The present invention refers to the use of hCNTF (human ciliary neurotrophic factor), mutants thereof or other molecules that activate the CNTF receptor, for the preparation of drugs for the treatment of obesity and associated disease, for example hyperglycemia. FIG. 1 shows the anti-obesity effect of hCNTF and leptin on body weight (left panels) and on food intake (right panels) in genetically obese mice and in mice with diet-induced obesity (DIO).

The present application is the national stage under 35 U.S.C. 371 of PCT/IT97/00283, filed Nov. 18, 1997.
The subject of the present invention is the use of molecules that activate the CNTF (ciliary neurotrophic factor) receptorxe2x80x94such as hCNTF (human CNTF) or mutants of hCNTFxe2x80x94as active principles in the formulation of pharmaceutical compositions suitable for the treatment of obesity and of related diseases. The term hCNTF mutant is intended to mean an amino acid sequence that can in theory be derived from hCNTF by substitution of one or more amino acids.
Obesity, which affects  greater than 30% of the adult population in the industrial world, is a major public health problem, since it is associated with type II diabetes, hypertension, hyperlipidemia and increased mortality rate. Obesity is the result of a positive energy balance, as a consequence of an increased ratio of caloric intake to energy expenditure. Treatment is generally unsuccessful due to the operation of mechanisms that restore adipose mass after both intentional or unintentional changes (1). The lipostasis theory postulates that the size of the body fat depot is regulated by a feedback loop, constituted by adipocyte-derived circulating molecules that act on the hypothalamus to decrease appetite and increase energy expenditure (2).
The recently identified 16-kilodalton plasma protein leptin (3) fulfills many of the criteria expected from such a lipostatic hormone. It is expressed in adipose tissue, and its plasma levels are highly correlated with body mass index in rodents and humans (4). The absence of leptin in obese (ob/ob) mutant mice leads to a massive increase in body fat, which can be reversed by systemic administration of the recombinant protein (5, 6, 7). However, human obesity does not appear to be due to deficient expression of leptin, since leptin mRNA and plasma protein levels were shown to be increased in obese versus lean subjects (4). Thus, obese humans may be insensitive to the lipostatic effect of leptin, possibly due to a defect at the level of leptin transport, leptin receptor activity, or post-receptorial signalling mechanisms (8).
There is thus a need in this specific field for new pharmacological agents capable of correcting obesity in people who are resistant to leptin.
Leptin resistance is a characteristic feature of the diabetic (db/db) mouse mutant, which expresses a truncated form of the leptin receptor lacking most of the intracytoplasmic domain (9). An animal model that more closely resembles human obesity is that of mice rendered obese by feeding a high-fat diet (DIO mice). Similar to human obese subjects, DIO mice have elevated plasma levels of leptin (4), suggesting that they are relatively insensitive to the weight-reducing effects of the hormone.
The present invention provides biologically active anti-obesity agents that can reverse obesity, as well as hyperglycemia and hyperinsulinemia associated therewith.
The subject of the present invention is therefore the use of substances that activate the CNTF receptor for the preparation of drugs for treatment of obesity and related diseases. These substances can be hCNTF (human ciliary neurotrophic factor; SEQ ID NO: 1) itself or mutants thereof (see for instance SEQ ID NOS:2 to 28). Good results have been obtained using the hCNTF mutant (Ser166Asp/Gln167His) hCNTF (10), which, from position 159 to position 178, has the following amino acid sequence (shown as SEQ ID NO: 5 in the annexed sequence listing):
Leu Lys Val Leu Gln Glu Leu Asp His Trp Thr Val Arg Ser Ile His Asp Leu Arg Phe [for sake of simplicity, this hCNTF mutant will be referred to hereinafter also as DH-CNTF]. For sake of simplicity, in the annexed sequence listing, it has been indicated only the portion from position 159 to position 178 of the mutants SEQ ID NOS: 2 to 22.
A further subject of the invention is the use of DNA coding for hCNTF or mutants thereof for the preparation of compositions for the treatment of obesity and diseases related thereto.
The present invention also has as its subject a drug for the treatment of obesity and the reduction of body weight, containing, as at least one of its active principles, hCNTF or a mutant thereof, and comprising a pharmaceutically acceptable vehicle. A pharmaceutically acceptable vehicle is intended to be a vehicle that is not dangerous for the patient, that does not degrade or deactivate the active principles or that does not interfere with the effects thereof. The preferred vehicle is a physiological saline solution, but other pharmaceutically acceptable vehicles can be used, and will easily be identified by those skilled in the art. In an embodiment that has shown good results hCNTF or mutants thereof can be used in combination with leptin: in this case the ratio wild type or mutant CNTF/leptin can be selected in the range 1:500 to 1:5, preferably 1:100 to 1:25.
hCNTF or hCNTF variants can be administered to patients in need of treatment in doses ranging from about 1 to 10,000 xcexcg/kg body weight. A preferred dose is between 10 and 1000 xcexc/kg body weight. A typical daily dose for an adult is between 1 and 100 mg. The necessary amount of active principle according to the invention can be administered in a single daily dose or in multiple doses throughout the day. The treatment regime can require administration for prolonged periods. The size of the dose administered must be determined by a physician and will depend on a number of factors, such as the nature and gravity of the disease, the age and state of health of the patient and the patient""s tolerance to the drug itself.
In a specific embodiment, hCNTF or a mutant thereof can be used for treatment of obese patients by means of a short-term (1-2 weeks) daily administration, in order to obtain a rapid, significant decrease in body weight (5-10%), which can be maintained subsequently using an appropriate diet and/or physical exercise.
The active protein molecules can be formulated for parenteral, nasal, bronchial or transdermal administration. The pharmaceutical composition according to the present invention is preferably administered parenterally by means of an injection. In the preferred embodiment, parenteral administration is subcutaneous or intramuscular. Other effective methods of administration are intravenous injections, slow-release parenteral formulations, inhalant mists, or suppositories. In the slow-release formulation the primary solvent can be either of an aqueous or of a non-aqueous type. Furthermore, the vehicle can contain other pharmacologically acceptable excipients to maintain or modify the pH, viscosity, clarity, colour, sterility, stability, speed of dissolution or odor of the formulation. Similarly, the vehicle can also contain other pharmacologically acceptable excipients to modify or maintain the stability, speed of dissolution, release, or absorption of the active principle. These excipients are substances that are normally used to formulate doses for parenteral administration, both in the form of single doses and in the form of multiple doses.
As mentioned above, the preferred parenteral form of administration of the formulation according to the invention is subcutaneous or intramuscular. The most preferred form of parenteral administration is subcutaneous. To obtain the required daily dose of active principle, it is possible to resort to single or repeated subcutaneous or intramuscular injections. In a preferred embodiment of the invention, the dose of active principle is between 10 and 1000 xcexcg/kg/day. For the treatment of obesity, it may be desirable to administer the active principle periodically. Periodic administration may take the form of monthly, bi-weekly, weekly, daily or hourly administration. The required frequency of administration will be apparent to those treating the patient on the basis of standard observational techniques.
It is also possible to consider oral administration of the pharmaceutical formulations according to the invention. In this case, the active principle administered is preferably encapsulated. The encapsulated active principle can be formulated with or without the vehicles usually employed in the preparation of solid doses. Preferably, the capsule is made in such a way that the active portion of the formulation is released in the gastro-intestinal tract when bioavailability is maximized and pre-systemic degradation is minimized. The formulation can also include further excipients with the aim of facilitating absorption of the active principle. It is also possible to use diluting agents, flavouring, low melting-point waxes, vegetable oils, lubricants, suspending agents, capsule disintegration agents and binding agents.
Independently of the method of administration, the specific dose is calculated according to the approximate body weight of the patient. Further refinement of the calculations necessary to determine the appropriate dose for treatment is routinely made by those of ordinary skill in the art, who are capable of reaching these results without the need for undue experimentation, especially in the light of the tests and dosing information provided herein.
According to the present invention, an obese patient is administered a therapeutically effective amount of active principle. As mentioned above, the dose required can be determined by those skilled in the art without the need for undue experimentation. A xe2x80x9ctherapeutically effective amountxe2x80x9d can be defined as the amount of active principle that is sufficient to cause an adequate loss of weight and to result in the consequent normalisation of metabolic parameters, such as the blood glucose level of the obese patient.
Up to this point a general description has been given of the present invention. With the aid of the following examples, a more detailed description will now be provided, with reference to specific embodiments, aimed at giving a better understanding of the aims, characteristics, advantages and operating methods of the invention. However, the scope of the present invention is not intended to be limited thereby.

Use of CNTF (ciliary neurotrophic factor) receptor activators for the treatment of obesity

Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.


A transmission comprises a first transmission case, a second transmission case connected to the case, a transmission shaft extending through the connection between the two cases, a tubular member fitting to and provided between the two cases at the position where the shaft extends through the cases, the tubular member having the shaft extending therethrough, and oil seals provided between the outer periphery of the tubular member and the two cases.

The present invention relates to a transmission comprising a first transmission case and a second transmission case connected together with a transmission shaft extending through the connected portions.
The first and second transmission cases contain oil for lubricating the transmission mechanisms, such as gear mechanisms, housed in the cases and must therefore be sealed off to confine the lubricating oil therein. Since the two cases are usually connected together over the entire opposed wall surfaces of the cases with a packing or the like interposed therebetween, the following problems have heretofore been encountered.
If it is attempted to connect the first and second transmission cases together over the entire wall surfaces, the cases will not be properly intimately fittable unless the wall surfaces are finished with high accuracy. Thus the cases require much labor to make. Additionally the two transmission cases are cumbersome to assemble because they must be fastened to each other uniformly over the entire opposed wall surfaces.


