The present invention provides for the treatment or prevention of Hepadnaviridae infection and disease caused by Hepadnaviridae infection. In particular, the invention provides compositions and methods that affect the ability of Hepadnaviridae to utilize the host's cellular machinery as part of the virus' lifecycle. The invention relates to the discovery that interfering with the normal ability of viruses to utilize the host cell machinery with LSD1 inhibitors reduces HBV replication. Thus, the treatment and prevention of Hepadnaviridae infection and disease caused by Hepadnaviridae according to the invention comprises administering to an individual in need of treatment, a therapeutically effective amount of a LSD1 inhibitor. The individual in need of treatment can be a human or, e.g., another mammal.

Viral infection of humans is a major health problem. Combating viral infection has proven to be highly effective in some cases like smallpox where the disease was essentially eradicated with the advent of the smallpox vaccination. Other viral infections have been much more difficult to fight. Hepatitis B and C, human immunodeficiency virus (HIV), and herpes viruses are just a few prominent members of a list of viruses that pose significant health threats worldwide. Treatments available for these viruses are associated with adverse side-effects. In some cases the viruses mutate and become resistant to a particular treatment. Accordingly, there is a clear need for new antiviral treatments.
Hepatitis virus B (HBV) is estimated to be responsible for approximately 4000-5000 deaths each year in the United States alone. The problem is substantially greater in the rest of the world and accounts for about 1 million deaths worldwide each year.
According to the Center for Disease Control, about one in twenty people in the United States will get infected with HBV. About two billion people worldwide have been infected with HBV, and 350 million of those have chronic infection. It is estimated that upwards of 10% of the population of the developing world (large parts of Asia, the Pacific, and sub-Saharan Africa) are chronically infected with HBV. Chronically infected individuals are at a much greater risk for hepatocellular carcinoma (liver cancer) and cirrhosis of the liver. Liver cancer caused by HBV is one of the leading causes of death in men by cancer in the developing world. By any analysis, HBV is one of the more serious health problems facing the world. HBV is transmitted by contact with blood or other body fluids of an infected person and is similar to the human immunodeficiency virus in that sense, but it is about two orders of magnitude more infectious than HIV. The main paths of transmission are from mother to infant at birth, child-to-child, unsafe injections and transfusions, and unsafe sexual contact.
HBV was probably first reported in the late 19th century in shipyard workers in Bremen who had been vaccinated against smallpox. Over the next one hundred years the association of hepatitis with the use of needles and syringes used for treating diseases like syphilis, diabetes, and the administration of vaccines for yellow fever, led scientists to discover HBV. Eventually a vaccine was developed from a viral envelope protein that was purified from the plasma of individuals with a chronic HBV infection. Later, a recombinant system was used to produce the protein used in the vaccines because the original source of the vaccine was those individuals infected with HBV and this same population was at high-risk for HIV infection.
The HBV vaccine was shown to be about 95% effective in preventing chronic infection in individuals if they were not previously infected. Unfortunately, the HBV vaccine does not cure the disease and there is a need from new treatments.
HBV is a circular DNA virus with double stranded and single stranded DNA with a genome of about 2300 nucleotides long for the full length strand and from about 1700-2800 nucleotides long for the short length strand.
After cell entry via attachment of HBV to host receptors and endocytosis, relaxed circular HBV DNA is transported to the nucleus where it is "repaired" to form covalently closed circular DNA (cccDNA). HBV DNA is replicated through an RNA intermediate.
This discovery now provides an entirely new class of HBV antivirals useful for treating and preventing HBV infection and related diseases like viral hepatitis and liver cancer.
One long standing difficult goal in antiviral research has been the search of host cell factors that can be target for treating and preventing viral infection.
A group of enzymes known as lysine methyl transferases and lysine demethylases are involved histone lysine modifications. One particular human lysine demethylase enzyme called Lysine Specific Demethylase-1 (LSD1) was recently discovered (Shi et al. (2004) Cell 119:941) and shown to be involved in histone lysine methylation. LSD1 has a fair degree of structural similarity, and amino acid identity/homology to polyamine oxidases and monoamine oxidases, all of which (i.e., MAO-A, MAO-B and LSD1) are flavin dependent amine oxidases which catalyze the oxidation of nitrogen-hydrogen bonds and/or nitrogen carbon bonds. Although the main target of LSD1 appears to be mono- and di-methylated histone lysines, specifically H3K4 and H3K9, there is evidence in the literature that LSD1 can demethylate methylated lysines on non-histone proteins like p53, E2F1, Dnmt1 and STAT3.
Several groups have reported LSD1 inhibitors in the literature. Sharma et al. recently reported a new series of urea and thiourea analogs based on an earlier series of polyamines which were shown to inhibit LSD1 and modulate histone methylation and gene expression in cells (J. Med. Chem. 2010 PMID: 20568780 [PubMed—as supplied by publisher]). Sharma et al. note that "To date, only a few existing compounds have been shown to inhibit LSD1." Some efforts were made to make analogs of the histone peptide that is methylated by the enzyme, other efforts have focused on more small molecule like molecules based on known MAO inhibitors. Gooden et al. reported trans-2-arylcyclopropylamine analogues that inhibit LSD1 with Ki values is the range of 188-566 micromolar (Gooden et al. ((2008) Bioorg. Med. Chem. Let. 18:3047-3051)). Most of these compounds were more potent against MAO-A as compared to MAO-B. Ueda et al. ((2009) J. Am. Chem. Soc. 131 (48): 17536-17537) reported cyclopropylamine analogs selective for LSD1 over MAO-A and MAO-B that were designed based on reported X-ray crystal structures of these enzymes with a phenylcyclopropylamine-FAD adduct and a FAD-N-propargyl lysine peptide. The reported IC50 values for phenylcyclopropylamine were about 32 micromolar for LSD1 whereas as compounds 1 and 2 had values of 2.5 and 1.9 micromolar respectively.
Importantly, studies have also been conducted on amine oxidase inhibitor compounds to determine selectivity for MAO-A versus MAO-B since MAO-A inhibitors can cause dangerous side-effects (see e.g., Yoshida et al. (2004) Bioorg. Med. Chem. 12(10):2645-2652; Hruschka et al. (2008) Biorg Med. Chem. (16):7148-7166; Folks et al. (1983) J. Clin. Psychopharmacol. (3)249; and Youdim et al. (1983) Mod. Probl. Pharmacopsychiatry (19):63).
Currently the treatments available for HBV and related diseases have serious drawbacks. There is a need for new drugs for these diseases that target novel points of intervention in the disease processes and avoid side-effects associated with certain targets.

Lysine demethylase inhibitors for diseases and disorders associated with


In a method for broadcasting account provisioning information, user datum encryption information is transmitted to a plurality of account processing systems. A request to share account provisioning information is received from a user device associated with an account holder. A user datum of the account holder is encrypted using the encryption information and transmitted to the account processing systems. A response is received from at least one of the account processing systems, the response including an indication that the account holder has a transaction account processed by that account processing system. A request for confirmation that the account provisioning information should be shared is sent to the user device and a confirmation response is received from the user device that includes permission to share account provisioning information. Account provisioning information is then transmitted to one or more of the account processing systems.

There are many instances where a user having a primary identification card, transaction card, or other primary account wishes to provide data relating to this primary account to administrators/processors of other accounts. Card account holders, for example, often have a number of separate accounts administered by various entities. When a card account holder wishes to provide provisioning information for the holder's card account (or other primary user account) to these entities, the card account holder generally is required to log into the account processing system for each entity and manually enter the card account provisioning information. Some card account administrators may facilitate this to a certain extent by giving their card holders the option of stepping through a list of account processing entities and identifying those that the card holder wishes to have provisioned with card account information. This approach still has the drawback that, for each entity, the card account holder must be taken through the entity's login process. The resulting process is not only time-consuming, it requires the account holder to provide login credentials for every entity.

System and method for facilitating account provisioning


A card shuffling device includes a top surface, a card receiving area for receiving an initial set of playing cards, a randomizing or arranging system for the initial set of playing cards, a collection surface in a card collection area for receiving randomized playing cards, the collection surface receiving cards positioned so that all cards collected are below the top surface of the device, and an elevator for raising the collection surface so that at least some randomized cards are elevated above the top surface of the device. An automatic card shuffler includes a microprocessor with memory. An automated calibration system is provided that calibrates the precise position of the card supporting platform in the elevator so that precise insertion of cards can be performed during card handling procedures. A preferred method operates by a position of the elevator being randomly selected and the support surface is moved to the selected position, and after the gripping arm grasps at least one side of the cards, the elevator lowers, creating a space beneath the gripping arm, wherein a card is moved from the infeed compartment into the space, thereby randomizing the cards.

