A content addressable memory (CAM) device having multiple index generators is described. Each of the index generators is coupled to at least one of a plurality CAM blocks. Each of the plurality of CAM blocks includes a CAM block array and a priority encoder. Each of the index generators includes a priority encoder and match enable circuits. Each index generators is configured to receive a block index and a block match flag from a corresponding CAM block and generate a device index corresponding to a highest priority matching entry in a respective CAM block or a group of associated CAM blocks participating in a compare operation.

Networks contain a collection of computing systems (e.g., clients and servers) that are interconnected by transmission lines to enable the transfer of data between them. A network typically includes multiple access points (e.g., routers and servers) that may switch and/or route data between transmission lines to transfer data from a source to a destination. Data is typically transmitted in the form of packets that are made up of smaller data cells. A packet is a unit of data that is routed between a source and a destination on a packet-switched network. When a file (e.g., e-mail, graphics, etc.) is sent from one place to another on a network, the file is divided into such smaller packets making them more efficient for transmission. The individual packets for a given file may travel different routes throughout networks with each packet containing both data and transmission information associated with the routing of data. As such, a packet may be described as having a payload containing the data, and one or more headers that contain the routing information (e.g., a destination address).
When all the packets have arrived at a destination, they are reassembled into the original file at the receiving end. Such a packet switching scheme is an efficient way to handle transmission on a connectionless network. This is in contrast to a circuit switching scheme where a connection (e.g., a voice connection) requires the dedication of a particular path for the duration of the connection.
A router is a device (e.g., hardware, firmware, software) that determines the next network segment to which a packet should be forwarded towards its destination. A router may be positioned at points within a network or where one network meets another, referred to as a gateway. A router may create and maintain tables of the available routes and their conditions for use with other information to determine the best route for a given packet. Typically, a packet may travel through a number of network points having routers before arriving at its destination.
When a data packet arrives at the input of a router, several lookups may be performed to determine the subsequent handling of the packet, as illustrated in FIG. 1. The lookups may include, for examples, where to send the packet next (Next Hop), the quality of service requirement (QoS), the Ethernet port address, etc. Consider, for example, a packet arriving at Router-A. Router-A needs to determine whether the packet is destined for local servers connected directly to Router-A, or if the packet should go to the next router on a route (Router-B) to a destination. Additionally, Router-A may assign a priority based on the destination address (DA) and the source address (SA) of the packet.
The packet header may first be parsed or processed to get the values from different fields (e.g., SA, DA, protocol type, QoS, etc) in order to perform the various lookups. A packet classification lookup, for example, may be performed using SA, DA and other relevant fields in the packet header. The Next Hop lookup, for example, may also be performed to determine whether the packet is meant for local servers or for Router-B. If the packet is destined for Router-B, the packet is then put in a queue for Router-B. If the packet is destined for a local server (e.g., Server-1 or Server-2), then a media access control (MAC) lookup is performed to send the packet to the appropriate server. In the preceding example, three lookups are necessary for sending the packet on its way: Packet Classification, Next Hop, and MAC. However, often there are other lookups performed on the packet header.
Routers may use processors and content addressable memory (CAM) devices to perform the various lookups on packets. As opposed to a random access memory (RAM) device, in which information is accessed by specifying a particular memory location address, the data stored in a CAM is accessed by the contents of the data. More specifically, instead of using an address to access a particular memory location, a CAM uses a key that contains a portion of the desired contents of a particular memory cell in the memory device. The CAM can be instructed by a processor to compare the key, also referred to as a comparand (e.g., packet header data) with data stored in its associative memory array, as illustrated in FIG. 2. The CAM simultaneously examines all of its entries and selects the stored data that matches the key.
When the entire CAM device, or blocks thereof, is searched simultaneously for a match of the stored data with the key/comparand, the CAM device indicates the existence of a match by asserting a match flag. Multiple matches may also be indicated by asserting a multiple match flag. The CAM device typically includes a priority encoder to translate the matched location into a match address or CAM index. The priority encoder may also sort out which matching memory location has the top priority if there is more than one matching entry.
Data may be represented in the form of strings of binary digits ("bits") having a low ("0") logic state and a high ("1") logic state. Different types of CAMs may be used with different data formats. A binary CAM is designed to operate with "0" and "1" states, while a ternary CAM is designed to operate with "0", "1", and "don't care" states. The bits may be organized into groups such as a word (e.g., 64 or 72 bits wide) and stored in different segments of a CAM. The keys used for different data fields may have different word sizes, for example, the key for a Classification lookup may be 128 bits wide and the key for a Next Hop lookup may be 32 bits wide.
A router may include multiple CAMs, with each CAM having a different table or, alternatively, a single CAM having multiple block arrays for each of the different tables, for performing the different lookups. For example, a router may include a 32 bit wide Next Hop CAM, a 128 bit Classification CAM, and a 48 bit MAC CAM.
Each of the multiple CAMs, or CAM block arrays, are typically connected to common buses that are used to communicate the various search keys, indices, and other input and output data with each of the CAMs, or CAM block arrays. Thus, lookups are typically performed sequentially before a packet is processed (e.g., routed to the next destination or classified). Because the buses are shared with so many input and output functions of all the CAMs or CAM block arrays, many clock cycles are required to multiplex data on the bus. This generally limits the search rate and overall throughput of conventional CAM devices.
In some prior multiple block CAM devices, all of the block arrays typically participate in a given lookup. This can cause an undesirable amount of power to be drawn during the lookup. Other prior multiple block CAM devices use class codes and search codes to perform searches of different types on one or more of the array blocks. For example, different lookup tables may be formed spanning one or more of the array blocks. The array blocks associated with each lookup table are given a unique class code that identifies information stored in the table such as table configuration (i.e., width and depth) and type of data stored in the table (e.g., IP, MPLS, MAC lookup, etc.). A search code is typically provided with the search key in order to identify a particular table to be searched that has an associated class code matching the search code. However, the lookups in such prior CAM devices are performed using only a single search code at any given time. In other words, a search code is provided to the CAM device and only a table having a class code that matches the search code is searched. Therefore, lookups in tables having different class codes, based on different search codes, are performed sequentially before a packet is processed, thereby increasing device throughput.
As the number of ports, segments, or devices that are supported by routers increase and as the number of lookups increase, conventional CAM devices and architectures can undesirably limit the system's overall throughput and power consumption.
Some CAM devices store data in a preordered or prioritized manner such that higher priority data may be stored in lower logical addresses of the CAM array than lower priority data. Particular route data has a higher priority than other route data when such route data is to be selected over the other route data even though both route data may match a search key. The prioritizing of route data is typically performed by table management hardware and/or software that adds overhead to the router. If the table is not prioritized correctly, then an incorrect route may be selected for an incoming packet. When data stored in a CAM array is changed by adding new route data that has a higher (or equal) priority than data already stored in the CAM array, the table management hardware and software needs to reprioritize or reorder all or part of the CAM array. This is typically accomplished by reloading the CAM array with a new prioritized group of data. This can add significant overhead to the router (e.g., delay and additional hardware and software) to change a single route data stored in the CAM array.

CAM device having multiple index generators


Methods of forming integrated circuit capacitors include the steps of forming an electrically insulating layer on a face of a semiconductor substrate and then patterning the electrically insulating layer to define a contact hole therein. A barrier metal layer is then formed in at least a portion of the contact hole. A lower electrode metal layer is then formed on the barrier metal layer and then planarized by reflowing the lower electrode metal layer at a temperature greater than about 650.degree. C. in a nitrogen gas ambient, to define a lower capacitor electrode. A layer of material having a high dielectric constant is then formed on the lower capacitor electrode. An upper capacitor electrode is then formed on the dielectric layer, opposite the lower capacitor electrode. The dielectric layer may comprise Ba(Sr, Ti)O.sub.3, Pb(Zr, Ti)O.sub.3, Ta.sub.2 O.sub.5, SiO.sub.2, SiN.sub.3, SrTiO.sub.3, PZT, SrBi.sub.2 Ta.sub.2 O.sub.9, (Pb, La)(Zr, Ti)O.sub.3 and Bi.sub.4 Ti.sub.3 O.sub.12. According to one embodiment of the present invention, the step of patterning the electrically insulating layer comprises patterning the electrically insulating layer to define a contact hole therein that exposes the face of the semiconductor substrate. The step of forming a barrier metal layer also preferably comprises depositing a conformal barrier metal layer on sidewalls of the contact hole and on the exposed face of the substrate. The barrier metal layer may be selected from the group consisting of TiN, CoSi, TaSiN, TiSiN, TaSi, TiSi, Ta and TaN.

Reductions in cell capacitance due to reductions in memory cell area impede the progress towards higher integration of memory devices, and make it more difficult to secure desired cell capacitance using typical dielectric materials such as nitride/oxide (NO) and tantalum pentoxide Ta.sub.2 O.sub.5. Therefore, research into methods for forming dielectric layers of capacitors using high dielectric materials such as Ba(Sr,Ti)O.sub.3 (BST) or Pb(Zr,Ti)O.sub.3 (PZT), has been conducted. At this time, it is also well known that metals of the platinum group (or an oxide thereof) have excellent oxidation resistance and relatively low inter-diffusibility with BST or PZT thin films and are suitable for use as capacitor electrode materials.
FIGS. 1A and 1B are sectional views for illustrating a conventional method for forming a capacitor storage electrode using platinum. Referring to FIG. 1A, an insulating layer 12 formed on a semiconductor substrate 10 is partially etched to form a storage contact hole 14, and then polysilicon is deposited and etched back to form a conductive plug 16 for filling the storage contact hole 14. A titanium nitride layer 18 (as a barrier layer) is then formed on the resultant structure where the conductive plug 16 is formed, and platinum is deposited on the titanium nitride layer 18 to form a platinum layer 20. Then, an oxide layer to be used as an etching mask is formed on the resultant structure where the platinum layer 20 is formed, and patterned to form a mask pattern 22.
Referring to FIG. 1B, using the mask pattern 22 as an etching mask, the platinum layer 20 and the titanium nitride layer 18 are sequentially etched to form a platinum layer pattern 24 and a barrier layer pattern 26 which collectively form a storage electrode 27. After removing the mask pattern 22, a dielectric layer 28 formed of BST or PZT is deposited as a blanket layer using a sputtering method or a metal organic chemical vapor deposition (MOCVD) method. Then, a plate electrode 30 is formed on the dielectric layer 28, opposite the storage electrode 27.
However, when forming a capacitor using a high dielectric material such as BST or PZT as described above, problems may occur. First, during the step of forming the dielectric layer 28, diffusion of oxygen through the side surfaces of an exposed barrier layer 26 may deteriorate the electrical characteristics of the capacitor. In particular, the oxygen atmosphere and the high temperature at which the high dielectric layer 28 (such as BST or PZT) is typically formed, accelerate the rate of oxygen diffusion into the barrier layer 28. Due to oxygen diffusion, the barrier layer pattern 26 may be partially oxidized, and a titanium oxide layer TiO.sub.2 (not shown) which has an insulating characteristic may be formed on an interface between the conductive plug 16 and the barrier layer pattern 26, or between the barrier layer pattern 26 and the platinum layer pattern 24. A discussion of these adverse consequences of oxygen diffusion is also provided in U.S. Pat. No. 5,478,772 to Fazan.
As will be understood by those skilled in the art, the titanium oxide layer may cause contact failure between the barrier layer pattern 26 and the platinum layer pattern 24. Also, the titanium oxide layer deteriorates the function of the barrier layer 26 in preventing diffusion of oxygen or metal atoms therethrough, and may cause generation of leakage currents between the storage electrode and the semiconductor substrate. Second, since the storage electrode including the platinum layer pattern 24 is required to be thickly formed, the titanium oxide layer may impede patterning and may generate a high step difference adjacent the capacitor. Alternatively, if the platinum layer pattern 24 of the storage electrode is thin, then oxygen may readily pass through the platinum layer pattern 24 to combine with the barrier layer pattern 26. Accordingly, the platinum layer pattern 24 is typically made to be about 2000 .ANG. thick or more. However, since platinum is very hard and refractory, it typically 2 0 cannot be easily etched through dry etching such as reactive ion etching. Accordingly, when the platinum layer pattern is 2000 .ANG. thick or more, patterning becomes very difficult and the platinum layer pattern 24 may create a large step difference around the capacitor. Third, it is typically difficult to secure an etching mask comprising a material that can be selectively etched at a much lower rate than platinum. This latter difficulty is further compounded when thick platinum layer patterns 24 are used.

