The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

U.S. Pat. No. 5,057,614 to Davis, et. al., describes substituted pyrrole compounds of formula I as therapeutically active substances for the use in control or prevention of inflammatory, immunological, bronchopulmonary and cardiovascular disorders:
wherein R1 signifies hydrogen, alkyl, aryl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, trialkylaminoalkyl, aminoalkylaminoalkyl, azidoalkyl, acylaminoalkyl, acylthioalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, alkylsulphonyloxyalkyl, alkylcarbonyloxyalkyl, cyanoalkyl, amidinoalkyl, isothiocyanatoalkyl, glucopyranosyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, hydroxyalkylthioalkyl, mercaptoalkylthioalkyl, arylthioalkyl or carboxyalkylthioalkyl or a group of the formula:—(CH2)n—W—Het (a), —(CH2)n-T-C(═V)-Z (b),—(CH2)n—NH—C(═O)-Im (c), or —(CH2)n—NH—C(═NH)—Ar (d)in which Het signifies a heterocyclyl group, W signifies NH, S or a bond, T signifies NH or S, V signifies O, S, NH, NNO2, NCN or CHNO2, Z signifies alkylthio, amino, monoalkylamino or dialkylamino, Im signifies 1-imidazolyl, Ar signifies aryl, and n stands for 2–6; R2 signifies hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylthio or alkylsulphinyl; R3 signifies a carbocyclic or heterocyclic aromatic group; R4, R5, R6 and R7 each independently signify hydrogen, halogen, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulphonyl; and one of X and Y signifies O and the other signifies O, S, (H,OH) or (H,H); with the proviso that R1 has a significance different from hydrogen when R2 signifies hydrogen, R3 signifies 3-indolyl or 6-hydroxy-3-indolyl, R4, R5 and R7 each signify hydrogen, R6 signifies hydrogen or hydroxy and X and Y both signify O and when R2 signifies hydrogen, R3 signifies 3-indolyl, R4, R5, R6 and R7 each signify hydrogen, X signifies (H,H) and Y signifies O; as well as pharmaceutically acceptable salts of acidic compounds of formula I with bases and of basic compounds of formula I with acids; wherein the R3 carbocyclic aromatic group is defined as a monocyclic or polycyclic group, preferably a monocyclic or bicyclic group such as phenyl or naphthyl which can be unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl; wherein the R3 carbocyclic aromatic group is selected from phenyl, 2-, 3- or 4-chlorophenyl, 3-bromophenyl, 2- or 3-methylphenyl, 2,5-dimethylphenyl, 4-methoxyphenyl, 2- or 3-trifluoromethylphenyl, 2-, 3- or 4-nitrophenyl, 3- or 4-aminophenyl, 4-methylthiophenyl, 4-methylsulphinylphenyl, 4-methylsulphonylphenyl or 1- or 2-naphthyl; wherein the R3 heterocyclic aromatic group is defined as a 5- or 6-membered heterocyclic aromatic group optionally fused with a benzene ring and substituted or unsubstituted with 1 or more, preferably 1 to 3, substituents selected from halogen, (C1-7)alkyl, hydroxy, (C1-7)alkoxy, (C1-7)alkyl-halo, nitro, amino, —NH—C(O)—(C1-7)alkyl, —NH(C1-7alkyl), —N(C1-7alkyl)2, —S—(C1-7)alkyl, —C(SO)—(C1-7)alkyl or —SO2—(C1-7)alkyl; wherein the R3 heterocyclic aromatic group is 2- or 3-thienyl, 3-benzothienyl, 1-methyl-2-pyrrolyl, 1-benzimidazolyl, 3-indolyl, 1- or 2-methyl-3-indolyl, 1-methoxymethyl-3-indolyl, 1-(1-methoxyethyl)-3-indolyl, 1-(2-hydroxypropyl)-3-indolyl, 1-(4-hydroxybutyl)-3-indolyl, 1-[1-(2-hydroxyethylthio)ethyl]-3-indolyl, 1-[1-(2-mercaptoethylthio)ethyl]-3-indolyl, 1-(1-phenylthioethyl)-3-indolyl, 1-[1-(carboxymethylthio)ethyl]-3-indolyl or 1-benzyl-3-indolyl; and, when the R3 heterocyclic aromatic group is 3-indolyl, the 3-indolyl nitrogen atom is substituted with a substituent selected from hydrogen, C1-7alkyl, aryl (wherein aryl is phenyl unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl), —(C1-7)alkyl-aryl (wherein aryl is phenyl unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl), —(C1-7)alkyl(C1-7)alkoxy, —(C1-7)alkyl-hydroxy, —(C1-7)alkyl-(halo)1-3, —(C1-7)alkyl-NH2, —(C1-7)alkyl-NH(C1-7alkyl), —(C1-7)alkyl-N(C1-7alkyl)2, —(C1-7)alkyl-N+(C1-7alkyl)3, —(C1-7)alkyl-NH(C1-7alkyl)NH2, —(C1-7)alkyl-N3, —C1-7alkyl-NH—C(O)—(C1-7)alkyl, —C1-7alkyl-S—C(O)—(C1-7)alkyl, —C1-7alkyl-NH—SO2—(C1-7)alkyl, —C1-7alkyl-NH—SO2-aryl (wherein aryl is phenyl unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl), —(C1-7)alkyl-SH, —(C1-7)alkyl-S—(C1-7)alkyl, —(C1-7)alkyl-C(SO)—(C1-7)alkyl, —(C1-7)alkyl-SO2—(C1-7)alkyl, —(C1-7)alkyl-O—SO2—(C1-7)alkyl, —(C1-7)alkyl-O—C(O)—(C1-7)alkyl, —(C1-7)alkyl-C(N), —(C1-7)alkyl-C(NH)—NH2, glucopyranosyl, —(C1-7)alkyl-CO2H, —(C1-7)alkyl-C(O)—O—(C1-7)alkyl, —(C1-7)alkyl-C(O)—NH2, —(C1-7)alkyl-S—(C1-7)alkyl-OH, —(C1-7)alkyl-S—(C1-7)alkyl-SH, —C1-7alkyl-S-aryl (wherein aryl is phenyl unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl), —(C1-7)alkyl-S—(C1-7)alkyl-CO2H, —(CH2)2-6—W-Het (wherein W is selected from NH, S or a bond; wherein Het is a saturated, partially saturated or aromatic 5- or 6-membered heterocyclic group optionally fused with a benzene ring and substituted or unsubstituted with 1 or more, preferably 1 to 3, substituents selected from halogen, (C1-7)alkyl, hydroxy, (C1-7)alkoxy, (C1-7)alkyl-halo, nitro, amino, —NH—C(O)—(C1-7)alkyl, —(C1-7)alkyl-NH(C1-7alkyl), —(C1-7)alkyl-N(C1-7alkyl)2, —S—(C1-7)alkyl, —C(SO)—(C1-7)alkyl or —SO2—(C1-7)alkyl; wherein when Het is an aromatic nitrogen-containing heterocyclic group, a nitrogen atom may be substituted with an oxide group; and, wherein Het is selected from imidazolyl, imidazolinyl, thiazolinyl, pyridyl or pyrimidinyl), —(CH2)2-6-T-C(V)-Z (wherein T is selected from NH or S; V is selected from O, S, NH, NNO2, NCN or CHNO2; and, Z is selected from —S—(C1-7)alkyl, NH2, NH(C1-7alkyl) or N(C1-7alkyl)2), —(CH2)2-6—NH—C(O)-1-imidazolyl or —(CH2)2-6—NH—C(═NH)-aryl (wherein aryl is phenyl unsubstituted or substituted with 1 or more, preferably 1 to 3, substituents selected from halogen, unsubstituted C1-7alkyl, hydroxy, unsubstituted C1-7alkoxy, (halo)1-3(C1-7)alkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulfonyl).
U.S. Pat. No. 6,037,475 to Faul, et. al., describes a method of making an N-subsituted indolylmaleimide of formula I as therapeutically active substances for the use in control or prevention of inflammatory, immunological, bronchopulmonary and cardiovascular disorders:
using an organometallic reagent and an optionally substituted activated organometallic-3-indole maleimide in the presence of a palladium transition metal catalyst wherein R2 is selected from a leaving group and an optionally substituted indol-3-yl, R3 is selected from hydrogen and a protecting group, R7's are hydrogen or up to four optional substituents independently selected from halo, alkyl, hydroxy, alkoxy, haloalkyl, nitro, —NHCO(alkyl), or —NR9R10; where R9 and R10 are independently hydrogen, or methyl, R8 is hydrogen or an optional substituent selected from, alkyl, haloalkyl, alkenyl, arylalkyl, alkoxyalkyl, hydroxyalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, acyloxyalkyl, cyanoalkyl, amidinoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aryl, alkylaryl, aminoalkyl, heteroaryl, carbonylalkyl, amidinothioalkyl, nitroguanidinoalkyl, a protecting group, an alkylglycose residue, or a group of the formula:
in which Het signifies a heterocyclyl group, W signifies NH, S or a bond, T signifies NH or S, V signifies O, S, NH or NCN, A signifies alkylthio, amino, monoalkylamino or dialkylamino, and Ar signifies aryl; R16 is hydrogen, alkyl, haloalkyl, acetyl, aryl, —CH(aryl)2, amino, monoalkylamino, dialkylamino, guanidino, —C(═N(alkoxy-carbonyl))-NH-(alkoxycarbonyl), amidino, hydroxy, carboxy, alkoxycarbonyl or heterocyclyl; R14 is hydrogen or an optionally substituted alkyl; or R8 and R14 are linked together through a group of the formula (—(CH2)r—X—(CH2)—) where X is —(C(—(CH2)6—R17)(—(CH2)6—R18))— where R17 and R18 are independently hydroxy, carboxy, acyloxy, amino, monoalkylamino, dialkylamino, trialkylamino, azido, acylamino, cyano, amidino or aminocarbonyl, and n is 1, 2, 3, 4, 5 or 6, p an q are 1, 2, 3 or 4, r is 1, 2 or 3, s is 0, 1, 2 or 3, t is 1 or 2, and u is 0 or 1.
U.S. Pat. No. 5,721,245 to Davis, et. al., describes substituted 4-[3-indolyl]-1H-pyrrolone compounds of formula I:
wherein R is hydrogen or hydroxy, R1 and R2 taken together are a group of the formula —(CH2)n— and R7 is hydrogen or R1 and R7 taken together are a group of the formula —(CH2)n— and R2 is hydrogen; R3 is an aryl or aromatic heterocyclic group; R4, R5 and R6 each independently are hydrogen, halogen, alkyl, hydroxy, alkoxy, haloalkyl, nitro, amino, acylamino, alkylthio, alkylsulfinyl or alkylsulfonyl; R8 is a group of the formula —(CH2)p—R9 or —(CH2)q—R10; R9 is hydrogen, alkylcarbonyl, aminoalkylcarbonyl, cyano, amidino, alkoxycarbonyl, aryloxycarbonyl, alkylsulfonyl, aminocarbonyl or aminothiocarbonyl; R10 is hydroxy, alkoxy, halogen, amino, monoalkylamino, dialkylamino, trialkylamino, azido, acylamino, alkylsulfonylamino, arylsulfonylamino, alkylthio, alkoxycarbonylamino, aminoacylamino, aminocarbonylamino, isothiocyanato, alkylcarbonyloxy, alkylsulfonyloxy or arylsulfonyloxy, a 5- or 6-membered saturated nitrogen-containing heterocycle attached via the nitrogen atom or a group of the formula -U-C(V)-W; U is S or NH; V is NH, NNO2, NCN, CHNO2; W is amino, monoalkylamino or dialkylamino; one of X and Y is O and the other is O or (H,H); Z is CH or N; m, p and q are, independently, an integer from 0 to 5, and n is an integer from 1 to 5, with the proviso that q and m are, independently, 2 to 5 when Z is N; as well as pharmaceutically acceptable salts of acidic compounds of formula I with bases and of basic compounds of formula I with acids, as therapeutically active substances for use in control or prevention of inflammatory, immunological, bronchopulmonary and cardiovascular disorders.
U.S. Pat. No. 5,624,949 to Heath, Jr., et. al., describes bis-indolemaleimide derivatives of the formula:
wherein W is —O—, —S—, —SO—, —SO2—, —CO—, C2–C6 alkylene, substituted alkylene, C2–C6 alkenylene, -aryl-, -aryl(CH2)mO—, -heterocycle-, -heterocycle-(CH2)mO—, -fused bicyclic-, -fused bicyclic-(CH2)mO—, —NR3—, —NOR3—, —CONH— or —NHCO—; X and Y are independently C1–C4 alkylene, substituted alkylene, or together, X, Y and W combine to form (CH2)n-AA-; R1 is independently hydrogen, halo, C1–C4 alkyl, hydroxy, C1–C4 alkoxy, haloalkyl, nitro, NR4R5 or —NHCO(C1–C4)alkyl; R2 is hydrogen, CH3CO—, NH2 or hydroxy; R3 is hydrogen, (CH2)maryl, C1–C4 alkyl, —COO(C1–C4 alkyl), —CONR4R5, —C(C═NH)NH2, —SO(C1–C4 alkyl), —SO2(NR4R5) or —SO2(C1–C4 alkyl); R4 and R5 are independently hydrogen, C1–C4 alkyl, phenyl, benzyl, or combine to the nitrogen to which they are bonded to form a saturated or unsaturated 5 or 6 member ring; AA is an amino acid residue; m is independently 0, 1, 2 or 3; and n is independently 2, 3, 4 or 5 as protein kinase C (PKC) inhibitors and as selective PKCβ-I and PKCβ-II inhibitors.
Patent application WO 00/06564 discloses disubstituted maleimide compounds of Formula (I):
wherein R1 represents hydrogen or alkyl; R2 represents aryl, cycloalkyl or a heterocycle; R3, R5, R6, R7 and R8 represent each hydrogen, halogen, hydroxy, amino, alkyl or alkoxy; and R4 is W, or R4 and R3 or R4 and R5 may form together a ring substituted by W thereon; wherein W represents —(CH2)l—(Y)m—(CH2)n-Z as PKCβ inhibitors.
Patent application WO 00/21927 describes 3-amino-4-arymaleimide compounds having formula (I):
or a pharmaceutically acceptable derivative thereof, wherein: R is hydrogen, alkyl, aryl or aralkyl; R1 is hydrogen, alkyl, aralkyl, hydroxyalkyl or alkoxyalkyl; R2 is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl; R3 is hydrogen, substituted or unsubstituted alkyl, cycloalkyl, alkoxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl or aralkyl wherein the aryl moiety is substituted or unsubstituted; or, R1 and R3 together with the nitrogen to which they are attached form a single or fused, optionally substituted, saturated or unsaturated heterocyclic ring and a method for the treatment of conditions associated with a need for inhibition of GSK-3, such as diabetes, dementias such as Alzheimer's disease and manic depression.
The substituted pyrroline compounds of the present invention have not been heretofore disclosed.
Accordingly, it is an object of the present invention to provide substituted pyrroline compounds useful as a kinase or dual-kinase inhibitor (in particular, a kinase selected from protein kinase C or glycogen synthase kinase-3; and, more particularly, a kinase selected from protein kinase C α, protein kinase C β-II, protein kinase C γ or glycogen synthase kinase-3β), methods for their production and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