1. Field of the Invention
This invention relates to shuffling and sorting apparatus for providing randomly arranged articles and especially to the shuffling of playing cards for gaming uses. The invention also relates to a method and apparatus for providing randomly shuffled deck(s) of cards in a rapid and efficient manner and a capability of automatically calibrating the apparatus for various cards sizes, card thicknesses, and for initial setup.
2. Background of the Art
In the gaming industry, certain games require that batches of randomly shuffled cards be provided to players and sometimes to dealers in live card games. It is important that the cards are shuffled thoroughly and randomly to prevent players from having an advantage by knowing the position of specific cards or groups of cards in the final arrangement of cards delivered in the play of the game. At the same time, it is advantageous to have the deck(s) shuffled in a very short period of time so that there is minimal down time in the play of the game.
Johnson et al., U.S. Pat. No. 5,944,310 (assigned to Shuffle Master, Inc., assignee of the present application) describes a card handling apparatus comprising: a loading station for receiving cards to be shuffled; a chamber to receive a main stack of cards; delivery means for delivering individual cards from the loading station to the chamber; a dispensing station to dispense individual cards for a card game; transfer means for transferring a lower most card from the main stack to the dispensing station; and a dispensing sensor for sensing one of the presence and absence of a card in the dispensing station. The dispensing sensor is coupled to the transfer means to cause a transfer of a card to the dispensing station when an absence of a card in the dispensing station is sensed by the dispensing sensor. Individual cards delivered from the loading station are randomly inserted by an insertion means into different randomly selected positions in the main stack to obtain a randomly shuffled main stack from which cards are individually dispensed. The insertion means includes vertically adjustable gripping means to separate the main stack into two spaced apart sub-stacks to enable insertion of a card between the sub-stacks by the insertion means. The gripping means is vertically positionable along the edges of the main stack. After gripping, the top portion of the stack is lifted, forming two sub-stacks. At this time, a gap is created between the stacks. This shuffler is marketed under the name QUICKDRAW® shuffler in the United States and abroad.
Similarly, Johnson et al., U.S. Pat. No. 5,683,085 (also assigned to Shuffle Master, Inc.) describes am apparatus for shuffling or handling a batch of cards including a chamber in which a main stack of cards are supported, a loading station for holding a secondary stack of cards, and a card separating mechanism for separating cards at a series of positions along the main stack. The separating mechanism allows the introduction of cards from the secondary stack into the main stack at those positions. The separating mechanism grips cards at the series of positions along the stack and lifts those cards at and above the separation mechanism to define spaces in the main stack for introduction of cards from the secondary stack.
U.S. Pat. No. 5,676,372 describes an automated playing card shuffler, comprising: a frame; an unshuffled stack holder for holding an unshuffled stack of playing cards; a shuffled stack receiver for holding a shuffled stack of playing cards; at least one ejector carriage mounted adjacent to said unshuffled stack holder, said at least one ejector carriage and said unshuffled stack holder mounted to provide relative movement between said unshuffled stack holder and said at least one ejector carriage; a plurality of ejectors mounted upon said at least one ejector carriage adjacent the unshuffled stack holder, for ejecting playing cards from the unshuffled stack, the ejecting occurring at various random positions along the unshuffled stack.
Breeding et al., U.S. Pat. Nos. 6,139,014 and 6,068,258 (assigned to Shuffle Master, Inc.) describe a machine for shuffling multiple decks of playing cards in a batch-type process. The device includes a first vertically extending magazine for holding a stack of unshuffled playing cards, and second and third vertically extending magazines each for holding a stack of cards, the second and third magazines being horizontally spaced from and adjacent to the first magazine. A first card mover is positioned at the top of the first magazine for moving cards from the top of the stack of cards in the first magazine to the second and third magazines to cut the stack of unshuffled playing cards into two unshuffled stacks. Second and third card movers are at the top of the second and third magazines, respectively, for randomly moving cards from the top of the stack of cards in the second and third magazines, respectively, back to the first magazine, thereby interleaving the cards to form a vertically registered stack of shuffled cards in the first magazine. Elevators are provided in the magazines to bring the cards into contact with the card movers. This shuffler design is currently marketed under the name MD-1™ shuffler and MD1.1™ shuffler in the United States and abroad.
Sines et al. U.S. Pat. No. 6,019,368 describes a playing card shuffler having an unshuffled stack holder that holds an infeed array of playing cards. One or more ejectors are mounted adjacent the unshuffled stack holder to eject cards from the infeed array at various random positions. Multiple ejectors are preferably mounted on a movable carriage. Extractors are advantageously used to assist in removing playing cards from the infeed array. Removal resistors are used to provide counteracting forces resisting displacement of cards, to thereby provide more selective ejection of cards from the infeed array. The automated playing card shuffler comprises a frame; an unshuffled stack holder for holding an unshuffled array of playing cards in a stacked configuration with adjacent cards in physical contact with each other and forming an unshuffled stack; a shuffled array receiver for holding a shuffled array of playing cards; at least one ejector for ejecting playing cards located at different positions within the unshuffled stack; and a drive which is controllable to achieve a plurality of different relative positions between the unshuffled stack holder and the at least one ejector. This shuffler design is currently marketed under the name Random Ejection Shuffler™ shuffler.
Grauzer et al., U.S. Pat. No. 6,149,154 (assigned to Shuffle Master, Inc.) describes an apparatus for moving playing cards from a first group of cards into plural groups, each of said plural groups containing a random arrangement of cards, said apparatus comprising: a card receiver for receiving the first group of unshuffled cards; a single stack of card-receiving compartments generally adjacent to the card receiver, said stack generally adjacent to and movable with respect to the first group of cards; and a drive mechanism that moves the stack by means of translation relative to the first group of unshuffled cards; a card-moving mechanism between the card receiver and the stack; and a processing unit that controls the card-moving mechanism and the drive mechanism so that a selected quantity of cards is moved into a selected number of compartments. This shuffler is currently marketed under the name ACE® shuffler in the United States and abroad.
Grauzer et al., U.S. Pat. No. 6,254,096 (assigned to Shuffle Master, Inc.) describes an apparatus for continuously shuffling playing cards, said apparatus comprising: a card receiver for receiving a first group of cards; a single stack of card-receiving compartments generally adjacent to the card receiver, said stack generally vertically movable, wherein the compartments translate substantially vertically, and means for moving the stack; a card-moving mechanism between the card receiver and the stack; a processing unit that controls the card-moving mechanism and the means for moving the stack so that cards placed in the card receiver are moved into selected compartments; a second card receiver for receiving cards from the compartments; and a second card-moving mechanism between the compartments and the second card receiver for moving cards from the compartments to the second card receiver. This shuffler design is marketed under the name KING™ shuffler in the United States and abroad.
Johnson et al., U.S. Pat. No. 6,267,248 (assigned to Shuffle Master, Inc.) describes an apparatus for arranging playing cards in a desired order, said apparatus including: a housing; a sensor to sense playing cards prior to arranging; a feeder for feeding said playing cards sequentially past the sensor; a storage assembly having a plurality of storage locations in which playing cards may be arranged in groups in a desired order, wherein the storage assembly is adapted for movement in at least two directions during shuffling; a selectively programmable computer coupled to said sensor and to said storage assembly to assemble in said storage assembly groups of playing cards in a desired order; a delivery mechanism for selectively delivering playing cards located in selected storage locations of the storage assembly; and a collector for collecting arranged groups of playing cards. The storage assembly in one example of the invention is a carousel containing a plurality of card storage compartments.
Pending U.S. patent application Ser. No. 09/967,502 (also assigned to Shuffle Master, Inc.) describes a device for forming a random set of playing cards including a top surface and a bottom surface, and a card receiving area for receiving an initial set of playing cards. A randomizing system is provided for randomizing the initial set of playing cards. A collection surface is located in a card collection area for receiving randomized playing cards, the collection surface receiving cards so that all cards are received below the top surface of the device. An elevator is provided for raising the collection surface so that at least some randomized cards are elevated at least to the top surface of the device. A system for picking up segments of stacks and inserting cards into a gap created by lifting the stack is described.
Although these and other structures are available for the manufacture of playing card shuffling apparatus, new improvements and new designs are desirable. In particular, it would be desirable to provide a batch-style shuffler that is faster, provides random shuffling and which is more compact than currently available shuffler designs.

Card shuffling apparatus with automatic card size calibration


An induction-displacement neutral wall air terminal unit includes a housing defining a supply airflow path, a connected return airflow path, and a heating airflow path separated from the supply and return airflow paths by at least one interior wall. The unit also includes a plurality of induction-type nozzles located within the supply airflow path, that are deliver a ventilation air flow stream into the supply air flow path. The nozzles induce a return air flow stream through the return air flow path that mixes with the ventilation air flow stream to form a supply air flow stream delivered to a supply air outlet. A heating element is disposed within the heating airflow path to heat air within the heating air flow path. A plurality of fans may be placed within the heating airflow path to increase the overall heating capacity of the unit.

Displacement ventilation systems are in wide spread use in the HVAC industry. One particular application for such systems is in school buildings. Typically, a number of displacement air terminal devices will be located along a perimeter wall of a classroom space and are configured to deliver ventilation air to the space. The ventilation air is generally several degrees below the space set point temperature to ensure that the ventilation air effectively pools across the floor of the space. Due to the heat generated by the occupants and equipment in the space, the ventilation air is naturally drawn up by convection which ensures fresh air is continually delivered to the breathing zone of the occupants. The heated air continues to rise to the ceiling level where it can be removed from the space. Thus, those skilled in the art readily recognize the advantages of displacement ventilation air systems to both cool and ventilate a space in a highly efficient manner.
It is also known to configure displacement air terminal devices to have induction nozzles such that room air from the space can be conditioned, filtered, and returned to the space in a mixture with the ventilation air. This type of unit is sometimes referred to as an induction-displacement unit. One such unit is sold as the "Trox QLCI Displacement Terminal" and is available from Trox USA, Inc. of Alpharetta, Ga. A similar unit and system are described in U.S. Pat. No. 7,013,969 to Loudermilk, the entirety of which is hereby incorporated by reference herein. In this type of system, a coil is provided in the return air path of the induction-displacement unit to condition the return air, as necessary. In the cooling mode, the coil will reduce the return air temperature to a few degrees below the space temperature to match the temperature of the ventilation air. In the heating mode, the coil may be set to raise the temperature of the return air such that the delivered air has a higher temperature than that of the air in the room. In this mode a minimum space temperature set point can be maintained. However, in doing so, the induction-displacement unit can no longer function as a displacement terminal unit due to the fact that the delivered air starts rising as soon as it leaves the unit instead of pooling across the floor. To prevent the necessity of having to place an induction-displacement unit in the heating mode, a separate heating system can be provided in the space, such as fin-tube radiation or radiant panels. However, as the induction-displacement units are placed along at least one wall of the space, such heating systems cannot be placed in the same location. This is especially troublesome where the induction-displacement units are located along an exterior wall of the space because this is the location where heating is generally most needed. As such, improvements are desired for induction-displacement units that can simultaneously provide heating to an exterior wall of a space and provide displacement ventilation air to the space.

