There is disclosed herein compounds of formula (I),

DP IV is a serine protease, which cleaves N-terminal dipeptides from a peptide chain containing, preferably, a proline residue in the penultimate position. Although the biological role of DP IV in mammalian systems has not been completely established, it is believed to play an important role in neuropeptide metabolism, T-cell activation, attachment of cancer cells to the endothelium and the entry of HIV into lymphoid cells.
Likewise, it was discovered that DP IV is responsible for inactivating glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide also known as gastric-inhibitory peptide (GIP). Since GLP-1 is a major stimulator of pancreatic insulin secretion and has direct beneficial effects on glucose disposal, in WO 97/40832 and U.S. Pat. No. 6,303,661 inhibition of DP IV and DP IV-like enzyme activity was shown to represent an attractive approach e.g. for treating type 2 diabetes (also known as non-insulin-dependent diabetes mellitus or NIDDM).
It is known that DP IV inhibitors may be useful for the treatment of impaired glucose tolerance and diabetes mellitus (WO 99/61431; Pederson R A et al, Diabetes 1998 47(8):1253-1258 and Pauly R P et al, Metabolism 1999 48(3):385-389). WO 99/61431 discloses DP IV inhibitors comprising an amino acid residue and a thiazolidine or pyrrolidine group, especially L-threo-isoleucyl thiazolidine, L-allo-isoleucyl thiazolidine, L-threo-isoleucyl pyrrolidine, L-allo-isoleucyl thiazolidine, L-allo-isoleucyl pyrrolidine, and salts thereof. WO 03/72556 discloses DP IV inhibitors comprising a glutaminyl residue and a thiazolidine or pyrrolidine group, especially glutaminyl thiazolidine and glutaminyl pyrrolidine, and salts thereof.
Further examples for low molecular weight DP IV inhibitors are agents such as tetrahydroisoquinolin-3-carboxamide derivatives, N-substituted 2-cyanopyroles and -pyrrolidines, N-(N′-substituted glycyl)-2-cyanopyrrolidines, N-(substituted glycyl)-thiazolidines, N-(substituted glycyl)-4-cyanothiazolidines, boronyl inhibitors and cyclopropyl-fused pyrrolidines. Inhibitors of DP IV are described in U.S. Pat. No. 6,011,155; U.S. Pat. No. 6,107,317; U.S. Pat. No. 6,110,949; U.S. Pat. No. 6,124,305; U.S. Pat. No. 6,172,081; WO 99/61431, WO 99/67278, WO 99/67279, DE 198 34 591, WO 97/40832, DE 196 16 486 C 2, WO 95/15309, WO 98/19998, WO 00/07617, WO 99/38501, WO 99/46272, WO 99/38501, WO 01/68603, WO 01/40180, WO 01/81337, WO 01/81304, WO 01/55105, WO 02/02560, WO 01/34594, WO 02/38541, WO 02/083128, WO 03/072556, WO 03/002593, WO 03/000250, WO 03/000180, WO 03/000181, EP 1 258 476, WO 03/002553, WO 03/002531, WO 03/002530, WO 03/004496, WO 03/004498, WO 03/024942, WO 03/024965, WO 03/033524, WO 03/035057, WO 03/035067, WO 03/037327, WO 03/040174, WO 03/045977, WO 03/055881, WO 03/057144, WO 03/057666, WO 03/068748, WO 03/068757, WO 03/082817, WO 03/101449, WO 03/101958, WO 03/104229, WO 03/74500, WO 04/007446, WO 04/007468, WO 04/018467, WO 04/018468, WO 04/018469, WO 04/026822, WO 04/032836, WO 04/033455, WO 04/037169, WO 04/041795, WO 04/043940, WO 04/048352, WO 04/050022, WO 04/052850, WO 04/058266, WO 04/064778, WO 04/069162, WO 04/071454, WO 04/076433, WO 04/076434, WO 04/087053, WO 04/089362, WO 04/099185, WO 04/103276, WO 04/103993, WO 04/108730, WO 04/110436, WO 04/111041, WO 04/112701, WO 05/000846, WO 05/000848, WO 05/011581, WO 05/016911, WO 05/023762, WO 05/025554, WO 05/026148, WO 05/030751, WO 05/033106, WO 05/037828, WO 05/040095, WO 05/044195, WO 05/047297, WO 05/051950, WO 05/056003, WO 05/056013, WO 05/058849, WO 05/075426, WO 05/082348, WO 05/085246, WO 05/087235, WO 05/095339, WO 05/095343, WO 05/095381, WO 05/108382, WO 05/113510, WO 05/116014, WO 05/116029, WO 05/118555, WO 05/120494, WO 05/121089, WO 05/121131, WO 05/123685 the teachings of which concerning the inhibitors, their production and their use are herein incorporated by reference in their entirety.
There is relatively little in the literature about the use of DP IV-inhibitors for the treatment of neurological diseases. WO 02/34242 and WO 02/34242 disclose the medical use of DP IV-inhibitors for maintenance or potentiation of endogenous neurological and neuropsychological effects of brain neuropeptide Y (NPY) systems via a potentiation of NPY Y1 receptor mediated effects within the central nervous system (CNS).
WO 01/34594 discloses DP IV-inhibitors comprising a proline mimetic, and a method of treating a patient having a disorder selected from the group consisting of strokes, tumors, ischemia, Parkinson's disease, memory loss, hearing loss, vision loss, migraines, brain injury, spinal cord injury, Alzheimer's disease, amyotrophic lateral, multiple sclerosis, diabetic neuropathy and prostate abnormalities.
WO 05/079795 relates to the use of a DP IV inhibitor for the prevention, delay of progression or the treatment of neurodegenerative disorders, cognitive disorders and for improving memory (both short term and long term) and learning ability.
Xu J et al, Bioorg Med Chem Lett 2006, Mar. 1;16(5):1346-9 discloses anti-substituted beta-methylphenylalanine derived amides as potent DP IV-inhibitors with selectivity over both DPP8 and DPP9. These compounds are optimized for the treatment of metabolic disorders and thus are preferably not able to cross the blood brain barrier.
Lankas G R et al, Diabetes 2005 54(10):2988-2994, have tested selective inhibitors of DP IV, DPP8/9 and QPP in 2-week rat toxicity studies and in acute dog tolerability studies. In rats, the DPP8/9 inhibitor produced alopecia, thrombocytopenia, reticulocytopenia, enlarged spleen, multiorgan histopathological changes and mortality. In dogs, the DPP8/9 inhibitor produced gastrointestinal toxicity. The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DP IV inhibitor. The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DP IV inhibitor was inactive in these assays. Moreover, it was found that DP IV inhibitors which were previously reported to be active in models of immune function are more potent inhibitors of DPP8/9. These results suggest that assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this class of agents.
Definitions:
The following definitions refer to the whole description and especially to the claims.
As used herein, the term "pharmaceutically acceptable" embraces both human and veterinary use: for example the term "pharmaceutically acceptable" embraces a veterinarily acceptable compound or a compound acceptable in human medicine and health care.
Stereoisomers:
All possible stereoisomers of the claimed compounds are included in the present invention. Where the compounds according to this invention have at least one chiral center, they may accordingly exist as enantiomers. Where the compounds possess two or more chiral centers, they may additionally exist as diastereomers. If the formation of an E configuration or, respectively, a Z configuration of a double bond in an "alkenyl group" is possible, both the E and Z configuration are comprised within the scope of the present invention.
It is to be understood that both individual isolated isomers (such as at least 75% pure, in particular at least 90% pure and especially at least 95% pure, for example at least 99% pure) and mixtures of isomers (for example a mixture of all possible isomers, or the two enantiomers of a diastereomer) are encompassed within the scope of the present invention.
Preparation and Isolation of Stereoisomers:
Where the processes for the preparation of the compounds according to the invention give rise to a mixture of stereoisomers, these isomers may be separated by conventional techniques such as preparative chromatography. The compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution. The compounds may, for example, be resolved into their components enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid, such as (−)-di-p-toluoyl-d-tartaric acid and/or (+)-di-p-toluoyl-l-tartaric acid followed by fractional crystallization and regeneration of the free base. The compounds may also be resolved by formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds may be resolved using a chiral HPLC column.
Pharmaceutically Acceptable Salts:
In view of the close relationship between the free compounds and the compounds in the form of their salts, whenever a compound is referred to in this context, a corresponding salt is also intended, provided such is possible or appropriate under the circumstances.
The pharmaceutically acceptable salt generally takes a form in which one or more basic moieties is protonated with an inorganic or organic acid. Representative organic or inorganic acids include hydrochloric, hydrobromic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic, hydroxyethanesulfonic, benzenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toulenesulfonic, cyclohexanesulfamic, salicylic, saccharinic or trifluoroacetic acid.
All pharmaceutically acceptable acid addition salt forms of the compounds of the present invention are intended to be embraced by the scope of this invention. Non-pharmaceutically acceptable salts forms of the compounds of the invention may be of use in the preparation of pharmaceutically acceptable salts.
Solvates:
Compounds of the invention may form solvates with water (i.e. hydrate) or common organic solvents which are embraced as an aspect of the invention. Pharmaceutically acceptable solvents (e.g. hydrates) are of particular interest.
Polymorph Crystal Forms:
Furthermore, compounds of the invention (including their salts and solvates) may exist as crystalline solids and all polymorphic forms thereof are included within the scope of the present invention.
Prodrugs:
