The present invention provides new Pestiviral RNA genomes (replicons) that are able to replicate, and can be packaged into infectious viral particles in cells that complement the missing protein(s), but do not produce infectious progeny virus. Such replicons can be useful for vaccine purposes.

Animals may be protected against pestiviruses by vaccination, however, conventional inactivated or modified live vaccines have disadvantages concerning safety as well as efficacy. Therefore, new types of vaccines should be developed.
Pestiviruses can be divided into two different biotypes, cytopathogenic (cp) and non cytopathogenic (ncp) viruses, respectively. Bovine viral diarrhea virus (BVDV), a member of the genus Pestivirus within the family Flaviviridae is the causative agent of bovine viral diarrhea, an economically important disease of cattle world-wide. Genetically and structurally closely related virus species are Classical Swine Fever Virus (CSFV) and the ovine Border Disease Virus (BDV). Pestiviruses can induce severe diseases with marked economical losses world wide. The major economic losses caused by BVDV infections are reduced fertility, abortions and the generation of persistently infected calves, which can develop fatal "Mucosal Disease". While cp BVDV induce apoptosis and cell death and express non-structural protein 3 (NS3), inoculation with ncp BVDV leads to persistent infection of cell cultures and NS3-expression is not detectable. The pestivirus genome consists of a single-stranded RNA of positive orientation. The RNA has a length of approximately 12.3 kb and contains one large open reading frame (ORF), which is flanked by non-translated regions (NTR) at both genome ends. The pestiviral ORF is translated into one polyprotein, which is co- and post-translationally processed into 11 (ncp BVDV) or 12 (cp BVDV) mature proteins by viral and cellular proteases. Pestivirus virions consist of four structural proteins, a capsid (C) protein and three glycosylated envelope proteins (ERNS, E1, E2). BVDV antibodies are directed against ERNS, E2 and NS3. Neutralizing activity was predominantly demonstrated for E2-specific antibodies.
Studies on the replication of pestiviruses have been considerably facilitated by reverse genetic systems and the discovery of autonomously replicating subgenomic RNAs (replicons) (4, 26).
Pestivirus genomes with deletions were first described as defective interfering particles (DI) for BVDV and CSFV (24, 27).
Since then many reports relating to the replication of pestiviruses have been published. Trans-complementation of structural proteins of viruses of the family Flaviviridae has been reported.
Pestivirus self-replicating RNAs are important tools for an understanding of virus replication, assembly and egress. Trans-complementation of deleted parts of the genome can be used, for example, for the identification of trans-acting elements of a pestiviral genome.
The minimal requirements for CSFV replication were investigated, for example, by creating defective CSFV genomes lacking the gene sequences for the structural proteins. It was found that the defective CSFV genomes still replicated and could be packaged into viral particles when introduced in SK-6 cells together with helper A187-CAT RNA (Moser et al., J. Virol., 7787-7794, 1999). An autonomously replicating defective BVDV genome which lacks the genes encoding C, Ems, E1, E2, p7 and NS2 had been described (Behrens et al., J. Virol., 72, 2364-2372, 1998). For the Kunjin virus (KUN) replicons with deletions in the structural regions were packaged into virons using a system where BHK-21 cells were transfected by two consecutive electropoartions, first with the mutated KUN replicons, and subsequently with a recombinant Semlike Forest Virus replicon expressing KUN structural proteins (Khromykh et al., J. Virol., 72(7), 5967-5977, 1998). For CSFV it had been recognized that trans-complemented defective virions that contained Ems deleted replicons could potentially serve as a basis for vaccines. CSFV, ERNS-deleted replicons were generated and trans-complemented using a swine kidney cell line (SK6) constitutively expressing CSFV ERNS. The resulting virions were able to infect SK6 cells without the production of infectious virus progeny and could be passaged on ERNS-expressing SK6 cells. Pigs were protected against lethal CSFV challenge after immunization with the complemented virions (40).
So far, there are only few reports concerning trans-complementation of BVDV replicons. Defects in the coding regions for non-structural proteins NS3, NSNS4a, NS4B and NS5B were found to be non complementable, whereas defects in the NS5A unit could be complemented in trans (Grassmann et al., J. Virol., 75, 7791-7802, 2001). (4, 18, 36) Trans-complementation of BVDV E2 and/or p7, using cell lines constitutively expressing BVDV E2 and/or p7 for complementation have also been described (Harada et al., J. Virol., 74, 9498-9506, 2000).

Replicons of pestviruses that do not express C and or E1 protein and infectious viral particles containing same, that can be used in vaccines


Technologies for live virtual machine migration include a plurality of compute nodes and a datacenter manager. The datacenter manager issues a request to migrate a virtual machine to a source compute node. The request includes a service level requirement such as a maximum migration time or downtime. The source compute node determines platform resources required to perform migration within the service level requirement and reserves the platform resources for a predicted migration time. The source compute node transfers virtual machine state to a destination compute node and releases the platform resources after the transfer is complete. The source compute node may use a hardware resource monitor or reservation manager to determine available platform resources and reserve the platform resources for exclusive use. If sufficient platform resources are not available, the source compute node may negotiate reduced service level requirements with the datacenter manager. Other embodiments are described and claimed.

Data centers increasingly rely on virtualization to deliver services to customers. A typical data center may include clusters of densely packed computing servers, called nodes, with each node potentially executing many virtual machines. Typically, each node includes a hypervisor or other virtualization framework, and the entire data center includes one or more datacenter managers that manage instantiation of virtual machines on the particular compute nodes. Virtual machines may be transferred, or "migrated," between nodes by transferring the complete state of the virtual machine from a source node to the destination node. Virtual machine migration may be performed "live," that is, without interrupting the state of the virtual machine and with minimal disruption to services provided. However, typical virtualized data centers may not provide time-critical or high-availability guarantees for virtual machine migration. Thus, virtual machine migration typically causes some amount of downtime when the virtual machine is unavailable, and that downtime may vary depending on virtual machine size, virtual machine load, network traffic, and other factors that may be unpredictable.
Telecommunication network functions are increasingly being consolidated into network data centers. For example, cellular base station functions that have historically been distributed among many cell towers may now be consolidated into a virtualized network data center. However, telecommunication networks typically have extremely high reliability requirements. Accordingly, typical live migration of virtual machines may have difficulty consistently achieving the reliability requirements for telecommunication network functions.

Reliable and deterministic live migration of virtual machines


According to one embodiment an antenna apparatus includes: a first conductor layer; a second conductor layer; a dielectric layer between the first and the second conductor layers; a plurality of first conductor vias corresponding to a first direction; a plurality of second conductor vias opposed to the first conductor vias corresponding to the first direction; and a plurality of first openings in the first direction in a region of the first conductor layer between the first and the second conductor vias. A plurality of third conductor vias are part of the plurality of first conductor vias and are arranged along the first openings. Positions of the third conductor vias in a second direction are different from positions of others of the first conductor vias in the second direction, the second direction is substantially orthogonal to the first direction and is substantially parallel to the first conductor layer.

A periodic leaky-wave antenna that includes a periodic leaking structure in a waveguide and radiates plane waves to space outside the waveguide is well-known. The periodic leaky-wave antenna can realize a beam-scanning antenna without a complicated feeding circuit because a radiation direction of the plane waves is changed depending on a frequency. As a kind of the periodic leaky-wave antenna, there is an antenna that uses, a waveguide structure in which conductor vias in two lines are densely arranged in a dielectric substrate including a conductor plate made of copper or the like on each of surfaces, and uses slots provided on one of the conductor plates as a leaking structure (radiation elements). The waveguide structure is called a post-wall waveguide or a substrate integrated waveguide (SIW).
In the above-described structure, the slots having the same dimension are arranged. Therefore, coupling amounts (obtained by dividing radiation power by incident power) of the respective slots are equal to one another. Accordingly, there are issues that an amplitude distribution on an antenna opening surface is exponentially reduced along the waveguide, and high antenna efficiency is not obtainable.


Novel .alpha.-amylase enzymes are disclosed in which one or more disulfide bonds are introduced into the enzyme via addition or substitution of a residue with a cysteine. The disclosed .alpha.-amylase enzymes show altered or improved stability and/or activity profiles.