Displacement-induction neutral wall air terminal unit


To provide a laminate which has a heat sealing property, a barrier property and mechanical strength, of which elution of impurities from the surface to be in contact with a chemical solution is suppressed, and of which peeling and the like hardly occur at the sealed portion of a bag and at the interfaces between the layers of the laminate when exposed to high temperature, a bag using it and a lithium ion battery.

A laminate to be used for a bag containing a chemical solution (such as an electrolytic solution, a medical drug solution and a chemical solution for photolithography), such as an exterior of a lithium ion battery or a chemical solution bag is required to have, for example, the following properties.
It has a heat bonding property (hereinafter sometimes referred to as "heat sealing property") when the peripheries of the laminate are heat-sealed to form a bag.
It has a barrier property such that it hardly transmits specific substances (such as water vapor and oxygen).
It has a mechanical strength so as to protect the bag itself (that is, the bag is hardly broken e.g. by piercing).
As a laminate having such properties, for example, the following are proposed.
(1) A laminate for an exterior of a lithium ion battery, comprising acid-modified polypropylene layer (heat-sealable resin layer)/chemical conversion treatment layer (adhesive layer)/fluororesin layer (barrier layer)/chemical conversion treatment layer (adhesive layer)/aluminum foil (barrier layer)/chemical conversion treatment layer (adhesive layer)/urethane adhesive (adhesive layer)/polyamide layer (protective layer) (Patent Document 1).
(2) A laminate for a chemical solution bag comprising polypropylene layer (heat-sealable resin layer)/urethane adhesive (adhesive layer)/oxygen-scavenging resin layer (barrier layer)/urethane adhesive (adhesive layer)/ethylene-vinyl alcohol copolymer layer (barrier layer)/urethane adhesive (adhesive layer)/polyamide layer (protective layer) (Patent Document 2).

Abstract: A laminate 10 comprising a first layer 12 containing a fluororesin, a second layer 14 containing a barrier material, a third layer 16 containing a fluororesin and a fourth layer 18 containing a polyamide in this order, wherein each of the fluororesin in the first layer 12 and the fluororesin in the third layer 16 is a fluororesin having a melting point of from 160 to 230° C. and having adhesive functional groups.


A connecting rod is provided with a bent portion in a substantially middle part thereof so that a lower section of the connecting rod below the substantially middle part in a vertical direction may be inclined, with respect to the longitudinal direction of a guide rail, toward a center of an opening, and at the same time, an upper section of the connecting rod above the substantially middle part may be substantially in parallel to the longitudinal direction of the guide rail and offset from a side face of the guide rail directed to the center of the opening toward the center of the opening, when the connecting rod is in a position corresponding to a closed position of an open/close member.

1. Field of the Invention
The present invention relates to a actuating device for an open/close member of a vehicle.
2. Related Art
In a conventional actuating device for an open/close member of a vehicle, on each of vehicle pillars formed at both sides of an opening in a back part of a vehicle body which is adapted to be opened or closed by a rear gate which is pivotally mounted to a back end part of a vehicle roof by means of a substantially horizontal hinge shaft, there are provided a guide rail which is fixed to the vehicle body pillar in such a posture as inclined toward a center of the opening, a rack which is guided by the guide rail in a vertical direction, that is, in a longitudinal direction of the guide rail, a motor unit for moving the rack in the vertical direction, and a connecting rod extending in a vertical direction which is connected at its upper end to the rear gate by means of a universal joint, and connected at its lower end to the rack by means of a universal joint. The rack is moved in the vertical direction along the longitudinal direction of the guide rail thereby to displace the rear gate from a closed position to an open position or from the open position to the closed position (See Japanese Patent Application No. JP-A-2001-253241, for example).
In the actuating device for the open/close member of the vehicle as described above, the opening formed in the back part of the vehicle is generally in a trapezoidal shape. For this reason, it has been necessary to arrange the guide rail for guiding the connecting rod at such a position that it may protrude from the vehicle pillar toward the opening to a large extent, so that a part of the connecting rod may not interfere with a side edge of the vehicle pillar which defines the opening, on occasion of moving the connecting rod for displacing the rear gate to the open position. In case where the guide rail has been arranged in this manner, the guide rail will protrude from the vehicle body pillar toward the opening to a large extent, when the rear gate is opened, which results in a problem that an appearance of the vehicle may be deteriorated and an opening width of the opening may be made narrow.

Actuating device for open/close member of vehicle


Devices, systems and methods for a portable printer are provided. An example disclosed printer includes a housing defining a ribbon receiving area, wherein the ribbon receiving area is configured to receive a ribbon cartridge comprising a cartridge frame structured to support a supply spool, a take-up spool, and a ribbon extending between the supply spool and the take-up spool; and a printhead support extending from the housing for receiving a printhead, wherein the printhead support defines first and second channels disposed on opposite sides of the printhead, and wherein each of the first and second channels is structured to receive at least part of the cartridge frame.

In some applications, it is beneficial to provide a portable printer. For example, portable printers may be beneficial for retail stores. These stores often provide all incoming goods with labels for inventory purposes. It is often easier to relocate a printer than the merchandise. In addition to portability, the stores often desire that the printer be able to produce quality prints and be acquired at an affordable price. Meeting all of these requirements presents several obstacles that printer manufacturers may have to overcome in order to produce a marketable product. Stores may also be interested in labeling shelves or inventory locations with prices or customer information, or possibly more permanent information, such as location. Some of those shelves and inventory locations may be outside, inside a cooler, or near a window or special lighting source. These conditions create additional requirements for the printer and the printed output that manufacturers must overcome.
Beyond stores, other labeling and tracking applications may also require a portable printer. Labeling large items, such as oil field equipment, furniture, or utility fixtures is often best done without moving the item to be labeled. Military supplies, and their containers, are often labeled at remote locations or while in transit. Materials that are hazardous, explosive, or fragile are often labeled without being moved. Items delivered by truck, rail, air, sea container, and even bicycle may need to be labeled in the field. These applications require high quality, durable labels, tags, wristbands, or receipts from a portable printer. Depending on the application, the diverse user of the printer may be a young retail associate, a U.S. Marine, or an oil field worker. The printer could be used in a refrigerated warehouse, an air conditioned department store, an urban delivery route, or a desert war zone. This variety of uses, users, and locations also create additional requirements for the printer and the printed output.
Applicant has identified a number of deficiencies and problems associated with the manufacture, operation, and use of portable printers. Through applied effort, ingenuity, and innovation, Applicant has solved many of these identified problems by developing a solution that is embodied by the present invention, which is described in detail below.

Portable printer with support for receiving ribbon cartridge


An apparatus and method for non-intrusive collection of off-gas data in a steelmaking furnace includes structure and steps for transmitting a laser beam through the off-gas produced by a steelmaking furnace, for controlling the transmitting to repeatedly scan the laser beam through a plurality of wavelengths in its tuning range, and for detecting the laser beam transmitted through the off-gas and converting the detected laser beam to an electrical signal. The electrical signal is processed to determine characteristics of the off-gas that are used to analyze and/or control the steelmaking process.