The present invention further includes within its scope prodrugs of the compounds of this invention. In general, such prodrugs will be functional derivatives of the compounds which are readily convertible in vivo into the desired therapeutically active compound. Thus, in with respect to prodrugs, in the methods of treatment of the present invention, the term "administering" shall encompass the treatment of the various disorders described with prodrug versions of one or more of the claimed compounds of the invention, but which convert to one or more of the compounds of the invention in vivo after administration to the subject.
Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985 and the patent applications DE 198 28 113, DE 198 28 114, WO 99/67228 and WO 99/67279 which are fully incorporated herein by reference.
DP IV-inhibitor
The term "DP IV-inhibitor" or "dipeptidyl peptidase IV inhibitor" is generally known to a person skilled in the art and means enzyme inhibitors, which inhibit the catalytic activity of DP IV.
DP IV-activity
"DP IV-activity" is defined as the catalytic activity of dipeptidyl peptidase IV (DP IV). These enzymes are post-proline (to a lesser extent post-alanine, post-serine or post-glycine) cleaving serine proteases found in various tissues of the body of a mammal including kidney, liver, and intestine, where they remove dipeptides from the N-terminus of biologically active peptides with a high specificity when proline or alanine form the residues that are adjacent to the N-terminal amino acid in their sequence.
DP IV-like Enzymes
Among the rare group of proline-specific proteases, DP IV was originally believed to be the only membrane-bound enzyme specific for proline as the penultimate residue at the amino-terminus of the polypeptide chain. However, other molecules, even structurally non-homologous with the DP IV but bearing corresponding enzyme activity, have been identified recently. DP IV-like enzymes, which are identified so far, are e.g. fibroblast activation protein α, dipeptidyl peptidase IV β, dipeptidyl aminopeptidase-like protein, N-acetylated α-linked acidic dipeptidase, quiescent cell proline dipeptidase, dipeptidyl peptidase II, attractin and dipeptidyl peptidase IV related protein (DPP 8), and are described in the review article by Sedo & Malik (Sedo & Malik, Dipeptidyl peptidase IV-like molecules: homologous proteins or homologous activities? Biochimica et Biophysica Acta 2001 36506: 1-10).
Further DPIV-like enzymes are disclosed in WO 01/19866, WO 02/04610, WO 02/34900 and WO02/31134. WO 01/19866 discloses novel human dipeptidyl aminopeptidase (DPP8) with structural und functional similarities to DPIV and fibroblast activation protein (FAP). WO 02/04610 provides reagents, which regulate human dipeptidyl peptidase IV-like enzyme and reagents which bind to human dipeptidyl peptidase IV-like enzyme gene product. These reagents can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, tumors and peripheral and central nervous system disorders including pain and neurodegenerative disorders. The dipeptidyl peptidase IV-like enzyme of WO 02/04610 is well known in the art. In the Gene Bank data base, this enzyme is registered as KIAA1492 (registration in February 2001, submitted on Apr. 4, 2000, AB040925).
WO 02/34900 discloses a dipeptidyl peptidase 9 (DPP9) with significant homology with the amino acid sequences of DP IV and DPP8. WO 02/31134 discloses three DP IV-like enzymes, DPRP1, DPRP2 and DPRP3. Sequence analysis revealed, that DPRP1 is identical to DPP8, as disclosed in WO 01/19866, that DPRP2 is identical to DPP9 and that DPRP3 is identical to KIAA1492 as disclosed in WO 02/04610.
Subject
The term "subject" as used herein, refers to an animal, such as a mammal, in particular a human, who has been the object of treatment, observation or experiment.
Therapeutically Effective Amount
The term "therapeutically effective amount" as used herein, means that amount of a compound of the invention compound or pharmaceutical agent that is sufficient to elicit a biological or medicinal response in a tissue system, animal or human, being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation of the symptoms of the disease or disorder being treated.
Composition
As used herein, the term "composition" is intended to encompass a product comprising the claimed compounds in the therapeutically effective amounts, as well as any product which results, directly or indirectly, from combinations of the claimed compounds.
Co-Administration, Combination
"Co-administration" or "combination" includes administration of a formulation, which includes at least one DP IV-inhibitor of the present invention and at least one further drug agent (for example as listed in the section "Pharmaceutical combinations") or the essentially simultaneous administration of separate formulations of each agent. The DP IV-inhibitor and the other drug agent may be administered concomitantly or sequentially, as may be required by the appropriate treatment regime, via the same or different routes of administration.
Prevention
The term "prevention" means prophylactic administration of the combination to healthy patients to prevent the outbreak of the conditions mentioned herein. Moreover, the term "prevention" means prophylactic administration of such combination to patients being in a pre-stage of the conditions, to be treated.
Delay
The term "delay of progression" used herein means administration of the combination, such as a combined preparation or pharmaceutical composition, to patients being in a pre-stage of the condition to be treated in which patients a pre-form of the corresponding condition is diagnosed.
Treatment
By the term "treatment" is understood the management and care of a patient for the purpose of combating the disease, condition, or disorder.
Though the causes may differ, patients with neurodegenerative disorders are likely to show localized to generalized atrophy of brain cells leading to compromises in both mental and physical functions.
Dementia
The term "dementia" as used herein includes Alzheimer type dementia, Parkinson type dementia, Huntington type dementia, Pick's type dementia, Creutzfeldt-Jakob type dementia, senile dementia, pre-senile dementia, idiopathic-related dementia, trauma-related dementia, stroke-related dementia, cranial bleed-related dementia, vascular dementia, and includes acute, chronic or recurring forms.
Chemical Definitions
Throughout the description and the claims the expression "alkyl", unless specifically limited, denotes a C1-12 alkyl group, such as a C1-6 alkyl group (for example a C1-4 alkyl group). Alkyl groups may be straight chain or branched. Suitable alkyl groups include, for example, methyl, ethyl, propyl (e.g. n-propyl and isopropyl), butyl (e.g. n-butyl, tert-butyl and sec-butyl), pentyl (e.g. n-pentyl, hexyl (e.g. n-hexyl heptyl (e.g. n-heptyl) and octyl (e.g. n-octyl).
Other suitable alkyl groups include 1-ethyl-propyl, 3-methyl-butyl and 2,2-dimethyl-propyl), and 3,3-dimethyl-butyl), nonyl (e.g. n-nonyl and 7-methyl-octyl) and decyl (e.g. n-decyl), in particular methyl and ethyl. Further suitable alkyl groups include isobutyl.
"Lower alkyl" refers to an alkyl group having 1-4 carbon atoms e.g. methyl or ethyl.
The expression "alk", for example in the expression "alkoxy", should be interpreted in accordance with the definition of "alkyl".
Exemplary alkoxy groups include methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy and octyloxy. Other examples include nonyloxy and decyloxy. Further examples include n-propoxy, n-butoxy, n-pentoxy, n-hexoxy, n-heptoxy and n-octoxy).
The expression "alk", in the expression "thioalkyl" should be interpreted in accordance with the definition of "alkyl". Exemplary thioalkyl groups include methylthio-.
The expression "alkan", for example in the expression "alkanoyl" should be interpreted in accordance with the definition of "alkyl". Exemplary alkanoyl (i.e. acyl groups) include ethanoyl (i.e. acetyl), propionyl and butyryl.
The expression "acyl", unless specifically limited, denotes a C1-12acyl residue, such as a C1-8acyl residue e.g. a C1-6 acyl residue and in particular a C1-4acyl residue. Examples of acyl include the alkanoyl groups mentioned previously.
The expression "alk" in the expressions "haloalkyl" and "haloalkoxy" should be interpreted in accordance with the definition of "alkyl". For instance, by the term "C1-6haloalkyl" is meant a C1-6alkyl group which is substituted by at least one halo atom (for example fluoro, chloro or bromo). C1-6fluoroalkyl represents a C1-6alkyl group (such as those specifically recited above) which is substituted by at least one fluoro atom, including for example, fluoromethyl, difluoromethyl and trifluoromethyl (in particular trifluoromethyl). The expressions C1-6haloalkoxy and C1-6fluoroalkoxy can be interpreted accordingly.
The expression "alkenyl", unless specifically limited, denotes a C2-12alkenyl group, such as a C2-6alkenyl group (for example a C2-4alkenyl group), which contains at least one double bond at any desired location and which does not contain any triple bonds. Alkenyl groups may be straight chain or branched. Exemplary alkenyl groups include propenyl, butenyl. Other examples include ethenyl, pentenyl and hexenyl. Exemplary alkenyl groups including two double bonds include pentadienyl, e.g. (1E, 3E)-pentadienyl.
The expression "alkynyl", unless specifically limited, denotes a C2-12 alkynyl group, such as a C2-6alkynyl group (for example a C2-4alkynyl group), which contains at least one triple bond at any desired location. Alkynyl groups may be straight chain or branched. Exemplary alkynyl groups include ethynyl, propynyl and butynyl. Further examples include ethynyl, pentynyl and hexynyl.