Substituted pyrrolines as kinase inhibitors


The object of the present invention is to solve the problems in the prior arts, and to find more improved reaction conditions for suppressing the racemization of the product and obtaining an optically active alcohol at a high optical purity. The inventors achieved to solve the above problems by using a solvent system that is capable of resolving both an asymmetric catalyst and a formate salt, allowing the hydrogen source and the asymmetric catalyst to be present in the same phase.

Asymmetric ruthenium complexes, rhodium complexes and iridium complexes, which take sulfonyl diamine as a ligand, are useful asymmetric reducing catalysts. These are employed for the asymmetric reduction of a ketone substrate for an efficient production of an optically active alcohol (Patent Literatures 1 and 2).
In Non-patent Literature 1,2-propanol is used as a hydrogen source. This reaction is a reversible equilibrium reaction that gives an optically active alcohol and acetone from ketone substrate and 2-propanol. Therefore, an (S,S) catalyst, for example, reduces acetophenone to give (S)-phenylethanol in a ratio of 99:1 ((S):(R)). However, this reaction preferentially dehydrogenates (S)-phenylethanol in a ratio of 99:1 to give acetophenone, compared to (R)-phenylethanol. Therefore, at initial phase of the reaction, when the concentration of the hydrogen source 2-propanol is high, (S)-phenylethanol and (R)-phenylethanol are produced in the reaction system in a ratio of 99:1. However, when the reaction proceeds and the concentration of (S)-phenylethanol is increased, the reverse reaction will reduce the composition ratio (optical purity) of (S)- and (R)-phenylethanols in the reaction system; their ratio will be reduced to 97:3 at 75% conversion. As being such an equilibrium reaction, in a reaction system where 2-propanol is employed as hydrogen source, in order to obtain an optically active alcohol in high optical purity, there have been problems that there must be a large excessive amount of the hydrogen source 2-propanol than the product optically active alcohol; and that the reaction must be carried out under the condition where the concentration of the ketone substrate is as low as approximately 0.1M.
In order to solve these problems, in Non-patent Literature 2, formic acid is used as the hydrogen source. In this method, formic acid is eliminated from the system as carbon dioxide after providing hydrogen, rendering the reaction irreversible and increasing the optical purity of the produced optically active alcohol. Although using this method, the optical purity and the S/C ratio (substrate/catalyst molar ratio) of the optically active alcohol were improved compared to the reaction using 2-propanol as the hydrogen source, there still is a necessity of improvement, such as in the S/C ratio (substrate/catalyst molar ratio).
Then Non-patent Literature 3 suggested a method to use sodium formate as the hydrogen source under a condition of a two-phase reaction system where water is employed as the solvent. In this method, although there is a large increase in the reaction rate and an improvement in the S/C ratio (substrate/catalyst molar ratio) compared to the reaction using formic acid, the optical purity of the alcohol is decreased. For example, a reaction of an acetophenone gives phenylethanol at 97% ee using formic acid, whereas a two-phase reaction system gives phenylethanol at 95% ee.
Meanwhile, a high catalytic activity of the two-phase reaction system is interpreted to be an effect exhibited by water (Non-patent Literatures 3 and 4), and therefore, in Non-patent Literature 5, many of the approaches for achieving a high optical purity were focused on the structural optimization of the catalyst and the development of an aqueous catalyst, while leaving the condition unchanged that water is present. On the other hand, Non-patent Literature 6 reported as an approach to improve the reacting conditions, a homogenous reaction system in which potassium formate in polyethyleneglycol is used as a hydrogen source. This approach, however, is focused on the recycle of catalyst by retaining the catalyst in polyethyleneglycol phase, and there is no mentioning about any suppressive effect on the racemization of the produced alcohol by the homogenous reaction.

Process for producing optically active alcohol


A transmission control system in an electric vehicle in which a battery is used as en energy source for a motor and is charged with an electric power generated through the motor by regenerative braking of driving wheels which are connected to the motor through a transmission. In the transmission control system, a regenerative energy capable of being generated at a current transmission ratio, a regenerative energy capable of being generated when such transmission ratio is increased, and a regenerative energy capable of being generated when such transmission ratio is decreased, are calculated and compared with one another, thereby shift-changing the transmission into a shift position which permits the largest regenerative energy to be provided. This ensures that the efficiency of recovery of the energy can be increased to the maximum to effectively charge the battery.