Conventional control technology in the steelmaking industry relies on static computer models, e.g., feed-forward heat and material balance computer models. The composition and weight of starting materials (e.g., pig iron, scrap steel, oxygen, fluxes, etc.) are input to the model, and oxygen flow rate and blowing time are calculated by the model. Due to the unknown composition of the scrap steel, significant inaccuracies occur in achieving the desired endpoint concentration of carbon and melt temperature in the final steel product. However, no practical real-time method is conventionally available for monitoring process characteristics of the steelmaking process, and therefore no dynamic control of a process can be performed.
The unavailability of real-time process monitoring and dynamic process control causes significant safety and efficiency problems for current steelmaking processes, such as the basic oxygen process. This process combusts oxygen with carbon contained in molten metal to transform the molten metal to steel. Safe and efficient transformation requires that process variables be controlled to maintain certain process characteristics (e.g., temperature and concentrations of CO, CO.sub.2, and H.sub.2 O) at preferred or optimum values. Since there presently is no on-line, real-time method to measure or monitor these process characteristics, dynamic adjustments cannot be made to ensure maximum safety and efficiency.
More particularly, current commercial methods for producing steel using the basic oxygen process involve transforming starting materials containing a relatively high carbon content (up to about 4 wt %) by blowing high velocity oxygen into the starting materials in a batch process called a "heat." The oxygen combusts with carbon contained in the starting materials to decrease the carbon content, resulting in steel containing carbon at levels of 0.03 to 0.6 wt %, depending on the desired alloy. The starting materials include molten metal and flux (collectively referred to as the "bath"), and during the steelmaking process they form both melt and slag phases in a furnace.
The process is carried out in a basic oxygen furnace (BOF), which includes a large vessel with a refractory lining for containing the bath, an oxygen lance for blowing oxygen into the bath, and exhaust ducts for removing gases produced by the steelmaking process. These gases are collectively referred to as the off-gas. One of the principal gases produced by the process is carbon monoxide (CO)--the primary reaction product of oxygen and carbon. A variety of schemes exist to further react this CO with oxygen prior to its exit from the furnace, to form carbon dioxide (CO.sub.2). This post-combustion reaction of CO and oxygen is highly exothermic, and therefore it releases heat to both the slag and the melt phases in the furnace. This additional heat accelerates the steel conversion process.
A significant problem with commercial steelmaking is making efficient use of the CO, i.e., efficiently controlling post-combustion of CO, which requires proper control of the oxygen flow rate. If insufficient oxygen is injected, then the maximum effective use of CO is not achieved. On the other hand, if too much oxygen is injected, then the process is not cost effective because oxygen is wasted and the off-gas becomes too hot, deleteriously affecting the refractory lining and the exhaust duct walls. Conventionally, post-combustion of CO is monitored in a time-averaged fashion using commercially-available mass spectrometry (MS) or non-dispersive infrared absorption (NDIR) methods. These methods require that a sample of the off-gas be extracted, cooled, and analyzed, and therefore there is a significant time delay in acquiring data. Some indication of post-combustion gas concentrations may also be derived by monitoring wall and cooling water temperatures in the exhaust ducting using standard thermocouple technology. However, this technique is severely limited in sensitivity, accuracy, and response time. This lack of on-line, real-time measurement of CO and CO.sub.2 concentrations in the off-gas prevents efficient control of the oxygen flow rate in conventional steelmaking processes to ensure optimal post-combustion of CO.
Another major problem with current commercial steelmaking methods is the lack of an on-line method to provide continuous, real-time data on the carbon content of the metal. In many commercial steel mills, the carbon endpoint concentration is determined by stopping the process at the predicted endpoint, extracting a sample of the molten steel, and performing an offline chemical analysis. Another technique involves using "sensor lance" technology, which requires the lowering of a water-cooled lance equipped with an expendable sensor into the furnace. The expendable sensor is immersed in the liquid steel near the predicted endpoint of oxygen blowing, a metal sample is extracted, and the cooling curve of the sample is measured. This cooling curve can then be related to the carbon concentration of the steel. Both of these methods yield only a single data point per heat rather than continuous data.
Other methods for carbon endpoint verification use MS or NDIR absorption methods to determine CO and CO.sub.2 concentrations in the exhaust gas after it has been cooled and particulates have been removed. These methods require the use of an off-gas treatment system to treat the gas, and such a system requires extensive maintenance.
As a result of the lack of continuous data, steelmakers sometimes resort to a technique in which a heat is "blown flat" to ensure that the molten metal has been adequately decarburized. The "blown flat" technique uses excess oxygen to reduce the carbon concentration in the melt down to the lower limit of the desired range, i.e., 0.03 wt %. After the vessel is tapped and the steel is transferred to a ladle, the carbon concentration is adjusted back up to the desired level by adding material in the ladle.
However, this process is inefficient for several reasons. First, excess oxygen is used to ensure the complete oxidation of carbon in the melt, necessitating an additional expense. Second, the use of excess oxygen causes iron in the molten bath to begin to oxidize when the dissolved carbon has been reduced to very low concentrations. This oxidation results in a loss of iron, which should form a portion of the commercial product, to iron oxide that ends up in the slag phase. Finally, the process of blowing flat requires the expenditure of unnecessary additional processing time, thereby reducing throughput in the industrial process and consequently increasing costs and lowering profits.
Another significant problem with current steelmaking methods is the creation of a highly reactive, foaming slag layer when certain combinations of hot metal chemistry and flux additions are used, which causes ejection of large amounts of liquid slag from the BOF vessel during oxygen blowing (referred to as "slopping"). This slopping causes undesirable rapid slag build-up on the vessel mouth and exhaust hood surfaces, and increased skull build-up on the lance. Slopping can be controlled by adjusting the lance parameters (e.g., the lance height above the bath and the oxygen flow rate), but this is difficult to achieve automatically, since current steelmaking techniques cannot detect the amount of liquid slag being ejected from the furnace.
Yet another significant difficulty with current steelmaking methods results from the presence of a large amount of water in the furnace. A large amount of water in the furnace causes rapid formation of molecular hydrogen at the melt surface, thereby creating a major safety hazard due to the risk of an explosion. The presence of excess water may be caused by unwanted leaks of cooling water from a water-cooled oxygen lance or water-cooled off-gas exhaust ducts. Conventionally, the potential for hydrogen formation in the steel conversion furnace is determined by monitoring input and output cooling water flows through the oxygen lance and an exhaust hood system. Large discrepancies or sudden changes in flow rates could indicate dangerous leaks into the furnace vessel. However, while water flow monitoring may indicate the source of water that may cause dangerous levels of hydrogen, this method does not indicate the levels of hydrogen actually present, and therefore this method fails to offer adequate safeguards against explosions.
In an effort to address the above-noted limitations of conventional monitoring techniques, research has been conducted on methods for sampling gas near the furnace mouth using water-cooled extractive probes. The extracted gas is then analyzed, either with Fourier transform infrared (FTIR) spectroscopy or mass spectrometry. The FTIR method provides a relatively real-time response for measuring gas-phase concentration, as compared with the methods described above. However, an extractive probe has a limited life due to its location above the furnace mouth. Further, the off-gas temperature is measured in this technique by a thermocouple located in the extraction probe, and such thermocouples have slow response times.
Accordingly, an improved monitoring method is needed that can provide real-time, continuous data about off-gas characteristics using a reliable, non-intrusive method.

Method and apparatus for off-gas composition sensing


This invention relates to a new parameter suitable for use in non-intrusive speech quality assessment system. The invention provides a method of generating a parameter from a signal comprising a sequence of values measured from voiced portions of said signal at a sampling frequency, said parameter suitable for use in a quality assessment tool. The method includes steps of selecting portions of frequency transformed sections of the signal in dependence upon a pitch estimate; generating an average value for each portion; and generating a section parameter depending upon the difference between the averages of successive portions. Said section parameter is averaged over a number of iterations of the method to generate the new parameter of the invention.

This application claims the benefit of United Kingdom Patent Application No. 0326043.7, filed Nov. 7, 2003, the entirety of which is incorporated herein by reference.
This invention relates to a new parameter suitable for use in non-intrusive speech quality assessment system.
Signals carried over telecommunications links can undergo considerable transformations, such as digitisation, encryption and modulation. They can also be distorted due to the effects of lossy compression and transmission errors.
Objective processes for the purpose of measuring the quality of a signal are currently under development and are of application in equipment development, equipment testing, and evaluation of system performance.
Some automated systems require a known (reference) signal to be played through a distorting system (the communications network or other system under test) to derive a degraded signal, which is compared with an undistorted version of the reference signal. Such systems are known as "intrusive" quality assessment systems, because whilst the test is carried out the channel under test cannot, in general, carry live traffic.
Conversely, non-intrusive quality assessment systems are systems which can be used whilst live traffic is carried by the channel, without the need for test calls.
Non-intrusive testing is required because for some testing it is not possible to make test calls. This could be because the call termination points are geographically diverse or unknown. It could also be that the cost of capacity is particularly high on the route under test. Whereas, a non-intrusive monitoring application can run all the time on the live calls to give a meaningful measurement of performance.
A known non-intrusive quality assessment system uses a database of distorted samples which has been assessed by panels of human listeners to provide a Mean Opinion Score (MOS).
MOSs are generated by subjective tests which aim to find the average user's perception of a system's speech quality by asking a panel of listeners a directed question and providing a limited response choice. For example, to determine listening quality users are asked to rate "the quality of the speech" on a five-point scale from Bad to Excellent. The MOS, is calculated for a particular condition by averaging the ratings of all listeners.
In order to train the quality assessment system each sample is parameterised and a combination of the parameters is determined which provides the best prediction of the MOSs indicted by the human listeners. International Patent Application number WO 01/35393 describes one method for paramterising speech samples for use in a non-intrusive quality assessment system.
This invention relates to improved parameters for a speech quality assessment system.
According to the invention there is provided a method of generating a parameter from a signal comprising a sequence of values measured from voiced portions of said signal at a sampling frequency, said parameter suitable for use in a quality assessment tool, said method comprising the steps of                a) selecting a section of said signal;        b) performing a frequency transform on said section to provide a sequence of frequency values;        c) generating a pitch frequency estimate;        d) selecting a plurality of portions of said sequence of frequency values in dependence upon said pitch frequency estimate, said portions having a frequency range and a central frequency;        e) generating an average value for each of said plurality of portions;        f) generating a section parameter in dependence upon the difference between the average value for one portion of said sequence of frequency values and the average value for a subsequent portion of said sequence of frequency values;        g) repeating steps a)-f) to provide a plurality of said section parameters and generating said parameter by generating an average in dependence upon said plurality of said section parameters.
Said section of said sequence of values may be selected such that a pitch mark is associated with a value central to said section.
The frequency transform may comprise a Fast Fourier Transform.
The step of generating a pitch frequency estimate may comprise the steps of using pitch marks associated with said sequence of values; comparing the number of values between a value associated with a pitch mark and a value associated with an immediately preceding pitch mark with the number of values between the value associated with the pitch mark and a value associated with an immediately following pitch mark; and generating said pitch frequency estimate in dependence upon the minimum number of said values, and the sampling frequency.
The portions of said sequence of frequency values may be selected by generating multiples of said pitch frequency estimate, said multiples representing harmonics of said pitch frequency estimate; and selecting portions in which the frequency range of the portion is substantially equal to half said pitch frequency estimate; and which the central frequency of each portion is either a frequency substantially equal to one of said multiples, or a frequency substantially half way between two of said multiples.
The invention also provides a method of training a quality assessment tool comprising the step of training a mapping for use in a method of assessing speech quality in a telecommunications network, such that a fit between a quality measure generated from a plurality of parameters for a signal and the mean opinion score associated with said signal is optimised by said mapping wherein said plurality of parameters includes a parameter generated according to any on of the preceding claims.
The invention also provides a method of assessing speech quality in a telecommunications network comprising the steps of generating a parameter according to any one of the preceding claims; generating a quality measure in dependence upon said parameter.
Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:


The present invention pertains to methods to promote outgrowth of, or extension across a substrate of, neuronal cells by inhibiting the interaction between the cytoplasmic tail of the L1-CAM cell surface adhesion molecule and the cytoskeletal protein ankyrin. The invention also pertains to a method to treat diseases characterized by axonal damage such as spinal cord injury, traumatic brain injury, stroke, and neurodegenerative disease by administration of novel peptides that inhibit the binding of the L1-CAM cytoplasmic tail to ankyrin, and to pharmaceutical compositions comprising such peptides. The invention further pertains to a method of blocking calcium flux to protect against neural cell death following stroke or traumatic head injury.