Methods of forming integrated circuit capacitors using metal reflow techniques


The present invention relates to two novel, testis-specific proteins (C19 and C23) that arc lysozyme paralogues. The proteins are believed to play a role in capacitation of sperm and the fertilization of the ovum. Therefore these compounds make ideal targets for the design of contraceptive agents. The C19 and C23 proteins can also be modified to establish lysozyme activity and the modified proteins can then be used in all applications that currently exist for lysozymes.

Lysozymes are hydrolases capable of lysing many bacteria. They cleave a beta-glycosidic bond between the C-1 of N-acetylmuramic acid and the C-4 of N-acetylglucosamine of the bacterial cell wall peptidoglycans (murein). Besides this muramidase activity they also display some chitinase (fungal cell wall component) activity. Lysozymes also are credited with antibacterial and antiviral capacities different from the bacteriolytic activity. For example, lysozymes have been demonstrated to have HIV 1 antiviral activity.
Lysozymes have been found in many biological tissues and secretions. Stomach lysozymes (cow, leaf-eating monkey) are even specialized to function at lower pH. There are two types of lysozymes found in the animal kingdom: C-type or chicken-type lysozymes represented by chicken egg white lysozyme, and G-type or goose type lysozymes represented by goose-egg white lysozyme. The C-type lysozymes are actually considered a superfamily including conventional lysozymes, calcium-binding lysozymes, and alpha-lactalbumins. All lysozymes have very similar tertiary structures, but vary in amino-acid composition.
Only one lysozyme has been identified and cloned from human tissues and body fluids. The gene coding for the human lysozyme is located on chromosome 12. A second lysozyme C gene was found on chromosome 17, but the corresponding protein has not been described (H. Nomiyama, J of Interferon and Cytokine Research 19: 227, 1999). Lysozyme C is a gene of 5856 bp and comprises four exons. The encoded protein is a secretory protein and comprises an 18 amino acid signal sequence and a mature protein of 130 residues. The mature protein contains four disulfide bonds between Cys 6—Cys 128, Cys 30—Cys 116, Cys 65—Cys 81, and Cys 77—Cys 95. This protein has been isolated from placenta, amniotic fluid, milk, tears, intestinal cells and leucocytes.
The present invention is directed to two human sperm proteins that have recently been isolated (C19 and C23) and appear to be lysozyme-C paralogues. These proteins are expressed specifically in sperm cell and are believed to function in the events relating to sperm/egg fusion and fertilization.
Definitions
In describing and claiming the invention, the following terminology will be used in accordance with the definitions set forth below.
As used herein, "nucleic acid," "DNA," and similar terms also include nucleic acid analogs, i.e. analogs having other than a phosphodiester backbone. For example, the so-called "peptide nucleic acids," which are known in the art and have peptide bonds instead of phosphodiester bonds in the backbone, are considered within the scope of the present invention.
The term "peptide" encompasses a sequence of 3 or more amino acids wherein the amino acids are naturally occurring or synthetic (non-naturally occurring) amino acids. Peptide mimetics include peptides having one or more of the following modifications:                1. peptides wherein one or more of the peptidyl —C(O)NR— linkages (bonds) have been replaced by a non-peptidyl linkage such as a —CH2— carbamate linkage (—CH2OC(O)NR—), a phosphonate linkage, a —CH2—sulfonamide (—CH2—S(O)2NR—) linkage, a urea (—NHC(O)NH—) linkage, a —CH2— secondary amine linkage, or with an alkylated peptidyl linkage (—C(O)NR—) wherein R is C1–C4 alkyl;        2. peptides wherein the N-terminus is derivatized to a —NRR1 group, to a —NRC(O)R group, to a —NRC(O)OR group, to a —NRS(O)2R group, to a —NHC(O)NHR group where R and R1 are hydrogen or C1–C4 alkyl with the proviso that R and R1 are not both hydrogen;        3. peptides wherein the C terminus is derivatized to —C(O)R2 where R2 is selected from the group consisting of C1–C4 alkoxy, and —NR3R4 where R3 and R4 are independently selected from the group consisting of hydrogen and C1–C4 alkyl.
Naturally occurring amino acid residues in peptides are abbreviated as recommended by the IUPAC-IUB Biochemical Nomenclature Commission as follows: Phenylalanine is Phe or F; Leucine is Leu or L; Isoleucine is Ile or I; Methionine is Met or M; Norleucine is NMe; Valine is Val or V; Serine is Ser or S; Proline is Pro or P; Threonine is Thr or T; Alanine is Ala or A; Tyrosine is Tyr or Y; Histidine is His or H; Glutamine is Gln or Q; Asparagine is Asn or N; Lysine is Lys or K; Aspartic Acid is Asp or D; Glutamic Acid is Glu or E; Cysteine is Cys or C; Tryptophan is Trp or W; Arginine is Arg or R; Glycine is Gly or G, and X is any amino acid. Other naturally occurring amino acids include, by way of example, 4-hydroxyproline, 5-hydroxylysine, and the like.
Synthetic or non-naturally occurring amino acids refer to amino acids which do not naturally occur in vivo but which, nevertheless, can be incorporated into the peptide structures described herein. The resulting "synthetic peptide" contain amino acids other than the 20 naturally occurring, genetically encoded amino acids at one, two, or more positions of the peptides. For instance, naphthylalanine can be substituted for trytophan to facilitate synthesis. Other synthetic amino acids that can be substituted into peptides include L-hydroxypropyl, L-3,4-dihydroxyphenylalanyl, alpha-amino acids such as L-alpha-hydroxylysyl and D-alpha-methylalanyl, L-alpha.-methylalanyl, beta.-amino acids, and isoquinolyl. D amino acids and non-naturally occurring synthetic amino acids can also be incorporated into the peptides. Other derivatives include replacement of the naturally occurring side chains of the 20 genetically encoded amino acids (or any L or D amino acid) with other side chains.
As used herein, the term "conservative amino acid substitution" are defined herein as exchanges within one of the following five groups:                I. Small aliphatic, nonpolar or slightly polar residues:                    Ala, Ser, Thr, Pro, Gly;                        II. Polar, negatively charged residues and their amides:                    Asp, Asn, Glu, Gln;                        III. Polar, positively charged residues:                    His, Arg, Lys;                        IV. Large, aliphatic, nonpolar residues:                    Met Leu, Ile, Val, Cys                        V. Large, aromatic residues:                    Phe, Tyr, Trp
As used herein, the term "purified" and like terms relate to the isolation of a molecule or compound in a form that is substantially free of contaminants normally associated with the molecule or compound in a native or natural environment.
As used herein, the term "C19 polypeptide" and like terms refers to polypeptides comprising SEQ ID NO: 2 and biologically active fragments thereof (such as the mature form represented by SEQ ID NO: 8, for example) and the term "C23 polypeptide" and like terms refers to polypeptides comprising SEQ ID NO: 4 and biologically active fragments thereof (such as the mature form represented by SEQ ID NO: 9, for example).
As used herein, the term "biologically active fragment" or "bioactive fragment" of a C19 or C23 polypeptide encompasses natural or synthetic portions of SEQ ID NO: 2 or SEQ ID NO: 4, respectively, that are capable of specific binding to at least one of the natural ligands of the respective native polypeptide.
"Operably linked" refers to a juxtaposition wherein the components are configured so as to perform their usual function. Thus, control sequences or promoters operably linked to a coding sequence are capable of effecting the expression of the coding sequence.
As used herein, the term "pharmaceutically acceptable carrier" encompasses any of the standard pharmaceutical carriers, such as a phosphate buffered saline solution, water and emulsions such as an oil/water or water/oil emulsion, and various types of wetting agents.

