The invention concerns a method for the determination of antigen-specific antibodies of the immunoglobulin M class in the presence of immunoglobulins of the G class and/or rheumatoid factors in body fluids by incubation with at least two different receptors R1 and R2 and optionally additional receptors wherein an essential component of R2 is a binding partner in a polymeric form and interference by IgG antibodies of the same antigen specificity is reduced by binding partners in a monomeric form; a reagent for determining an antigen-specific antibody of the immunoglobulin M class, as well as the use of binding partners in a monomeric form to reduce interference by IgG antibodies in the determination of antigen-specific IgM antibodies.

The invention concerns a method for the determination of antigen-specific antibodies of the immunoglobulin M class in body fluids by incubating the sample with at least two different receptors R1 and R2 where both receptors are capable of binding specifically to the antibody, R1 is bound or can be bound to a solid phase and R2 carries a label, wherein an essential component of R1 and optionally also of R2 is a binding partner in polymeric form which is specifically recognized by the antibody to be determined and binding partners of the same specificity are used in monomeric form to reduce interference by IgG antibodies.
In particular the invention concerns a method for the specific detection of immunoglobulins of the IgM class in the presence of immunoglobulins of the IgG class and interfering factors such as rheumatoid factors.
In response to the introduction of foreign substances the immune system of a mammalian organism produces antibodies which are also called immunoglobulins. They defend against foreign substances which are also referred to as antigens. The immunoglobulins can be divided into five different classes. One distinguishes between immunoglobulins of the M, G, A, E and D classes. Each of these five immunoglobulin classes differ in the composition of the heavy chain which is referred to as the xcexc, xcex3, xcex1, xcex5 and xcex4 chain.
Each immunoglobulin class has a different function in the organism. Immunoglobulins of the M class appear after the first contact with the antigen, the so-called primary immunization. However, the concentration of these immunoglobulins decreases rapidly as the infection progresses. The immunoglobulins of the G class are firstly slowly formed after a primary immunization and occur in large quantities when there is a second infection with the same antigen. The immunoglobulins of the A class are found on the mucous membrane surfaces of the organism and are responsible for the defence processes there. The immunoglobulins of the E class are mainly responsible for allergic reactions. The exact function of immunoglobulins of the D class is hitherto unknown.
The individual immunoglobulin classes occur in very different concentrations in the blood. Thus immunoglobulins of the G class (IgG) are the major class in normal human serum with a share of about 75% that corresponds to a serum content of 8 to 18 mg/ml. The second most frequently occurring immunoglobulin is IgA which has an average serum concentration of 0.9 to 4.5 mg/ml. Immunoglobulins of the M class are present at a concentration of 0.6 to 2.8 mg/ml, immunoglobulins of the D class are present at a concentration of 0.003 to 0.4 mg/ml. The proportion of IgE antibodies is lowest and they only occur at a concentration of 0.02 to 0.05 xcexcg/ml in serum.
For the differential diagnosis of many diseases it is important to detect antibodies of one or several quite particular immunoglobulin classes which are specific for a particular antigen. A satisfactory diagnosis of viral, bacterial and parasitic infections can only be ensured by means of a class-specific antibody test or by excluding the presence of certain immunoglobulin classes (e.g. detection of IgG and IgA antibodies but no detection of IgM antibodies). This is particularly important for distinguishing between fresh or acute infections and infections that have occurred earlier as well as for the clinical monitoring of the course of an infection. The class-specific detection of antibodies is especially important for HIV, hepatitis A, hepatitis B, toxoplasmosis, rubella and chlamydia infections. The class-specific detection of antibodies specific for a particular antigen is also necessary when determining the titre of protecting antibodies and to check the success of an immunization. For the diagnosis of fresh, acute infections it is of particular interest to detect antibodies of the IgM class which are specific for an antigen. However, various interfering factors such as for example the presence of IgG antibodies of the same specificity frequently interfere with the detection of antigen-specific IgM antibodies.
Various methods have been described in the state of the art for detecting antibodies of a particular class that are specific for an antigen. Hence antigen-specific antibodies of a particular class are frequently detected by binding the specific antibodies to a solid phase coated with the specific antigen. The immunoglobulins (Ig) specific for the antigen which are now bound to the solid phase are detected by binding antibodies which are specifically directed towards human Ig of a certain class to the Ig molecules to be detected. The antibodies directed towards human Ig are provided with a label by means of which the detection takes place. However, such a test procedure is only possible if all unspecific non-bound Ig is removed by washing before the reaction with the class-specific labelled antibodies directed towards human Ig. Thus a one-step test procedure as is often required for automated systems is not possible. In addition antibodies of all classes which are specific for the antigen bind to the solid phase in the first step. If the antigen coating of the solid phase is not high enough, competing reactions of the various antibody classes for binding to the antigen can occur. This can impair the sensitivity of the test.
One possibility of carrying out an antibody detection in a one-step test is provided by the so-called bridge test. The bridge test concept is described in EP-A-0 280 211. In this method a first receptor such as for example an antigen which is capable of specific binding to the antibody to be determined is bound to a solid phase. The antibody to be determined binds to the solid phase-bound antigen. In addition a further specific antigen is present in the test mixture which is provided with a label. The antibody is detected by means of the label. However, in this test all antigen-specific antibodies are detected and not only the antibodies of a particular class.
An additional interference when determining antigen-specific IgM antibodies is caused by rheumatoid factors. Rheumatoid factors are themselves usually antibodies of the IgM class which generally have a high affinity for the Fc regions of IgG antibodies. As a result rheumatoid factors seemingly present IgG antibodies so that the rheumatoid factors are bound in an immunoassay for specific IgM antibodies. If the rheumatoid factors have bound IgG molecules with the specificity that is to be detected, this can result in false-positive measurement results.
This problem in the class-specific detection of antigen-specific antibodies is the subject matter of DE 33 03 793. This describes a method for the detection. of an antigen-specific antibody of a certain Ig class (xe2x80x9cIgXxe2x80x9d) in which interference by rheumatoid factors is eliminated by adding anti-IgG antibodies. In the method the specific antigen, such as a virus antigen, is applied to a solid carrier. The virus antigen bound to the solid phase is contacted with the sample. In the next step the unbound sample is removed and the solid phase-bound complex of antigen-IgX is detected with an anti-IgX antibody. In order to avoid interference by rheumatoid factors especially in IgM tests, the sample is treated with anti-IgG antibodies before the test. The IgG antibodies complexed in this manner are thus no longer available for attack by rheumatoid factors so that the rheumatoid factors are not able to bind antigen-specific IgG molecules which could in turn result in false-positive results. However, all IgG antibodies are bound regardless of their specificity. The precipitation of interfering IgG antibodies with anti-IgG antibodies can lead to undesired precipitates and turbidity which can have an adverse effect on the entire test. In addition sample pretreatment with anti-IgG antibodies is complicated.
A further method of eliminating interference by antibodies of other classes with the same specificity is disclosed in WO 96/14337. In this case antibodies or antibody fragments which react specifically with the Fd section of the heavy chain of IgG are used to eliminate interference by IgG antibodies. As a result the antigen binding capability of the IgGs is masked so strongly that they are no longer able to recognize the specific antigens. A similar concept is described in WO 96/14338.
In this case anti-Fd antibodies or fragments thereof are used as an interference-eliminating reagent to reduce interference by rheumatoid factors. However, reduction of interference by a highly specific anti-Fd reagent is complicated and costly.
The methods known in the prior art do not enable detection of an antigen-specific antibody of the immunoglobulin IgM class in a one-step method without having to add elaborate and expensive interference-eliminating reagents and/or several specific antibodies. The immunological methods of detection known from the state of the art based on the bridge test concept in which a labelled antigen and an antigen capable of binding to a solid phase are used, do indeed enable a one-step test. However, up to now it has only been possible to jointly detect antibodies of the IgG and IgM classes using this simple principle.
Therefore the object was to provide an improved method for the detection of antibodies of the IgM class directed against a specific antigen. This method should not require elaborate and expensive interference-eliminating reagents and should preferably consist of a one-step test principle in order to be used advantageously in automated systems.
This object is achieved by the method according to the invention for the determination of an antigen-specific antibody of the immunoglobulin M class by incubating the sample with at least two different receptors R1 and R2 where both receptors are capable of binding specifically to the antibody, R1 is bound or can be bound to a solid phase and R2 carries a label, wherein an essential component of R1 is a binding partner in polymeric form which is specifically recognized by the antibody to be determined, and interference by IgG molecules of the same specificity present in the sample is eliminated by adding binding partners in monomeric form.
The IgA, IgD and IgE antibodies present in the sample which have the same specificity as the IgM antibodies to be detected occur in very low concentrations compared to IgG antibodies so that no interference by the classes IgA, IgD and IgE would be expected. The antibody classes IgA, IgD and IgE arexe2x80x94like IgG molecules and in contrast to the IgM antibodies that are present as a pentamerxe2x80x94antibodies which are present in the form of single molecules and each has two binding sites for the antigen. Hence due to the structural similarity of IgG, IgA, IgD and IgE antibodies, interference by IgD, IgA and IgE antibodies is also presumably reduced in addition to that caused by IgG antibodies by the method for antigen-specific IgM detection described in the following.
The method according to the invention allows the determination of antigen-specific antibodies of the immunoglobulin M class in samples in which antibodies of the IgG class with the same antigen specificity are present. In addition the method according to the invention can be carried out in the presence of rheumatoid factors. An elaborate pretreatment of the sample is not necessary.
It has surprisingly turned out that the use according to the invention of binding partners in a monomeric form in an immunoassay for the detection of antigen-specific IgM antibodies enables an effective elimination of interference caused by IgG antibodies with the same antigen-specificity. In this method the binding partners in a monomeric form bind specifically to the antigen binding sites of the IgG antibodies. The IgM antibodies to be detected with the same specificity which are present in the same sample surprisingly do not react or only to a negligibly weak extent with the binding partners in a monomeric form. The term xe2x80x9cnegligibly weakxe2x80x9d means that the antigen binding sites of the IgM antibodies are not blocked by the binding partners in monomeric form. This is presumably due to the much lower affinity of the pentameric IgM antibodies for monomeric epitopes compared to the IgG antibodies present in the form of individual molecules which have a substantially higher affinity for monomeric epitopes. This means that despite the presence of binding partners in a monomeric form, the sensitivity of the IgM test is not impaired. The IgG antibodies masked by the binding partners in a monomeric form do not interfere with the IgM test.