Generally, the term "alkynyl group" comprises also compounds having double bonds as well as triple bonds, i.e. "alkeninyl groups", for example having one double bond and additionally, one triple bond. As an example therefore, the group 4,7-dimethyl-oct-6-en-2-in-1-yl (i.e. —CH2—C≡C—CH(CH3)—CH2—CH═C(CH3)2) may be given.
The expression "amino" means a primary, secondary or tertiary amine group. Suitably amino is represented by formula —NRaRb wherein Ra and Rb are selected from hydrogen or alkyl (e.g. C1-4alkyl) or Ra and Rb may be joined to form a 4-7 membered ring optionally containing a further N or O atom. Examples of amino include NH2, NHMe, NMe2, NHEt, NEt2, NMeEt, azetidine, pyrrolidine, piperidine, morpholine, piperazine and N-methylpiperazine.
The expression "amine", unless qualified as "secondary amine" or "tertiary amine" means NH2.
Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
The expression "carbocycle", unless specifically limited, denotes any ring system in which all the ring atoms are carbon and which typically contain between three and twelve ring carbon atoms, suitably between three and ten carbon atoms and more suitably between three and eight carbon atoms. Carbocycle groups may be saturated or partially unsaturated, but do not include aromatic rings. Examples of carbocycle groups include monocyclic, bicyclic, and tricyclic ring systems, in particular monocyclic and bicyclic ring systems. Other carbocylcyl groups include bridged ring systems (e.g. bicyclo[2.2.1]heptenyl). A specific example of a carbocycle group is a cycloalkyl group. A further example of a carbocycle group is a cycloalkenyl group. A further example of a carbocycle group is a cycloalkynyl group.
The term "cycloalkyl", unless specifically limited, denotes a C3-12cycloalkyl group, such as a C3-10cycloalkyl (for example a C3-8 cycloalkyl group). Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. A most suitable number of ring carbon atoms is three to six. The term "cycloalkenyl", unless specifically limited, denotes a C5-12cycloalkenyl group, for example a C5-10cycloalkenyl group such as a C5-8cycloalkenyl (for example a C6-8 cycloalkenyl group or a C5-6 cycloalkenyl group). A specific example is cyclohexenyl. Further specific examples include cyclopropenyl, cycloheptenyl and cyclooctenyl. A most suitable number of ring carbon atoms is five to six.
Other exemplary carbocycle groups include bridged ring systems (e.g. bicyclo[2.2.1]heptanyl bicyclo[2.2.1]heptenyl and adamantane, which are considered to be examples of cycloalkenyl and cycloalkyl groups respectively).
By the term "C3-6cycloalkylimine" is meant C3-6cycloalkyl group in which one of the ring carbon atoms is replaced by a nitrogen atom. Exemplary C3-6cycloalkylimine groups include azetidine (also known as trimethylene imine, which may be 1-azetidine, 2-azetidine or 3-azetidine, in particular 3-azetidine), pyrrolidine (including pyrrolidin-1-yl, pyrrolidin-2-yl and pyrrolidin-3-yl) and piperidine (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and piperidin-4-yl).
The expression "heterocyclic" or "heterocycle", unless specifically limited, denotes a carbocyclic residue (for example a cycloalkyl group, e.g. cyclopentyl or more particularly cyclohexyl), wherein one or more (e.g. 1, 2, 3 or 4, such as 1, 2 or 3, in particular 1 or 2, especially 1) ring atoms are replaced by heteroatoms selected from N, S or O. By the term "C3-12heterocycle" is meant a C3-12carbocyclyl group in which at least one of the ring carbon atoms is replaced by a heteroatom. A heterocyclic group could therefore be monocylic or could alternatively be bicyclic. More usually it will be monocyclic. Exemplary heterocyclic groups containing one hetero atom include: three membered rings (e.g. oxirane aziridine, thiirane); four membered rings (e.g. oxetane, azetidine, thietane); five membered rings (e.g. pyrrolidine and tetrahydrofuran, but also pyrroline and tetrahydrothiophene); and six membered rings (e.g. piperidine or tetrahydropyran). Exemplary heterocyclic groups containing two hetero atoms include five membered rings (e.g. pyrazoline, imidazoline, pyrazolidine, imidazolidine, dioxolane, thiazolidine, oxazolidine); and six membered rings (e.g. morpholine and piperazine but also dioxane). A further specific example of a heterocycle group is a cycloalkenyl group (e.g. a cyclohexenyl group) wherein one or more (e.g. 1, 2 or 3, particularly 1 or 2, especially 1) ring atoms are replaced by heteroatoms selected from N, S and O. An example of such a group is dihydropyranyl (e.g. 3,4-dihydro-2H-pyran-2-yl-).
An example of a bridged heterocyclic group is utropine.
The expression "aryl", unless specifically limited, denotes a C6-12 aryl group, suitably a C6-10 aryl group, more suitably a C6-8 aryl group. Aryl groups will contain at least one aromatic ring (e.g. one, two or three rings), but may also comprise partially or fully unsaturated rings. An example of a typical aryl group with one aromatic ring is phenyl. Examples of aromatic groups with two aromatic rings include naphthyl. Examples of naphthyl include naphth-1-yl- and naphth-2-yl-. Examples of aryl groups which contain partially or fully unsaturated rings include pentalene, indene and indane. Other aryl groups include tricyclic rings such as anthracene.
The expression "heteroaryl", unless specifically limited, denotes as an aryl residue, wherein one or more (e.g. 1, 2, 3, or 4, such as 1, 2 or 3) ring atoms are replaced by heteroatoms selected from N, S and O or else a 5-membered aromatic ring containing one or more (e.g. 1, 2, 3, or 4, such as 1, 2 or 3) ring atoms selected from N, S and O. Exemplary monocyclic heteroaryl groups having one heteroatom include: five membered rings (e.g. pyrrole, furan, thiophene); and six membered rings (e.g. pyridine, such as pyridin-2-yl, pyridin-3-yl and pyridin-4-yl). Exemplary monocyclic heteroaryl groups having two heteroatoms include: five membered rings (e.g. pyrazole (e.g. pyrazol-3-yl), oxazole, isooxazole, thiazole, isothiazole, imidazole, such as imidazol-1-yl, imidazol-2-yl imidazol-4-yl); six membered rings (e.g. pyridazine, pyrimidine, pyrazine). Exemplary monocyclic heteroaryl groups having three heteroatoms include: triazole e.g. 1,2,3-triazole and 1,2,4-triazole. Exemplary monocyclic heteroaryl groups having four heteroatoms include tetrazole.
Exemplary bicyclic heteroaryl groups include quinoline, benzothiophene, indazole, indole and purine. Exemplary bicyclic heteroaryl groups also include isoquinoline, quinolizine, benzodioxolane, benzodioxane, benzodioxepine (e.g. indol-6-yl), indoline, benzimidazole Further examples of bicyclic heteroaryl groups include (e.g. 1H-indol-6-yl), benzimidazole, chromene, benzodioxolane, benzodioxane (e.g. 2,3-dihydro-benzo[1,4]dioxin-6-yl) and benzodioxepine.
Exemplary tricyclic heteroaryl groups include carbazole and acridine groups.
The expression "-alkylaryl", unless specifically limited, denotes an aryl residue which is connected via an alkylene moiety such as a C1-6alkylene moiety e.g. a C1-4alkylene moiety. Examples of -alkylaryl include: -methylaryl and -ethylaryl (e.g. 1-arylethyl- or 2-arylethyl-); or phenylalkyl-, which may be optionally substituted. Specific examples of -alkylaryl functions include: phenylmethyl- (i.e. benzyl), phenylethyl- (e.g. 2-phenyleth-1-yl or 1-phenyl-eth-1-yl), p-tolyl-methyl-, (p-tolyl)-ethyl-, (m-tolyl)-methyl-, (m-tolyl)-ethyl-, (o-tolyl)-methyl-, (o-tolyl)-ethyl-, 2-(4-ethyl-phenyl)-eth-1-yl-, (2,3-dimethyl-phenyl)-methyl-, (2,4-dimethyl-phenyl)-methyl-, (2,5-dimethyl-phenyl)-methyl-, (2,6-dimethyl-phenyl)-methyl-, (3,4-dimethyl-phenyl)-methyl-, (3,5-dimethyl-phenyl)-methyl-, (2,4,6-trimethyl-phenyl)-methyl-, (2,3-dimethyl-phenyl)-ethyl-, (2,4-dimethyl-phenyl)-ethyl-, (2,5-dimethyl-phenyl)-ethyl-, (2,6-dimethyl-phenyl)-ethyl-, (3,4-dimethyl-phenyl)-ethyl-, (3,5-dimethyl-phenyl)-ethyl-, (2,4,6-trimethyl-phenyl)-ethyl-, (2-ethyl-phenyl)-methyl-, (3-ethyl-phenyl)-methyl-, (4-ethyl-phenyl)-methyl-, (2-ethyl-phenyl)-ethyl-, (3-ethyl-phenyl)-ethyl-, (4-ethyl-phenyl)-ethyl-, 2-fluoro-benzyl, (1-methyl-2-fluoro-phen-6-yl)-methyl-, (1-methyl-2-fluoro-phen-4-yl)-methyl-, (1-methyl-2-fluoro-phen-6-yl)-ethyl-, (1-methyl-2-fluoro-phen-4-yl)-ethyl-, 1H-indenyl-methyl-, 2H-indenyl-methyl-, 1H-indenyl-ethyl-, 2H-indenyl-ethyl-, indanyl-methyl-, indan-1-on-2-yl-methyl-, indan-1-on-2-yl-ethyl-, tetralinyl-methyl-, tetralinyl-ethyl-, fluorenyl-methyl-, fluorenyl-ethyl-, dihydronaphthalinyl-methyl-, dihydronaphthalinyl-ethyl-, or (4-cyclohexyl)-phenyl-methyl-, (4-cyclohexyl)-phenyl-ethyl-.
The expression "-alkylheteroaryl", unless specifically limited, denotes a heteroaryl residue which is connected via an alkylene moiety such as a C1-6alkylene moiety e.g. a C1-4alkylene moiety. Examples of -alkylheteroaryl include -methylheteroaryl and -ethylheteroaryl (e.g. 1-heteroarylethyl- and 2-heteroarylethyl-). Specific examples of -alkylheteroaryl groups include pyridinylmethyl-, N-methyl-pyrrol-2-methyl-N-methyl-pyrrol-2-ethyl-, N-methyl-pyrrol-3-methyl-, N-methyl-pyrrol-3-ethyl-, 2-methyl-pyrrol-1-methyl-, 2-methyl-pyrrol-1-ethyl-, 3-methyl-pyrrol-1-methyl-, 3-methyl-pyrrol-1-ethyl-, 4-pyridino-methyl-, 4-pyridino-ethyl-, 2-(thiazol-2-yl)-ethyl-, 2-ethyl-indol-1-methyl-, 2-ethyl-indol-1-ethyl-, 3-ethyl-indol-1-methyl-, 3-ethyl-indol-1-ethyl-, 4-methyl-pyridin-2-methyl-, 4-methyl-pyridin-2-yl-ethyl-, 4-methyl-pyridin-3-methyl-, 4-methyl-pyridin-3-ethyl-.
The terms "halogen" and "halo" include fluorine, chlorine, bromine and iodine, especially fluorine, chlorine and bromine, in particular fluorine and chlorine (e.g. fluorine).

