Compounds selected from those of general formula ##STR1##. and A is selected from specified aminoacyl compounds are inhibitors of DP-IV mediated processes.

DP-IV (EC 188.8.131.52) is a membrane-bound serine protease first identified in rat kidney by its ability to cleave dipeptides from the N-terminus of certain peptides (Hopsu-Havu, V. K. and Glenner, G. G., Histochemie, 1966, 2, 197). The dipeptides must be of the type X-Pro or X-Ala where X=any amino acid X-Proline is more efficiently cleaved than X-Ala.
DP-IV is widely distributed in mammalian tissues and is found in great abundance in the kidney, intestinal epithelium and placenta (Yaron, A. and Naider, F., Critical Reviews in Biochem. Mol. Biol. 1993, 28 (1), 31). In the human immune system the enzyme is expressed almost exclusively by activated T-lymphocytes of the CD4.sup.+ type where the enzyme has been shown to be synonymous with the cell-surface antigen CD26.
The exact role of DP-IV in human physiology is not completely understood but recent research has shown that the enzyme clearly has a major role in human physiology and pathophysiology, eg.
(a) The immune response: DP-IV expression is increased in T-cells upon mitogenic or antigenic stimulation (Mattem, T. et al., Scand. J. Immunol. 1991, 33, 737). It has been reported that inhibitors of DP-IY and antibodies to DP-IV suppress the proliferation of mitogen- and antigen-stimulated T-cells in a dose-dependant manner (Schon, E. et al., Biol. Chem. Hoppe-Seyler, 1991, 372, 305 and refs. within). PA1 Various other functions of T-lymphocytes such as cytokine production, IL-2 mediated cell proliferation and B-cell helper activity have been shown to be dependant on DP-IV activity (Schoin, E. et al., Scand. J. Immunol. 1989, 29, 127). Recently, DP-W inhibitors based on boroproline where reported (Flentke, G. R. et al., Proc. Nat. Acad. Sci. USA, 1991, 88, 1556) which, although unstable, were effective in inhibiting antigen-induced lymphocyte proliferation and IL-2 production in murine CD4.sup.+ T-helper cells. Such boronic acid inhibitors have been shown to have an effect in vivo in mice causing suppression of antibody production induced by immune challenge (Kubota, T. et al., Clin. Exp. Immunol. 1992, 89 192). Other recent papers also provide evidence for the involvement of DP-IV in the immune response (eg. Tanaka, T. et al., Proc. Natl. Acad. Sci. N.Y., 1993, 9, 4586; Hegen, M. et al., Cell Immun. 1993, 146, 249; Subramanyan, M. et al., J. Immunol. 1993, 150, 2544). PA1 The importance of DP-IV is attributed by some investigators to its cell-surface association with the transmembrane phosphatase CD45 (Torimoto, Y. et al., J. Immunol. 1991, 147, 2514). The CD45 - DP-IV association is possibly disrupted by DP-IV inhibitors or non-active site ligands. CD45 is known to be an integral component of T-cell signaling. PA1 (b) Recently, a press release from the Pasteur Institute in Paris (and subsequently a presentation by A. G. Hovanessian at the 8th Cent. Gardes Meeting, Paris, 25-27th October 1993) reported that DP-IV was essential for the penetration and infectivity of HIV-1 and HIV-2 viruses in CD4.sup.+ T-cells. The French group claimed that DP-IV interacted with and may have cleaved the V3 loop of the gp120 envelope glyco-protein of the virus. They also reported that inhibitors or antibodies to DP-IV successfully prevented entry of the virus into cells. It was known previously that there is a selective decrease of CD26 expression in T-cells from HIV-1 infected individuals (Valle-Blazquez, M et al., J. Immunol. 1992, 149, 3073), and that HIV-1 Tat protein binds to DP-IV (Subramanyam, M. et al., J. Immunol. 1993, 150, 2544). PA1 (c) It has been shown recently that lung endothelial DP-IV is an adhesion molecule for lung-metastatic rat breast and prostate carcinoma cells (Johnson, R. C. et al., J. Cell. Biol. 1993, 121, 1423). DP-IV is known to bind to fibronectin and some metastatic tumour cells are known to carry large amounts of fibronectin on their surface. PA1 (d) DP-IV has been shown to associate with the enzyme adenosine deaminase (ADA) on the surface of T-cells (Kameoka, J. et al., Science, 193, 26 466). ADA deficiency causes severe combined immunodeficiency disease (SCID) in humans This ADA-CD26 interaction may provide clues to the pathophysiology of SCID. PA1 (e) High levels of DP-IV expression have been found in human skin fibroblast cells from patients with psoriasis, rheumatoid arthritis (RA) and lichen planus (Raynaud, F. et al., J. Cell. Physiol. 1992, 151, 378). PA1 (f) High DP-IV activity has been found in tissue homogenates from patients with benign prostate hypertrophy and in prostatosomes. These are prostate derived organelles important for the enhancement of sperm forward motility (Vanhoof, G. et al., Eur. J. Clin. Chem. Clin. Biochem. 1992, 30, 333). PA1 (g) DP-IV has been shown to be responsible for the degradation and inactivation of circulating peptides with penultimate proline or alanine at the N-terminus, eg. substance P, growth hormone releasing factor and members of the glucagon/vasoactive intestinal peptide family (Menthein, R. et al., Eur. J. Biochem. 1993, 214, 829). PA1 (h) Raised levels of DP-IV have been observed in the gingiva of patents with periodontitis (Cox, S. W. et al., Arch. Oral. Biol. 1992, 37, 167). PA1 (i) There are also a number of other reports of raised (or sometimes lowered) levels of DP-IV in various pathological conditions. PA1 (a) Immunosuppressants, eg. in organ transplantation; cytoline release suppressants eg. in various autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, RA. PA1 (b) Drugs for the prevention of HIV entry into T-cells and therefore useful in the prophylaxis and treatment of AIDS. PA1 (c) Drugs for the prevention of metastases, particularly of breast and prostate tumours to the lungs. PA1 (d) Agents to treat dermatological diseases, eg. psoriasis, lichen planus. PA1 (e) Drugs to suppress sperm motility and therefore act as male contraceptive agents. PA1 (f) Agents beneficial in benign prostate hypertrophy. PA1 A is attached to Y; PA1 --Y=--N, --CH or .dbd.C (when the --CO group of A is replaced with CH.dbd. or CF.dbd.); PA1 R=H, CN, CHO, B(OH).sub.2, C.tbd.C--R.sub.7, or CH.dbd.N--R.sub.8 ; PA1 R.sub.7 =H, F, lower alkyl (C.sub.1 to C.sub.6), CN, NO.sub.2, OR.sub.9, CO.sub.2 R.sub.9 or COR.sub.9 ; PA1 R.sub.8 =Ph, OH, OR.sub.9, OCOR.sub.9, or OBn; PA1 R.sub.9 =lower alkyl (C.sub.1 -C.sub.6); and either .omega. or both .epsilon.'s may be absent. PA1 A is an .alpha.-amino-acyl group derived from an .alpha.-amino-acid bearing a cycloaliphatic side-chain (e.g. C.sub.4 to C.sub.10, mono or bicyclic) whose ring may contain one or more heteroatoms e.g. L-cyclohexylglycine, L-cyclopentylglycine, L-decahydronaphthylglycine, L-piperidylglycine; PA1 or PA1 A is a .beta.-amino-acyl group of general formula ##STR3## PA1 where p=1-6 and the ring may also contain one or more heteroatoms replacing CH.sub.2 unit(s). PA1 Both .alpha. and .beta.-amino acyl groups in (a) above may contain unsaturation in their rings e.g. ##STR4## PA1 and also may contain one or more heteroatoms. PA1 A is as defined in (a) above but in addition may be derived from any L-.alpha.-amino acid bearing a lipophilic side-chain, eg. Ile. PA1 A is a .beta.-amino-acyl group as defined in (a) above. The resulting A-B compounds are stable, unlike .alpha.-aminoacyl derivatives of the same type which undergo a facile intramolecular cyclisation. In compounds (c) B(OH).sub.2 may be present as a boronate ester eg. ##STR5## PA1 these being labile in water giving the free boronic acids. PA1 where PA1 D.sup.1 =D with G.noteq.O; PA1 R.sub.4 =Z--NH--(CH.sub.2).sub.c -- or NH--Z--(CH.sub.2).sub.c -- where c=1-12 and Z=CO, CH.sub.2 or SO.sub.2 ; and PA1 R.sub.3 =CO.sub.2 H or ester [e.g. any lower alkyl, fluoroalkyl or cycloalkyl (C.sub.1 to C.sub.8), or aromatic or heteroaromatic (5 or 6membered rings, mono- or bicylic) ester] thereof; CONH.sub.2 ; CONHNH.sub.2 ; CONR.sub.5 R.sub.6 ; CONHNR.sub.5 R.sub.6 ; PO.sub.3 H (or ester thereof e.g. as defined under CO.sub.2 H); SO.sub.3 H; SO.sub.2 NH.sub.2 ; SO.sub.2 NR.sub.5 R.sub.6 ; OH; OR.sub.5 ; aryl or heteroaryl (e.g. 5 or 6membered rings, monocyclic or bicyclic) [including substituted aryl or heteroaryl with substituents preferably chosen from F, Cl, I, Br, OH, OR.sub.5, NO.sub.2, SO.sub.3 H, SO.sub.2 NH.sub.2, SO.sub.2 NR.sub.5 R.sub.6, NH.sub.2, NR.sub.5 R.sub.6, CO.sub.2 R.sub.5, CF.sub.3, CN, CONH.sub.2, CONR.sub.5 R.sub.6, NHCO.sub.2 R.sub.5, CH(:NR.sub.5)NR.sub.5 R.sub.6, NH--CH(:NR.sub.5)NR.sub.5 R.sub.6 and R.sub.5 ]; NH.sub.2 ; NR.sub.5 R.sub.6 ; NHCO.sub.2 R.sub.5 ; NHSO.sub.2 NR.sub.5 R.sub.6 ; NHCOR.sub.5 ; NH--SO.sub.2 R.sub.5 ; NH--CH(:NR.sub.5)NR.sub.5 R.sub.6 ; NHCONR.sub.5 R.sub.6 ; sugar (which may be attached via an ether or a glycosidic bond); CO-aminosugar (attached via the --NH.sub.2) eg. glucosamine or galactosamine; NHCO-aminosugar; or NHCS-aminosugar. PA1 In the above definition of R.sub.3 "sugar" refers to any carbohydrate or oligosaccharide, and R.sub.5 and R.sub.6 are independently selected from H and alkyl, fluoroallyl and cycloalkyl groups (of up to 8 atoms), aryl, heteroaryl and alkylheteroaryl groups (of up to 11 atoms) or R.sub.5 and R.sub.6 together comprise a chain and (C.sub.3 to C.sub.8). ##STR7## PA1 where R.sup.1 =H, Me; the ring may also contain more heteroatoms; PA1 E=J--(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3 ; J=CO, CH.sub.2 or SO.sub.2 ; and a, b, q, R.sub.3 and R.sub.4 as defined under (i) ##STR8## PA1 where R.sup.2 =H or Me; the ring may also contain one or more heteroatoms; PA1 L=(CH.sub.2).sub.d --[CO].sub.r --(CH.sub.2).sub.b --(R.sub.4).sub.1 --R.sub.3 or (CH.sub.2).sub.e --NR.sup.1 --(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3 ; r=0 or 1; d=0-4; e=2-4; and b, q, R.sub.3 and R.sub.4 as defined under (i). PA1 where .omega.=CH.sub.2, O, NH, CO, S, SO.sub.2, Ph or NMe and, independently, .epsilon.=CH.sub.2, O, NH, CO, S, SO.sub.2, Ph or NMe.
It follows from the above that potent inhibitors of DP-IV may be useful as drugs for the treatment of human disease. Such inhibitors could be useful as:
Inhibitors of DP-IV
The only competitive inhibitors of DP-IV enzyme activity reported so far are the unstable boronic acids (t1/2 30-90 min at pH 7) mentioned above. (Bachovchin et al, WO 91/16339, October 1991) having K.sub.i values in the nanomolar range for DP-IV, and simple amino-acid pyrrolidides or thiazolides (Neubert et al., DD 296 075 A5, November 1991) which have only modest potency (K.sub.i >0.1 .mu.M). Amino-acyl proline aldehydes claimed in the same German patent cannot be synthesised due to a facile intramolecular condensation of the N-terminal amino group with the aldehyde function.