Human sperm specific lysozyme-like proteins

University of Virginia Patent Foundation


The present invention relates to compounds of formula (I)

The present invention relates to novel compounds which are protein kinase C inhibitors. methods for their preparation, intermediates therefor and pharmaceutical compositions comprising them.
Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine-specific protein kinases which play an important role in cellular growth control, regulation and differentiation.
Since the activation of PKC has been implicated in several human disease processes, including various forms of cancer, different forms of inflammatory and/or immunological disorders as well as some neurological disorders, inhibition of PKC could be of therapeutic value in treating these conditions.
Several classes of compounds have been identified as PKC inhibitors, e.g. isoquinoline sulphonamides, sphingosine and related sphingolipids, indolocarbazoles and bisindolyl-maleimides.
EP 0 328 026 describes the use of certain bisindolylmaleimides, a class of compounds related to the indolocarbazoles, in medicaments for the treatment of various conditions.
Baskakow et al.; SU 389096; 1973 describes 1,5 substituted diphenyl imidazolones although these are not suggested to be of any therapeutic potential.
Although PKC inhibitors are described in the prior art, there is a need for specific anti-inflammatory and immuno suppressive compounds, which are suitable for oral administration, and for inhalation. Furthermore. there is a need for such compounds, which are more soluble and less colored than the presently known PKC inhibitors.
The present invention provides kinase inhibitors that are particularly PKC inhibitors. methods for their preparation and intermediates used for their preparation.
The kinase inhibitors of the present invention are surprisingly more soluble and less colored than the kinase inhibitors, especially the PKC inhibitors, known in the prior art.
The present invention also provides the use of the compounds of the present invention for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
Also provided by the present invention are pharmaceutical compositions comprising a compound according to the present invention, as active ingredient, together with a pharmaceutically acceptable adjuvant, diluent or carrier.
The present invention provides compounds of formula (I):
wherein:
Ar1 or Ar2 is an optionally substituted indole, and the other group is an optionally substituted aromatic or heteroaromatic group, suitably an optionally substituted bicyclic heteroaromatic group, preferably an optionally substituted indole.
X is O or S,
R is H, OH, NH2, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, and
R1 is H, C1-6alkyl, fluoro substituted C1-6alkyl, phenyl, benzyl, carboC1-6alkoxy, carbobensyloxy, carbohydroxy, carbamoyl, or methyl(N-C1-6alkylcarbamoyl)
and salts and solvates thereof and solvates of such salts.
Preferred embodiments of formula (I) are compounds of formula (II), and (III)
wherein:
Ar is an optionally substituted aromatic or heteroaromatic group,
X is O or S,
R is H, OH, NH2, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl,
R1 is H, C1-6alkyl, fluoro substituted C1-6alkyl, phenyl, benzyl, carboC1-6alkoxy, carbobensyloxy, carbohydroxy, carbamoyl, or methyl(N-C1-6alkylcarbamoyl),
R2 is H, C1-6alkyl, benzyl, C1-3alkoxy substituted benzyl, hydroxy(C1-6)alkyl, hydroxy(C3-7)cycloalkyl, nitrile(C1-6)alkyl, azido(C1-6)alkyl, amino(C1-6)alkyl, amino(C3-7)cycloalkyl, aminomethyl(C3-7)cycloalkyl, amino(C5-7)cycloalkenyl, (mono- or di-C1-6alkyl) amino(C1-6)alkyl, benzylamino(C1-6)alkyl, (mono- or di-C1-6alkyl) amino(C3-7)cycloalkyl, (mono- or di-C1-6alkyl) aminomethyl(C3-7)cycloalkyl, (amino(C1-3)alkylphenyl)(C1-3)alkyl, amino(C1-3)alkylphenyl, guanidino(C1-6)alkyl, amidino(C1-6)alkyl, amidinothio(C1-6)alkyl, [N,N-di-(C1-6)alkyl]amidino(C1-6)alkyl, amidino(C1-3)alkylphenyl, [N,N-mono- or di-(C1-6)alkyl]amidino(C1-3)alkylphenyl, (N-benzyl)amidino(C1-3)alkylphenyl, (4-morpholinyl)imino(C1-3)alkylphenyl, benzimic acid methyl ester(C1-3)alkyl, hydroxy(C1-3)alkylamino (C1-6)alkyl, carboxy(C1-3)alkylamino (C1-6)alkyl, carboxymethyl(C1-3)alkylamino (C1-6)alkyl, amino(C1-3)alkyloxy (C2-6)alkyl, formamide(C1-6)alkyl, (N,N-dimethyl)imidoformamide(C1-6)alkyl, or a group of the formula
xe2x80x94(CH2)nxe2x80x94Het
in which
n is an integer of 0-6;
Z is carbonyl or methylene;
Het is an optionally substituted 5- or 6-membered heterocyclic group,
R3 and R5 are each independently H, halogen, C1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, hydroxy, amino, nitro, nitrile, and
R4 is H, C1-3alkyl or together with R2, forms an annulated ring which may be substituted by hydroxyC1-3alkyl, amidinothioC1-3alkyl, or aminoC1-3alkyl,
or a salt or solvate thereof or a solvate of a salt thereof.
Preferred embodiments of compounds of formula (II), and (III) are
wherein:
Ar is an optionally substituted aromatic or heteroaromatic group,
X is O or S,
R is H, OH, NH2, C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl,
R1 is H, C1-6alkyl, fluoro substituted C1-6alkyl, phenyl, benzyl, carboC1-6alkoxy, carbobensyloxy, carbohydroxy, carbamoyl, or methyl(N-C1-6alkylcarbamoyl),
R2 is H, C1-6alkyl, haloC1-6alkyl, bensyl, C1-3alkoxy substituted bensyl, nitrileC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, (pyridinylmethyl)aminoC1-6alkyl, (mono- or di-C1-6alkyl)aminoC1-6alkyl, (mono- or di-C1-3haloalkyl)aminoC1-6alkyl, aminoC3-7cycloalkyl, (mono- or di-C1-6alkyl)aminoC3-7cycloalkyl, (aminoC3-7cycloalkyl)C1-3alkyl, (hydroxyC1-6alkyl)aminoC1-6alkyl, (aminoC1-6alkyl)aminoC1-6alkyl, (C1-6alkynyl)aminoC1-6alkyl, (bensyl)aminoC1-6alkyl, (mono- or di-C1-3alkoxy substituted bensyl)aminoC1-6alkyl, (aminoC1-3alkylphenyl)C1-3alkyl, (aminoC1-3alkylthiophenyl)C1-3alkyl, (aminoC1-3alkylpyridinyl)C1-3alkyl, guanidino C1-6alkyl, (guanidinoC1-3alkylphenyl)C1-3alkyl, amidinoC1-6alkyl or amidinothioC1-6alkyl or a group of the formula
xe2x80x94Zxe2x80x94(CH2)nxe2x80x94Het
in which
Z is carbonyl or methylene
n is an integer of 0-5, and
Het is an optionally substituted 5- or 6-membered heterocyclic group,
R3 and R5 are each independently H, halogen, C1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, hydroxy, amino, nitro, nitrile, and
R4 is H, C1-3alkyl or together with R2, forms an annulated ring which may be substituted by hydroxyC1-3alkyl, amidinothioC1-3alkyl, or aminoC1-3alkyl,
and salts and solvates thereof and solvates of such salts.
For compounds of formula (II) and (III), the following independent preferences apply:
Ar is an optionally substituted bicyclic aromatic or an optionally substituted bicyclic heteroaromatic group,
R is H
X is O
R1 is H or methyl; or if a fluoro substituted C1-6alkyl, is preferably CF3,
when R4 is H, R2 is H, methyl, hydroxyC1-6alkyl, aminoC1-6alkyl, (mono- or di-C1-6alkyl)aminoC1-6alkyl, aminoC3-7cycloalkyl, (mono- or di-C1-6alkyl)aminoC3-7cycloalkyl, guanidino C1-6alkyl, amidinoC1-6alkyl or amidinothioC1-6alkyl,
when R2 and R4 together form an annulated ring, they together comprise 4 or 5 carbons,
R3 and R5 are independently H or methoxy.
In more preferred embodiments of formula (II) and (III), Ar comprises a single heteroatom selected from N, O and S.
In yet more preferred embodiments of formula (II) and (III), Ar is selected from benzothiophene, naphthyl, phenoxyphenyl, or an optionally substituted indolyl which if substituted is preferably substituted with aminopropyl, dimethylaminopropyl, aminobutyl, aminocyclopentyl, aminomethylbensyl, or amidinothiopropyl.
Preferred compounds according to the present invention include:
5-[1-(3-Aminopropyl)-3-indolyl]-1-(3-indolyl)-1,3-dihydroimidazol-2-one,
5-[1-(3-Aminopropyl)-3-indolyl]-1-(3-benzo[b]thoiphenyl-1,3-dihydroimidazol-2-one,
5-[1-(3-Aminopropyl)-3-indolyl]-1-(1-naphthyl)-1,3-dihydroimidazol-2-one,
5-[1-{3-(Aminomethyl)benzyl}-3-indolyl]-1-(3-indolyl)-1,3-dihydroimidazol-2-one,
5-[-1-(3-Aminopropyl)-3-indolyl]-1-(3-indolyl)-4-methyl-1,3-dihydroimidazol-2-one,
5-[1-(3-Amidinothiopropyl)-3-indolyl]-1-(3-indolyl)-1,3-dihydroimidazol-2-one,
5-{1-[3-(N,N-Dimethylamino)propyl]-3-indolyl}-1-(3-indolyl)-1,3-dihydroimidazol-2-one; and
5-[1-(3-Aminopropyl)-3-indolyl]-1-(3-indolyl)-4-phenyl-1,3-dihydroimidazol-2-one;
and salts and solvates thereof and solvates of such salts.
Salts of the compounds of formula (I) according to the invention are preferably pharmaceutically acceptable salts. Other salts may however be useful in the preparation of the compounds or in the preparation of pharmaceutically acceptable salts.
Pharmaceutically acceptable salts of compounds of the present invention are preferably those well known in the art as being suitable and are preferably acid addition salts and more preferably acetate salts or trifluoroacetate salts.
Solvates of the compounds or salts of the present invention are conveniently hydrates, such as monohydrates or dihydrates.
Compounds of the present invention include all pure stereoisomers and all mixtures thereof.
Preparation of the Compounds of the Invention
Compounds of formula (I) may be synthesised in the following ways:
(A) Compounds of formula (I) may be synthesised by converting a compound of formula (I) to a salt, especially a pharmaceutically acceptable salt, thereof, or vice versa; or converting a salt, especially a pharmaceutically acceptable salt, of a compound of formula (I) into a different salt, especially a pharmaceutically acceptable salt.
(B) Compounds of formula (I) may be synthesised by intramolecular condensation of a compound of formula (IV):
in which X, R, R1, Ar1 and Ar2 are as defined for formula (I).
The condensation may be performed under acidic conditions, preferably using acetic acid or scandium(III)trifluoromethanesufonate, at a temperature in the range of from about 90xc2x0 C. to about 130xc2x0 C., suitably from 100xc2x0 C. to 120xc2x0 C. and preferably at about 100xc2x0 C., for a period of time in the range of from about 5 min to about 6 h, suitably from 15 min to 3 h, preferably for about 1 h.
Compounds of formula (II) and (III) in which X is O may be synthesised by intramolecular condensation of a compound of formula (V) or (VI) respectively:
in which Ar, R and R1-R5 are as defined for formula (II) and (III).
Compounds of formula (I), (II) or (III) carrying one or more functional groups which might be sensitive to or interfere with the reaction conditions in process (B), can be prepared using a corresponding compound of formula (I), (II) or (III) respectively, but in which the functional groups are suitably protected, followed by subsequent deprotection.
Functional groups that might be sensitive for or interfere with the reaction conditions in process (B), as well as suitable protecting groups and deprotecting methods, are evident to those skilled in the art.
Compounds of formula (II) or (III), in which at least one of R2 or Ar carries an amino, or hydroxy group; and pharmaceutically acceptable salts thereof, may be prepared by deprotecting a compound of formula (II) or (III), respectively, but in which at least one of R2 or Ar carries a protected amino or hydroxy group.