Abstract: wherein:    R1, R2, R3, R4 and R5 are defined throughout the description and the claims. The compounds of formula (I) are useful for the treatment of neurological diseases and neurodegenerative diseases, e.g. anxiety, depression, Alzheimer's disease etc.


A pharmacy workflow platform and prescription checking and medicament dispensing station and method comprising (a) script display means; (b) scanning means for providing script data and stock bottle label data in electronic format from the prescription and a stock bottle label; (c) CPU means comprising i) means for receiving and storing the script data and stock bottle data in electronic format; ii) means for transferring the script data to the script display means to effect display of the script; iii) means cooperable with medicament dispensing weighing and counting means; (d) medicament-dispensing weighing means in communication with the CPU means; and (e) control means for controlling the CPU means. Medication is dispensed in a more safe, efficient and cost-effective manner.

There is an increasing need to dispense medicaments to individuals in pharmacies, hospitals, health centres and the like, in a safe, efficient and cost effective manner. Currently, medication errors can result from confusion over "look-alike" or "sound-alike" product names. If patients receive an incorrect drug or dosage, these errors can result in serious harm to the patient. One common cause of confusion is from a name mix-up, caused by what human factors experts call "confirmation bias", where a practitioner reads a poorly written drug name and is most likely to see in that name that which is most familiar to him;—overlooking any disconfirming evidence.
The modern pharmacy practice therefore requires equipment and record keeping capabilities in order to enhance the safe and accurate dispensing of prescriptions. However, recently, there is the desire to also provide pharmacy services to the public, without a pharmacist being physically present. This is a process that creates the need to provide a safe and efficient communication tool for the pharmacist, in order that he/she can remotely supervise the prescription filling procedures.

Method and apparatus for dispensing medicaments


A bunt training aid is described. The bunt training aid is used by baseball, softball and other game players to improve their bunting ability. The bunt training aid teaches the player how to catch a ball with a bat.

Bunting is a fundamental skill needed in baseball and softball. Bunting is especially important in softball. Bunting may be used by a batter to advance a runner that is already on base. Bunting allows the player to softly hit the ball in a desired direction, preferably away from a fielder, while still hitting the ball in the playing field. As opposed to normal hitting, the bunter is not attempting to make contact with the ball in order to direct the ball with high velocity to the infield or out of the infield and into the outfield. Instead, bunting involves contacting the bat with the ball in relatively slow, directionally orientated movement in order to place the ball in the infield area away from a fielder.
When bunting, the player attempts to deaden the ball directed towards the player by gently receiving the ball against a contact surface of the bat. When learning to bunt, the player is often taught or trained to attempt to attempt "catch" the ball with the bat. A conventional baseball or softball bat is not able to catch a ball.

Abstract: The bunt training aid includes a handle portion, a barrel portion, and a receiving member. The receiving member defines an opening sized to permit a ball to pass through the opening. The receiving member includes a first attachment member to attach the receiving member to the handle portion. The receiving member includes a second attachment member to attach the receiving member to the barrel portion. The receiving member is positioned between the handle portion and the barrel portion. A net is attached to the receiving member in order to hold the ball that has passed through the opening.


The animal control apparatus has a hollow cylindrical tube with a first and second end. A handle is attached to the first tube end. A cable within the tube has a first end with a cable movement member. The spring has a first and second end, and a spring stop and a spring compression plate are formed in the tube. There is a top end cap and a bottom end cap. The bottom end cap has a first and second pivot point, a first and a second clasp arms are attached to the first and second pivot points. The clasp arm movement means is attached to the cable second end and interacts with the first and second clasp arms to open and close the arms. The clasp arm movement means can be t-shaped, and have a central arm attached to the cable and a pair of opposed engagement arms, with pins that extend outwardly from the engagement arms and engage slots in the clasp arms.

Many offerings exist by which an individual can control animals while exercising or walking them. The devices offered, however, do not solve all problems associated with quick collar release and increased control of the animal. When a flexible leash is used, the animal can move as desired, and no leverage can be exerted on the animal, through the leash, as is possible with a rigid leash.


Techniques for determining whether a speaker element, or “earpiece,” of an earphone or headphone set is located within, or proximate to, a right ear, a left ear, or neither ear of a user of the set may include receiving a first temperature value from a first temperature sensor, receiving a second temperature value from a second temperature sensor, and determining whether the speaker element is located within, or proximate to, the right ear, left ear, or neither ear, based on (e.g., a difference between) the first and second temperature values. The techniques may further include receiving a third temperature value from a third temperature sensor, such as an user ambient temperature sensor, or a user body temperature sensor, and further determining whether the speaker element is located within, or proximate to, the right ear, left ear, or neither ear, based on the third temperature value.

A number of industrial and consumer electronic devices, such as desktop, laptop, and hand-held (e.g., so-called "tablet") computers, portable media players (e.g., compact disc (CD) players, MPEG-2 Audio Layer III (MP3) and similar digital audio players, and digital video players), as well as numerous other devices (e.g., so-called "smartphones"), are capable of providing users with a variety of media content. For example, many stationary and portable (e.g., so-called "mobile") electronic devices are configured to provide an audio output to a user in the form of music, speech, or any combination thereof. For this purpose, many such devices include one or more integrated electroacoustic transducers, including loudspeakers, piezoelectric speakers, and other speaker types. These devices are configured to provide an audio output to a user in the form of sound waves that originate at one or more such transducers and travel toward the user's ears through air and/or other media. In contrast, many other electronic devices are configured to provide an audio output to a user via one or more miniature electroacoustic transducers, which may be referred to as "speaker elements," that are integrated into so-called "earphone" or "headphone" sets designed to be placed within, or proximate to, one or more of the user's ears. In these examples, sound waves produced by the speaker elements are transmitted directly into one or more of the user's ears, allowing enhanced sound directionality and noise isolation. In some examples, the audio output provided to the user may contain stereophonic information, such as, e.g., differential content, or so-called "phasing," between right and left components, or so-called "channels," of a stereo audio signal that are intended for the user's right and left ears, respectively. In such instances, for the user to perceive the audio output correctly, the user may receive each of the right and left components of the stereo audio signal via the speaker elements at the corresponding designated ear.

Detecting headphone earpiece location and orientation based on differential user ear temperature


A method and apparatus are provided for addressing a memory device. The apparatus receives a system address from a memory access device having an endianess. The system address has a word address bit corresponding to word boundaries within the memory device. The apparatus selectively inverts the word address bit as a function of the endianess of the memory access device to produce a selectively modified system address. The apparatus then accesses a memory location with the memory device based on the selectively modified system address.

The present invention relates to semiconductor integrated circuits and more particularly to a computer system having multiple memory access devices and a shared memory space.
In a computer system having multiple memory access devices, a memory controller is often used to coordinate the transfer of data to and from a memory device. Each memory access device is coupled to the memory controller through a system bus. The memory controller is in turn coupled to the memory device through a memory bus. Access to the system bus and thus to the memory controller is typically coordinated by a system bus arbiter. From the memory access device""s point of view, the memory device is just a data warehouse. The memory access device does not need to know how the data is stored in memory.
In a typical memory, successive data units or xe2x80x9cwordsxe2x80x9d are stored in successive columns in memory. The order in which these words are acccessed depends on the endianess of the memory device. A xe2x80x9clittle endianxe2x80x9d memory device stores the least significant word part of a double word group into the smaller address location of a double word location in the memory, and stores the most significant word part of the double word group in the larger address location of the double word location. In contrast, a xe2x80x9cbig endianxe2x80x9d memory device stores the least significant word part of a double word group in the larger address location of a double word location and stores the most significant word part of the double word group in the smaller address location of the double word location.
In some applications, it may be desirable to have multiple devices having different endianess access the same memory space. A xe2x80x9clittle endianxe2x80x9d memory access device views the smaller and larger double word locations, in terms of their addresses, as containing the least significant word part and the most significant word part, respectively, of a double word group. In contrast, a xe2x80x9cbig endianxe2x80x9d memory access device views the smaller and larger double word locations as containing the most significant word part and the least significant word part, respectively, of a double word group.
In a system having multiple memory access devices, which can have different endianess, data words stored in a memory location by one device could be retrieved by another device with a different endianess. If the system bus is wider than the memory bus, a memory access device with a different endianess would view the data words on the system bus differently than the other memory access device. As a result, the data words retrieved from shared memory could be put on the wrong portion of the system data bus if the endianess of each memory access device is not taken into careful consideration. To avoid this difficulty, multi-processor systems typically require all devices sharing the same memory space to have the same endianess. Alternatively, the memory could be split into xe2x80x9cbit endianxe2x80x9d and xe2x80x9clittle endianxe2x80x9d areas such that devices having different endianess would not share the same memory space.
This type of arrangement, with the system bus being wider than the memory bus, is common for systems containing a double data rate (DDR) synchronous dynamic random access memory (SDRAM). A DDR SDRAM transfers data on each rising and falling edge of a memory clock signal. A DDR SDRAM therefore transfers two data units per clock cycle. For example, a x16 DDR SDRAM has a 16-bit memory data bus which transfers one 16 bit half word on each clock edge. Therefore one 32-bit word is transferred during each memory clock cycle. A x32 DDR SDRAM has a 32-bit memory data bus, with one 32-bit word being transferred on each clock edge for a total of one 64-bit double word transfer for each memory clock cycle. A typical system bus has 64 data bits. Thus when a x16 DDR SDRAM is used, the width of the system bus (64 bits) is wider than the effective width of the memory bus (32 bits).
An improved memory interface is therefore desired which is capable of maintaining consistent data storing and retrieving in a shared memory space by more than one memory accessing device having different endianess, particularly for use with a DDR SDRAM.
One embodiment of the present invention relates to a method for addressing a memory device. The method includes the steps of: receiving a system address from a memory access device having an endianess, wherein the system address has a word address bit corresponding to word boundaries within the memory device; selectively inverting the word address bit as a function of the endianess of the memory access device to produce a selectively modified system address; and accessing a memory location with the memory device based on the selectively modified system address.
Another embodiment of the present invention relates to a memory interface. The memory interface includes a write data path and a read data path extending through the memory interface, a system address input and a memory address output. The system address input has multiple bits, including a word address bit. A memory address generator is coupled between the system address input and the memory address output. An endianess flag within the memory interface indicates an endianess of a memory access device coupled to the system address input. A selective inversion circuit is coupled in series between the word address bit of the system address input and the memory address generator and includes an inversion control input coupled to the endianess flag.
Yet another embodiment of the present invention relates to a computer system, which includes a memory bus, a system bus, a memory device coupled to the memory bus and a memory access device coupled to the system bus. The memory access device has an endianess and generates a system address on the system bus, which has a word address bit corresponding to word boundaries within the memory device. A memory interface device is coupled between the system bus and the memory bus and includes a selective inversion circuit for selectively inverting the word address bit as a function of the endianess of the memory access device to produce a selectively modified system address, and includes an address generator for producing a memory address on the memory bus based on the selectively modified system address.