We now disclose highly potent competitive inhibitors of DP-IV (with K.sub.i values in the 10.sup.-6 -10.sup.-10 range) which are also chemically stable (t1/2>24 h). They fall into three broad groups of compounds (Groups I, II and III).
GROUP I
These are molecules designed to bind tightly in the active site of DP-IY and to inhibit its proteolytic activity without interfering with attachment of any accessory ligands which may bind to the surface of DP-IV (i.e. not at its active site). Such Group I compounds could be useful as immunosuppressants; anti-HIV infectivity agents; agents to suppress release of certain cytokines (eg. IL-2, IL-6, .gamma.-INF) from activated T-cells. The boronic acids and pyrolidides referred to earlier also fall into this category.
GROUP II
These are evolved from Group I compounds; however they contain long-chain extensions to the side-chains of the amino-acid defined as A in the general structure. The resulting compounds bind tightly to the active-site of DP-IV but the long-chain extensions protrude from the enzyme active site and serve to prevent the attachment of any other ligand which may bind to the surface of DP-IV. Such compounds could have the same uses as Group I compounds but in addition could block the interaction of DP-IY with (i) CD45 (ii) the gp 120 V3 loop of HIV-1 (iii) tumour cell surface fibronectin (iv) any other ligand important for T-cell activation, virus entry into T-cells or tumour cell adhesion.
GROUP III
This group comprises novel dimers in which two active-site directed inhibitors of DP-IV are linked via the side-chains of their amino-acid residues designated A in the general structure by a long chain. Such dimers can inhibit two molecules of DP-IV concurrently and also prevent accessory ligands binding to the surface of DP-IV. These dimers would have the same uses as Group II compounds but may be more effective.
The invention provides inhibitors of DP-IV mediated processes, the inhibitors being of general formula: ##STR2##
The structure of A is dependent on the nature of R in moiety B and on the nature of the group to which the resulting compound belongs.
Group I Compounds
(a) R=H
(b) R=CN; C.tbd.C--R.sub.7 or CH.dbd.N--R.sub.8
(c) R=CHO or B(OH).sub.2
Group II Compounds
Where R.dbd.H, CN, C.tbd.C--R.sub.7 or CH.dbd.N--R.sub.8, A is an .alpha.-amino acid derivative whose side-chain carries a functional group which is derivatised to produce a long chain terminating in various groups R.sub.3. A may be of the following three types of structure: ##STR6##
a=1-5; D=G--(CH.sub.2).sub.b (R.sub.4).sub.q --R.sub.3 ; G=O, NH, or NMe; PA2 b=0-12; q=0-5;
Group III
Group III compounds are defined by the general formula: ##STR9##
These compounds are symmetrical dimers. They may have any B structure as defined previously. A may be chosen from any group II structure [(i), (ii) or (iii)], but in this case he terminal group R.sub.3 in each A residue is deleted and replaced with a shared symmetrical group [.epsilon.--.omega..epsilon.] which connects the two halves of the dimer; .omega. may be absent, in which case both .epsilon.'s are joined together to constitute the chain linking the two A-B moieties; alternatively both .epsilon.'s may be absent in which case to solely joins the two A-B moieties.
The stricture of .epsilon.--.omega.--.epsilon. must of course be chemically feasible eg. NH--CO--NH, CO--NH--CO--, SO.sub.2 --NMe--SO.sub.2 ; it will be obvious to those skilled in the art which structures are not feasible, eg. --NH--NH--NH--. A specific possible example is shown in Table 7.
In such compounds as described under Groups II and III certain --CH.sub.2 -- groups present in the long chains could be replaced with known bioisosteres eg. --O-- without affecting inhibitory or binding activity towards DP-IV. Also such groupings as --CONHCH.sub.2 CH.sub.2 NHCO if they occur could be replaced by eg. ##STR10##
Further, for compounds in Groups I, II and III any amide bond connecting A and B or any amide in the side-chains of A (in Groups II and E) may be replaced by known bioisosteres of amides eg. ##STR11##
See Table 8 for examples of such replacements.
Biochemistry
All compounds were tested in vitro against pure human DP-IV (purchased from M & E, Copenhagen, Denmark). Inhibition of DP-IV was determined using the fluorescent substrate Ala--Pro--AFC (K.sub.m 0.8 .mu.M) at three concentrations for each inhibitor. A typical assay (total volume 0.4 ml) comprised sodium Hepes 83.3 mM, EDTA 1.67 mM, BSA 1.5 mg ml.sup.-1 pH 7.8, DP-IV 25 .mu.U ml.sup.-1, inhibitor (in 10 mM acetate pH 4.0). The reaction was started by the addition of substrate and readings taken every 30 s for 7.5 min, excitation at 395 nm, emission 450 nm. K.sub.i values were determined using Dixon plots.
Chemistry
152 Examples of compounds synthesised are shown in Tables 1-8 followed by schemes and experimental details for the preparation of different structural types. All final products were characterised by FAB mass spectrometry and purity assessed by reverse phase hplc; all intermediates were characterised by .sup.1 H NMR.
Table 9 shows selected K.sub.i values against DP--IV determined for inhibitors of different structural types.
TABLE 1 Examples of Group I (a) Calculated FAB Mass No. A X R n Formula Mol. Wt. spec. [M + H].sup.+ 1 ##STR12## CH.sub.2 H 1 C.sub.11 H.sub.20 N.sub.2 O 196.2 197.2 2 ##STR13## CH.sub.2 H 1 C.sub.12 H.sub.22 N.sub.2 O 210.2 211.2 3 ##STR14## CH.sub.2 H 1 C.sub.10 H.sub.20 N.sub.2 O 184.2 185.2 4 ##STR15## CH.sub.2 H 1 C.sub.12 H.sub.20 N.sub.2 O 208.2 209.2 5 cis ##STR16## CH.sub.2 H 1 C.sub.11 H.sub.20 N.sub.2 O 196.1 197.2 6 trans ##STR17## CH.sub.2 H 1 C.sub.11 H.sub.20 N.sub.2 O 196.1 197.2 7 trans ##STR18## CH.sub.2 H 1 C.sub.11 H.sub.18 N.sub.2 O 194.1 195.2 8 trans ##STR19## CH.sub.2 H 1 C.sub.10 H.sub.18 N.sub.2 O 182.1 183.2 9 ##STR20## CH.sub.2 H 1 C.sub.11 H.sub.14 N.sub.2 O 190.1 191.2 10 trans ##STR21## CH.sub.2 H 1 C.sub.13 H.sub.24 N.sub.2 O 224.2 225.2
TABLE 2 Examples of Group I (b) ##STR22## Calculated FAB Mass No. A X n R.sup.1 R Formula Mol. Wt. spec. [M + H].sup.+ 11 H-Ile CH.sub.2 1 H CN C.sub.11 H.sub.19 N.sub.3 O 209.3 210.2 12 H-Lys(Z) CH.sub.2 1 H CN C.sub.19 H.sub.26 N.sub.4 O.sub.3 358.2 359.2 13 H-Pro CH.sub.2 1 H CN C.sub.10 H.sub.15 N.sub.3 O 193.1 194.1 14 ##STR23## CH.sub.2 1 H CN C.sub.9 H.sub.13 N.sub.3 OS 211.1 212.2 15 ##STR24## CH.sub.2 1 H CN C.sub.9 H.sub.13 N.sub.3 OS 211.1 212.2 16 ##STR25## CH.sub.2 1 H CN C.sub.13 H.sub.21 N.sub.3 O 235.2 236.3 17 ##STR26## CH.sub.2 1 H CN C.sub.12 H.sub.19 N.sub.3 O 221.2 222.2 18 ##STR27## CH.sub.2 1 H CN C.sub.11 H.sub.19 N.sub.3 O 209.2 210.2 19 H-Ile S 1 H CN C.sub.10 H.sub.17 N.sub.3 OS 227.1 228.1 20 H-Ile S 1 CN H C.sub.10 H.sub.17 N.sub.3 OS 227.1 228.1 21 ##STR28## S 1 H CN C.sub.12 H.sub.19 N.sub.3 OS 253.1 254.1 22 H-Lys(Z) S 1 H CN C.sub.18 H.sub.24 N.sub.4 O.sub.3 S 376.2 3.2 23 ##STR29## S 1 H CN C.sub.11 H.sub.17 N.sub.3 OS 239.1 240.2 24 H-Ile O 1 H CN C.sub.10 H.sub.17 N.sub.3 O.sub.2 211.1 212.2 25 H-Ile CH.sub.2 2 H CN C.sub.12 H.sub.21 N.sub.3 O 223.2 224.2 26 H-Ile S 2 H CN C.sub.11 H.sub.19 N.sub.3 OS 241.1 242.1 27 H-Ile SO.sub.2 1 H CN C.sub.10 H.sub.17 N.sub.3 O.sub.3 S 259.1 260.1 28 H-Ile ##STR30## 1 H CN C.sub.10 H.sub.17 N.sub.3 O.sub.2 S 243.1 244.1 29 H-Ile ##STR31## 1 H CN C.sub.10 H.sub.17 N.sub.3 O.sub.2 S 243.1 244.2 30 ##STR32## CH.sub.2 1 H CN C.sub.12 H.sub.19 N.sub.3 O 221.2 222.2 31 ##STR33## CH.sub.2 1 H CN C.sub.12 H.sub.19 N.sub.3 O 221.2 222.2 32 ##STR34## CH.sub.2 1 H CN C.sub.11 H.sub.17 N.sub.3 O 207.2 208.2 33 ##STR35## CH.sub.2 1 H CN C.sub.11 H.sub.17 N.sub.3 O 207.2 208.2 34 ##STR36## CH.sub.2 1 H CN C.sub.12 H.sub.17 N.sub.3 O 219.1 220.1 35 ##STR37## CH.sub.2 1 H CN C.sub.12 H.sub.17 N.sub.3 O 219.1 220.1 36 ##STR38## CH.sub.2 1 H CN C.sub.12 H.sub.19 N.sub.3 O 221.2 222.2 37 ##STR39## CH.sub.2 1 H CN C.sub.12 H.sub.17 N.sub.3 O 219.1 220.1
TABLE 3 Example of Group I (c) ##STR40## Calculated FAB Mass No. A X R n Formula Mol. Wt. spec. [M + H].sup.+ 38 ##STR41## CH.sub.2 CHO 1 C.sub.12 H.sub.20 N.sub.2 O.sub.2 224.2 225.2 39 ##STR42## CH.sub.2 CHO 1 C.sub.11 H.sub.18 N.sub.2 O.sub.2 210.2 211.2 40 ##STR43## CH.sub.2 CHO 1 C.sub.11 H.sub.18 N.sub.2 O.sub.2 210.2 211.2 41 ##STR44## CH.sub.2 B* 1 C.sub.20 H.sub.33 BN.sub.2 O.sub.3 360.3 361.3 42 ##STR45## CH.sub.2 B* 1 C.sub.21 H.sub.35 BN.sub.2 O.sub.3 374.3 375.1 43 ##STR46## CH.sub.2 B* 1 C.sub.21 H.sub.35 BN.sub.2 O.sub.3 374.3 375.1 44 ##STR47## CH.sub.2 B* 1 C.sub.21 H.sub.33 BN.sub.2 O.sub.3 372.3 373.3 45 ##STR48## CH.sub.2 B* 1 C.sub.21 H.sub.33 BN.sub.2 O.sub.3 372.3 373.3 B*= ##STR49##
TABLE 4 Examples of Group II (i) ##STR50## Calculated FAB Mass No. n Q X m R Formula Mol. Wt. spec. [M + H].sup.