1. Field of the Invention
The present invention relates to a transmission control system in an electric vehicle in which a battery is used as an energy source for a motor and is charged with electric power generated by the motor by regenerative braking of a driving wheel connected to the motor through a transmission.
2. Description of the Prior Art
There are conventionally known transmission control systems in vehicles driven to travel by an electric motor using a battery as an energy source, in which the battery is charged with an electric power generated by the motor through regenerative braking of driving wheels, thereby prolonging the possible travel distance of the vehicle obtained by one charging (for example, see Japanese Patent Publication No. 6204/81 and U.S. Pat. No.3,621,929).
The magnitude of a regenerative energy provided by a regenerating braking varies depending upon a transmission ratio of a transmission mounted between the driving wheels and the motor. In the vehicles described in the above prior art references, however, the transmission ratio cannot arbitrarily be changed and hence, the kinetic energy of the vehicle cannot be recovered as regenerative energy without any waste, to effectively charge the battery.

Transmission control system in electric vehicle


The present disclosure provides a neural network processor and neural network computation method that deploy a memory and a cache to perform a neural network computation, where the memory may be configured to store data and instructions of the neural network computation, the cache may be connected to the memory via a memory bus, thereby, the actual compute ability of hardware may be fully utilized, the cost and power consumption overhead may be reduced, parallelism of the network may be fully utilized, and the efficiency of the neural network computation may be improved.

Artificial neural networks (ANN) abstract human neural networks from the perspective of information processing to establish simple models and create different networks according to different ways of connections. Currently, artificial neural networks have made great progress in many fields, and are widely used to solve practical problems in pattern recognition, intelligent robots, automatic control, predictive estimation, biology, medicine, economy, and other fields.
As a new type of dedicated processor, single-core neural network processors use special instructions to fully utilize parallelism of neural networks to perform neural network computations. However, since single-core neural network processors need to be compatible with most neural network models and support different existing neural networks and neural network computations with different scales, existing single-core neural network processors often have complex structures and high cost. In addition, single-core neural network processors also have problems of wasting hardware resources and high power consumption overhead. Meanwhile, single-core neural network processors are not accelerated for parallelism between different layers during a neural network computation, and still have room for optimization.
In this situation, it has become a direction for the improvement of neural network computation devices to complete neural network computations, make full use of neural network computation devices, and reduce redundancy in functional components by aiming at different neural network models and the scale of neural network computations under the condition of fully utilizing parallelism within a layer and between different layers during neural network computations.

Neural network processor and neural network computation method

SHANGHAI CAMBRICON INFORMATION TECHNOLOGY CO., LTD


Desalination plant containing a plurality of membrane trains each having a plurality of RO membrane units and a plurality of NF membrane units. The ratio of RO membrane units to NF membrane units in each membrane train is in the range of 2:1 to 40:1, and each membrane train is provided with (a) a feed line for a source water that divides to provide a feed line for the RO membrane units and a feed line for the NF membrane units, (b) a permeate line for the RO membrane units and a permeate line for the NF membrane units that combine to provide an injection water line; (c) a retentate line for the RO membrane units and a retentate line for the NF membrane units; and (d) a flow controller and pressure let-down valve on the NF feed line.

As described in International patent application WO 2008/029124, it is known to inject water of low salinity into an oil-bearing formation of a reservoir in order to enhance the recovery of oil from the reservoir.
A problem associated with low salinity water-flooding is that desalination techniques may yield water having a salinity lower than the optimal salinity for enhanced oil recovery. Indeed, the desalinated water may be damaging to the oil-bearing rock formation of the reservoir and inhibit oil recovery, for example, by causing swelling of clays in the formation. There is an optimal salinity for the injection water that provides the benefit of enhanced oil recovery whilst avoiding formation damage, and, the optimum value will vary from formation to formation. Typically, where an oil-bearing formation comprises rock that contains high levels of swelling clays, formation damage may be avoided when the injection water has a total dissolved solids content (TPS) in the range of 500 to 5,000 ppm, preferably, 1,000 to 5,000 ppm.
However, it is not desirable to mix a desalinated water of low multivalent cation content with a high salinity water such as seawater owing to the high sulfate anion content and/or high multivalent cation content of the high salinity water. Thus, the high sulfate anion content of the such mixed water streams may result in reservoir souring and/or the precipitation of unacceptable levels of insoluble mineral salts (scale formation) when the injected water contacts precipitate precursor cations such as barium, strontium and calcium cations that are commonly present in the connate water of the formation. In addition, mixing of desalinated water with a high salinity water such as seawater may result in the mixed water stream containing unacceptable levels of multivalent cations, in particular, calcium and magnesium cations. Thus, in order to achieve incremental oil recovery with a low salinity injection water, the ratio of the concentration of multivalent cations in the low salinity injection water to the concentration of multivalent cations in the connate water of the reservoir should be less than 1, preferably, less than 0.9, more preferably, less than 0.8, in particular, less than 0.6, for example, less than 0.5.
As described in International patent application WO 2007/138327, one way in which the salinity of a water supply of overly low salinity might be increased is by blending with water of higher salinity. According to WO 2007/138327, this may be achieved by the steps of:                substantially desalinating a first feed supply of water to provide a first supply of treated water of low salinity;        treating a second feed supply of water to provide a second supply of treated water having a reduced concentration of divalent ions in comparison to the second feed supply and a higher salinity than the first supply of treated water; and        mixing the first supply of treated water and the second supply of treated water to provide a supply of mixed water having a desired salinity suitable for injection into an oil bearing reservoir.
In preferred embodiments of the invention of WO 2007/138327, the first feed supply is substantially desalinated by a reverse osmosis process while the step of treating the second feed supply of water is preferably performed by nanofiltration.
Nanofiltration is commonly used in the oil industry to remove sulfate ions from a source water. The treated water can then be injected into a formation without the risk of forming unacceptable levels of insoluble mineral salts when the injected water contacts precipitate precursor cations present in the connate water of the formation. The invention of WO 2007/13832 therefore permits the supply of a mixed water having the desired salinity suitable for injection into the oil bearing reservoir and having a reduced level of sulfate anions thereby mitigating the risk of mineral scale precipitation either within the formation or in production wells.
It is known that injection of a water that contains high levels of sulfate anions can stimulate the growth of sulfate reducing bacteria that produce hydrogen sulfide as a metabolite resulting in souring of a reservoir. Where it is desired to mitigate the risk of mineral scale formation, the Level of sulfate anions in the supply of mixed water should be less than 40 ppm. However, where it is desired to mitigate the risk of souring in a reservoir, the level of sulfate anions in the supply of mixed water should be as low as possible, for example, less than 7.5 ppm, preferably, less than 5 ppm.

Process of supplying water of controlled salinity

BP EXPLORATION OPERATING COMPANY LIMITED


A vertical thermal C shaped metallic stud having a web with a pair of spaced apart generally parallel legs extending therefrom forming surfaces to receive exterior and interior wall structures. At least one of said legs including an upset struck outwardly from the leg to act as the bearing surface for wall material to be affixed thereto, so that a thermal space is created between the stud and wall material to prevent transfer or lessen the transfer of ambient exterior air temperature by thermal conductivity to the interior of a building using the thermal C shaped studs.

1. Field of the Invention
This invention relates to a C shaped metallic thermal building stud that is provided with structure to reduce or eliminate thermal conductivity of exterior ambient air temperature through a building to its interior.
2. Description of the Prior Art
In present day architecture buildings as well as homes utilize a support structure of a framework comprising vertical steel C shaped studs positioned between horizontal steel floor and ceiling steel bases and caps, such as illustrated and described in U.S. Pat. No. 4,235,054.
Heretofore, the C shaped studs have had generally smooth end flanges or legs to which interior finish wall boards have been secured to the inside flange. The outside flange or leg usually has attached thereto plywood with an exterior finish such as exterior plaster or a siding attached thereto. With the prior art structure the entire surface of the flanges both exterior and interior are in complete contact with the exterior and interior surfaces of the wall material respectively.
Thus, with full contact ambient exterior air temperature has passed by thermal conductivity through the exterior surface into the flange or leg along its entire surface and the through the C shaped stud web to the interior leg and through the full surface contact with the interior wall into the room. Thus the exterior temperature has passed into a building so that extreme cold or heat renders the interior very uncomfortable.
Such transmission of winter air temperatures in some regions into the house is not only unwanted but increases heating costs to overcome the temperature reduced internal air. Also the opposite is true in the summer when the ambient air may be extremely hot, the temperature is conveyed by the building stud as a thermal conduit directly into the interior of the house or building. Again, this is undesirable because of the interior discomfort and the additional expense of operating air conditioning equipment.


A multichip module of the present invention includes a substrate having an upper surface, a hole provided on the upper surface of the substrate and a chip provided in the hole. The upper surface of the chip and the upper surface of the substrate forms an even, or substantially even, surface. A first insulating layer is formed on the upper surface of the chip and the upper surface of the substrate and a first wiring layer is formed on the first dielectric layer. A method for manufacturing a multichip module, which includes a substrate having a cavity provided thereon, and a chip, includes providing the chip in the cavity so that the upper surface of the chip and the upper surface of the substrate becomes even, or substantially even. The method also includes forming a first insulating layer on the upper surface of the chip and the upper surface of the substrate, and forming a first wiring layer on the first insulating layer.