An image forming apparatus includes a housing, a conveying member, a nip member, an urging member, a changing portion, a first transmission portion, a motor, a second transmission portion, and a switching member. The urging member is configured to urge one of the conveying member and the nip member. The changing portion is configured to change an urging force of the urging member. The opening/closing member is configured to generate a moving force when being moved. The second transmission portion is configured to transmit drive force of the motor to the first transmission portion to generate the moving force. The switching member is configured to switch to one of a transmitting state and a cutoff state. The switching member interrupts the transmission of the drive force from the second transmission portion to the first transmission portion in the cutoff state.

Among the various conventional image forming apparatuses in the art, there are electro-photographic type image forming apparatuses provided with a fixing device for fixing a toner image on a sheet. The image forming apparatus includes a housing, a heat member, and a pressure member in pressure contact with the sheet in cooperation with the heat member. The image forming apparatus is provided with a front cover to cover a front opening of the housing. A nip pressure between the heat member and the pressure member can be changed in interlocking relation to opening/closing motion of the front cover. More specifically the nip pressure at opening state of the front cover is set smaller than the nip pressure at closing state of the front cover for facilitating sheet removal when sheet jamming occurs.

Image forming apparatus including fixing device


An information processing method and device are provided. The information processing method includes: obtaining link state information of a target link; determining whether link exception exists in the target link or not according to the link state information; and when the link exception is determined to exist in the target link, transmitting link exception indication information to a primary node, wherein the link exception indication information is used to indicate to the primary node that the link exception exists in the target link.

A forthcoming mobile communication system will support a larger transmission bandwidth and a higher transmission rate, wherein the transmission bandwidth may be in an order of Giga Hertz (GHz), and the transmission rate may be in an order of ten Giga bits per second (Gbps). For purpose of handling above scenarios, a scenario in which a large amount of high-frequency micro cells are deployed will be a common deployment scenario. In order to coordinate the micro cells and enable the micro cells to operate effectively, it is a good solution for enhancing a system efficiency and satisfying a user experience that a central node for performing a uniform management function and acting as a data anchor node is deployed.
In a relevant communication system, a data transmission between a User Equipment (UE) and an evolved Node B (eNB) is generally implemented through a Packet Data Convergence Protocol (PDCP) layer, a Radio Link Control (RLC) layer, a Media Access Control (MAC) layer, and a Physical Layer (PHY). Directed to a scene in which a Primary cell and a Secondary cell are overlapped and uses same or different frequencies or a non-ideal scene in which only a backhaul link exists between a secondary cell and a coverage cell, a dual-connection technique is introduced. The dual-connection refers to a case in which a plurality of network nodes having non-ideal backhaul links provide radio resources for a UE. That is, the UE keeps air-interface connections with both a Master eNB (MeNB) and a Secondary eNB (SeNB), and this means that both the MeNB and the SeNB may provide services to the UE.
In an architecture based on the dual-connection, data of a user may be divided between different eNBs and separately processed by the two eNBs below the RLC layer. In such an architecture, traffic control is performed between the SeNB and the MeNB through signalings at an X2 interface, and feedback being failed is transmitted through the X2 interface.

Information processing method and device

CHINA ACADEMY OF TELECOMMUNICATIONS TECHNOLOGY


A tiltrotor aircraft having a fixed wing and tilting rotors has a rotor blade with a shaped tip portion that provides improved hover performance. The shaped tip portion preferably has a terminal anhedral of at least 20° with respect to its stacking line, and the blade has an overall twist from root to tip of at least 20°, and a thickness ratio between 19% and 30% at a radial station of 10%. These features advantageously conspire to provide a hover figure of merit of at least 0.84 and a cruise propulsive efficiency of at least 0.85. A controller preferably limits the rotor speed in sustained airplane-mode forward flight cruise of at most 40% of a hover maximum rotor speed, and alternatively or additionally limits a rotor edgewise advance ratio to at most 0.20.

Rotorcraft are now a well-established means of transportation, and generally offer a vertical takeoff and landing capability, making them particularly valuable for transport applications without access to lengthy runways. Helicopters are the predominant type of rotorcraft, and have widespread civil and military application. In contrast to fixed-wing aircraft, which use wings to generate sufficient lift to sustain flight, rotorcraft use spinning rotors to generate lift at least in rotor-borne flight.
Rotors comprise blades that can rotate in the air about an axis. As these blades rotate, blade sections encounter an air velocity which is the vector sum of rotorcraft motion, rotor rotation, and air inflow. As a blade section, generally of an airfoil shape, encounters this velocity it produces lift in a direction perpendicular to the velocity vector. Associated with the generation of this circulatory lift is the generation of shed and trailed vorticity into the air. Strong bundles of vorticity are trailed from the tips of the rotor blades, forming a rotor wake. In many flight conditions, the rotor wake can be visualized as a set of intermeshed helices that form from the rotor and gradually decay. This trailed vortex wake can have a strong effect on local rotor blade loads.
The edgewise advance ratio of a rotor is defined as rotor forward velocity divided by rotor tip speed, or μ=V cos(α)/(ΩR). For an ideally hovering rotor, the advance ratio is zero, and the rotor blades trail an un-skewed helical wake below the rotor. As the rotor begins forward motion and advance ratio increases, the wake skews backward. As rotor blades pass near or through trailed vorticity, there is a strong aerodynamic interaction, leading to changes in local blade loading. These changes can lead to reduced performance from increased induced losses, increased vibration, and increased noise. The classical problems of rotor aerodynamics are discussed in the 2006 book "Principles of Helicopter Aerodynamics, 2e" by J. Gordon Leishman.
This and all other extrinsic materials discussed herein are incorporated by reference in their entirety. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Modern prior art helicopters use specially designed rotor blades to help reduce the adverse effects of interaction between trailed vorticity and blade loading. Some helicopter blades use special tip shapes to modify the vortex trajectory or separate the trailed vorticity into multiple bundles. However, all of the prior art methods have limited effect because dramatic changes in tip geometry will create increased drag and adversely affect performance.
U.S. Pat. No. 5,199,851 to Perry, et al. describes helicopter rotor blades with a tip vane for reducing helicopter blade noise that covers the outer 4 to 8% of the blade and has a dihedral of about five degrees. U.S. Pat. No. 4,324,530 to Fradenburgh, et al. discloses a twisted helicopter blade with the outer 4% of the tip having an anhedral of twenty degrees for improving the rotor performance in hover. US Patent Application 2005/0265850 describes a helicopter rotor blade with a small protruding tip vane that can have an anhedral angle. Similarly, U.S. Pat. No. 6,142,738 to Toulmay describes a helicopter blade with a small tip winglet for reducing noise, the winglet having a leading edge sweep between twenty and thirty degrees.
What these prior art systems and methods have in common is that they all involve relatively minor adjustments to blade tip geometry, both in terms of the percent span affected, and in terms of the amount of anhedral or sweep. There is good reason for this because, for example, excessive anhedral will greatly increase rotor drag in forward flight, negating any benefit of increased hover performance and compromising the utility of the aircraft. Likewise, excessive rotor blade sweep can compromise the vibrational characteristic and aeroelastic stability of the rotor.
In the related field of tiltrotors, rotor blades are generally straight, and do not feature complex tip geometry. As examples of tiltrotors with straight blades, consider the prior art Bell™ V-22, XV-15, and BA-609 tiltrotor aircraft, or U.S. Pat. No. 6,607,161 to Krysinski, which all have straight, tapered blades without tip sweep, tip anhedral, or tip vanes. Because tiltrotors spend much of their flying time in airplane mode with the rotors operating as propellers, there is little need or motivation to create specialized blade tips to alleviate helicopter mode noise, vibration, and performance issues.
Similarly, airplane propellers benefit from tip sweep, but not anhedral or other more complex tip geometries because airplane propellers substantially do not engage in edgewise flight, but remain in predominantly axial flight throughout operation. For propellers, blade-vortex interaction or hover performance are of essentially no concern. U.S. Pat. No. 5,927,948 to Perry, et al. describes a propeller blade with a tip portion of enlarged chord and some sweep, but without any anhedral.
In general, tiltrotors have highly twisted blades and operate at higher thrust coefficients as compared with helicopters. The higher thrust coefficients tend to improve performance in airplane-mode axial flight at the expense of some hover performance. Because tiltrotor aircraft generally hover on takeoff and benefit from ample vertical takeoff capability, there is a continued need for improved tiltrotor hover performance.
Thus, there is still a need for advanced rotors for tiltrotors that can improve hover performance and maintain or improve axial forward flight performance.

Anhedral tip blades for tiltrotor aircraft


A dynamically reconfigurable framework manages processing applications in order to meet time-varying constraints to select an optimal hardware architecture. The optimal architecture satisfies time-varying constraints including for example, supplied power, required performance, accuracy levels, available bandwidth, and quality of output such as image reconstruction. The process of determining an optimal solution is defined in terms of multi-objective optimization using Pareto-optimal realizations.

