The present invention comprises a method for the quantitative or qualitative detection of antigen-specific CD4+ T cells and/or CD8+ T cells in a subject, said method comprising quantitatively or qualitatively detecting the expression of cell surface marker CD25 and one or more of cell surface markers CD134 and CD137 in a suitable lymphocyte-containing sample from said subject in response to exposure to an antigen. A method for determining the immunocompetence of a subject and a method for isolating antigen-specific CD4+ and/or CD8+ T cells is also disclosed.

The CD4+ subpopulation of T lymphocytes (CD4+ T cells) play a major role in the body's defense against intracellular pathogens such as pathogenic intracellular bacteria (e.g. Mycobacteria) and fungus (e.g. Candida), viruses and protozoa. In particular, the CD4+ T cells help to regulate the cell-mediated immune response to infection by such intracellular pathogens, and indeed are often referred to as "helper" T cells, by promoting a variety of immune responses from other cells (e.g. promotion and maturation of B lymphocytes and antibody responses, activation of macrophages, and enhancement of natural killer (NK) cell and CD8+ cytotoxic T cell (CTL) activity) through the release of cytokines in response to antigenic stimulation. Such antigenic stimulation is achieved by the recognition by "primed" CD4+ T cells (i.e. CD4+ T cells which have been previously exposed to an antigen to become "antigen-specific CD4+ T cells") of an antigen presented by any antigen presenting cell expressing an appropriate class II major histocompatibility complex (MHC) protein. As mentioned above, one of the immune responses, or "effector functions", brought about by stimulated CD4+ T cells is the activation of macrophages. Activated macrophages play a vital role in killing pathogens at sites of infection through increased phagocytic activity (i.e. activated macrophages show an increased ability to phagocytose pathogens) and other activities. The interaction between antigen-specific CD4+ T cells and macrophages forms the basis of the so-called delayed type hypersensitivity response (DTH) which has been exploited in various skin tests to determine whether a subject has been previously exposed or "sensitised" to a particular antigen (e.g. an antigen from a pathogen or an allergen). One well known type of DTH skin test is the Mantoux test which employs tuberculin as an antigen in the testing for latent tuberculosis (caused by Mycobacterium tuberculosis) in a subject or for determining whether a subject has been previously vaccinated with bacille Calmette-Guerin (BCG) tuberculosis vaccine.
The Mantoux test, and other similar delayed-type hypersensitivity skin tests such as the BioMerieux Multitest, have been widely used in the clinic and diagnostic and research laboratories for detecting antigen-specific responses, presumptively mediated by CD4+ T cells. They do, however, require a considerable amount of time to perform (i.e. in order to achieve a readable result), require the patient to return for the reading of the result, and there is considerable intra-operator variability in the application and reading of these tests. These problems combine to limit their effective use. For example, for the Mantoux test, any DTH response must be observed some 2-3 days after administration of the tuberculin antigen, which may not be feasible or desirable for the effective testing of persons living in remote locations. Moreover, assessment of skin test results are relatively subjective, leading to qualitative, rather than quantitative results.
Apart from DTH skin tests, antigen-specific CD4+ T cells can be detected, and indeed measured, by other methods. For example, using peripheral blood mononuclear cells (PBMC), antigen-specific CD4+ T cells can be measured by the method known as the lymphoproliferation assay (LPA). However, this method, which utilises the ability of CD4+ T cells to proliferate in vitro and involves detecting the incorporation of 3H-thymidine into newly synthesised DNA after 6-7 days in culture, has several limitations making it unattractive for diagnostic laboratories, namely: (i) the use of high levels of radionucleotides; (ii) a long "turnaround" time; (iii) the requirement for lengthy processing of blood samples to prepare PBMC; (iv) the dependence on carefully screened human serum, with variability from batch to batch; (v) the need for culture techniques which require a high level of training; (vi) the fact that the response can only be attributed to CD4+ T cells if CD4+ T cells are first purified; and vii) substantial inter- and intra-assay variability making standardisation between laboratories problematical. Presently, LPAs are seldom performed except in research laboratories.
Another example is a flow cytometric version of the LPA, using carboxy-fluorescein diacetate, succinimidyl ester (CFSE)-labelled PBMC (1). This assay has been widely used in research laboratories, and although it has the distinct advantages that it does not use radioactivity and also allows for the direct identification of responding CD4+ T cells, it still suffers from the other disadvantages of the LPA. In addition, this assay has the disadvantage that the flow cytometric analysis must be very carefully performed since the number of relevant cells can be very low, often amidst substantial background staining.
A further example is the so-called intracellular cytokine (ICC) assay. This has become a relatively widely used assay in research laboratories, and it allows for the direct detection of antigen-specific CD4+ T cells in whole blood cultures (2). This assay is, however, quite labour-intensive; requiring either a 6 hour culture with whole protein antigens (2 hours for antigen processing and presentation, plus 4 hours with brefeldin A) or 6 hour culture with peptides and brefeldin A. Further, when samples are obtained late in the day, they require a processing step late at night, or are otherwise left until the next day, which is not optimal. Moreover, a 2 hour intracellular staining step is then required after the culture, followed by flow cytometric analysis. Automation of the ICC assay is possible (3), but not generally available. Also, standardisation between laboratories is problematical.
Accordingly, there is no method for detecting antigen-specific CD4+ T cells amongst those that are presently available that are readily applicable to the clinic and diagnostic and research laboratories. Further, of those that are suitable for use in diagnostic laboratories, various problems and difficulties with them have made them unpopular. However, assays for detecting antigen-specific CD4+ T cells are not the only kind of immune response assay that have fallen from favour in diagnostic laboratories. That is, the response of lymphocytes of the immune system to the polyclonal mitogen, phytohaemagglutinin (PHA), has been previously widely used as a measure of general T cell immunocompetence (e.g. for cases of suspected primary immunodeficiency (4)); however, since this assay is based on the 3H-thymidine LPA, with the exception that the cells are harvested at day 3, it is subject to essentially the same disadvantages as the LPA.
A simpler whole blood method has been proposed in which small aliquots of anti-coagulated samples of whole blood are incubated with an antigen or PHA for 4 hours (up to 24 hours), and activation measured by up-regulation of the early T-cell activation marker antigen, CD69, on CD4+ T cells, by flow cytometry (5). This whole blood assay, with a short turnaround time and very simple cell surface readout, was an attractive approach. However, in the hands of the present applicant, it has been found that while the assay is useful for measuring polyclonal PHA responses, it is not sufficiently specific for detecting antigen-specific CD4+ T cells since an unfeasibly large number of CD4+ T cells up-regulate CD69 in response to antigen indicating a lack of specificity with this readout. Further, it was found that the analysis of results was complicated by the presence of CD69 on a small but significant subset of CD4+ T cells ex vivo.
Another example of a whole blood assay for antigen-specific CD4+ T cells that is in use is the Quantiferon® whole blood stimulation assay (CSL Limited, Melbourne, VIC, Australia). In this assay, following antigenic stimulation, the plasma is collected and assayed for IFN-γ by ELISA. However, as with the standard LPA, the response is not confirmed as being due to CD4+ T cells, since much IFN-γ is produced by CD8+ T cells, particularly in response to viral antigens, as well as by NK cells present in the cultures. At present, this assay is only licensed for detection of responses to M. tuberculosis. However, the assay has been observed to give high numbers of indeterminate results in young paediatric populations. There is a second assay for the detection of IFN-γ responses stimulated by M. tuberculosis known as the T spot TB assay approved for use in the Europe. This assay is an ELIspot based method, requiring separation of PBMC before plating out in an ELIspot plate. The assay appears to have similar specificity and sensitivity, but a lower rate of indeterminate results in paediatric and immuno-suppressed patients.
Accordingly, there remains a need for an alternative and relatively simple and cost effective method for detecting, particularly, antigen-specific CD4+ T cells, but also antigen-specific CD8+ T cells.
While investigating the kinetics of the up-regulation of the cell surface marker antigen CD25 (a transmembrane protein that is the α-chain of the interleukin-2 (IL-2) receptor) and cell division using CFSE-labelled PBMC, the present applicant found that CD25 was highly up-regulated on CD4+ T cells in response to antigen or mitogen from 24 hours onwards, preceding cell division which begins at about 48 hours onwards. At the same time, the kinetics of expression of certain co-stimulation cell surface proteins such as CD134 (OX40) and CD137 (4-1BB) was being investigated, and it was found that up-regulation of these proteins also occurred from 24 hours onwards. Genetic studies in mouse models have shown that the interaction between OX40 on CD4+ T cells and OX40 ligand (OX40L) on antigen-presenting cells is crucial for the generation of "memory" CD4+ T cells (i.e. primed CD4+ T cells that have developed into so-called memory cells able to confer immediate protection as well as the capacity to mount a more rapid and effective immune response to antigenic stimulation), and the promotion of effector CD4+ T cells survival after antigen priming. Since it had been previously reported that CD134 expression on CD4+ T cells peaks at 24-48 hours after stimulation of the T cell receptor by antigen or mitogen, and returns to baseline about 120 hours later (6), the present applicant therefore investigated whether CD25 and CD134 were co-expressed just prior to 48 hour (i.e. a timepoint that corresponded with maximal CD134 expression, but prior to the commencement of cell division), using whole blood cultures stimulated with antigens or mitogens, and might therefore be used as the basis of a relatively simple and cost effective method for the detection and/or measurement of antigen-specific CD4+ T cells. It was found that these cell surface markers for antigen-specific CD4+ T cells can be readily measured by flow cytometry after 40-44 hours incubation with antigen using sodium heparin anti-coagulated whole blood samples. Therefore, the method combines simplicity of set up (i.e. without the need for preparation of PBMC) with a simple flow cytometry read-out (i.e. without the need to permeabilise cells and detect cytokines). Further, it was found that the method has a surprisingly low background (<0.03% of CD4+ T cells), and by using the method, it has to-date been possible to readily detect specific CD4+ T cells responses to antigens contained in preparations of mycobacterial antigens, tetanus toxoid, Cytomegalovirus (CMV) lysate, vaccinia lysate and peptides of Human Immunodeficiency Virus (HIV-1). Moreover, it has been found that the method can also be used in assessing the broader responses to mitogens such as PHA and Staphylococcal enteroantigen B (SEB), as a measure of general immunocompetence. Still further, the method has application in cell sorting of antigen-specific or mitogen-activated CD4+ T cells, whereby fixation and permeabilisation steps may be avoided.