.alpha.-Amylases (.alpha.-1,4-glucan-4-glucanohydrolase, EC 188.8.131.52) hydrolyze internal .alpha.-1,4-glucosidic linkages in starch, largely at random, to produce smaller molecular weight malto-dextrins. .alpha.-Amylases are of considerable commercial value, being used in the initial stages (liquefaction) of starch processing; in alcohol production; as cleaning agents in detergent matrices; and in the textile industry for starch desizing. .alpha.-Amylases are produced by a wide variety of microorganisms including Bacillus and Aspergillus, with most commercial amylases being produced from bacterial sources such as Bacillus licheniformis, Bacillus amyloliquefaciens, Bacillus subtilis, or Bacillus stearothermophilus. In recent years, the preferred enzymes in commercial use have been those from Bacillus licheniformis because of their heat stability and performance under commercial operating conditions.
In general, starch to fructose processing consists of four steps: liquefaction of granular starch, saccharification of the liquefied starch into dextrose, purification, and isomerization to fructose. The object of a starch liquefaction process is to convert a concentrated suspension of starch polymer granules into a solution of soluble shorter chain length dextrins of low viscosity. This step is essential for convenient handling with standard equipment and for efficient conversion to glucose or other sugars. To liquefy granular starch, it is necessary to gelatinize the granules by raising the temperature of the granular starch to over about 72.degree. C. The heating process instantaneously disrupts the insoluble starch granules to produce a water soluble starch solution. The solubilized starch solution is then liquefied by .alpha.-amylase (EC 126.96.36.199.).
A common enzymatic liquefaction process involves adjusting the pH of a granular starch slurry to between 6.0 and 6.5, the pH optimum of .alpha.-amylase derived from Bacillus licheniformis, with the addition of calcium hydroxide, sodium hydroxide or sodium carbonate. The addition of calcium hydroxide has the advantage of also providing calcium ions which are known to stabilize the .alpha.-amylases against inactivation. Upon addition of .alpha.-amylases, the suspension is pumped through a steam jet to instantaneously raise the temperature to between 80-115.degree. C. The starch is immediately gelatinized and, due to the presence of .alpha.-amylases, depolymerized through random hydrolysis of a (1-4) glycosidic bonds to a fluid mass which is easily pumped.
In a second variation to the liquefaction process, .alpha.-amylase is added to the starch suspension, the suspension is held at a temperature of 80-100.degree. C. to partially hydrolyze the starch granules, and the partially hydrolyzed starch suspension is pumped through a jet at temperatures in excess of about 105.degree. C. to thoroughly gelatinize any remaining granular structure. After cooling the gelatinized starch, a second addition of .alpha.-amylase can be made to further hydrolyze the starch.
A third variation of this process is called the dry milling process. In dry milling, whole grain is ground and combined with water. The germ is optionally removed by flotation separation or equivalent techniques. The resulting mixture, which contains starch, fiber, protein and other components of the grain, is liquefied using .alpha.-amylase. The general practice in the art is to undertake enzymatic liquefaction at a lower temperature when using the dry milling process. Generally, low temperature liquefaction is believed to be less efficient than high temperature liquefaction in converting starch to soluble dextrins.
Typically, after gelatinization the starch solution is held at an elevated temperature in the presence of .alpha.-amylase until a DE of 10-20 is achieved, usually a period of 1-3 hours. Dextrose equivalent (DE) is the industry standard for measuring the concentration of total reducing sugars, calculated as D-glucose on a dry weight basis. Unhydrolyzed granular starch has a DE of virtually zero, whereas the DE of D-glucose is defined as 100.
The maximum temperature at which the starch solution containing .alpha.-amylase can be held depends upon the microbial source from which the enzyme was obtained and the molecular structure of the .alpha.-amylase molecule. .alpha.-Amylases produced by wild type strains of Bacillus subtilis or Bacillus amyloliquefaciens are typically used at temperatures no greater than about 90.degree. C. due to excessively rapid thermal inactivation above that temperature, whereas .alpha.-amylases produced by wild type strains of Bacillus licheniformis can be used at temperatures up to about 110.degree. C. The presence of starch and calcium ion are known to stabilize .alpha.-amylases against inactivation. Nonetheless, .alpha.-amylases are used at pH values above 6 to protect against rapid inactivation. At low temperatures, .alpha.-amylase from Bacillus licheniformis is known to display hydrolyzing activity on starch substrate at pH values as low as 5. However, when the enzyme is used for starch hydrolysis at common jet temperatures, e.g., between 102.degree. C. and 109.degree. C., the pH must be maintained above at least pH 5.7 to avoid excessively rapid inactivation. The pH requirement unfortunately provides a narrow window of processing opportunity because pH values above 6.0 result in undesirable by-products, e.g., maltulose. Therefore, in reality, liquefaction pH is generally maintained between 5.9 and 6.0 to attain a satisfactory yield of hydrolyzed starch.
Another problem relating to pH of liquefaction is the need to raise the pH of the starch suspension from about 4, the pH of a corn starch suspension as it comes from the wet milling stage, to 5.9-6.0. This pH adjustment requires the costly addition of acid neutralizing chemicals and also requires additional ion-exchange refining of the final starch conversion product to remove the chemical. Moreover, the next process step after liquefaction, typically saccharification of the liquefied starch into glucose with glucoamylase, requires a pH of 4-4.5; therefore, the pH must be adjusted back down from 5.9-6.0 to 4-4.5; requiring additional chemical addition and refining steps.
Subsequent to liquefaction, the processed starch is saccharified to glucose with glucoamylase. A problem with present processes occurs when residual starch is present in the saccharification mixture due to an incomplete liquefaction of the starch, e.g., inefficient amylose hydrolysis by amylase. Residual starch is highly resistant to glucoamylase hydrolysis. It represents a yield loss and interferes with downstream filtration of the syrups.
Additionally, many .alpha.-amylases are known to require the addition of calcium ion for stability. This further increases the cost of liquefaction.
In U.S. Pat. No. 5,322,778, liquefaction between pH 4.0 and 6.0 was achieved by adding an antioxidant such as bisulfite or a salt thereof, ascorbic acid or a salt thereof, erythorbic acid, or phenolic antioxidants such as butylated hydroxyanisole, butylated hydroxytoluene, or a-tocopherol to the liquefaction slurry. According to this patent, sodium bisulfite must be added in a concentration of greater than 5 mM.
In U.S. Pat. No. 5,180,669, liquefaction between a pH of 5.0 to 6.0 was achieved by the addition of carbonate ion in excess of the amount needed to buffer the solution to the ground starch slurry. Due to an increased pH effect which occurs with addition of carbonate ion, the slurry is generally neutralized by adding a source of hydrogen ion, for example, an inorganic acid such as hydrochloric acid or sulfuric acid.
In PCT Publication No. WO 95/35382, a mutant .alpha.-amylase is described having improved oxidation stability and having changes at positions 104, 128, 187 and/or 188 in B. licheniformis .alpha.-amylase.
In PCT Publication No. WO 96/23873, mutant .alpha.-amylases are described which have any of a number of mutations.
In PCT Publication No. WO 94/02597, a mutant .alpha.-amylase having improved oxidative stability is described wherein one or more methionines are replaced by any amino acid except cysteine or methionine.
In PCT publication No. WO 94/18314, a mutant .alpha.-amylase having improved oxidative stability is described wherein one or more of the methionine, tryptophan, cysteine, histidine or tyrosine residues is replaced with a non-oxidizable amino acid.
In PCT Publication No. WO 91/00353, the performance characteristics and problems associated with liquefaction with wild type Bacillus licheniformis .alpha.-amylase are approached by genetically engineering the .alpha.-amylase to include the specific substitutions Ala-111-Thr, His-133-Tyr and/or Thr-149-IIe.
Studies using recombinant DNA techniques to explore which residues are important for the catalytic activity of amylases and/or to explore the effect of modifying certain amino acids within the active site of various amylases and glycosylases have been conducted by various researchers (Vihinen et al., J. Biochem., Vol. 107, pp. 267-272 (1990); Holm et al., Protein Engineering, Vol. 3, pp. 181-191 (1990); Takase et al., Biochemica et Biophysica Acta, Vol. 1120, pp. 281-288 (1992); Matsui et al., FEBS Letters, Vol. 310, pp. 216-218 (1992); Matsui et al., Biochemistry, Vol. 33, pp. 451-458 (1992); Sogaard et al., J. Biol. Chem., Vol. 268, pp. 22480-22484 (1993); Sogaard et al., Carbohydrate Polymers, Vol. 21, pp. 137-146 (1993); Svensson, Plant Mol. Biol., Vol. 25, pp. 141-157 (1994); Svensson et al., J. Biotech. Vol. 29, pp. 1-37 (1993)). Researchers have also studied which residues are important for thermal stability (Suzuki et al., J. Biol. Chem., Vol. 264, pp. 18933-18938 (1989); Watanabe et al., Eur. J. Biochem. Vol. 226, pp. 277-283 (1994)); and one group has used such methods to introduce mutations at various histidine residues in a Bacillus licheniformis amylase, the rationale being that Bacillus licheniformis amylase which is known to be relatively thermostable when compared to other similar Bacillus amylases, has an excess of histidines and, therefore, it was suggested that replacing a histidine could affect the thermostability of the enzyme. This work resulted in the identification of stabilizing mutations at the histidine residue at the +133 position and the alanine residue at position +209 (Declerck et al., J. Biol. Chem., Vol. 265, pp. 15481-15488 (1990); FR 2 665 178-A1; Joyet et al., Bio/Technology, Vol. 10, pp. 1579-1583 (1992)).
The introduction of di-sulphide bonds into proteins by site-directed mutagenesis affords a means of stabilizing native, folded conformations, see e.g., Villafranca et al., Science, Vol. 222, pp. 782-788 (1983). Hazes et al., Prot. Eng., Vol. 2, No. 2, pp. 119-125 (1988) suggest introducing disulfide bonds to a protein via a modeling algorithm which starts with the generation of the C.beta. position from the N, C.alpha. and C atom positions available from a known three-dimensional model. A first set of residues is selected on the basis of the C.beta.-C.beta. distances; the S.gamma. positions are generated which satisfy the requirement that, with ideal values for the C.alpha.-C.beta. and C.beta.-S.gamma. bond lengths and for the bond angle at C.beta., the distance between the S.gamma. of residue 1 and C.beta. of residue 2 in a pair (determined by the bond angle at S.gamma.2) is at, or very close to, its ideal value; and the two acceptable S.gamma. positions are found for each cysteine and the four different conformations for each disulfide bond established. Finally the four conformations are subjected to energy minimization procedure to remove large deviations from ideal geometry and their final energies calculated. Sowdhamini et al., Prot. Eng., Vol. 3, No. 2, pp. 95-103 (1989) discloses that the introduction of disulfide bonds into proteins by site directed mutagenesis affords a means of stabilizing native folded conformations and suggests computer modeling techniques for assessing the stereochemical suitability of pairs of residues in proteins as potential sites for introduction of cysteine disulfide crosslinks. The authors suggest that the elemental condition for considering residue positions in proteins, as potential sites for cysteine introduction, to generate unstrained disulfides is that the alpha carbon distance between the two cysteine residues to be joined via the disulfide bond (C.alpha.-C.alpha.) be less than or equal to 6.5 Angstroms and that the beta carbon distance between the two cysteine residues to be joined via the disulfide bond (C.beta.-C.beta.) distance of less than or equal to 4.5 Angstroms.
Despite the advances made in the prior art, a need exists for an .alpha.-amylase which is more effective in commercial liquefaction processes but which allows activity at lower pH than currently practical. Additionally, a need exists for improved amylases having characteristics which makes them more effective under the conditions of detergent use. Because commercially available amylases are not acceptable under many conditions due to stability problems, for example, the high alkalinity and oxidant (bleach) levels associated with detergents, or temperatures under which they operate, there is a need for an amylase having altered, and preferably increased, performance profiles under such conditions.