The adhesion and migration of adherent cells depends on the function of cell-surface glycoproteins that mediate the adhesive contact between the cell surface and molecules in the cellular microenvironment. In quiescent, non-migratory cells, adhesion receptors are responsible for maintaining stable contact between the cell and its environment. As cells translocate, adhesion proteins transduce traction forces from the cytoskeleton across the cytoplasmic membrane to the substrate, permitting cells to pull against their environment. Thus, receptor-mediated traction-force generation depends on connections between adhesion receptors and the cytoskeleton. In addition, receptor-cytoskeleton interactions play a crucial role in the stabilization of adhesive complexes thus modulating binding avidity.
The establishment and maintenance of neuronal connections are essential features of nervous system function. The activity of adhesion proteins on the cell surface is essential to both of these processes. During development, the translocation of the neuronal growth cone depends critically on adhesion proteins that mediate the recognition of molecules in the extracellular environment (Tessier-Lavigne and Goodman. Science 1986;274:1123-1133). In the adult, many of the same adhesion proteins help maintain axon fascicles and synaptic contacts. Whereas receptors involved in adhesive contacts mediate largely static connections between adjacent cells, adhesion receptors in migrating cells serve to elaborate cellular traction forces between the cell and its environment (Harris et al. Science 1980;208: 177-179 and Galbraith and Sheetz J. Cell Biol 1999; 147:1313-1324). A variety of adhesion receptor families have been shown to serve as receptors for permissive, substrate-bound molecules that promote axon outgrowth, including integrins, Ig-CAM's and cadherins (Kamiguchi and Yoshihara J. Neurosci 2001;21:91941-9203). This common activity raises the possibility of a common traction-based mechanism for transducing permissive cues. However, while the biophysical basis of integrin-mediated traction-force generation and adhesion is fairly well characterized (Felsenfeld et al. Nature 1996;383:438-440; Choquet et al. Cell 1997;88:39-48; Galbraith and Sheetz. Proc Natl Acad Sci USA 1997;94:9114-9118; and Yauch et al. J Exp Med 1997;186:1347-1355), little is known about the differential regulation of adhesion and migration in other families of adhesion receptors.
Immunoglobulin-family cell adhesion molecules (Ig-CAMs) have been implicated in the guided growth of neuronal processes during development (Kamiguchi and Lemmon. Curr Opin Cell Biol 2000; 12:598-605 and Rutishauser J Cell Biol 2000; 149:757-760). In the vertebrate central nervous system, L1-CAM, an Ig-CAM, plays an essential role in the growth and guidance of axons towards their targets (Daline et al. Nat Genet 1997;17:346-349 and Cohen et al. Curr Biol 1998;8:26-33). L1-CAM mutations in humans lead to a variety of developmental defects including corpus callosum hyperplasia, mental retardation, adducted thumbs, spastic paraplegia and hydrocephalus (CRASH syndrome), suggesting that L1-CAM plays a crucial role in the development of the central nervous system (Fransen et al. Eur J Hum Genet 1995;3:273-284). Moreover, the capacity of substrate-immobilized L1-CAM-ligands to promote neurite extension in vitro through interactions with cell-surface L1-CAM (Lemmon et al. Neuron 1989;2:1597-1603; Kuhn et al. J Cell Biol 1991;115:1113-1126; and Felsenfeld et al. Neuron 1994; 12:675-690) raises the possibility that L1-CAM on the growth cone may mediate the generation of traction forces in a mechanism similar to that observed for integrins in other cell types. In addition, L1-CAM may play other roles in the development and maintenance of the nervous system, including the stabilization of axon fascicles in the mature animal (Dahme et al. Nat Genet 1997;17:346-349). To accomplish each of these diverse functions, the movement of L1-CAM in the plane of the membrane must be regulated across the cell surface.
The regulation of adhesion receptor distribution, movement, and function in adhesion and migration depends on the connection between these glycoproteins and components of the cytoskeleton. L1-CAM interacts with as many as four cytosolic binding partners through two discrete sites in the cytoplasmic tail (Kamiguchi et al. J Neurosci 1998; 18:5311-5321; Zhang et al. J Biol Chem 1998;273:30785-30794; Dickson et al. J Cell Biol 2002;157:1105-1112; and Kizhatil et al. J Neurosci 2002;22:7945-7958). The binding of L1-CAMs to members of the ankyrin family of cytoskeletal adaptor proteins is perhaps the best characterized of these interactions (Davis and Bennett J Biol Chem 1994;269:27163-27166; Garver et al. J Cell Biol 1997;137:703-714; and Hortsch et al. Cell Adhes Commun 1998;5:61-73). In vertebrates, three distinct genes encoding ankyrin family members, ankyrinB, ankyrinG and ankyrinR, have been identified with distinct but overlapping expression patterns (Bennett and Baines Physiol Rev 2001;81:1353-1392). In the nervous system and heart, ankyrins appear to play a crucial role in the organization of cellular structures involved in signaling (Lambert et al. J Neurosci 1997; 17:7025-7036 and Tuvia et al. J Cell Biol 1999; 147:995-1008). The L1-CAM family member neurofascin binds to ankyrin through a motif that is highly conserved among L1-CAM-family members near the carboxy-terminus of the cytoplasmic tail (Garver et al. J Cell Biol 1997; 137:703-714). The ankyrin binding site, mapped based on the interaction between neurofascin and ankyrinG, is comprised of a 12 amino acid motif, QFNEDGSFIGQY (SEQ ID NO: 1), which includes a carboxy-terminal tyrosine and is identical in neurofascin and L1-CAM from rat (Miura et al. FEBS Lett 1991;289:91-95 and Zhang et al. J Biol Chem 1998;273:30785-20794). Ankyrin binds to this motif in its dephosphorylated state (Garver et al., supra). In addition, when phosphorylated, this site serves as a binding partner for the protein doublecortin (Kizhatil et al., supra), a protein which has been implicated in the migration of neuronal progenitors to their proper lamina in the mature cerebral cortex (Francis et al. Neuron 1999;23:247-256 and Gleeson et al. Neuron 1999;23:257-271). Mutations at this site in human L1-CAM lead to a similar disruption in ankyrin binding (Needham et al. J Neurosci 2001;21:1490-1500). However, the drosophila L1-CAM homolog neuroglian, while requiring the FIGQY (SEQ ID NO: 8) motif for ankyrin recruitment, appears to be regulated primarily through ligation of the extracellular domain (Hortsch et al., supra). At a functional level, the binding of ankyrin to L1-CAMs like neurofascin plays a critical role in L1-CAM-mediated cell adhesion (Tuvia et al. Proc Natl Acad Sci USA 1997;94:12957-12962).
In addition to ankyrin binding, a distinct phosphorylation site (YRSLE; SEQ ID NO: 7) upstream of the ankyrin site binds both the μ2 chain of the AP-2 clathrin complex (Kamiguchi and Lemmon J Neurosci 1998;18:3749-3756 and Schaefer et al. J Cell Biol 2002; 157: 1223-1232) and ERM proteins (Dickson et al. J Cell Biol 2002; 157:1105-1112). The binding to AP-2 appears to play a critical role in the endocytosis and recycling of L1-CAM at the back of the growth cone, a process essential to the function of L1-CAM in growth cone migration (Kamiguchi and Yoshihara. J Neurosci 2001;21:9194-9203).
Axonal damage characterizes diseases such as spinal cord injury, traumatic brain injury, stroke, and neurodegenerative disease. Spinal cord injury affects millions of individuals worldwide, resulting in severe impairment of the physical function of affected persons (e.g., as seen in paraplegia and quadriplegia). Traumatic brain injury is a major health problem in all developed countries. Stroke is the second largest cause of death worldwide, and the main cause of long-term neurological disability. Neurodegenerative disease is of increasing concern with the aging of the population of the developed world. Currently available therapies are unable to repair the axonal damage. Therefore, the need exists in the art for therapies to repair neuronal damage, which therapies depend upon the ability to promote the outgrowth of spinal cord neurons to reestablish the damaged neuronal connections.
The outline of the sensory pathway is well known in the art. From the source of pain, pain messages move through peripheral sensory neurons and up the dorsal root ganglion of the spinal cord, where they stimulate interneurons in a relay destined for the brain. Pain messages can be blocked, enhanced, or modified at the relay between the peripheral neuron and the interneuron before progressing to the brain. From the spinal cord, the signal reaches the thalamus and cortex of the brain, where the location, intensity, and nature of the pain is decoded. Once the brain has interpreted the pain signal, the brain sends pain-suppressing chemicals to the pain source and triggers other related responses.
Neurotransmission between cells can be regulated by voltage-gated calcium channels, which mediate calcium influx in response to membrane depolarization. Voltage-dependent calcium channels are the primary trigger for electrically stimulated release of chemical transmitters in the nervous system that lead to stimulation of specific neuronal pathways. Electrical currents are used in neurons to rapidly transmit signals. All cells have a resting potential: an electrical charge across the plasma membrane, where the exterior of the cell is positive and the interior negative, due to the concentrations of different populations of charged ions. In neurons, voltage gated channels open or close in an "all-or-none" fashion in response to changes in the charge (measured in volts) across the plasma membrane of the cell. Activity- and receptor-dependent redistribution of ionotropic receptors has been widely studied in the post-synaptic density (Zhu J J et al., Cell. 2002 Aug. 23; 110(4): 443-55. Rao A, Craig A M., Neuron. 1997 Oct.; 19(4): 801-12.), but such studies have not previously been extended to proteins in the presynaptic active zones.
Dunlap and Fischbach (Dunlap K, et al. J. Physiol. 1981, 317: 519-5335) have suggested that transmitter-mediated shortening of the duration of the action potential could be due to a decrease in calcium conductance or a decrease in the number of functional channels in the membrane. Inhibition of Ca2+ channels can be voltage-dependent, and is mediated by G protein beta-gamma subunits (Ikeda S R. Nature. 1996 Mar. 21; 380(6571): 255-8.; Herlitze S, et al. Nature. 1996 Mar. 21; 380(6571): 258-62.). In addition, kinases such as protein kinase C and tyrosine kinases have been shown to inhibit Ca2+ channels (Hille B. Trends Neurosci. 1994 Dec.; 17(12): 531-6). Subsequent work has established that G protein-dependent inhibition of calcium current is in part a result of a decrease in the open probability of the channel, reducing current density (Delcour, Ah, and Tsien R W. 1993. Science February. 12, 259 (5097):989-4.). The idea that changes in channel density could underlie calcium channel modulation has not previously been tested. Alteration of a presynaptic calcium channel plasma membrane density to modulate calcium channel function will be useful in the control of neuronal signal propagation.
Chronic pain affects millions of individuals; it results in severe impairment of a patient's physical function and is often associated with psychological depression. Currently available therapies teach the use of analgesics to treat the symptoms of pain that result from the activation of pain pathways. These analgesics become less effective over time as patients become sensitized. Therefore, the need exists in the art for novel therapies for chronic pain that block pain pathway signals before they reach the brain.
Stroke and traumatic head injury result in similar pathological processes in the brain. In traumatic head injury, neurons die because they are crushed, setting off an inflammatory cascade that triggers further neuronal apoptosis. In stroke, the infarct results a similar cascade in the brain. Progressive inflammation and cell death downstream of the primary event is mediated by calcium flux across the neuronal cell membrane. Calcium flux through L type channels across the neuronal membrane and release from calcium stores leads to apoptosis. By blocking the calcium flux, one may block the cell death resulting from a or stroke traumatic head injury (Mattson M P, et al., Neuromolecular Med. 2003;3(2):65-94; Mody I, et al., Trends Pharmacol Sci. 1995; Oct.; 16(10):356-9; Zheng Z. et al., Curr Mol Med. 2003 Jun.;3(4):361-72). Thus, there exists in the art the need for novel methods to locally block calcium flux in the brain, in order to minimize apoptotic neuronal cell death immediately after stroke and traumatic head injury.