+ 46 1 --CONHCH.sub.2 CO.sub.2 Bn CH.sub.2 1 H C.sub.17 H.sub.23 N.sub.3 O.sub.4 333.2 334.2 47 1 --CONHCH.sub.2 CO.sub.2 H CH.sub.2 1 H C.sub.10 H.sub.17 N.sub.3 O.sub.4 243.1 244.2 48 1 --CONH(CH.sub.2).sub.3 CO.sub.2 H CH.sub.2 1 H C.sub.12 H.sub.21 N.sub.3 O.sub.4 271.2 272.2 49 1 --CONH(CH.sub.2).sub.2 CO.sub.2 Bn CH.sub.2 1 H C.sub.18 H.sub.25 N.sub.3 O.sub.4 347.2 348.2 50 1 --CONH(CH.sub.2).sub.2 CO.sub.2 H CH.sub.2 1 H C.sub.11 H.sub.19 N.sub.3 O.sub.4 257.1 258.2 51 1 --CONH(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 H C.sub.21 H.sub.31 N.sub.3 O.sub.4 389.3 390.3 52 1 --CONH(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.14 H.sub.25 N.sub.3 O.sub.4 299.2 300.2 53 1 --CONH(CH.sub.2).sub.3 CO.sub.2 Bn CH.sub.2 1 H C.sub.19 H.sub.27 N.sub.3 O.sub.4 361.2 362.2 54 2 --CONHCH.sub.2 CO.sub.2 Bn CH.sub.2 1 H C.sub.18 H.sub.25 N.sub.3 O.sub.4 347.2 348.2 55 2 --CONHCH.sub.2 CO.sub.2 H CH.sub.2 1 H C.sub.11 H.sub.19 N.sub.3 O.sub.4 257.1 258.1 56 2 --CONH(CH.sub.2).sub.2 CO.sub.2 Bn CH.sub.2 1 H C.sub.19 H.sub.27 N.sub.3 O.sub.4 361.2 362.3 57 2 --CONH(CH.sub.2).sub.3 CO.sub.2 Bn CH.sub.2 1 H C.sub.20 H.sub.29 N.sub.3 O.sub.4 375.2 376.3 58 2 --CONH(CH.sub.2).sub.3 CO.sub.2 H CH.sub.2 1 H C.sub.13 H.sub.23 N.sub.3 O.sub.4 285.2 286.2 59 2 --CONH(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 H C.sub.22 H.sub.33 N.sub.3 O.sub.4 403.3 404.3 60 2 --CONH(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.4 313.2 314.2 61 2 --CONH(CH.sub.2).sub.2 CO.sub.2 H CH.sub.2 1 H C.sub.12 H.sub.21 N.sub.3 O.sub.4 271.2 272.2 62 2 --CONH(CH.sub.2).sub.7 CO.sub.2 Bn CH.sub.2 1 H C.sub.24 H.sub.37 N.sub.3 O.sub.4 432.3 432.4 63 2 --CONH(CH.sub.2).sub.7 CO.sub.2 H CH.sub.2 1 H C.sub.17 H.sub.31 N.sub.3 O.sub.4 341.3 342.5 64 2 --CONH(CH.sub.2).sub.7 CONH--(CH.sub.2).sub.3 NHZ CH.sub.2 1 H C.sub.28 H.sub.45 N.sub.5 O.sub.5 531.3 532.3 65 2 --CONH(CH.sub.2).sub.6 CONH--(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 H C.sub.29 H.sub.46 N.sub.4 O.sub.5 530.4 531.2 66 2 --CONH(CH.sub.2.sub.6 CONH--(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.22 H.sub.40 N.sub.4 O.sub.5 440.3 441.3 67 2 --CONH(CH.sub.2).sub.7 CONH--(CH.sub.2).sub.3 NH.sub.2 CH.sub.2 1 H C.sub.20 H.sub.39 N.sub.5 O.sub.3 397.3 398.3 68 2 --CONH(CH.sub.2).sub.11 CO.sub.2 Bn CH.sub.2 1 H C.sub.28 H.sub.45 N.sub.3 O.sub.4 487.3 488.4 69 2 --CONH(CH.sub.2).sub.11 CO.sub.2 H CH.sub.2 1 H C.sub.21 H.sub.39 N.sub.3 O.sub.4 397.3 398.3 70 2 --CONH(CH.sub.2).sub.6 CO.sub.2 Bn CH.sub.2 1 H C.sub.23 H.sub.35 N.sub.3 O.sub.4 417.3 418.3 71 2 --CONH(CH.sub.2).sub.6 CO.sub.2 H CH.sub.2 1 H C.sub.16 H.sub.29 N.sub.3 O.sub.4 327.2 328.2 72 2 --CONH(CH.sub.2).sub.5 CONH--CH.sub.2 CF.sub.3 CH.sub.2 1 H C.sub.17 H.sub.29 F.sub.3 N.sub.4 O.sub.3 394.2 395.3 73 2 --CONH(CH.sub.2).sub.5 CONH--CH.sub.2 (CF.sub.2).sub.2 CF.sub.3 CH.sub.2 1 H C.sub.19 H.sub.29 F.sub.7 N.sub.4 O.sub.3 494.2 495.2 74 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.6 OH CH.sub.2 1 H C.sub.21 H.sub.40 N.sub.4 O.sub.4 412.3 413.2 75 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.3 Ph CH.sub.2 1 H C.sub.24 H.sub.38 N.sub.4 O.sub.3 430.3 431.2 76 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.4 Ph CH.sub.2 1 H C.sub.25 H.sub.40 N.sub.4 O.sub.3 444.3 445.2 77 2 --CONH(CH.sub.2).sub.5 CON-(.sup.n Bu).sub.2 CH.sub.2 1 H C.sub.23 H.sub.44 N.sub.4 O.sub.3 424.3 425.3 78 2 --CONH(CH.sub.2).sub.5 CON-(.sup.n Hx).sub.2 CH.sub.2 1 H C.sub.27 H.sub.52 N.sub.4 O.sub.3 480.4 481.4 79 2 --CONH(CH.sub.2).sub.5 CONH--CH.sub.2 Ph CH.sub.2 1 H C.sub.22 H.sub.34 N.sub.4 O.sub.3 402.3 403.4 80 2 --CONH(CH.sub.2).sub.4 CO.sub.2 Bn CH.sub.2 1 H C.sub.21 H.sub.31 N.sub.3 O.sub.4 389.2 390.3 81 2 --CONH(CH.sub.2).sub.4 CO.sub.2 H CH.sub.2 1 H C.sub.14 H.sub.25 N.sub.3 O.sub.4 299.2 300.3 82 2 --CONH(CH.sub.2).sub.5 CONH--CH.sub.2 CH.sub.3 CH.sub.2 1 H C.sub.17 H.sub.32 N.sub.4 O.sub.3 340.3 341.3 83 2 --CONH(CH.sub.2).sub.6 OH CH.sub.2 1 H C.sub.15 H.sub.29 N.sub.3 O.sub.3 299.2 300.3 84 2 --CONH(CH.sub.2).sub.5 CO-1-Pip CH.sub.2 1 H C.sub.20 H.sub.36 N.sub.4 O.sub.3 380.3 381.4 85 2 --CONH(CH.sub.2).sub.5 CONH.sub.2 CH.sub.2 1 H C.sub.15 H.sub.28 N.sub.4 O.sub.3 312.2 313.3 86 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.9 CH.sub.3 CH.sub.2 1 H C.sub.25 H.sub.48 N.sub.4 O.sub.3 452.4 453.5 87 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.6 CH.sub.3 CH.sub.2 1 H C.sub.22 H.sub.42 N.sub.4 O.sub.3 410.3 411.4 88 2 --CONH(CH.sub.2).sub.5 CONH--CH.sub.2 Ch CH.sub.2 1 H C.sub.22 H.sub.40 N.sub.4 O.sub.3 408.3 409.4 89 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.3 NHZ CH.sub.2 1 H C.sub.26 H.sub.41 N.sub.5 O.sub.5 503.3 504.4 90 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.3 NH.sub.2 CH.sub.2 1 H C.sub.18 H.sub.35 N.sub.5 O.sub.3 369.3 370.3 91 2 --CONH(CH.sub.2).sub.5 CONH--(CH.sub.2).sub.3 --Gua CH.sub.2 1 H C.sub.19 H.sub.37 N.sub.7 O.sub.3 411.3 412.4 92 2 --CONH(CH.sub.2).sub.5 CONH--Ph(4-SO.sub.3 H) CH.sub.2 1 H C.sub.21 H.sub.32 N.sub.4 O.sub.6 S 468.2 469.2 93 2 --CONH(CH.sub.2).sub.5 CONH-4-Pip(1-Bn) CH.sub.2 1 H C.sub.27 H.sub.43 N.sub.5 O.sub.3 485.3 486.3 94 2 --CONH(CH.sub.2).sub.5 CONH-4-Pip CH.sub.2 1 H C.sub.20 H.sub.37 N.sub.5 O.sub.3 395.3 396.3 95 2 --CONH(CH.sub.2).sub.4 N(Z)--(CH.sub.2).sub.3 NHZ CH.sub.2 1 H C.sub.32 H.sub.45 N.sub.5 O.sub.6 595.3 596.3 96 2 --CONH(CH.sub.2).sub.4 NH--(CH.sub.2).sub.3 NH.sub.2 CH.sub.2 1 H C.sub.16 H.sub.33 N.sub.5 O.sub.2 327.2 328.2 97 2 --CONH(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 CN C.sub.23 H.sub.32 N.sub.4 O.sub.4 428.3 429.3 98 3 --CONH(CH.sub.2).sub.6 CONH--(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 H C.sub.30 H.sub.48 N.sub.4 O.sub.5 544.4 545.2 99 3 --CONH(CH.sub.2).sub.6 CONH--(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.23 H.sub.42 N.sub.4 O.sub.5 454.3 455.3 100 3 --CONH(CH.sub.2).sub.5 CO.sub.2 Bn CH.sub.2 1 H C.sub.23 H.sub.35 N.sub.3 O.sub.4 417.3 418.2 101 3 --CONH(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.16 H.sub.29 N.sub.3 O.sub.4 327.2 328.2 102 2 --SO.sub.2 NH(CH.sub.2).sub.5 CO.sub.2 H CH.sub.2 1 H C.sub.14 H.sub.27 N.sub.3 O.sub.5 S 349.2 350.2 103 2 --CONH(CH.sub.2).sub.8 NH--G* CH.sub.2 1 H C.sub.24 H.sub.45 N.sub.5 O.sub.7 S 547.4 548.5 G*= ##STR51##
TABLE 5 Example of Group II (ii) ##STR52## Calculated FAB Mass No. n Q X m R Formula Mol. Wt. spec. [M + H].sup.+ 104 1 --CO(CH.sub.2).sub.6 CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.4 313.2 314.3 105 1 --CO(CH.sub.2).sub.6 CO.sub.2 Bn CH.sub.2 1 H C.sub.22 H.sub.33 N.sub.3 O.sub.4 403.3 404.3 106 3 --CO(CH.sub.2).sub.4 CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.4 313.2 314.3 107 3 --CO(CH.sub.2).sub.4 CO.sub.2 Me CH.sub.2 1 H C.sub.16 H.sub.29 N.sub.3 O.sub.4 327.2 328.3 108 4 --CO(CH.sub.2).sub.5 NH.sub.2 CH.sub.2 1 H C.sub.16 H.sub.32 N.sub.4 O.sub.2 312.3 313.3 109 4 --CO(CH.sub.2).sub.3 NH.sub.2 CH.sub.2 1 H C.sub.14 H.sub.28 N.sub.4 O.sub.2 284.2 285.2 110 4 --CO(CH.sub.2).sub.3 NHSO.sub.2 Pfp CH.sub.2 1 H C.sub.20 H.sub.2 F.sub.5 N.sub.4 O.sub.4 S 514.2 515.2 111 4 --CO(CH.sub.2).sub.3 NHCOPfp CH.sub.2 1 H C.sub.21 H.sub.27 F.sub.5 N.sub.4 O.sub.3 478.2 479.2 112 4 --CO(CH.sub.2).sub.3 NHSO.sub.2 --CH.sub.2 CF.sub.3 CH.sub.2 1 H C.sub.16 H.sub.29 F.sub.3 N.sub.4 O.sub.4 S 430.2 431.3 113 4 --CO(CH.sub.2).sub.11 NHCO--(CH.sub.2).sub.6 NHZ CH.sub.2 1 H C.sub.37 H.sub.63 N.sub.5 O.sub.5 657.5 658.6 114 4 --CO(CH.sub.2).sub.11 NH--CO(CH.sub.2).sub.6 NH.sub.2 CH.sub.2 1 H C.sub.29 H.sub.57 N.sub.5 O.sub.3 523.4 524.4 115 4 --CO(CH.sub.2).sub.5 NHCO--(CH.sub.2).sub.5 NHCO(CH.sub.2).sub.5 --NHZ CH.sub.2 1 H C.sub.36 H.sub.60 N.sub.6 O.sub.6 672.5 673.6 116 4 --CO(CH.sub.2).sub.5 NHCO--(CH.sub.2).sub.5 NHCO(CH.sub.2).sub.5 --NH.sub.2 CH.sub.2 1 H C.sub.28 H.sub.54 N.sub.6 O.sub.4 538.4 539.4 117 4 --CO(CH.sub.2).sub.3 CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.4 313.2 314.3 118 4 --CO(CH.sub.2).sub.3 CO.sub.2 Bn CH.sub.2 1 H C.sub.22 H.sub.83 N.sub.3 O.sub.4 403.3 404.3 119 4 --CO(CH.sub.2).sub.6 NH.sub.2 CH.sub.2 1 H C.sub.17 H.sub.34 N.sub.4 O.sub.2 326.3 327.3 120 4 --CO(CH.sub.2).sub.7 NH.sub.2 CH.sub.2 1 H C.sub.18 H.sub.36 N.sub.4 O.sub.2 340.3 341.3 121 4 --CO(CH.sub.2).sub.16 Me CH.sub.2 1 H C.sub.28 H.sub.55 N.sub.3 O.sub.2 465.4 466.4 122 4 --CO(CH.sub.2).sub.6 --Gua CH.sub.2 1 H C.sub.18 H.sub.36 N.sub.6 O.sub.2 368.3 369.3 123 4 --SO.sub.2 (CH.sub.2).sub.7 CH.sub.3 CH.sub.2 1 H C.sub.18 H.sub.37 N.sub.3 O.sub.3 S 375.3 376.3 124 4 --CO(CH.sub.2).sub.11 NH.sub.2 CH.sub.2 1 H C.sub.22 H.sub.44 N.sub.4 O.sub.2 396.4 397.4 125 4 --COCH.sub.2 NHZ CH.sub.2 1 H C.sub.20 H.sub.30 N.sub.4 O.sub.4 390.2 391.3 126 4 --CO(CH.sub.2).sub.2 NHZ CH.sub.2 1 H C.sub.21 H.sub.32 N.sub.4 O.sub.4 404.2 405.3 127 4 --CO(CH.sub.2).sub.3 NHZ CH.sub.2 1 H C.sub.22 H.sub.34 N.sub.4 O.sub.4 418.3 419.3 128 4 --CO(CH.sub.2).sub.2 NH.sub.2 CH.sub.2 1 H C.sub.12 H.sub.24 N.sub.4 O.sub.2 256.2 257.2 129 4 --CO(CH.sub.2).sub.5 NHZ CH.sub.2 1 H C.sub.24 H.sub.38 N.sub.4 O.sub.4 446.3 447.4 130 4 --COCH.sub.2 --Gua CH.sub.2 1 H C.sub.13 H.sub.26 N.sub.6 O.sub.2 298.2 299.3 131 4 --CO(CH.sub.2).sub.2 NH.sub.2 CH.sub.2 1 H C.sub.13 H.sub.26 N.sub.4 O.sub.2 20.2 271.3 132 4 --CO(CH.sub.2).sub.2 --Gua CH.sub.2 1 H C.sub.14 H.sub.28 N.sub.6 O.sub.2 312.2 313.3 133 4 --CO(CH.sub.2).sub.3 --Gua CH.sub.2 1 H C.sub.15 H.sub.30 N.sub.6 O.sub.2 326.3 327.3 134 4 --CO(CH.sub.2).sub.5 --Gua CH.sub.2 1 H C.sub.17 H.sub.34 N.sub.6 O.sub.2 354.3 355.3 135 4 --CO(CH.sub.2).sub.6 NH.sub.2 CH.sub.2 1 CN C.sub.18 H.sub.33 N.sub.5 O.sub.2 351.3 352.4 136 4 --CO(CH.sub.2).sub.7 NH.sub.2 CH.sub.2 1 CN C.sub.19 H.sub.35 N.sub.5 O.sub.2 365.3 366.3
TABLE 6 Examples of Group II (iii) ##STR53## Calculated FAB Mass No. R R.sup.1 X n Y Formula Mol. Wt. spec. [M + H].sup.+ 137 H --OCH.sub.2 CONH(CH.sub.2).sub.5 --CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.5 329.2 330.3 138 H --OCH.sub.2 CONH(CH.sub.2).sub.5 --CO.sub.2 Bn CH.sub.2 1 H C.sub.22 H.sub.33 N.sub.3 O.sub.5 419.3 420.3 139 H --OCH.sub.2 CONH(CH.sub.2).sub.4 --CO.sub.2 Bn CH.sub.2 1 H C.sub.21 H.sub.31 N.sub.3 O.sub.5 405.2 406.3 140 H --OCH.sub.2 CONH(CH.sub.2).sub.4 --CO.sub.2 H CH.sub.2 1 H C.sub.14 H.sub.25 N.sub.3 O.sub.5 315.2 316.3 141 CH.sub.3 --OCH.sub.3 CH.sub.2 1 H C.sub.9 H.sub.18 N.sub.2 O.sub.2 186.1 187.2 142 CH.sub.3 --OC.sub.2 H.sub.5 CH.sub.2 1 H C.sub.10 H.sub.20 N.sub.2 O.sub.2 200.1 201.2 143 CH.sub.3 --O(CH.sub.2).sub.5 CH.sub.3 CH.sub.2 1 H C.sub.14 H.sub.28 N.sub.2 O.sub.2 256.2 257.3 144 CH.sub.3 --OCH.sub.2 CONH(CH.sub.2).sub.5 --CO.sub.2 Bn CH.sub.2 1 H C.sub.23 H.sub.35 N.sub.3 O.sub.5 433.3 434.3 145 CH.sub.3 --OCH.sub.2 CONH(CH.sub.2).sub.5 --CO.sub.2 H CH.sub.2 1 H C.sub.16 H.sub.29 N.sub.3 O.sub.5 343.2 344.3 146 CH.sub.3 --OCH.sub.2 CONH(CH.sub.2).sub.4 --CO.sub.2 Bn CH.sub.2 1 H C.sub.22 H.sub.33 N.sub.3 O.sub.5 419.2 420.3 147 CH.sub.3 --OCH.sub.2 CONH(CH.sub.2).sub.4 --CO.sub.2 H CH.sub.2 1 H C.sub.15 H.sub.27 N.sub.3 O.sub.5 329.2 330.3
TABLE 7 Example of Group III Calculated FAB Mass No. Structure Formula Mol. Wt. spec. [M + H].sup.+ 148 ##STR54## C.sub.32 H.sub.54 N.sub.8 O.sub.4 614.4 615.4
TABLE 8 Specific examples of compounds A-B, containing amide bond bioisosteres. FAB Mass Calculated spec. No. A-B Formula Mol. Wt. [M + H].sup.+ 149 ##STR55## C.sub.11 H.sub.21 N 167.2 168.2 150 ##STR56## C.sub.12 H.sub.20 N.sub.2 192.2 193.2 151 ##STR57## C.sub.12 H.sub.20 N.sub.2 192.2 193.2 152 ##STR58## C.sub.10 H.sub.20 N.sub.2 S 200.1 201.2
TABLE 9 Selected K.sub.i values against DP-IV. No. K.sub.i (M) 2 6.4 .times. 10.sup.-8 7 7.6 .times. 10.sup.-6 11 2.2 .times. 10.sup.-9 20 1.7 .times. 10.sup.-9 23 .sup. 5.0 .times. 10.sup.-10 35 3.7 .times. 10.sup.-8 38 9.8 .times. 10.sup.-9 44 2.0 .times. 10.sup.-9 59 1.5 .times. 10.sup.-7 66 1.8 .times. 10.sup.-7 97 .sup. 5.0 .times. 10.sup.-10 110 2.5 .times. 10.sup.-7 136 1.7 .times. 10.sup.-8 143 9.4 .times. 10.sup.-7 150 1.7 .times. 10.sup.-6
Schematic Representations for General Preparation of all Classes of Compounds