It has also surprisingly turned out that interference by rheumatoid factors that have bound IgG antibodies can also be effectively eliminated by the binding partners in monomeric form which bind to the antigen binding sites of the IgGs. Since the antigen binding sites of the IgG antibodies are blocked, the antigen-specific IgM antibodies can be detected without prior separation of the IgG antibodies or the rheumatoid factors. The binding partners used in monomeric form are not able to trigger an agglutination reaction of the masked IgG antibodies or the rheumatoid factors. This prevents undesired turbidities due to precipitates which can adversely influence the entire test procedure.
Hence a successive test procedure for separating the IgG antibodies is not absolutely necessary in the method according to the invention since these do not interfere. A particular advantage of the method is therefore the simplicity of the test procedure.
Apart from the so-called wet tests in which the test reagents are present in a liquid phase, all standard dry test formats which are suitable for the detection of proteins or antibodies can also be used. In these dry tests or test strips as described for example in EP-A-0 186 799, the test components are applied to a carrier. Hence if the method according to the invention is carried out in a test strip format no wash step is necessary. However, the method according to the invention is preferably carried out as a wet test.
It is possible to incubate all receptors and the binding partners in a monomeric form together with the sample and to carry out the method in one step. This optionally requires only one wash step after the incubation.
Normally two different receptors R1 and R2 and the binding partners in a monomeric form are used to carry out the method according to the invention. If a wet test is used, the receptor R2 is present in a liquid phase. R1 can be present in a liquid phase or already bound to the solid phase. The binding partners in a monomeric form are preferably present in the liquid phase.
If a receptor capable of binding to a solid phase but which is not yet bound to the solid phase is used as R1 the sample is then incubated together with the receptors R1 and R2 and the binding partners in a monomeric form.
In this process the sample antibody binds to R1 and R2. This incubation can occur in the presence of the solid phase. A complex is formed in this process composed of solid-phase-R1-sample antibody-R2. Subsequently the solid phase is separated from the liquid phase, the solid phase is optionally washed and the label of R2 is measured. The label is usually measured in the solid phase but it can also be determined in the liquid phase.
If the incubation of the sample with R1 and R2 and the binding partners in a monomeric form is carried out in the absence of the solid phase, then the entire test mixture must subsequently be contacted with the solid phase, the washing is optionally carried out and the label measured.
If the receptor R1 is already in a solid phase-bound form, then the sample and receptor R2 are added to the solid phase-bound receptor R1 and incubated together. In this test procedure the sample is preferably preincubated with the binding partners in a monomeric form and R2 before the test mixture is added to the solid phase-bound receptor R1. The further procedure corresponds to the method stated above.
It is also possible to carry out the method according to the invention in several steps. In this case the sample is preferably incubated with the binding partners in a monomeric form and then with the receptors R1 and R2. The test mixture can subsequently be incubated with other receptors whereby this can be carried out in several steps. The further test procedure corresponds to the previously described method.
An important component of R1 is a binding partner in a polymeric form which is specifically recognized by the IgM antibodies to be determined which can also be referred to as a polyhapten. A binding partner in a polymeric form according to the invention is understood as structures in which several, preferably identical or similar, equivalent epitope regions are coupled to a carrier which react specifically with the antibody to be determined. The term xe2x80x9csimilarxe2x80x9d or xe2x80x9cequivalentxe2x80x9d means that the structures present on the binding partner in a polymeric form do not necessarily all have to be identical. The only condition is that the IgM antibodies to be determined bind specifically to these epitope regions. The epitope region can for example be derived from an antigen or anti-idiotype antibody. The epitope region can also be derived from sugar chains like those which for example occur in glycated proteins. It can also be derived from lipid structures like those which for example occur in phospholipids or lipoproteins. Hence the polyhapten or the binding partner in a polymeric form is composed of many identical or similar epitope regions and thus has many similar binding sites for the sample antibody as already set forth above. A binding site in the case of a protein as an antigen is understood as a peptide the sequence of which is a part of the protein sequence of a protein antigen (analyte) and to which an antibody specifically binds which is directed against this protein. In the case of an antigen which contains a sugar structure, the binding site would be the region of sugar molecules to which the sample antibody specifically binds. In the case of lipid structures, the lipid molecules can be the binding site for the sample antibody. A binding site can also be composed of combinations of peptidic regions with sugars and/or lipids. However, polyhaptens based on peptides are preferably used as binding partners in a polymeric form. In the case of the binding partners in a polymeric form according to the invention a high epitope density is of primary importance so that the pentameric IgM sample antibodies are able to specifically bind with high affinity to the binding partners in a polymeric form. The other criteria for the individual peptide components of the binding partners according to the invention in a polymeric form correspond to the requirements described below for the binding partners in a monomeric form.
Particles of for example latex, polystyrene, polyacrylate, polymethacrylate or gold can be used as the carrier material for the polyhaptens. Polymers such as dextran or polypeptides such as polylysine, bovine serum albumin, xcex2-galactosidase, unspecific immunoglobulins or fragments thereof can also be used as a carrier material for the polyhaptens. The only condition in selecting the carrier is that it has no cross-reactivity with antibodies in the sample liquid. A further condition is that it must be possible to couple the haptens to the carrier. The epitope regions or haptens are coupled to the carrier material by methods known to a person skilled in the art as described for example in EP-A-0 650 053 and WO 96/03652. In addition spacer regions can be inserted between the epitope region and carrier material which are also described in the aforementioned unexamined laid-open patent application. All spacer regions known to a person skilled in the art can be used. A requirement is that they are immunologically inactive i.e. they do not cross-react with antibodies in the sample.
R1 can either be bound directly to the solid phase or it is bound indirectly to the solid phase by means of a specific binding system. The direct binding of R1 to the solid phase is achieved by methods known to a person skilled in the art. If R1 is indirectly bound to the solid phase by means of a specific binding system, then R1 is a conjugate which is composed of a binding partner according to the invention in a polymeric form and a reaction partner of a specific binding system. A specific binding system is in this case understood as two partners which can react specifically with one another. In this case the binding capability can be based on an immunological reaction or on another specific reaction. A combination of biotin and avidin or biotin and streptavidin is preferably used as a specific binding system. Other preferred combinations are biotin and antibiotin, hapten and anti-hapten, Fc fragment of an antibody and antibody against this Fc fragment or carbohydrate and lectin. One of the reaction partners of this specifically bindable pair is then a part of the conjugate that forms the receptor R1.
The other reaction partner of the specific binding system is then present in a solid phase. The other reaction partner of the specific binding system can be bound to an insoluble carrier material by conventional methods known to a person skilled in the art. In this case a covalent as well as an adsorptive binding is suitable. Solid phases that are particularly suitable are test tubes or microtitre plates made of polystyrene or similar plastics the inner surfaces of which are coated with the reaction partner of the specific binding system. Particulate substances such as latex particles, molecular sieve materials, glass beads, plastic tubes etc. are also suitable and particularly preferred. Porous layered carriers such as paper can also be used as the carrier.
The receptor R2 is composed of a molecule which reacts specifically with the sample antibody and a label. The molecule that reacts specifically with the sample antibody can for example be an antibody, an antibody fragment, a protein, an antigen or a hapten which bind specifically to the sample antibody. The only condition for the molecule as a component of R2 is that it reacts specifically with the sample antibody to be detected. This molecule is preferably a binding partner according to the invention in a polymeric form which specifically binds the sample antibody. The binding partners in a polymeric form which are contained in R2 are prepared by the same methods as the binding partners in a polymeric form for R1.
A further component of the receptor R2 is the label. A directly detectable substance is preferably used as a label for example a chemiluminescent, fluorescent or radioactive substance or a metal sol, latex or gold particle. Enzymes or other biological molecules are also preferred as the label such as for example haptens. Digoxigenin is a particularly preferred label among the haptens. Processes for labelling are familiar to a person skilled in the art and do not need to be elucidated further here. The label is detected directly in a well-known manner by measuring the chemiluminescent, fluorescent or radioactive substance or the metal sol, latex or gold particle or by measuring the substrate converted by the enzyme.
The label can also be detected indirectly. In this case a further receptor which itself is in turn coupled to a signal-generating group binds specifically to the label of R2 such as a hapten like digoxigenin. The signal-generating group, for example a chemiluminescent, fluorescent or radioactive substance or an enzyme or gold particle, is detected by methods familiar to a person skilled in the art. An antibody or an antibody fragment can for example be used as the further receptor which binds specifically to the label of R2. If this indirect detection of the label is used then the R2 label is preferably digoxigenin or another hapten and the detection is carried out via an antibody coupled to peroxidase which is directed against digoxigenin or against the hapten.
In order to reduce interference by IgG antibodies of the same antigen specificity, binding partners in a monomeric form are added according to the invention to the test mixture. The term xe2x80x9cmonomerxe2x80x9d means that the binding partners in a monomeric form according to the invention only contain one epitope region or only one binding site for the antibody whose interference is to be reduced i.e. a structure which immunologically reacts specifically with the IgG antibody. The monomeric structure of these binding partners is important in order to ensure that only the antigen-specific IgG antibodies whose interference is to be reduced bind to the binding partners in a monomeric form and not the IgM antibodies to be detected.