Peptides for treating axonal damage, inhibition of neurotransmitter release and pain transmission, and blocking calcium influx in neurons

Mount Sinai School of Medicine of New York University


An optical device includes a light source configured to provide a light beam. The optical device includes a light source configured to generate a light beam, and a spatial light modulator (“SLM”) configured to modulate the light beam to provide a hologram for generating a display image. The optical device includes a polarization-selective steering assembly configured to provide a plurality of steering states for the modulated light beam. The optical device includes an image combiner configured to focus the modulated light beam steered by the polarization-selective steering assembly to generate an array of spots at an eye-box of the optical device.

Holographic displays can provide natural monocular focus cues and a high resolution as well as vision-correction ability, making them strong candidates for near-eye displays ("NEDs"). Optical see-through holographic display is a key device for augmented reality ("AR") applications and mixed reality ("MR") applications. However, the limited bandwidth of spatial light modulator ("SLM") has been an important bottleneck of holographic display technology that limits performance. In particular, the limited SLM bandwidth imposes a critical trade-off between field of view ("FOV") and eye-box size for near-eye displays, because the product of the FOV and the eye-box size made by the system is often constant, which is determined by the size and pixel pitch of the SLM.
It is often desirable to have a large FOV in a holographic display to provide immersive user experience. However, enlarging the FOV may directly reduce the eye-box size. For example, the typical eye-box size of a commercially available 2k SLM is approximately 1 mm for a 60-degree FOV, and the pupil position of the user has to be fixed at a pinpoint, which is difficult for practical near-eye display applications. The disclosed near-eye display with pupil shifting and the disclosed method for pupil shifting are directed to solve one or more of the problems set forth above and other problems.

Holographic near-eye display having pupil steering


Resilient routing management approaches are provided based on primary/backup and failover/failback relationships in a clustered network environment, where each user and/or resource is assigned to a primary cluster and at least one backup cluster. A distributed handover mechanism enables global knowledge of primary/backup relationships between clusters and their assigned users or resources.

Fault tolerance and scalability are two important requirements for server based systems. In a typical system, a server owns resources (e.g. a user's log-in to the server or files stored on the server) and provides the ability to find a resource. For example a file server provides the ability for users to store files on the server and also provides the ability for a user to look up a file in the system. The latter operation requires the ability to find the file in the system given a unique file name. Traditional approaches to fault tolerance typically use the primary/backup failover/failback model to assign resources to clusters. In this architecture, there is typically a standby backup cluster that takes over from the primary cluster once the primary cluster becomes unavailable.
Enhanced communication systems providing multi-modal communications operate in a similar fashion to (sometimes the same) data exchange networks where designated servers and their backups provide services (e.g. routing of calls). Session Initiation Protocol (SIP) is a commonly used communication protocol between components of such systems. When primary-backup relationships are used to assign users to clusters of servers in an enhanced communication system, several challenges may have to be overcome. For example, when and how to assign a user to a primary cluster or its backup, communication between the primary and backup clusters to determine when the user is to be handed over to the backup and back to the primary cluster, and comparable ones.

Resilient routing for session initiation protocol based communication systems


A balloon catheter comprises a catheter shaft and a balloon carried on the shaft, an inflation lumen being provided. The balloon comprises a plurality of holes of a size to permit medication delivered through the lumen to pass outwardly through the holes. The balloon carries on an outer surface a substantially hydrophilic, tubular microporous membrane covering the holes, to break up streams of flowing medication.

In the prior art, for example Shockey et al. U.S. Pat. No. 4,994,033 and the C. R. Bard Inc. European Patent Application No. 383,429A2, published Aug. 22, 1990, a catheter is taught for the application of medication to a blood vessel wall, for example to a stenosis. The medication is administered through a balloon in the catheter which carries an array of minute holes or micropores, so that the medication may flow into the balloon through a lumen in the catheter, and then by the action of pressurization in the balloon it is forced out of the holes or micropores.
It has been found that at pressures of about two atmospheres and above, the velocity of fluid that passes out of the holes of such a balloon often can create a forceful stream which directly impinges the arterial wall. This, in turn, can actually cause tissue damage, even to the extent of extending and increasing a dissection within the arterial wall which is caused by an angioplasty procedure such as PCTA.
Thus there is a need for an infusion balloon catheter for administering medication to the arterial wall in which the medication can be administered under a reasonable pressure for rapid flow of medication out of a single perforated balloon, but the forceful streams are avoided, so that the fluid does not forcefully impinge against the arterial wall, but rather it diffuses out of the perforations in a substantial but non-damaging manner.
Baran U.S. Pat. No. 4,417,576 discloses a double-wall surgical cuff in which a surgical fluid such as an anesthetic may be inserted in a sponge rubber material emplaced between the two surgical cuffs. The outer surgical cuff is perforated, so that the surgical fluid can pass out outwardly through the outer surgical cuff, while the inner surgical cuff is not perforated. This relatively complex device may have a substantially increased outer diameter due to the presence of the two balloons and the sponge rubber, which restricts its entry into the smallest of arteries and the like.


A resilient track-tensioning device for tracked automotive vehicles has a track tensioning wheel arrangement (26) which includes a generally elongated pendular arm (38) which rotatably supports a track-tensioning wheel unit (62), a pretensioning or biassing arm (72) which is much shorter than the pendular arm and which has a first end-part for force transmission engagement with the pendular arm (38) at its end-part (74) that carries the track-tensioning wheel unit (62), and a second end-part for pivotal attachment to a carrier (20) through the medium of a pretensioning or biassing means (76). The device further includes an element (66) for adjustably fixing the distance between the rotational center of the track-tensioning wheel unit (62) and the attachment point (46) of the pendular arm (38). The invention also relates to a track support assembly which includes an inventive track-tensioning device.