While a computer system is operating, resources are spent to'manage various aspects of the system. Systems may be configured before operation to prioritize certain resources of the system over others. Other systems may include an embedded system that configures system resources. Embedded systems typically maintain a dedicated function within a larger mechanical, electrical or computer system, often with real-time computing constraints.
Embedded systems include, for example, hardware components such as programmable logic devices (PLDs). PLDs, including field-programmable gate arrays (FPGAs), are integrated circuits (ICs) that can be programmed to implement user-defined logic functions.
FPGAs are an important and commonly used circuit element in conventional electronic systems. FPGAs are attractive for use in many designs in view of their low non-recurring engineering costs and rapid time to market. FPGA circuitry is also being increasingly integrated within other circuitry to provide a desired amount of programmable logic. Many applications can be implemented using FPGA devices without the need of fabricating a custom integrated circuit.
Scalable solutions for embedded systems are desired that can deliver different solutions based on one or more constraints. As an example, it is desirable to have a low-energy solution when there is a requirement for long-time operation and a high-performance solution when there is no power (or energy) constraint. More specifically, scalable solutions are desired that can allocate hardware resources based on constraints, for example minimize energy consumption, minimize bitrate requirements, increase accuracy, increase performance, and/or improve image quality.
The invention satisfies the demand for a dynamically reconfigurable framework and methods that provide optimal scalable solutions that can meet real-time constraints.

This patent is subject to a terminal disclaimer.

System and methods for dynamic management of hardware resources


A new and distinct cultivar of Chrysanthemum plant named ‘Cool Yocheryl’, characterized by its compact, upright and outwardly spreading plant habit; freely branching habit; dense and full plant habit; uniform and freely flowering habit; decorative-type inflorescences with elongated oblong to ligulate-shaped ray florets; white-colored ray florets with purple-colored apices; and natural season flowering about October 6th in the Northern Hemisphere.

The present invention relates to a new and distinct cultivar of Chrysanthemum plant, botanically known as Chrysanthemum×morifolium, commercially grown as a garden Chrysanthemum and hereinafter referred to by the name 'Cool Yocheryl'.
The objective of the breeding program is to create new garden-type Chrysanthemum cultivars having inflorescences with desirable inflorescence forms, attractive floret colors and good garden performance.
The new Chrysanthemum is a naturally-occurring whole plant mutation of the Chrysanthemum×morifolium cultivar Soft Yocheryl, disclosed in U.S. Plant Pat. No. 16,296. The new Chrysanthemum was discovered and selected by the Inventor as a single flowering plant within a population of plants of the parent cultivar in December, 2003, in Alva, Fla. The selection of this plant was based on its desirable inflorescence color and good form and substance.
Asexual reproduction of the new Chrysanthemum by vegetative cuttings was first conducted in Alva, Fla. in February, 2004. Asexual reproduction by cuttings has shown that the unique features of this new Chrysanthemum are stable and reproduced true to type in successive generations.


The invention relates to a bioreactor for cultivating microorganisms, as well as a method for its production. The invention is characterized in that the bioreactor (1) comprises two identically constructed base elements (2,3) that are constructed in trough shape and consist of a bottom part (4) and four side parts (5) arranged on a bottom part (4) and having an inside depth T1. The base element (2,3) consists of a light permeable material. The identically constructed base elements (2,3) are arranged on each other so as to exactly cover each other. A flow guide device is arranged inside the identically constructed base elements (2,3).

Bioreactors are fermenters in which biological conversions of substances are performed with enzymes, microorganisms (bacteria, fungi, yeast, algae) as well as animal and plant cells. It should be possible to create optimum conditions, specific to each process, with respect to temperature, pH value, and nutrient concentration in the bioreactor. The tasks of a bioreactor therefore include mass transfer within the fluid phase (mixing), dispersion in a second phase—in most cases air—in order to obtain a large phase boundary surface for good mass transfer (separation), and thermal transfer for dissipating the generated heat. The design of a bioreactor depends on its applications and therefore must take into account the specific requirements of the biological system used.
In order to cultivate phototrophic microorganisms, so-called photobioreactors are used. Among potential designs, the airlift photobioreactor is considered to be especially suitable for cultivating phototrophic microorganisms and growing them to a high cell density. The airlift photobioreactor often has a column-shaped reactor vessel, in which introduction of air creates a fluid circulation within a loop established by the construction. The airlift bioreactor is divided thus into a gassed and ungassed zone, which are interconnected at the bottom and top so that the hydrostatic pressure differential causes a pump effect that results in an outflow of fluid in the gassed zone. As the mixing of the reactor medium is due exclusively to the aeration, this photobioreactor design enables good mixing and a high gas-fluid mass exchange with low energy consumption. Such an airlift photobioreactor is described, for example, in DE 199 16 597.
As cultivation of phototrophic microorganisms requires high-intensity incident light radiation, especially deep in the reactor, photobioreactors preferably have a large surface-to-volume ratio and thus require a relatively high expenditure of material. Because of the materials used, such as glass or Plexiglas, the production of such a photobioreactor is relatively complicated, material- and cost-intensive.

Bio-reactor for the cultivation of micro-organisms and method for the production thereof

Fraunhofer-Gesellschaft zur Forderung der angewandten Forschung e.V


An object of the present invention is to lower the sintering temperature required for a sintered body of yttrium-aluminum garnet, to improve the corrosion resistance of the sintered body and to prevent the reduction of the transmittance thereof. A sintered body of yttrium-aluminum garnet is produced from a source compound for yttrium and a source compound for aluminum using aluminum nitride as a sintering aid. It maybe considered that aluminum nitride reacts with alumina and yttria to generate liquid phase and to reduce the sintering temperature during the sintering process.

1. Field of the Invention
The present invention relates to a method of producing a sintered body of yttrium-aluminum garnet, a sintering aid therefor, and a sintered body produced by the method.
2. Related Art Statement
Yttrium-aluminum garnet (Y3Al5O12: YAG) ceramics has an excellent transmittance over a wide range of wavelengths from visible to infrared lights. Applications of the ceramics such as a substitute material for a sapphire window, a material for a vessel for a discharge lamp and a corrosion resistant member have been studied.
Yttrium-aluminum garnet, however, has a melting point of about 1950° C. and thus requires a high sintering temperature so that the reduction of the production cost is rather difficult. For example, according to a Japanese Patent publication 5-286, 761A, alumina powder and yttria powder are mixed with a sintering aid added, shaped and sintered at 1600 to 1860° C. The sintering aid includes lithium oxide, sodium oxide, magnesium oxide, calcium oxide and silicon oxide.

Sintered bodies of yttrium-aluminum garnet, a method of producing the same and sintering aid therefor


In one aspect a power amplifier comprises a first plurality of laser disks disposed in a first vertical plane and a second plurality of laser disks disposed in a second vertical plane, opposite the first vertical plane, wherein the plurality of laser disks are disposed in a central horizontal plane, and a first plurality of reflecting mirrors disposed in the first vertical plane and a second plurality of reflecting mirrors disposed in the second vertical plane, wherein a first set of reflecting are disposed in a lower horizontal plane and a second set of reflecting mirrors are disposed in an upper horizontal plane, wherein respective laser disks and reflecting mirrors adjacent along an optical axis are positioned to provide a 1:1 imaging system therebetween. Other aspects may be described.

Solid state laser disks have an active thin disk gain medium that is mounted along its back surface to a heat sink. The back surface is highly reflective at the laser and pump wavelengths and the front surface is highly transmissive at the laser and pump wavelengths. An external laser beam enters the disk at its front surface, or "face", propagates to the back surface, is reflected by the back surface back to the front surface, where it leaves the disk. While propagating in the disk, the laser beam extracts energy from the disk.
The energy lost is restored by the pumped laser beam which also enters the disk at its front surface, propagates to the back surface, is reflected and propagates to the front surface where it leaves the disk. While propagating through the disk the pump beam deposits energy into the disk and stimulates the medium. An example active medium is Yb:YAG (ytterbium-doped yttrium aluminum garnet) which is provided in a circular disk format that may be 10 to 2000 millimeter (mm) in diameter and 200 micron (0.20 mm) thick. A pumping light source is typically provided by a diode laser array which provides a greater than unity gain at the laser wavelength, so as to have the laser disk function as an active mirror. The pumping beam is presented to the face at an angle of incidence that avoids interference with the laser beam.
Laser disk output beam power may be increased by increasing the power delivered by the pumping light source, and/or by combining multiple laser disks in a laser disk resonator. A stable laser disk resonator is used to combine the individual output laser power of multiple disks into a multi kilowatt laser output beam used, for example, in metal working applications. The high power output beams produced by stable laser disk resonators are multimode, and are typically fifty times diffraction limit. While this is suitable for industrial applications, such as laser welding, it is not suitable for applications which require a more precise and tightly focused output laser beam. It is, therefore, desirable to provide a multiple laser disk resonator that produces a high energy, near diffraction limited laser beam that may be used for more precise laser beam applications.


A communication system for providing wireless local loop services comprises an intelligent base station for communicating with one or more customer premises remote units (CPRUs), each of which connects to a non-wireless device. Each CPRU has a wireless transceiver for over-the-air communication with the intelligent base station. The intelligent base station connects, without the assistance of a base station controller, to a mobile switching center (MSC), through a GSM A-interface or a specialized derivative thereof, and thereby to a public switched telephone network (PSTN). The intelligent base station employs a subset of GSM functionality, enabling the CPRU to take advantage of various advanced telephony features. A transcoder and rate adapter unit may be added between the intelligent base station and the mobile switching center. The intelligent base station may be capable of communicating with both mobile users and fixed wireless local loop customers, using time division multiple access (TDMA) to communicate with multiple users. The intelligent base station may transmit and receive messages using spread spectrum encoding. If mobility is provided within the system, intelligent base stations within a cluster may be connected over physical links so that signalling and bearer channels supporting a call from a mobile user are tunneled through one intelligent base station to the other during handover.