Method for detecting antigen specific or mitogen-activated T cells


The present embodiments are generally directed to layers that are useful in imaging apparatus members and components, for use in electrophotographic, including digital, apparatuses. More particularly, the embodiments pertain to an electrophotographic imaging member having a charge transport layer in which a charge transport molecule (CTM) concentration gradient is formed through a single coating pass using only a single charge transport layer solution, and time-of-flight based methods of measuring the CTM gradient through the thickness of the charge transport layer.

This disclosure is generally directed to layered imaging members, photoreceptors, photoconductors, and the like. More specifically, the present disclosure is directed to rigid or drum photoreceptors, and to multilayered flexible, belt imaging members, or devices comprised of an optional supporting medium like a substrate, a photogenerating layer, a charge transport layer, and a polymer coating layer, an optional adhesive layer, and an optional hole blocking or undercoat layer. The photoreceptors illustrated herein, in embodiments, have excellent wear resistance; extended lifetimes; provide for the elimination or minimization of imaging member scratches on the surface layer or layers of the member, and which scratches can result in undesirable print failures where, for example, the scratches are visible on the final prints generated; permit excellent electrical properties; minimum cycle up after extended electrical cycling, such as 10,000 simulated cycles; increased resistance to running deletion, know as LCM; and mechanical robustness. Additionally, in embodiments the imaging or photoconductive members disclosed herein possess excellent, and in a number of instances low Vr (residual potential), and the substantial prevention of Vr cycle up when appropriate; high sensitivity, and desirable toner cleanability.
Also included within the scope of the present disclosure are methods of imaging and printing with the photoreceptor devices illustrated herein. These methods generally involve the formation of an electrostatic latent image on the imaging member, followed by developing the image with a toner composition comprised, for example, of thermoplastic resin, colorant, such as pigment, charge additive, and surface additive, reference U.S. Pat. Nos. 4,560,635; 4,298,697 and 4,338,390, the disclosures of which are totally incorporated herein by reference, subsequently transferring the image to a suitable substrate, and permanently affixing the image thereto. In those environments wherein the device is to be used in a printing mode, the imaging method involves the same operation with the exception that exposure can be accomplished with a laser device or image bar. More specifically, the photoreceptors disclosed herein can be selected for the Xerox Corporation iGEN3® and Nuvera® machines that generate with some versions over 100 copies per minute. Processes of imaging, especially xerographic imaging and printing, including digital, and/or color printing, are thus encompassed by the present disclosure. The imaging or photoconductive members disclosed are in embodiments sensitive in the wavelength region of, for example, from about 400 to about 900 nanometers, and in particular from about 650 to about 850 nanometers, thus diode lasers can be selected as the light source.
There is an intense competitive pressure to improve the functional performance of xerographic photoreceptors. For example, it is desirable to reduce Lateral Charge Migration (LCM) and improve mechanical strength. Also, it is desirable to minimize changes in its electrical characteristics during prolonged electrical cycling. The concentration of the charge transport molecules at the surface of the charge transport layer (CTL) is a known factor in the severity of lateral charge migration (LCM) caused by oxidation of the transport molecule. Also, the concentration of the charge transport molecule in the bulk CTL is a known factor in the formation of printable stress cracks in PR devices. The lower the concentration of the transport molecule at the surface, the lower the severity of LCM. Also, the lower the concentration of the transport molecule in the bulk, the less susceptible the device will be to printable cracks. The presently disclosed embodiments relate to an imaging or photoconductive member having a charge transport layer in which a charge transport molecule (CTM) concentration gradient, wherein the concentration of the CTM is lower at the surface of the CTL than it is toward the substrate side of the CTL.

Methods for measuring charge transport molecule gradient


The invention relates to oligopeptide derivatives whose C-terminal amino acid is arginine which is linked to the remainder of an electroactive aniline or aminoquinoline derivative by an amide bond. The oligopeptide derivatives are split by enzymes of the class of peptide hydrolases, especially proteinases and their inhibitors, of the coagulation system, the fibrinolytic system and the complement system. These oligopeptide derivatives serve as substrates for quantitatively determining such enzymes, especially thrombin, in complex sample liquids, especially capillary blood. This determination is carried out by measuring the increase in the water-soluble amperogenic aniline or aminoquinoline compound. The oligopeptide derivatives and their salts can be produced according to usual methods in peptide chemistry.