In the processes described above, the protecting groups and conditions for deprotection are well known to those skilled in the art. Suitable protecting groups for amino groups are e.g. phthaloyl groups and the deprotecting agent may be methylamine in e.g. water. The deprotecting step may be carried out in a suitable solvent, e.g. tetrahydrofuran at about 10-30xc2x0 C., e.g. for about 5 hours. The hydroxy groups may be protected as their corresponding acetoxy groups and the deprotecting agent may be methylamine in e.g. water. The deprotecting step may be carried out in a suitable solvent, e.g. tetrahydrofuran at about 10-30xc2x0 C., e.g. for about 16 hours.
The use of protecting groups is fully described in xe2x80x9cProtective Groups in Organic Chemistryxe2x80x9d, edited by J. W. F. McOmie, Plenum Press (1973) and xe2x80x9cProtective Groups in Organic Synthesisxe2x80x9d, 2nd edition, T. W. Greene and P. G. M. Wutz, Wiley-Interscience (1991).
The starting materials for the above processes (A) and (B) may be made by the methods described herein and particularly by those methods set out in the Examples or by methods analogous thereto. Other conventional methods for making the starting materials will be evident to those skilled in the art.
Compounds of formula (V) and (VI) in which R2 is not H may be synthesised by alkylation with an optionally substituted alkylating agent, of compounds of formula (VII) and (VIII), respectively. The alkylating agent may be an alkyl halide, or an alkyl halide carrying a dialkyl amino group, or an alkylating agent carrying a protected amino or hydroxy group.
in which Ar, R, R1-R5 are as defined for formula (II) and (III).
Compounds of formula (V) and (VI), in which Ar, R, R1-R5 are as defined for formula (II) and (III), provided that R2 is not H, may also be prepared by reaction of the appropriate isocyanate with a relevant alpha-ketoamine, wherein either the isocyanate or the alpha-ketoamine carries the R2 group, using standard techniques.
Compounds of formula (VII) and (VIII) may be prepared by reaction of the appropriate isocyanate with a relevant alpha-ketoamine using standard techniques.
Compounds of formula (II) in which X is O, R2 is alkyl and Ar is an indole, substituted on the indole nitrogen with an alkyl carrying an amino or hydroxy group, may be prepared by deprotecting a compound of formula (IX)
in which R6 is an alkyl carrying a protected amino or hydroxy group, and R1, R3, R4 and R5 are as defined for formula (II).
The protecting groups and conditions for the deprotection are the same as mentioned earlier.
Compounds of formula (IX) may be prepared by selective removal of a Troc group from a compound of formula (X)
in which R2 is alkyl and R1, R3, R4 and R5 are as defined for formula (II),
followed by subsequent alkylation under standard conditions, with an alkyl carrying a protected amino or hydroxy croup. Selective deprotection of the Troc group may be carried out with cadmium in acetic acid and DMF.
Compounds of formula (X) may be prepared by introducing a Boc group, under standard conditions, to a compound of formula (II) but in which R is H and the Ar group is a Troc protected indole. Such a compound is prepared from a compound of formula (V), but in which R is H and the Ar group is a Troc protected indole.
Persons skilled in the art will appreciate that, in order to obtain compounds of the invention in an alternative, and, on some occasions, more convenient, manner, the individual process steps mentioned herein may be performed in a different order, and/or the individual reactions may be performed at a different stage in the overall route. This will e.g. on factors such as the nature of other functional groups present in a particular substrate, the availability of key intermediates and the protecting group strategy (if any) to be adopted.
Prodrugs and Intermediates
It will also be appreciated by those skilled in the art that, although certain protected derivatives of compounds of formula (I), (II) and (III) which may be made prior to a final deprotection stage, may not possess pharmacological activity as such, they may be administered parenterally or orally and thereafter metabolized in the body to form compounds of the invention which are pharmacologically active. Such derivatives may therefore be described as xe2x80x9cprodrugsxe2x80x9d. Moreover, certain compounds of formula (I), (II) and (III) may act as prodrugs of other compounds of formula (I), (II) and (III).
All prodrugs of compounds of formula (I) are included within the scope of the present invention.
Novel intermediates as described hereinbefore and their use in the manufacture of other compounds of the present invention also form part of the invention. Thus, according to a further aspect of the invention there is provided compounds of formulae (V) to (X) as defined hereinbefore, or protected derivatives of any of these compounds.
Medical and Pharmaceutical Use
Also provided according to the present invention are compounds of the present invention for use in medical therapy; the use of compounds of the present invention in the manufacture of medicaments for use in medical therapy, and more particularly in the treatment of the conditions described herein; and methods of medical therapy comprising the administration of a therapeutically effective amount of a compound of the present invention to an individual requiring such therapy.
The term xe2x80x98medical therapyxe2x80x99 as used herein is intended to include prophylactic, diagnostic and therapeutic regimens carried out in vivo or ex vivo on humans or other mammals.
The compounds of formula (I), (II) and (III) and salts, especially pharmaceutically acceptable salts, and solvates thereof, and solvates of such salts are useful because they demonstrate pharmacological activity. In particular they demonstrate activity as kinase inhibitors, especially PKC inhibitors, e.g. as is shown by their activity in the in vitro assays described in Granet, R. A. et al, Analyt. Biochem. 1987; 163, 458-463; Olsson, H. et al. Cell Signal 1989, 1, 405-410: and Chakravarthy, B. R. et al, Analyt. Biochem. 1991, 196, 144-150.
The compounds of the invention are indicated for use in the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders; preferably for oral or topical treatment of inflammatory and/or immunological disorders, such as the oral or topical treatment of airway diseases involving inflammatory conditions, e.g. asthma, bronchitis; or atopic diseases, e.g. rhinitis or atopic dermatitis; inflammatory bowel diseases. e.g. Crohn""s disease or colitis; autoimmune diseases e.g. multiple sclerosis, diabetes, atherosclerosis, psoriasis, systemic lupus erythematosus or rheumatoid arthritis; malignant diseases, e.g. skin or lung cancer; HIV infections or AIDS; or for inhibiting rejection of organs/transplants. The compounds of the invention are also indicated for use in treatment of heart failure, and in treatment of diabetic patients with macular edema or diabetic retinopathy.
Pharmaceutical Preparations
The dose of the compound to be administered will depend on the relevant indication, the age, weight and sex of the patient and may be determined by a physician. The dosage will preferably be in the range of from 0.01 mg/kg to 10 mg/kg.
The compounds may be administered topically, e.g. to the lung and/or the airways, in the form of solutions, suspensions, HFA aerosols or dry powder formulations, e.g. formulations in the inhaler device known as the Turbuhaler(copyright); or systemically, e.g. by oral administration in the form of tablets, pills, capsules, syrups, powders or granules, or by parenteral administration, e.g. in the form of sterile parenteral solutions or suspensions, or by rectal administration, e.g. in the form of suppositories.
The compounds of the invention may be administered on their own or as a pharmaceutical composition comprising the compound of the invention in combination with a pharmaceutically acceptable diluent, adjuvant and/or carrier. Particularly preferred are compositions not containing material capable of causing an adverse, e.g. an allergic, reaction.
Dry powder formulations and pressurized HFA aerosols of the compounds of the invention may be administered by oral or nasal inhalation. For inhalation the compound is desirably finely divided. The finely divided compound preferably has a mass median diameter of less than 10 xcexcm, and may be suspended in a propellant mixture with the assistance of a dispersant, such as a C8-C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, a phospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
The compounds of the invention may also be administered by means of a dry powder inhaler. The inhaler may be a single or a multi dose inhaler, and may be a breath actuated dry powder inhaler.
One possibility is to mix the finely divided compound with a carrier substance, e.g. a mono-, di- or polysaccharide, a sugar alcohol, or another polyol. Suitable carriers are sugars, e.g. lactose, glucose, raffinose, melezitose, lactitol, maltitol, trehalose, sucrose. mannitol; and starch. Alternatively the finely divided compound may be coated by another substance. The powder mixture may also be dispensed into hard gelatin capsules, each containing the desired dose of the active compound.
Another possibility is to process the finely divided powder into spheres which break up during the inhalation procedure. This spheronized powder may be filled into the drug reservoir of a multidose inhaler, e.g. that known as the Turbuhaler(copyright) in which a dosing unit meters the desired dose which is then inhaled by the patient. With this system the active compound, with or without a carrier substance, is delivered to the patient.
For oral administration the active compound may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol; a starch, e.g. potato starch, corn starch or amylopectin; a cellulose derivative; a binder, e.g. gelatin or polyvinylpyrrolidone, and/or a lubricant, e.g. magnesium stearate, calcium stearate, polyethylene glycol, a wax, paraffin, and the like, and then compressed into tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatin, talcum, titanium dioxide, and the like. Alternatively, the tablet may be coated with a suitable polymer dissolved in a readily volatile organic solvent.
For the preparation of soft gelatin capsules, the compound may be admixed with e.g. a vegetable oil or polyethylene glycol. Hard gelatin capsules may contain granules of the compound using either the above mentioned excipients for tablets. Also liquid or semisolid formulations of the drug may be filled into hard gelatin capsules.
Liquid preparations for oral application may be in the form of syrups or suspensions, for example solutions containing the compound, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol. Optionally such liquid preparations may contain coloring agents, flavoring agents, saccharine and/or carboxymethylcellulose as a thickening agent or other excipients known to those skilled in art.
The compounds of the invention may also be administered in conjunction with other compounds used for the treatment of the above conditions.