A preform element includes a facing table of super hard material having a from face, an outer peripheral surface, and a rear surface bonded to a substrate which is less hard than the super hard material. The facing table comprising a peripheral region surrounding an inner region, the peripheral region having an inner surface which is inclined at an angle of greater than 90.degree. to the rear surface of the facing table so as to face in a direction having a component rearwardly away from the facing table as well as inwardly towards said inner region. The inner region of the facing table may be formed with projections extending into the substrate.

The invention relates to elements faced with super hard material, and particularly to preform elements comprising a facing table of super hard material having a front face, a peripheral surface, and a rear surface bonded to a substrate of material which is less hard than the super hard material. Preform elements of this kind are often used as cutting elements on rotary drag-type drill bits and the present invention will be particularly described in relation to such use. However, the invention is not restricted to cutting elements for this particular use, and may relate to preform elements for other purposes. For example, elements faced with super hard material, of the kind referred to, may also be employed in workpiece-shaping tools, high pressure nozzles, wire-drawing dies, bearings and other parts subject to sliding wear, as well as elements subject to percussive loads as may be the case in tappets, cams, cam followers, and similar devices in which a surface of high wear resistance is required.
Preform elements used as cutting elements in rotary drill bits usually have a facing table of polycrystalline diamond, although other super hard materials are available, such as cubic boron nitride. The substrate of less hard material is often formed from cemented tungsten carbide, and the facing table and substrate are bonded together during formation of the element in a high pressure, high temperature forming press. This forming process is well known and will not be described in detail. Each preform cutting element may be mounted on a carrier in the form of a generally cylindrical stud or post received in a socket in the body of the drill bit. The carrier is often formed from cemented tungsten carbide, the surface of the substrate being brazed to a surface on the carder, for example by a process known as "L bonding". Alternatively, the substrate itself may be of sufficient thickness as to provide, in effect, a cylindrical stud which is sufficiently long to be directly received in a socket in the bit body, without being brazed to a carrier. The bit body itself may be machined from metal, usually steel, or may be molded using a powder metallurgy process. Such cutting elements are subjected to extremes of temperature during formation and mounting on the bit body, and are also subjected to high temperatures and heavy loads when the drill is in use down a borehole. It is found that as a result of such conditions spalling and delamination of the super hard facing table can occur, that is to say the separation and loss of the diamond or other super hard material over the cutting surface of the table. This may also occur in preform elements used for other purposes, and particularly where the elements are subjected to repetitive percussive loads, as in tappets and cam mechanisms.
Commonly, in preform elements of the above type the interface between the super hard table and the substrate has usually been flat and planar. However, particularly in cutting elements for drill bits, attempts have been made to improve the bond between the super hard facing table and the substrate by configuring the rear face of the facing table so as to provide a degree of mechanical interlocking between the facing table and substrate.
One such arrangement is shown in U.S. Pat. No. 5120327 where the rear surface of the facing table is integrally formed with a plurality of identical spaced apart parallel ridges of constant depth. The facing table also includes a peripheral ring of greater thickness, the extremities of the parallel ridges intersecting the surrounding ring.
An alternative arrangement is shown in our co-pending British Patent Application No. 9323207.2 where the rear surface of the facing table is integrally formed with a plurality of circumferentially spaced generally radial ribs, the outer extremities of which intersect a peripheral ring extending rearwardly from the rear surface of the facing table.
In such arrangements the peripheral ring is substantially rectangular in cross-section, although the corners may be rounded. Consequently, the inner surface of the peripheral ring extends substantially at 90.degree. to the rear surface of the facing table so as to be generally parallel to, and face towards, the central axis of the cutting element. As a consequence, the inner surface of the peripheral ring meets the rear surface of the facing table at a substantially 90.degree. angle. It is found in practice that such arrangements may result in two serious disadvantages. Firstly, as is well known, the preform element is formed in a high pressure, high temperature press in a process where the substrate is a preformed solid element having a front surface which is pre-shaped to the required configuration. A layer of diamond particles is then packed on to the configured surface of the substrate, filling the recesses therein and forming a continuous facing layer. Pressing of the combined body in the high pressure, high temperature press causes the diamond particles to be bonded together, with diamond-to-diamond bonding, and also bonded to the surface of the substrate, which is usually cemented tungsten carbide. In order to form the rectangular-sectioned peripheral ring on the rear surface of the diamond layer, the substrate is formed with a corresponding rectangular-sectioned peripheral rebate into which the diamond particles are packed.
It is believed that, due to the rectangular shape of the rebate in the substrate, the diamond particles may be less closely packed in the region of the comer of the rebate and less firmly compressed against the cylindrical inner wall of the rebate, resulting in imperfect bonding between the diamond particles and the material of the substrate in this area. Secondly, the 90.degree. junction between the peripheral ring and the rear surface of the facing table forms a stress concentration at this junction. Both of these features, it is believed, can increase the tendency for the facing table to separate from the substrate in use of the cutting element, when it is subjected to substantial temperatures and stresses. It is an object of the invention to provide a new and improved configuration of cutting element where these disadvantages may be overcome.


A marine propeller with break away hub has an insert cavity with pentagonal cross section extending coaxially with the axis of rotation of the propeller, along at least a portion of the length of the propeller. A resilient insert corresponding to the insert cavity is positioned in the insert cavity. The insert is sized for slip fit with the cavity and is adapted for connection with a propeller drive shaft. Preferably, the insert has a cylindrical aperture with a series of grooves disposed circumferentially thereabout extending coaxially through the insert and the insert is connected with the propeller shaft through a shaft sleeve. The shaft sleeve corresponds to the aperture in the insert, has a cylindrical outer surface with a series of teeth disposed circumferentially thereabout, and has a mounting aperture extending coaxially through the shaft sleeve. The shaft sleeve is sized for hand force slip fit engagement with the insert. The mounting aperture is adapted for mounting the marine propeller on the propeller shaft.

The present invention relates to torque transmission couplings specifically as applied to marine propellers and the transfer of torque from a propeller shaft or an engine drive shaft to the propeller for rotating the propeller to create thrust and propel a vessel.
Many methods are known for accomplishing the task of transferring torque from a propeller shaft to a propeller. Perhaps the simplest is a direct mechanical connection between the shaft and the hub such as by welding, by cross pinning the propeller to the shaft, or by using a splined shaft arrangement for example. However, direct mechanical connection between a propeller and a propeller shaft will result in significant damage to any one of or all of the components of the propulsion system if the rotation of the driven propeller is abruptly interrupted by striking an underwater obstacle or the like. Such an occurrence develops severe torque loading of the propulsion system and can damage one or all of the blades of the propeller; destroy the propeller hub or the connection between the propeller and the propeller shaft; overload and burn propeller shafting bearings; overload and break transmission and reversing gearing used in the propulsion system, including clutch mechanisms for engaging and disengaging the engine from the propeller shaft; and overtorque the engine, resulting in a variety of damage.
An early remedy to minimize the kind and extent of damage resulting from a propeller striking an obstacle relates to cross pinning the propeller to the propeller shaft, but by using a shear pin. The propeller is journaled for slip fit engagement with the propeller shaft and is precluded from such slippage by the insertion of a shearable cross pin which in its simplest form extends through the propeller hub and the propeller shaft. However, this remedy also has its problems insofar as a shear pin may fail to shear at the design torque loading. Even if the pin does properly shear, it then may potentially scour the journaled surface of the propeller hub, causing the propeller to cease to the propeller shaft. Another potential problem with using a shear pin relates to inattentive or inexperienced operators who may not recognize a failure situation after the shear pin has done its job, namely shear, and who will allow the propeller shaft to spin excessively inside the disconnected propeller, again causing the propeller to cease to the propeller shaft. Finally, a shear pin may all too often and easily be replaced with any piece of metal of suitable size, commonly a nail or steel rod for example, which will typically have shear characteristics far exceeding the design shear of the appropriate shear pin. This unwitting substitution results in a mechanical connection between the propeller and propeller shaft of the variety discussed above.
No safety propulsion measure, whereby some degree of residual torque transfer to the propeller remains after the propeller strikes an object, is designed into the propeller mounting systems discussed above. Thus, the vessel is commonly rendered nonoperational and must rely upon other sources for passage to a safe harbor where repairs may be effected.
A common contemporary resolution to the above problems is what might be called a rubber insert or bushing propeller mount. This typically includes a tubular, hard rubber bushing which circumscribes and is vulcanized to a centrally located, metal propeller mounting sleeve. The bushing and sleeve assembly is force fit into a center opening in the propeller hub by application of large forces to the hub and the bushing and sleeve assembly. The propeller mounting sleeve is mechanically connected with the propeller shaft and the rubber insert provides a slip clutch effect between the propeller hub and the propeller mounting sleeve insofar as the propeller shaft and mounting sleeve are allowed to rotate or slip relative to the propeller with severe torque loading of the propeller. Torque transfer to some degree may resume in this propeller mount after the impact or severe torque condition is removed. Thus, this variety of propeller mount provides a degree of damage safety and residual torque transfer subsequent to release.
However, this mount also has various problems. One problem is that the rubber bushing will typically harden with age. Another is that the bushing will also adhere to the inner cylindrical wall of the propeller hub with age. Either of these conditions significantly increases the torque value at which the slip clutch effect will occur. Thus, the damage safety feature of the rubber bushing mount diminishes as the propeller, specifically the rubber bushing, ages.
Another difficulty with the rubber bushing propeller mount is that the amount of torque transferable through the bushing will typically change significantly once slippage occurs. Sometimes the torque transfer capacity of the mount will be greatly diminished, more frequently the torque transfer capacity of the mount will be greatly increased and result in diminished safety for subsequent impacts.
Yet another problem with the rubber bushing propeller mount is found in the repair of this propeller mount. A mechanical press of some sort is required to disassemble the rubber bushing propeller mount and a force as high as sixteen tons is commonly required to press out such rubber bushings from a propeller hub. This amount of force is often unobtainable in many repair shops. Further, this level of force may easily damage and destroy a propeller which is under repair. If the old or damaged rubber bushing is removed from the propeller hub, then a new bushing must be pressed into place in the propeller hub and this procedure again requires a mechanical press capable of large forces, as high as twelve tons.