The epitope region canxe2x80x94as described above for binding partners in a polymeric formxe2x80x94for example be derived from an antigen or an anti-idiotype antibody. In accordance with the prerequisites for binding partners in a polymeric form, the epitope regions of binding partners in a monomeric form can also be derived from sugar and/or lipid structures or combined structures with peptide, lipid and/or sugar components. All structures that can be derived from an epitope region can be used which have a binding site to which the antibody of the IgG class whose interference is to be reduced specifically binds in the presence of IgM antibodies of the same specificity. The only prerequisite for the binding site i.e. for the binding partners used in monomeric form, is that the specific capability of binding to IgG is retained. This condition also applies to the case where sugar or lipid structures are present in the binding site.
According to the invention it is also possible to use binding partners in a monomeric form which flank or overlap the binding site to which the IgG antibody whose interference is to be eliminated specifically binds. Hence it is also possible to eliminate interference by IgG antibodies whose binding site includes an epitope which is not exactly identical with the epitope that is recognized by the IgM antibodies to be detected. These IgG antibodies can have a greater or lesser degree of cross-reactivity with the IgM antibodies to be detected. The addition of binding partners in a monomeric form which correspond to the epitopes of these cross-reacting antibodies and thus have a high affinity for these, also eliminates interference by these IgG antibodies. A mixture of binding partners in a monomeric form which overlap to a greater or lesser extent the epitopes of the IgM antibodies to be detected are preferably used to eliminate interference by IgG antibodies.
Peptides are preferably used as binding partners in a monomeric form. In the case of a protein as an analyte a binding site is understoodxe2x80x94like the definition for the binding partner in a polymeric formxe2x80x94as a peptide, the sequence of which is part of the protein sequence of a protein antigen and to which an antibody directed towards this protein, which in the case of the present invention is an IgG antibody, specifically binds. In addition to these peptides a binding site is also understood to include peptides with amino acid sequences which have an essentially equivalent specificity and/or affinity of binding to the IgG antibody to be detected as the aforementioned peptides. These peptides can preferably be derived from the aforementioned peptides by substitution, deletion or insertion of individual amino acid residues.
Peptides according to the invention which correspond to a specific binding site are also understood to include peptide derivatives in which one or several amino acids have been derivatized by a chemical reaction. Examples of peptide derivatives according to the invention are in particular those molecules in which the backbone or/and reactive amino acid side groups, for example free amino groups, free carboxyl groups or/and free hydroxyl groups, have been derivatized. Specific examples of derivatives of amino groups are sulfonamides or carboxamides, thiourethane derivatives and ammonium salts for example hydrochlorides. Carboxyl group derivatives are salts, esters and amides. Examples of hydroxyl group derivatives are O-acyl or O-alkyl derivatives. The peptides are preferably produced by chemical synthesis according to methods known to a person skilled in the art and do not need to be especially elucidated here.
In addition the term peptide derivative also encompasses such peptides in which one or several amino acids are replaced by naturally occurring or non-naturally occurring amino acid homologues of the 20 xe2x80x9cstandardxe2x80x9d amino acids. Examples of such homologues are 4-hydroxyproline, 5-hydroxylysine, 3-methylhistidine, homoserine, ornithine, xcex2-alanine and 4-aminobutyric acid. The peptide derivatives must have an essentially equivalent specificity or/and affinity of binding to the IgG antibodies whose interference is to be reduced as the peptides from which they are derived.
Peptides according to the invention which correspond to a specific binding site are also referred to as peptide-mimetic substances named peptide-mimetics in the following which have an essentially equivalent specificity or/and affinity of binding to the IgG antibodies whose interference is to be reduced as the aforementioned peptides or peptide derivatives. Peptide-mimetics are compounds which can replace peptides with regard to their interaction with the antibody to be determined and can have a higher stability than the native peptides in particular towards proteinases and peptidases. Methods for the production of peptide-mimetics are described in Giannis and Kolter, xe2x80x9cAngew. Chem.xe2x80x9d 105 (1993), 1303-1326 and Lee et al., Bull. Chem. Soc. Jpn. 66 (1993), 2006-2010.
The length of a binding site i.e. the length of a monomeric peptide according to the invention is usually at least 4 amino acids. The length is preferably between 4 and 20, 6 and 15 or particularly preferably 9 and 12 amino acids. In the case of peptide-mimetics or peptide derivatives an analogous length is necessary with regard to the size of the molecule.
The monomeric peptides according to the invention as a binding partner in a monomeric form contain the epitope to which the IgG antibody whose interference is to be reduced binds specifically. However, further flanking peptide sequences which no longer correspond to the specific epitope may be present at the N-terminal and/or at the C-terminal end of the peptide. This measure may be necessary to improve the solubility of the peptide. The only prerequisites are that the peptide as a binding partner in a monomeric form is actually present as a monomer and the ability to bind strongly to the IgG antibodies whose interference is to be reduced is retained.
A prerequisite for the use of the binding partners in a monomeric form (in this case: peptides) is that the same epitope is present in the monomeric form as that epitope which is present on the binding partners in a polymeric form or the polyhaptens in a polymeric form. This means that in order to effectively eliminate interference, the IgG antibodies which bind to the binding partners in a monomeric form, must have the same immunological specificity as the IgM antibodies to be detected. In an IgM antibody test interference should always be eliminated from IgG antibodies of the same antigen specificity.
The binding partners in a monomeric form are preferably used in a 10-fold to 10,000-fold excess compared to the concentration of the epitopes on the binding partners in a polymeric form. The binding partners in a monomeric form are preferably used in a 10-fold to 1000-fold and particularly preferably in a 100-fold excess. The concentration of the binding partners in a monomeric form is only limited insofar as the binding partners in a monomeric form are no longer soluble above a certain concentration. The concentration of the epitopes on the binding partners in a polymeric form depends on the size of the carrier material and can easily be individually determined by a person skilled in the art for any test procedure and any detection parameters. A guide value for the concentration of the epitopes on the binding partners in a polymeric form of 5 to 500 ng peptide per ml carrier material has proven to be suitable in the case of peptidic epitopes (length: 6 to 20 amino acids).
In addition to the binding partners in a monomeric form, additional interference-eliminating agents such as for example anti-Fd antibodies described in the introduction can also be used in order to additionally reduce interference by IgG antibodies.
Heterogeneous as well as homogeneous methods can be used as test procedures for the antigen-specific IgM test. In a homogeneous test procedure the complex composed of R1, sample-IgM and R2 is not bound to a solid phase. Instead the agglutination of several such complexes with one another leads to a turbidity which is a measure for the concentration of IgM. The binding partners in a monomeric form which reduce IgG interference do not inhibit the agglutination.
However, a heterogeneous method is preferably carried out. A method according to the bridge-test principle (see EP-A-0 280 211) is particularly preferably carried out. In one of the preferred embodiments a conjugate of a polyhapten according to the invention and a binding partner of a specific binding system, preferably biotin is used as R1. R2 is composed of a polyhapten according to the invention or binding partners in a polymeric form and a label, preferably digoxigenin. The same polyhaptens are particularly preferably used in R1 and R2. In this preferred embodiment the receptors R1 and R2 are incubated in the presence of the, in this case preferred, solid phase coated with avidin or streptavidin simultaneously with the sample and the binding partners in a monomeric form, preferably peptides. In this process the binding partners in a polymeric form of R1 and R2 react specifically with the IgM antibodies to be determined whereas the IgG antibodies of the same specificity are masked by the peptides i.e. by the binding partners in a monomeric form so that they cannot bind to the binding partners in a polymeric form. Thus the entire complex of avidin/streptavidin-R1-IgM-sample antibody-R2 is bound to the solid phase. After separating the solid phase from the liquid phase and optionally washing the solid phase, the complex bound to the solid phase is incubated with an additional receptor (in this case with an antibody directed against digoxigenin) which specifically recognizes the label of R2. The further receptor is coupled to a signal-generating group preferably with the enzyme peroxidase. After a further optional washing step, the sample antibody is detected via the signal-generating group, in this case by the substrate converted by the enzyme. In this test procedure the incubation of the sample with R1, R2 the binding partners in a monomeric form and the additional receptor can also be carried out concurrently. This additionally simplifies the test procedure.
The test procedure described above is also very well suited for an application to automated systems. It is also possible to detect several antigen-specific IgM antibodies such as HIV antibodies against various HIV antigens. In such a case the additional receptor can also be used as a universal label since the additional receptor specifically recognizes the label of R2. If several IgM antibodies with different antigen specificities are detected simultaneously, the polyhapten components of R1 and R2 as well as the binding partners in a monomeric form that are used to reduce interference must have the appropriate specificities.
All biological liquids known to a person skilled in the art can be used as samples. Body fluids such as whole blood, blood serum, blood plasma, urine, saliva etc. are preferably used as the sample.
In addition to the sample, the solid phase and the aforementioned receptors, other additives which may be required depending on the application such as buffer, salts, detergents, protein additives such as BSA may be present in the test mixtures. The necessary additives are known to a person skilled in the art or can be determined by him in a simple manner.
A subject matter of the invention is also a reagent for the determination of an antigen-specific antibody of the immunoglobulin M class which, in addition to the usual test additives for immunoassays, contains binding partners in a monomeric form i.e. preferably peptides and a receptor R1 capable of binding to the antibody to be determined which is capable of binding to the solid phase and whose essential component is a binding partner in a polymeric form that is specifically recognized by the antibody to be determined.
A further subject matter of the invention is a reagent for the determination of an antigen-specific antibody of the immunoglobulin M class which, in addition to the usual test additives for immunoassays, contains binding partners in a monomeric form i.e. preferably peptides and two receptors R1 and R2 capable of binding to the antibody to be determined of which R1 is capable of binding to a solid phase and R2 carries a label wherein an essential component of each of the receptors R1 and R2 is a binding partner in a polymeric form that is specifically recognized by the antibody to be determined.
A further subject matter of the invention is the use of binding partners in a polymeric form for the antigen-specific determination of IgM antibodies by one of the aforementioned methods according to the invention.
An additional subject matter of the present invention is the use of binding partners in a monomeric form i.e. preferably peptides to reduce interference by IgG antibodies and/or rheumatoid factors in the determination of antigen-specific IgM antibodies.
The invention is elucidated by the following example.