Abstract: wherein:

Abstract: Ar1 or Ar2 is an optionally substituted indole, and the other group is an optionally substituted aromatic or heteroaromatic group, suitably an optionally substituted bicyclic heteroaromatic group, preferably an optionally substituted indole,

Abstract: X is O or S,

Abstract: and salts and solvates thereof and solvates of such salts,

Abstract: and the use of such compounds in medical therapies.


A system (10) and method (50) of equalizing an audio signal from an existing radio or head unit (30) using an interface unit (10) between the radio or head unit and a replacement load (34) can include the steps analyzing (64) an existing equalization to provide a measure of an existing frequency response, generating (66) a substantially inverted frequency response to the existing frequency response, and applying (74) the inverted frequency response to the replacement load to provide a desired response. Such as system can include an interface unit (12) having an automatic input level control unit (14), an analog to digital converter or digitizer (16), a DSP (18) providing an output to a DAC (20), a level booster unit (22) and a processor such as a microcontroller unit (24).

Stereo systems for existing vehicles commonly have a fixed equalization setting that is specifically designed for a particular vehicle, stereo system and load in terms of amplifiers and speakers. In most instances, existing vehicles tend to have integrated dashboards that fail to provide easy provisioning or removal of entertainment devices such as the factory installed stereo equipment. Such scenario creates problems for anyone wishing to install a replacement system or alternative amplifiers or loudspeakers since the factory-installed radio is likely to contain a fixed equalizer which corrects for deficiencies in the original speaker system. Such fixed equalizer will more than likely be inappropriate for the replacement system. No existing system enables the easy modification of an audio output of a built-in radio in such a way as to remove the factory equalization. To appropriately equalize a replacement system in most existing systems today, a skilled technician using test equipment is typically needed to set up a manually-controlled graphic equalizer.
For example, EQS by AudioControl is a standard analog multi-channel manual equalizer. The EQS requires manual adjustment of equalization which still requires an analyzer and technical skills to provide optimal equalization. Again, no existing system enables an easy or automatic modification of an audio output of a built-in radio in such a way as to remove the factory equalization and provide a suitable equalization for a replacement system.

This patent is subject to a terminal disclaimer.

Method and system for equalization of a replacement load


A laser device has a laser medium responsive to an excitation light for generating a laser beam consisting of a plurality of longitudinal modes when excited by an energy of the excitation light, two mirrors constituting a laser resonator for forming an optical path of the laser beam passing through said laser medium, and a nonlinear optical element, arranged in the laser resonator, for generating a second harmonic caused by one of the plurality of longitudinal modes constituting the laser beam generated in said laser medium and a sum-frequency caused by two of the plurality of longitudinal modes constituting the laser beam generated in said laser medium. Wavelength and phase of the longitudinal modes constituting the laser beam generated in said laser medium are controlled to a condition that said nonlinear optical element generates the second harmonic and the sum-frequency, including a second harmonic and a sum-frequency, or sum-frequency-to-sum-frequency, which have the same wavelength as one another and phases serving to weaken one another.

1. Field of the Invention
The present invention relates to an internal resonator type of laser device which generates a second harmonic.
1. Description of the Related Art
In a laser device in which a nonlinear optical crystal is inserted into a laser resonator to generate a second harmonic with a high efficiency, wherein the laser device has a plurality of longitudinal modes, there will be generated a sum-frequency between the longitudinal modes as well as a second harmonic on each of the plurality of longitudinal modes of laser beams. It happens that a generation of the sum-frequency causes strong mode competition noises, called a "green problem", to be generated. It has been desired from various application sides that the "green problem" is solved, and hitherto, there has been proposed several solutions to this problem.
FIG. 9 is an illustration of low-noise operation of a laser according to the earlier technology. Such a laser is equivalent to the internal resonator type of solid state laser device which generates a second harmonic of low noises, as disclosed in the document: Michio Oka and Shigeo Kubota, Optics Letters, Vol. 13, No. 10, P.805 (October 1988).
FIG. 9 shows the configuration of the laser cavity comprising: an Nd:YAG crystal 31 serving as the laser medium; a KTP crystal 32, that is, a Type II phase-matched nonlinear crystal, which generates the second harmonic of the laser beam having the wavelength 1064 nm emitted from the Nd:YAG crystal 31; a quarter-wave plate (QWP) 33 inserted at the laser beam having the wavelength 1064 nm emitted from the Nd:YAG crystal 31, the fast axis of the QWP 33 being arranged with angle 45.degree. with respect to the extraordinary axis of the KTP crystal 32; and an output mirror 34 for outputting the second harmonic generated in the KTP crystal 32, the output mirror 34 constituting a laser resonator.
According to the laser mentioned above, the fast axis of the QWP 33 is arranged with angle 45.degree. with respect to the extraordinary axis of the KTP crystal 32. Thus, the eigenpolarization modes of laser beams in the resonator are controlled to cancel a nonlinear polarization which causes a sum-frequency to be generated in the KTP crystal 32. As a result, there is generated no sum-frequency and thus no noises due to the green problem.
FIG. 10 is an illustration of low-noise operation of a laser according to the earlier technology, which is different in system from that shown in FIG. 9. Such a laser is equivalent to the solid state laser device as disclosed in the document: Hideo Nagi, et al, IEEE, Journal of Quantum Electronics, Vol. 28, No. 4, P. 1164 (April 1992).
FIG. 10 shows a laser system comprising: an Nd:YAG crystal 41; a laser diode 36 for emitting excitation light 37; a lens 38 for focusing the excitation light 37 to be introduced into the Nd:YAG crystal 41; a KTP crystal 42, that is, a Type II phase-matched nonlinear crystal, which generates the second harmonic of the laser beam emitted from the Nd:YAG crystal 41; and a Brewster plate 43 arranged in such a manner that the angle between the field direction of polarization, in which the highest transmission is obtained at the plate and that of the extraordinary ray in the KTP crystal 42 is 45.degree..
According to this laser system, the well known birefringent filter is formed in view of the fact that the KTP crystal 42 has a birefringence property and a transmission of the Brewster plate 43 depends on the direction of polarization, so that the different resonance loss is given on each of the longitudinal modes of the laser beams. Consequently, only a certain one longitudinal mode, which is involved in the lowest loss, is selectively effective for an oscillation. Hence, a sum-frequency is not generated. Thus, it is possible to suppress the noise generation. As a scheme in which a laser is oscillated in a single longitudinal mode, there is also well known one using a ring type resonator.
FIG. 11 is an illustration of low-noise operation of a laser according to the earlier technology, which is different in system from that shown in FIGS. 9 and 10. Such a laser is equivalent to the laser device as disclosed in the document: W. L. Nighan et al, Technical Digest of Advanced Solid State Lasers, Post Deadline PD4 (1996).
FIG. 11 shows a laser system comprising: an Nd:YVO.sub.4 crystal 45 which is a laser medium having a wide oscillation wavelength width; a laser resonator constituted of mirrors 51-57; and two excitation optical systems each comprising an optical fiber end 46, a collimating lens 48 and a condenser lens 49. Excitation light emitted from each of the excitation optical systems is fed to the Nd:YVO.sub.4 crystal 45 passing through the mirror 52 or 53.
The laser resonator includes: an LBO crystal 40 for generating a second harmonic of the laser beam generated in the Nd:YVO.sub.4 crystal 45, the LBO crystal 40 being a non-linear optical crystal; and a lens 41 for controlling a laser mode of the LBO crystal 40. According to this laser system, the Nd:YVO.sub.4 crystal 45, which is a laser medium having a wide oscillation wavelength width, is used and the laser resonator is extent up to about 1 m by means of doubling the light path using the mirrors 54, 55 and 56, so that a number of longitudinal modes of the laser oscillation light is increased to about 100 axial modes. Thus, a fluctuation of the longitudinal mode output, which is caused by the green problem of the second harmonic generated in the LBO crystal 40, is decreased by mutual cancellation of fluctuations of outputs of a large number of longitudinal modes. Consequently, it is possible to apparently reduce the noises on the overall output of the laser system.
However, according to the scheme shown in FIG. 9 in which quarter-wave plate is inserted, it is needed that two orthogonal polarization modes are oscillated in the associated single longitudinal axial modes, respectively. And a tolerance as to a reflecting power of the coating of the respective crystals and an alignment angle of the mirrors is narrow. Further, in order to maintain the noise-less state for a long time, there is a need to perform a temperature control for the respective parts and the resonator in its entirety with great accuracy.
Also in the scheme shown in FIG. 10 in which the Brewster plate is disposed, in order to stably maintain a single longitudinal mode, there is a need to control a temperature of the KTP crystal and a resonator length with great accuracy. Further, in the event that it is desired to obtain a high output power over 1 w, a high gain of laser medium is required. This makes it easy to bring about a plurality of longitudinal modes on the laser beam. The plurality of longitudinal modes causes noises due to the green problem to be generated. Thus, it is feared that an operational stability of the laser is damaged.
According to the laser system shown in FIG. 11, the resonator length is elongated and a number of longitudinal modes is established above 100 axial modes. This causes an oscillating wavelength band to expand. Thus, it is feared that the wavelength conversion efficiency is lowered since there is a limit in wavelength tolerance of the phase matching. Further, a distribution of the longitudinal modes is easily influenced by reflection of the optical elements or the like inserted into the resonator, and there is the possibility that the longitudinal modes each associated with mutually different frequencies are oscillated. In this case, it is feared that noises due to the green problem are generated. Furthermore, it is difficult to provide a miniaturization of the device because there is a need to provide a resonator length not less than 1 m. And in addition, the resonator is complicated in structure. Thus, it is feared that the mechanical stability is lowered. It is noted that it is very important for assembling parts into a laser device that an adjustment is easy and a degree of freedom in design is large.

Biophotonics Information Laboratories Ltd.


An image forming apparatus at least includes a photoreceptor, a light emitter, a detector and a controller. The light emitter irradiates the photoreceptor with a laser beam so as to form an electrostatic latent image thereon. The detector detects an incident amount of the laser beam falling on a light receiving portion of the detector on a main scan line. The controller changes at least one of a detection sensitivity of the detector for a laser beam and an emission amount of the laser beam emitted from the light emitter when the incident amount of the laser beam detected by the detector is not greater than a predetermined value.

1. Field of the Invention
Exemplary aspects of the present invention generally relate to a method, an apparatus, and a computer-readable recording medium for image forming, and more particularly to a method, an apparatus, and a computer-readable recording medium for accurately detecting an optical beam emitted to a photoreceptor.
2. Discussion of the Background
Conventionally, in a method for correcting the magnification of an image formed on a photoreceptor when forming an image, laser beams emitted on the photoreceptor are detected by a laser beam detector provided at two places: at a scan start side and at a scan finish side on a main scan line.
Subsequently, a time lag from the time one laser beam detector detects a laser beam to the time the other laser beam detector detects the laser beam is calculated. Based on the calculated time lag, the frequency of a pixel clock is changed so as to adjust the magnification of the image formed on the photoreceptor.
Furthermore, a method of minimizing a number of measurements of the time lag detected by the two laser beam detectors has been proposed.
However, according to related arts, when the laser beam detectors fail to detect the laser beam at the two places, that is, at the scan start side and the scan finish side on a main scan line, the magnification of the image may not be corrected, thereby causing an image deviation. Consequently, a high quality image may not be obtained.