The present invention relates to oligopeptide derivatives of the formula (I)
in which
R1 is
(a) a hydrogen atom, a C2-8-alkanoyl group optionally having an amino group in the xcfx89 position, a phenyl-C2-4-alkanoyl group whose phenyl radical is optionally substituted in the p position by an amino group; or
(b) a cyclohexylcarbonyl group which is optionally substituted in the 4 position by an aminomethyl radical, a benzoyl group which is optionally substituted in the o or p position by methyl, amino or halogen, a C1-8-alkoxycarbonyl group, a benzyloxycarbonyl group which is optionally substituted in the p position by methoxy, methyl or chlorine; or
(c) a radical of the formula xe2x80x94SO2xe2x80x94R5 where R5 can be a C1-6-alkyl radical, an optionally substituted aryl or heteroaryl radical or a radical of a bicyclic terpene derivative; or
(d) a group of the formula xe2x80x94COxe2x80x94CH(R6)xe2x80x94NHxe2x80x94R7, where R6 is hydrogen, a C1-6-alkyl radical, a 1- or 2-hydroxyethyl radical, a methylmercaptoethyl radical, an aminobutyl radical, a guanidinopropyl radical, a carboxy-C1-4-alkyl radical, a carboxamido-C1-4-alkyl radical, a phenyl-C1-4-alkyl radical whose phenyl radical is optionally substituted by OH, halogen, C1-4-alkyl or methoxy, or a cyclohexyl or cyclohexylmethyl radical whose ring is optionally substituted by OH, halogen, C1-4-alkyl or methoxy, or a nitrogen-containing heteroaryl-C1-4-alkyl radical with 3 to 8 carbon atoms in the heterocyclic system, where the group xe2x80x94COxe2x80x94CH(R6)xe2x80x94NHxe2x80x94R7 may be racemic or have the D or L configuration, and R7 can be a group of type (a), (b) or (c); or
(e) a group of the formula
where R7 has the above meaning, m can be 1 or 2, and one of the methylene groups can be substituted by hydroxyl, carboxyl, C1-4-alkyl or aryl-C1-4-alkyl;
R2 is hydrogen, C1-6-alkyl, C1-2-hydroxyalkyl, C1-4-alkoxy-C1-6-alkyl, benzyloxy-C1-2-alkyl, an xcfx89-carboxy-C1-3-alkyl radical, an xcfx89-C1-4-alkoxycarbonyl-C1-3-alkyl radical, an xcfx89-benzyloxycarbonyl-C1-3-alkyl radical or a cyclohexyl, cyclohexylmethyl, 4-hydroxycyclohexylmethyl, phenyl, benzyl, 4-hyroxybenzyl or imidazolyl-4-methyl radical;
R3 is
(a) hydrogen or C1-4-alkyl and R3xe2x80x2 is hydrogen; or
(b) together with R3xe2x80x2 a tri- or tetramethylene group, where one of the methylene groups can be substituted by hydroxyl, carboxyl, C1-4-alkyl or aryl-C1-4-alkyl; and
R4 is
(a) an aniline residue of the formula
where R8 can be hydroxyl or amino and R9 can be hydrogen, halogen, amino, nitro, C1-4-alkyl, C1-4-alkoxy or C1-4-alkanoyl; or
(b) a quinoline residue of the formula
where one of R10, R11 and R12 is an xe2x80x94NH group via which the quinoline residue is linked to the Arg residue, a second one can be hydroxyl or amino, and the third one can be hydrogen, hydroxyl or amino;
and the salts thereof.
These oligopeptide derivatives and the salts are novel. They are cleaved by enzymes of the peptide hydrolase enzyme class (E.C. 3.4.), in particular proteinases (E.C. 3.4.21-99) and inhibitors thereof, of the blood coagulation system, of the fibrinolytic system and of complement, in particular of thrombin. They thus serve as substrates for the quantitative and qualitative determination of the abovementioned enzymes, in particular thrombin, in complex sample liquids, in particular capillary blood.
The present invention relates to novel oligopeptide derivatives of the formula (I) and salts thereof, to the preparation of these oligopeptide derivatives and salts, and to a method for the quantitative determination of a protease or antiprotease, in particular of the blood coagulation system, of the fibrinolytic system or of complement, in particular thrombin, which is carried out by means of the novel oligopeptide derivatives or salts thereof.
The term xe2x80x9calkylxe2x80x9d used in this description designates, on its own or in combinations such as xe2x80x9chydroxyalkylxe2x80x9d or xe2x80x9cbenzyloxyalkylxe2x80x9d, straight-chain or branched saturated hydrocarbon radicals such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like. The term xe2x80x9calkoxyxe2x80x9d designates an alkyl radical within the meaning of the above definition of xe2x80x9calkylxe2x80x9d, which is linked via an oxygen bridge. The term xe2x80x9calkanoylxe2x80x9d designates the acyl radical of an alkylcarboxylic acid which may be straight-chain or branched, such as acetyl, propionyl and the like. The term xe2x80x9carylxe2x80x9d designates the radical of an aromatic hydrocarbon and comprises radicals such as phenyl, naphthyl and the like. The term xe2x80x9cheteroarylxe2x80x9d designates the radical of an aromatic heterocyclic system such as imidazolyl, indolyl, quinolinyl, isoquinolinyl and the like.
If R1 in formula (I) is a radical of the formula xe2x80x94SO2R5, then R5 can be, for example, methyl, isopropyl, phenyl, tert-butylphenyl, 4-methylphenyl, 2,4,6-trimethylphenyl, 2,4,6-triisopropylphenyl, 4-methoxy-2,3,6-trimethylphenyl, anthraquinoyl, 1- or 2-naphtyl, quinolyl or isoquinolyl or a radical derived from camphor. If, in formula (I), R1 is a group of the formula xe2x80x94COxe2x80x94CH(R6)xe2x80x94NHxe2x80x94R7 and R6 is heteroarylalkyl, then R6 can be, for example, imidazolylmethyl or indolylmethyl.
If the N-terminal amino acid in the molecule carries a protective group, then this protective group is expediently tert-butoxycarbonyl (xe2x80x9cBocxe2x80x9d), p-toluenesulfonyl (xe2x80x9cTosxe2x80x9d), tert-butylphenylsulfonyl (xe2x80x9ct-Bupsxe2x80x9d), methylsulfonyl (xe2x80x9cMesxe2x80x9d), naphthylsulfonyl (xe2x80x9cNapsxe2x80x9d), benzoyl (xe2x80x9cBzoxe2x80x9d), benzyloxycarbonyl (xe2x80x9cZxe2x80x9d), isopropylsulfonyl or camphorsulfonyl.
If R4 is an aniline residue, then expediently R8 is hydroxyl in the o- or p position and R9 is halogen in the m position or R8 is hydroxyl in the o, m or p position and R9 is nitro or C1-4-alkanoyl in the m or p position. The radical R4 is preferably derived from 2-amino-4-nitrophenol, 4-amino-2-nitrophenol, 4-amino-3-nitrophenol, 2-amino-5-nitrophenol, 2,4-diaminotoluene, 2,4-diaminophenol, 4-amino-m-cresol, 2,5-diaminoanisole, 4-nitro-o-phenylenediamine, 2-amino-4-chlorophenol, 4-amino-2-chlorophenol, 4-amino-3-chlorophenol, 4-fluoro-2-aminophenol, 2-fluoro-4-aminophenol, 5-fluoro-2-aminophenol, 5-amino-8-hydroxyquinoline or 2-amino-8-hydroxyquinoline.
The oligopeptide derivatives of the formula (I) contain L-arginine (xe2x80x9cArgxe2x80x9d) as C-terminal amino acid. Further amino acids which may be present in the molecule are, for example, 2-aminobutyric acid, alanine, 3-cyclohexylalanine, 2-cyclohexylglycine, phenylalanine, pipecolic acid, proline and valine, it being possibe for these amino acids to be in the L, D or DL form, and glycine; preference is given in this connection to L-alanine (xe2x80x9cAlaxe2x80x9d), L-2-aminobutyric acid (xe2x80x9cAbuxe2x80x9d), D-3-cyclohexylalanine (xe2x80x9cD-Chaxe2x80x9d), D-2-cyclohexylglycine (xe2x80x9cD-Chgxe2x80x9d), glycine (xe2x80x9cGlyxe2x80x9d) and L-proline (xe2x80x9cProxe2x80x9d).
Representative examples of oligopeptide derivatives of the formula (I) are:
H-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
Boc-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
Tos-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
t-Bups-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
Mes-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
Naps-2-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
Z-(D)-Chg-Gly-Arg 3-chloro-4-hydroxyanilide;
H-(D)-Cha-Gly-Arg 3-chloro-4-hydroxyanilide;
Boc-(D)-Cha-Gly-Arg 3-chloro-4-hydroxyanilide;
H-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
Boc-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
Tos-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
t-Bups-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
Mes-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
isopropylsulfonyl-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
Naps-2-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
(xe2x88x92)-camphorsulfonyl-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
H-(D)-Cha-Pro-Arg 3-chloro-4-hydroxyanilide;
Boc-(D)-Cha-Pro-Arg 3-chloro-4-hydroxyanilide;
H-(D)-Cha-Ala-Arg 3-chloro-4-hydroxyanilide;
Boc-(D)-Cha-Ala-Arg 3-chloro-4-hydroxyanilide;
Boc-(D)-Cha-Abu-Arg 3-chloro-4-hydroxyanilide;
Z-Gly-Pro-Arg 2-chloro-4-hydroxyanilide;
Z-Gly-Pro-Arg 5-chloro-2-hydroxyanilide;
Z-Gly-Pro- Arg 8-hydroxyquinolin-5-ylamide;
Boc-(D)-Chg-Gly-Pro-Arg 3-chloro-4-hydroxyanilide;
H-(D)-Chg-Gly-Pro-Arg 3-chloro-4-hydroxyanilide; and
t-Bups-(D)-Chg-Gly-Pro-Arg 3-chloro-4-hydroxyanilide.
In the bloodstream numerous proteinases reach their site of action in the body. This underlines the importance of knowledge of the enzymic activity for understanding a wide variety of pathological states. Derangements of the balance between enzyme and inhibitor are responsible for the onset of an illness. It is therefore of inestimable value to be able to determine the enzymic activity present.
Blood or plasma are, however, not easy to handle as analysis media because of their properties (viscosity, absorption of visible light). In most cases, enzyme assays are carried out by photometric methods. There are limits to this especially in the case of blood, plasma or serum.
Photometric detection methods usually require clear sample solutions because the chromogenic properties of the synthetic substrates used and the chromophores thereof otherwise cannot have an effect. This often gives rise to preceding purification steps in order to obtain a measurable solution (compare DE 3616496 A1 and DE 19549117 A1).
Measurements of the enzymes of the blood coagulation system are, for example, d desired and carried out in patients with heart valve replacement or after myocardial infarctions. Patients of these types are subjected to a therapy with oral anticoagulants. The intention therewith is to prevent further thrombo-embolic events. For this purpose, the patients are treated at regular intervals with medicaments from the class of coumarin derivatives. However, this therapy requires monitoring for optimal dosage. The parameter of choice in order r to be able to derive an optimal dosage is determination of the Quick prothrombin time (PT).
The oligopeptide derivatives according g to the present invention make it possible to determine the prothrombin time using a substrate which generates an electrochemical signal. It is additionally possible to generate a sufficiently good signal from capillary blood.
European patent EP 0018002 B1 describes an electrochemical method for the determination of proteases of the blood coagulation systems, in particular of antithrombin, in citrated plasma using amperogenic substrates. Unfortunately, inaccuracies of measurement are possible in this elegant method for direct determination of thrombin or trypsin, because the addition of a solubilizer (DMSO) to the reaction medium is necessary to keep the amperogenic substrate dissolved in the reaction medium (J. M. Nigretto et al., Thrombosis Research 20, 299-306, 1980; Thrombosis Research 22, 303-308). The addition of a cosolvent may lead to an inaccuracy in the measurement of thrombin for practical use, for example screenings in the complex system of blood plasma or blood, for example through inducing coagulation, compromising an enzyme in the cascade, local substrate precipitation effects or the like.
The oligopeptide derivatives of the present invention now make possible a novel, direct amperogenic thrombin determination method which is better adapted to practice than previously disclosed determination methods. In this method, the increase in a water-soluble amperogenic compound resulting from the hydrolysis of the substrate by the enzyme is measured. This involves cleavage of a peptide residue whose C-terminal peptide residue is L-arginine, and of an electroactive residue which is connected by an amide linkage to the L-arginine, by the enzyme. The electroactive residue is then electrochemically oxidized or reduced, the change in the current is measured, and the latter is proportional to the concentration of the amperogenic residue formed during the enzymatic hydrolysis.
The method of the invention makes quantitative determination of a protease of antiprotease possible, in particular of the blood coagulation system, of the fibrinolytic system or of complement, in particular thrombin; it is characterized in that the enzyme is contacted in an aqueous or organic medium with an oligopeptide derivative of the formula (I) or a salt thereof, and the electroactive amine of the formula Hxe2x80x94R4, in which R4 has the above meaning, which is cleaved off by the enzyme to be determined and which can be electrochemically oxidized or reduced, is determined by amperometry.
The amperometry is expediently carried out using an apparatus with a potentiostat and a measuring cell with two or three electrodes, a measuring electrode made of steel or a noble metal, such as platinum or gold, a reference electrode and/or an auxiliary electrode, where the oligopeptide derivative of the formula (I) or salt thereof and possible water-soluble additions such as Ca++ salts, phospholipids or thromboplastin reagents is or are applied to the electrodes.
The change in the concentration of the electroactive amine of the formula R4xe2x80x94H in which R4 has the above meaning can be determined in the measuring cell through the measured oxidation or reduction current.
In a preferred embodiment of the determination method of the invention, a direct adhesion of these water-soluble substrates and of possible water-soluble additions such as, for example Ca++, phospholipids, Innovin(copyright) (from DADE-Behring) on a conducting surface made of steel or noble metal is possible, with the necessary electrodes being separated by an isolated bar. After addition of media which contain thrombin or which has been generated beforehand, for example in the blood or blood plasma with activators, for example Ca++, phospholipids, thromboplastin reagents or the like, the substrate is completely dissolved so that, through the liberation of the amperogenic amino compound, a direct determination of the current, proportional to the concentration of the electroactive amino compound, and thus the determination of the enzyme concentration in the medium, is possible.
It is surprising that, in contrast to EP 0 565 665, a mixture of 0-35% of L-xcex1-phosphatidylcholine (PC) and 65-100% of L-xcex1-phosphatidyl-L-serine (PS) is preferably used as phospholipids.
A particularly preferred mixing ratio of the phospholipids PC:PS is 65 to 75% PS and 25 to 35% PC.
The determination method of the invention can be used to determine thrombin in whole blood: whole blood is applied directly, without removal of blood cells and without removal of other constituents of blood, onto an electrode to which an oligopeptide derivative of the formula (I) or a salt thereof and possible water-soluble additions are adhering.
The substrate of the determination method of the invention, namely an oligopeptide derivative of the formula (I), consists of an oligopeptide residue to which the residue of a water-soluble aromatic or heteroaromatic amine is bonded. These residues of aromatic or heteroaromatic amines have additional functional groups such as, for example, hydroxyl groups or halogen atoms, which advantageously contribute to a lower electrochemical potential and crucially determine the solubility of the substrate in aqueous medium.
The oligopeptide derivatives of the formula (I) and salts thereof can be prepared according to the invention by using methods customary in peptide chemistry (general methods of M. Bodanszky xe2x80x9cThe Practice of Peptide Synthesisxe2x80x9d Springer Verlag, 2nd edition 1994) to link an amine of the formula Hxe2x80x94R4 in which R4 has the above meaning to the carboxyl group of arginine, whose amino group is protected or already has the appropriately protected residue of the peptide part of the desired product or a part thereof, and whose arginine group is protected, and, if necessary, the peptide part of the desired product is assembled completely, after which, if desired, the remaining protective group(s) is/are cleaved off and, if desired, a free amino group is acylated and/or, if desired, a resulting oligopeptide derivative of the above formula (I) is converted into an acid addition salt and/or a resulting acid addition salt of such an oligopeptide derivative is converted into a free oligopeptide derivative or into another salt.
The procedure can be such, for example, that the electroactive amino group is attached to the carboxyl group of the C-terminal arginine, its amino group being protected by a protective group, for example a benzyloxycarbonyl or tert-butyloxycarbonyl group, and the guanidino group of arginine being protected by protonization, for example with HCl or p-toluenesulfonic acid. The C-terminal electroactive amino group likewise serves as protective group during the stepwise assembly of the peptide chain. The other protective groups can be cleaved off selectively as required in order to attach the other amino acid residues, until the desired chain length is completely assembled. Finally, the remaining protective groups can be cleaved off completely without involving the electroactive amino group.
Oligopeptide derivatives with free N-terminal amino group can be acylated, for example with t-butylphenylsulfonyl chloride, tosyl chloride, acetyl chloride, butyl chloride, octanoyl chloride, benzoyl chloride, p-methylbenzoyl chloride, 2-chlorobenzoyl chloride, methylsulfonyl chloride, n-butylsulfonyl chloride, t-butylsulfonyl chloride, isopropylsulfonyl chloride, phenylsulfonyl chloride, 1- or 2-naphthylsulfonyl chloride, (+)- or (xe2x88x92)-camphorsulfonyl chloride or with malonyl chloride.
Preferred salts of oligopeptide derivatives of the formula (I) are those in which the strongly basic guanidino group of arginine is stabilized by protonization with HCl, HBr, H2SO4 or H3PO4 or with formic, acetic, propionic, phthalic, citric, oxalic, tartaric, benzoic, lactic, trichloroacetic or trifluoroacetic acid, in particular with HCl, acetic acid or trifluoroacetic acid.
In the determination method of the invention, the enzyme to be determined cleaves the bond between the carboxy-terminal amino acid arginine and the water-soluble aromatic or heterocyclic amine. The measurement method comprises electrochemical determination of the amount of liberated amine (xe2x80x9celectroactive speciesxe2x80x9d). This electrochemcial determination method is suitable for determining proteases of the blood coagulation systems, in particular thrombin.
The substrate of this determination method consists, for example, of tosyl-glycyl-prolyl-arginyl-3-chloro-4-hydroxyanilide monoacetate salt, in which case the following enzymatic reaction occurs:
Substrate: Tos-Gly-Pro-Arg 3-chloro-4-hydroxyanilidexc3x97AcOH+enzyme↓thrombin
Product: Tos-Gly-Pro-Arg-OH+4-amino-2-chlorophenol
The particular advantage of the determination method of the invention is that the substrates are dissolved homogeneously in any aqueous reaction medium without addition of solubilizers such as, for example, DMSO. It is therefore possible with this electrochemical determination method to determine the enzyme concentration in the reaction medium with high measurement accuracy.