The present invention relates to a multichip module and manufacturing method, and particularly to a multichip module and manufacturing method which transmit a signal at a high speed and prevents noises from being generated.
As the integration density of a large-scale integrated circuit (LSI) is improved and the signal transfer speed of the LSI is increased, it is necessary for a multichip module to increase the signal transfer speed by improving the wiring density.
Increased wiring density can be achieved by making wires finer. In a conventional multichip module, however, it is difficult to making wires finer because step and stage disconnection occur on the surface toward upper layers of multiple metallic layers. In addition, as wires are made finer, the wiring resistance increases. This increases attenuation of signal amplitude, thus, high-speed signal transfer becomes difficult. Thus, it is difficult to transfer a signal at a high speed solely by improving wiring density.
Moreover, a wire or a solder ball is used as a conventional way of connecting wiring to an LSI chip. However, because the impedance between the wire or solder ball and the wiring is not equal, signal waveform deteriorates.
An object of the invention is to provide a multichip module and manufacturing method which transfer a signal at a high speed without deterioration.
According to one aspect of the present invention, a multichip module is provided which includes: a substrate having an upper surface; a hole provided on the upper surface of the substrate; a chip provided in the hole, wherein the upper surface of the chip and the upper surface of the substrate form an even, or substantially even, surface; a first insulating layer formed on the upper surface of the chip and the upper surface of the substrate; and a first wiring layer formed on the first dielectric layer.
According to another aspect of the present invention, a multichip module is provided which includes: a substrate having an upper surface; a first hole and a second hole provided on the substrate; a first chip provided in the first hole, wherein an upper surface of the first chip and the upper surface of the substrate form an even, or substantially even, surface; a second chip provided in the second hole, wherein an upper surface of the second chip and the upper surface of the substrate form an even, or substantially even, surface; a first dielectric layer formed on the upper surfaces of the substrate, the first chip and the second chip; and a first wiring layer formed over the first dielectric layer.
According to another aspect of the present invention, a method for manufacturing a multichip module, which includes a substrate having a cavity provided thereon, and a chip, is provided which includes: providing the chip in the cavity so that the upper surface of the chip and the upper surface of the substrate become even, or substantially even; forming a first insulating layer on the upper surface of the chip and the upper surface of the substrate; and forming a first wiring layer on the first insulating layer.


Oscillation and other disturbance damping is provided for a system having a load driven by an electric motor, e.g., an electromagnetic actuator. Damping is achieved using feedback in an active mode, where power is supplied in a normal operation mode of the electromagnetic actuator. Feedback may be provided by measured force (or torque) transmitted between the actuator and load mass. A gear train or other mechanical advantage device may be connected between the electromagnetic actuator output and load, this combination forming an electromechanical actuator (EMA). Instead of force or torque, acceleration of the load may be used as a feedback signal. In one embodiment, active mode damping uses the motor's actual current as a feedback signal. In certain or all active damping versions of the invention, a high pass filter is preferably used to receive feedback signals and filter out low frequency feedback. Alternatively, damping is achieved in an inactive (passive) mode of motor operation, e.g., where the electric motor is not receiving power drive signals. The motor coils are shorted, e.g., using a switch. The induced motor currents act to inhibit load oscillations. Preferably, a resistance, e.g., a number of resistors, are in the short circuit to tailor the damping characteristics of the motor. In at least the active current feedback and passive modes of operation, inertia of the electric motor is substantially reduced in relation to typical motor inertia, by changing the stator to rotor diameter ratio from a typical ratio of at or about 2:1 or less, to a substantially higher ratio than 2:1.

1. Field of the Invention
The present invention relates to oscillation damping in systems having electric motors for moving and positioning a load, such as a nose wheel of an airborne vehicle.
2. Description of the Related Art
For a long time, hydraulic systems have been used to move and position various components of aircraft and other vehicles and devices. One application of hydraulics has been in aircraft nose wheel steering (moving the aircraft's front wheel to a desired angular position). Nose wheels, like many other components, can be subject to shimmy or oscillation. These oscillations, particularly when at or near the resonant frequency, can cause damage to system components, reduce their life, weaken control and hinder accuracy. Accordingly, it is desirable to dampen vibrations of the load. Damping is often achieved when hydraulic power is used by forcing hydraulic fluid through an orifice.
It is desirable to use electric motors and in particular electromechanical actuators (EMAs) to move a nose wheel or other load. EMAs have no hydraulic fluid, so another form of damping is required. Unlike hydraulic actuators, EMAs intrinsically require a power train with a large gear ratio to deliver to the load the force (or torque) required by many applications, such as a steering actuator. It has been found that such a high gear ratio causes the system to be generally unresponsive to damping. In addition, conventional wisdom is that the requirement of power typically results in use of an electric motor with a stator diameter to rotor diameter ratio of equal to or about 2 to 1 or less.
One example of how damping has been attempted involves placing elastomeric damping elements in selected positions on the nose wheel assembly, such as in U.S. Pat. No. 6,247,687.
Oscillation damping with an electric motor such as in an EMA may be needed in nose wheel steering on an aircraft, such as a commercial aircraft, in shimmy damping of any vehicle steered with EMA or an electric motor, and any other electric motor or EMA actuation system for a load where load damping is used or required.


A sewing or embroidering machine with an electronic control device including a microcomputer. Access authorization for the individual modes of operation of the sewing and embroidering machine can be changed by the buyer of the machine. The assignment of access authorization to individual modes of operation of the sewing machine is stored in a first write-read memory in the form of a table, access authorization table. The first write-read memory is connected with the microprocessor and with a first input device such that after a corresponding operating function is called up or requested by a person authorized to do so, the access authorization can be correspondingly changed for the mode of operation in question by the input means.

Industrial sewing machines and embroidering machines must be operated by sewing machine operators, plant mechanics and service personnel. Not all input and operating functions usually need to be accessible by the different persons. Certain functions were therefore made accessible to only certain persons, and distinctions can be made concerning authorized access between access via a code number, access via a key and free access.
The access of the different groups of persons to the different modes of operation of a machine is frequently set at the time of the shipping of a sewing machine. However, such a setting has the drawback that it does not take into account the greatly different work processes in different plants, because, e.g., the sewing machine operator is to use only the basic modes of operation in one plant, while the sewing machine operator shall also perform additional settings and programming of the machine in another plant.
A sewing machine with an electronic control device containing a microcomputer, in which the control device and consequently the microcomputer are connected to at least one input means for entering the actually desired mode of operation of the sewing machine (in the form of control codes), has already been known from DE 40 00 765 A1. The input means also includes, among other things, a keyboard.
A process and a device for checking the access authorization between a chip card and a terminal unit, in which a plurality of authorization codes are stored in corresponding memories in both the chip card and the terminal unit, have been known from DE 43 06 819 C2.
A relatively complicated process for determining the access authorization of the user of a computer of a networked computer system has been known from DE 44 43 339 A1. The user of the computer in question identifies himself by means of his computer against an identification server via his name, an identifier for the type of the access method (e.g., a password or a chip card) and a coded sequence of his personal data and a key for a coding process.
Furthermore, a locking system, in which data can be inductively transmitted between a code module and a lock module, has been known from DE 44 22 081 C2.


An outdoor lighting system for illumination of an outdoor area, the system configured to provide dynamical control in the outdoor area, the system comprising: a plurality of luminaires configured in the outdoor area; a plurality of street devices connected with the plurality of luminaires; at least one remote processor; at least one secondary processor; a cloud to which the plurality of luminaires and the plurality of street devices are connected; and the at least one remote processor and the at least one secondary processor are connected to the cloud; wherein the plurality of luminaires and the plurality of street devices are controlled in a plurality of functional modes.