1. Field of the Invention
The field of the present invention relates to communication systems and methods and, in particular, to wireless local loop systems and methods of communicating in wireless local loop systems.
2. Background
Telephone service has traditionally been provided to business and residential customers through fixed landlines that are routed from the telephone network through switching stations to their local destinations. However, the costs associated with providing telephone services to some customers (i.e., those located in remote regions, or geographically harsh environments, or high rise buildings) using conventional cabling methods can be prohibitively expensive. For many network operators this expense is unavoidable, because the provision of service to such customers is often not optional under regulatory requirements to deliver service universally regardless of the cost, sometimes referred to as a xe2x80x9cuniversal service obligation.xe2x80x9d
In addition, conventional landlines can be expensive and time-consuming to deploy. Service to potential customers can be delayed while telephone lines and cables are being 25 deployed, causing frustration to such customers. In certain areas, the telephone provider may have to spend an excessive amount on telephone lines which might ultimately serve only a small client base. Moreover, maintenance of telephone cabling (e.g., copper lines) can be expensive, and such cabling can be subject to occasional faults which require repair or replacement and can be a significant inconvenience for customers.
The delay and expense of establishing landlines may also be a disadvantage to a telephone provider desiring to enter a new market quickly and cost effectively. Recent legislation in the United States has increased competition in local markets for provision of basic and enhanced telephone services. Telephone providers wanting to enter these markets rapidly so as to compete against or bypass an incumbent local access network operator may be at a disadvantage if required to deploy an extensive ground network of cabling in order to provide service.
Certain telephone customers have specialized needs that are difficult or unduly expensive to meet using only landlines to connect service. In particular, customers which experience high xe2x80x9cchurnxe2x80x9d (i.e., call turnover) or which require temporary provisioning may not be adequately served by existing landline connections. At the same time, it may not be cost effective to add expensive landlines where only temporary provisioning is required. Examples of customers having such specialized needs may include, e.g., universities and other educational institutions, hospitals, marinas, shopping malls, large exhibitions, construction sites, caravan parks, and the like.
As an additional consideration, a single type of telephone service may not be adequate to address the needs of disparate customers. For example, industrially undeveloped or under-developed countries or regions may require only basic telephone service (i.e., POTS service), whereas industrially advanced countries or regions may require high quality voice, data capability and custom calling features. Customers starting out with basic service may eventually want or need to upgrade to more advanced telephone features.
There is a need for a communication system allowing rapid and/or expedient rollout, so as to provide service in a timely fashion to both presently served markets as well as remotely located or otherwise hard-to-access customers. There is also a need for a communication system allowing easier and more cost-effective service for remote or rural customers. There is further a need for a telephone service that accounts for the needs of both basic and relatively advanced users, and which allows upward migration of features such as high quality voice, data and custom calling options. Additionally, there is need for a communication system that can provide economic telephone service to select customers who have specialized needs, including high churn or temporary provisioning.
The invention provides in one aspect a communication system for providing wireless local loop services which can be deployed relatively rapidly and which offers the benefits of advanced telephony features.
In one embodiment, a customer premises remote unit (CPRU) has a wireless transceiver for over-the-air communication, and is physically located at or near a customer site. The CPRU communicates wirelessly with an intelligent base station (IBS) that is preferably capable of supporting multiple access communication so as to enable support of multiple CPRUs and/or other users. The intelligent base station directly connects, without the assistance of a base station controller, to a mobile switching center (MSC), preferably through a GSM A-interface or a derivative thereof. The mobile switching center allows access to a public switched telephone network (PSTN). Telephones or other devices connected to the CPRU can thereby communicate with the PSTN over the connection established between the CPRU and the intelligent base station, through the mobile switching center. The intelligent base station preferably employs a subset of GSM functionality, enabling the CPRU to take advantage of various advanced telephony features, and offering an upward migration path for those users initially starting with basic telephone service. Because the intelligent base station can connect directly to the mobile switching center, deployment can be conducted more rapidly, without the need for connecting and configuring base station controllers in the area to be serviced.
In another embodiment, a transcoder and rate adapter unit is added between the intelligent base station and the mobile switching center. In this embodiment, the transcoding rate adaption unit and the CPRU represent peer-to-peer endpoints for ciphering.
In another aspect, an intelligent base station connected directly to a GSM mobile switching center is capable of communicating with both mobile users and fixed wireless local loop customers, by employing a flexible and robust over-the-air protocol for multiple access communication. In a preferred embodiment, the intelligent base station communicates with user stations (such as mobile handsets, or fixed CPRUs) by dividing a time frame into time slots and assigning the time slots to individual user stations, thereby carrying out time division multiple access communication. The intelligent base station preferably transmits and receives messages which have been encoded using spread spectrum techniques, and thereby transmits and receives messages over a bandwidth that is relatively wide compared with typical narrowband techniques. In one embodiment, the intelligent base station transmits over a first frequency band, while the user stations transmit over a second frequency band, thereby implementing frequency division multiple access (FDMA) and/or frequency division duplex (FDD) communication.
In another embodiment, a wireless local loop subsystem and a wireless mobile subsystem coexist in a single communication system. The wireless local loop subsystem comprises one or more intelligent base stations. The intelligent base stations are connected to a mobile switching center (MSC) over a GSM A-interface. In a particular version of such an embodiment, a intelligent base stations within a cluster are connected over physical links, and when a mobile station communicating with a first intelligent base station in the cluster is handed over to a second intelligent base station in the cluster, signalling and bearer channels supporting the call are tunneled through the first intelligent base station (which becomes the anchor base station) to the second intelligent base station (which becomes the relay base station) over a physical link. The call then proceeds with communication being carried through both the anchor and relay base stations.
Further embodiments as well as modifications, variations and enhancements of the invention are also described herein.

Wireless local loop with intelligent base station


A method and apparatus of automatically locating in an image of a blood vessel the lumen boundary at a position in the vessel and from that measuring the diameter of the vessel. From the diameter of the vessel and estimated blood flow rate, a number of clinically significant physiological parameters are then determined and various user displays of interest generated. One use of these images and parameters is to aid the clinician in the placement of a stent. The system, in one embodiment, uses these measurements to allow the clinician to simulate the placement of a stent and to determine the effect of the placement. In addition, from these patient parameters various patient treatments are then performed.

Coronary artery disease is one of the leading causes of death worldwide. The ability to better diagnose, monitor, and treat coronary artery diseases can be of life saving importance. Intravascular optical coherence tomography (OCT) is a catheter-based imaging modality that employs safe, non-ionizing near-infrared light to peer into coronary artery walls and present images valuable for the study of the vascular wall architecture. Utilizing broad-band coherent light, interferometry, and micro-optics, OCT can provide video-rate in-vivo tomography within a diseased vessel with resolution down to the micrometer level. This level of detail enables OCT to diagnose as well as monitor the progression of coronary artery disease.
The quantitative assessment of vascular pathology and its progression involves the calculation of different quantitative measures such as the vessel cross-sectional area, mean diameter, and blood flow resistance, all of which rely on the accurate identification of the luminal border. While the luminal border in OCT images is clearly identifiable by the human eye, it is tedious, expensive, and time consuming to manually trace the luminal border. Thus there is a need for a reliable technique that can automatically identify the luminal border.
OCT produces images that are higher in resolution and contrast compared to those of intravascular ultrasound (IVUS). As opposed to IVUS which images through blood, OCT images are typically acquired with blood cleared from the view of the optical probe. This is one reason the luminal border in OCT images is sharper and more defined compared to that in IVUS images.
Cross-sectional diameter and area measurements provide interventional cardiologists with useful guidance for stent sizing and placement. However, the relationship of these geometric measurements to clinically relevant variables, such as ability of the artery to supply an adequate flow of blood to the myocardium when metabolic demands are high, is not well understood. In early studies, the percent stenosis of an individual coronary lesion measured by angiography was found to be a relatively poor predictor of the physiological significance of the lesion. In contrast, several later studies demonstrated that lumen measurements made by quantitative coronary angiography (QCA) and IVUS correlate closely with physiologic measurements of coronary obstruction, including coronary flow reserve (CFR) and fractional flow reserve (FFR). For example, several studies found a high correlation between area stenosis, measured by QCA, and CFR measured by a Doppler flow wire. It appears that the standard angiographic (and IVUS) measures of lesion severity—the minimum lumen area (MLA), percentage stenosis, and lesion length—do indeed convey physiologically relevant information. However, the value of any single geometrical measure as an independent predictor of the physiological significance of a lesion in a wide patient population is not clear.
Several factors contribute to the limitation of standard angiographic and IVUS lumen measurements for assessment of the physiological significance of coronary stenoses. First, the accuracy and reproducibility with which cross-sectional areas can be measured with angiography, which generally has a spatial resolution of 0.2-0.4 mm, are relatively low. The angle of the X-ray projection, in addition to the shadowing effect of lesions with irregular contours, can increase errors significantly beyond the theoretical minimums Even state-of-the-art IVUS imaging systems, which have resolutions of approximately 0.15 mm in the axial dimension and 0.3 mm in the angular dimension, cannot accurately measure the cross-sectional areas of small eccentric lesions or lesions with irregular borders.
Second, the hemodynamic effects of a lesion depend on local variations of its cross-sectional area integrated over the entire length of a lesion. Therefore, the minimum cross sectional area alone is insufficient to characterize the pressure drop across a lesion at a given flow rate, especially in patients with diffuse coronary disease.
Third, when assessing the physiological significance of a lesion and the potential value of revascularization, it is important to know the relative areas of the reference and stenotic segments, in addition to the absolute value of the minimum lumen area. No single geometrical measure in clinical use today conveys information about both percent stenosis and MLA.
Fourth, the flow resistance or pressure drop caused by an incremental segment of a lesion depends on its shape as well as its cross-sectional area and length. Especially at high blood flow rates, the eccentricity and local slope of the walls of the artery can influence the effective resistance of a lesion, because losses due to flow separation and turbulence depend on local flow velocity.
Finally, in certain patients, the flow reserve of the myocardium supplied by the vessel can be low, due to microvascular disease, flow through collateral branches, or capillary shunts within infarcted myocardium. Therefore, even if the vascular resistance of a lesion in the vessel is high, revascularization may be contraindicated, because the pressure drop across the lesion may be clinically insignificant.
Intravascular OCT imaging, applied in combination with new clinical parameters based on advanced analysis of lesion morphology, has the potential to overcome many of the limitations of conventional measures of lesion severity based on angiography and IVUS. The high resolution of OCT enables accurate measurement of the shape and dimensions of the vessel lumen over the length of the lesion and its adjacent reference segments. Furthermore, advanced models of flow dynamics enable the physiological significance of lesions to be estimated under both normal and hyperemic conditions. It should be realized, however, that the clinical value of quantitative lesion morphology measurements—even when accurate—may be limited by physiological conditions in certain patients. Finally, high-frequency OCT imaging has the advantage that it can precisely delineate three-dimensional contours of long segments of coronary arteries in a few seconds to assist cardiologists in their real-time diagnosis and treatment during PCI procedures.
In spite of advances in intravascular imaging, cardiologists frequently do not take full advantage of the capabilities of OCT and IVUS for planning and evaluating stent deployment, because the measurements currently derived from the images provide insufficient information to predict the effectiveness of treatment. For example, many cardiologists rely on minimum lumen area (MLA) as a key variable in their stenting decisions. If MLA measurements are sufficiently low, the cardiologist may decide to implant a stent. Based on the diameters and locations of reference vessel segments, the cardiologist must then choose the proper position, length, and diameter of the stent. The wrong choice of the size or location of the stent may lead to the failure to restore blood flow and may even cause potentially serious clinical complications, such as stent migration, stent thrombosis, or dissection of the vessel wall. There is a need for new methods for optimization of stent sizing and positioning based on measurements derived from intravascular images. To achieve maximum clinical benefit, these new methods should enable cardiologists to predict the potential physiological consequences of implanting stents of different diameters and lengths in different locations.
The present invention addresses these needs.