A method and system controls motion of an armature 112 of a fuel injector 100. The armature moves between an open coil 118 and a close coil 116 of the injector. Acceleration current of a certain polarity is applied to the open coil 118 with the armature disposed at the close coil 116. De-latching current of a polarity opposite of the certain polarity is applied to the close coil 116 to release magnetic latch on the armature thereby accelerating movement of the armature towards the open coil 118. Deceleration current is applied the close coil 116 thereby decelerating the armature prior to reaching the open coil. Latching current of the certain polarity is applied to the open coil 118 prior to or just after impact of the armature 112 with the open coil 118 to magnetically latch the armature to the open coil 118 thereby reducing bounce of the armature at impact.

In hydraulically actuated fuel injection systems, a control valve body is provided with a valve system having grooves or orifices which allow fluid communication between working ports, high pressure ports, and venting ports of the control valve body of the fuel injector and the inlet area. The working fluid is typically engine oil or other types of suitable hydraulic fluid which is capable of providing a pressure within the fuel injector in order to begin the process of injecting fuel into the combustion chamber.
In current configurations, a driver will deliver a current or voltage to an open side of an open coil solenoid. The magnetic force generated in the open coil solenoid will shift an armature into the open position so as to align grooves of the control valve body and the armature. The alignment of the grooves permits the working fluid to flow into an intensifier chamber from an inlet portion of the control valve body (via working ports). The high pressure working fluid then acts on an intensifier piston to compress an intensifier spring and hence compress fuel located within a high pressure plunger chamber. As the pressure in the high pressure plunger chamber increases, the fuel pressure will begin to rise above a needle check valve opening pressure. At the prescribed fuel pressure level, the needle check valve will shift against the needle spring and open the injection holes in a nozzle tip. The fuel will then be injected into the combustion chamber of the engine.
However, in such a conventional system, the armature has a tendency to bounce or repeatedly impact against the open coil during the opening stroke. During this bouncing, it is difficult to control the armature motion and hence results in the inability to efficiently control the supply of fuel to the combustion chamber of the engine. For example, in conventional systems it is not possible to quickly move the armature away from the open coil in order to minimize the bouncing effect during an injection of a pilot quantity of fuel. Accordingly, the initial quantity of fuel provided during the pre-stroke event cannot be easily controllable, resulting in a larger injection quantity of fuel than desired. This may result in a retarded start of injection, as well as the inability to control the armature and hence the injection of a small, pilot quantity of fuel. That is, during this bouncing or repeated impact, a small quantity of fuel cannot be metered accurately in order to efficiently inject this small quantity of fuel into the combustion chamber of an engine. Additionally, it is also very difficult, if not impossible, to vary the amount of fuel during this small injection.
Thus, injection shot-to-shot variations can occur on a single fuel injector.
It is also known that the bouncing phenomenon may differ from injector to injector, and over time. For example, different manufacturing tolerances may affect the bouncing phenomenon from, for example, small variations in armature diameter to different coil characteristics. Additionally, over time, in the same injector, variations may result from different operating conditions such as temperature and wear on the parts due to aging and other factors. Hence, the control of fuel quantity may vary from fuel injector to fuel injector, as well as over time with the same fuel injector. This also may lead to higher emissions and engine noise. Thus, injector shot-to-shot variations can occur on the same engine between multiple injectors.
The shot-to-shot variations mentioned above can cause idle stability issues that are detectable by the vehicle's operator and can cause decreased engine efficiency and increased emissions. Currently, manufacturing tolerances of the injector require sorting or rework to improve shot-to-shot variations.
Thus, there is a need to reduce injector shot-to-shot variations in an injection system by reducing the bounce of an armature of a control valve of the system.

Control method for closed loop operation with adaptive wave form of an engine fuel injector oil or fuel control valve


A forming apparatus for forming objects by forming a sheet of thermoformable material includes a thermal conditioning station including a kiln for heating the material to an operating temperature, and a heating station positioned downstream of the thermal conditioning station and including a heating device to heat set portions of the material to a temperature near a softening temperature of the material. In order to reduce reject material at the restart of the apparatus following machine downtime, the kiln and the heating device are positioned near one another in such a manner that a part of the material interposed between the thermal conditioning station and the heating station is heated by the heat generated by a kiln and/or by the heating device.

The invention relates to a forming apparatus for forming objects from a thermoformable sheet material, for example polypropylene.
The invention further relates to heating stations that are insertible into a forming apparatus arranged for forming objects by forming a thermoformable sheet material, for example polypropylene.
Also, the invention relates to a method for heating set portions of a thermoformable sheet material following a machine downtime of a forming apparatus.

Forming apparatus, heating station and method for heating set portions


A system includes a stand having a first axis, a first arm, and a second arm. The first arm and the second arm extend from the axis. The first arm is configured to rotate about the axis and the second arm is configured to rotate about the axis. The system includes a first can coupled to the first arm. The first can is configured to be disposed around a first tip of a first airfoil, the first can is configured to receive a first gas flow, and the first can is configured to distribute the first gas flow to a first work cavity around the first tip of the first airfoil. The system further includes a second can coupled to the second arm. The second can is configured to be disposed around a second tip of a second airfoil, the second can is configured to receive a second gas flow, and the second can is configured to distribute the second gas flow to a second work cavity of the second airfoil.

The subject matter disclosed herein relates to airfoils of a gas turbine system, and more specifically, to welding fixture for airfoils, such as turbine blades.
Gas turbine systems typically include a gas turbine engine having a compressor, a combustor, and a turbine. The compressor is configured to use compressor blades to compress and feed air into the combustor for combustion with fuel. For example, the compressor blades may extend radially outwards from a supporting rotor, and the rotation of the compressor blades may force air into the combustor. The combustion gases may flow through one or more turbine stages of the turbine to generate power to drive a load. Each turbine stage may include multiple turbine blades disposed around a rotor. During operation of the gas turbine system, the tips of the blades (e.g., compressor and/or turbine blades) may wear down due to rapid rotation and/or high operating temperatures. The tips of the airfoils may be welded to repair the tips.


An iron type golf club with an improved weight configuration including a peripheral weight extending around a rear surface of the club head body including a secondary weight system formed of a centrally located weight member located on a shelf defined by the peripheral weight directly below the center of percussion and a pair of auxiliary weight members integrally formed with and disposed on opposite sides of the centrally located weight member.

The present invention relates to iron type golf clubs and in particular to an iron type golf club head having a unique weight configuration.
Many conventional iron type golf clubs are structured with a peripheral weight and back cavity. These clubs have gained wide acceptance because they are more forgiving when a golf ball is struck off of the center of percussion of the club face. The peripheral mass permits mis-hit golf balls to receive more energy from the swing and therefore go farther and straighter than golf clubs without the peripheral weighting structure. However, a shortcoming of these type golf clubs is golf balls struck precisely on the center of percussion tend to feel less solid than golf clubs with an even weight distribution. To overcome this there have been many attempts at weighting of clubs within the rear cavity in order to provide all the benefits of peripheral weighting and also to maximize the performance of golf clubs when golf balls are struck directly on the center of percussion. Prior art patents of this type include my own U.S. Pat. Nos. 5,011,151, 5,046,733, 5,014,993, 4,905,386 and 4,826,172, as well as others well known in the art, including the patents to Winquist (U.S. Pat. No. 3,814,437) and McNally (U.S. Pat. No. 5,026,056), among others.

Iron type golf club with improved weight configuration


The invention provides human transferase proteins (TRNSFS) and polynucleotides which identify and encode TRNSFS. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provide methods for diagnosing, treating, or preventing disorders, associated with expression of TRNSFS.