Oligopeptide derivatives for the electrochemical measurement of protease activity


Disclosed are improved devices, systems and methods for storing, protecting and/or dispensing/delivering products that are particularly sensitive to pressure changes, alterations in gas distributions and/or partial pressures, physical impacts, temperature changes and/or other variations in the ambient environment.

Oxygen is one of the basic essentials for sustaining life and comprises approximately 20.95% of dry atmospheric air. While humans and other mammals are capable of passively absorbing some levels of oxygen directly from the atmosphere (via upper layer skin cells and the cells in the front surface of the eyes, for example), human and/or mammalian bodies have a huge demand for oxygen, and thus their need for lungs which actively pull in oxygen and transfer it to the blood, allowing the body to transport oxygen to various cells throughout the body.
Recently, methods of providing oxygenation to various anatomical structures utilizing pathways other than via the lungs have been proposed, including in U.S. Pat. Nos. 10,124,126 and 10,058,837 and others. Many of these approaches utilize microbubbles containing oxygen and/or other substances (including oxygen microbubbles or OMBs), which can be introduced into and/or can contact various anatomical structures, and which promote oxygen and/or carbon dioxide exchange (and/or flow of other nutrients and/or wastes) into and/or out of the anatomical structures and/or surfaces thereof. The oxygen microbubble (OMB) carrier may comprise oxygen gas filled bubbles having a shell composed of an amphiphilic surfactant phospholipid monolayer or cross-linked polymers or a combination of phospholipids and polymers, and may include other substances to enable and/or facilitate transfer of gases and/or other compounds into and/or out of the microbubbles. In various embodiments, the amphiphilic phospholipid monolayer shell variation of an exemplary OMB embodiment can have similar composition to lung surfactant and may require comparable physical properties, such as rapid adsorption to and mechanical stabilization of the gas/liquid interface and high gas permeability. Thus, OMBs can be designed to mimic the mechanical and gas transport properties of the alveolus to deliver the oxygen payload. By transport into and/or through the other anatomical structures, phospholipid monolayer, cross-linked polymer or mixed phospholipid-polymeric stabilized OMBs will desirably provide oxygen for uptake through tissue surfaces to underlying tissue layers and/or even to the bloodstream for transfer to more remote regions of the patient's body.
Unfortunately, microbubbles can often be relatively "fragile" structures that can "degrade" and/or assume various undesirable properties after manufacture, such as a tendency of some microbubbles to "pop" or "destruct" by experiencing a breakdown of the microbubble shell—typically in response to shear forces. Alternatively, individual microbubbles may coalesce together, some may reduce in size to become smaller microbubbles, and others may increase in size via absorption and/or incorporation of other substances, including oxygen obtained from other microbubbles. Microbubbles may also "destruct" or otherwise alter in size and/or shape through the absorption of the lipid shell, causing the microbubbles to break down and/or release the gaseous contents such as oxygen or other gases. Microbubbles can even degrade due to the effects of changing temperatures, natural or atmospheric pressure changes, and even changes in the humidity levels of the surrounding environment.
Large volume, sterile liquid products for medical use are generally produced on highly automated production lines to allow for economies of scale, as well as to aid in maintaining cleanliness and sterility, as human input is often the largest source of contamination during production. In many cases, the products must then be packaged and shipped to point-of-use locations such as clinics and hospitals. However, large volume, sterile products such as intravenous (IV) solutions are commonly supplied in plastic containers, which are generally not suitable for packaging of more fragile or delicate items such as microbubble products including phospholipid gas spheres. These containers are typically gas permeable and over time will allow specific gas concentrations in the product to equilibrate with the ambient atmosphere. Additionally, such non-rigid containers typically do not provide adequate protection from pressure changes through either atmospheric pressure changes or physical compression of the container, which pressure changes can lead to significant degradation of the microbubbles and/or their payloads.
In many cases, it would be desirous to be able to manufacture and store microbubbles containing gases, such as oxygen, for extended periods of time without significant degradation of the microbubbles. Moreover, it would be advantageous to transport such microbubble carriers and be able to dispense and/or distributer the microbubbles with a minimum of handling and/or transference between multiple containers.

