to retain the ability to methylate short RNA's that correspond to the 5′ end of SeV mRNA (43). The ability to functionally separate a domain of the SeV L is consistent with studies of measles virus (MV), in which the coding sequence of green fluorescent protein was inserted at two positions within L protein (17). The resulting polymerase was functional, suggesting that the MV L protein folds and functions as a series of independent globular domains (17).
The NNS RNA viruses include some of the most significant human, animal and plant pathogens extant. For many of these viruses there are no vaccines or efficacious antiviral drugs. The development of effective vaccines against such viruses is an ongoing need.

Attenuated nonsegmented negative-sense RNA viruses with reduced mRNA cap methyltransferase activity comprising mutations within conserved domain VI of the large polymerase

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