Inhibitors of DP-mediated processes, compositions, and therapeutic methods thereof


The present invention relates to an apparatus and method for encoding and decoding an image by skip encoding. The image-encoding method by skip encoding, which performs intra-prediction, comprises: performing a filtering operation on the signal which is reconstructed prior to an encoding object signal in an encoding object image; using the filtered reconstructed signal to generate a prediction signal for the encoding object signal; setting the generated prediction signal as a reconstruction signal for the encoding object signal; and not encoding the residual signal which can be generated on the basis of the difference between the encoding object signal and the prediction signal, thereby performing skip encoding on the encoding object signal.

There is a need to code an image signal so as to effectively write still pictures or moving pictures in a storage medium or effectively transmit the still pictures or the moving pictures. Various methods have been proposed so as to improve efficiency at the time of coding. As a representative method, there are a method of using temporal prediction and a method of using spatial prediction.
The temporal prediction is to detect a prediction block having the smallest residual coefficients for object blocks of a current frame from other frames temporally approaching the current frame and is referred to as inter prediction.
The spatial prediction uses reconstructed pixel values of reference blocks adjacent to object blocks within a single frame to obtain prediction pixel values of the object blocks and is referred to as intra prediction.
Deblocking filtering may not be applied to spatially adjacent reconstructed signals that are used during a process of performing the intra prediction according to the related art, such that blocking artifacts occur. In addition, the adjacent reconstructed signals use only pixels in an integer pel unit. Further, the process of performing the intra prediction according to the related art is performed by using only the object signals of coding and the adjacent reconstructed signals, such that the spatially limited intra prediction is performed.

This patent is subject to a terminal disclaimer.