Mutant .alpha.-amylase having introduced therein a disulfide bond


A vacuum canister includes a canister body and a cover body, wherein the cover body has a cover seat with an opening facing upwards, a through rod is disposed on a bottom wall of the cover seat, a valve seat is disposed at a lower opening end of the through rod, and a check valve is disposed on the valve seat. The cover seat is provided with an air extracting device including an inner barrel and an outer barrel. An opening end of the outer barrel is sleeved on the inner barrel. A through hole is axially opened in the inner barrel. The through rod passes through the through hole. The air extracting device includes a pressing handle sleeved on the outer barrel, wherein a lower end of the pressing handle abuts the push block. A limiting block is disposed on an outer circumferential wall of the pressing handle.

Canisters are common daily necessities and come with various types. A most common canister includes a canister body and a cover body. After food, medicine or the like is placed in the canister body, the cover body is covered to adequately isolate an article placed in the canister body from dust or the like. An existing canister can achieve adequate sealing performance and prevent air from entering, thus playing a certain role in keeping the article fresh. However, instead of being in a vacuum state, the article in the canister body is still exposed to air in the canister body and can only be preserved for a relatively short time.
A vacuum canister including a canister body and a canister cover is disclosed in the Chinese Patent No. CN201520041305.7. The canister cover includes an upper canister cover and a lower canister cover. An accommodating space is formed between the upper canister cover and the lower canister cover. An air outlet seat and an air inlet seat are disposed in the accommodating space. An air outlet hole is opened through the air outlet seat. An air inlet hole is opened through air inlet seat. A T-shaped sealing gasket is disposed in each of the air outlet hole and the air inlet hole. In the air outlet hole, a transverse side of the T-shaped sealing gasket abuts an upper surface of a first step of the air outlet hole. In the air inlet hole, a transverse side of the T-shaped sealing gasket abuts a lower surface of a second step of the air inlet hole. When the canister cover is pressed from an opening of the canister body towards the interior of the canister body, air within the canister body pushes up the transverse side of the T-shaped sealing gasket to be expelled from the air outlet hole. When air within the canister is expelled, the transverse side of the T-shaped sealing gasket is tightly attached to the surface of the air outlet seat. To take out food, the canister cover is pulled outwards to allow air to enter the canister body through the air inlet hole until the canister cover completely slides out from the canister body.
In such vacuum canister, both the air inlet seat and the air outlet seat need to be disposed on the canister body, leading to a complex structure. A push-pull rod is further disposed on the canister cover. The total length of the entire canister cover and the push-pull rod is almost equal to that of the canister body, and as a result it is inconvenient to carry such a vacuum canister. The canister cover is pressed into the canister body to expel air within the canister body. If a stored article has an irregular shape, air within the canister body cannot be completely expelled. Even if the article has a regular shape, air still remains in the air inlet hole and the air outlet hole, and a desired degree of vacuum cannot be ensured in the canister body. During the storage of liquid food such as soup and drink, the canister needs to be prevented from shaking, even less being put upside down, or otherwise liquid may flow out through the air inlet hole and the air outlet hole.


Apparatus for removing a burr from an aperture in a workpiece, using a rotating deburring tool having a flexible or partly flexible shaft, an abrasive mechanism that rotates on the shaft and a collar that protects the workpiece from abrasion when the abrasive mechanism is being positioned for deburring. Optionally, the shaft and abrasive mechanism move laterally as they rotate. Optionally, a shaft holder includes a protective surrounding sleeve to catch or deflect any fragment of the shaft holder that might fly off. Optionally, the shaft and the workpiece rotate independently of each other. Two or more different abrasive mechanisms can be simultaneously attached to the shaft. The cross-sectional shape of the abrasive mechanism may be curvilinear and/or polygonal, depending upon shape of the workpiece surface. Optionally, a shaft restrictor receives the shaft and limits lateral motion of the rotating shaft. The shaft optionally includes a rotatable mass that provides additional rotational inertia after the shaft is initially spun up.

Removal of undesirable projections (collectively referred to as "burrs" herein) from a surface, such as a metal or other relatively hard material, is important in the metal finishing industry, especially where presence of an unremoved burr can interfere with flow of a liquid or with the positioning of electrical charge-carrying lines. Producers of vehicles, such as automotive vehicles, water-borne vehicles and aircraft are especially concerned with burr removal on surfaces of tubes, cylinders and other containers and housings. However, many of the surfaces that contain burrs (referred to herein as "burred surfaces") are relatively inaccessible, located in small spaces and cannot be de-burred by a conventional de-burring tool. For example, when two intersecting vias or apertures are drilled in a metal, breakthough of the drill for the second aperture into the space that is part of the first aperture will often produce a large metal burr at or near the intersection.
Further, in some situations two or different burr removal materials may be needed within a single container or housing. One example occurs where rough burr removal is to be followed by finishing, each requiring a different burr removal material or tool shape. Another example occurs when a container includes two or more different materials, each with a burred surface that requires its own burr removal mechanism and associated material.
When a burr removal tool is positioned to remove a burr, operation of the tool may unintentionally, and undesirably, contact and remove material that is preferably left intact. A burr removal tool often has a connecting rod extending between an abrasive nodule used for burr removal and a motor that provides mechanical movement of the nodule. Occasionally, the nodule briefly binds against the material to be removed, causing the rod to move laterally or in another uncontrollable manner.
What is needed is a burr removal tool that is flexible for reaching around obstructions and corners, can fit into relatively small spaces, provides two or more different burr removal materials in a single tool, and provides protection of a burred surface as the tool is moved into position for burr removal. Preferably, the tool should be small and flexible enough to permit rapid interchange of one type of burr removal mechanism by another. Preferably, the shape of the burr removal nodule should be chosen to minimize the amount of non-burr material that is removed. Preferably, motion of the shaft should be controlled to prevent occurrence of undesired excursions when the burr removal nodule temporarily binds against material being removed.


The present invention is directed to a novel process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents that are useful in the synthesis of a variety of pharmaceuticals, in particular certain cysteine protease inhibitors.

1. Field of the Invention
The present invention is directed to a novel process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents that are useful in the synthesis of a variety of pharmaceuticals, in particular certain cysteine protease inhibitors.
2. State of the Art
Heteroaryl and unsaturated heterocycloalkylmagnesium reagents are useful in the synthesis of a variety of pharmaceuticals, such as renin inhibitors and cysteine protease inhibitors. For example, heteroarylmagnesium reagents are used in the synthesis of 1-hydroxy-1-(heteroaryl or unsaturated heterocycloalkyl)-2-N-protected-aminoethyl intermediates which are then used in the synthesis of a number of peptidic pharmaceutically active agents (see EP 0376012 which discloses the use of 1-hydroxy-1-(heteroaryl)-2-aminoethyl in the synthesis of renin inhibitors and PCT Application Publication No. WO 00/55144 and Ohmoto, K. et. al., J. Med. Chem. 2001, 44, 1268 which disclose the use of 1-hydroxy-1-(heteroaryl or heterocycloalkyl)-2-aminoethyl in the synthesis of protease inhibitors). At present, 1-hydroxy-1-(heteroaryl)-2-N-protected-aminoethyl intermediates used are prepared by reacting an aldehyde with a heteroarylmagnesium reagent or by assembly of the heterocyclic/heteroaryl ring. The heteroarylmagnesium reagent used in this process is prepared by first treating a heteroaryl with an organolithium reagent and then converting the resulting lithiated species into a Grignard reagent under transmetallation reaction conditions. The drawbacks of these procedures are that they require very low reaction temperatures, typically −78° C., or are not the most economical or expedient route.
In order to avoid low temperature chemistry, the heteroarylmagnesium reagent can be prepared by reacting the corresponding heteroaryl halide with magnesium turnings in the presence of an initiation mixture containing ethyl bromide and iodine crystals. The drawback of this procedure is that the initiation of the reaction is very unpredictable and the reaction is highly exothermic and hence requires appropriate set up to keep the reaction temperature under control. Additionally, this method can be subject to undesirable side reactions, such as Wurtz coupling. These drawbacks make the use of heteroaryl or unsaturated heterocycloalkylmagnesium reagents unattractive for large-scale synthesis of pharmaceuticals.
Accordingly, there is a need for a synthetic process that would be amenable to large-scale synthesis of these compounds without the limitations discussed above. The present invention fulfills this and related needs.