In the case of a known articulated tracked vehicle unit comprising a front and a rear carriage which are pivotally connected together and each of which has two track support assemblies of essentially similar construction for driving an endless drive track or tread which runs around the track-support assembly includes a carrier, a so-called saddle beam, on which there is journalled a drive wheel unit, a plurality of carrier wheel units and a track tensioning wheel unit. The tensioning wheel unit on the track support assembly is positioned furthest to the rear of the saddle beam and is also required to function as a tensioning wheel, i.e. is required to be positionable in the longitudinal direction of the track support assembly so as to enable track tension to be adjusted, and also to function as a track carrier wheel so as to therewith minimize the pressure exerted by the track support assembly on the underlying ground surface. The carrier wheel units and the tensioning wheel unit are pivotally mounted on the saddle beam by means of pendular arms that are pretensioned or biassed by means of torsion springs such as to enable respective wheel units to move resiliently over ground irregularities. The pendular arm of the known tensioning wheel unit is shorter than the pendular arm of the carrier wheel units, meaning that the suspension of the tensioning wheel unit will be more rigid, i.e. less resilient, than the spring suspension of the carrier wheel units. This limits passenger and driver comfort when driving over rough country and also results in an unfavourable distribution of the pressure exerted on the ground beneath the tracks. Furthermore, a tensioning wheel unit that includes a relatively short pendular arm will result in wide variations in track stretch as the tensioning wheel unit springs back and forth (up and down). This is because the pendular arm of the tensioning wheel unit has relatively pronounced movement in the longitudinal direction of the track as the unit springs inwardly.

Resilient track tensioning device for track-driven vehicles and track unit comprising such a track tensioning device


A first output buffer having a large current driving capability and a second output buffer having a small current driving capability are connected in parallel between an input terminal and an external lead. The first and second output buffers each includes two CMOS inverters connected in series between the input terminal and the external lead. The P-channel and N-channel MOSFETs of the two CMOS inverters in the second output buffer have gate widths smaller than each of the P-channel and N-channel MOSFETs, respectively, of the two CMOS inverters in the first output buffer. Also disclosed is an output buffer having P-channel and N-channel MOSFETs arranged as a CMOS inverter, but with a base of a first bipolar transistor connected to a source of the N-channel MOSFET. An emitter of the first bipolar transistor is connected to ground and its collector is connected to an output of the output buffer. A base of a second bipolar transistor is connected to an output of the CMOS inverter and its emitter is connected to the output of the output buffer. An input of the output buffer is supplied to an input of the CMOS inverter. Another transistor is connected between the output of the output buffer and ground and is responsive to the input of the output buffer.

1. Field of the Invention
The present invention relates to an output buffer circuit particularly, but not exclusively, for a semiconductor integrated circuit device (LSI).
2. Description of the Related Art
FIG. 10 is a circuit diagram showing a construction of a conventional output buffer circuit. This output buffer circuit has been widely used in complementary metal oxide semiconductors (will as called as "CMOSs" hereinafter) using P-channel type metal oxide semiconductor field effect transistors (will be called as "P-channel type MOS field effect transistors" hereinafter) and N-channel type metal oxide semiconductor field effect transistors (will be called as "N-channel type MOS field effect transistors" hereinafter).
In FIG. 10, an output buffer circuit 10 includes first and second CMOS inverters I1 and I2. First CMOS inverter I1 includes a P-channel type MOS field effect transistor P1 and an N-channel type MOS field effect transistor N1. Second CMOS inverter I2 includes a P-channel type MOS field effect transistor P2 and an N-channel type MOS field effect transistor N2.
Transistor P1 is connected between a power supply terminal Vcc for receiving a positive power supply potential (e.g., +5 V) and an output node O1. Transistor N1 is connected between a ground terminal Gnd for receiving a grand potential (0 V) and an output node O1. Gates of transistors P1 and N1 are connected to an input terminal IN. Transistor P2 is connected between power supply terminal Vcc and an output terminal OUT. Transistor N2 is connected between ground terminal Gnd and output terminal OUT. Gates of transistors P2 and N2 are connected to output node O1.
Substrates (sources) of transistors P1 and P2 are connected to power supply terminal Vcc. Substrates (sources) of transistors N1 and N2 are connected to grand terminal Gnd.
Input terminal IN is connected to an internal circuit 2. Internal circuit 2 and an output buffer circuit 10 is formed on a semiconductor chip CH. Output terminal OUT is wire-bonded to an external lead (external output terminal) OL of a package PAC. External lead OL is connected to an external element 3 of other LSI.
"Li" indicates an inductance, which is parasitically accompanied to an aluminium wire and a package internal interconnection line. "CL" indicates an external load capacity existing between external lead OL and external element 3, and includes an input capacity of external element 3, an interconnection line capacity and a package capacity of package PAC.
An operation of output buffer circuit in FIG. 10 will be described below with reference to an operation waveform diagram of FIG. 11.
When an input signal of "H" (e.g., +5 V) is applied to input terminal IN, transistor P1 is cut off, and transistor N1 is turned on. Thereby, output node 01 is short-circuited to grand terminal Gnd through transistor N1, and an output signal of output node 01 becomes "L" (ground potential). Thus, transistor P2 is turned on, and transistor N1 is cut off. Thereby, an output signal of output terminal OUT becomes "H" (+5 V).
Conversely, when input signal of "L" (e.g., 0 V) is applied to input terminal IN, transistor P1 is turned on, and transistor N1 is cut off. Thereby, output node 01 is short-circuited to power supply terminal Vcc through transistor P1, and output signal of output node 01 becomes "H" (+5 V). Thus, transistor P2 is cut off, and transistor N2 is turned on. Thereby, the output signal of output terminal OUT becomes "L".
In this manner, the input signal applied to input terminal IN is delayed for a delay time of output buffer circuit 10, as shown in FIG. 11, and the output signal of the same polarity as the input signal is obtained at output terminal OUT.
In FIG. 11, an abscissa represents a time, and an ordinate represents a voltage. "IN" represents a waveform of the input signal at input terminal IN, and "OUT" represents a waveform of the output signal at output terminal OUT.
Propagation delay times of first and second CMOS inverters I1 and I2 in the conventional output buffer circuit described above are determined by charging/discharging times of a load capacitance (output capacitance), which is primarily formed of a stray capacitance of the circuit, an input capacitance of a gate at a subsequent stage and others. The charging/discharging times are proportional to a product of a value of output capacitance CL and a value of ON-resistance of transistor P2 or N2.
Therefore, assuming that output capacitance CL has a constant value, the delay time of the second CMOS inverter I2 is determined by the ON-resistance of transistor P2 or N2.
In the output buffer circuit for driving a large current, it is necessary to design transistor P2 or N2 to have a small ON-resistance. This reduces the charging or discharging time of output capacitance CL of the output buffer circuit, i.e., a rising or falling time of the output voltage, resulting in rapid rising or falling of the output voltage waveform.
In addition to output capacitance CL, inductance L1 is added to output terminal OUT. Further, undershoot is caused in the output waveform during the falling operation, and overshoot is caused in the output waveform during the rising operation, because an impedance of output buffer circuit 10 is not matched with an impedance of the external circuit. Particularly, since an interface at a TTL level has a logical threshold of about 1.6 V which is close to the ground potential, wrong operation of external equipments may be caused due to the undershoot.
Owing to the recent development of the fine working technology, the semiconductor devices have been highly integrated, and operation speeds of gates in the integrated circuits have increased, whereby the responsibility of the output buffer circuits has also increased. This increases the significance of the above problem.

Output buffer circuit having output bouncing controlled circuits


A catalyst composition, a process for producing the composition, and a hydrotreating process for converting a hydrocarbon stream such as, for example, gasoline, to olefins and C.sub.6 to C.sub.8 aromatic hydrocarbons such as toluene and xylenes are disclosed. The catalyst composition comprises a zeolite, a clay, and optionally a coke suppressor and/or an activity promoter. The process for producing the composition comprises the steps: (1) optionally contacting a zeolite with steam whereby a steamed zeolite is formed; (2) optionally contacting a zeolite or the steamed zeolite with an acid to produce an acid-leached zeolite; (3) combining a zeolite, which can also be the steamed zeolite or the acid-leached zeolite, with a clay under a condition sufficient to bind the clay to the zeolite to produce a clay-bound zeolite; and (4) calcining the clay-bound zeolite to produce a calcined clay-bound zeolite. The hydrotreating process comprises contacting a hydrocarbon stream with the catalyst composition under a condition sufficient to effect the conversion of a hydrocarbon to an olefin and a C.sub.6 to C.sub.8 aromatic hydrocarbon.

It is well known to those skilled in the art that aromatic hydrocarbons and olefins are each a class of very important industrial chemicals which find a variety of uses in petrochemical industry. It is also well known to those skilled in the art that catalytically cracking gasoline-range hydrocarbons produces lower olefins such as, for example, propylene; and aromatic hydrocarbons such as, for example, benzene, toluene, and xylenes (hereinafter collectively referred to as BTX) in the presence of catalysts which contain a zeolite. The product of this catalytic cracking process contains a multitude of hydrocarbons including unconverted C.sub.5 + alkanes; lower alkanes such as methane, ethane, and propane; lower alkenes such as ethylene and propylene; C.sub.6 -C.sub.8 aromatic hydrocarbons; and C.sub.9 + aromatic compounds which contain 9 or more carbons per molecule. Recent efforts to convert gasoline to more valuable petrochemical products have therefore focused on improving the conversion of gasoline to olefins and aromatic hydrocarbons by catalytic cracking in the presence of zeolite catalysts. For example, a gallium-promoted zeolite ZSM-5 has been used in the so-called Cyclar Process to convert a hydrocarbon to BTX.
Olefins and aromatic hydrocarbons can be useful feedstocks for producing various organic compounds and polymers. However, the weight ratio of olefins to aromatic compounds produced by the conversion process is generally less than 50%. Additionally, a zeolite catalyst is generally deactivated in a rather short period, especially in a high sulfur and/or high polyaromatic environment, because of depositions of carbonaceous material, generally coke, on the surface of the catalyst. Moreover, the BTX purity in the product is generally not desirably high. Therefore, development of a catalyst and a process for converting hydrocarbons to the more valuable olefins and BTX and for reducing coke deposition would be a significant contribution to the art and to the economy.