Apparatus for encoding and decoding image by skip encoding and method for same

Electronics and Telecommunications Research Institute

Kwangwoon University Industry-Academic Collaboration Foundation

University-Industry Cooperation Group of Kyung Hee University


A system includes a plurality of computers interconnected by a network including one or more switching nodes. The computers transfer messages over virtual circuits established thereamong. A computer, as a source computer for one or more virtual circuit(s), schedules transmission of messages on a round-robin basis as among the virtual circuits for which it is source computer. Each switching node which forms part of a path for respective virtual circuits also forwards messages for virtual circuits in a round-robin manner, and, a computer, as a destination computer for one or more virtual circuit(s), schedules processing of received messages in a round-robin manner. Round-robin transmission, forwarding and processing at the destination provides a degree of fairness in message transmission as among the virtual circuits established over the network. In addition, messages are transmitted in one or more cells, with the round-robin transmission being on a cell basis, so as to reduce delays which may occur for short messages if a long messages were transmitted in full for one virtual circuit before beginning transmission of a short message for another virtual circuit. For each virtual circuit, the destination computer and each switching node along the path for the virtual circuit can generate a virtual circuit flow control message for transmission to the source computer to temporarily limit transmission over the virtual circuit if the amount of resources being taken up by messages for the virtual circuit exceeds predetermined thresholds, further providing fairness as among the virtual circuits. In addition, each switching node or computer can generate link flow control messages for transmission to neighboring devices in the network to temporarily limit transmission thereto if the amount of resources taken up by all virtual circuits exceeds predetermined thresholds, so as to reduce the likelihood of message loss.

The invention relates generally to the field of digital communications systems and more particularly to digital networks for facilitating communication of digital data in, for example, digital image, audio and video distribution systems and among digital computer systems. The invention is more particularly directed to flow control and scheduling arrangements for regulating the flow of information through the network to avoid congestion, prevent loss of data and preserve fairness among a plurality of devices that are transferring information over the network.
Digital networks have been developed to facilitate the transfer of information, including data and programs, among digital computer systems and other digital devices. A variety of types of networks have been developed and implemented using diverse information transfer methodologies. In some networks, such as the well-known Ethernet, a single wire is used to interconnect all of the devices connected to the network. While this simplifies wiring of the network in a facility and connection of the devices to the network, it results in generally slow information transfer, since the wire can only carry information, in the form of messages, from a single device at a time. To alleviate this to some extent, in some Ethernet installations, the network is divided into a number of sub-networks, each having a separate wire, with interfaces interconnecting the wires. In such installations, wires can carry messages for devices connected thereto simultaneously, which increases the number of messages that can be transferred simultaneously. It is only when a device connected to one wire needs to send a message to a device connected to another wire that wires in two or more sub-networks will be used, making them unavailable for use by other devices connected thereto.
To further alleviate this, networks have been developed in which communications are handled through a mesh of switching nodes. The computer systems and other devices are connected to various switching nodes. Since the switching nodes themselves are interconnected in a variety of patterns, a number of paths may be available between pairs of the devices, so that if one path is congested, another may be used. Such an arrangement may result in a network which is more complicated than an Ethernet network, but it can provide substantially higher information transfer rates, particularly if optical fiber is used as the media interconnecting the switching nodes and devices. A problem which may arise with such networks is that, in such networks, a switching node or a device, when it is receiving information from another switching node or device in the network, does not have a mechanism to provide xe2x80x9cflow-controlxe2x80x9d information to the transmitting switching node or device. While this does reduce the cost of a network, it may result in congestion, in which either a switching node may receive information at a rate faster than it can transmit it, or a destination device may receive information at a rate faster than it can buffer and process it.
The invention provides a new and improved flow control arrangement for regulating message flow in a communications network.
In brief summary, the invention in one embodiment provides a system comprising at least two devices interconnected by a network including at least one communication link. Each device includes a network interface for transferring messages over the network. At least one of the devices as a source device, transmits messages over one or more virtual circuits established over the network, and at least one other of said devices, as a destination device for the respective virtual circuits, receives the messages thereover. The network interface of the destination device includes a receive section including a buffer configured to buffer messages received over all virtual circuits for which the device is a destination device, and a destination flow control circuit. The destination flow control circuit (i) generates a virtual circuit flow control message associated with a virtual circuit for which the device is a destination device for transfer over the communication link to the source device for the virtual circuit when the portion of said buffer occupied by messages received over the one virtual circuit exceeds a selected virtual circuit flow control threshold level, and (ii) generates a link flow control message for transmission over said communication link when the portion of said buffer occupied by messages exceeds a selected link flow control threshold level. The network interface of the source device includes a transmit section configured to transmit messages over the virtual circuit(s) for which it is source device, and a source flow control circuit. The source flow control circuit (i) in response to receipt by said source device of a virtual circuit flow control message associated with a virtual circuit, disables the transmit section from transmitting messages over the virtual circuit, and (ii) in response to receipt by the source device of a link flow control message over the communication link connected thereto, disables the transmit section from transmitting messages over the communication link. Accordingly, the destination device, by transmitting the virtual circuit flow control messages for a virtual circuit when the virtual circuit""s occupancy of the buffer exceeds the virtual circuit flow control threshold level, limits the amount of its buffer resources that will be occupied by messages associated with any one virtual circuit, effectively ensuring fairness among all virtual circuits for buffer resources. In addition, the destination device, by transmitting link flow control messages, will ensure that the buffer does not overflow, which can result in message loss.
In another embodiment, the network includes a switching node which forms part of the path for one or more virtual circuits between the source device and the destination device. The switching node is connected to receive messages transmitted by the source device over the virtual circuit(s) for which it forms part of the path over one communication link connected thereto, buffer the received messages in an internal buffer, and transmit the buffered messages over the virtual circuit(s) over another communication link connected thereto, thereby to forward messages for the virtual circuit(s) downstream over the respective virtual circuit(s). If the switching node receives a virtual circuit flow control message for a virtual circuit over the communication link over which it would transmit messages over the virtual circuit, it will forward the virtual circuit flow control message over the communication link over which it would receive messages for the virtual circuit, thereby to forward the virtual circuit flow control message upstream over the virtual circuit. If the switching node receives a link flow control message over a communication link, it will stop transmitting messages thereover. In addition, if the occupancy of the switching node""s buffer by messages from a particular virtual circuit exceeds a selected virtual circuit threshold level, which in one embodiment varies based on the number of virtual circuits for which the switching node forms part of the path, the switching node will generate and transmit a virtual circuit flow control message over the communication link over which it would receive messages for the virtual circuit, thereby to forward the virtual circuit flow control message upstream over the virtual circuit to disable the source device for that virtual circuit from transmitting messages thereover. If the occupancy of the switching node""s buffer exceeds a selected link threshold level, the switching node will generate and transmit link flow control messages over the communication links connected thereto over which it receives messages. Accordingly, the switching node, by transmitting the virtual circuit flow control messages for a virtual circuit when the virtual circuit""s occupancy of its buffer exceeds the virtual circuit flow control threshold level, limits the amount of its buffer resources that will be occupied by messages associated with any one virtual circuit, effectively ensuring fairness among all virtual circuits for buffer resources. In addition, the switching node, by transmitting link flow control messages, will ensure that its buffer does not overflow, which can result in message loss.

System and method for regulating message flow in a digital data network


A mixing apparatus, puncturing mechanism, and cartridge are disclosed. The mixing apparatus has a housing and a drawer with a recess. Corresponding cartridges may be inserted into the drawer and slid into the housing to facilitate mixing a liquid with contents of the cartridge. The liquid may originate from a reservoir in the mixing apparatus or a direct line. Also inside the housing of the mixing apparatus is the puncturing mechanism. The puncturing mechanism has a nozzle configured to puncture a lid of a cartridge and inject liquid to mix with the contents of the cartridge. The puncturing mechanism is further configured to drive an internal puncturing unit inside of the cartridge through a lower portion of the cartridge to allow liquid from the nozzle and contents of the cartridge to be dispensed into a receptacle.

Many mixtures that are made for human consumption require a minimal level of care in mixing together the mixture ingredients. However, in many instances, the quality or character of the mixture can be inadvertently compromised if the minimal level of care is not used in mixing the ingredients of the mixture. For example, the mixing ratios may be improper due to mixing an incorrect amount of liquid (e.g., water) with a mixture ingredient (e.g., concentrate). The temperature of the liquid mixed into the mixing ingredient may be incorrect making consumption of the mixture difficult or unpleasant, and in some cases, causing incomplete dissolution of the mixture ingredient in liquid. Moreover, when making the same mixture at several different times, the resulting mixtures may be inconsistent, for example, the mixtures made at different times may have different mixing ratios and may be made at different mixing temperatures.
In many instances, variations in the quality and character of the mixture is not the result of carelessness, but of the circumstances at the time the mixture is made. For example, where the mixture is an infant nutritional supplement, such as formula, mixing may occur in the middle of the night or under urgent time constraints due to the demands of the infant. Fatigue or the rushed nature of the situation can detrimentally affect the level of care the parent uses when mixing the formula. As known, maintaining consistency of the quality of the formula consumed by the infant is desirable for the health and well being of the infant.
Machines for automated mixing have been developed to address some of the problems presented by manually mixing. The machines automate the dispensing of the appropriate amount of water and at the correct temperature during mixing with the mixture ingredient. The resulting mixture is dispensed into an awaiting receptacle. Some of these machines are designed for mixing a single serving of a mixture, for example, single servings of coffee. In such machines, single serving cartridges are used that contain a mixture ingredient to be mixed with water, the quantity and temperature of which is controlled by the machine. Other machines have a larger container with multiple servings of a mixture ingredient (e.g., "bag-in-box"), which is dispensed under the control of the machine and mixed with an appropriate amount of water and at the correct temperature.
Although these machines automate the mixing process, the machines are often designed in such a way that residue from the mixture remains on part of the machine after the mixture is mixed and dispensed. For example, some machines have a channel, tube, or guide that guides a mixture to an opening where the mixture is dispensed into a receptacle. In other machines, a device that punctures a container to allow the ingress and egress of water during the mixing operation comes into contact with the container contents. As a result, residue from a previous mixing operation may contaminate the mixture of a current mixing operation. This is an issue particularly relevant to machines that mix single-servings of mixtures. Where the mixture ingredient is perishable, the residue may create an environment for the growth of bacteria or other organisms, which will be introduced into subsequently made mixtures and may present health concerns. In these types of machines, regular cleaning and maintenance is necessary to maintain a sanitary condition.

Apparatus and method for preparing a liquid mixture


A wireless caller identification system employing master and remote units. Microcontrollers at both master and remote units facilitate secure communications between units, providing the identity of the source of calls received at the master unit over a connected telephone line from a telephone central office. Radio frequency (RF) or infrared (IR) modes of communication may be used.

1. Field of the Invention
The present invention is drawn to subscriber telephone apparatus, and more particularly to a caller identification device which displays the caller's telephone number and name, or similar identification, and then distributes the displayed information to remote areas by means of a wireless medium.
2. Background Art
Many telephone companies throughout the world are now offering calling number display features (CND) as part of optional service to regular telephone subscribers. In the usual arrangement, and particularly in the United States, many operating companies providing this service provide a device to the customer, or telephone subscriber, which provides identification of the calling party via a visual display connected to the telephone line. This feature allows the user to screen incoming calls and answer only when desired. With this arrangement, the telephone system provides from the telephone central office a set of signals during the ring cycle which are decoded at the customer's premises and displayed on the calling number display.
As outlined above, the arrangement described is quite satisfactory for a single subscriber, but is not applicable to telephone systems wherein a number of stations are connectable to the same telephone line. There are a number of techniques provided to overcome this particular drawback, and accordingly a search of the background art directed to the subject matter of the present invention conducted in the U.S. Patent and Trademark Office disclosed the following U.S. Letters Patent:
______________________________________ 4,942,598 5,228,073 5,063,588 5,274,699 5,070,521 5,327,486 5,155,759 5,375,161 ______________________________________
U.S. Pat. Nos. 4,942,598 and 5,375,161 both deal with paging systems employing wireless communication medium as a means for accessing parties to be paged. U.S. Pat. No. 4,942,598 also includes a caller number identification system, while U.S. Pat. No. 5,375,161 includes a memory for storing electronic signals representative of telephone network addresses.
U.S. Pat. No. 5,063,588 provides the identity of a calling subscriber to the called subscriber by requiring the calling subscriber to identify himself to a central station requesting access to communication resources. The central station then forwards the identity of the calling subscriber to the called subscriber enabling the called subscriber to decide whether to answer the call or not. Radio frequency communication links are utilized once a connection is established between the two subscriber units.
U.S. Pat. No. 5,070,521 pertains to wireless communication and the method for identifying the origin of calls through the communication unit. Calls from the telephone network typically provide a special prefix or suffix to alert the subscriber the call was made from the telephone network as a means to alert the operator.
U.S. Pat. No. 5,155,759 deals with simultaneous calling request signals for a plurality of portable telephones. When simultaneous requests are sent to portable telephones, any telephone that is busy will not receive the request. The requester will thus be aware that the busy telephone has not received the request . Accordingly, the response of any receiving portable telephone will be returned to the requester or calling party, followed by means of a display signal.
U.S. Pat. No. 5,228,073 discloses a caller identification display system with remote user units. It is indicated that the communication between the master and the remote may be by conventional interface electronics located in the reception unit with the remote units interconnected by cables, or by means of radio frequency or laser transmitter and receiver system.
U.S. Pat. No. 5,274,699 teaches a device that allows a signalling word to be transmitted from the transceiver section to the central controller indicating that it wishes to transmit. After this a central station accesses a data base to check for the identification transmitted by the requesting unit. The controller then selects the appropriate displayable source indicator and provides such display to the recipient unit.
U.S. Pat. No. 5,327,486 deals with an automated reception arrangement which utilizes a computer in a wireless system. In the arrangement taught, the name of the calling person is presented after which a reception judgment is made as to whether or not the call is important enough to notify the person being called by means of a wireless link.
None of the above units are believed to teach or claim a system like that disclosed herein.
Accordingly, it is the object of the present invention to provide a new and improved caller identification system which discloses a method to receive, display, process, and distribute caller information to remote areas.