The invention relates to an arrangement (18) for retrieving large-calibre ammunition (10), such as shells, from an ammunition magazine and transferring these to a loading and ramming position, in which the respective ammunition unit (10) is located directly behind and coaxially aligned with a barrel (20) of a large-calibre weapon which is mounted in such a way that it can pivot around a horizontal axis (22) to assume different elevation positions. The transferring arrangement comprises a swing arm (26) which is mounted in such a way that it can pivot around the said horizontal axis (22) between a retrieving position and a delivery position for each ammunition unit, and an ammunition pickup unit (30) which is mounted on the swing arm (26) in such a way that it can pivot. The ammunition pickup unit (30) is arranged to assume a first angular position relative to the swing arm (26) when this assumes its retrieving position, and to assume a second angular position relative to the swing arm when this assumes its delivery position.

Gun turrets which house large-calibre weapons, such as mortars and possibly guns, and where the ammunition magazine is located relatively close to the weapon, have previously been difficult to give a relatively small and compact design on account of the mechanism for retrieving and loading the ammunition requiring space so that it is not in the way of the rear end of the weapon when this recoils upon firing. In order to make possible handling of ammunition in this way, known mechanisms have had a complicated and relatively bulky design, which has made it difficult to give the gun turret a compact design at the same time.
SE 513 006 C2 describes a known arrangement of the type described in the introduction for loading a large-calibre weapon (gun) with artillery shells, where the ammunition pickup unit is arranged, after insertion of a shell from a magazine located to the rear, first to be pivoted around a rear axis by means of guide curves attached to the gun and a link system into such an angular position relative to the swing arm that the shell can assume an angle that approximately corresponds to the elevation of the gun, after which the shell is released from the ammunition pickup unit and is transferred to a separate shell cradle which is then moved sideways on guide rails attached to the gun into a position for insertion of the shell into the barrel of the gun by means of a ram on the cradle. This arrangement is relatively complicated and does not allow direct transferring of a shell from a magazine to a loading position by means of only one pivoting movement of the swing arm and the ammunition pickup unit mounted upon it.
SE 500 600 C2 shows a known mortar arrangement, where two or more barrels are arranged parallel to each other in a common cradle.