Optical coherence tomography lumen morphology and vascular resistance measurements methods for blood vessel evaluations


Disclosed are a display device and a driving method thereof. The display device includes a first common electrode line connected to a first common electrode of a plurality of common electrodes, and formed to overlap a data line formed in a panel where the plurality of common electrodes are formed. The plurality of common electrodes are separated from each other in a block form, receive a common voltage in an image output period, and receive a touch driving voltage in a touch sensing period. The display device includes a second common electrode separated from the first common electrode line with a protective layer therebetween, and configured to include two second common electrode plates which are separated from each other in a left and right direction with respect to the first common electrode line.

1. Technical Field
The present disclosure relates to a display device and a driving method thereof, and more particularly, to a display device including a panel with a built-in touch panel and a driving method thereof.
2. Discussion of the Related Art
Touch panels are a type of input device included in or built into display devices such as liquid crystal display (LCD) devices, plasma display panels (PDPs), organic light emitting display device (OLED), and electrophoretic displays (EPDs). A touch panel enables a user to input information by directly touching a screen of a display device with a finger, a pen or the like while looking at the screen of the display device.
Particularly, the demand for display devices integrated with in-cell type touch screens is recently increasing. In-cell type touch screens include a plurality of built-in elements configuring the touch screen for slim portable terminals such as smart phones and tablet personal computers (PCs).
In-cell type display devices may be categorized into mutual display devices and self-capacitive display devices.
FIG. 1 is an exemplary diagram illustrating a configuration of a related art mutual display device. FIG. 2 is an exemplary diagram illustrating a related art self-capacitive display device. FIG. 3 is an exemplary view illustrating a cross-section taken along line C-C′ of FIGS. 1 and 2.
A mutual display device 10, as illustrated in FIG. 1, includes: reception electrodes RX1, RXn-1, RXn (collectively referred to herein as a reception electrode RX) formed in a block form in parallel with a data line in a display area A of a panel; driving electrodes TX1, TXm-1, TXm (collectively referred to herein as a driving electrode TX) configured with a plurality of driving electrode parts 11 which are disposed with the reception electrode RX therebetween, and is formed in parallel with a gate line in the display area A; a display driver 19 that is provided in a non-display area B of the panel that controls the data line and the gate line, and applies a common voltage or a touch driving voltage to the driving electrode TX and the reception electrode RX; a reception electrode line 15 that extends from the reception electrode RX, and is connected to the display driver 19; a driving electrode line 12 that extends from the driving electrode TX in parallel with the data line, and is connected to the display driver 19; and a touch driver (not shown) that determines whether there is a touch, by using the driving electrode and the reception electrode which are connected to the touch driver through the display driver.
A self-capacitive display device 20, as illustrated in FIG. 2, includes: a plurality of touch electrodes 21 that are formed in a display area A of a panel; a display driver 29 that is provided in a non-display area B of the panel, and drives the touch electrodes 21; and a touch driver (not shown) that is connected to the touch electrodes 21 through the display driver 29, and determines whether there is a touch. In this case, in each of the touch electrodes 21, a touch electrode line 22 is formed in parallel with the data line. Also, when the number of width-direction touch electrodes is Q number and the number of height-direction touch electrodes is P number, the touch driver (not shown) includes a total of n (where n is Q×P) number of sensing units.
In the display device, a cross-sectional surface taken along line C-C′ of FIGS. 1 and 2 is as illustrated in FIG. 3. Referring to FIG. 3, in the in-cell type display device, a gate insulating layer 10b (20b) is coated on a base substrate 10a (20a), and a data line 10c (20c) is formed thereon. A buffer layer 10d (20d) is coated on the data line 10c (20c), and an insulating layer 10e (20e) is formed thereon. The driving electrode line 12 (or the touch electrode line 22) and a pixel electrode 10f (20f) are formed on the insulating layer 10e (20e), a protective layer 10g (20g) is coated thereon, and the driving electrode part 11 (or the touch electrode 21) is formed thereon. In FIG. 3, units Nos. 10 to 19 denote elements of the mutual display device illustrated in FIG. 1, and units Nos. 20 to 29 denote elements of the self-capacitive display device illustrated in FIG. 2. In FIG. 3, as an example of the driving electrode parts 11, a #(m,1)th driving electrode part 11b of FIG. 1 is illustrated, and as an example of the touch electrodes 21, a #Pth touch electrode 21b of FIG. 3 is illustrated.
Here, referring to FIGS. 1 to 3, the driving electrode line 12 connected to a #(1,1)th driving electrode part 11a is disposed with the protective layer 10g between the driving electrode line 12 and the #(m,1)th driving electrode part 11b.
Also, referring to FIGS. 1 to 3, the touch electrode line 22 connected to a #1st touch electrode 21a is disposed with the protective layer 20g between the touch electrode line 22 and a #Pth touch electrode 21b.
During a touch sensing period, in the mutual display device of FIG. 1, different touch driving voltages are supplied to the #(1,1)th driving electrode part 11a and the #(m,1)th driving electrode part 11b, and thus, as illustrated in FIG. 3, a parasitic capacitance D is generated between the driving electrode line 12 connected to the #(1,1)th driving electrode part 11a and the #(m,1)th driving electrode part 11b.
Moreover, during the touch sensing period, in the self-capacitive display device of FIG. 2, the same touch driving voltage is supplied to the #1st touch electrode 21a and the #Pth touch electrode 21b, but since the touch electrode line 22 connected to the #1st touch electrode 21a is adjacent to the #Pth touch electrode 21b, as illustrated in FIG. 3, the parasitic capacitance D is generated.
The parasitic capacitance D can cause noise. Due to the noise, a touch sensitivity can be reduced, or a touch error can occur.
In the related art mutual display device and the self-capacitive display device, during the touch sensing period, the driving electrode part 11 and the driving electrode line 12 or the touch electrode 21 and the touch electrode line 22 are parallelly disposed with the protective 10g or 20g therebetween, and for this reason, the parasitic capacitance D that is a cause of noise is generated between the two elements.
FIG. 4 is a waveform diagram showing an image output ('display') period and a touch sensing ('Touch') period in the related art in-cell type display device, and FIG. 5 is an exemplary diagram showing a waveform of a touch driving voltage supplied to a driving electrode and a reception electrode in the related art mutual display device.
In the related art mutual display device and self-capacitive display device, as shown in FIG. 4, the image output period and the touch sensing period are temporally divided (e.g., mutually distinct, non-overlapping, and optionally, interleaved).
Particularly, a touch panel applied to the mutual display device of FIG. 1 includes a driving electrode TX, which receives the common voltage (Vcom) in the image output ('display') period and receives the touch driving voltage in touch sensing period, and a reception electrode RX which receives the common voltage in the image output period, and receives a reference voltage in the touch sensing period.
In this case, in the touch sensing period of the mutual display device, block dim can occur in a panel of the mutual display device due to a difference between root mean square values (Vrms) of voltages respectively input to the driving electrode TX and the reception electrode RX.
That is, during the image output period, the common voltage Vcom is supplied to the driving electrode TX and the reception electrode RX.
However, during the touch sensing period, as shown in FIG. 5 (a), a pulse-type touch driving voltage is supplied to the driving electrode TX, and as shown in FIG. 5 (b), the reference voltage VRX_REF is supplied to the reception electrode RX. The touch driving voltage swings between the maximum value VTX_HIGH and the minimum value VTX_LOW. The value of VTX_LOW is also equal to the value of VRX_REF.
In this case, as shown in FIG. 5, a root mean square value TX_RMS of the touch driving voltage is a value between the common voltage Vcom and the maximum value VTX_HIGH. The reference voltage VRX_REF is the same as a root mean square value RX_RMS of the reference voltage. The root mean square value TX_RMS of the touch driving voltage differs from the root mean square value RX_RMS of the reference voltage.
Therefore, in the panel of the mutual display device, block dim can occur due to a difference between the root mean square values.

Display device and driving method thereof