Process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents and uses thereof


In a processor executing instructions in at least a first instruction set execution mode having a first minimum instruction length and a second instruction set execution mode having a smaller, second minimum instruction length, line and counter index addresses are formed that access every counter in a branch history table (BHT), and reduce the number of index address bits that are multiplexed based on the current instruction set execution mode. In one embodiment, counters within a BHT line are arranged and indexed in such a manner that half of the BHT can be powered down for each access in one instruction set execution mode.

The present invention relates generally to the field of processors and in particular to an effective organization for a branch history table in a processor having variable length instruction set execution modes.
Traditional instruction set architectures for processors have a uniform instruction length. That is, every instruction in the instruction set comprises the same number of bits (e.g., 16 or 32). Processors having variable length instruction set execution modes—wherein the processor may execute instructions having different bit lengths—are known in the art. For example, recent versions of the ARM architecture include 16-bit instructions that are executed in a 16-bit instruction set execution mode (Thumb mode) as well as the traditional 32-bit ARM instructions that are executed in a 32-bit instruction set execution mode (ARM mode).
One problem with processors executing variable length instructions is that instructions do not fall on uniform memory boundaries. Accordingly, circuits or operations that increment through, or randomly address, instructions (or ancillary constructs associated with instructions) cannot utilize a uniform incrementing or addressing scheme. Rather, they must alter the addressing scheme based on the length of instructions currently being executed, i.e., the current instruction set execution mode.
Most modern processors employ a pipelined architecture, where sequential instructions, each having multiple execution steps, are overlapped in execution. For maximum performance, the instructions should flow continuously through the pipeline. Any situation that causes instructions to stall in the pipeline detrimentally affects performance. If instructions must be flushed from the pipeline and subsequently re-fetched, both performance and power consumption suffer.
Virtually all real-world programs include conditional branch instructions, the actual branching behavior of which is not known until the instruction is evaluated deep in the pipeline. To avoid the stall that would result from waiting for actual evaluation of the branch instruction, most modern processors employ some form of branch prediction, whereby the branching behavior of conditional branch instructions is predicted early in the pipeline. Based on the predicted branch evaluation, the processor speculatively fetches and executes instructions from a predicted address—either the branch target address (if the branch is predicted taken) or the next sequential address after the branch instruction (if the branch is predicted not taken). When the actual branch behavior is determined, if the branch was mispredicted, the speculatively fetched instructions must be flushed from the pipeline, and new instructions fetched from the correct next address. Speculatively fetching instructions in response to an erroneous branch prediction adversely impacts processor performance and power consumption. Consequently, improving the accuracy of branch prediction is an important design goal.
Several methods of branch prediction are based on the branch evaluation history of the branch instruction being predicted and/or other branch instructions in the same code. Extensive analysis of actual code indicates that recent past branch evaluation patterns may be a good indicator of the evaluation of future branch instructions.
One known form of branch prediction utilizes a Branch History Table (BHT) to store an indication of recent branch evaluations. As one example, the BHT may comprise a plurality of saturation counters, the MSBs of which serve as bimodal branch predictors. For example, each counter may comprise a 2-bit counter that assumes one of four states, each assigned a weighted prediction value, such as:
11—Strongly predicted taken
10—Weakly predicted taken
01—Weakly predicted not taken
00—Strongly predicted not taken
The counter increments each time a corresponding branch instruction evaluates "taken" and decrements each time the instruction evaluates "not taken." The MSB of the counter is a bimodal branch predictor; it will predict a branch to be either taken or not taken, regardless of the strength or weight of the underlying prediction. A saturation counter reduces the prediction error of an infrequent branch evaluation, as a single branch evaluation in one direction will not change the prediction of a counter that is saturated in the other direction.
In the case of a "local" BHT, each branch instruction, the branch evaluation of which is being predicted, is associated with a single BHT counter. Accordingly, the BHT is indexed with part of the branch instruction address (BIA). Many modern processors fetch a plurality of instructions in blocks or fetch groups, in a single fetch operation. In this case, the address associated with the block or fetch group is considered a BIA, as the term is used herein. In the case of a "global" BHT, recent global branch evaluation history may be concatenated with (gselect) or hashed with (gshare) the BIA prior to indexing the BHT counters.
Instruction sets having different instruction lengths complicate the design of BHTs. In particular, the BHT is ideally indexed differently in each different instruction set execution mode, since each counter is associated with a branch instruction, and the instructions fall on different memory boundaries in different instruction set execution modes. One known solution is to simply size the BHT based on the largest instruction length, but address it based on the smallest instruction length. This solution leaves large pieces of the table empty, or with duplicate entries associated with longer branch instructions. Another known solution is to multiplex the BHT index addresses, effectively using a different part of the instruction address in each different instruction set execution mode. This adds a large number of multiplexers, which increases silicon area and power consumption. More critically, however, it adds delay to a critical path, thus increasing the cycle time and adversely impacting processor performance.

Effective use of a BHT in processor having variable length instruction set execution modes


The invention provides a vending machine for cooling food products. The vending machine includes a housing defining an interior. The vending machine also includes a plurality of holding members substantially thermally isolated from one another and disposed in the interior. Each of the plurality of holding members includes inner and outer hollow members telescopically engaged with one another to define an inner cavity with an opening operable to communicate an individual food product and an outer cavity with an inlet and an outlet spaced from the inlet. The vending machine also includes a refrigeration system disposed outside of the interior and fluidly communicating individually with each of the outer cavities to cool each of the inner cavities.

Vending machines include an interior which houses food products and is cooled by a refrigeration system. The food products are disposed in the interior to be commonly cooled. A heat exchanger is disposed in the interior and one or more fans blow air across the heat exchanger to cool the air in the interior. The cooled air then cools the food products concurrently. In a basic design of a beverage machine, the machine is divided into two chambers—the lower chamber to house the refrigeration system, generally a vapor compression system, and the upper chamber to house the stack of beverage cans or bottles. The beverage cans and bottles are loaded vertically or horizontally and then dispensed by gravity into the dispensing chute. The entire upper chamber is cooled in these machines.
Vending machines generally are made in three sizes—small, medium and large. Typically the beverage can capacity of the small machines is 100 to 300 cans, of the medium 300 to 800 cans and of the large 800 to 1,500 cans. The steady state power consumption to maintain the machines at the beverage dispensing temperature in the range 36° F. to 38° F. is 325 W for small, 800 W for the medium and 1,200 W for the large machines. The steady state energy consumption is a component of the cost associated with operating the vending machine.

High efficiency beverage vending machine


A method and apparatus are disclosed for scheduling and confirming meetings in a data processing system which includes stored calendars for prospective attendees. A prompting screen is presented to a scheduler with blanks for keying in a desired meeting parameters including at least: a list of desired attendees; a desired date range; and a desired time span. A prompting screen is also presented to each prospective attendee to permit an attendee to key in attendee confirmation parameters which specify the conditions under which the prospective attendee will agree to attend a desired meeting. In a depicted embodiment of the present invention, a prospective attendee may identify selected attendees who must or must not attend a desired meeting in order to confirm the prospective attendees attendance at that meeting. A comparison of each prospective attendees' calendar with the desired meeting parameters and the attendee confirmation parameters is then utilized to determine if an available meeting time complies with all required parameters.

1. Technical Field
The present invention relates in general to meeting scheduling and in particular to a method and apparatus for scheduling meetings in a data processing system. Still more particularly, the present invention relates to a method and apparatus for permitting a prospective meeting attendee to specify conditions under which the attendee will attend a meeting.
2. Description of the Related Art
Scheduling of meetings has always been fraught with problems. This is particularly the case when one scheduling a meeting, or a meeting scheduler, has no management or other control over those whose attendance is either desired or necessary.
The prior art initially eased the scheduling burden in that keyboard/display terminal user's schedules could be stored in varying calendar forms, and all could be available for call-up at each terminal. These schedules could be called and scanned to determine common available times. This was extremely time consuming if schedules were only available in narrative form on a day-at-a-time basis. Even when monthly abbreviated schedules or calendars were available for call-up, mental or pencil and paper notation of available times was both error-prone and no minor chore.
The prior art has now gone further in solving the above-noted problems. Calendar application programs, stored in a host computer to which the terminal users are connected, are able to read calendars of prospective attendees and provide a listing of available meeting times and dates. One example of such a system is disclosed in U.S. Pat. No. 4,626,836 issued to Donald E. Curtis, et al., and assigned to the assignee of the present application. Curtis et al. teaches a technique whereby available times and dates are derived from date and time ranges provided by the scheduler and from this listing a meeting scheduler may select a suitable time and date.
More recently, this technique has been enhanced in U.S. Pat. No. 5,050,077, assigned to the assignee herein, wherein the method whereby prospective attendees, calendars are examined has been greatly enhanced by providing an efficient method whereby prospective attendees' calendars may be examined and the contents thereof utilized to modify a preselected time span within a predetermined date span to provide possible options for desired meetings.
Despite the advances these systems represent in the calendaring art, there currently exists no method or apparatus whereby a prospective attendee may specify selected conditions under which that attendee will consent to attend a desired meeting. For example, a prospective attendee may determine that it will only be necessary for that attendee to attend a desired meeting if another specific attendee does not attend. By providing a system which permits prospective attendees to specify attendee confirmation parameters, the process of scheduling meetings in a data processing system may be greatly enhanced.