Packaging for pressure and gas sensitive products


Provided are azeotrope-like compositions comprising tetrafluoropropene and hydrofluorocarbons and uses thereof, including use in refrigerant compositions, refrigeration systems, blowing agent compositions, and aerosol propellants.

Fluorocarbon based fluids have found widespread use in industry in a number of applications, including as refrigerants, aerosol propellants, blowing agents, heat transfer media, and gaseous dielectrics. Because of the suspected environmental problems associated with the use of some of these fluids, including the relatively high global warming potentials associated therewith, it is desirable to use fluids having low or even zero ozone depletion potential, such as hydrofluorocarbons ("HFCs"). Thus, the use of fluids that do not contain chlorofluorocarbons ("CFCs") or hydrochlorofluorocarbons ("HCFCs") is desirable. Furthermore, some HFC fluids may have relatively high global warming potentials associated therewith, and it is desirable to use hydrofluorocarbon or other fluorinated fluids having global warming potentials as low as possible while maintaining the desired performance in use properties. Additionally, the use of single component fluids or azeotrope-like mixtures, which do not substantially fractionate on boiling and evaporation, is desirable. However, the identification of new, environmentally-safe, non-fractionating mixtures is complicated due to the fact that azeotrope formation is not readily predictable.
The industry is continually seeking new fluorocarbon based mixtures that offer alternatives, and are considered environmentally safer substitutes for CFCs and HCFCs. Of particular interest are mixtures containing both hydrofluorocarbons and other fluorinated compounds, both of low ozone depletion potentials. Such mixtures and their uses are the subject of this invention.

Azeotrope-like compositions of tetrafluoropropene and hydrofluorocarbons


The present invention comprises a brace adapted to secure a fence rail to a fence post. The present invention brace may optionally be installed onto an existing fence or on a new fence. The invention includes a first fence rail brace member adapted to connect to two or more sides of a first fence rail, a second fence rail brace member adapted to connect to two or more sides of a second fence rail, and a fence post member adapted to connect to two or more sides of a fence post. The fence post brace member may form a vertical picket fastener slot, the first fence rail brace member may form a first horizontal picket fastener slot, and the second fence rail brace member may form a second horizontal picket fastener slot.

Fence and fence structure are subject to damage due to high winds, torrential rains, heavy snowfall, vehicular accidents, termites, vandalism, earthquakes and falling trees and branches. The most common of these causes is high winds. Wind damages fences all around the world every year. Fences made of wood are especially susceptible to wind damage because wood is weakened by prolonged exposure to rain, snow, wind, and other elements. Despite the potential for damage, wood is still by far the most common residential fencing material in the United States. In 2007 alone, Americans put up 59,000 miles of wood fencing, enough to circle the globe twice. Wood is inexpensive and lightweight, and a wood fence can easily be shaped to give properties character and individuality. There are many styles, including linear post-and-rail and crisscrossing lattice, as well as myriad picket patterns and post-cap designs. And the wood may be painted or stained to match almost any landscape.
Fences could be built much stronger using heavy materials such as steel and sturdy construction. However, this might drive the costs of the fence up above what is acceptable. As well, there are the aesthetic considerations discussed above. Also, it is unlikely that a property owner would replace an existing fence merely because of the possibility that it could be damaged by the elements.
There is an unmet need, therefore, for an inexpensive way to provide a fence with additional structural support. The need is especially great with respect to existing fences and with respect to wooden fences.
The following detailed description of certain embodiments of the present disclosure will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the disclosure, certain embodiments are shown in the drawings. It should be understood, however, that the present disclosure is not limited to the arrangements and instrumentality shown in the attached drawings.

This patent is subject to a terminal disclaimer.


A new and improved electrical socket contact has good structural integrity and a design which forestalls the possibility of having a male contact inadvertently inserted behind the spring contact. This is accomplished first through an overall design in which a spring contact section is completely surrounded by four side walls and a back wall, the walls having a generally box-like configuration. The spring section has a pair of overlying spring members, the innermost member having an overlying spring assist portion. The portion of the innermost spring portion nearest the socket opening is protected by a curved end portion of an overlying wall which also acts to protect the spring section. The socket contact of the present invention is formed from a single piece of flat material and is formed through several folding steps to achieve the final construction. The socket contact formed enables a high reliability very miniaturized contact.

A wide variety of pin and socket contacts are known, and have a similar variety of active structures which must mechanically cooperate to give an adequate surface area of electrical contact, as well as provide mechanical holding integrity. It is relatively easy to satisfy these goals in a connector of sufficient size where the material strengths are adequate. However for very small female contacts which are smaller than about 1/2 inch in length and have to exist in a densely packed area, have very small magnitude of the other dimensions, which may be much less than 1/8 of an inch. Smaller dimensioning translates into thinner material, and the goals of small size and strength are more difficult to achieve.
The electrical contact within a socket connector is insured by the use of a spring member to bear against the male member when inserted into the socket. The spring member may be provided separately or extend from the front mouth of the socket. In both cases, and especially where the socket and pin are small, the male pin member might be inadvertently wedged behind the spring member rather than against the side of the spring member intended for contact.
This unintended wedging action can destroy the spring member, and the socket contact if the wedging is violent enough. Even where the wedging is not violent, where the spring member is bent across the mouth of the contact, the contact becomes unusable. Further poking with the male contact will further damage the contact, and the technician, if available, will have to spend significant time replacing the contact, since repair of the contact, even if it were possible, would not leave it in a reliable condition.
Where a female socket contact consists of three walls and uses the fourth wall, opposing the middle of the three walls, as its spring contact, the chances for jamming are significant. In today's zero defects environment, the miniaturization of contacts is limited by this type of significant failure rate.
What is therefore needed is a contact which is inexpensive, has high reliability generally, good contact and especially which forestalls the possibility of inadvertent insertion of the pin behind the spring member.


When a user operates a touch sensor panel having an LCD device outdoors or in a bright environment, light reflecting off the device can create glare. In order to reduce glare, a user can view the device through polarized filters such as polarized sunglasses. Doing so can reduce the visibility of the image displayed on the LCD. A quarter-wave retardation film can be added to the touch sensor panel's LCD device to mitigate these effects by producing circularly polarized light. However, adding a separate quarter-wave retardation film can increase the thickness and cost of manufacturing the touch sensor panel. Embodiments of the present disclosure are directed to a touch sensor panel constructed from a base film having quarter-wave retardation properties that can produce circularly polarized light. Because the base film has the desired optical properties, a separate quarter-wave retardation film may not be needed.

Display screens of various types of technologies, such as liquid crystal displays (LCDs), organic light emitting diode (OLED) displays, etc., can be used as screens or displays for a wide variety of electronic devices, including such consumer electronics as televisions, computers, and handheld devices (e.g., cellular telephones, audio and video players, gaming systems, and so forth). LCD devices, for example, typically provide a flat display in a relatively thin package that is suitable for use in a variety of electronic goods including touch sensor panels. LCD technology is based on polarization optics and typically employs a linear polarizer on the front surface that emits linearly polarized light. Linearly polarized light has an electric field that vibrates in only one particular direction.
When a user operates a touch sensor panel having an LCD device outdoors or in a bright environment, light reflecting off the device can create glare. Polarized sunglasses can be worn to reduce the effects of glare by only allowing the passage of light that vibrates in a given direction (e.g., in a vertical direction). Depending on the angle that the touch sensor panel is held or oriented, the display image produced from the LCD device can appear clear, completely dark, or somewhere in between to a user wearing polarized sunglasses.

Dual purpose touch sensor panel and optical retarder


Described is the 2(1-vinyl-5-hexenyl)cyclopentanone having the structure: ##STR1## a process for preparing same by reacting the compound having the structure: ##STR2## with the compound having the structure: ##STR3## and then heating the resulting intermediate, and organoleptic uses of the compound having the structure: ##STR4## in perfumery.

This invention relates to the 2(1-vinyl-5-hexenyl)cyclopentanone having the structure: ##STR5## and the process for preparing same by reacting the ketal having the structure: ##STR6## with the unsaturated alcohol having the structure: ##STR7## and then heating the resulting intermediate and uses thereof in augmenting or enhancing the aroma of perfume compositions, perfumed articles and colognes. This invention also relates to the novel intermediates having the structures: ##STR8##
Inexpensive minty, peppery, pineapple and jasmine aromas with natural oily and waxy undertones are highly desirable in the art of perfumery. Many of the natural materials (e.g., natural jasmine oil) which provide such fragrances and contribute such desired nuances are high in cost, vary in quality from one batch to another and/or are generally subject to the usual variations of natural products. Indeed, at times, jasmine oil itself has been impossible to obtain at any reasonable price.
In the course of the last five years, particularly, an increasing amount of attention has been devoted to the preparation and utilization of artificial perfumes and odor modifying agents possessing the aroma attributes of jasmine oil.
Cyclopentanone derivatives having jasmine undertones are known in the perfumery trade. Thus, "APRITONER" manufactured by Bedoukian Research Inc. of 21 Finane Drive, Danbury, Conn. 06810-4192 has the structure: ##STR9## and is described as having a "peach-apricot aroma with jasmine undertones".
Bortolin and Musco, Journal of Molecular Catalysis, Volume 22 (1984) pages 319-326 shows a synthesis which yields a very small amount of the compound having the structure: ##STR10## according to the reaction: ##STR11## whereby the major material produced in this reaction has the structure: ##STR12##
Nothing in the prior art, however, discloses an efficient process for producing the compound having the structure: ##STR13## or discloses the use in perfumery particularly as a jasmine substitute of the compound having the structure: ##STR14##

Use in perfumery of 2(1-vinyl-5-hexenyl) cyclopentanone, a process for preparing same, and process intermediates


A running vehicle is photographed at a predetermined frame period by an image pickup unit (TV camera) provided at a position above a road. Two images of a present frame image and a previous frame image which were photographed are successively stored in an image storing unit. A vehicle detecting unit detects a motion of a license plate in a head portion of the running vehicle on the basis of the present frame image and the previous frame image stored in the image storing unit. A character recognizing unit recognizes all of the characters on the license plate on the basis of a dictionary in which character images of all of the characters used for the license plate have been registered and an image in a license plate area detected by the vehicle detecting unit by collating with the character images registered in the dictionary.