Wireless caller information processing system


An information processing device includes: a display portion that can display a plurality of icons including first information; a detection portion that detects a contact to the display portion; and a control unit that, in a case in which the detection portion detects a contact having a trajectory encircling at least one icon displayed on the display portion in a state in which the icons are displayed on the display portion in a first display mode, displays the at least one icon in a second display mode with a greater display area and displays the at least one icon in a central region of the display portion.

The present disclosure relates to an information processing device that enlarges and reduces an image displayed on a display portion and an image forming apparatus that is provided with the information processing device.
An information processing device is known that is provided with a touch screen composed of: a display portion that displays an image; and a detection portion that detects contact by an object to the display portion. Such an information processing device is known that enlarges an image displayed on the display portion if a circle is drawn in a clockwise direction by a user's finger in contact with the display portion; and reduces the image displayed on the display portion if a circle is drawn in a counterclockwise direction by the user's finger (Related Art 1).
However, Related Art 1 discloses only enlargement and reduction of an entire image displayed on the display portion and does not disclose enlargement and reduction of only a part of an image (for example, a specific icon) that interests a user.

Information processing device and image forming apparatus


A receiver body is provided herein having a plurality of barrel-tightening portions with at least one relief recess therebetween and relief recesses defined in the body on either proximal end. The relief recesses and barrel-tightening portions are sized to allow the barrel-tightening portions to be tightened and loosened independently of each other.

Firearms include a receiver, an action, a trigger mechanism, and a barrel. The barrel is often threaded to one end of the receiver. The manner in which the barrel is secured to the receiver may result in significant variations in the amount of stress at the coupling locations as well as variations of stress at other locations within the receiver. Significant variations in stress and/or strain may cause shortened functional life of the firearm or degradations in accuracy.
The subject matter claimed herein is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one exemplary technology area where some embodiments described herein may be practiced.


A window blind cord control apparatus for controlling the disposition of a set of two or more closely gathered cords extending out from an opening in a headrail and extending longitudinally through the headrail to separate positions where they are respectively attached to a window blind for raising and lowering the blind, including a headrail comb defining an array of parallel slots for receiving and guiding the gathered cords, for placement within the headrail near the opening from which the cords extend for preventing the gathered cords from becoming raveled within the headrail; and a cord collector for collecting the cords extending out from the opening in said headrail. The cord collector includes a multiple spool reel for respectively winding the cords on separate spools; a spring for biasing the reel for winding the cords onto the spools; a sleeve for gathering the cords; and a cord collector comb defining an array of parallel closed-end slots for receiving and guiding each of the gathered cords. The cord collector comb is placed between the sleeve and the reels for preventing the gathered cords from becoming raveled outside of the headrail.

The present invention generally pertains to cord-controlled apparatus for varying the disposition of a window blind, and is particularly directed to an improvement in such apparatus for controlling the disposition of the cords themselves to prevent closely gathered cords from becoming raveled.
A cord-controlled window blind apparatus, essentially includes a window blind; a set of cords coupled to the blind for raising and lowering the blind by operating the cords; a headrail from which the blind may be suspended and through which the cords extend longitudinally to separate positions where they are respectively attached to the blind. The headrail also contains an opening at which the cords are closely gathered out from which the cords extend.
A locking device is disposed in the headrail adjacent the opening for clamping the cords to hold the blind at whatever height it has been moved to by operation of the cords.
The types of window blinds that typically are controlled by such an apparatus include venetian blinds and woven wood blinds. A particularly popular type of venetian blind controlled by this type of apparatus is commonly known as "Levalors". In the cord control apparatus, two or four separate cords are used to control the raising and the lowering of the blind. These cords are gathered and extend from the opening in the headrail that is adjacent the locking device and have a tendency to become raveled.
Raveling of the cords has not been a significant problem in cord-controlled window blind apparatus having only two cords. It is when there are more than two cords that the cords become so raveled as to impair smooth operation of the apparatus.


A railroad car wheelset (10) has an axle (12) with one wheel rigidly attached as in conventional railroad practice. This wheel (10) is permitted to rotate by means of journal bearings either on the extreme ends of the axle (12) or inboard of each wheel location (14A and 14B). At the location of the other wheel, the axle (12) is provided with a smooth surface and a self-lubricating bearing (24) is provided as a pant of a hub (20) on the axle (12). The axle (12) shaft is provided with a boss (18) or other means of preventing the independently rotating wheel from migrating laterally out of proper alignment A self-lubricating thrust bearing (32) is located between this boss (18) and the side of the wheel to eliminate any possible galling between the two moving surfaces. A removable retainer plate (46) is located on the other side of the independently rotating wheel to prevent the wheel from moving laterally in that direction. Adjacent the removable retainer plate (46) is an electrical contactor which can conduct an electrical current from the wheel to the axle shaft, to permit the wheelset (10) to properly operate railway signals or other systems dependent on electrical continuity. In lieu of the self-lubricating bearings, the bearings can be comprised of a lubricant coating permanently bonded to the bearing surface of the hub (20) adjacent the independently rotatable wheel. An alternate embodiment uses a separate hub (60) press-fit on the axle.

Wheelsets for railroad cars are usually comprised of an axle and two wheels. The wheels are pressed on to the axle shaft and are rigidly mounted so that both wheels turn exactly the same degree of rotation during operation. The wheelset assembly may be supported by journal bearings outboard of each wheel or the bearings may be located inboard of the wheels. The rigid assembly of the wheels on the axle and the lack of independent rotation of the wheels is the cause of slippage on the rail when the wheelset operates in curved sections of track. This slippage causes wear on the wheel treads and rails and is a prime cause of corrective maintenance on both the wheels and the track.
Efforts have been made to overcome the problems associated with the rigid assembly of conventional wheelsets by placing bearings between the axle and the wheel on at least one end of the axle to permit differential speeds of rotation of the wheels at opposite ends of the axle. In such cases, a hub is located on at least one end of the axle and a wheel is mounted on the hub or on the axle and its rotation with respect to the axle is facilitated by a bearing assembly. As discussed hereafter, electrical continuity from the two rails through the wheels and the axle is necessary for operation of signal devices or the like. This electrical continuity was established with the conventional railroad wheelsets wherein the wheels were rigidly fixed through opposite ends of the axle. However, with the advent of one of the wheels being mounted on the axle by means of a bearing assembly, the electrical continuity between the wheels was less than perfect. With the advent of non-metal bearings, the electrical continuity was not possible.
A typical signal device for a road crossing, for example which utilizes a crossing arm, flashing lights, and the like, derives electrical energy from any conventional source. A low voltage is imposed on a given dedicated length of rail on opposite sides of the signal, with the opposite rail being electrically connected to the signal whereupon the signal circuit is closed when the wheel assembly of a train initially moves onto the dedicated length of rail. The circuit is completed between the opposite rails through the wheels and axle of the train""s wheel assemblies which allow the flow of energy therethrough to electrically connect the opposite rails.
The wheels are conventionally secured to hubs that are integral with the axles. These integral hubs require a single billet of material which is large in diameter and which requires substantial machining to achieve correct final dimensions, which is expensive.
It is a therefore a principal object of this invention to provide a railroad wheelset with independent rotation of wheels with respect to each other which will consistently retain the electrical continuity between the opposite wheels and the rails upon which they are supported.
A further object of this invention is to provide a wheelset with independent rotation of the wheels with respect to each other which can be used in existing truck designs without modification to the truck structures or the braking system.
A still further object of this invention is to provide a railroad wheelset which requires no additional maintenance than conventional rigid wheelsets after installation and during service.
A still further object of this invention is to provide a railroad wheelset with independently rotating wheels in which the differential action is made available with no decrease in safety or reliability.
A still further object of this invention is to provide a railroad car wheelset with independent wheel rotation which can be economically manufactured and applied to railroad cars of all types.
A still further object of this invention is to provide a railroad car wheelset with independent wheel rotation wherein the bearings for the independently rotatable wheel is comprised of a lubricating coating.
A still further object of this invention is to provide press-on hubs for the axles in lieu of integral hubs.
These and other objects will be apparent to those skilled in the art.
The railroad car wheelset of the present invention includes an axle with one wheel rigidly attached as in conventional railroad practice. This wheel is permitted to rotate by means of journal bearings either on the extreme ends of the axle or inboard of each wheel location. At the location of the other wheel, the axle is provided with a smooth surface and a self-lubricating bearing is provided. The axle shaft is provided with a boss or other means of preventing the independently rotating wheel from migrating laterally out of proper alignment. A self-lubricating thrust bearing is located between this boss and the side of the wheel to eliminate any possible galling between the two moving surfaces. A removable retainer plate is located on the other side of the independently rotating wheel to prevent the wheel from moving laterally in that direction. Adjacent the removable retainer plate is an electrical contactor which can conduct an electrical current from the wheel to the axle shaft, to permit the wheelset to properly operate railway signals or other systems dependent on electrical continuity. In lieu of the self-lubricated bearings, the bearings can be comprised of a lubricant coating permanently bonded to the bearing surface of the hub adjacent the independently rotatable wheel. The hubs are either integral with the axle, or pressed on the axle.

Differential action railroad car wheelset


Techniques are described for an adaptive low density parity check (LDPC) decoder. The techniques include receiving a first set of values corresponding to a first low density parity check codeword and noise, performing a first plurality of iterations of an iterative decoding algorithm using a first set of decoding parameters to decode the received first set of values, comparing a metric with a first threshold, and upon determining that the metric is larger than the threshold: selecting a second set of decoding parameters for the iterative LDPC decoder and performing a second plurality of iterations of the iterative LDPC decoding algorithm using the second set of decoding parameters to decode the received first set of values and generate a first set of decoded bits.

Error correction codes (ECC) are used to detect and/or correct errors in received data in order to increase performance and efficiency of systems. Low-density parity check codes (LDPCs) are a class of ECC codes that have very good performance. LDPC codes are used in storage systems, communication systems, and the like to reduce power consumption while allowing higher throughput, and/or increased reliability.