The current invention relates to an outdoor lighting system and specifically to systems and devices used to illuminate streets, roads, parking lots, railways, and large outdoor areas. More specifically, embodiments of the current invention relate to lighting systems that provide both a lighting function and a processing platform having connectivity such as IP connectivity and connected elements.
In the specification and claims hereinbelow, the term "outdoor area" when used in conjunction with a lighting system is used interchangeably with "public space" and is intended to mean streets, roads, parking lots, railways, and any other extended outdoor area.
In recent years, several fields of advanced technologies made significant advances and gained large attention from global markets such as: LED lighting; IoT/IoE—Internet of Things/Internet of Everything; Smart City concepts and applications; and cellular, Wi-Fi and other wireless communications
The following are definitions of terms used in the specification and claims which follow.
A "LED lamp" is a light-emitting diode (LED); a component assembled for use in lighting fixtures. The word "luminaire" is used in the specification and claims which follow to mean a lighting fixture, as known in the art, and specifically a lighting fixture having at least one LED lamp therein. The term "street light" and "street light" used in the specification and claims which follow is intended to mean a luminaire which is typically configured on an elevated platform, such as, but not limited to a typical lighting fixture pole.
LED lamps have a lifespan and electrical efficiency that is several times superior to that of incandescent lamps, and significantly better than most fluorescent and high intensity discharge (HID) lamps; with some LED devices capable of emitting over 100 lumens per Watt. The LED fixture market is projected to grow by more than twelve-fold over the next decade.
LED lighting is widely-applied for street lighting and many cities worldwide have been changing their street lighting systems to LED-based systems. The reason for this fast adoption of LED lighting by various municipalities is the dramatic energy savings of LED versus-conventional-lighting, which approaches about 60-70%.
"Internet of Things (IoT)" has been defined as a global infrastructure for the information society, enabling advanced services by interconnecting (physical and virtual) objects based on existing and evolving interoperable information and communication technologies. IoT is typically the network of physical objects (or "things") having electronics, software, sensors, and network connectivity embedded therein, enabling collection and exchange of data to and from the objects. IOT allows objects to be sensed and controlled remotely across existing network infrastructure creating opportunities for more direct integration between the physical world and computer-based systems, and resulting in improved efficiency, accuracy and economic benefit. Each object is uniquely identifiable through its embedded computing system, however the object is able to interoperate within the existing Internet infrastructure. Experts estimate that the IoT will consist of almost 50 billion objects by 2020.
"Things," as used with IoT, refers to a wide variety of devices such as, but not limited to: heart monitoring implants, biochip transponders on farm animals, electric clams in coastal waters, automobiles with built-in sensors, or field operation devices that assist firefighters in search and rescue operations. These devices collect useful data with the help of various existing technologies and then autonomously direct data between other devices. Examples of such things in the current market include, but are not limited to: smart thermostat systems and washer/dryers that use Wi-Fi for remote monitoring.
"Smart city" or "smarter city" are cities using digital technologies or information and communication technologies (ICT) to enhance quality and performance of urban services, to reduce costs and resource consumption, and to engage more effectively and actively with its citizens. Market sectors which have developed smart city technology include, but are not limited to: government services, transport and traffic management, energy, health care, water and waste services. Smart city applications are developed with the goal of improving the management of urban information flows and allowing for real time responses to challenges. A smart city may be more prepared to respond to an array of challenges, as opposed to one simple 'transactional' relationship with its citizens. Other terms that have used for similar concepts include "cyberville, "digital city", "electronic communities", "flexicity", "information city", "intelligent city", "knowledge-based city", "MESH city", "telecity", "teletopia", "Ubiquitous city", "wired city".
"Wireless communications" is intended to mean widespread means for connecting people, vehicles and elements in a cost-effective way. These means include, but are not limited to: cellular (e.g. 3G, 4G, 5G), Wi-Fi, LWPAN, V2X, V2V, V2I, 802.11p, DSRC, Zigbee, RF, UHF, VHF, MicroWave (MW), Li-Fi, Free Space Optics (FSO), SATCOM, any type of network topology—mesh, star, point-to-point, and any operator, technology, and protocol spectrum.
In some cases, the communication to at least some lamp posts is provided by fiber or similar wired connection and the term "connected", is intended to include both "wireless communication" and "wired communication" in this context.
Traditionally, streetlighting systems incorporating LED or other technologies, are used to illuminate roads and sidewalks. Usually streetlighting systems are used with a singular on/off option. Recently, with the introduction of LED technology, remote control and some dimming functionalities have been added. In parallel, cities, government agencies and various service providers have improved in and out-of-home services, municipality services, communication services or others, integrating multiple smart city systems, sensors, data, and logic, as well as private sources, commercial systems, end user use of the services and devices, and any other user or potential user of the public space. Such improvements and applications include autonomous vehicles, drones, smart billboards and other IoT devices and their respective service provider networks.
All of these functionalities must be performed securely, protecting user data and privacy, and in a timely fashion, integrating relevant data and systems in a timely and cost-effective fashion. In this environment, there is a plethora of sensor meters and other IoT devices, such as luminescence sensors, air quality sensors, parking sensors, motion sensors, climate sensors, humidity sensors, radiation sensors, speeding sensors, visual sensors, radar sensors, acoustic sensors, fire sensors, and others. Additionally, there are multiple applications, application providers, and service providers. Some of the service providers are associated with single sensor/application, IoT, autonomous and communication devices, and some are not associated with any. This means that, for example, a weather-related information service provider installs its IoT sensors in the public space, usually collects the sensor data on its own network, or uses its communication devices and processors and processing environment being associated with his own sensors pays for communication, processing and maintenance. The service provider usually processes and uses its own data. This is done mostly in a central location such as the cloud. Such a reality presents many problems that impedes an evolution of the smart city and a coherent, optimal utilization of resources and wholesome services to public space users.
Additionally, it is challenging to introduce new sensors or other devices into the public area and, even more so, to introduce new applications that use such new and existing/deployed devices. Today there is typically virtually no sharing of resources, which results in high cost, low resource utilization, and a fragmented rather than a holistic approach and solutions for the public space. A holistic/integrated approach integrates data from multiple relevant sensors, whether being co-located or distributed, to integrate logic and decision-making by several different systems, vendors, providers and individuals, to share resources as much as possible including street processing power and communications, and to reduce communications and cost by data processing on streetlights or similar public-space installed processors connected on the network, integrating data and decisions at the street-level on the local processor. This approach enables improved decision locally, as well as reducing communication, latency and faults, costs and use of cloud processing resources. This allows multiple operators, vendors and applications providers to run their applications on a standard processor using standard tools for software development and software deployment such as the common Android OS, standard software languages, and App store paradigms to authenticate and deploy applications while sharing street-deployed sensors and platforms.
There is therefore a need to resolve such problems by allowing multiple processing devices to use one another's IoT and sensors; to share decisions and data and to coordinate their actions—all at the street or neighborhood local environment, rather than having to transmit all the information to some central cloud location and back to the field. Further, there is a need to allow using the streetlight in many ways besides a simple on/off/dimming street/road lighting. There is a need for a system to allow lighting to be responsive to various conditions and decisions according to multiple sensors, softwares, and applications, passer-by requirements/impacts, IoT devices, autonomous users of the public infrastructure, or others—either installed or associated with the same streetlight (such as Edge Computing) and/or with others, in a decentralized or centralized way as best fit to reduced latency, increase resource utilization, reduce costs and increase serviceability and forward compatibility with additional software or applications or IoT devices being introduced to the streetlight or to the public space. For example, solving the problems noted hereinabove may contribute to preventing road accidents with human-driven or autonomous vehicles by responding to changing conditions such as weather, fog, traffic, pedestrian movement, prediction of such being based in AI, or other parameters and either informing the vehicle or driver in-advance and/or dynamically adapting the lighting of a single or multiple streetlights or other sources of light or other waveforms or frequencies in coordination to better alert the road users to any specific hazard. It may improve the lighting conditions or other waveform illumination conditions to specific needs or autonomous vehicles sensors in different distances or directions or shading conditions or others. It may help protect assets in the streets. These are just a few examples currently not resolved and which could be addressed in a standard-based platform, App-store deployment, and management manner.


Systems, methods, and computer-readable storage media for location-aware call processing for routing a call to a provider are provided. A telephone call from an end-user communication device may be received. An indication of a first provider category may be identified. A first set of provider information may be processed based on the first provider category. A heat map may be generated to identify correlations between user information, location information, and/or provider information. An area proximate to a first location of an end-user communication device may be calculated. A second set of provider information may be identified based on the first location and/or the area proximate to the first location. A provider is selected based on rankings of the providers. A provider is selected based on the ranking, a telephone reference is determined for the selected provider, and a connection of a telephone call is facilitated to the selected provider.

Certain embodiments of the present disclosure relate generally to telephonic connections with providers and content provisioning systems, and in particular to systems and methods for location-aware call processing.
As access and demand for information increases, end-users demand more products and services than ever before. Providers of such services are expected to compete to provide greater levels of accuracy and more tailored services to each end-user. Providers operate ever increasing numbers of complex computer systems to achieve this. Accessing and using sources of information that have previously been unavailable is now expected. Accordingly, there is a need for location-based services to provide access to time-sensitive information to end-users and providers in the fastest manner possible. Additionally, there is a need to provide location-specific and filtered provider information to end-users using minimal system resources. Further, there is a need to transmit end-user information to providers in an efficient manner.
Therefore, there is a need for systems and methods for location-aware call processing. This and other needs are addressed by the present disclosure.

Systems and methods for location-aware call processing


A digital waveform generator reads out simulated .DELTA..SIGMA. ADC data for a desired periodic analog waveform from a memory and converts it, using a low-resolution high speed DAC, into a synthesized analog waveform. The .DELTA..SIGMA. digital waveform generator is preferably designed to take advantage of the natural evolution of device technologies. The memory is fabricated with older technologies, which tend to be slower but have a much higher integration. The DAC is implemented in more recent technologies, which are faster but have less integration. A speed up buffer or buffers in intermediate speed intermediate integration technologies may be included to provide a bridge between the low speed memory and the low integration DAC. As the current technologies become more well developed, and thus more integrated, and new higher speed technologies take their place, the technologies for the various components will gradually change, but the architecture should remain viable and superior to the known digital generators.