Arrangement for transferring large-calibre ammunition from an ammunition magazine to loading position in a large-calibre weapon


A descrambling method is suitable for improving the data transfer rate and fast data processing separate scrambled data into a plurality of data groups each including plural pieces of scrambled unit data. Initial scramble patterns are respectively assigned to the data groups. An initial scramble pattern is prepared and assigned to a specific data group. A first scramble pattern is generated in one clock cycle using the prepared initial scramble pattern and then one of the scrambled unit data pieces in the specific data group is prepared. A descrambling operation using the first scramble pattern and the prepared one scrambled unit data piece is then performed to produce an original data piece.

1. Field of the Invention
The present invention generally relates to a method of descrambling scrambled data using a scramble pattern. More particularly, this invention relates to a method of descrambling scrambled data recorded on a recording medium in a disk apparatus, and a circuit for generating a scramble pattern.
2. Description of the Related Art
Since digital video disk (DVD) media promises large-capacity, individual makers are trying to develop DVD systems. Recently, enthusiastic efforts have been, and are being, made to standardize the DVD specifications.
FIG. 1 presents a flow diagram showing a data demodulating process in a DVD drive designed exclusively to read data. A disk 100 has data recording tracks arranged in a spiral form. Physical sector data is recorded on each track in a sector by sector manner. Physical sector data read from the disk 100 is subjected to EFM (Eight to Fourteen Modulation) Plus demodulation to yield recorded sector data 101. The recorded sector data 101 includes plural pieces of sector data 102, plural pieces of first error correction code (ECC) data PI affixed to the individual row data in the sector data 102, and plural pieces of second error correction code data PO affixed to the individual column data in the sector data 102. The data are recorded on the disk 100 in the order of the sector data 102, the first error correction codes PI and the second error correction codes PO.
Sixteen pieces of sector data 102, sixteen first error correction codes PI and sixteen second error correction codes PO are grouped in the recording order, thus yielding ECC-affixed data 103. Sixteen pieces of sector data 102 form one block.
Error correction is performed on one block of sector data 102 using the first error correction codes PI. Then, error correction is performed on one block of sector data 102 using the second error correction codes PO. In this manner, sixteen pieces of scrambled data 104 are generated. Each scrambled data 104 is data generated by performing an exclusive OR operation on the original data and a scramble pattern.
To generate sixteen pieces of original sector data 105, an exclusive OR operation on each scrambled data 104 and a scramble pattern used for the generation of each scrambled data 104, or descrambling, is executed.
As shown in FIG. 2, sector data 105 includes main data of 2048 (2K) bytes, 4-byte identification data ID, a 2-byte error correction code IEC for the identification data ID and a 6-byte reserve area RSV, all of the latter three being affixed to the front portion of the main data. The sector data 105 further includes a 4-byte error correction code EDC, which is affixed to the end portion of the main data to detect an error in the main data. The identification data ID includes a 1-byte sector information field and a 3-byte sector number field.
FIG. 3 shows a conventional scramble pattern generator 110 which is used to descramble scrambled data. The scramble pattern generator 110 includes a feedback type shift register 111 of fifteen bits b14 to b0, and an exclusive OR (EOR) gate 112.
The EOR gate 112 receives the logic values of the bits b14 and b10 and performs an exclusive OR operation thereon. The resultant logic value is supplied to the bit b0. The shift register 111 receives an initial scramble pattern in response to the first pulse of a clock CK. The shift register 111 further successively shifts the logic values of the bits b13-b0 to the adjoining bits b14-b1, respectively, every time each pulse of the clock CK is input. The shift register 111 receives the output logic value of the EOR gate 112 at its bit b0 and outputs the logic values of the bits b7-b0 as an 8-bit scramble value SK for every eight pulses of the clock CK.
As shown in FIG. 4, the initial value of a scramble pattern is determined by the ID value of the bits b7-b4, which is assigned to the sector number field of the identification data ID. That is, one initial pattern is assigned to one block formed by sixteen data sectors. When the ID value "0(h)" ((h): a hexadecimal notation) of the bits b7-b4 is assigned to the sector number field, for example, in the first block, the initial scramble pattern "0001(h)" is determined. At this time, 00000000000001(2) ((2): a binary notation) is set in the bits b14-b0 of the shift register 111. Accordingly, the logic value 00000001(2) of the bits b7-b0 is output as the initial 8-bit scramble value SK from the shift register 111.
An exclusive OR operation on the initial 8-bit scramble value SK and the first 8-bit main data of the scrambled data 104 is performed to generate 1-byte original data. The next 1-byte main data is descrambled using 8-bit scramble value SK outputted from the shift register 111 after receiving eight pulses of the clock CK.
Since the conventional scramble pattern generator 110 acquires an 8-bit scramble value SK from the shift register 111 in accordance with the transfer rate of main data, it requires the clock CK, the frequency of which is eight times the transfer rate of main data. When the transfer rate of main data is set to 10 Mbytes/sec, for example, the scramble pattern generator 110 needs a clock CK that has a frequency of 80 megahertz (MHz). The high frequency of the clock CK stands in the way of improving the transfer rate of main data and fast data processing.
The last data of the data sector 105, or the 2048th data, is descrambled by using an 8-bit scramble pattern, which has been generated by the input of 2047.times.8 clock pulses to the shift register 111. In other words, the 2048th data is acquired only after 2047.times.8 clock pulses are input to the shift register 111. Furthermore, when the shift register 111 inputs 1023.times.8 clock pulses, descrambling 1024-byte data is obtained using a corresponding 8-bit scramble pattern. It is therefore not possible to acquire the desired original byte data immediately after the descrambling operation is initiated. This obstructs fast data processing.

Method of descrambling scrambled data using a scramble pattern and scramble pattern generator


An assembly of a tub and liquid massage system, comprises a tub defining a bathing cavity for receiving liquid. A tub wall of the tub has a plurality of openings. A liquid massage system comprises a liquid circuit for collecting liquid from the tub, the liquid having at least a pump device for exposing the liquid in the liquid circuit to a pump action. A plurality of nozzles are provided at ends of the liquid circuit, each nozzle having a nozzle body with at least one connector portion in fluid communication with the liquid circuit. The nozzle body defines an outlet adapted to be mounted to a tub wall opposite one said opening in the tub wall for feeding liquid from the liquid circuit to the outlet into the bathing cavity of the tub, at least some of the nozzles having a throat portion in the outlet, the nozzles with the throat portion having an inner diameter reduction ratio between the nozzle body and the outlet of at least 2.5.

Tubs are well known for their primary use, namely a washroom installation in which a user person washes/bathes. Tubs have, however, evolved to add pleasure and comfort to practicality, and are found in many forms, such as bathtubs, spas and whirlpools. For instance, tubs are now provided with water massage systems, as known as whirlpool systems.
Massage systems of various configurations have been provided to inject fluids, such as air or water, into the liquid of the tub, so as to procure a massaging effect for the occupant of the tub. One known water massage system comprises a network featuring a pump that collects water from the tub, and re-injects the water with velocity and/or pressure via nozzles strategically positioned at strategic locations in the wall of the tub. These water massage systems typically have a venturi to add air to the water flow, and hence inject a mixture of air/water in the water of the tub.
Despite creating a strong massaging effect, there remains a need to perform additional effects to provide different types of treatment with water massage systems.


An apparatus and method for protection switching of an optical channel at each node in an optical network based on wavelength division multiplexing optical transmission technology are provided. The method can be applied to any node having at least two optical fiber inputs and outputs. The apparatus includes: a splitter receiving an electrical signal and splitting the received electrical signal into a plurality of electrical signals which are substantially identical to the received electrical signal; an output switching unit selecting output paths of the electrical signals split by the splitter according to an optical channel path control command of the optical network; and a plurality of optical transponders being assigned to the respective output paths of the electrical signals, converting the electrical signal input by the selection of the output switching unit to an optical signal, and transmitting the converted optical signal to another node of the optical network.