Method and apparatus for meeting confirmation in a data processing system

International Business Machines Corporation


A tube attachment for microscopes which facilitates visual microscope work particularly over extended periods and which can be used universally for different types of microscopes and, at the same time, can be produced economically using simple manufacturing techniques, it is suggested that a tube attachment is constructed as a holder which can be adjusted with respect to height and, optionally, with respect to angle and can be fastened directly to a binocular tube of a microscope. The holder includes two carriers which are displaceable axially relative to one another and which have a forehead rest and a chin support or one carrier with the forehead rest for a user, and devices are provided at the carriers for clamping the adjusting movements of the carriers.

a) Field of the Invention
The invention is directed to a tube attachment for microscopes comprising a microscope stand with optical components for beam guidance and beam deflection, an illumination carrier arranged at the microscope stand, and a microscope tube.
b) Description of the Related Art
Generally, in order to work successfully with microscopes for extended periods of times the microscope must be comfortable to use and not cause fatigue. Therefore, many microscopes not only have a comfortable and handy arrangement of the operating elements, but are also already provided with a microscope tube which can be adjusted to any body size and displaced vertically in a continuous manner.
A great disadvantage in working with microscopes consists in that owing to the almost upright body posture of the user and the attitude of the user's head it may come about over extended periods at the microscope as a result of involuntary movements on the part of the user in a constant effort to achieve an optimal distance from the exit pupils of the eyepieces at the microscope tube that the exit pupils of the eyepieces not longer correspond, or correspond only partly, to the eye pupils of the user. This is a severe visual impediment for microscope work especially over extended periods of microscope use.
Auxiliary devices are known from ophthalmology, such as the auxiliary device described in DE 37 08 633 A1 for correcting ametropia for a user in binocular microscope tubes of surgical microscopes. This auxiliary device comprises a holder for the eyepieces which can be attached in a rotatable manner and which is outfitted with receptacles for eyeglasses. The receptacles are connected to one another by a telescope rod located at the distance of an eyeglass frame from the user's eye in order to afford possibilities for correcting defective vision in the user.
Further, DE 692 15 479 T2 discloses a contactless pressure measuring device and a method for measuring intraocular pressure in an eye. A supporting system for the patient's head comprising a chin support and a forehead rest is mounted at a base of the device.


The present invention provides to methods and compositions that treat or prevent deleterious effects associated with alcohol consumption including alcohol-induced flush reaction and hangover. The methods and compositions include famotidine and optionally succinic acid. The present invention further demonstrates compositions that include famotidine are effective at treating symptoms associated with a flush reaction in subjects that are not significantly responsive to treatments with the H1 antagonist loratidine or the H2 antagonist cimetidine.

Metabolism of alcohol involves a two step enzymatic reaction. First, alcohol is oxidized to acetaldehyde by alcohol dehydrogenase. Second, the acetaldehyde is oxidized to acetic acid by acetaldehyde dehydrogenase and glutathione. Acetic acid is then transported to the muscles and adipose tissue where it is further broken down into carbon dioxide and water. Thus, the rate at which alcohol is metabolized to acetic acid depends in part upon the balance of both alcohol dehydrogenase and acetaldehyde dehydrogenase. This balance is important because although alcohol is toxic to the body, acetaldehyde is actually more toxic than alcohol.
Polymorphisms in the acetaldehyde dehydrogenase gene correlate significantly to particular populations, such as those having Asian ancestry and even more significantly to those having Japanese ancestry. These polymorphisms frequently result in slowed conversion of acetaldehyde to acetic acid. Accordingly, without significant slowing of alcohol dehydrogenase activity, acetaldehyde begins to build up in the body. Rapid accumulation of acetaldehyde causes redness in the skin, primarily along the face and limbs. This condition is referred to as alcohol-induced flush reaction, also known as Asian flush.
A combination treatment for controlling alcohol-induced flush reaction is proposed in published U.S. patent application Ser. No. 11/009,559. Specifically, the authors propose a combined treatment prior to imbibing in alcohol, the treatment including administering both an H1 receptor histamine antagonist and a H2 receptor histamine antagonist. The proposed H1 receptor antagonists include terfenadine, astemisole and fenoxifene. The proposed H2 receptor antagonists included cimetidine, famotidine, nizatidine and ranitidine. Such treatments do not address the conversion of alcohol to acetic acid but instead propose to competitively antagonize H1 and H2 histidine receptors while in circulation, which temporarily reduces the appearance of symptoms. However, the proposed treatments suffer from two drawbacks. First, many that suffer from alcohol-induced flush reaction do not respond to many of the proposed antagonists, which indicates the antagonists are not interchangeable. Second, in some instances temporarily masking symptoms may lead to increased alcohol consumption, which may intensify deleterious effects once temporary relief ends.
Although alcohol-induced flush reaction is typically associated with redness that occurs relatively shortly after consumption of alcohol, the build up of acetaldehyde also contributes to hangover, which is often felt by many the morning after alcohol consumption. Common hangover effects include headache, nausea, dizziness, fatigue, thirst, tension, anxiety, paleness, tremor and perspiration. It is commonly believed that black coffee or further consumption of alcohol in the morning reduces the symptoms; however, the effectiveness varies across individuals.
Accordingly, there remains a need to develop new methods and compositions for the treatment and prevention of deleterious effects associated with alcohol consumption.

Treatment and prevention of deleterious effects associated with alcohol consumption


A method of making an antiperspirant active composition and the use of a heating step at elevated temperature to convert Al13 polyhydroxyoxoaluminum cations in the species detectable by 27Al NMR within an aqueous aluminum salt solution into Al30 polyhydroxyoxoaluminum cations in the species detectable by 27Al NMR without increasing a SEC Peak 3 area in the SEC chromatogram of the aluminum salt.