1. Field of the Invention
The invention relates to license plate reading apparatus and method for recognizing a license plate by an image of a vehicle photographed on a road. More particularly, the invention relates to license plate reading apparatus and method for automatically detecting a running vehicle from information of an image photographed by one television camera and reading characters on the license plate at a high precision.
2. Description of the Related Arts
In recent years, a system for recognizing a license plate of a vehicle running a road has socially played an important role. Therefore, there has been developed a system in which a TV camera is put on a road and a license plate of a vehicle is recognized from a photographed image. A license plate reading apparatus has to satisfy two requirements such that, first, all running vehicles can be detected without missing a detection, and second, the license plate of the detected vehicle is correctly read. As a conventional technique for this purpose, for example, there is an apparatus disclosed in JP-B-2893814. In such an apparatus, a head of a running vehicle is detected by extracting an edge of an image. A license plate is read by a method of binarizing the image by a background difference.
However, the method of detecting the vehicle head of the running vehicle by extracting the edge of the image has a drawback such that the vehicle head is easily erroneously discriminated as a shadow of the vehicle, a reflection of headlights, or the like. Also a method of reading a license plate by binarizing an image by a background difference has a problem such that it is difficult to avoid an adverse influence on conditions of external illuminance and a reading precision is low. In order to read the license plate of the vehicle at a high precision, it is necessary to raise a resolution of characters. However, to keep the high resolution, it is necessary to use a plurality of cameras or use a camera of a high resolution, so that the costs become very high. Therefore, in case of using an ordinary TV camera, a passing position such as a gate or the like of the vehicle is extremely limited and the system is limited to an application in which the position of the license plate has been fixed on the image. Therefore, it is difficult to read the license plate of the vehicle which is running a road at a high precision by using the ordinary TV camera.
According to the invention, there are provided license plate reading apparatus and method for certainly detecting a running vehicle from an image of a relatively low resolution photographed by one camera and reading a license plate from the detected image at a high precision.
A license plate reading apparatus of the invention comprises: an image pickup unit (TV camera) which is set above a road and photographs a running vehicle at a predetermined frame period; an image storing unit for successively storing two images of a present frame image and a previous frame image which were photographed by the image pickup unit; a vehicle detecting unit for detecting a motion of a license plate in a head portion of the running vehicle on the basis of a difference between the present frame image and the previous frame image which were stored in the image storing unit; a dictionary in which character images of all characters used for the license plate have been registered; and a character recognizing unit for recognizing all of the characters of the license plate from an image in a license plate area detected by the vehicle detecting unit by correlating with the registered character images in the dictionary. Therefore, even for a video image photographed by one camera by a sight of about two times as wide as a width of an ordinary vehicle, the license plate can be recognized at a high precision.
The vehicle detecting unit comprises: a block dividing unit for dividing each of the present frame image and the previous frame image into blocks of a predetermined pixel size; a vector calculating unit for obtaining a pixel position, as a block moving position, where a sum of differences between each pixel in the block of the previous frame and all pixels in the blocks of the present frame is equal to a minimum value bg, thereby calculating a motion vector of the block; and a vehicle head detecting unit for scanning all of the blocks, searching a group of blocks in which sizes and directions of the motion vectors are almost the same in an area of a rectangular size corresponding to the license plate, detecting the vehicle on the basis of the presence or absence of the group of blocks which satisfy such conditions, and at the same time, detecting a license plate area of the vehicle head. Since the vehicle detection is performed by paying attention only to the motion of the license plate in the image of the running vehicle as mentioned above, the vehicle can be accurately detected without being influenced by an image other than the license plate.
Further, in order to improve the detecting precision of the vehicle, the vehicle detecting unit can also have: a block dividing unit for dividing each of the present frame image and the previous frame image into blocks of a predetermined pixel size; a luminance level threshold value setting unit for always measuring a luminance of a predetermined area on the road in the frame image, discriminating statistical external illuminance state by obtaining an average value of a predetermined time, and obtaining and setting a luminance level threshold value (bg_th) which monotonously increases in accordance with the illuminance state by a predetermined simple increasing curve; a vector calculating unit for obtaining a pixel position, as a block moving position, where a sum of a difference between each pixel in the block of the previous frame and all pixels in the block of the present frame is equal to the minimum value (bg), thereby calculating a motion vector of the block; a reliability amount calculating unit for calculating a motion vector reliability amount (bgm) by subtracting a sum (bg0) of a difference between each pixel in the block of the present frame and all pixels in the block of the previous frame from the minimum difference value (bg) calculated by the vector calculating unit; and a vehicle head detecting unit for scanning all blocks, searching a group of blocks in which sizes and directions of the motion vectors are almost the same and the reliability amount (bgm) is equal to or larger than the luminance level threshold value (bg_th) in an area of a rectangular size corresponding to a license plate, detecting a vehicle on the basis of the presence or absence of the group of blocks which satisfy those conditions, and at the same time, detecting a license plate area at the head of the vehicle. As mentioned above, by always measuring the luminance level of a part of the image, setting the difference of a correlation result between the image and the position where the motion is equal to zero to the reliability amount of the vector, and discriminating the motion from a shadow and noises of the vehicle, the vehicle and its license plate area can be detected accurately from the image.
The character recognizing unit comprises: a low resolution recognizing unit for recognizing a character at a position of the character having the largest size on the license plate with respect to the frame image of a low resolution obtained by thinning out the original image as a target; and a high resolution recognizing unit for returning the resolution of the frame image to the original resolution, recognizing the character at the character position recognized by the low resolution recognizing unit, and recognizing a character at a position of another small character on the license plate in which a relative position has previously been known on the basis of a character recognition result. As mentioned above, by performing the recognition of two stages such that the character recognition of the license plate is performed with respect to the image of a low resolution, as a target, obtained by thinning out the pixels from the image in which the vehicle head has been detected and with respect to candidate positions thus obtained, the resolution is returned to the original resolution and the character recognition is performed, the reading at a high speed and a high precision is realized.
In the dictionary which is used for the character recognition, each of a sample character image obtained by photographing each character which is used for the license plate and a sample character image obtained by thinning out the above sample character image to the image as that of the low resolution recognizing unit is reduced to a size corresponding to the size of the character image at the time of reading the license plate, thereafter, converted into a Laplacian character image by applying a Laplacian filter, and registered into the dictionary. Each of the low resolution recognizing unit and high resolution recognizing unit applies the Laplacian filter to the inputted character image and converts and, thereafter, performs a normalization correlation arithmetic operation between the converted image and the Laplacian character image of the corresponding resolution which has been registered in the dictionary, thereby recognizing the characters of the license plate. The image having the highest correlation degree can be set to the collation result by the normalization correlation calculation between the dictionary character image converted by applying the Laplacian filter and the input character image, and the character recognition can be performed at a high precision.
The high resolution recognizing unit calculates an average value of the luminance of a background portion of the license plate, calculates an accumulation average value for a predetermined time, predicts an external illuminance, and when the accumulation average value is equal to or less than a predetermined threshold value, performs a contrast correction for improving the luminance of the character image to a predetermined level, and performs the character recognition of the license plate. Therefore, even if the ambient brightness decreases, the contrast of the license plate image is automatically improved, thereby improving the character recognizing precision in nighttime or the like. As for the dictionary which is used for the character recognition, further, as dictionary character images of the characters of small sizes used for the license plate, a plurality of kinds, for example, nine kinds of shift character images are formed by shifting the photographed sample character image in the vertical, lateral, and oblique directions and reduced to a size corresponding to the size of the character image at the time of reading the license plate, and thereafter, the images are converted into the Laplacian character images by applying the Laplacian filter and registered into the dictionary. By registering the images obtained by shifting the sample character in the lateral, oblique, and vertical directions as mentioned above into the dictionary, a fine sampling error at the low resolution caused by photographing the image by the ordinary TV camera is absorbed and the characters are recognized at a high precision.
Further, when the sample character is registered into the dictionary, the dictionary image is formed by selecting the Laplacian filter having a structure in which each size and/or the vertical/lateral sizes have been determined in correspondence to the kind (Hiragana, Kanji, or small number) of character of a small size used in the license plate. The high resolution recognizing unit selects the Laplacian filter of each character font used in the dictionary formation and recognizes the characters of the input character image. Therefore, the recognition at the low resolution can be performed at a high precision in accordance with the character kind.
According to the invention, there is provided a license plate reading method comprising:
a dictionary forming step of forming a dictionary in which character images of all characters which are used on a license plate have been registered;
an image pickup step of photographing a running vehicle at a predetermined frame period from a position above a road;
an image memory step of successively storing two images of a present frame image and a previous frame image photographed in the image pickup step;
a vehicle detecting step of detecting a motion of the license plate in a front portion of the running vehicle on the basis of a difference between the present and previous frame images stored in the image memory step; and
a character recognizing step of recognizing all characters of the license plate from an image in a license plate area detected in the vehicle detecting step by collating them with registration character images in the dictionary.
The details of the license plate reading method are substantially the same as those in case of the apparatus construction.