Image forming method, apparatus and computer-readable recording medium having image forming program


A controlled nitric acid process employing oxygen and nitric acid as co-oxidants is used to oxidize organic compounds subject to nitric acid oxidation, to their corresponding carboxylic acids. Oxidation of some carbohydrates by this process can produce one or more of their corresponding acid forms. The process is carried out at moderate temperatures, typically in the range of 20° C. to 45° C. in a closed reactor, with oxygen gas being introduced into the reaction chamber as needed in order to sustain the reaction. Computer controlled reactors allow for careful and reproducible control of reaction parameters. Nitric acid can be recovered by a distillation/evaporation process, or by diffusion dialysis, the aqueous solution made basic with inorganic hydroxide, and the residual inorganic nitrate removed using a filtration (nanofiltration) device. The method eliminates issues of thermal control of the oxidation, release of nitrogen into the atmosphere, and post-reaction difficulties in the removal of nitric acid and inorganic nitrates.

Carbohydrate acids, and in particular carbohydrate diacids (aldaric acids) offer significant economic potential as carbon based chemical building blocks for the chemical industry, as safe additives or components of products use in pharmaceutical preparations and food products, and as structural components of biodegradable polymers, if they can be effectively produced on an industrial scale. Glucaric acid, for example, is produced through the oxidation of glucose and in salt form is currently in use as a nutraceutical for preventing cancer. The price of this material however is high, approximately $100/lb. Industrial scale production of aldaric acids would also provide sufficient materials for the production of other useful compounds, that include environmentally degradable polyamides with varying properties and applications, which are otherwise not commercially available.
Carbohydrate diacids are produced a number of ways from reducing sugars using a variety of oxidizing agents, nitric acid being among the earliest reported.1 An example of a nitric acid oxidation of a carbohydrate is that of D-glucose to give D-glucaric acid, typically isolated as its mono potassium salt.2,3,4 Alternatively, D-glucaric acid can be isolated from nitric acid oxidation of D-glucose as a disodium salt5 or as the 1,4:6,3-dilactone.6 Routes have been described showing synthesis of diacids through catalytic oxidation with oxygen over a noble metal catalyst.7 An additional route of synthesis exists by use of oxoammonium salts in combination with hypophalites as the terminal oxidants. For example, Merbough and coworkers describe oxidation of D-glucose, D-mannose and D-galactose to their corresponding diacids using 4-acetylamino-2,2,4,6-tetamethyl-1-piperidinyloxy (4-AcNH-TEMPO) with hypohalites as the oxidizing medium.8,9 A microbial oxidation of myo-inositol to glucuronic acid which is then oxidized enzymatically or by catalytic oxidation to glucaric acid has also been recently described.10
When used to oxidize carbohydrates to carbohydrate acids, nitric acid offers the advantages of conveniently serving as the solvent medium for the oxidation and as an oxidizing agent. However, there are also specific disadvantages. Such oxidation reactions can be very exothermic and may run away if care is not taken to control the exotherm in the early stages of the reaction. These reactions also generate significant amounts of NOX gases which are environmental hazards if they are vented into the atmosphere rather than being captured and rendered harmless and/or recycled in a process that regenerates nitric acid. Thus, it would be desirable to utilize a more controlled nitric acid oxidation process that does not run the burdensome, time consuming, and inefficient risk of over-reaction, thereby rendering the products essentially useless, while at the same time employing a process that does not vent NOX gases into the atmosphere, and recycles these gases into nitric acid.
In the nitric acid oxidation of many compounds, product isolation can be encumbered by the residual nitric acid that remains in the usually syrupy product. Thus, in order to properly isolate the desired oxidation product, it is generally necessary to remove the residual nitric acid. This is particularly the case in the nitric acid oxidation of alcohol compounds, such as carbohydrates. In order to isolate the desired oxidation product of a carbohydrate, nitric acid must be at least partially removed. A number of methods have been described for removing residual nitric acid.
The first technique involves neutralizing aqueous nitric acid and organic/carbohydrate acids solution at the end of the oxidation step with hydroxide solution. In the case of D-glucose oxidation to obtain D-glucaric acid, potassium hydroxide is the base of choice and back titration with nitric acid yields the monopotassium salt of D-glucaric acid.3,4 This technique is not advantageous due to the cost and difficulty involved in the neutralization step.
A second technique for removing residual nitric acid from the oxidation product involves repeated concentrations, by a distillation process, using additions of fresh quantities of water between each step,2,6 after the bulk of the nitric acid has been removed by a distillation process of some type. Removal of residual nitric acid in this manner is very energy intensive requiring multiple additional distillations and does not efficiently remove all of the nitric acid.
Yet a third technique for removing residual nitric acid involves adding large volumes of 2-propanol in order to destroy any excess nitric acid.11 The 2-propanol addition is followed by water dilution and concentration of the remaining product. This process further requires the consumption of 2-propanol, resulting in acetone and other residuals that must also be isolated and separated from the oxidation product. Further, this technique also describes treatment with water and hydrogen chloride, both of which must be removed from the oxidation product. This third technique involves too many steps to be economically viable.
As mentioned earlier, another disadvantage to nitric acid carbohydrate oxidation processes previously reported is the big exotherm normally associated with these oxidations. In those previous processes, the entire amount of solid carbohydrate, along with the entire amount of inorganic nitrite, which serves as a reaction activating agent, is mixed with the nitric acid at the outset of the reaction, thereby creating the conditions for a large and difficult to control exotherm that develops as the reaction warms. Alternatively, the solid carbohydrate is added portion-wise to the nitric acid. This process still promotes an extensive exothermic reaction and is also encumbered by the difficulty in adding solid carbohydrate portion-wise to the liquid/gaseous reaction mixture. Furthermore, isolation of the carbohydrate acid as a salt can also be made difficult due to the presence of inorganic nitrate which can contaminate carbohydrate acid salts during their isolation process.
Thus, significant industrial scale production of aldaric acids requires an economically efficient and a less complicated method for synthesizing aldaric acids from their corresponding carbohydrates. At this time, for example, D-glucaric is not manufactured on a significant industrial scale because there is no economically viable means for such production. The potential importance of D-glucaric acid as a chemical staple from renewable resources was recently underscored in a report by T. Werpy and G. Petersen.12 From among hundreds of compounds considered as potential key chemical building blocks from renewable resources, glucaric acid was targeted as one of the top twelve molecules with significant potential as a chemical building block for a range of potential applications. Also included with glucaric acid were the structurally related pentaric acids, xylaric acid11 from biomass xylose and arabinaric acid from biomass arabinose. The need for suitable oxidation methods of the precursor monosaccharides was emphasized by Werpy and Peterson. If a suitable economic means for the oxidation of carbohydrates could be found, the production of D-glucaric acid and other aldaric acids could see increased production, lower prices, and greater public availability.
All patents, patent applications, provisional patent applications and publications referred to or cited herein, are incorporated by reference in their entirety to the extent they are not inconsistent with the teachings of the specification.


A notebook computer is disclosed in the present invention which comprises: a screen, which is a touch screen configured to be operable via touching; a host, which is integrated in the screen; and a keyboard, which is detachably connected with the screen so that the keyboard and the screen can be in a state of being connected to each other or in a state of being separated from each other in use. When the notebook computer is used, the keyboard and the screen can be in the state of being separated from each other in use, so that the screen and the keyboard of the notebook computer are used separately. And the keyboard and the screen can be separated when needed and the notebook computer can be use by touching operation on the screen.

In the current notebook computer, the keyboard is integrated with the host and connected to the main board by data wires, and the keyboard is pivotally connected to the screen so as to form the whole notebook computer. However, sometimes (such as in a small meeting or when showing products, items to clients) the users wish to use the screen and the keyboard separately to operate the keyboard and view the screen at different locations. In addition, the users also wish to separate the keyboard and the screen and perform touch-operation of the notebook computer on the screen individually.
Therefore, there is a need of providing a notebook computer to solve the above problems.


In one aspect of the present invention, an apparatus is provided for testing a processor running a software program. The apparatus includes a bus having control, data and address lines and a device assigned at least one address. The bus connects the device to the processor. The apparatus includes a multiple input signature register having a plurality of parallel input terminals connected to the data lines. The apparatus includes a control unit having first and second input terminals connected to the address and control lines respectively. The control unit is adapted to enabling the parallel input terminals of the multiple input signature register in response to detecting on the address and control lines at least one preselected triggering event executed by the software program to a preselected address of the device. The apparatus includes a signature comparator adapted to comparing a test signature number from the multiple input signature register to a reference signature number.