The invention relates to antiperspirant active compositions comprising an aluminum salt and to methods of making an antiperspirant active composition.
Antiperspirant salts, such as aluminum chlorohydrex (also called aluminum chlorohydrex polymeric salts and abbreviated here as "ACH") and aluminum zirconium glycine salts (abbreviated here as "ZAG", "ZAG complexes" or "AZG"), are known to contain a variety of polymeric and oligomeric species with molecular weights (MW) of 100 Da-500,000 Da. It has been clinically shown that, in general, the smaller the species, the higher the efficacy for reducing sweat.
In an attempt to increase the quality and quantity of smaller aluminum and/or zirconium species, a number of efforts have focused on: (1) how to select the components of ACH and ZAG that affect the performance of these materials as antiperspirants; and (2) how to manipulate these components to obtain and/or maintain the presence of smaller types of these components. These attempts have included the development of analytical techniques to identify the components. Size exclusion chromatography ("SEC") or gel permeation chromatography ("GPC") are methods frequently used for obtaining information on polymer distribution in antiperspirant salt solutions. With appropriate chromatographic columns, generally five distinctive groups of polymer species can be detected in commercial ACH and ZAG complexes appearing in a chromatogram as peaks 1, 2, 3, 4 and a peak known as "5, 6", referred to hereinafter as Peak 5. Peak 1 is the larger Zr species (greater than 60 Angstroms). Peaks 2 and 3 are larger aluminum species. Peak 4 is smaller aluminum species (aluminum oligomers, or small aluminum clusters) and has been correlated with enhanced efficacy for both Al and Al/Zr salts. Peak 5 is the smallest aluminum species. Various analytical approaches for characterizing the peaks of ACH and various types of ZAG actives are found in "Antiperspirant Actives—Enhanced Efficacy Aluminum-Zirconium-Glycine (AZG) Salts" by Dr. Allan H. Rosenberg (Cosmetics and Toiletries Worldwide, Fondots, D. C. ed., Hertfordshire, UK: Aston Publishing Group, 1993, pages 252, 254-256).
Attempts to activate antiperspirant salts to produce materials having improved efficacy have included developing processes for obtaining composition having large amounts of Peak 4 species.
The Applicant's earlier WO-A-2009/076591 discloses, inter alia, an antiperspirant composition having a composition with little or no Peak 3 and optionally little or no Peak 5. However, there is still a need for yet further improved antiperspirant compositions.
Solutions of partially neutralized aluminum are known to contain a variety of hydrolytic Al species. The identity and distribution of these various forms depends on the hydrolysis ratio (i.e. the OH:Al molar ratio), the Al precursor and the choice of the reaction condition. In the field of antiperspirant (AP) technology, SEC chromatography is the traditional method used for elucidating the distribution of these Al species. Conventional SEC physically separates Al species into domains which are subsequently measured using a concentration detector. It is generally recognized that at least five domains of Al species can be differentiated by size-exclusive chromatography. These domains are commonly referred to Peak 1, Peak 2 . . . Peak 5, where increasing peak number indicates smaller relative size of the eluting species. As discussed above, Peak 4 and Peak 5 have been implicated as highly efficacious Al domains. Monomeric Al, which is undesirable because of its acidity, is known to elute under Peak 5.
It is well known in the art that such a variety of hydrolytic Al species exists and that it is possible to distinguish large aqueous aluminum hydroxide molecules using spectroscopic methods such as 27Al NMR which elucidates the structural environment surrounding Al atoms which are embodied in various forms (Casey W H, "Large Aqueous Aluminum Hydroxide Molecules", Chem. Rev. 2006, 106 (1), pages 1 to 16.
There are two regions in a 27Al NMR spectrum that represent Al nuclei which are octahedrally coordinated (0 ppm-60 ppm) and tetrahedrally coordinated (60 ppm-80 ppm). The octahedral region is exemplified by the hexa-aqua Al species, i.e. monomeric Al, which resonates sharply at 0 ppm. The tetrahedral region is exemplified by resonance at 62.5 ppm from the Al13 polyhydroxyoxoaluminum cation. Al13 is composed of 12 octahedrally coordinated Al atoms surrounded by one centrally-cited Al atom which is tetrahedrally coordinated. The Al30 polyhydroxyoxoaluminum cation is essentially a dimer of the Al13 polyhydroxyoxoaluminum cation and contains 2 tetrahedrally sited Al atoms which yield a somewhat broad resonance at 70 ppm.
It is known that 27Al NMR spectroscopy may not fully elucidate the chemical composition of a partially neutralized Al salt solution, since there are a variety of Al species which give rise to broad, low resolution resonance peaks and thus can be considered as effectively NMR-invisible. Unless the 27Al NMR spectroscopy is carried out quantitatively, the relative concentration of these NMR-invisible species cannot be determined and must be inferred from SEC chromatography.
The state of the art discloses a number of methods for synthesizing and purifying the Al13 polyhydroxyoxoaluminum cation (for example Fu G. et al, "Aging Processes of Alumina Sol-Gels; Characterization of New Aluminum Polycations by 27Al NMR Spectroscopy" Chem. Mater. 1991, 3(4), pages 602 to 610).
It is known that the Al13 polyhydroxyoxoaluminum cation may be converted to obtain the Al30 polyhydroxyoxoaluminum cation by heating a solution of the Al13 polyhydroxyoxoaluminum cation (Roswell J et al, "Speciation and Thermal Transformation in Alumina Sols; Structures of the Polyhydroxyoxoaluminum Cluster [Al30O8(OH)56(H2O)26]18+ and its δ-Keggin Moieté", J. Am. Chem. Soc. 2000, 122, pages 3777 to 3778; Chen Z et al, "Effect of thermal treatment on the formation and transformation of Keggin Al13 and Al30 species in hydrolytic polymeric aluminum solutions", Colloids and Surfaces A: Physiochem. Eng. Aspects, 292 (2007) pages 110 to 118; and Allouche L et al, "Conversion of Al13 Keggin ε into Al30: a reaction controlled by aluminum monomers", Inorganic Chemistry Communications, 6 (2003) pages 1167-1170).
Heating an Al13 solution is the only high-yield synthetic pathway to achieving Al30 which has been described in the literature. As well as the references identified above, WO-A-2006/103092 and Shafran K L et al, "The static anion exchange method for generation of high purity aluminum polyoxocations and monodisperse aluminum hydroxide nano-particles", J. Mater. Chem., 2005, 15, pages 3415 to 3423, disclose the use of an ion-exchange process to synthesize Al13 to achieve greater than 90% purity, and disclose heating the thus-formed Al13 solution to form Al30.
However, as discussed above, when synthesizing aluminum salts for use as antiperspirant active compositions, in order to provide enhanced antiperspirant efficacy it is necessary to have a particular peak distribution for the SEC chromatogram of the Al species. The Chen et al paper identified above demonstrates that the concentration of 27Al NMR-undetectable Al species, increases dramatically during Al30 production. Table 1 below is an extract of data from the Chen et al paper.
Table 1 shows the Al species distribution measured by 27Al NMR in hydrolytic polymeric aluminum solutions which were synthesized at 80° C. and then heated at 95° C. for different durations shown.
TABLE 1Al Species distribution measured by 27Al NMRAlcontent (M)Heating TimeAlm (%)Al13 (%)Al30 (%)Alu (%)0.2M24 hr5.346.4573.0715.140.2M48 hr5.011.0771.7622.160.5M24 hr4.651.1635.1259.070.5M48 hr4.861.2738.4855.391.0M24 hr8.380.7214.7376.171.0M48 hr8.110.2116.0275.66
For different molar Al contents of 0.2M, 0.5M and 1.0M, it may be seen from table 1 that for each 24 hour heating time sample the Al30 proportion in the Al species was at most less than 75% and that increasing the heating time to 48 hours does not significantly increase, or even reduces, the Al30 species while potentially increasing the Alu NMR-inactive Al species. Therefore the data published by Chen et al shows that prolonged heating of an Al13 solution with the aim of trying to synthesize Al30 may result in unacceptably low Al30 concentrations and, importantly for aluminum antiperspirant actives, produce NMR-inactive Al species that may elute under Peak 2 or Peak 3 and reduce antiperspirant efficacy.
There is a need in the art for aluminum antiperspirant actives which have high antiperspirant efficacy.
There is also a need in the art for aluminum antiperspirant actives which have high stability.
There is also a need in the art for aluminum antiperspirant actives which have the combination of high antiperspirant efficacy and high stability.

Antiperspirant active compositions and manufacture thereof


A console for performing a medical procedure has connection ports for electrically coupling equipment. Each connection port may have an associated indicator that signals whether a piece of equipment should be connected to the respective connection port. The indicators may be selectively activated depending on the procedure being performed with the console.

Medical catheterizations are routinely carried for many procedures. In one representative example, cardiac arrhythmias including atrial fibrillation may be diagnosed as well as treated by employing a variety of catheters to access the patient's heart in a minimally invasive manner. Diagnosing such conditions may involve mapping the cardiac tissue to locate aberrant electrical pathways and currents within the heart, as well as to determine mechanical and other aspects of cardiac activity. Various methods and devices have been described for mapping the heart. Such methods and devices are described, for example, in U.S. Pat. Nos. 5,471,982, 5,391,199 and 5,718,241 and in PCT patent publications WO94/06349, WO96/05768 and WO97/24981. These techniques may employ catheters having electrodes for sensing cardiac electrical activity and as well as sensors for determining the position of the catheter relative to an externally-applied magnetic field. By determining the electrical activity at a plurality of locations and determining the spatial coordinates of the locations, a three dimensional (3D) map including the sampled points may be produced. Correspondingly, treatment of arrhythmia may rely on such maps to identify areas for treatment, which may include selectively ablating cardiac tissue by application of energy, e.g., radiofrequency energy via a catheter. The formation of nonconductive lesions may block or modify the propagation of unwanted electrical signals from their origin to help restore more normal function.
To coordinate the procedures described above, as well as others, a console may be provided with processing capabilities to receive and transmit signals associated with mapping or treatment. One or more catheters, each of which may exhibit wide variability in capability and function, may be connected to the console to supply or deliver electrical signals as warranted depending on the procedure being performed. For example, a mapping catheter may employ one or more diagnostic electrodes to sample electrical activity. Notably, many designs employ an electrode array, such as in a basket configuration, to record the signals at multiple locations simultaneously. Likewise, an ablation catheter may be configured to deliver energy to one or more locations, to perform focal ablation or linear ablation, respectively. Both types of catheters may employ position sensors to determine the position and orientation of the electrodes. Still further, depending on the desired functionality, a catheter may have any number of other sensors, such as temperature sensors and/or contact sensors, as well as other components that may require electrical connection to the console. In addition to catheters, a wide variety of other equipment including external positioning sensors, irrigation pumps, ultrasound transducers, electrocardiogram leads and others may also require connection to the console.
Therefore, it will be appreciated that the console must offer a relatively large number of ports or other types of connectors in order to perform its intended role in coordinating and enabling different procedures using different equipment, yet only a subset of the ports may in use during a given procedure. Accordingly, a user must match multiple cables with the appropriate ports and one or more ports may remain unconnected. In light the current trend of increasing numbers and types of catheters or other equipment that may be in potential use, the console connections will likely become yet more complicated.
Prior art attempts to reduce confusion associated with connecting equipment to the console have involved color coding the associated cables and ports. Other conventional attempts employ keyed connectors, so that a given piece of equipment will only couple with the correct port. Although such techniques may reduce the potential of connecting a piece of equipment to the wrong port, the risk of connecting additional equipment that may not be required for a procedure remains. Further, there is no immediate feedback when a necessary piece of equipment has not been connected, and the absence may not be noticed until after the equipment is needed, at which point correction may be more difficult.
What has been needed are systems and methods for reducing confusion associated with connecting catheters and other equipment to a console. It would be desirable to provide indication of which ports should be in use for the procedure being performed. It would also be desirable to provide ready indication when a necessary piece of equipment has not been connected. The techniques of this disclosure as described in the following materials satisfy these and other needs.