This invention relates to nucleic acid and amino acid sequences of human transferase proteins and to the use of these sequences in the diagnosis, treatment, and prevention of cancer, developmental disorders, gastrointestinal disorders, genetic disorders, immunological disorders, neurological disorders, reproductive disorders, and smooth muscle disorders.
Transferase Proteins
Transferases are enzymes that catalyze the transfer of molecular groups from a donor to an aceeptor molecule. The reaction may involve an oxidation, reduction, or cleavage of covalent bonds and is often specific to a substrate or to particular sites on a type of substrate. Transferase proteins participate in reactions essential to such functions as synthesis and degradation of cell components, and regulation of cell functions, including cell signaling, cell proliferation, inflammation, apoptosis, secretion and excretion. Transferases are involved in key steps in disease processes involving these functions. These enzymes are frequently classified according to the type of group transferred. For example, methyl transferases transfer one-carbon methyl groups, amino transferases transfer nitrogenous amino groups, and similarly denominated enzymes transfer aldehyde or ketone, acyl, glycosyl, alkyl or aryl, isoprenyl, saccharyl, phosphorous-containing, sulfur-containing, or selenium-containing groups, as well as small enzymatic groups such as Coenzyme A.
One example of a glycosyl transferase is O-linked N-acetylglucosamine (O-GlcNAc) transferase, an enzyme that catalyzes the reaction of monosaccharide N-acetylglucosamine linking to the hydroxyl group of a serine or threonine residue. O-GlcNAc and N-acetyl-xcex2-D-glucosaminidase (O-GlcNAcase), regulate the attachment and removal, respectively, of O-GlcNAc from proteins in a manner analagous to regulation of protein phosphorylation by kinases and phosphotases. O-GlcNAc transferase has been localized primarily in the nucleus and the cytosol of cells and has been shown to play a role in several cellular systems such as transcription, nuclear transport, and cytoskeletal organization. O-GlcNAc transferase is a heterodimer consisting of two catalytic 110-kDa (p110) subunits and one 78-kDa (p78) subunit. The gene encoding this enzyme is highly conserved. The amino terminus of the p110 subunit has homology to the tetratricopeptide repeat (TPR) motif while the carboxyl terminus has no significant homology (Kreppel, L. K. et al. (1997) J. Biol. Chem. 272:9308-9315). Proteins containing the TPR motif interact through this TPR domain to form regulatory complexes. TPR motifs are believed to play a role in modulation of cellular processes such as cell cycle, transcription, and protein transport (Das, A. K. et al. (1998) EMBO J 17:1192-1199).
The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine and guanine to their respective mononucleotides. HGPRT is ubiquitous, is known as a xe2x80x98housekeepingxe2x80x99 gene, and is frequently used as an internal control for reverse transcriptase polymerase chain reactions. There is a serine-tyrosine dipeptide that is conserved among all members of the HGPRT family and is essential for the phosphoribosylation of purine bases(Jardim, A. and Ullman, B. (1997) J. Biol. Chem. 272:8967-8973). A partial deficiency of HGPRT can lead to overproduction of uric acid, causing a severe form of gout. An absence of HGPRT causes Lesch-Nyhan syndrome, characterized by hyperuricaemia, mental retardation, choreoathetosis, and compulsive self-mutilation (Sculley, D. G. et al. (1992) Hum Genet 90:195-207).
Polyprenyl transferases catalyze the addition of polyprenyl groups to molecules. For example, the enzyme 1,4-dihydroxy-2-napthoate octaprenyltransferase catalyzes the conversion of the soluble 1,4-dihydroxy-2-napthoic acid (DHNA) to the membrane-bound demethylmenaquinone by attaching a 40-C side chain to DHNA, a key step in the biosynthesis of menaquinone (vitamin K2). This octaprenyltransferase is a membrane protein in Escherichia coli that is necessary for the synthesis of menaquinone (Suvarna, K. et al. (1998) J. Bacteriol. 180:2782-2787). Quinones, in many cases, take part in the oxidation-reduction cycles essential to living organisms (Morrison, R. T. and Boyd, R. N. (1987) Organic Chemistry, Allyn and Bacon, Inc., Newton, Mass., pp. 1092-1093). Other octaprenyltransferase have been shown to allow the synthesis of quinones under anaerobic conditions and, therefore, may play a role in anaerobic metabolism (Alexander, K. and Young, I. G. (1978) Biochemistry 17:4750-4755).
The synthesis of 3xe2x80x2-phosphoadenosine-5xe2x80x2-phosphosulfate (PAPS) requires two enzymes, adenosine triphosphate (ATP) sulfurylase and adenosine 5xe2x80x2-phosphosulfate (APS) kinase. ATP sulfurylase catalyzes the formation of APS from ATP and free sulfate. APS kinase phosphorylates APS to produce PAPS, the sole source of donor sulfate in higher organisms. In bacteria, fungi, yeast, and plants, these two enzymes are separate polypeptides. In animals, ATP sulfurylase and APS kinase are present in a single protein. The bifunctional enzyme found in mammals shows extensive homology to known sequences of both ATP sulfurylases and APS kinases. APS kinase peptide sequences are well conserved and contain an ATP-GTP binding motif (P-loop) flanked by cysteine residues and a PAPS-dependent enzyme motif. ATP sulfurylase peptide sequences have a PP-motif found in ATP sulfurylases and PAPS reductases (Rosenthal, E. and Leustek, T. (I995) Gene 165:243-248; Li, H. et al. (1995) J. Biol. Chem. 270:29453-29459; Deyrup, A. T. et al. (1998) J. Biol. Chem. 273:9450-9456; Bork, P. and Koonin, E. V. (1994) Proteins 20:347-355).
The enzyme phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes the methylation of phosphatidylethanolamine. Hepatocytes in the liver synthesize phosphatidylcholine (PC) by stepwise methylation of phosphatidylethanolamine and have abundant activity for PEMT. Other cells and tissues express minimal activities for PEMT. All mammalian cells, including hepatocytes, synthesize PC from choline via the CDP-choline pathway. Evidence suggests that one function of hepatic PEMT is to maintain PC synthesis and generate choline when dietary supply of choline is insufficient, as occurs during pregnancy, lactation, or starvation (Walkey, C. J. et al. (1998) J. Biol. Chem. 273:27043-27046). Forms of PEMT may also play a role in hepatocyte proliferation and liver cancer (Walkey, C. J. et al. (1999) Biochim. Biophys. Acta 1436:405-412). In the brain, decreased PEMT activity has been associated with Alzheimer""s disease (Guan, Z. Z. et al. (1999) Neurochem. Int. 34:41-47).
Sulfotransferase enzymes catalyze the transfer of sulfur-containing groups to molecules. For example, HNK-1 sulfotransferase (HNK-1ST) forms the HNK-1 carbohydrate epitope by adding a sulfate group to glycoproteins and glycolipids. The HNK-1 epitope was discovered by an antibody against human natural killer cells and is found in neural adhesion molecules, including N-CAM and myelin-associate glycoprotein. The HNK-1 carbohydrate epitope was recognized to have functional significance as an auto-antigen involved in peripheral demyelinative neuropathy. The HNK-1ST is a type II membrane protein with a consensus sequence shared by Golgi-associated sulfotransferases. The human and rat HNK-1STs share 90% homology in amino acid sequence. Human HNK-1ST was predominantly detected in fetal brain and in adult brain, testis, and ovary. (See Ong, E. et al. (1998) J. Biol. Chem. 273:5190-5195.)
Camnitine palmitoyitransferase I (CPT I) is an enzyme that catalyzes the transfer of fatty acyl groups from coenzyme A to carnitine, the rate-determining step in mitochondrial fatty acid xcex2-oxidation (a major source of energy production in the cell). CPT I has two structural genes (xcex1 and xcex2) that are differentially expressed in tissues that utilize fatty, acids as fuel. The xcex1 structure is expressed most highly in the liver, pancreatic xcex2 cells, and heart. The xcex2 structural gene of CPT I is predominately expressed in skeletal muscle, adipose tissue, heart, and testis (Yu, G. S. et al. (1998) J. Biol. Chem. 273:32901-32909). CPT I deficiency is a life-threatening disorder that appears to be treatable with medium-chain triglycerides. The disorder first presents, between 8 and 18 months, with Reye syndrome-like episodes associated with fasting due to viral infection or diarrhea. Coma, seizures, hepatomegaly, and hypoketotic hypoglycemia characterize these episodes. Persistent neurological defects are common (Online Mendelian Inheritance in Man entry #255120; ExPASy Enzyme:EC 188.8.131.52).
The enzyme glycine N-methyltransferase catalyzes the transfer of the methyl group from S-adenosyimethionine to glycine to form S-adenosylhomocteine and sarcosine. Glycine N-methyltransferase is a tetramer of identical subunits, has a nucloetide binding region, and is localized in the liver. Amino acid sequence homology is found between glycine N-methlytransferases from rat, rabbit, pig, and human livers. Glycine N-methyltransferase can exist as a dimer which binds polycyclic aromatic hydrocarbons (PAHs) and acts as a transcriptional activator (Ogawa, H. et al. (1998) Int. J. Biochem. Cell Biol. 30:13-26; Bhat, R. and Bresnick, E. (1997) J. Biol. Chem. 272:21221-21226).
Myristoyl CoA:protein N-myristoyl-transferase
N-acylation with the 14-carbon fatty acid, myristate is found on the amino groups of N-terminal glycines of a number of proteins that are essential to normal cell functioning and/or are potential therapeutic targets of disease. Examples of such proteins include subunits of heterotrimeric G proteins, GTP-binding arfl, human immunodeficiency virus gag and nef proteins, myristolated alanine-rich C kinase substrate (MARCKS), the protein phosphatase calcineurin B, the pp60src protein tyrosine kinase, the retinal calcium-binding recoverin, the caveolae-associated endothelial nitric oxide synthase, the catalytic subunit of cAMP-dependent protein kinase, and mitochondria-associated cytochrome b5 reductase. (Glover, C. J. et al. (1997) J. Biol. Chem. 272:28680-28689.) N-myristoylated proteins ate associated with a variety of organelles with the myristate moiety required for such diverse functions as specific protein-protein or protein-lipid interactions, ligand-induced protein conformnational changes, and correct subcellular targeting.
Protein myristoylation occurs almost exclusively cotranslationally during protein synthesis of the first 100 amino acids. The reaction is catalyzed by the enzyme myristoyl CoA:protein N-myristoyl-transferase (NMT) 1 (EC 184.108.40.206). (Towler, D. A. et al. (1987) Proc. Natl. Acad. Sci. 84:2708-2712.) Immunofluorescence microscopy reveals NMT to be distributed uniformly throughout the cytoplasm of yeast and mammalian cells. This finding, plus evidence that N-myristoylation occurs on nascent polypeptides bound to free polyribosomes, establish that NMT is physically localized and functionally active in the cell cytoplasm. (Wilcox, C. et al. (1987) Science 238:1275-1278.)
Protein N-myristoylation appears to be a tightly regulated process involving i) the coordinated participation of several different enzvmes/proteins, e.g. N-methionylaminopeptidase, fatty acid synthetase, long chain acyl-CoA synthetase, acyl-CoA-binding proteins; ii) access of NMT to pools of myristoyl-CoA substrate; and iii) N-myristoyiation of nascent polypeptide substrates during protein synthesis to avoid potential interfering reactions such as N-acetylation and polypeptide folding. The ability of NMT to function in regulated N-myristoylation has implied the existence of mechanisms designed to ensure targeting of NMT to the appropriate protein synthesis machinery. These mechanisms may involve interactions with other cooperating components that facilitate the recognition and efficient N-myristoylation of the rapidly growing polypeptide substrates. (Glover, et al. supra.) Protein N-myristoylation activity may be a chemotherapeutic target for cancer, infectious diseases, and immune disorders. Antagonists of NMT may reduce posttranslational myristoylation of oncoproteins and other growth-activating cellular proteins. (Felsted, R. L. et al., (1995) J. Natl. Cancer Inst. 87:1571-1573; Furuishi, K. et al., (1997) Biochem. Biophys. Res. Comm. 237:504-511.)