1. Field of the Invention
The present invention relates to an optical network based on wavelength division multiplexing optical transmission technology and, more particularly, to an apparatus and method for protection switching of an optical channel at each node in an optical network.
This work was supported by the IT R&D program of Ministry of Information and Communication (MIC)/Institute for Information Technology Advancement (IITA) [2006-S059-02. ASON based Metro photonic cross-connector technology].
2. Description of the Related Art
Wavelength division multiplexing (WDM) optical transmission technology has been rising as a solution to the sharp increase in demand for transmission capacity. The WDM optical transmission technology makes it possible to simultaneously transfer a plurality of wavelength channels through a single optical fiber. For example, assuming that one wavelength channel transfers 50 wavelength channels at a rate of 10 Gb/s, the total transfer rate amounts to 500 Gb/s. As can be seen from this example, the WDM optical transmission technology is very useful in high-capacity data transmission.
Meanwhile, in order to increase the efficiency and flexibility of an optical network that puts the WDM optical transmission technology into practice, technology for adding and dropping a wavelength channel at a network node is required. Such a requirement is fulfilled by fixed optical add-drop multiplexer (FOADM) technology. Furthermore, reconfigurable optical add-drop multiplexer (ROADM) technology makes it possible not only to increase the efficiency of the optical network but also to make a more economical use of network resources, etc. The use of the ROADM technology allows a certain channel to be added or dropped at a certain node, so that the network can be operated with higher efficiency.
Meanwhile, in order to further increase the efficiency of the ROADM technology, along with the development of the ROADM technology, it is predicted that an optical network topology will gradually develop from a simple point-to-point or ring type to a complicated mesh type.
However, due to its high transfer rate of 2.5 Gb/s to 40 Gb/s and the transmission of high-capacity data, situations may become serious when the signal quality of optical channel is degraded during the transmission. In order to solve this problem, an increasing interest is taken in the problems associated with protection switching of the optical channel, and furthermore it is essential to find a solution to this problem. The optical network topology of a simple point-to-point or ring type, which is commonly used at present, employs a 1+1 protection switching method. If a signal is not transmitted through one of optical fibers due to cutoff of the optical fiber or problems with, for example, an optical amplifier, another signal transmitted through the other optical fiber is detected and processed. In other words, a main signal and a sub signal are set on the basis of a signal transmission system. Thus, when the main signal has a problem with the transmission, the sub-signal is processed.
Hereinafter, reference will be made about conventional protection switching of an optical channel signal in the optical network that puts into practice the WDM optical transmission technology having this technical background with reference to FIGS. 1 through 3.
FIG. 1 illustrates the configuration of a ring-type optical network in which a conventional method for protection switching of an optical channel is realized.
As illustrated in FIG. 1, four nodes A, B, C and D interact to transmit and receive data. Each node is connected to neighboring nodes through two optical fibers P and W. One of the optical fibers P and W is a working fiber W as a main optical fiber, through which traffic runs in a clockwise direction. The other optical fiber P is a protection fiber, through which traffic runs in a counterclockwise direction when the working fiber W has any problem.
For example, in the case of traffic proceeding from the node B to the node A, a transmitter of the node B splits a signal into two identical signals, and then transfers one of the two signals through the working fiber W and the other signal through the protection fiber P. A receiver of the node A has a switch to select data received through the working fiber W and the protection fiber P. As illustrated in FIG. 1, the receiver of the node A receives the signal through the working fiber W in a normal condition. However, when the working fiber W is partly cut off, the receiver of the node A may receive the signal through the protection fiber P. This technique is known as a unidirectional path switched ring (UPSR). More specifically, the traffic, which is transmitted through one transmission path, is additionally transmitted using another transmission path, so that the signal can be transmitted to its destination even when the signal fails to be transmitted through one transmission path.
FIG. 2 is a block diagram illustrating the configuration of a conventional apparatus for protection switching of an optical channel. As illustrated in FIG. 2, the conventional optical channel protection switching apparatus includes a splitter 200 for splitting a signal, which is input in order to conduct the aforementioned 1+1 protection switching, into multiple signals, a switch 210, and optical transponders 220a and 220b. Each of the optical transponders 220a and 220b includes an optical transmitter, an optical receiver, and other additional elements, and performs optical/electrical and electrical/optical signal conversion, that is, converts an optical signal to an electrical signal, and an electrical signal to an optical signal.
First, when transmitting the signal, the splitter 200 splits an input electrical signal into two electrical signals and outputs the two electrical signals to the optical transponders 220a and 220b. The optical transponders 220a and 220b convert the input electrical signals to optical signals. The optical signals are transmitted to another node through the working fiber P and the protection fiber P, respectively, via a device, such as ROADM or FOADM, or a photonics cross-connect switch (PXC).
Further, the optical signals, which are received from the other node through the working fiber P and the protection fiber P, are converted to electrical signals by the optical transponders 220a and 220b, and then the converted electrical signals are output. At this time, the switch 210 selects the signal received through the working fiber W in a normal operation. However, when the working fiber W is not in a normal condition, the switch 210 selects the signal received through the protection fiber P.
FIG. 3 is a block diagram illustrating the configuration of another conventional apparatus for protection switching of an optical channel. As illustrated in FIG. 3, the conventional optical channel protection switching apparatus includes an optical transponder 300, a splitter 200 and a switch 210. The optical transponder 300 converts an electrical signal to an optical signal, and outputs the optical signal. The splitter 200 splits the optical signal, which is output from the optical transponder 300, into two identical signals, and then transmits the two signals through the working and protection fibers W and P, respectively. The splitter 200 may be either an optical divider or an optical coupler. The split signals are transmitted to another node through the working fiber W and the protection fiber P, respectively, via a device, such as ROADM or FOADM, or a photonics cross-connect switch (PXC).
Further, the switch 210 selects one of the optical signals, which are received from the other node through the working and protection fibers. During normal operation, the switch 210 selects the signal received through the working fiber W. However, when the working fiber W is not in a normal condition, the switch 210 selects the signal received through the protection fiber P. The optical transponder 300 converts the optical signal, which is selected by the switch 210, to an electrical signal, and then outputs the electrical signal.
The conventional protection switching of the optical channel signal has been described above with reference to FIGS. 1 through 3. The protection switching of the optical channel signal as described above may be applied to an existing point-to-point or ring topology. However, as already mentioned above, the optical network topology is predicted to become more complicated, and ultimately develop into the mesh topology.
FIG. 4 illustrates the configuration of a mesh-type optical network. Twelve nodes A through L are connected to one another, each of which is connected to neighboring nodes through two optical fibers. In the case of a point-to-point or ring type optical network, each node is connected with two neighboring nodes and thus has two inputs and two outputs for the optical fibers. However, in the case of the mesh-type optical network, each of the nodes A, D, I and L has two inputs and two outputs, each of the nodes F and G has four inputs and four outputs, and each of the nodes B, C, E, H, J, and K has three inputs and three outputs. In other words, in the case of the mesh-type optical network, the number of the inputs and the number of outputs vary depending on the position of the node. Thus, the optical channel protection switching apparatus, in which each node has two inputs and outputs of the optical fibers as illustrated in FIGS. 2 and 3, can no longer be applied to the mesh-type optical network. Furthermore, the mesh-type optical network can set various traffic paths, where intermediate nodes may be included in more traffic paths. However, one or more protection fibers may be provided in addition to the working fiber, causing a wastage of resources.

Apparatus and method for protection switching of optical channel

Electronics and Telecommunications Research Institute


A take-up pulley is provided with a power input member and a power output member which are radially divided, both of the members being engaged with each other over their peripheral surfaces. An elastic force of an annular elastic member acts on the engagement portion between both the power output member and the power input member in the peripheral direction in order to obtain a predetermined frictional engagement force between the power input member and the power output member.