1. Field of the Invention
This invention relates to digital data synthesis (DDS) of analog waveforms and more specifically to a digital waveform generator and method for synthesizing periodic analog waveforms using table readout of simulated delta-sigma (.DELTA..SIGMA.) analog-to-digital conversion data.
2. Description of the Related Art
Waveform generators are used extensively in transmitters and receivers in audio, radar, satellite and cellular telephone communications systems as well as in other applications such as calibration and test systems. The generation of stable, accurate and high resolution periodic analog waveforms over a wide frequency range is critical to the performance of these systems. For example, a high frequency carrier signal, e.g. a sinewave, is modulated by an information signal for transmission over a communications channel. At the other end of the channel, the same sinewave is used to demodulate the signal. Any distortion in the sinewaves induces distortion in the received information signal.
Known waveform generators are implemented with both analog and digital architectures. The analog waveform generators use crystal oscillators to generate the fundamental sinewaves and then synthesize the different sinewaves to produce a desired waveform. Current analog generators can produce waveforms up to approximately 100 GHz, but the signal-to-noise ratio (SNR) is poor due to harmonics and distortion. Any arbitrary frequency can be generated from DC to 100 GHz, but extensive feedback circuitry is required to control the frequency stability of the waveforms.
Known digital waveform generators store samples of a desired periodic analog waveform as N-bit codewords in a high speed memory. Typically, samples for one or more periods of the desired waveform are stored and read out cyclically to generate an N-bit digital waveform. An N-bit DAC converts the successive codewords into an analog waveform having 2.sup.N discrete levels. The waveform is then passed through a smoothing filter to generate the synthesized periodic waveform.
The quality of the synthesized waveform depends on the DAC's clock speed and bit rate. Current high speed fabrication technologies such as indium phosphide (InP) or gallium arsenide (GaAs) provide a maximum clock speed of approximately 1 GHz with 12-14 bits of resolution. The DAC's voltage levels must be allowed to settle and their ratios must be matched exactly to avoid introducing distortion into the analog waveform. This is difficult to accomplish, and thus has the effect of limiting the DAC's performance. Current digital synthesizers are capable of generating waveforms with about 10 bits of resolution at frequencies up to approximately 200 MHz to 300 MHz.
To read out the codewords at the DAC's clock speed, the memory has to be implemented in the same high speed technology as the N-bit DAC. Historically high speed technologies typically have a relatively low level of circuit integration. As a result, high speed memory is at a premium in terms of chip space and cost. Current research is directed at increasing the storage efficiency of the waveform to reduce the amount of memory required. For example, one-quarter of a period may be read out and reflected about different axis' of symmetry to regenerate a full period. In addition, the high speed readout of the N-bit codewords produces a significant amount of thermal energy that must be dissipated in the waveform generator.
In a digital generator, the frequency of the analog waveform can be changed by simply reading out the codewords faster or slower. Thus, many different sinewave frequencies can be generated by storing a fraction of the period and varying the readout rate. Due to the premium placed on memory, this is an important feature of known digital generators.
In the related fields of analog-to-digital (A/D) and digital-to-analog (D/A) real-time data conversion, delta-sigma (.DELTA..SIGMA.) modulation has been used in place of the conventional N-bit ADCs or DACs to improve the SNR of the converted signal. "Mixed-Signal Design Seminar," Analog Devices, Inc. Section VI:1-24, 1991 discloses a .DELTA..SIGMA. modulator that utilizes oversampling and noise shaping to increase the SNR of the converted signal. The .DELTA..SIGMA. modulator includes a comparator and a filter in a feedback loop. The comparator digitizes an input signal at a very low resolution, typically 1-bit, at a very high sampling rate relative to the signal frequency. Oversampling expands the bandwidth so that the signal spectrum occupies only a portion of the total bandwidth. The filter shapes the comparator's otherwise uniform quantization noise spectrum so that the bulk of the quantization noise occurs outside the signal spectrum. As a result, the SNR in the signal spectrum is increased dramatically with respect to a comparable N-bit ADC or DAC.
A .DELTA..SIGMA. DAC includes a digital interpolation filter that increases the sampling rate of the N-bit digital input signal. The sampling rate of a voiceband signal having a bandwidth of 4 kHz and an initial sampling rate of 8 kHz may be increased by a factor of 128 to a sampling rate of 1.024 MHz. The .DELTA..SIGMA. modulator noise-shapes the 16-bit 1.024 MHz data stream and reduces the sample width to 1-bit. Unlike the .DELTA..SIGMA. modulator in the .DELTA..SIGMA. ADC, this modulator is all digital although it performs the same function. A 1-bit DAC converts the serial bit stream into a binary analog signal, does not have the mismatch problems associated with higher resolution DACs and can be clocked at much higher rates.
The DAC's output is meaningless until it is averaged in some manner. An analog filter, whose characteristics are matched to the modulator's filter characteristics, averages the binary analog signal and thereby reduces the signal's bandwidth to the 4 kHz bandwidth of the voiceband signal and rejects the shaped quantization noise. The .DELTA..SIGMA. DAC produces a higher resolution analog signal than would a direct N-bit DAC. For example, using a 16-bit digital input signal, the .DELTA..SIGMA. DAC produces an analog signal having approximately 20 bits of resolution.
A principal drawback to .DELTA..SIGMA. modulators is that they are computationally intense, and hence quite slow. Using current technology, the maximum clocking speed of a .DELTA..SIGMA. DAC is approximately 10 MHz, which limits signal bandwidths to approximately 300 KHz with effectively 16 bits of resolution. Higher order .DELTA..SIGMA. modulators can be used to improve the SNR, but the additional logic circuitry required further reduces speed. Secondarily, any hardware implementation introduces some distortion into the signal due to the fixed register lengths used to perform the mathematical operations, delays and non-linearities in transistor performance.
Computer programs for simulating the .DELTA..SIGMA. modulation process are well known in the art and commonly used to design .DELTA..SIGMA. modulators for DACs. The designer can vary the modulator's parameters such as filter type (low pass or band pass) and order, register lengths, bit-rate, delay elements and clock frequency for a given N-bit input signal resolution and then simulate the results. The hardware implementations of .DELTA..SIGMA. modulators are complicated, and thus extensive simulations are often required to find an architecture that achieves the desired SNR performance.
To provide a standard against which the actual performance can be measured, the designer can switch the program to an ideal mode, in which those parameters associated with the .DELTA..SIGMA. modulator's practical limitations are set to their ideal values. For example, the registers, which are typically 14 bits, can be set to the floating point accuracy of the computer running the simulation. Boser et al. "Simulating and testing oversampled analog to digital converters," IEEE Transactions on Computer Aided Design, Vol. CAD-7, pp. 668-674, June 1988 discloses the theory behind one such program, which is commonly referred to as "Midas." The operational details for the Midas program are provide by Louis A. Williams et al., Stanford University, Version 2.1, 1990.
Because of their extremely low bandwidth, .DELTA..SIGMA. modulators have not been used in digital waveform generators, but have been limited to the conversion of real-time data for signal bandwidths below 300 KHz. If a .DELTA..SIGMA. modulator were used to read out and convert the N-bit codewords into the synthesized waveform, the distortion performance would improve but the maximum waveform frequency would be limited by the modulator. Such a waveform generator would have minimal practical utility.
Furthermore, the .DELTA..SIGMA. modulator generates a different sequence of 1s and 0s for each frequency. Thus, multiple waveforms cannot be generated from the samples of a single stored waveform. Furthermore, the reflection algorithms for improving storage efficiency are not applicable to .DELTA..SIGMA. modulation. Therefore, a full period of each desired waveform would have to be stored.

Digital waveform generator and method for synthesizing periodic analog waveforms using table readout of simulated .DELTA.- .SIGMA. analog-to-digital conversion data


A method and apparatus for performing modulated fluid delivery and aspiration during a surgical procedure such as phacoemulsification is provided. The method and apparatus include delivering fluid and/or aspirating fluid in a modulated or pulsed manner during a surgical procedure, including applying fluid and/or aspirating fluid in connection with ultrasonic energy at a level and for a time period sufficient to induce transient cavitation. Fluid may be applied and/or aspirated at a timing sequence and duty cycle similar to or different from application of ultrasonic energy delivery.

Field of the Invention
The present invention relates generally to the field of surgical tissue removal systems, and more specifically to modulated irrigation and aspiration during surgical procedures such as phacoemulsification.
Description of the Related Art
Phacoemulsification surgery has been successfully employed in the treatment of certain ocular problems, such as cataracts. Phacoemulsification surgery utilizes a small corneal incision to insert the tip of at least one phacoemulsification handheld surgical implement, or handpiece. The handpiece includes a needle which is ultrasonically driven once placed within an incision to emulsify the eye lens, or break the cataract into small pieces. The broken cataract pieces may subsequently be removed using the same handpiece or another handpiece in a controlled manner. The surgeon may then insert lens implants in the eye through the incision. The incision is allowed to heal, and the results for the patient are typically significantly improved eyesight.
As may be appreciated, the flow of fluid to and from a patient through a fluid infusion or extraction system and power control of the phacoemulsification handpiece is critical to the procedure performed. Different medically recognized techniques have been utilized for the lens removal portion of the surgery. Among these, one popular technique is a simultaneous combination of phacoemulsification, irrigation and aspiration using a single handpiece. This method includes making the incision, inserting the handheld surgical implement to emulsify the cataract or eye lens. Simultaneously with this emulsification, the handpiece provides a fluid for irrigation of the emulsified lens and a vacuum for aspiration of the emulsified lens and inserted fluids.
Currently available phacoemulsification systems include a variable speed peristaltic pump, a vacuum sensor, an adjustable source of ultrasonic power, and a programmable microprocessor with operator-selected presets for controlling aspiration rate, vacuum and ultrasonic power levels. A phacoemulsification handpiece is interconnected with a control console by an electric cable for powering and controlling the piezoelectric transducer. Tubing provides irrigation fluid to the eye and enables withdrawal of aspiration fluid from an eye through the handpiece. The hollow needle of the handpiece may typically be driven or excited along its longitudinal axis by the piezoelectric effect in crystals created by an AC voltage applied thereto. The motion of the driven crystal is amplified by a mechanically resonant system within the handpiece such that the motion of the needle connected thereto is directly dependent upon the frequency at which the crystal is driven, with a maximum motion occurring at a resonant frequency. The resonant frequency is dependent in part upon the mass of the needle interconnected therewith, which is typically vibrated by the crystal.
Power control of the phacoemulsification handpiece is highly critical to successful phacoemulsification surgery. Certain previous systems address the requirements of power control for a phacoemulsification handpiece based on the phase angle between voltage applied to a handpiece piezoelectric transducer and the current drawn by the piezoelectric transducer and/or the amplitude of power pulses provided to the handpiece. The typical arrangement is tuned for the particular handpiece, and power is applied in a continuous fashion or series of solid bursts subject to the control of the surgeon/operator. For example, the system may apply power for 150 ms, then cease power for 350 ms, and repeat this on/off sequence for the necessary duration of power application. In this example, power is applied through the piezoelectric crystals of the phacoemulsification handpiece to the needle causing ultrasonic power emission for 150 ms, followed by ceasing application of power using the crystals, handpiece, and needle for 350 ms. It is understood that while power in this example is applied for 150 ms, this application of power includes application of a sinusoidal waveform to the piezoelectric crystals at a frequency of generally between about 25 kHz and 50 kHz and is thus not truly "constant." Application of power during this 150 ms period is defined as a constant application of a 25 kHz to 50 kHz sinusoid. In certain circumstances, the surgeon/operator may wish to apply these power bursts for a duration of time, cease application of power, then reapply at this or another power setting. The frequency and duration of the burst is typically controllable, as is the length of the stream of bursts applied to the affected area. The time period where power is not applied enable cavitation in the affected area whereby broken sections may be removed using aspiration provided by the handpiece or an aspiration apparatus.
As described in U.S. patent application Ser. No. 10/387,327 to Kadziauskas et al., entitled "System and Method for Pulsed Ultrasonic Power Delivery Employing Cavitation Aspects," filed Mar. 12, 2003, discusses the beneficial aspects of transient cavitation and provides a system and method for applying energy at a level and for a time period sufficient to induce transient cavitation, and reducing applied energy after applying energy during a second nonzero lower energy period. Various ultrasonic power delivery profiles may be employed utilizing the beneficial effects of transient cavitation, including more powerful removal with reduced risk of burning or damaging the affected area.
Generally, irrigation and aspiration are employed by the surgeon using the device to remove unwanted tissue and maintain pressure within the eye. In the presence of high frequency power applications, cavitation may be generated through the needle to the unwanted tissue in an effort to break the tissue. Alternately, mechanical fragmentation may be employed using rotary, oscillatory, or reciprocating cutters to segment or grind unwanted tissue. The resultant tissue is aspirated in slurry form from the surgical site.
Issues associated with aspiration and irrigation in this environment can include difficulty in acquiring or purchasing the tissue and holding the tissue with the tip for proper removal. Use of pulsed ultrasonic power delivery, and capture and removal of unwanted tissue, particularly in high power environments where transient cavitation is encountered, can be difficult. Power delivery in the presence of relatively constant or slowly changing fluid flow characteristics can cause disruption of purchase, holding, and removal of unwanted tissue. Additionally, a mechanical cavity or cavitation cloud may form in the presence of ultrasonic cavitational energy, and such a mechanical cavity can provide a virtual barrier to efficient tissue processing. Such a mechanical cavity results from pressure differentials formed by ultrasonic energy application in the presence of a relatively constant fluid flow, and is undesirable.
Further, in the environment described, tissue may occasionally clog the lumen, or fluid passage, within the tip of the handpiece. Such clogging creates unpredictable performance characteristics and can result in undesirable pressure surges. The vacuum levels typically employed with aspiration and irrigation tend to be low to avoid clogging and other undesirable fluid flow effects. Use of low pressure can inhibit a surgeon's ability to purchase and hold unwanted tissue.
Based on the foregoing, it would be advantageous to provide an irrigation and aspiration system that effectively and efficiently operates in the presence of high ultrasonic power delivery, such as systems generating transient cavitation, and minimizes those drawbacks associated with previous tissue removal systems.