1. Field of the Invention
This invention relates generally to a method and apparatus for testing computers and processors during manufacture, and more particularly, to a method and apparatus for using software and signature analysis tools to perform tests.
2. Description of the Related Art
The testing process is an important part of the manufacture of micro-processors and computers. A modern processor may have over three million transistors and even more internal connections. In devices of such complexity, it is difficult to test all combinations of data and operations of the device and to ensure the absence of defects therein.
FIG. 1 shows a simple processor 18 that will be employed to illustrate a "faulty unit" signature test. The processor 18 is composed of several units, including: an arithmetic logic unit (ALU) 20, an address translation unit (ATU) 22, a floating point unit (FPU) 24, and an instruction decode unit (IDU) 26. The ALU 20, ATU 22, FPU 24, and IDU 26, have a number of control and/or data connections 28, 30, 32. A bus unit 34 connects the processor 18 to memory and input/output ports (I/O) (both not shown). The units 20, 22, 24, 26 of the processor 18 communicate with the memory and I/O by bus lines 36, 38.
FIG. 2 illustrates a prior art test apparatus 50 for performing a signature based "faulty unit" test on the processor 18 of FIG. 1. Each functional unit 20, 22, 24, 26 of the processor 18 is individually connected to parallel input terminals (not shown) of a multiple input signature register (MISR) 42, 44, 46, 48. Each MISR 42, 44, 46, 48 ordinarily has one parallel input terminal for each output terminal of the functional unit 20, 22, 24, 26 connected thereto (not shown). During the test, each MISR 42, 44, 46, 48 accumulates data from the associated functional unit 20, 22, 24, 26 in response to receiving a clock pulse on a line 59 connected to a clock 49. The MISR's 42, 44, 46, 48 add new data to data stored during prior clock pulses through an operation that is specified by a preselected polynomial and that reproducibly gives a single signature number.
The signature number ordinarily has one binary bit for each parallel input terminal, and each bit thereof is affected by data from all parallel input terminals of the MISR. Signature testing uses the signature number like a parity bit. The signature number is compared to a reference signature number, and an error is reported if any bit does not match. For signature numbers having many bits, the risk of "aliasing" or false matches is reduced, because the probability of aliasing is approximately 2.sup.-D where D is the number of bits of the signature number provided that the polynomial is constructed correctly.
Since each of the functional units 22, 24, 26, 28 of the processor 18 is connected directly to a separate MISR 42, 44, 46, 48, the test apparatus 50 concurrently and individually tests the various functional units 22, 24, 26, 28, of the processor 18. The MISR's 42, 44, 46, 48 have serial input terminals 51, 52, 53, 54 and output terminals 55, 56, 57, 58 for inputting initial signature patterns and outputting final signature numbers. The MISR's 42, 44, 46, 48 also have control lines 60 for controlling respective input terminals, output terminals, and data accumulation. The test apparatus 50 may be permanently embedded on the die holding the processor 18 itself.
FIG. 3 illustrates a prior art method 61 for performing a "faulty unit" test with the test apparatus 50 of FIG. 2. At a block 62, the sequential logic units (not shown), of each MISR 42, 44, 46, 48 are initialized to a predetermined state by serially inputting initial patterns through the input lines 51, 52, 53, 54. Though the exact form of the initial state is not essential, the reproducibility of the initial state is essential to the test method 61. At block 64, a second set of initial patterns, e.g., data and instructions, is placed in the sequential circuit elements such as registers, flip-flops, latches and buffers (not shown) of the functional units 20, 22, 24, 26 of the processor 18 itself. Typically, the initial patterns are placed in the functional units 20, 22, 24, 26 from input/output ports (not shown) and external devices (not shown) connected to the bus 36. Several clock cycles may be employed to set up the initial patterns in the processor 18 and MISR's 42, 44, 46, 48.
After setting up the initial state, signature data collection proceeds in loop-like fashion. At block 66, the processor 18 runs for a preselected number of clock cycles. Then, at block 68, the parallel input terminals of the MISR's 42, 44, 46, 48 are enabled by control signals on the lines 60, and data is taken from the functional units 22, 24, 26, 28 connected to each MISR 42, 44, 46, 48. At block 70, the input data is added to the data already stored in the individual MISR's 42, 44, 46, 48 in response to receipt of a pulse from the clock 49 on the clock lines 59. The cycles of running the processor 18, enabling the parallel input terminals of the MISR's 42, 44, 46, 48, and adding new data to data already stored in the MISR's 42, 44, 46, 48 as shown in blocks 66, 68, 70 are repeated for a predetermined number of clock cycles as measured by the clock 49. The cycles of data taking produce a single signature number at any time in each MISR 42, 44, 46, 48. After the predetermined number of clock cycles selected for the test, the signature number from each MISR 42, 44, 46, 48 is serially read from the output terminals 55, 56, 57, 58.
Since the initial states, cycle lengths, and number of data taking cycles are reproducibly controlled, the output signal of each MISR 42, 44, 46, 48 is a reproducible signature number. At block 72, the signature number from each MISR 42, 44, 46, 48 is compared with a reference signature number that would result from performing the same test on a properly functioning processor 18 of the same type. As block 74 illustrates the reference signature number is determined empirically by performing the test on a "good" processor 18 prior to performing any tests on "unknown" processors 18. If the signature number from the test does not match the reference signature number, the functional unit 22, 24, 26, 28 of the processor associated with the non-matching number is not operating correctly, and the processor 18 fails the test. If the test and reference signature numbers match, the associated processor 18 passes the test.
Though the "faulty unit" test detects many defects, the test cannot detect all defects that may be present in the processor. In particular, the "faulty unit" test focuses on defects of individual functional units 22, 24, 26, 28 of the processor 18. Typically, more than 99.9 percent of all processors that pass the "faulty unit" test may be defect free. Nevertheless, processors are expensive devices and quality control to a fraction of 0.1 percent is not sufficient for the high standards of the computer industry.
The "faulty unit" test and equivalent tests may miss system-level defects that lead to occasional problems when the processor runs software operating systems such as WINDOWS.RTM., UNIX.RTM., a disk operating system (DOS), or applications such as EXCEL.RTM., WORD.RTM., or paint programs and custom software written to check certain features. The system-level defects are not typically associated with one functional 20, 22, 24, 26 unit of the processor 18. Thus, the "faulty unit" test often is unable to detect them. Unfortunately, using the high level software itself to detect the system-level defects is also problematic, because complex software performs a variety of non-reproducible acts such as reading disks, responding to interrupt requests and reading system clocks in the course of normal operation. If the software performs non-reproducible acts, the output signals produced by running the software are not directly amenable to the detailed comparisons inherent in simple signature tests. Finally, tests for system-level defects that employ high level software without signature analysis are extremely time consuming and costly. Thus, industry standards demand the detection and elimination of processors having system-level, manufacturing defects, because such defects interfere with operating modern operating systems. Nevertheless, the present forms of inexpensive signature testing do not detect such defects.
The present invention is directed to overcoming, or at least reducing the effects of, one or more of the problems set forth above.

Methods and apparatus for system testing of processors and computers using signature analysis


A vehicle assembly includes an engine having a damper assembly secured to the engine. The damper assembly includes a ring gear. A hybrid transmission having an input shaft is mounted on the mounting shaft of the damper assembly. The damper assembly includes an engine face plate and a transmission face plate secured to the engine face plate. The ring gear is secured to at least one of the transmission face plate and the engine face plate.

Vehicles having traditional transmissions, i.e. those powered by a combustion engine alone, require the use of a flywheel mounted on the engine. In addition to being required for vehicle operation, the flywheel is used at an engine assembly plant for starting the engine to confirm the engine will run properly. This is typically done prior to sending the engine to a vehicle assembly location for final assembly.
Vehicles having hybrid transmissions do not require a flywheel for vehicle operation. However, a flexplate is still included as part of the assembly to provide a starter ring gear for start capability at the engine assembly plant. The engine and flexplate are then assembled by bolting the flexplate to a transmission damper at the vehicle assembly location. The transmission damper is typically mounted within the transmission housing for the hybrid transmission, thus making assembly of the flexplate to the damper difficult.

Integrated damper and starter ring gear for a hybrid vehicle


An auxiliary frame having propulsion and steering devices is combined with a wheelchair to form a composite vehicle therewith. A coupling mechanism is provided to couple the auxiliary frame to a wheelchair. A steerable wheel is mounted on the wheelchair to steer and provide forward and reverse movement to the wheelchair, and, a control device is provided to permit the operator to control the direction the wheelchair is to be driven.

For many years, the most usual vehicle or means of transportation for paraplegics and others has been the conventional wheelchair. The conventional wheelchair is a four wheel vehicle having two relatively large rear wheels and two smaller front wheels. The two front wheels are usually pivotally mounted so that the wheelchair can be turned or steered by independent rotation of the two large rear wheels. Typically, the two larger rear wheels are turned by manual manipulation, and for this purpose, an outer concentric rim is normally mounted on the wheel and the concentric rim is turned by the hand to drive and steer the wheelchair.
In recent years, there have been numerous developments which improve wheelchairs. These developments relate primarily to wheelchairs that are driven electrically by battery packs. The electrically driven wheelchairs serve their purpose and provide numerous advantages over the conventional manually manipulated wheelchairs but they also have many disadvantages or deficiencies such as the need to regularly recharge the batteries, the relatively high cost of the wheelchair, and the heavy weight of the motorized wheelchair.
There are numerous prior art devices that allow a person to propel and steer a wheelchair by means other than the manual manipulation of rims adjacent the relatively large rear wheels of the wheelchair. The following patents reflect the state of the art of which the applicant is aware insofar as they are germane or pertinent to his invention: U.S. Pat. No. 3,381,973 to Carr; U.S. Pat. No. 4,316,616 to Boivin; U.S. Pat. No. 4,471,972 to Young; U.S. Pat. No. 4,506,901 to Tosti; U.S. Pat. No. 5,312,127 to Oxford; and U.S. Pat. No. 5,501,480 to Ordelman et al.
The patent to Carr discloses a combination wheelchair and cot that includes a removable chair propelling attachment that can be either hand pedal or foot pedal operated, selectively, depending upon the preference or capabilities of the user. The patent to Boivin discloses a self-propelling and steering attachment for a wheelchair which can be installed and removed by the wheelchair user and which is power driven through a hand actuated crank mechanism through the intermediary of a multi-speed transmission whereby the user can select the right transmission ratio in accordance with the slope or type of ground on which he is travelling. The patent to Young discloses a propulsion and steering attachment for conventional wheelchairs which includes a frame, means for securing the frame to several types and sizes of conventional wheelchairs, steering and propelling means which include a hand crank and a single steerable front wheel, and means formed on the frame for allowing it to collapse for convenient storage. The patent to Tosti discloses a hand-propelled wheelchair which includes hand crank operated, chain and sprocket, direct drives to the rear, relatively large, wheels of the wheelchair to turn the rear wheels in either direction. The patent to Oxford discloses an attachment for a conventional wheelchair which allows the wheelchair occupant to propel and guide the wheelchair by reciprocating an actuating arm. The patent to Ordelman et al. discloses an attachment frame for a conventional wheelchair which includes a coupling assembly for attaching the frame to the wheelchair, at least one steerable wheel, and a hand crank for rotating the steerable wheel through chain and sprocket means for propelling the wheelchair.

Auxiliary frame with propulsion and steering means for attachment to wheelchair


A herbicidal aqueous solution comprising from 30% by weight, of said solution to saturation of a water soluble glyphosate salt; from 8 to 20% by weight of said solution is surfactant, said surfactant comprising from 10 to 100% by weight based on the total weight of said surfactant of an amphoteric surfactant; and from 30% to 90% by weight of ether carboxylate, based on the total weight of surfactant; said solution containing less than 0.035% of sodium ion.