The present invention relates to a magnetic and reproducing apparatus such as a video tape recorder for domestic use (a household VTR), and more particularly, to a rotational force control mechanism for a reel drive device in the magnetic recording and reproducing apparatus.
Conventionally, as disclosed in Japanese Patent Publication No. 2-10499B (58-53049A), for example, a belt (a rubber belt or the like) having a rectangular cross-section is used for transmission of a rotational force from a capstan motor to a take-up pulley to drive a reel. Little notice is normally taken of controlling the rotational force to be transmitted between the capstan motor and the take-up pulley.
As in the above-described prior art, when a rubber belt is used for power transmission, a reliability of the belt to transmit the power is sometimes lowered due to deterioration of the rubber under long use. In order to solve the problem, a so-called toothed belt which is provided with a number of teeth (projections) has recently been used to transmit the power in order to ensure a reliability over a long period of time.
Here, the toothed belt will be explained more in detail. In the toothed belt, generally, high-strength plastic fibers are provided in a core portion so as to obtain a longtime reliability; a soft material such as urethane resin is coated on an outer side of the belt; and a number of teeth (projections) are provided on an inner side of the belt for the purpose of securely transmitting the power. In case of using the toothed belt, a belt pulley of the capstan motor and the take-up pulley, between which the toothed belt is extended, are formed on their outer peripheries with toothed portions corresponding to the teeth (projections) of the toothed belt. In a rotational force transmitting mechanism utilizing the toothed belt constructed in the above-mentioned manner, if an excessive power is applied between the teeth of the toothed belt and the toothed portions of the pulleys when the capstan motor is rapidly started or stopped or when an extraordinarily large load is applied serious accident such as damage of the teeth of the toothed belt or cutting of the belt may occur.
In order to prevent these accidents, it is known to provide a rotational force control device in the toothed belt rotational force transmitting mechanism. More specifically, in the case where an excessive load over a certain value (allowable value) is applied to the toothed belt rotational force transmitting mechanism, a predetermined portion of the mechanism is designed to race upon application of a predetermined rotational force, to thereby prevent the members of the mechanism from damage. In a conventional rotational force control mechanism, however, as disclosed in the aforementioned Japanese Patent Publication No. 2-10499B (58-53049A), a so-called opposed disk frictional type clutch mechanism is used in which disk-like rotary members are pressed against each other from the outer sides thereof by means of spring members with a frictional member such as a wool felt interposed between the rotary members. This structure involves such disadvantages as to require a number of component parts, to bring about a high cost and to increase the size of the mechanism.
In view of the above-described problems, the present invention aims to provide a magnetic recording and reproducing apparatus including a rotational force control mechanism with a simplified structure which enables reduction in cost and size of the magnetic recording and reproducing apparatus.

Take-up pulley with torque-limiting mechanism for magnetic recording and reproducing apparatus


An example embodiment includes a thermal conduction system for dissipating thermal energy generated by operation of an optical subassembly that is disposed within a shell of a communication module. The thermal conduction system can include a thermally conductive flexible member that contacts the optical subassembly and the shell of the communication module. By contacting the optical subassembly and the shell, the thermal energy generated by operation of the optical subassembly can transfer from the optical subassembly to the shell. The thermally conductive flexible member defines thermally conductive flexible member holes that correspond to pins extending from the optical subassembly. The pins pass through the thermally conductive flexible member holes enabling the thermally conductive flexible member to contact the optical subassembly.

Field of the Invention
Embodiments described herein relate generally to communication modules. More particularly, example embodiments relate to a communication module that implements one or more thermally conductive members to transfer thermal energy away from an optical subassembly. Thermally conductive members may include a thermally conductive flexible member and/or a thermally conductive pad that may be deformable.
Related Technology
Communication modules, such as electronic or optoelectronic transceivers or transponder modules, are increasingly used in electronic and optoelectronic communication. Each communication module typically communicates with a host device printed circuit board by transmitting and/or receiving electrical data signals to and/or from the host device printed circuit board. The communication module can also transmit electrical data signals outside a host device as optical and/or electrical data signals. Many communication modules include optical subassemblies such as transmitter optical subassemblies (individually, a "TOSA") and/or receiver optical subassemblies (individually, a "ROSA") to convert between the electrical and optical domains.
Generally, a ROSA transforms an optical signal received from an optical fiber or other source to an electrical signal provided to the host device, while a TOSA transforms an electrical signal received from the host device to an optical signal emitted onto an optical fiber or other transmission medium. A photodiode or similar optical receiver contained by the ROSA transforms the optical signal to the electrical signal. A laser diode or similar optical transmitter contained within the optical subassembly is driven to emit an optical signal representing the electrical signal received from the host device.
The process of converting optical signals to electrical signals and electrical signals to optical signals can generate thermal energy in the optical subassembly. The thermal energy generated in the optical subassembly can cause damage to the optical subassembly. Additionally, high-temperature environments can create unstable thermal conditions that can cause ineffective optical subassembly function. For example, high temperature environment can reduce laser performance or can cause premature laser failure. High temperatures may also cause problems to epoxies, solder, and/or other bonding materials in the optical subassembly. These high temperatures may be too great to be effectively dissipated and controlled by a thermoelectric cooler installed in the optical subassembly.
The subject matter claimed herein is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one exemplary technology area where some embodiments described herein may be practiced.

Thermally conductive flexible member for heat transfer


An apparatus and method for transmitting and receiving a bit stream. On the transmission side, coded bits (Y.sub.t) and an interleaved version of the coded bits (X.sub.t) are separately modulated and transmitted. On the reception side, a priori output probabilities produced by a probability generator (34) are combined (112) and then input to a SISO decoder (111). Combined a posteriori output probabilities (115) produced by the SISO decoder are split (113) and then fed back to the probability generator.

Each of the documents listed below is referred to herein by the corresponding number enclosed in square brackets to the left of the document. Each of these documents is also incorporated herein by reference.    [1] Y. Liu, M. P. Fitz, and O. Y. Takeshita, "Qpsk space-time turbo codes," in IEEE ICC, June 2000.    [2] X. Li and J. A. Ritcey, "Bit-interleaved coded modulation with iterative decoding," using soft feedback, "Electronic Letters, vol. 34, pp. 942–943, 4 March 1998.    [3] X. Li and J. A. Ritcey, "Bit-interleaved coded modulation with iterative decoding," in IEEE ICC, vol. 2, pp. 858–863, June 1999.    [4] X. Li and J. A. Ritcey, "Trellis-coded modulation with bit interleaving and iterative decoding," IEEE Journal on Selected Areas in Communications, vol. 17, pp. 715–724, April 1999.    [5] X. Li and J. A. Ritcey, "Bit-interleaved coded modulation with iterative decoding," IEEE Communications Letters, vol. 1, pp. 169–171, November 1997.    [6] V. Tarokh, N. Seshadri, and A. R. Calderbank, "Space-Time Codes for High Data Rate Wireless Communication: Performance Criterion and Code Construction," in IEEE Transactions on information theory, vol. 44, No. 2, pp. 744–765, March 1998.    [7] A. R. Hammons and H. E. Gamal, "On the Theory of Space-Time Codes for PSK Modulation," in IEEE Transactions on information theory, vol. 2, No. 2, pp. 524–542, March 2000.
Coding and interleaving techniques are often used in wireless communication systems to improve the communication performance. FIG. 1 illustrates an example of a conventional wireless communication system described in [1]. This example implements turbo coding by using two convolutional coders (CC). One of the convolutional coders receives at its input the data stream that is to be transmitted, and the other convolutional coder receives at its input an interleaved (see 10) version of the data stream. The outputs of the convolutional coders are then modulated using QPSK (Quadrature Phase Shift Keying) and transmitted by respective transmit antennas. At the receiver, the signal from the antenna is input to a probability generator which generates symbol (or bit) probabilities. These symbol probabilities are fed to soft-input, soft-output (SISO) decoders that iterate to get estimates of the transmitted symbols (or bits). The SISO decoders use knowledge of the trellis of the convolutional coders to produce the estimates.
FIG. 2 illustrates an example of a conventional wireless communication system described in [2] and [3]. The system of FIG. 2 uses a single convolutional coder and an interleaver 21 before modulation and transmission by a single antenna. At the receiver, the signal from the antenna is demodulated and de-interleaved (see 22), and is then input to a SISO decoder. The a posteriori symbol probabilities output from the SISO decoder are interleaved (see 23) and fed back into the demodulator to get a better estimate of the symbol probabilities. This loop is iterated over. Systems similar to the one illustrated in FIG. 2 have also been suggested in [4] and [5], but those systems implement hard decoding decisions instead of soft decisions.
FIG. 8 illustrates an example of a conventional wireless communication system described in [6]. In this example, bits are encoded with a single encoder, and separate sets of the encoded bits are applied to respective modulators in separate branches. The modulators perform constellation mapping, and the separate branches permit transmit diversity. Special care is exercised in order to provide a full diversity stream. At the receiving end, conventional Viterbi decoding is performed. The work in [6] was followed by the work in [7], wherein it is demonstrated that, for all BPSK constellations, it is very easy to achieve diversity, and that coding advantage should be a primary optimization goal.
It is desirable in view of the foregoing to provide for improved performance in wireless communication systems that utilize turbo coding and transmit diversity.
According to the invention, coded bits and an interleaved version of the coded bits are separately modulated and transmitted. On the receiver side, a priori output probabilities produced by the probability generator are combined and then input to a SISO decoder, and combined a posteriori output probabilities produced by the SISO decoder are split and then fed back to the probability generator. This advantageously permits the probability generator to produce an improved estimate of the received symbols.