System and method for modulated surgical procedure irrigation and aspiration


A fluid container having at least one internal chamber for receiving a fluid, and having at least one connector for hydraulically connecting the internal chamber to a downstream hydraulic apparatus, wherein the connector at the end thereof toward the internal chamber has a mouth portion. In order to propose an improved fluid container by way of which high volumetric flows can also pass through the connector at high throughflow rates with low losses and reduced resistance, it is proposed that an escape value of the connector is provided so as to be larger than 0.82, and the mouth portion in relation to a container wall region that directly surrounds the mouth portion is at least in portions designed so as to be raised in the direction of the internal chamber.

Such fluid containers are used, for example, as pressurizing medium containers for hydraulic motor vehicle brake systems where said fluid containers serve in particular for supplying classic master brake cylinders which are coupled to a separate booster stage, or combined pressure-generation apparatuses which include the booster stage in an integral manner. The fluid containers herein can be connected to the downstream apparatus by way of hydraulic lines, but said fluid containers are mostly fastened directly to the hydraulic apparatus. The connectors herein, apart from the function thereof as a hydraulic interface, also have a fastening function in that said connectors are received in corresponding connector receptacles on the connected apparatus and fully or partially assume the positional securing of the fluid container in the vehicle.
Diverse requirements are therefore set in terms of the geometry and shape of the connectors. On the one hand, a sufficiently large cross section for a flawless throughflow of the pressurizing medium has to be made available in the case of all operating conditions and at all temperatures, and the height, or the axial length, respectively, of the connector and the stability have to be designed such that said connector is guaranteed to hold and seal in a reliable manner, on the other hand. The production herein is to be as simple as possible. Against this background, connectors in the manner of cylindrical attachment pipes have in particular established themselves.
The modern highly automated and highly dynamic brake apparatuses in particular require relatively large quantities of readily flowing pressurizing medium within relatively short temporal intervals, this leading to high volumetric flows and throughflow rates in the connectors. High volumetric flows at high throughflow rates can cause various negative effects in the known and relatively narrow cylindrical connectors. Said negative effects include, for example, turbulences on the mouth edge of the connector in the internal chamber and, on account thereof, increased internal fluid friction, thus higher resistance, a creation of cavity regions having an associated generation of noise and formation of gas bubbles, a formation of inflow vortices in the internal chambers of the fluid container which drag the air thereinto and can optionally affect other components such as floats of sensor devices.
From DE 10 2007 037 225A1, incorporated herein by reference, it is known for the mouth edge of the connector to be slightly radiused so as to improve the flow behavior and to address the aforementioned negative effects. However, only a relatively minor improvement can be achieved by blunting the edges in such a manner. A further aspect to be considered is that dirt particles can accumulate and be deposited over time in a pressurizing medium container. The access of dirt to the downstream apparatus is to be minimized or prevented as far as possible; a radiused feature of this type does not prevent this and may even facilitate this because the dirt is suctioned from the surrounding wall region of the fluid container and entrained by the flow.

Fluid container comprising a flow-optimised connecting piece


Relatively small cyclic peptides that mimic the biological and/or chemical activity of larger cyclic peptide such as somatostatin, as well as synthetic methods therefor. In certain embodiments, cyclic peptides of the invention have structure: ##STR1## wherein R.sub.NP1 is H, an amine protecting group, or a solid support and R.sub.NP2 is H or an amine protecting group.

Peptides are implicated in a wide variety of biochemical processes in humans and other mammals. The design of peptide mimics which are resistant to degradation by proteolytic enzymes has become of increasing interest to peptide chemists. A primary goal has been to reduce the susceptibility of mimics to cleavage and inactivation by peptidases.
Somatostatin (SRIF; somatotropin release inhibiting factor), a cyclic tetradecapeptide, was first isolated from bovine hypothalamus and characterized as an inhibitor of growth hormone secretion. SRIF receptors have been found not only on pituitary cells but also in the brain, on gastric or pancreatic cells, and elsewhere. This has stimulated interest in the isolation of SRIF receptors by affinity chromatography in amount sufficient for partial sequence determination. For example, He, et al, Proc. Natl. Acad. Sci. (USA), 1989, 86, 1480, have described the use of D-Trp.sup.8 SRIF as an affinity ligand.
The bioactive conformation of SRIF is believed to include a .beta.-turn involving residues 7-10 (Phe.sup.7 -Trp.sup.8 -Lys.sup.9 -Thr.sup.10) (SEQ ID NO:1). These four amino acids have been shown to be necessary and sufficient for receptor recognition and activation, so long as they are held in the proper orientation. Somatostatin accomplishes this proper orientation through its ten remaining amino acids and the cystine bridge contained therein. In a number of active cyclic hexapeptide analogs for somatostatin, proper orientation of the four amino acids is maintained via dipeptide segments. For example, Veber and Hirschmann, et al., Life Sciences, 1984, 34, 1371 and Nature, 1981, 292 have reported that cyclic hexapeptides typified by cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) are potent mimics of somatostatin.

Somatostatin mimics and synthetic methods therefor

The Trustees Of The University Of Pennsylvania


An observation device includes a housing and an optical lens having a field of view. The housing includes an outer dome having at least one transparent portion and an inner dome. The optical lens is accommodated within the housing. The outer dome is transparent in the field of view of the lens and is configured to protect the lens. The observation device is resistant to impact by an object with a maximum impact energy of a first magnitude. A like observation device, but lacking an inner dome, is resistant to impact by the object with a maximum impact energy of a second magnitude. The ratio between the first magnitude and the second magnitude is at least 1.1.

An observation device comprising an inner dome is known from European patent application EP 1136 964 A2 and from U.S. Pat. No. 3,819,856.
Cameras comprising at least an outer dome are generally used as observation cameras, in particular attached to a ceiling, with the outer dome functioning to protect the lens. Considering the nature of the use of such cameras, it is at least desirable or even necessary for such cameras to be vandal-proof. This implies that the outer dome must be resistant to a certain extent to impact with or by an object, such as a club or the like, so that the deformation that the outer dome undergoes as a result of such impact will be so small that the lens does not come into contact with the inner side of the outer dome and/or of the inner dome, for example, in which case the camera may require some form of repair as a consequence of the impact but continues to function as such.
In order to comply with this wish/requirement, the diameter of the outer dome is generally selected so large that there is a considerable spacing between the inner side of the outer dome and the lens. Thus the outer dome can deform to a large extent without the lens being touched. This solution to the problem as described above is contrary to the general wish/requirement to make the cameras small and compact so that they will be as inconspicuous as possible. After all, practice teaches that the less conspicuous a camera is, the less vandals will be inclined to test the camera's resistance to vandalism. In addition to that, thicker outer domes generally result in greater image distortion.
An alternative solution to increasing the resistance of cameras to vandalism is to user a thicker material for the outer dome. Apart from the fact that this leads to a relatively great increase of the manufacturing costs of such outer domes, it has become apparent that it may have a contrary effect on the impact-resistance, because the internal stresses that occur upon impact will be higher, which may lead to unacceptable failure of the outer dome.
The camera as described in U.S. Pat. No. 3,819,856 comprises an outer dome as well as an inner dome. The reason for using two domes for each camera as described in the aforesaid two documents is to provide a visual screen for the lens, so that it will be difficult for persons to detect the direction of the scanning beam and thus find out if they are in the camera's field of view. The outer dome in EP 1 136 964 A2 functions to provide a universal screen for different types of cameras.
From U.S. Pat. No. 4,920,326 there is known a surveillance camera comprising a substantially spherical housing. The housing substantially comprises an upper dome and a lower dome. The upper dome is formed of three layers, viz. an outer layer of a rubber-containing plastic alloy having good ballistic properties, an acrylic intermediate layer, and an aluminum inner layer. The lower dome comprises the same three layers, with two transparent polycarbonate layers additionally being present on the inner side and on the outer side. Pop rivets are provided to keep the transparent polycarbonate layers and the three layers present therebetween together. On the outside, the lower dome is finally provided with a methyl acrylate cover. The scanning beam passes through the two transparent polycarbonate layers and through the methyl acrylate layer, and air is present between the three layers. A very important drawback of the known observation device is the constructional complexity thereof, as a result of which the manufacture of the various parts and the assembly thereof will be time-consuming and costly. Another important drawback is the use of the large number of dome layers, resulting in a loss of light with the attendant risk of significant refraction of the light. Moreover, it is difficult to gain access to the interior of the observation device.