A dual clutch transmission, in particular of a motor vehicle, includes a hydraulic circuit for cooling the dual clutch transmission, wherein the hydraulic circuit includes at least one pump for conveying a hydraulic medium flow, at least one cooler for cooling the hydraulic medium flow, and a volume control valve for adjusting the hydraulic medium flow for at least one cooling system associated with clutches of the dual clutch transmission. The volume control valve is designed to convey the hydraulic medium flow in a first switching state to a first cooling system associated with a first of the clutches, and in at least one second switching state to a second cooling system associated with a second of the clutches.

The invention relates to a dual clutch transmission, in particular of a motor vehicle, with a hydraulic circuit for cooling the dual clutch transmission, having at least one pump for conveying a hydraulic medium flow, at least one cooler for cooling the hydraulic medium flow, and a volume control valve for adjusting the hydraulic medium flow for at least one cooling system associated with the clutches of the dual clutch transmission.
The invention further relates to a method for operating a dual clutch transmission, in particular as described above, with a hydraulic circuit for the cooling of the dual clutch transmission, wherein a hydraulic medium flow is conveyed with a pump and cooled by a cooler, and wherein the hydraulic medium flow for at least one cooling system associated the dual clutch transmission is adjusted by a volume control valve.
Dual clutch transmissions are preferably used in passenger cars. A dual clutch transmission generally has two coaxially disposed transmission input shafts, wherein each is associated with a corresponding sub-transmission. A clutch is associated with each of the transmission input shafts, with which the transmission input shaft of the respective sub-transmission can be frictionally coupled to the output of an engine, preferably an internal combustion engine of a motor vehicle.
Typically, one of the sub-transmissions is active while driving, which means that the transmission input shaft associated with this sub-transmission is coupled to the engine via its associated clutch. A gear providing a current gear ratio is engaged in the active sub-transmission. A controller determines whether the next higher or next lower gear is to be engaged depending on the driving situation. This gear which will probably be used next is selected in the second, inactive sub-transmission. When changing gears, the clutch of the inactive sub-transmission is engaged, while the clutch of the active portion is disengaged. Preferably, opening of the clutch of the active sub-transmission and closing of the clutch of the inactive sub-transmission overlap so that the flow of force from the engine to the drive shaft of the motor vehicle is not at all or only briefly interrupted. As a result of the gear change, the previously active sub-transmission becomes inactive, while the previously inactive sub-transmission becomes the active sub-transmission. Thereafter, the gear expected to be used next can be engaged in the now inactive sub-transmission. The operation of a dual clutch transmission is otherwise known and will therefore be discussed here in detail.
Usually, the cooling systems of the clutches are served by a fixed displacement pump driven by an internal combustion motor. At least one control or regulating valve is used for adequate cooling of the clutch. The accuracy of the volume flow used for cooling the clutch depends strongly on the employed control or regulating valve. Typically, the hydraulic medium conveyed by the pump is cooled by a cooler and subsequently supplied to the cooling system associated with the clutches, so that only a single cooling medium volume flow is provided for the two clutches. The common cooling system for the clutches thereby worsens the control performance of the clutches.

Hydraulic circuit, method for operating the same


Sport equipment, for example in boot form, consists of a pair of sole plates, each having two gliding edges along its sides. To permit both gliding or skating steps and ordinary walking, the present invention provides for sole plates whose width increases from the toe end to the part for the ball of the foot and then remains the same to the heel end. The underside of the sole plate has a generally flat standing surface from the heel end to the part for the ball of the foot, and a walking surface that slopes up from there to the toe end. The heel end may be formed as a heel-brake skid and the toe end may be formed as a spade tip. The equipment may be made either in the form of boots, or as a pair of sole plates with suitable means of attachment to shoes or boots.

Proposals for sport equipment of a similar kind are already known, for example DE-OS 19 43 298, CH-PS 651 478, which is worn on the feet and is supposed to permit gliding or skating steps on snow-covered flat or sloping surfaces. However, such known equipment has to date not achieved a breakthrough, generally because the design of the sole plates inhibited smooth, flowing motion. Apparently, straight, parallel gliding edges running from the toe end to the heel end have been regarded as necessary, but in this known type of equipment the relatively wide front part of the sole prevents or makes it difficult to change step from one foot to the other, as in normal walking or, for example, in skating.
The present invention, therefore, attempts a further development of the type of winter sport equipment described, in such a way as to allow its ready use free from such limitations, in the most varied types of terrain and conditions, in the execution of gliding steps and including so-called skating steps on flat ground and swinging turns in descent, as well as normal walking.


A Self-Aligning Zipper is disclosed that allows for one handed operation by anyone who would, otherwise use a zipper or use of the Self-Aligning Zipper by those with physical and developmental limitations or equipment such, as cold weather gloves or mittens. The proper alignment of each half of the Self-Aligning Zipper is accomplished by way of magnets of opposite polarity along with structural guide elements to ensure proper alignment and operation of the zipper.

1. Field of the Invention
The present invention relates generally to fastening devices, and more particularly to a Self-Aligning Zipper that allows for alignment and closure with one hand.
2. Description of Related Art
The common zipper was invented more than 100 years ago. In 1851, Elias Howe, who also invented the sewing machine, received U.S. Pat. No. 8,540 for an "Automatic Continuous Clothing Closure." Through lack of marketing, Howe's closure device gained little acceptance. Years later, Whitcomb Judson marketed a "Clasp Locker" (U.S. Pat. Nos. 504,038 and 504,037) and started the Universal Fastener Company, but the product again met with little commercial success. Then in 1906 Gideon Sundbäck, a Swedish-American electrical engineer, was hired by the Universal Fastener Company. In 1913 he had designed what has come to be known as the modern zipper. The patent for his "Separable Fastener" was issued in 1917 as U.S. Pat. No. 1,219,881.
The term "Zipper", however, was popularized by the B.F. Goodrich Company when they used Sundbäcks fastener on a new type of rubber boots. For nearly twenty years, the zipper was used primarily for rubber boots and closures on tobacco pouches. It was not until the 1930's that the zipper became popular on garments. Today the zipper is by far the most popular fastener. The zipper is found on clothing such as jackets, luggage, bags, camping equipment, and many other objects. Zippers can be found on all types of clothing such as pants, dresses, and jackets, on carriers such as bags and luggage, and in gear such as sleeping bags and tents. In addition to serving as decoration, zippers can join together two sides of a garment, such as in the operation of a dress, and can serve as means to removably attach two pieces of fabric, such as in the attachment of a removable hood to a jacket.
Fastening devices such as zippers can be separating or non-separating, and can be one-way or two-way devices. In a separating zipper, each of the two zipper tracks, comprising the tape and attached teeth, are connected to different elements that are primarily joined only by the interlocking zipper teeth. In a non-separating zipper, both zipper tracks are connected to a single element such that interlocking and unlocking the zipper teeth creates an opening in that element. A two-way zipper comprises two slider bodies that can work together or separately to interlock and unlock the zipper teeth. A one-way zipper comprises a single slider body as well as a pin and box assembly that aligns the zipper teeth contained on at least one of the zipper tracks.
In their simplest form, one-way separating zippers are composed of relatively few parts, including: an origination assembly with a pin and a retainer body at the lower limit of each row of zipper teeth; two pieces of tape that are attached to fabric on one side and contain zipper teeth on the other; a slider body with a pull-tab; and two top stops at the upper limit of each row of teeth.
To fasten two pieces of fabric together, the operator inserts the pin from the lower limit of one row of teeth into the retainer box at the matching lower limit of the other row of teeth. This aligns the teeth into an operable interlocking format. Once aligned, the operator pulls the latching mechanism, called the slider body, along the teeth track. Wedges inside the slider body force the teeth of each track to interact. If the teeth are aligned, the hook of each tooth settles into the hollow of an opposing tooth. The operator can continue to pull the slider body and interlock the teeth until the slider terminates at the top stops located at the upper limit of each row of teeth.
To unfasten the pieces of fabric, the operator pulls the slider body back along the closed track. The wedges inside the slider body force the interlocking teeth apart and separate the zipper closure.
Despite the ease with which zipper-type closures operate, many individuals encounter difficulty joining together the pin and body. Others may have difficulty grasping the small slider body or pulling it along the zipper's teeth. Examples of individuals who often encounter these difficulties include small children, people wearing gloves for protection, elderly, and people with poor vision, macular degeneration, or cataracts. Additionally, people with disabilities such as arthritis, multiple sclerosis, cerebral palsy, pervasion developmental disorders, Down's syndrome, ataxia, diabetes with neuropathy, stroke (CVA), paraplegics, Lou Gehrig's Disease, Parkinson's, and other ailments can also find the operation of zippers to be difficult.
There has been very little advancement in technologies relating to zippers since their first introduction more than 100 years ago. U.S. Pat. No. 8,146,214 to Peters et al. describes a zipper that is improved over the basic zipper design of Gideon Sundbäck, the entire disclosure of this published application, and any and all continuations, divisionals, continuations in part, and issued patents resulting therefrom being incorporated herein by reference in their entirety.
It is therefore an object of the present invention to provide an improved zipper that allows for easy alignment and closure, it is another object of the present invention to provide an improved zipper for one handed operation. It is another object of the present invention to provide an improved zipper for use by individuals with limited dexterity. It is another object of the present invention to provide an improved zipper that can be used while wearing gloves or mittens. It is yet another object of the present invention to provide an improved zipper that can be operated easily by small children. These and other objects of the present invention are not to be considered comprehensive or exhaustive, but rather, exemplary of objects that may be ascertained after reading this specification with the accompanying drawings and claims.


A compact, easily transportable, surface preparation apparatus which includes a surface treatment unit having a cutter drum powered by its own power source. The apparatus includes transport/support wheels and a tow bar preferably interconnected at each end, of the surface treatment unit the rearward connection being a pivotal connection. The surface treatment unit has a longitudinal axis and a transverse axis, with the longitudinal axis perpendicular to the towing direction and the transverse axis coincident with the towing direction. The cutter drum has a rotational axis and is contained within the surface treatment unit and arranged such that the rotational axis is parallel to the longitudinal axis of the surface treatment unit. The cutter drum is off-set relative to the transverse axis of the surface treatment unit such that the cutter drum operates at one end of the surface treatment unit. The surface treatment unit is pivotally attached to the tow bar to enable the surface modifier to operate adjacent edges of a surface to be treated e.g., the shoulder of a road surface. The height and sideways tilt of the surface treatment unit may be adjusted as desired to produce surface profiles of different configurations.

The present invention relates to a surface preparation apparatus (SPA) for asphalt, concrete and other road surfaces, and in particular to a surface preparation apparatus which can be towed by various vehicles, which can be offset with respect to the direction of towing, and which can be adjusted in three axes. The preferred SPA is an asphalt reclaiming unit for being towed behind a truck of other prime mover.
Road surfaces, particularly asphalt road surfaces form a majority of road surfaces in the United States. Asphalt is also used in other applications, such as parking lots, biking paths and walking paths. A problem with asphalt is that is has a limited, useful life. When that useful life has been exceeded, the surface must be replaced or rehabilitated. Often, it is not desirable or cost effective to rehabilitate the entire road surface, particularly when only portions or segments of a paved section have deteriorated. As a result, the road surface is allowed to continue to deteriorate until use of a conventional full surface resurfacing unit becomes cost effective. The need to wait until the use of conventional resurfacing units becomes cost effective, results in temporary repairs such as patching, which are not as desirable as resurfacing. However, without a more cost effective manner resurfacing small areas, or portions of larger areas, resurfacing which might otherwise be completed if smaller, more flexible resurfacing units were available, will be delayed. Furthermore, there will be a tendency to redo surfaces which might not need to be done because only larger areas can be accommodated by the larger conventional units. Conventional units tend to be very large and heavy. They are often self propelled or attached to existing vehicle frames. The power for such units is generally supplied by one unit which means that some of the power is used to drive the vehicle and some of the power is used in the surface treatment apparatus. For this reason, those units are very slow. In addition, they can only be used to resurface large areas. It will be appreciated, therefore, that a need exists for a device for moving at greater speeds and preparing on a variety of surfaces such as shoulders, crowns, transitions, pipe lines, pot holes and the like.
Accordingly, it will be appreciated that there is a need for an efficient way of resurfacing asphalt, concrete and other surfaces used for roadways, walkways, parking lots and the like. The present invention provides advantages over the prior devices and the prior methods used to resurface these and other surfaces, and also offers other advantages over the prior art and solves other problems associated therewith.