Hydrocarbon conversion catalyst composition and processes therefor and therewith


A method for fabricating a chip carrier, such as a printed circuit board, which includes at least one through hole or via hole, is disclosed. In accordance with this method, an electrically conductive layer is formed on at least one of the major surfaces of the corresponding chip carrier substrate, as well as for the surface of the through hole or via hole. Significantly, the electrically conductive layer on the at least one major surface is relatively thin, which permits the formation of a relatively high density of circuit lines in this layer. On the other hand, the electrically conductive layer on the surface of the through hole or via hole is relatively thick, which prevents the formation of defects in this layer.

1. Field of the Invention
The present invention relates to a method for forming an electrically conductive layer on a chip carrier substrate, such as a printed circuit board substrate, and, more particularly, to a method for forming an electrically conductive layer on a chip carrier substrate having through holes or via holes.
2. Description of the Related Art
To increase the component density of a chip carrier, such as a printed circuit board or a printed circuit card, on which electronic components such as integrated circuit (IC) chips are to be mounted, so-called double face mounting, in which electronic components are mounted on both the upper and lower surfaces of the chip carrier, is now practiced. In double face mounting, a chip carrier substrate is provided with through holes, that is, holes extending through the thickness of the substrate, to establish electrical connections between circuit patterns on opposite surfaces of the substrate.
In a substrate having through holes, the internal surface of each through hole is covered by a conductive layer which extends to the circuit patterns on the opposing upper and lower surfaces of the substrate, whereby the circuit patterns on the two surfaces are electrically connected to each other.
Multilayer chip carrier substrates to which patterned conductive layers (circuitry patterns) are laminated are also used to attain high component densities. Such a multilayer substrate includes, for example, via holes, that is, small holes extending from a conductive layer on the substrate surface to a conductive layer internal to the substrate. In such a substrate, a conductive layer provided on the internal surface of each via hole electrically connects the conductive layer on the substrate surface to the conductive layer in the substrate.
The conductive layer provided on the internal surface of a through hole or via hole is conventionally formed simultaneously and integrally with the conductive layer on the substrate surface by so-called plating, that is, depositing metal such as copper typically through a chemical reaction.
When a conductive layer on a chip carrier substrate is formed by plating, because the diameter of each through hole or via hole is small, the metal-containing solution fails to fully penetrate into the hole, so that the conductive layer formed on the internal surface of the through hole or via hole tends to be thinner than the conductive layer simultaneously formed on the substrate surface.
The thinner conductive layer in the through hole or via hole often includes defects such as pinholes or cracks, leading to an open circuit, which is obviously undesirable in an electrical connection. Therefore, the conductive layer in the through hole or via hole needs to have sufficient thickness to assure a continuous electrical connection. Thus, it is normal practice to extend the plating time so that a sufficient thickness is achieved for the conductive layer in the through hole or via hole to avoid pinholes or cracks.
However, when the plating time is extended, not only is the thickness of the conductive layer in the through hole or via hole increased, but the conductive layer on the substrate surface becomes undesirably thick, leading to the following problem. For a substrate with through holes, for example, as shown in FIG. 21, the spacing between the circuit lines formed in a conductive layer 200 (which spacing is indicated by reference d in FIG. 21) on the substrate surface is reduced during the etching of these circuit lines into the conductive layer, leading to the occurrence of short circuits between the circuit lines. Similar problems also arise in a substrate with via holes. The reason why such a problem arises is because the etching procedure employed is so-called wet etching, which results in the cross-section of the etched circuit lines being trapezoidal.
If the spacing between the circuit lines in the design (specification) is increased to achieve a predetermined spacing d, then the density of circuit lines is necessarily decreased, which is undesirable. Thus, it is desirable to increase the thickness of the conductive layer in the through holes without thickening the conductive layer on the substrate surface.
Regarding prior attempts to solve the above problem, Japanese Published Unexamined Patent Application No. 2-174194 discloses a method for thickening metal layers in through holes. According to this method, the surface of a printed circuit board substrate, except for the interior surfaces of the through holes, is coated with a plating resist layer after plating metal onto the substrate surface, including the surfaces of the through holes. Thereafter, because of the presence of the plating resist layer, which prevents plating, metal is plated for a second time onto only the surfaces of the through holes.
When the above-described conventional technique is employed, however, there arises the following problem. In the conventional technique, since the second metal plating is carried out for the substrate with the plating resist layer being present, the plating resist gets mixed into the plating solution, thereby contaminating it, so that uniform plating cannot be attained and defects such as cracks in the plated metal often occur.
In addition to the above problem, the plating solution needs to be filtered over and over to remove contaminants from the plating solution. Furthermore, since plating conditions vary significantly depending upon the existence or absence of the plating resist layer, when the same plating facility is used, different plating conditions need to be established for the first and second platings, which complicates the manufacturing process.
Of course, the first and second platings may be performed in separate plating facilities to avoid contaminating the plating solution. That is, a plating facility dedicated to plating the substrate in the presence of the plating resist layer may be used.

Method for forming electrically conductive layers on chip carrier substrates having through holes or via holes

International Business Machines Corporation


Polypeptides having alkanoyl-CoA activity have been identified and characterized, as have nucleic acids encoding these polypeptides. Expression or over-expression of the nucleic acids alters levels of cannabinoid compounds in organisms. The polypeptides may be used in vivo or in vitro to produce cannabinoid compounds.

Cannabis sativa L. (cannabis, hemp, marijuana) is one of the oldest and most versatile domesticated plants, which today finds use as source of medicinal, food, cosmetic and industrial products. It is also well known for its use as an illicit drug owing to its content of psychoactive cannabinoids (e.g. Δ9-tetrahydrocannabinol, Δ9-THC). Cannabinoids and other drugs that act through mammalian cannabinoid receptors are being explored for the treatment of diverse conditions such as chronic pain, multiple sclerosis and epilepsy.
Cannabinoids have their biosynthetic origins in both polyketide and terpenoid metabolism and are termed terpenophenolics or prenylated polyketides (Page J., Nagel J. (2006) Biosynthesis of terpenophenolics in hop and cannabis. In J T Romeo, ed, Integrative Plant Biochemistry, Vol. 40. Elsevier, Oxford, pp 179-210.). Cannabinoid biosynthesis occurs primarily in glandular trichomes that cover female flowers at a high density. Cannabinoids are formed by a three-step biosynthetic process: polyketide formation, aromatic prenylation and cyclization (see FIG. 1).
The first enzymatic step in cannabinoid biosynthesis is the formation of olivetolic acid by a polyketide synthase enzyme that catalyzes the condensation of hexanoyl-coenzyme A (CoA) with three molecules of malonyl-CoA. The major cannabinoids, including Δ9-tetrahydrocannabinolic acid and cannabidiolic acid, are formed from the precursor hexanoyl-CoA, which is a medium chain fatty acyl-CoA (see FIG. 1). Other cannabinoids with variant side-chains are formed from aliphatic-CoAs of different lengths (e.g. Δ9-tetrahydrocannabivarinic acid is formed from an n-butyryl-CoA primer).
Hexanoyl-CoA and other acyl-CoA thioesters in plants are synthesized by acyl-activating enzymes (AAEs, also called acyl-CoA synthetases) that catalyze the activation of carboxylic acid substrates using ATP. These enzymes act on a variety of carboxylate acids including short-, medium-, long- and very long-chain fatty acids, jasmonate precursors, phenylpropanoid-derived acids (e.g. cinnamic acid) and other organic acids such as malonate, acetate and citrate. Very few medium-chain acyl CoA synthetases have been previously identified in nature. In plants, three enzymes from A. thaliana, AAE7, At4g05160 and At5g63380 have been shown to form hexanoyl-CoA from hexanoate (Schneider K et al. (2005) A new type of peroxisomal acyl-coenzyme A synthetase from Arabidopsis thaliana has the catalytic capacity to activate biosynthetic precursors of jasmonic acid. The Journal of Biological Chemistry 280:13962-72; Shockey J M, Fulda M S, Browse J (2003) Arabidopsis contains a large superfamily of acyl-activating enzymes. Phylogenetic and biochemical analysis reveals a new class of acyl-coenzyme a synthetases. Plant Physiology 132:1065-76.) Acyl-CoA synthetases from Pseudomonas spp. have been shown to act on medium-chain fatty acids such as hexanoate (Fernandez-Valverde M, Reglero A, Martinez-Blanco H, Luengo J M (1993) Purification of Pseudomonas putida acyl coenzyme A ligase active with a range of aliphatic and aromatic substrates. Applied Environmental Microbiology 59:1149-1154.)
Cannabinoids are valuable natural products. Genes encoding enzymes involved in cannabinoid biosynthesis will be useful in metabolic engineering of cannabis to produce plants that contain very low levels, or zero levels, of THCA and other cannabinoids via targeted mutagenesis (e.g. TILLING) or other gene knockout techniques. Such genes may also prove useful for creation, via marker-assisted selection, of specific cannabis varieties for the production of cannabinoid-based pharmaceuticals, or for reconstituting cannabinoid biosynthesis in heterologous organisms such as bacteria or yeast, or for producing cannabinoids in cell-free systems that utilize recombinant proteins.
Genes encoding enzymes of cannabinoid biosynthesis can also be useful in synthesis of cannabinoid analogs and synthesis of analogs of cannabinoid precursors. Cannabinoid analogs have been previously synthesized and may be useful as pharmaceutical products.
There remains a need in the art to identify enzymes, and nucleotide sequences encoding such enzymes, that are involved in the synthesis of aromatic polyketides.

Genes and proteins for alkanoyl-CoA synthesis