An apparatus for providing information services to a user includes a microserver disposed at the user's home or office. The microserver is connected to a communication network which is connected to a global computer network, and the user's mobile or fixed telephone terminal. At least one service server is connected to the user's mobile or fixed terminal via the global computer network, the communication network and the microserver. Through the disposition of microserver at the user's primary location, the service server can transmit general or user specific service information to the user via their mobile and/or fixed terminal. The problems of localization of the user are eliminated by the implementation of the microsever at the user's primary communication location.

1. Field of the Invention
The present invention relates to communication systems, and more particularly, to an apparatus for providing information/data services to a telecommunication device user from data networks.
2. Description of the Related Art
European Patent No. 0797368 discloses a telecommunication system and radio base station and portable telecommunication terminal thereof. In that system, information is stored in the base station (i.e., cells), which determines the minimum localization range of the portable/mobile telephone. Generally, in any given case, this range is equivalent to the cell size, and in some instances may be as large as 35 sq. km. Thus, it is clear that user localization is somewhat indeterminable, which results in the inability to use or even provide services to a mobile terminal user that require precise location information. Only when a call is placed to the mobile terminal can the stored information be transmitted to the mobile terminal from the base station. The information storage in this system is limited to the telecommunication operator's telecommunication network, thereby resulting in a limitation on the ability to provide additional services to the mobile terminal user. In addition, the inability to accurately locate the mobile terminal coupled with the fact that there is no connection between data networks and the communication network prevents the direct sending of data services to the mobile terminal user.
PCT Patent Publication No. WO 98/36585 discloses a sponsored call and cell service that suffers from the same previously mentioned localization and information storage problems, and lack of connection to data networks to enable it to provide data services to the end user/subscriber. In accordance with the disclosed system, subscriber location is determined when the subscriber makes an outgoing call. This, however, results in a determination as to the cell location of the mobile user and does not provide any more accurate localization of the user. As mentioned previously, the cell size can be up to 35 sq. km.

This patent is subject to a terminal disclaimer.

Apparatus for providing information services to a telecommunication device user


A new Sedum plant particularly distinguished by greenish-yellow variegated foliage, is disclosed.

The present invention comprises a new and distinct cultivar of Sedum, botanically known as Sedum hybrid, and hereinafter referred to by the cultivar name 'Diamond Edge'. The new cultivar originated as a naturally occurring mutation in the Sedum plant 'Matrona' (unpatented) found in 2001 in a nursery in Zwaanshoek, The Netherlands. Sedum 'Matrona' is a hybrid between S. spectabile and S. telephium 'Atropurpureum'.
The new cultivar was created in 2001 in Zwaanshoek, The Netherlands and has been asexually reproduced repeatedly by vegetative cuttings and tissue culture in Zwaanshoek, The Netherlands over a four-year period. The present invention has been found to retain its distinctive characteristics through successive asexual propagations.
Plant Breeder's Rights for this cultivar were applied for with the European Union on Apr. 3, 2006.


The invention relates to measurement of a fluid flow, wherein a flow rate component of the fluid is measured along a selected direction. A magnetic field whose polarity varies over time is applied to the fluid, which presumed to contain electrically charged elements. First and second sensor electrodes (120, 121) are arranged to be wetted by the flowing fluid. The electrodes (120, 121) are spaced apart from one another along a line being substantially perpendicular both to the selected flow direction and a magnetic axis of the magnetic field. A DC-level drift of the sensor electrodes (120, 121) is prevented by supplying a control current (Ictrl-0; Ictrl-1) to each of the sensor electrode (120, 121), which has such sign and magnitude that a direct-current voltage level at the sensor electrodes (120, 121) relative areference potential is controled towards a predetermined voltage (DCset).

The present invention relates generally to measurement of a fluid flow. More particularly the invention relates to a flow sensor according to the preamble of claim 1, an ultra-filtration measuring unit according to the preamble of claim 8 and a method for measuring a flow rate component according to the preamble of claim 10.
There are many technical areas in which an accurate fluid flow measurement is required. Numerous representative applications can, for instance be found in the field of medical technology. However, some kind of flow measurement is normally required in most instances where a fluid/liquid is to be transported from one point to another. Fluid flow measurements may also be used to determine the velocity of a craft traveling in water or a similar liquid. Naturally, mechanical flow sensors may here be employed. Nevertheless, when a high accuracy is required, electromagnetic flow measurement sensors are generally preferable. This type of sensors are based on a well-known technique where a magnetic field is applied to interact with electrically charged elements, such as ions, in the flowing fluid to produce a resulting electric field. Thus, according to Faraday's law, the magnitude of the induced electric field constitutes a measure of the flow rate of the fluid.
The applicant develops and manufactures medical equipment, for instance renal products in the form of dialysis apparatuses, which utilize such an electromagnetic flow measurement technique. Commonly, flow sensors with platinum electrodes have been employed to deliver accurate and reliable values of the registered fluid flows. Platinum, and platinum black in particular, namely accomplishes a good electrical contact between the electrodes and the dialysis liquid, so that the electrode dimensions can be held comparatively small, and consequently give rise to a linear magnetic field pattern in the fluid conduit cross section.
In recent years, a so-called glucose-charging practice has been introduced wherein glucose is added to the dialysis liquid in order to better imitate the composition of the patient's own blood, and thereby i.a. avoid certain metabolic risks for the patient. However, glucose also produces undesired effects due to its electrochemical activity with platinum. During operation of a dialysis apparatus with a glucose-charged dialysis liquid, a catalytic reaction causes glucose to be oxidized on the flow sensors' platinum surfaces. This decreases the reliability of the flow measurements. Namely, the oxidation may result in a varying DC-level (DC=Direct Current) at the sensor electrodes, which in turn renders it difficult to determine the contribution to the registered electric field caused by the electromagnetic interaction between the applied magnetic field and the charged elements in the flowing liquid (i.e. here ions in the dialysis liquid).
The U.S. Patent Application No. 2002/0050175 describes a magnetic flow sensor and method, wherein an undesired drift of the electrode voltages is compensated for, either by interconnecting the sensing electrodes or by connecting them to a common potential, such as ground. Also in this case, a voltage indicative of the flow rate is measured by means of at least two electrodes. A high-impedance voltage-measurement circuit is used to register a voltage between the electrodes. Thus, during the measurement, the electrodes are in an open circuit state, and may therefore be electrically influenced by electrode polarization and other measurement error-inducing factors that develop relatively slowly. In order to avoid such effects, the electrodes are in a closed circuit state for most of the time and placed in an open circuit state only during a relatively brief measurement interval portion of the operating cycle.
Although this strategy may solve the drifting problem, it results in a limited maximum sampling frequency, and consequently also an accuracy constraint with respect to the detection of rapid changes in the flow rate. Moreover, the procedure requires a considerable amount of high-speed switching, and is therefore both expensive to implement and relatively prone to malfunction.

Flow sensor and method for measuring a flow rate component of a fluid containing electrically charged elements


One aspect of the present invention is to provide a method for compensating a system duty cycle of a system clock signal. The method in one embodiment comprises the following steps: locking a duty cycle center of the system duty cycle by a delay lock loop; detecting a current system duty cycle of the system clock signal; determining a duty cycle correction amount, wherein the duty cycle correction amount is a gap of the current system duty cycle from a target duty cycle; and changing a polarity of an input reference clock signal according to whether the duty cycle correction amount exceed a threshold amount or not.

1. Field of Invention
The present invention relates to an integrated circuit. More particularly, the present invention relates to a clock cycle compensator and the method thereof.
2. Description of Related Art
Along with the manufacturing process scaling down in recently years, the environmental degradation becomes an issue on integrated circuits. For example, negative bias temperature instability (NBTI) degradation leads to a variation on a threshold voltage of the P-type metal-oxide-semiconductor field-effect transistor (MOSFET), and the variation affects a stability and a performance of an integrated circuit. For example, as the NBTI degradation impacts on a clock generation circuit in a dynamic random access memory (DRAM), a duty cycle of a clock signal generated from the clock generation circuit may be shifted. Further, in certain cases, the NBTI degradation may causes a failure in the DRAM.
Referring to FIG. 1, the effect of the NBTI degradation on a system clock signal is schematically shown. At time of beginning (i.e., timing axis, Time 0), the original effective in-system operational duty cycle range 100, EISODCR0, is denoted as EISODCR0=DC0±DCR, where the DC0 is the intrinsic duty cycle center point of the system clock signal and ±DCR is range of the duty cycle of the system clock signal. At time x, the time after the NBTI degradation, the corresponding effective in-system operational duty cycle range 120, EISODCRX, is denoted as EISODCRX=DC0±DCR±DCDX, where ±DCDX is the time shifted by the NBTI degradation. In other words, the NBTI degradation effectively shifts the intrinsic duty cycle by DCDX, which may cause certain potential clocking issues.
Therefore, a heretofore-unaddressed need exists for compensating the NBTI degradation to address the aforementioned deficiencies and inadequacies.

Clock cycle compensator and the method thereof