Surface preparation apparatus and method of using the same


A supporting apparatus for an optical scanning apparatus includes an optical source which emits an optical beam. A deflector deflects the optical beam from the optical source. A focusing lens focuses the optical beam from the deflector. An optical housing is provided with the optical source, deflector and the focusing lens. A positioning device supports the optical housing and positions the optical housing, relative to a frame. An adjusting device moves an end of the optical housing in a sub-scanning direction so that an inclination of the optical housing in the sub-scanning direction can be adjusted.

1. Field of the Invention
The present invention relates to a supporting apparatus for an optical scanning apparatus which may be utilized in a laser printer, a digital copying machine, a laser facsimile machine, etc., and more particularly to a supporting apparatus for plural optical scanning apparatus.
2. Discussion of the Background
One of a conventional optical scanning apparatus includes an optical housing in which a laser source, a deflector having a polygon mirror, and a focusing system are installed. In the optical scanning apparatus, a laser beam emitted from the laser optical source is deflected by the polygon mirror and is focused on, for example, a scanning surface of a photoconductive element by a focus lens of the focusing system. Such an optical housing for an optical scanning apparatus includes a mounting reference surface for a polygon motor which is one element of a deflecting device and for an optical system. The polygon mirror and the optical system are often mounted on the reference surface in a vertical direction. Further, there is a conventional image forming apparatus which is composed of plural optical scanning apparatus, such as a color image forming apparatus. In the color image forming apparatus, the plural optical housings are installed as a frame structure.
In order to compensate for an inclination error in a sub-scanning direction, a relation between the scanning surface and each optical scanning apparatus needs to be adjusted accurately. However an adjustment work is difficult because of a rigidity of the optical housing, the frame, etc., and because an adjustment structure is large. Especially, when the plural optical scanning apparatus are installed and plural image forming stations are required in order to form the color image, the adjustment structure is much larger.
Therefore, as described in Japanese Laid Open Patent Nos. 4-131872 or 4-131876, it is proposed that an error of an image with respect to a reference image forming station is compensated for by a method that an angle of a mirror for returning a laser beam is changed by actuators. However, as plural actuators are needed in order to change the mirror in the apparatus, the structure is complicated and the assembly time increases.

Supporting apparatus for optical scanning apparatus


The present invention relates to processes to produce nanocomposites. In particular, the invention relates to solution processes using organic solvents and mixtures of solvents to produce polymeric nanocomposites.

Nanocomposite materials have been the subject of much academic and industrial literature due to a large extent on their ability to impart new properties for a given a material. In particular, polymeric nanocomposite materials have been of considerable interest. As used here, nanocomposites or polymeric nanocomposites are typically polymer systems containing inorganic particles with at least one dimension in the nanometer range of the polymer matrix.
Although much work has been done with nanocomposites, only a few methods have been suggested for producing nanocomposites much less a method that would lend itself to producing nanocomposites on a commercial scale such as through in situ production. For example, melt blending has been a method of choice in the art. See e.g., U.S. Pat. Nos. 5,807,629, 6,060,549, WO 02/100935, and WO 02/100936.
In other areas, aqueous solutions are used to produce coatings comprising, inter alia, an elastomer and a dispersed exfoliated layered filler. See e.g., U.S. Pat. No. 6,087,016 and U.S. Patent Application Publication No. 2003/0198767 A1. See also U.S. Pat. No. 5,576,372 (Example 1).
In yet another area, U.S. Pat. No. 6,339,121 discloses, inter alia, a polymer blend composition including a first polymer and a second polymer, which are immiscible, and a compatibilizer. The compatibilizer includes an organoclay, which has been functionalized by an intercalation agent, whereby it has an affinity for each of the polymers. The intercalation agent is a reaction product of a polyamine and an alkyl halide in a polar solvent. The preferred alkyl halides are alkyl chloride and alkyl bromide and the preferred polar solvents are water, toluene, tetrahydro furan, and dimethylformamide.
However, past endeavors have yet to provide for processes to produce polymeric nanocomposites that provide for optimal flexibility in producing a finished product and/or lend themselves to commercial production such as, for example, providing processes that allow for high throughput and/or simplicity in design when combining the reactor system with downstream finishing processes.

Polymeric nanocomposites and processes for making the same


A refresh leveraging driving method is provided which includes deciding a unit of word lines to be driven at a refresh leveraging operation to be the same as a redundancy repair row unit setting a lower row address of an input refresh leveraging address corresponding to the decided refresh leveraging row driving unit to a don't care state; and internally generating the don't care lower row address of the refresh leveraging address to drive word lines according to a combined refresh leveraging address.

The inventive concepts described herein relate to a semiconductor memory, and more particularly, relate to a volatile semiconductor memory device and a refresh leveraging driving method thereof.
If at least one memory cell in a semiconductor memory device, such as a dynamic random access memory DRAM), is defective, the semiconductor memory device may not perform a required function normally. In this case, the semiconductor memory device may be discarded. However, discarding semiconductor memory devices due to a few defective memory cells is inefficient in terms of a yield.
A semiconductor memory device may include redundancy memory cells. When the semiconductor memory device includes defective memory cells, the defective memory cells may be replaced with the redundancy memory cells of the semiconductor memory device. In this case, the semiconductor memory device may continue to be used. This may mean that a yield may be improved.
A repair operation of a memory device using redundancy memory cells may be accomplished by replacing defective memory cells with redundancy memory cells by a row/column unit. If defective memory cells are detected at a test level after a wafer is processed, addresses of the defective memory cells may be replaced with addresses of redundancy memory cells. In the case that an address signal corresponding to a defective line is received, it may be provided to a spare line instead of the defective line. A row repair operation may be performed through a repair logic circuit, for example, by a unit of four word lines.
A general refresh leveraging (GRL) scheme for reinforcing the refresh ability may be applied to a semiconductor memory device (e.g., DRAM) to improve a data retention characteristic of a weak memory cell. Memory cells determined to be soft failed at a test level may be not repaired with redundancy memory cells but used as normal memory cells. Soft-failed memory cells, that is, weak memory cells may be specifically managed in comparison with normal memory cells. If the GRL scheme is used, weak memory cells may be refreshed more frequently in comparison with normal memory cells at a refresh mode of operation. In general, a GRL operation may be performed by a word line unit.

Semiconductor memory device and refresh leveraging driving method thereof


A method, a processing device, and a computer program product are provided. In various embodiments, a computing device reads predefined policy information defining one or more conditions for restarting a container. The computing device monitors the container to detect an occurrence of any one of the one or more conditions defined by the predefined policy information. The computing device automatically restarts the container after detecting the occurrence of any one of the one or more conditions defined by the predefined policy information. In some embodiments, the computing device waits a certain amount of time, as specified in the predefined policy information, before automatically restarting the container.

Present invention embodiments pertain to containers residing on a computing device and, more specifically, to automatic restarting of a container according to a container restart policy that specifies one or more conditions of a container, which, when detected, causes the automatic restarting of the container.
A container is a computing unit that includes at least one application and all dependencies, but shares a kernel with other containers running as isolated processes in user space on a host operating system. Containers do not imply any specific infrastructure: containers of various kinds run on various computers and in various infrastructure, including cloud infrastructure.

International Business Machines Corporation


A loudspeaker design for use in transmitting and receiving sound waves is disclosed. The loudspeaker consists of a basket (12) and magnet assembly (14). The magnet assembly consists of a sandwich of front (16) and back (20) plates on either side of a ring-shaped ceramic magnet (18). The back plate (20) has a pole piece (22) projecting outward therefrom. The ceramic magnet (18) has a center aperture. The magnet (18) is affixed to back plate (20) concentrically around the projecting pole (22). The front plate (16) is circular in shape and also has a center aperture (31). A centering device and shield (24) is placed concentrically around the projecting pole (22) and is adjacent to the inside surface of the back plate (20), the inner surface of the aperture (30) within the ceramic magnet (18), and the inner surface of front plate (16) when it is affixed to the ceramic magnet, thereby creating the above-mentioned sandwich. The front plate (16) has a lip (34) on its outer surface and a recess (42) in its inner surface. Lip (34) has an outer diameter (38) slightly less than that of the center hole in the speaker basket (12). The speaker basket is attached to the magnet assembly by placing lip (34) within the hole in the speaker basket and staking the two together. The inner recess (42) of the front plate (16) is designed to accept the vertical wall of the magnet centering device and shield (24) so as to prevent the entry of particles of magnet and other foreign materials into the air gap (46) in which the speaker voice coil must move.

As is well known, a loudspeaker comprises a frame or "basket" which supports the rim of a speaker cone of light, fairly rigid material such as stiff paper, the cone terminating near its apex by a cylindrical "voice coil", through which the audio frequency energization to the speaker passes. The basket also supports a magnet assembly to create a fixed radial magnetic field in which the voice coil can move axially because of the resilience of the speaker cone. Magnet assemblies typically employ ceramic magnets although some use alnico magnets. Many magnet assemblies employ a flat front plate which forms part of the assembly and serves as the surface to which the basket is attached, as well as completing the magnetic path outside the voice coil, which it is apertured to pass. In the prior art, numerous methods were employed to secure the front plate to the basket, including welding or bolting the two parts together or forming staking studs in the front plate and piercing the basket with corresponding holes for accepting the studs, and then staking the studs thereby, bonding the two parts to each other.
All of these prior methods had significant drawbacks which resulted in increased cost of production. Bolting, for example, requires expensive drilling and tapping of the front plate. Stud staking requires specially designed front plates and the extra step of staking. In the welding process, alignment of the basket and front plate is difficult and quality control is a problem. These methods have also proved unsatisfactory for use in attaching a large magnet assembly to a small basket due to the lack of available surface area on the basket necessary to weld, bolt or stud stake.


A clutch assembly includes an output shaft extending along an axis and output teeth. A movable component is disposed adjacent to the output component. The movable component includes drive teeth and an annular engagement weight track including a groove circumscribing the axis. The movable component is movable between an engaged position, wherein the drive teeth are drivingly engaged with the output teeth, and a disengaged position, wherein the drive teeth are not engaged with the output teeth. An input component is disposed adjacent to the movable component. The input component includes engagement weight pockets. Spherical engagement weights are disposed in each engagement weight pocket. The groove has a generally uniform radial cross section across its circumference.

This application relates to a synchronous engagement clutch, such as a clutch for use in a turbine starter for a gas turbine engine.
Turbine starters are used to drive engines, such as gas turbine engines, up to speed before ignition. A typical turbine starter may be driven by a power source, such as an auxiliary power unit (APU) or a ground air supply unit that supplies pressurized air to generate torque. A clutch is used to transfer torque from the power source to a shaft in the engine during startup and to disengage the power source from the engine after the engine starts running.
One variety of clutches uses spherical flyweights to engage and disengage depending on the state of the power source and engine operating speed. The power source drives a fixed member and a translating member, both having sloped pockets for the flyweights. The pockets are typically shallow relative to a diameter of the flyweights.
When the power source is running, the air turbine starter engagement and flyweights, or engagement balls, are centrifugally driven to outer ends of their respective pockets. The outward travel of the flyweights against the slope of the engagement ball pockets pushes the translating member into engagement with an assembly that transmits torque to the engine. The power source is cut off after the engine begins to run, and an opposing set of flyweights (disengagement balls) on the gearbox engine shaft side of the clutch pushes the translating member back out of position.