Mannose-1-phosphate guanvitransferase
Many secretory proteins and membrane proteins are glycosylated proteins that have covalently attached carbohydrate chains, or oligosaccharides. Some of these glycoproteins have only one or a few carbohydrate groups while others have numerous oligosaccharide side chains, which may be linear or branched. The sugar residues of many plasma membrane glycoproteins orient these proteins in membranes. Sugar residues of glycoproteins are hydrophilic and strongly prefer to be located near the aqueous or extracellular surface rather than the hydrocarbon core of the plasma membrane. Because there is a high energy barrier to the rotation of a glycoprotein from one side of the membrane to the other, the carbohydrate groups of membrane glycoproteins help to maintain the asymmetric character of biological membranes. One of the best-characterized glycoproteins is glycophorin, a protein found in the membrane of red blood cells. Many soluble glycoproteins are known as well, including carrier proteins, antibodies, and many of the proteins contained in lysosomes. Carbohydrate groups of plasma membrane glycoproteins play a major role in cell-cell recognition. Oligosaccharides are involved in many inflammatory processes and may also provide targets for tumor immunotherapy.
Glycoproteins are often linked to their oligosaccharides through asparagine (N) residues. These N-linked oligosaccharides are very diverse, but the many pathways by which they all form have a common first step. A 14 residue core oligosaccharide, containing two N-acetylglucosamine, nine mannose, and three glucose residues, is transferred from a dolichol phosphate donor molecule to certain N residues on the proteins (reviewed in Lehninger, A. L. et al. (1993) Principles of Biochemistry, Worth Publishers, New York, N.Y., pp. 931). Glycosylation is the most extensive of all post-translational modifications in proteins and is essential for the secretion, antigenicity, and clearance of glycoproteins.
A variety of enzymes which are involved in sugar metabolism participate directly or iridirectly in glycosylation, such as certain pyrophosphorylases. ADP-glucose pyrophosphorylases play an important role in the biosynthesis of alpha 1,4-glucans (glycogen or starch) in bacteria and plants. Specifically, ADP-glucose pyrophosphorylases catalyze the synthesis of the activated glucosyl donor, ADP-glucose, from glucose-1-phosphate and ATP. ADP-glucose pyrophosphorylases are tetrameric, allosterically regulated enzymes. There are a number of conserved regions in the sequence of bacterial and plant ADP-glucose pyrophosphorylase subunits. Additionally, there are three regions which are considered signature patterns (ExPASy PROSITE database, documents PS00808-PS00810). The first two regions are N-terminal and have been proposed to be part of the allosteric and substrate-binding sites in the Escherichia coli enzyme. The third pattern corresponds to a conserved region in the central part of the enzymes.
In eukaryotic cells, mannose-1-phosphate guanyltransferase is involved in eariy steps of protein glycosylation. This enzyme participates in mannose metabolism, and its enzymatic products are channeled into glycdprotein synthesis. Mannose-1-phosphate guanyltransferase (MPG), also referred to as NDP-hexose pyrophosphorylase or GDP-mannose pyrophosphorylase B, catalyzes the conversion of GTP and xcex1-D-mannose 1-phosphate into diphosphate and CDP-ethanolamine. This enzyme is very similar to CDP-glucose pyrophosphorylase and may be involved in the regulation of cell cycle progression. A cDNA coding for MPG 1 was recently isolated from a Trichoderma reesei cDNA library (Kruszewska, J. S. et al. (1998) Curr. Genet. 33:445-500). The nucleotide sequence of the 1.6 kb cDNA revealed an ORF which encodes a protein of 364 amino acids. Sequence comparisons demonstrate that this protein shares 70% identity with the yeast Saccharomvces cerevisiae MPG 1 gene and 75% identity with the Schizosaccharomvces pombe gene. MPGs are conserved among diverse organisms. For example, recent genome sequencing projects have identified MPG homologs in the plant Arabidousis thaliana and thenematode Caenorhabditis elerans (SEQ ID NO:32 and SEQ ID NO:33, respectively).
Alterations in glycosylation are known to occur in a number of disorders and diseases such as carbohydrate-deficient glycoprotein syndromes (CDGSs). In the biochemical pathway upstream of MPG is an important enzyme called phosphomannomutase (PMM) which provides the mannose 1-phosphate required for the reaction catalyzed by MPG. PMM catalyzes the conversion of D-mannose 6-phosphate to D-mannose 1-phosphate and has been implicated in CDGSs. CDGSs are a group of hereditary multisystem disorders (Matthijs, G. et al. (1 997) Nat. Genet. 16:88-92). The clinical phenotype of most CDGSs is dominated by severe psychomotor and mental retardation, as well as blood coagulation abnormalities as seen in thrombosis, bleeding, or stroke-like episodes. The characteristic biochemical abnormality of CDGSs is the hypoglycosylation of glycoproteins. Depending on the type of CDGS, the carbohydrate side chains of glycoproteins are either truncated or completely missing from the protein core.
A new type of CDGS, designated as CDGS type 1B, has recently been described (Niehues, R. et al. (1998) Clin. Invest. 101:1414-1420). The clinical phenotype of this new disorder is fundamentally different from other types of CDGS in that no psychomotor or mental retardation is present. Instead, CDGS type 1B is a gastrointestinal disorder characterized by protein-losing enteropathy. Some patients who are affected with CDGS type 1B suffer from thrombosis and life-threatening bleeding. A deficiency of phosphomannose isomerase was identified as the most likely cause of this syndrome, and a therapy was developed in the form of oral administration of mannose (Niehues, supra). Mannose treatment can correct the clinical phenotype in CDGS type 1B. It is noteworthy that CDGS is the first inherited disorder in human metabolism that shows a decrease in available mannose. The above findings indicate that increasing blood mannose levels might correct some protein giycosylation deficiencies.
The discovery of new human transferase proteins and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of cancer, developmental disorders, gastrointestinal disorders, genetic disorders, immunological disorders, neurological disorders, reproductive disorders, and smooth muscle disorders.
The invention features substantially purified polypeptides, human transferase proteins, referred to collectively as xe2x80x9cTRNSFSxe2x80x9d and individually as xe2x80x9cTRNSFS-1,xe2x80x9d xe2x80x9cTRNSFS-2,xe2x80x9d xe2x80x9cTRNSFS-3,xe2x80x9d xe2x80x9cTRNSFS-4,xe2x80x9d xe2x80x9cTRNSFS-5,xe2x80x9d xe2x80x9cTRNSFS-6,xe2x80x9d xe2x80x9cTRNSFS-7,xe2x80x9d xe2x80x9cTRNSFS-8,xe2x80x9d xe2x80x9cTRNSFS-9,xe2x80x9d xe2x80x9cTRNSFS-10,xe2x80x9d xe2x80x9cTRNSFS-11,xe2x80x9d xe2x80x9cTRNSFS-12,xe2x80x9d xe2x80x9cTRNSFS-13,xe2x80x9d xe2x80x9cTRNSFS-14,xe2x80x9d and xe2x80x9cTRNSFS-15.xe2x80x9d In one aspect, the invention provides a substantially purified polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 (SEQ ID NO:1-15), and fragments thereof.
The invention further provides a substantially purified variant having at least 90% amino acid identity to at least one of the amino acid sequences selected from the group consisting of SEQ ID NO:1-15 and fragments thereof. The invention also provides an isolated and purified polynucleotide encoding the polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-1 5 and fragments thereof. The invention also includes an isolated and purified polynuclebtide variant having at least 90% polynucleotide sequence identity to the polynucleotide encoding the polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof.
Additionally, the invention provides an isolated and purified polynucleotide which hybridizes under stringent conditions to the polynucleotide encoding the polypepptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof. The invention also provides an isolated and purified polynucleotide having a sequence which is complementary to the polynucleotide encoding the polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof.
The invention also provides a method for detecting a polynucleotide in a sample containing nucleic acids, the method comprising the steps of (a) hybridizing the complement of the poiynucieotide sequence to at least one of the polynucleotides of the sample, thereby forming a hybridization complex; and (b) detecting the hybridization complex, wherein the presence of the hybridization complex correlates with the presence of a polynucleotide in the sample. In one aspect, the method further comprises amplifying the polynucleotide prior to hybridization.
The invention also provides an isolated and purified polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30 (SEQ ID NO:16-30), and fragments thereof. The invention further provides an isolated and purified polynucleotide variant having at least 90% polynucleotide sequence identity to the polynucieotide sequence selected from the group consisting of SEQ ID NO:16-30 and fragments thereof. The invention also provides an isolated and purified polynucleotide having a sequence which is complementary to the polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:16-30 and fragments thereof.
The invention further provides an expression vector containing at least a fragment of the polynucleotide encoding the polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof. In another aspect, the expression vector is contained within a host cell.
The invention also provides a method for producing a polypeptide, the method comprising the steps of: (a) culturing the host cell containing an expression vector containing at least a fragment of a polynucleotide under conditions suitable for the expression of the polypeptide; and (b) recovering the polypeptide from the host cell culture.
The invention also provides a pharmaceutical composition comprising a substantially purified polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof, in conjunction with a suitable pharmaceutical carrier.
The invention further includes a purified antibody which binds to a polypeptide selected from the group consisting of SEQ ID NO:1-15 and fragments thereof. The invention also provides a purified agonist and a purified antagonist to the polypeptide.
The invention also provides a method for treating or preventing a disorder associated with decreased expression or activity of TRNSFS, the method comprising administering to a subject in need of such treatment an effective amount of a pharmaceutical composition comprising a substantially purified polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof, in conjunction with a suitable pharmaceutical carrier.
The invention also provides a method for treating or preventing a disorder associated with increased expression or activity of TRNSFS, the method comprising administering to a subject in need of such treatment an effective amount of an antagonist of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-15 and fragments thereof.