System and method for catheter connections


A compact memory uses magnetic bubble technology for providing data storage. A three-dimensional arrangement, in the form of stacks of magnetic bubble layers, is used to achieve high volumetric storage density. Output tracks are used within each layer to allow data to be accessed uniquely and unambiguously. Storage can be achieved using either current access or field access magnetic bubble technology. Optical sensing via the Faraday effect is used to detect data. Optical sensing facilitates the accessing of data from within the three-dimensional package and lends itself to parallel operation for supporting high data rates and vector and parallel processing.

In many applications, nonvolatile, secondary memory is achieved by using magnetic disk recording. While areal density improvements are underway in magnetic recording, the fact that they are mechanical systems limits their reliability, volumetric data storage capacity, access time, data rate, and usefulness in harsh environments such as in spaceflight.
U.S. Pat. No. 4,660,173 and published reports describe a means for achieving three-dimensional storage using magnetic bubble technology for storage and magneto-optic sensing for readout. These published reports are the following:
1. F. Mehdipour, U.S. Pat. No. 4,660,173, "Three Dimensional Magnetic Bubble Data Storage and Optical Retrieval System.";
2. A. J. Mendez and F. Mehdipour, "Three Dimensional Mass Memory Compatible with Parallel Processing Architectures," Accepted for publication, IEEE Fourth Annual Symposium on Parallel Processing;
3. "Firm Developing optical Media Based on Magnetic Bubble Technology." Optical Memory News, October, 1989, Rothchild Consultants, San Francisco;
4. F. Mehdipour and H. Bagherzadeh, "New Memory Technology Supports Parallel Processing," Defense Electronics, Volume 22, Number 11, November 1990, pp. 55-58.
However problems exist in the two methods that comprise the current state of the art. First, in one method, the optical path is common along one axis to the storage layers. Such a system is simple, and uses the Faraday effect, as depicted in FIG. 1, in which the polarization of the incident, linearly polarized light is rotated in one sense or the opposite, depending upon the direction of magnetization. However, as shown in FIG. 2, since only the net Faraday rotation can be measured at an output, the data at each of the bit locations along the optical path cannot be uniquely recovered. Thus, proper readback cannot occur as described in the prior art.
A second method in the prior art places a single magnetic bubble layer between two layers which serve as optical waveguides. Such an arrangement allows data to be recovered uniquely since unique optical paths are provided, but this capability is achieved at the expense of considerable material and processing complexity. This additional complexity may degrade memory performance to an unacceptable level since the physical stresses and temperature dependencies encountered during device processing for such a module are significant. The relatively high temperatures needed to fabricate the optical waveguide layers are likely to stress and alter the magnetic bubble storage material, which often is an epitaxially grown garnet crystal containing a variety of rare-earth constituents and is fabricated using relatively low-temperature processes. These problems can change the anisotropy, mobility, magnetization, characteristic length, etc. of the bubble film, and affect the operational storage and propagation functions. (See for example P. H. L. Rasky, D. W. Greve, and M. H. Kryder, "The Feasibility of Silicon on Garnet Technology," Journal of Applied Physics, Volume 57, Number 1, Apr. 15, 1985, pp. 4077-4079) A general text in the relevant art is " Magnetic Bubble Technology" by A. H. Eschenfelder, 2nd Edition, 1981 published by Springer-Verlag, Berlin/New York.

Three-dimensional magnetic bubble memory system


To provide fast access times with very large key fields, an associative memory utilizes a location addressable memory and lookup table to generate from a key the address in memory storing an associated record. The lookup tables, stored in memory, are constructed with the aid of arithmetic data compression methods to create a near perfect hashing of the keys. For encoding into the lookup table, keys are divided into a string of symbols. Each valid and invalid symbol is assigned an index value, such that the sum of valid index values for symbols of a particular key is a unique value that is used as an address to the memory storing the record associated with that key, and the sum of keys containing invalid index values point to a location in memory containing similar data. Utilizing the lookup tables set and relational operations maybe carried out that provide a user with a maximum number of key records resulting from a sequence of intersection, union and mask operations.