The present invention relates to concentrated herbicidal compositions comprising water soluble glyphosate salts and a surfactant.
A number of formulations have been proposed whereby the herbicide N-(phosphonomethyl)glycine, alias glyphosate, may be supplied as a concentrated aqueous solution with a surfactant synergist which aids wetting and penetration, when the composition is diluted and applied to herbage.
Factors governing the choice of surfactant include wetting power, herbicidal or synergistic action, environmental profile and ability to form stable solutions with glyphosate at as high a concentration as possible, as well as cost.
The surfactant which have so far proved most cost effective for these purposes have been ethoxylated amines. The latter however have a poor environmental profile being biotoxic and poorly biodegradable. There is a demand for a more environmentally acceptable alternative to amine ethoxylates.
We have discovered that ether carboxylates meet most of the above criteria but are insufficiently soluble in concentrated glyphosate solutions. We have furthers noted that amphoteric surfactants also meet most of the above criteria and can act as cosurfactants, solubilising ether carboxylates, but solutions of commercial amphoteric surfactants in concentrated glyphosate are unstable and have been found to deposit crystals of glyphosate salts.
Amphoteric surfactants comprise betaines, sulpho betaines and phosphobetaines. However the great majority of the amphoteric surfactants sold commercially are betaines. The betaines of commerce are normally made by quaternising an amine by reaction with sodium chloracetate. This reaction forms sodium chloride as an unavoidable by-product. As a result commercial betaines contain about 6 to 12% of sodium chloride. We have now discovered that it is possible to use amphoteric surfactants at the required levels in glyphosate solution concentrates without instability, if the sodium chloride content is substantially reduced. Low salt betaines typically contain less than 3% preferably less than 2%, more preferably less than 1% e.g. less than 0.5% especially less than 0.2% sodium ion expressed as wt. sodium chloride based on the weight of surfactant.
The invention provides a herbicidal aqueous solution comprising from 30% by weight, to saturation of a water soluble glyphosate salt and from 8 to 20% by weight of surfactant comprising 10 to 100% by weight based on the total weight of surfactant of an amphoteric surfactant and from 0 to 90% by weight based on the total weight of surfactant of ether carboxylate, said solution containing less the 0.035% by weight of sodium ion.
Sodium ion may be removed from amphoteric surfactants, either by electrosmosis, e.g. as described in our GB 1 525 692 or in EP 0 736 521, or by membrane filtration, for example as described in EP 0 626 881, or, less preferably, by displacing sodium ion with, for example, potassium or ammonium, e.g. using ion exchange. Alternatively, it is possible to prepare betaines with low salt levels by quarternising with acrylic acid.
The glyphosate is preferably present as its potassium, ammonium, C2 to 3 amine or mono or diethanolamine salt, or metho sulphate or as a mixture of two or more of said salts. Particularly preferred is the isopropylamine salt.
We prefer that the total level of inorganic salt be less than 0.39% by weight.
The amphoteric surfactant is preferably a betaine, e.g. a betaine of the formula: RR12N+CH2COOxe2x88x92, wherein R is an alkyl, alkenyl or alkyl phenyl group having an average of from 6 to 20, e.g. 8 to 14 aliphatic carbon atoms and R1 is an alkyl or hydroxy alkyl group having an average of from 1 to 4 carbon atoms. Particularly preferred are the so called quaternary imidazoline betaines, also called ampho acetates, and commonly ascribed the formula:
(although they are actually present predominantly as the corresponding non cyclic amido amine) wherein R and Rxe2x80x2 are alkyl, alkenyl, cycloalkyl, alkaryl or hydroxyalkyl groups having an average of from 1 to 20 aliphatic carbon atoms and R preferably has an average of from 6 to 20, e.g. 8 to 14 aliphatic carbon atoms and Rxe2x80x2 preferably has 1 to 4 carbon atoms. Other amphoteric surfactants for use according to our invention include alkyl amine polyalkoxy sulphates, sulphobetaines and other quaternary amine or quaternised imidazoline sulphonic acids and their salts, and Zwitterionic surfactants, e.g. N-alkyl taurines, carboxylated amido amines such as RCONH(CH2)nN+Rxe2x80x22CH2COxe2x88x922 where n is 2 to 4, and amino acids having, in each case, hydrocarbon groups capable of conferring surfactant properties (e.g. alkyl, cycloalkyl alkenyl or alkaryl groups having from 6 to 20 aliphatic carbon atoms). Typical examples include 2-tallow alkyl, 1-tallow amido alkyl, 1-carboxymethyl imidazoline, 2-coconut alkyl N-carboxymethyl 2 (hydroxyalkyl) imidazoline, alkyl amido ethyl, propyl or butyl dimethyl betaine and C6-20 alkyl dimethyl betaine. Generally speaking any water soluble amphoteric or Zwitterionic surfactant compound which comprises a hydrophobic portion including C6-20 alkyl or alkenyl group and a hydrophilic portion containing an amine or quaternary ammonium group and a carboxylate, sulphate or sulphonic acid group may be used in our invention.
We particularly prefer short chain alkyl amido betaines, ampho acetates and alkyl betaines in which the alkyl group has 6 to 10 carbon atoms since they give very low foaming and permit high levels of ether carboxylate to be solubilised.
The surfactant preferably comprises at least 20% more preferably at least 30%, most preferably at least 40% e.g. 50 to 100% by weight of the amphoteric surfactant based on the total weight of surfactant.
We strongly prefer that the surfactant comprises an ether carboxylate. The ether carboxylate is preferably present in an amount of at least 10%, preferably more than 20% e.g. 30 to 60% by weight based on the total weight of surfactant. Generally the shorter the long alkyl chain of the betaines the higher the proportion of ether carboxylate that can be readily dissolved in a stable solution.
The ether carboxylate preferably has the formula R(OCH2CH2)nOCH2CO2xe2x88x92 wherein R is a straight or branched alkyl, alkenyl, alkylphenyl or polypropylene oxy group having from 6 to 20 e.g. 8 to 14 aliphatic carbon atoms and n is from 1 to 30, preferably, 2 to 20 e.g. 3 to 10.
The counter ion of the ether carboxylate may preferably comprise ammonium, potassium and or an amine or alkanolamine having up to six carbon atoms.
The surfactant may optionally but preferably comprise up to 20% by weight, e.g. 5 to 10% based on the total weight of surfactant, of a non-ionic wetting agent. The non-ionic wetting agent is preferably an ethoxylated alcohol such as a C6 to 25 straight or branched alkyl 1 to 30 mole ethoxylate e.g. a C10 to 18 alkyl 5 to 20 mole ethoxylate. The wetting agent gives better coverage of the leaf and superior herbicidal action.
We prefer that the surfactants should be pre-blended as a concentrate for supply to formulators of glyphosate compositions. To maintain sufficient mobility and to formulators of glyphosate compositions. To maintain sufficient mobility and dispersibility of such concentrates we prefer to add a suitable water miscible solvent such as a water miscible glycol or glycol ether, e.g. polyethylene glycol having a mean mol weight between 90 and 600 especially 130 to 250.
Such concentrates containing from 10 to 70% by weight ether carboxylate, from 20 to 80% by weight of low salt amphoteric surfactant and from 10 to 50% by weight of solvent are a further embodiment of the invention.
Preferably said concentrates additionally contain from 3 to 20% of a non-ionic wetting agent and/or from 1 to 6% of a sequestrant such as an aminophosphonate, e.g. of the formula.
(M2PO3CH2)2N[CH2CH2NCH2PO3M2]nCH2PO3M2
where n is from 0 to 10 preferably 2 to 6 and M is a compatible cation to provide a water soluble product.
The formulation may typically contain from 1 to 3% of sequestrant.
The concentrates contain, typically less than 70% water, preferably less than 60% water most preferably 10 to 55% water by weight of the concentrate.

Herbicidal compositions and surfactant concentrates


A card connector includes a housing for accommodating a card; a terminal for contacting with the card when the card is inserted into the housing; an ejection unit for placing the card and capable of sliding in the housing along a direction that the card is inserted into and pulled out; and a spring member for urging the ejection unit in a direction that the card is pulled out. The card has an inclined surface at a middle of a side surface thereof in a width direction thereof. In the card connector, the ejection unit includes a plate portion and a pair of sidewalls extending from the plate portion. The sidewalls sandwich the card placed on the plate portion from both sides in the width direction of the card. At least one of the sidewalls includes an inclined surface corresponding to the inclined surface of the card.

The present invention relates to a card connector, and more specifically, to a card connector with an ejection mechanism of a push-push type. In the card connector of the invention, it is easy to insert a card.
Patent Reference 1 has disclosed a conventional card connector with an ejection mechanism of a push-push type. In such a card connector, a tray is disposed to eject outside the card connector for covering a bottom surface and side surfaces of a card, so that the card is inserted into the card connector. When the card is removed from the card connector, the tray is ejected again. In the conventional card connector, the tray holds substantially all of side surfaces of the card, and does not sandwich the card.
Patent Reference 2 has disclosed another conventional card connector with an ejection mechanism of a push-push type. In the conventional card connector, a card has an inclined surface having a width decreasing toward an insertion direction of the card. The inclined surface is provided at a middle of one of side surfaces in a width direction. An ejection force is applied to the inclined surface provided on one of the side surfaces, so that the card is discharged. The other side surface is pressed against an inner wall of a housing, thereby holding the card.
Patent Reference 1: Japanese Patent Publication No. 2000-148927
Patent Reference 2: Japanese Patent Publication No. 2005-108763
In the conventional card connector disclosed in Patent Reference 1, the tray is provided for covering a whole bottom surface and the side surfaces of the card. Accordingly, it is difficult to reduce a size of the tray, thereby increasing a size of the card connector.
In the conventional card connector disclosed in Patent Reference 2, the ejection force is applied on only one of the side surfaces of the card. Accordingly, when the card is ejected, the card tends to be inclined, thereby making it difficult to smoothly eject the card. Further, the inner wall of the housing receives the force applied to one of the side surfaces. Accordingly, it is difficult to hold the card within the card connector with a sufficient force.
In view of the problems described above, an object of the present invention is to provide a card connector capable of solving the problems in the conventional card connectors. That is, in the invention, it is possible to reduce a size of the card connector, and to hold a card with a sufficient force.
Further objects will be apparent from the following description of the invention.


A method for obtaining data items from an unresponsive database host. The method includes receiving an indication that the database host is unresponsive, receiving, from a management server via a diagnostic connection, a first request for a first organized data item, and sending a first query, using a first interface, to a memory for the first organized data item. The method further includes receiving, from the management server via a normal connection, a second request for a second organized data item, retrieving, from memory on the database host, a first data item in response to the first query, converting the first data item into the first organized data item, and sending the first organized data item to the management server, wherein the first organized data item is analyzed to determine a source causing the database host to be unresponsive.

Database systems are an integral part of many enterprise and commercial computer systems. Periods of down-time can result in costly delays for a business. If a database system becomes unresponsive, database administrators must attempt to resolve the issue as quickly as possible. Retrieving information about the unresponsive system can be essential in determining the cause of the unresponsiveness, as well as a solution.

Real-time automatic database diagnostic monitor