A write path scheme in a synchronous DRAM having: a data converter unit to convert serial input data to parallel output data, a multiplexer to output data from the data converter unit depending on a first mode selection signal and a second mode selection signal, and a data input/output sense amplifier having a plurality of sense amplifiers to separately operate the plurality of sense amplifiers depending on the first mode selection signal and the second mode selection signal to sense data from the multiplexer and then load the data on a global input/output line. Also included is a write driver to load data from the global input/output line on a local input/output line.

1. Technical Field of the Invention
The present patent relates to a write path scheme in a synchronous dynamic random access memory (DRAM) and, more particularly, to a write path scheme in a DDR II SDRAM.
2. Discussion of Related Art
As a DDR I SDRAM has been replaced with a DDR II SDRAM, new regulations for write latency have been applied in order to increase efficiency of buses. According to the new regulations, column operations are defined on two-clock basis, and specification for interrupt operations is defined not to be stringent.
FIG. 1 is a block diagram showing a conventional write path scheme. Referring to FIG. 1 input data DIN are input to a data input buffer 10 in a serial manner. Such serial input data are latched in a data converter unit which includes first to seventh latches 20 to 80 depending on the rising and the falling edge signals dsrp4 and dsfp4 of a data strobe signal DQS from a DQS buffer 80. Then, four-by-four aligned data (i.e., Algn—dinr0, Algn—dinf0, and Algn—dinr1, Algn—dinf1) are simultaneously input to a Din multiplexer 100 in a parallel manner depending on the rising and the falling edge signals dsrp4 and dsfp4 of the data strobe signal DQS. The Din multiplexer 100 outputs 16, 32, or 64 data din—algn—data to a data input/output sense amplifier 110 depending on X4, X8, or X16 mode. The data input/output sense amplifier 110 is constructed with 64 sense amplifiers, which outputs the data sensed in the data input/output sense amplifier 110 through 64 global input/output lines GIO to a write driver 120 depending on a control signal dinstbp generated from a data input strobe signal generator 90.
The write driver 120 is separately operated depending on X4 and X8 mode selection signals to load input data on local input/output lines LIO and LIOB.
For the conventional write path scheme described above, 64 sense amplifiers in the data input/output sense amplifier unit are arranged to be operated irrespective of X4, X8, or X16 mode, so that 64 global input/output lines are toggled. As a result, since the global input/output lines, which are not used in the X4 or X8 mode, are also toggled, there is a problem with how much power consumption is needed.


A method for reporting a streaming quality is shown, wherein at least one continuous media stream is streamed to a client (601), and wherein the streaming is controlled by a protocol (109) that is operated between the client (601) and a server (600), the method including selecting at least one quality metric and a quality metrics class from a pre-defined set of at least two quality metrics classes, and reporting to the server (600) the quality of the streaming based on the at least one selected quality metric and the selected quality metrics class. The protocol (109) is preferably a Real-time Streaming Protocol (RTSP) in combination with a Session Description Protocol (SDP) in the context of the 3GPP Packet-Switched Streaming Service (PSS). Also shown is a computer program, a computer program product, a system, a client, a server and a protocol.