Data communication between computers has become a standard part of worldwide networks in many areas of endeavors. These individual networks gather data about diverse subjects and exchange information of common interest among various media groups. Most of these networks are independent communication entities that are established to serve the needs of a particular group. Some use high speed connections while others use slow speed networks. Some use one type of protocol while others use a different type of protocol. Other well-known differences between networks also exist. There has been considerable effort expended in an attempt to make it possible to interconnect disparate physical networks and make them function as a coordinated unit.
Whether they provide connections between one computer and another or between terminals and computers, communication networks are divided basically into circuit-switched or packet-switched types. Circuit-switched networks operate by forming a dedicated connection between two points. Such a dedicated circuit could be represented by a telephone connected through a circuit from the originating phone to a local switching office, across trunk lines to a remote switching office and finally to the destination telephone. When that circuit is complete, no other communications can travel over the wires that form the circuit. The advantage of such circuit lies in the fact that once it is established, no other network activity will decrease the capacity of the circuit. The disadvantage is that concurrent communication cannot take place on the line or circuit.
Packet-switched networks take an entirely different approach. In such system, traffic on the network is divided into small segments of information called packets that are multiplexed on high capacity intermachine connections. Each packet carries identification that enables other units on the network to know whether they are to receive the data or are to transmit it to another destination. The chief advantage of packet-switching is that multiple communications among information sources such as computers can proceed concurrently with connections between machines being shared by all machines that are communicating. The disadvantage is that as activity increases, a given pair of communicating devices can use less of the network capacity.
A new technology has been developed that is called Internet and it accommodates information or communication networks having multiple, diverse underlying hardware technologies, or physical media protocols, by adding both physical connections and a new set of conventions. One of the problems with the use of Internet is that addresses refer to connections and not to the device itself that is sending the information. Thus, if a communication source, such as an aircraft for example, moves from one communication network to another, its Internet address must change. Specifically, if an aircraft is transmitting a particular location address code in one communication network in the Internet system and it moves to another, its Internet address must change. It is similar to a traveler who has a personal computer operating with a first communication network. If the computer is taken on a trip and connected into the information system after reaching the new destination, a new location address for the computer must be obtained for the new destination. It is also similar to moving a telephone from one location to another. A new telephone number must be assigned to the telephone at the new location. The telephone cannot be reached at the new location with the old number. Further, when routing a signal from one station to another through a plurality of nodes forming multipath connections, the message format contains a destination location address that is used to make the routing decisions. When the system has multiple addresses, the route taken by the packets traveling to a particular station address depends upon the location code embedded in the station address.
Thus, two problems occur in such message communication networks. The first is the requirement to change the address code of the communication source when it is at different locations in the network and the second is routing the message to the receiver if the address has changed. It can be seen, then, that with the presently existing system, if host A transmits a message to host B with a specific location code, by the time the message arrives at that location, host B may have moved to a new information processing network and changed its location code to conform to the new system and thus could not receive the message transmitted by host A. Host A must know that host B has entered the new information processing system and then must change the format of the new location address in order to contact host B.
The present system overcomes the disadvantages of the prior art by simply assigning a fixed, unique and unchanging identification code to both host A and host B. As host B enters into a new network access system, it transmits its identification code to the nearest node and all of the nodes interconnecting all of the disparate networks each store, with the unique identification code of host B, the address of those nodes which can communicate with host B so that a path can be completed through the nodes between host A and host B.
In the prior art, hierarchical logical routing is used to address highly mobile end-systems (computers on ships and aircraft, etc.) that are simultaneously connected to multiple communication paths and employ multicast message traffic. Hierarchical routing schemes have great difficulty solving this combined set of problems and a new approach must be used to overcome the difficulties in using hierarchical routing to meet the user's diverse requirements.
Further, in the prior art, a logical network address of larger than 32 bits was too large to be used as a directory access method to locate a receiver at a location address specified in the message format. Specialized hierarchical address structures which embed network location information have been employed to reduce the size of the access index to the routing table and also to reduce the size of the routing table. This approach couples the address structure to the Internet routing software design.
There are various "hidden assumptions" of hierarchical addressing. These "hidden assumptions" are (1) the processing load of the router CPU increases as the size of the routing table increases and (2) computer memory is a scarce and expensive resource. The present invention overcomes the first of these problems while computer memory technology has addressed the second problem by making very large memories cost effective.
Traditional approaches for designing a network address structure have either been intimately entwined in the design of efficient routing look-up tables or assigned by a central authority such as ARPANET. Neither of these approaches gives much if any thought to the needs, desires or ease of use of the group which must make operational use of the system. In an age of fourth generation database languages and high level compilers, network addresses are basically hand-coded in low level language. Addresses and address structures are difficult to change as a mobile end-unit moves from one communication network to another. Experts are often required to ensure that operational equipment is properly integrated into the system. ISO (International Standards Organization) addressing provides a basis for a much better approach but the overall design and administration of a network addressing structure must be elevated to an easily supported, user friendly, distributed architecture to effectively support the user's long-term needs.
Traditional directory access methods, whether for Internet routing, databases or compiler symbol tables, fall into three basic categories:
(1) Sorted Tables. The keys are sorted by some rule which allows a particular search strategy (e.g., binary search) to locate the key. Associated with the key location is a pointer to the data. PA1 (2) Tree Structures. Parts of the key field are used to traverse a tree data structure to a leaf node which holds the data or a pointer to the data. PA1 (3) Hashing. Some arithmetic function is applied to the key which compresses the key field into a chosen integer range which is the initial directory size. This integer is the index into the directory which usually contains a pointer to the data.
Each of these techniques has advantages and disadvantages when applied to the Internet routing table access design. Sorted tables provide the potentially most compact storage utilization at the cost of having access computations which grow with the number of addresses (keys) active in the system. Computations for sorted tables grow proportional to the log of the number of keys plus one. Using sorted tables, the router processing will slow down as the number of active addresses increases. But the desirable result is to make computation independent of the number of active addresses. It has been theorized, without providing a method, that a scheme to access sorted tables could exist which always allows access in two probes. To date, no methods have been proposed which approaches this theoretical result.
Tree data structures have been widely employed for directories, particularly for file systems, such as the UNIX file system where larger amounts of auxiliary disc storage is being managed. Trees offer access times that are proportional to the length of the address (key). Trees trade off memory space for processing load. More branches at each level decreases the processing but uses much more memory. For example, a binary tree uses two locations at each level for each bit in the address field for which there is an active address. The binary tree processing of an eight bit octet requires eight memory accesses as well as unpacking the bits from the octet. On the other hand, processing a 256 way tree takes one memory access using the address octet as an index at each level. A 256 way tree requires 256 locations at the next level for every different octet active (a valid value) at the current level. An address of six octets with ten valid octet values in each octet position would require 256.times.10.sup.6 (256 million) locations, rapidly reaching an unrealizable size on current computer equipment. With current realizable computer memory sizes, pure tree structures do not appear to offer a viable structure for real time, address independent directory access method.
Hashing has often been used over the last several decades to create directories where fast access is desired. One system uses a multi-level hashing scheme as the file system directory structure. The Total database system is based on hashed key access. Many language compilers use hash tables to store symbols. Hash table schemes have good average access costs--often a single access, but can degrade drastically when the table becomes too full or the hashing function does not perform a good job of evenly distributing the keys across the table. Some techniques called "linear hashing" and "dynamic hashing" have provided the method of expanding the hash table when a particular bucket becomes too full instead of using the traditional linked list overflow methods. These techniques generally require about 40% more space than the number of active addresses (keys) to achieve single access speed without employing overflow methods.
All general hashing techniques use a variation of several common randomizing functions (such as dividing the key by a prime number and using the remainder) to "compress" the key field into a much smaller integer index into the hash table. Hashing functions have traditionally been viewed as one-way, randomized mapping of the key set into the hash space. The index computed by the hashing function could not be used to reconstruct the key. If for a particular hash function there exists a reciprocal function which maps the index to the unique key which generated the index, then the compressed keys could be stored in the directory.
The present invention overcomes the disadvantages of the prior art by considering a flat, as opposed to hierarchical, logical routing address space with unique identifiers assigned to each transmitter and receiver to vastly simplify the modern communication problems of addressing highly mobile end-systems which are simultaneously connected to multiple communication paths and employ multicast message traffic.
Further, the present invention employs a reversible arithmetic code compression technique to reduce the logical network address of up to 128 bits to a unique integer value which preserves any hierarchical ordering of the network address.
Also, the present invention employs dynamic hashing and memory allocation techniques to automatically adjust the size of the routing table directory and routing records to accommodate the number of end-system addresses currently active in the communication system. These techniques provide a selection of approaches to allow graceful degradation of the routing efficiency when the memory available for routing tables is full.
Finally, the system improves over the prior art by using a message format that is structure independent of the location of the destination of the message receiver.
Arithmetic coding, when applied to addresses as known length keys, provides several advantages for table look-up when the addresses are known or can be learned in advance as they are in communications applications. The proposed arithmetic coding routing table design provides direct support for mobile, multi-homed, shared network end-systems employing multicast and unicast messaging while minimizing the effects of the "hidden assumptions" that have lead to reducing the routing table size by embracing hierarchical routing schemes.
First, the identification encoding parameter tables are easily constructed by counting the occurrence of a particular symbol value and the accumulative distribution over all octet occurrences. That is, the tables are scaled to the statistical occurrence of each octet value. When a "bucket" overflows, dynamic hashing approaches can be used to expand the directory or parameter tables.
Secondly, arithmetic coding can be constructed to operate on each symbol position in the address field as it arrives, allowing processing to begin as soon as the first address symbol arrives.
Thirdly, arithmetic coding preserves the hierarchical (left to right precedence) of the ISO addresses being encoded. This is desirable if an Internet router only has knowledge of the network address but the Internet header carries the full destination address of a succeeding system node.
Finally, a constant known set of computations is required for each symbol of the address field independent of the number of address symbols or the number of active Internet addresses.
These features make the arithmetic coding used herein an ideal candidate for the routing table directory structure that is independent of a location address in a router, gate way or end-system.
The present invention provides a very fast, automatically expandable, source filtered Internet routing scheme totally independent of the internal logical or physical structure of the network addresses in the message format that it is routing. Addresses are just unique identification numbers represented by a string of symbols of known length. Each Internet router learns the location of these numbers within the network from the Internet protocol traffic, from the source addresses of the packets it receives, and from a network management protocol.
Address independent routing tables provides the following direct benefits:
They provide a very fast routing table access scheme that is capable of supporting fast packet switch designs for very high speed media such as FDDI (i.e., routers which begin the outbound transmission of the packet as soon as possible after receiving the Internet header and before the whole packet has been received).
They allow source address filtering for efficient multicast operation and security partitioning of the network.
They allow independent automatic generation of network addresses from a user name space by a network name service. This facilitates using the same Internet software in disconnected networks with different addressing authorities and different address structures.
They allow for orderly expansion, restructuring and redesign of the user name space without changing the Internet code or table structure.
They reduce initial system procurement and logistic support costs because no special coding is needed for different networks.
They reduce life cycle system costs because the Internet routers automatically adapt to network changes and they can be expanded without routing table modification.
The present invention combines arithmetic coding with dynamic hashing to provide a very high speed method and system for detecting the 48 bit physical addresses in a Media Access Controller (MAC). The present system guarantees the acceptance or rejection of a frame. This technique always performs address detection functions within the transmission time of the address field plus a small fixed number of octet clocks depending on the logic implementation chosen. Specifically, the present system provides the following features: (1) variable length addresses with no known internal structure and processed with a number of memory accesses and a processing time proportional to the number of octets in the address field; (2) the size of the routing tables is directly proportional to the number of active addresses known to the router and within the practical limits of currently available microprocessing systems; (3) and the computational operations required to access the routing table for any address is linearly proportional to the length of the address field and these computations are reasonably performed by currently available microprocessor systems.

Method and apparatus for use of associated memory with large key spaces


A new and distinct cultivar of Bracteantha named ‘KLEBA04075’, characterized by its upright, compact and bushy growth habit; freely-flowering habit; bright yellow-colored involucral bracts and golden yellow-colored disc florets; and good garden performance.

The present invention relates to a new and distinct cultivar of Bracteantha plant, botanically known as Bracteantha bracteata and referred to by the name 'KLEBA04075'.
The new Bracteantha is a product of a planned breeding program conducted by the Inventor in Stuttgart, Germany. The objective of the program is to create and develop new compact and early-flowering Bracteantha cultivars with attractive involucral bract coloration and good garden performance.
The new Bracteantha originated from an open-pollination by the Inventor during the summer of 2001, of a proprietary selection of Bracteantha bracteata identified as code number SZ 005, not patented, as the female, or seed, parent with an unknown selection of Bracteantha bracteata, as the male, or pollen, parent. The new Bracteantha was discovered and selected by the Inventor as a plant within the progeny of the stated open-pollination in a controlled environment in Stuttgart, Germany in June, 2002.
Asexual reproduction of the new Bracteantha by terminal cuttings in a controlled environment in Stuttgart, Germany since 2002, has shown that the unique features of this new Bracteantha are stable and reproduced true to type in successive generations.


An imaging apparatus includes an image capturing unit for obtaining still-image data, a recording unit for recording, in a recording medium, the still-image data obtained by the image-capturing unit, and a play-list generating unit which, in a continuous shooting mode for obtaining a series of still images and recording a series of still-image-data items representing the still images recorded in the recording medium, generates a play list specifying a process for playing back the series of still-image-data items.

1. Field of the Invention
The present invention relates to imaging apparatuses, and in particular, to an imaging apparatus having a continuous shooting function.
2. Description of the Related Art
Conventionally, digital cameras that record data of captured images as digital data in memory cards, etc., are known. A digital camera has various functions such as a single shooting function of capturing still images one by one, a continuous shooting function of continuously capturing plural still images, an automatic exposure bracketing (AEB) function of capturing a set of plural images while changing the brightness, and photo stitch that combines a set of still images to generate a still image.
Methods for viewing still images recorded in recording media include an index display function of displaying, on a screen, reduced images based on image-data items, and a slide show function (e.g., Japanese Patent Laid-Open No. 2003-209809) of sequentially displaying recorded images.
Among these functions, the slide show function sequentially displays image-data items recorded on a recording medium at regular intervals. After displaying all of the image-data items, the slide show function repeatedly displays the image-data items from the initially displayed image.
However, the slide show function has a problem in that, since all of the still-image-data items recorded in the recording medium are all displayed, the digital camera cannot play back a set of related still images captured by using a function such as continuous shooting or photo stitch in a form in which they are associated with one another or in an integrated manner.

Imaging apparatus having a continuous shooting function