License plate reading apparatus and method


A method of fabricating a light extraction substrate for an OLE) by which the flatness of the light extraction substrate for an OLED can be increased. Particles of a first metal oxide and a sol of a second metal oxide are inputted and mixed into an organic solvent. A base substrate is coated with a mixture of the first and second metal oxides and the organic solvent. A resultant coating film on the base substrate is heat-treated. The coating film is coated with the second metal oxide to form a metal oxide thin film on the base substrate. In the metal oxide thin film, the particles of the first metal oxide are impregnated in a matrix of the second metal oxide.

1. Field of the Invention
The present invention relates to a light extraction substrate for an organic light-emitting device (OLED), and more particularly, to a method of fabricating a light extraction substrate for an OLED by which the flatness of the light extraction substrate for an OLED can be increased.
2. Description of Related Art
In general, an organic light-emitting device (OLED) includes an anode, a light-emitting layer and a cathode. When a voltage is applied between the anode and the cathode, holes are injected from the anode into a hole injection layer and then migrate from the hole injection layer through a hole transport layer to the organic light-emitting layer, and electrons are injected from the cathode into an electron injection layer and then migrate from the electron injection layer through an electron transport layer to the light-emitting layer. Holes and electrons that are injected into the light-emitting layer recombine with each other in the light-emitting layer, thereby generating excitons. When such excitons transit from the excited state to the ground state, light is emitted.
Organic light-emitting displays including an OLED are divided into a passive matrix type and an active matrix type depending on the mechanism that drives the N*M number of pixels which are arranged in the shape of a matrix.
In an active matrix type, a pixel electrode which defines a light-emitting area and a unit pixel driving circuit which applies a current or voltage to the pixel electrode are positioned in a unit pixel area. The unit pixel driving circuit has at least two thin-film transistors (TFTs) and one capacitor. Due to this configuration, the unit pixel driving circuit can supply a constant current irrespective of the number of pixels, thereby realizing uniform luminance. The active matrix type organic light-emitting display consumes little power, and thus can be advantageously applied to high definition displays and large displays.
However, as shown in FIG. 8, only about 20% of light generated by an OLED is emitted to the outside and about 80% of the light is lost by a waveguide effect originating from the difference in the refractive index between a glass substrate 10 and an organic light-emitting layer 30 which includes an anode 20, a hole injection layer, a hole transport layer, a light-emitting layer, an electron transport layer and an electron injection layer and by a total internal reflection originating from the difference in the refractive index between the glass substrate 10 and the air. Specifically, the refractive index of the internal organic light-emitting layer 30 ranges from 1.7 to 1.8, whereas the refractive index of indium tin oxide (ITO) which is generally used for the anode 20 ranges from 1.9 to 2.0. Since the two layers have a very small thickness ranging from 100 to 400 nm and the refractive index of glass used for the glass substrate 10 is about 1.5, a planar waveguide is thereby formed inside the OLED. It is calculated that the ratio of the light lost in the internal waveguide mode due to the above-described reason is about 45%. In addition, since the refractive index of the glass substrate 10 is about 1.5 and the refractive index of the ambient air is 1.0, when the light is directed outward from the inside of the glass substrate 10, a ray of the light having an angle of incidence greater than a critical angle is totally reflected and is trapped inside the glass substrate 10. Since the ratio of the trapped light is up to about 35%, only about 20% of the generated light is emitted to the outside. Herein, reference numerals 31, 32 and 33 indicate components of the organic light-emitting layer 30. Specifically, 31 indicates the hole injection layer and the hole transport layer, 32 indicates the light-emitting layer, and 33 indicates the electron injection layer and the electron transport layer.
The typical method for overcoming the problem of the light trapping was to increase external light extraction efficiency using a microlens array. However, the microlens array is easily damaged by external impacts or be contaminated by impurities since convex-concave portions of a light extraction layer protrude outward. When the microlens array is used in a display, it also has the problem of blurred images caused by lenses.
In addition, a light extraction layer which changes an optical waveguide path is provided between the glass substrate 10 and the anode 20 in order to increase internal light extraction. Such internal light extraction layer extracts light that would otherwise be lost by the waveguiding effect, and thus the possibility of increasing the internal light extraction efficiency is significantly higher than the possibility of increasing the external light extraction efficiency. In order to increase the light extraction efficiency of the internal light extraction layer, the surface of the light extraction layer must have a convex-concave structure. In this case, however, the anode 20 which adjoins to the light extraction layer must have a similar shape. This increases a danger in that the anode 20 has a localized sharp portion. When the anode 20 has a sharp protruding portion, the current is concentrated in the sharp portion. This consequently causes a leakage current or lowers the power efficiency.
In order to overcome this problem, several approaches were proposed in the related art, among which there was a method of impregnating light-scattering particles in a matrix material. This method includes properly mixing a matrix material and light-scattering particles and then coating the glass substrate 10 with a mixture of the matrix material and the light-scattering particles, for example, by spin coating or bar coating or using a slot die. When the matrix material is implemented as a metal oxide, a sol is also used. However, the use of the sol disadvantageously causes evaporation and/or loss in an organic matter included in the sol during drying and curing, thereby reducing the volume to a range from 1/10 to 1/20 of the thickness of a metal oxide thin film that is initially formed. In addition, since the light-scattering particles do not shrink during the drying or curing, the light-scattering particles protrude from the surface of the metal oxide thin film that is shrunk. This disadvantageously increases the surface roughness of the metal oxide thin film that is supposed to act as an internal light extraction layer that requires high flatness. The increased surface roughness of the metal oxide thin film has an adverse effect on the longevity of an OLED that uses the metal oxide thin film as an internal light extraction layer.
The information disclosed in the Background of the Invention section is provided only for or better understanding of the background of the invention, and should not be taken as an acknowledgment or any form of suggestion that this information forms a prior art that would already be known to a person skilled in the art.

Method of fabricating light extraction substrate for OLED


Aimed at improving adhesiveness between upper and lower interconnects in semiconductor devices, a semiconductor device of the present invention includes a second dielectric multi-layered film formed on a substrate, and containing a lower interconnect; a first dielectric multi-layered film formed on the second dielectric multi-layered film, and having a recess; an MOx film formed on the inner wall of the recess, and containing a metal M and oxygen as major components; an M film formed on the MOx film, and containing the M as a major component; and an electric conductor formed on the M film so as to fill the recess, and containing Cu as a major component, wherein the surficial portion of the interconnect fallen straight under the bottom of the recess has an oxygen concentration of 1% or smaller.