Streaming refers to the ability of an application settled in a client to play synchronized media streams like audio and video streams in a continuous way while those streams are being transmitted to the client over a data network.
Applications that can be built on top of streaming services can be classified into on-demand and live information delivery applications. Examples of the first category are music and news-on-demand applications. Live delivery of radio and television programs are examples of the second category.
Streaming over fixed Internet Protocol (IP) networks is already a major application today. While the Internet Engineering Task Force (IETF) and the World Wide Web Consortium (W3C) have developed a set of protocols used in fixed-IP streaming services, no complete standardized streaming framework has yet been defined. For Third Generation (3G) mobile communications systems, according to the standards developed by the Third Generation Partnership Project (3GPP), the 3G Packet-switched Streaming Service (PSS, 3GPP TS 26.233) fills the gap between the 3G Multi-media Messaging Service (MMS), for instance downloading applications, and conversational services.
The PSS enables mobile streaming applications, wherein the complexity of the terminals is lower than that required for conversational services, because no media input devices and encoders are required, and because less complex protocols can be used. The PSS includes a basic set of streaming control protocols, transport protocols, media codecs and scene description protocols.
FIG. 1 schematically depicts the PSS protocol stack 1 that controls the transfer of both streamable and non-streamable content between a content or media server and a client.
Streamable content 101, such as video, audio and speech, is first converted to the payload format of the Real-time Transport Protocol (RTP) 102 in an adaptation layer 103. Said RTP as defined by the IETF provides means for sending real-time or streaming data by using the services of an underlying User Datagram Protocol (UDP) 104, which in turn uses the services of an underlying Internet Protocol (IP) 105.
Non-streamable content 106, as for instance still images, bitmap and vector graphics, text, timed text and synthetic audio are transferred by the Hypertext Transfer Protocol (HTTP) 107, which uses the services of the underlying Transport Control Protocol (TCP) 108 and the further underlying IP 105.
Whereas for the non-streamable content 106, the built-in session set-up and control capabilities of the HTTP 107 are sufficient to transfer the content, in case of streamable content 101, an advanced session set-up and control protocol has to be invoked, for instance to start, stop and pause a streaming video that is transferred from the content server to the client via the RTP/UDP/IP. This task is performed by the Real-time Streaming Protocol (RTSP) 109, which may either use the underlying TCP 108 or the underlying UDP 104. RTSP requires a presentation description 110 at least to set-up a streaming session. Such a presentation description 110 may for instance be available in the form of a Session Description Protocol (SDP) file. Said SDP file contains the description of the session, for instance session name and author, the type of media to be presented, information to receive said media, as for instance addresses, ports, formats and so on, and the bitrate of the media.
If streaming content is to be viewed at the client side, for instance at a mobile terminal, the user of said terminal is first provided with a Universal Resource Identifier (URI) to specific content that suits his terminal. This URI may come form a WWW server, a Wireless Application Protocol (WAP) server, or may have been entered manually via the keyboard of the terminal. This URI specifies a streaming or RTSP server and the address of the content on that or another content server. The corresponding SDP file may now be obtained in a number of ways. It may be provided in a link inside the HTML page that the user downloads, for instance via an embed tag, or may also be directly obtained by typing it as a URI. The SDP file, i.e. the presentation description 110, then is transferred via the HTTP 107 as indicated in the middle column of the protocol stack of FIG. 1. Alternatively, it may also be obtained through RTSP 109 signalling, for instance by using the DESCRIBE method of the RTSP 109, as indicated by the right column of the protocol stack in FIG. 1. Note that the presentation description may equally well be transmitted by said RTP 102. However, for simplicity of presentation, this possibility was not included in FIG. 1.
The subsequent session establishment is the process in which the browser or the user of the mobile terminal invokes a streaming client to set up the session against the content server. The terminal is expected to have an active radio bearer that enables IP-based packet transmission at the start of session establishment signalling.
The subsequent set-up of the streaming service is done by sending an RTSP SETUP message for each media stream chosen by the client. This returns the UDP 104 and/or TCP 108 port to be used for the respective media stream. The client sends an RTSP PLAY message to the content server that then starts to send one or more streams over the IP network.
In order to offer service providers in PSS systems means to evaluate the end user streaming experience, streaming service quality metrics have been introduced in PSS systems, as presented in 3GPP Technical document (Tdoc) S4-030860: "Draft Rel-6 PSS Quality Metrics Permanent Document v.0.10", which refers to 3GPP TSG-SA4 meeting #29 in Tampere, Finland, Nov. 24-28, 2003. The streaming client measures and feedbacks information on the quality of the actual streaming application to a streaming server, wherein said quality is defined in terms of said quality metrics. Said streaming server may for instance be an RTSP server, and said quality metrics may for instance be transported by using said RTSP and SDP.
Because the service is transparent to the type of RAN and CN, only the streaming client and the streaming server are impacted by the PSS quality metrics. One consequence of this is that the measurements may not rely on information from protocol layers below the RTP layer (e.g. UDP, IP, PDCP, RLC).
The terminal in a PSS system with quality feedback is responsible to perform the quality measurements in accordance to the measurement definition, aggregate them into streaming client quality metrics and report the metrics to the streaming server. This requirement does not preclude the possibility for the streaming client to report raw quality measurements to be processed by the streaming server into quality metrics.
The streaming server is responsible to signal the activation of the streaming client's quality metrics reporting and to gather the streaming client's quality metrics. The streaming server may process the received streaming client's quality metrics to build aggregated quality metrics. E.g. it could receive a raw lost packets report and build the Min, Max, Avg and Std packet loss rate for a particular streaming client.
The objective of the quality metric definition is to obtain consistent measurements across content type, terminals, and types of Radio Access Network (RAN).
The constraints are to minimize the size of the quality metrics report that will be sent to the streaming server and, the complexity for the terminal.
The quality metrics can be divided in 3 different types:
A first set of metrics are computed from terminal-based media quality measurements (measured within the decoder or predicted at the decoder input), e.g. the corruption duration, which is defined as the time from the start of the first corrupted media (audio/speech/video) decoded frame to the start of the first subsequent decoded good frame or the end of the reporting period (whichever is sooner), not including the buffering freezes/gaps and pause freezes/gaps.
A second set of metrics are computed by the terminal based on the general PSS protocol and the operation of the player that renders the streaming application. E.g. abnormal termination of a session.
A third set of quality metrics are computed based on terminal-measured network characteristics. E. g. number of packets lost in succession.
As already mentioned, in PSS systems RTSP is used for the feedback of quality reports according to the quality metrics. FIG. 2a lists the definition of an RTSP protocol data unit header 2a QoE-Metrics for the negotiation of the quality metrics between the streaming client and the streaming server, and FIG. 2b lists the definition of an RTSP protocol data unit header 2b QoE-Feedback for the actual feedback of quality metrics from the streaming client to the server, wherein QoE stands for "Quality of Experience".
The negotiation header 2a of FIG. 2a can be used in two ways:    1. If only the Off parameter is used, this is an indication that either the streaming server or the streaming client wants to cancel the quality metrics monitoring and reporting.    2. If the header 2a contains other parameters, then the quality metrics transmission is requested to start (or restart in case of mid-session monitoring).
If the negotiation header 2a is used with the RTSP Session Control url information, then QoE-Metrics is used at the session level. If the url is an RTSP Media Control url, then QoE-Metrics is used at the media level and each media gets its own QoE-Metrics line.
It is required to set the sending rate. If the Sending-rate value is 0, then the streaming client can send feedback messages at any time depending on events occurring in the streaming client. Values ≥1 indicate a precise message-sending interval. The shortest interval is once a second and the longest interval is undefined. The feedback sending interval can be different for different media, but it is recommended to keep a sort of synchronization, to avoid extra traffic in the uplink direction. The value End indicates that only one message is sent at the end of the session. The Range field can be used to define the time limit of feedback sending. In this way it is possible to decide the monitoring time range during the negotiation phase.
The actual quality metrics feedback can be conveyed to the PSS server by using the SET_PARAMETER method of the RTSP with the feedback header 2b of FIG. 2b.
In the feedback header 2b of FIG. 2b, Stream-url is the RTSP session or media control URL identifier for the feedback parameter. The Metrics field in the Parameters definition contains the name of the metrics/measurements (for instance corruption duration, etc.) and it shall be the same as the Metrics field in the negotiation QoE header 2a (QoE-Metrics). It is recommended to keep the order of metrics the same to simplify parsing. The Value field indicates the results. There is the possibility that the same event occurs more than once during a monitoring period. In that case the metrics value can occur more than once, which indicates the number of events to the server. The optional Timestamp indicates the time when the event (or measurement) occurred or when the metric was calculated since the beginning of the session. Also no events can be reported (using the SP—space). The optional Range indicates the reporting period.
Quality metrics reporting is normally done by the PSS client using the SET_PARAMETER method of the RTSP. However, in particular cases, it is more efficient to use other methods to carry the information, as for instance the TEARDOWN message or the PAUSE message.
Turning back to the above-stated quality metrics definition of the corruption duration as a representative of a first set of quality metrics that are computed from terminal-based media quality measurements, it is readily seen that, apart from the dependency of this quality metrics definition on the further definition of a "corruption" and a "reporting period", this quality metrics definition particularly depends on a definition of a "good frame".
A good frame is a media (audio/speech/video) decoded frame that is not corrupted, i.e. that doesn't contain any freezes/gaps or quality degradations. To declare a video or audio frame as good, in Tdoc S4-030860, the following definition is introduced: "A good frame is the earlier of N frames after last loss or a complete I-frame, where N is either (a) signalled or (b) defaults to ∞ (for video) or 1 (for audio)".
The application of this definition is not mandatory, resulting in a wide range of interpretations of the definition of a good frame. Thus different streaming clients may report different streaming qualities, because for the same quality metric (for instance corruption duration), different definitions for a "good frame" are applied. A similar ambiguity arises when different terminals use different error tracking algorithms, so that even when using the same definition of a "good frame", the reported streaming quality in terms of the same quality metric may differ across the terminals. These ambiguities cause the reported quality metrics to be imprecise and effectively worthless.

This patent is subject to a terminal disclaimer.


A speed governor for an integrated circuit which prevents the operation of the integrated circuit above a selected frequency. The speed governor generates a frequency reference and compares the frequency reference to the frequency of the external clock signal that clocks the integrated circuit. As a result of the comparison, if the frequency of the input clock signal is greater than the frequency reference then operation of the integrated circuit is disrupted.

In some computers systems, the need may arise to disable the computer when an input clock signal exceeds an upper limit. For instance, using a clock that is too fast may cause problems in a system, since some of the components in the system may not be able to operate at the higher frequency.
In the fabrication of microprocessors, it is common to find out that some of the microprocessors are able to operate at higher frequencies than others even though all are fabricated with the same processor. Process variations affecting, for example, the thickness of oxides can cause some wafer runs to yield parts that operate at much higher frequencies than in other wafer runs. Some companies test the upper frequency performance of newly fabricated microprocessors and sort them into "frequency" bins. Consequently, some microprocessors when sold are graded (and labeled) for higher frequencies than others. The microprocessor may not function properly for frequencies above its labeled frequency, especially under stressful ambient conditions or marginal power supply potential.
Companies have found that parts labeled with one frequency are sometimes relabeled after being sold by the manufacturer with higher frequencies, and then resold. These relabeled parts could end up in computer systems sold to operate at higher frequencies than the manufacturer intended. An innocent purchaser of such a computer could find that the computer operates well part of the time but fails at other times. The failures may be difficult to trace, and if traced to the microprocessor, reflect badly on the manufacturer.
At least one manufacturer has incorporated a speed governor in its microprocessors which cause the microprocessors to fail if the clocking signals applied to them are higher than the frequency they were originally sold for. When this is done, the microprocessor could never be used in higher frequency applications since it will never operate at the higher frequencies.
In U.S. Pat. No. 5,107,523, entitled "Processor Clock Governor", issued Apr. 21, 1992 and assigned to the assignee to the present invention, a circuit is described for disabling a microprocessor when a clock with an improper frequency is used. A problem with this circuit is that the manner in which the "kill" signal is generated is itself subject to process variations and hence may not be settable with the precision desired.
In U.S. Pat. Nos. 5,280,605 and 5,274,337, a clock speed limiter is disclosed and uses an integrated resistor as the basis for a timing reference. The resistance value is sensitive to temperature variation, which makes the timing reference variable with temperature. In other words, because the resistance value is sensitive to temperature variation, the cut-off frequency is not constant with temperature, making it difficult to set a reliable cut-off value without losing yield.
As will be disclosed, the present invention provides a circuit that is substantially independent of temperature and process variation and additionally provides other advantages.

Clock speed limiter for an integrated circuit


A tone color control apparatus for a musical tone signal producer has a first memory and a second memory. The first memory memorizes plural sets of tone color data for control of each tone color of plural different musical tone signals produced at the musical tone signal producer. The second memory memorizes plural sets of index data for indexing the plural sets of tone color data and also memorizes plural sets of modification data respectively corresponding with each set of index data. A desired set of the memorized index data and the corresponding set of the modification data are simultaneously read out from the second memory under control of tone color selection by a player. The tone color data are also read out from the first memory under control of the read out index data. The read out tone color data are modified based on the read out modification data to be applied to the musical tone signal producer for controlling a tone color of a musical tone signal produced therefrom.

1. Field of the Invention
The present invention relates to a tone color control apparatus for controlling a tone color of a musical tone signal produced at a musical tone signal producer.
2. Description of the Prior Art
In Japanese Patent Application Laid-Open No. 3-120594 and Japanese Utility Model Publication No. 63-28477, there is disclosed a tone color control apparatus having a memory for memorizing plural sets of tone color data and an editor for editing the tone color data memorized in the memory, wherein each set of the tone color data is read out from the memory and applied to a musical tone signal producer for controlling each tone color of different musical tone signals produced therefrom under modification of the tone color data by the editor. It is, therefore, obliged for a player to edit the tone color data whenever he needs various musical tone signals each tone color of which is slightly different.
U.S. Pat. No. 3,897,709 discloses a tone color control apparatus having plural sets of preset memories each comprised of a plurality of fixed resisters and a set of variable memories comprised of a plurality of variable resisters, wherein one of the plural sets of preset memories is selected by a player to produce a set of voltage control signals, and wherein the voltage control signals are modified by a set of modification voltage signals from the set of variable memories and applied to a musical tone signal producer for controlling a tone color of the musical tone signal produced therefrom under control of the modified voltage control signals. In this case, it is also obliged for a player to manipulate the variable resisters for producing various musical tone signals slightly different in their tone colors. Moreover, the tone color control apparatus becomes relatively large in size due to provision of the fixed and variable resistors.

Tone color control apparatus for musical tone signal producer


A cover for enclosing a belt of a back support brace. The inventive device includes an outer cover assembly for coextensively covering an outer rear surface of a lumbar support belt. A securing assembly is extendable about the belt to releasably couple the outer cover assembly thereto so as to protect and improve aesthetic appearance of the belt.

1. Field of the Invention
The present invention relates to covering devices and more particularly pertains to an back support belt cover for enclosing a belt of a back support brace.
2. Description of the Prior Art
The use of covering devices is known in the prior art. More specifically, covering devices heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art covering devices include U.S. Pat. Nos. 5,228,609; 5,257,419; 5,188,586; 5,111,806; and 4,384,372.
While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not disclose a back support belt cover for enclosing a belt of a back support brace which includes an outer cover assembly for coextensively covering an outer rear surface of a lumbar support belt, and a securing assembly extendable about the belt to releasably couple the outer cover assembly thereto so as to protect and improve aesthetic appearance of the belt.
In these respects, the back support belt cover according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of enclosing a belt of a back support brace.


A measuring sensor for use in determination of the heat flux through a solid medium according to the method in which two thermoelements are arranged at a defined distance and a temperature gradient of the medium is measured from which the heat flux is determined, composed of a body shaped to be fitted into an opening provided in the medium to be axially penetrated by the heat flux through the medium while the lateral surface of the body is thermally insulated from the medium, and constructed such that the integrated coefficient of thermal conductivity of the body is substantially equal to the coefficient of thermal conductivity of a volume of the medium having dimensions corresponding to those of the opening, the body including components of two different thermoelectric materials defining at least two spaced thermoelectrically effective contact points, and signal leads associated with the contact points and spaced apart in the direction of the heat flux; and wherein the exterior lateral surface of said body is insulated from the medium.

The present invention relates to a measuring sensor for determining heat flux through a solid medium, such as, for example, the cooled walls of a heating rod, the measurement being effected by arranging two thermoelements at a defined distance to effect a measurement of a temperature gradient of the mwedium, from which the heat flux is determined.
In many cases, heat flux in the interior or on the surface of bodies must be determined experimentally. Aside from the very integral method of determining a heat balance, there exist basically two different methods: measurement of the temperature gradient; and measurement of the temperature at one point, and determination of the heat flux by solving the so-called inverse heat conduction problem.
If, for example, the heat flux which is transmitted from the wall of a tube to a medium flowing through the interior of the tube is to be measured by measurement of the temperature gradient, two separate thermoelements are usually installed in the wall of the tube at different distances from its interior surface. The heat flux is calculated from the difference between the two temperatures, the distance between the points of mesurement and the heat conductivity of the tube wall. In many cases, however, this method fails because the dimensions are too small and the attainable accuracy is insufficient.
If, for example, a heat flux of 5 W/cm.sup.2 is to be determined by means of two thermoelements disposed at a distance of one millimeter, the temperature to be measured in a stainless steel wall is about 2.5.degree. K. If at a temperature of 500.degree. C. each one of the two temperatures is determined with an accuracy of .+-.1 per thousand, this tolerance alone results in an inaccuracy in the heat flux of .+-.40%. An additional inaccuracy is produced in the determination of the distance between the measuring locations, which without damage can be determined only roughly, and, even when a transverse cut is made in the tube wall, can be effected with an accuracy of .+-.0.05 mm, at most. Added to this is the interfering effect which the thermoelements have on the heat flow. For these reasons, this method can be used with sufficient accuracy only with large heat fluxes and relatively thick-walled tubes.
The method based on measurement of the temperature at one point and determination of the heat flux by solution of the inverse heat conduction problem can be used only for one-dimensional problems.
If, for example, the transient heat flux at the surface of a rod is to be measured, a thermoelement is usually installed in the outer layer of the rod and is used to measure the temperature directly below the surface of the rod as a function of time. The resulting temperature profile in the rod is calculated, taking into consideration the rod structure, including possible contact resistance between various layers
The heat flux is then varied in steps over a period of time to permit determination of that heat flux for which the temperature calculated for the site of the thermoelement coincides with the measured temperature. The solution of this inverse heat conduction problem often produces numerical instabilities which can be avoided only at considerable expense and which adversely influence the accuracy of the measurement.
However, the most significant adverse influence on the accuracy of this method is a lack of knowledge of the thermal behavior of the rod. Particularly the contact resistances pose a great uncertainty.

Sensor for determining heat flux through a solid medium


A method of determining a lowest point of a target object in an image of a scene. A region of the target object in the image is received. A horizontal vanishing line of the image is received. At least one reference object in the scene is selected. At least a first line connecting the received region of the target object and a highest point of the reference object is determined. At least an intersection point of the first line and the horizontal vanishing line is determined. At least a second line connecting the determined intersection point to a lowest point of the reference object is determined; and a lowest point of the target object is determined based on the second line.

Public venues such as shopping centres, parking lots and train stations are increasingly subject to surveillance using large-scale networks of video cameras. Application domains of large-scale video surveillance include security, safety, traffic management and business analytics. In one example application from the security domain, a security officer may want to view any video feed containing a particular suspicious person in order to identify undesirable activities. In another example from the business analytics domain, a shopping centre may wish to track customers across multiple cameras in order to build a profile of shopping habits. The aforementioned surveillance applications typically require persons to be detected, tracked, matched and analysed across multiple camera views even when the persons are partially occluded by other persons or objects in a scene. This is especially true when tracking persons in crowded scenes such as shopping malls, train stations etc. Tracking a person in a crowded scene requires robust detection of the person in the presence of occlusions.
One method of detecting a target object in an image detects objects using part based models. The part based model method uses a mixture of multi-scale deformable part models. For example, a part model may refer to a model of a part of the human body for detecting objects. However, there is a high computational load associated with the method since an occluded person in the scene needs to be matched against a potentially large number of part models to obtain a matching score. Further, the part based model method can still fail in the presence of severe occlusions.
Another method of detecting a target object in an image of a scene uses a calibrated camera and specifies a width for a person to be detected. Assuming that the feet of the person is visible in the image, the width and height of a bounding box enclosing a person can be determined iteratively by evaluating symmetry within the bounding box. However, the calibrated camera method fails when the feet of the person are not observable or if the presence of occlusions affects the symmetry within the bounding box.
Another method of detecting a target object in an image use training data to learn the size of a bounding box enclosing a person in the scene. Assuming a foreground mask is available for the scene representing foreground objects (e.g. moving persons), an objective function is used to maximise a trade-off between unary confidence scores and pairwise overlap penalties. However, this training data method requires a large amount of training data to learn the bounding box size to a high degree of accuracy. Despite this training date method is not robust to severe occlusions.
A camera may be calibrated from a vertical vanishing point and a horizon line. One method of estimating a vertical vanishing point is to track a moving person in a scene. However, the persons tracked in the scene to obtain a vertical vanishing point must be fully visible in the scene, or in other words completely unoccluded.

Method, system and apparatus for determining a lowest point of a target object in an image


Various embodiments are described that relate to directing of a signal. An incoming signal can be compared to a threshold voltage. If the signal does not meet the threshold voltage, then the signal can be used for normal usage, such as communication with a software-defined radio. However, if the signal does meet the threshold, then the signal can be directed away from normal usage. In one example, the signal can be directed away from a communication component and directed to an energy harvesting component that charges a battery of the software-defined radio.

A radio can be used as a communication device. The radio can receive a wireless signal that communicates information. In one example, the wireless signal can contain voice information. After reception, the radio can process the wireless signal such that the voice information is broadcast by way of a speaker. Similarly, the radio can transmit a wireless signal that contains voice information. These radios can be susceptible to damage from various factors.

The United States of America, as represented by the Secretary of the Army


An apparatus includes a socket and a housing. The socket and the housing can define an interior region for receiving an integrated circuit package. The housing includes a conductive member with a first portion exposed adjacent a bottom surface of the housing and a second portion at a side surface adjacent the interior region. The first portion can be electrically in contact with a printed circuit board. The second portion can be electrically in contact with a conductive member at a side surface of the integrated circuit package.

The invention relates to a shunt power connection for an integrated circuit package.
A socket electrically connects pins of a package to a printed circuit board. A package can contain various circuit elements as well as conductive paths such as vias for carrying input/output (I/O) signals or power for integrated circuits on a die connected to the package.
Depending on a particular die""s power requirements, additional vias may be required to deliver large amounts of current through a package to a die. This can result in high operating temperatures within a package.
Industry trends of reducing device sizes and increasing package densities also can result in high current densities and, consequentially, high operating temperatures inside packages.
High integrated circuit power requirements may require that a large number of available pin/socket combinations be dedicated to deliver power. Therefore, fewer pin/socket combinations may be available for I/O signal delivery.

Shunt power connection for an integrated circuit package