1. Technical Field
The present invention relates to a semiconductor device and a method of manufacturing the same.
2. Related Art
In recent semiconductor devices, delay in signal transmission on interconnects may sometimes determine operation speed of LSI circuits. Delay constant of signal transmission on interconnects is expressed by a product of interconnect resistance and parasitic capacitance. In order to reduce the parasitic capacitance, a low-dielectric-constant material (low-k material) having a dielectric constant smaller than that of the conventionally-used silicon dioxide (SiO2) has been used as a material for composing insulating interlayer. On the other hand, in view of reducing resistivity of the interconnects so as to raise operation speed of the LSI circuits, copper (Cu) having a small resistivity has been used as an electro-conductive material.
Cu multi-layered interconnect may be formed by the damascene process. The damascene process includes a step of depositing an insulating film such as an insulating interlayer, a step of forming recesses (interconnect trenches for forming interconnects, or viaholes for forming via plugs), a step of depositing barrier metal layer, a step of depositing a Cu thin film called Cu seed, a step of filling the recesses by depositing Cu using the Cu thin film as a cathode of electrolytic plating, a step of removing a portion of the barrier metal layer formed outside the recesses by chemical mechanical polishing, and a step of depositing a barrier insulating film.
As for the insulating interlayer, porous low-dielectric-constant materials have been discussed aiming at reducing the dielectric constant to as small as 2 or around.
N. Ohashi, K. Misawa, S. Sone, H. J. Shin, K. Inukai, E. Soda, S. Kondo, A. Furuya, H. Okamura, S. Ogawa and N. Kobayashi, "Robust Porous MSQ (k=2.3, E=12 GPa) for Low-Temperature (<350° C.) Cu/Low-k Integration Using ArF Resist Mask Process", Proceedings of IEEE International Electron Devices Meeting 2003, pp. 35.5.1-35.5.4. points out problems in the porous low-dielectric-constant materials, such as lowering in the material strength, elevation of dielectric constant caused by moistening, and corrosion of the porous dielectric materials called low-k void, and discloses a technique of solving these problems by optimizing composition of the low-dielectric-constant material, and etching method in the damascene process.
N. Matsunaga, N. Nakamura, K. Higashi, H. Yamaguchi, T. Watanabe, K. Akiyama, S. Nakao, K. Fujita, H. Miyajima, S. Omoto, A. Sakata, T. Katata, Y. Kagawa, H. Kawashima, Y. Enomoto, T. Hasegawa and H. Shibata, "BEOL Process Integration Technology for 45 nm Node Porous Low-k/Copper Interconnects", Proceedings of the IEEE International Interconnect Technology Conference 2005, pp. 6-8 discloses a technique of providing a dummy pattern, aiming at preventing oxidation of the barrier metal layer due to gas released by the porous insulating interlayer.
Japanese Laid-Open Patent Publication No. 2005-236285 discloses a technique of depositing a high-density dielectric material between the porous low-dielectric-constant material and the barrier metal layer, in order to prevent the barrier metal layer from being thinned due to irregularities conforming to voids of the porous low-dielectric-constant material, and from being degraded in reliability.
On the other hand, as for the electro-conductive material, thinning of the Cu seed has been discussed, aiming at improving Cu filling. Because holes in Cu interconnects (called voids, referred to as "voids" hereinafter) are known to degrade electrical characteristics (resistance, reliability, yield ratio, etc.), void-less filling is of importance in Cu plating.
Rate of formation of film in the Cu plating is faster at around the frontage and the bottom of the recess. Therefore, the void-less filling may successfully be achieved if Cu plating grown from the bottom of the recess reaches the frontage of the recess, before the frontage of the recess is clogged by the Cu plating. It may therefore be understood that wider frontage can facilitate the void-less filling.
On the other hand, the Cu seed has been becoming more thinner with recent progress of shrinkage of devices, so that it has been discussed to directly plate Cu on the barrier metal using the barrier metal per se as a seed, rather than depositing the Cu seed.
In particular, ruthenium (Ru) showing a good adhesiveness with Cu has been attracting much public attention as a barrier metal. Because Ru retains the electro-conductivity even after being oxidized, it has been attracting much attention also from the viewpoint of widening process margin with respect to the filling by plating. Japanese Laid-Open Patent Publication No. 2002-75994 discloses a technique of using a barrier metal composed of a metal (Ru, etc.) showing electro-conductivity even after being oxidized, or an oxide thereof. Use of Ru as the barrier metal, however, suffers from a problem in adhesiveness, because the metal state of which shows only a poor adhesiveness to the insulating interlayer, and an oxide state of which shows only a poor adhesiveness to Cu. Efforts of improvements have been made typically as seen in Japanese Laid-Open Patent Publication Nos. 2000-269455, 2005-347510, 2006-5305, and 2006-19325.
Japanese Laid-Open Patent Publication No. 2000-269455 discloses a technique of using a barrier metal composed of a metal showing electro-conductivity even after being oxidized (Ru, etc.) or its oxide, added with Pd or the like.
Japanese Laid-Open Patent Publication No. 2005-347510 discloses a technique of using a barrier metal composed of a C, N or Si compound of a metal showing electro-conductivity even after being oxidized (Ru, etc.), a transition layer, and a metal showing electro-conductivity even after being oxidized, stacked in this order as viewed from the insulating film side.
Japanese Laid-Open Patent Publication No. 2006-5305 discloses a technique of using a barrier metal composed of an oxide of a metal showing electro-conductivity even after being oxidized (Ru, etc.), a transition layer, and a metal, stacked in this order as viewed from the insulating film.
Japanese Laid-Open Patent Publication No. 2006-19325 discloses a technique of raising elastic modulus of the transition layer, in order to improve a poor mechanical strength in the configuration shown in Japanese Laid-Open Patent Publication No. 2006-5305.
However, the present inventor found out, from his investigation, a problem in that use of the metal oxide film, as described in Japanese Laid-Open Patent Publication Nos. 2000-269455, 2005-347510, 2006-5305, and 2006-19325 may degrade the adhesiveness between the upper interconnect and the lower interconnect, and may consequently degrade electrical characteristics and reliability. This is because Cu contained in the lower interconnect is oxidized due to an oxidative atmosphere used for forming the metal oxide film.
A possible method of preventing oxidation of Cu contained in the lower interconnect in the process of forming the metal oxide film may be such as depositing a high-density dielectric film on the insulating interlayer, and then depositing the barrier metal, based on combination of the inventions described in Japanese Laid-Open Patent Publication Nos. 2005-236285, 2000-269455, 2005-347510, 2006-5305, and 2006-19325. Oxidation of Cu contained in the lower interconnect is, however, inevitable because the thickness of the high-density dielectric film at the bottom of the recess will be as small as several nanometers in the generation of a technical node of 45 nm or thereafter. Oxidation of Cu contained in the lower interconnect may raise problems of increase in resistivity of the interconnects, and degradation of the reliability.
Although the description in the above has been made assuming the cases where a via-forming layer is formed on an interconnect layer by the single damascene process, or where a via-and-interconnect-forming layer is formed by the dual damascene process, the same problem resides also for the case where an interconnect layer is formed on the via plug.

Semiconductor device and method of manufacturing the same


In one aspect provides a method of manufacturing a semiconductor device having improved transistor performance. In one aspect, this improvement is achieved by conducting a pre-deposition spacer deposition process wherein a temperature of a bottom region of a furnace is higher than a temperature of in the top region and is maintained for a predetermined period. The pre-deposition temperature is changed to a deposition temperature, wherein a temperature of the bottom region is lower than a temperature of the top region.

Sub-micron sized transistors are very well known and are used extensively in all types of electrical devices. It is also well known that these transistors often include deep source/drains and shallower source/drain extensions, that are located adjacent the gate electrodes of the transistors and between which a channel region is formed during an applied voltage. The source/drain extensions are typically formed by placing dopants into a semiconductor substrate through well known processes, such an implantation. The source/drain extensions are implanted immediately adjacent the gate electrodes and are ultimately intended to extend up to, if not slightly extend under, the gate electrode to reduce channel length.
The deeper source/drains, however, are offset from the gate electrodes. This is accomplished typically by using a spacer, which may also be referred to as, a sidewall spacer, an oxide spacer, or gate spacer. The spacer is formed by depositing a spacer layer over the gate electrodes in a deposition furnace, patterning, and etching the spacer layer to form an offset. Implantation processes are then used to implant deep source/drain dopants into the substrate. The spacer partially blocks the implantation of the dopants, and thus, offsets the deep source/drains from the gate electrodes.
Problems can arise, however, in that once implanted, the dopants that form the source/drain extensions are susceptible to moving within the substrate when subjected to high temperatures, such as the temperatures used to deposit the spacer layer. Thus, during the deposition of the spacer layer, the source/drain extension dopants are susceptible to some movement, which can affect channel length. If the movement is significant enough, it can negatively affect transistor performance, particularly as device sizes continue to shrink to 130 nm and below.

Method of manufacturing a semiconductor device having improved transistor performance


Inefficiencies in reclaiming foundry sand from foundry cores made up of sand and an organic resin binder are reduced in a method of reclaiming such sand that includes the steps of reducing a foundry core made up of sand and an organic resin binder to small clumps or individual particles, placing the small clumps or individual particles in a bed and introducing a heated gaseous oxidant into the bed generally from the bottom thereof in sufficient volume to fluidize the bed and at sufficient temperature to oxidize the resin binder on the small clumps or individual particles. Also disclosed is an apparatus for performing the method.

Sand has long been used in foundry operations in making cores. The cores are employed in a casting process to ultimately provide voids in the casting. The cores are shaped so as to provide a void of a desired size and shape and to serve this purpose, it is necessary that the cores retain their integrity through the casting process until the molten metal employed in the casting process has solidified. When that occurs, the core is then broken up typically in a so-called "shake out" process, leaving a void of the desired size and shape within the casting.
To assure that the sand cores retain their desired size and shape during the casting process and yet can be broken up relatively easily to separate from the casting resulting from the process, it has been conventional to employ various organic resins as a binder to bind the grains of sand together to provide the structural integrity required. Although the amount of binder employed may vary depending upon the type of resin used, it is fairly typical to employ a resin content of about 2%, particularly in the so-called phenolic ester nobake process. Other foundry binder system include phenolic urethane coldbox, furan nobake, phenolic urethane nobake, and phenolic hotbox.
While these resins work well for their intended purpose, at the conclusion of the casting process, following shake out, a resin residue remains on the grains of sand and/or the sand may be in clumps, still held together by the binder. Whereas in the past, such sand was simply disposed of, environmental concerns have strongly suggested that the sand be reused wherever possible. Unfortunately, the presence of spent resin binder on the sand makes it impossible to use the same effectively and efficiently without first removing the resin residue.
To accomplish reclamation of the sand, one system proposed includes an indirectly heated rotary kiln, a rotary sand cooler, a pneumatic scrubber and classifier, a second rotary kiln, a second rotary sand cooler, and a second pneumatic scrubber and classifier. Shake out sand and other sand containing resin that results from the foundry operation, including the formation of the cores, is first reduced to small clumps or individual particles using a vibratory crusher. The sand may then be run through a magnetic separator to remove so called "tramp" metal and then is transported to the first kiln. The kiln is basically a drum including internal lifter bars which run lengthwise and lift the sand and carry it from the bottom of the drum to near the top where the sand then falls off of the lifter bar and tumbles through the interior of the drum which is provided with hot air from a heater. The hot air may be 1,250.degree. F. or more and as a consequence, the oxygen in the air and the heat act to combust the resin on the sand. Such residue as remains is dried and embrittled so that it can be scrubbed from the sand grains in the first scrubber/classifier. This process is essentially repeated in the second set of kiln, cooler and scrubber/classifier and the result is sand that has been reclaimed to the quality needed for reuse in resin binder systems.
While the system is operative to achieve its intended purpose, it is unnecessarily complex, and therefore, expensive. Furthermore, because heat transfer to the sand is achieved basically only by the heated air and/or contact of the sand grains with a heated drum, it is relatively slow and residence time is undesirably long. This in turn results in relatively large equipment in order to process a given quantity of sand to be reclaimed over a given time period. And, of course, the large equipment necessitates an undesirably large amount of floor space to house the same.
The present invention is directed to overcoming one or more of the above problems.

Method and apparatus for reclaiming foundry sand