Using SISO decoder feedback to produce symbol probabilities for use in wireless communications that utilize single encoder turbo coding and transmit diversity


Embodiments of the present application generally relate to controlling ingress/egress through entryway devices. More particularly, but not exclusively, embodiments of the present invention relate to attaining confirmation of intent relating to access to a controlled opening. According to certain embodiments, the credential device and/or the user of the credential device is prompted to provide a response, or otherwise is to perform certain actions, that can demonstrate a confirmation of intent to gain access to the controlled opening. Such responses and/or actions can be evaluated to determine authority to gain access to the controlled opening. Further, such intent confirmation events may, depending on the embodiment, be performed before or after credential information is communicated from the credential device and/or before or after pairing of the access control device and the credential device. According to other embodiments, intent may be confirmed, at least in part, based on changes in the characteristics of signals communicated from the credential device.

Embodiments of the present invention generally relate to controlling ingress/egress through entryway devices. More particularly, but not exclusively, embodiments of the present invention relate to attaining confirmation of intent relating to access to a controlled opening(s) as part of an approach to controlling the opening/closing of entryway devices.
Security management systems often utilize a variety of access control devices to control ingress and/or egress through a controlled opening, including, for example, an entryway that can be closed through the use of an entryway device, including, but not limited to, a door or gate. The operation and management of such security management systems typically involves the transmission and/or receipt of certain electronic communications between different credential devices and an access control system. Often, the communications between the credential device and the access control system are generally omni-directional. For example, a mobile credential device may transmit signals containing information relating to authorization to unlock an lock device from a variety of positions relative to a receiving component of the access control system. Further such communication from the credential device may be automatically transmitted in that such communications often do not require specific prompting by a user of the credential device.
Yet, in at least certain situations, the credential device being able to automatically communicate information relating to authorization to pass through the controlled opening does not necessarily correlate to an intent by a user of the credential device to actually pass through a controlled opening. For example, the credential device may pass through a hallway having a plurality of controlled openings and associated lock devices. In certain situations, the presence of the credential device in relative close proximity to the lock device can lead to the credential device automatically communicating to the lock device information corresponding to authorization to unlock lock device and/or to pass through the associated controlled opening. Yet, the presence of the credential device in such a location does necessarily always equate to an intent of a user of the credential device to actually pass through any or all of those controlled openings. Moreover, in at least certain situations, despite the presence or position of the credential device, the actual intent of the user may be that the status(es) of at least one of the access control devices remain unchanged, such as, for example, the access control device(s) remains in a locked state and/or the associated entryway device(s) for the controlled entryway(s) remain closed.
Additionally, the omni-directional nature of at least some credential devices can present issues with determining which side(s) of the controlled opening the credential device is, or is no longer, positioned. For example, the omni-directional nature of communications at least with the credential device may present issues with determining whether the authorized credential device has, or has not, passed through, or is in the process of passing through, the associated controlled opening. For example, often, for at least some systems, following authorization for the lock device to be unlocked, and subsequent opening of the associated entryway device and corresponding passage through the controlled opening, the credential device may continue to communicate to the lock device an intent to pass through the controlled opening and/or a request that the lock device be in an unlocked state. Such continued communication can, in at least certain situations, lead to the lock device continuing to be in an unlocked state and/or leave the controlled opening otherwise susceptible to subsequent passage by unauthorized users, including people who may tailgate or otherwise subsequently follow the authorized credential device through the controlled opening.


A multi-piece iron-type golf club head with a substantial weight member is disclosed and claimed. The golf club head includes a plurality of body members. A first body member includes a face, a rear surface, and a hosel. A viscoelastic material is attached to the rear surface, and a second body member is attached to the viscoelastic material. The second body member, which may be a weight member, has a substantially larger mass than in known golf clubs.

1. Field of the Invention
The present invention relates to a golf club head, and, more particularly, the present invention relates to a multi-piece iron-type golf club head with a substantial weight member.
2. Description of the Related Art
Golf club heads come in many different forms and makes, such as wood- or metal-type, iron-type (including wedge-type club heads), utility- or specialty-type, and putter-type. Each of these styles has a prescribed function and make-up.
Iron-type golf clubs generally include a front or striking face, a top line, and a sole. The front face interfaces with and strikes the golf ball. A plurality of score lines or grooves is provided on the face to assist in imparting spin to the ball. The top line is generally configured to have a particular look to the golfer and to provide weight. The sole of the golf club is particularly important to the golf shot because it contacts and interacts with the ground during the swing.
In conventional sets of iron-type golf clubs, each club includes a shaft with a club head attached to one end and a grip attached to the other end. The club head includes a face for striking a golf ball. The angle between the face and a vertical plane is called the loft angle.
The set generally includes irons that are designated number 2 through number 9, and a pitching wedge. Other wedges, such as a lob wedge, a gap wedge, and a sand wedge, may be optionally included with the set. Each iron has a shaft length that usually decreases through the set as the loft for each club head increases from the long irons to the short irons. The length of the shaft, along with the club head loft, moment of inertia, and center of gravity location, impart various performance characteristics to the ball's launch conditions upon impact and determine the distance the ball will travel. Flight distance generally increases with a decrease in loft angle. However, difficulty of use also increases with a decrease in loft angle.
Iron-type golf clubs generally can be divided into three categories: blades, muscle backs, and cavity backs. Blades are traditional clubs with a substantially uniform appearance from the sole to the top line, although there may be some tapering from sole to top line.
Muscle backs have a substantially traditional appearance and are similar to blades, but have extra material on the back. This extra material, which may be in the form of a rib, can be used to lower the club head center of gravity. Having the club head center of gravity lower than the ball center of gravity at contact facilitates the golf shot.
Since blade and muscle back designs have a small sweet spot (that is, the area of the face that results in a desirable golf shot upon striking a golf ball), they are relatively difficult to use and are therefore typically only used by skilled golfers. However, these clubs have the benefit of producing longer golf shots than other designs. Furthermore, since these designs are typically made of relatively soft forged steel, they allow the golfer to work the ball and shape the golf shot as desired.
Cavity backs are modern designs that move some of the club mass to the perimeter of the club by providing a hollow or cavity in the back of the club, opposite the striking face. This produces a more forgiving club with a larger sweet spot. This also allows the size of the club face to be increased, also resulting in a larger sweet spot. The perimeter weighting created by the cavity also increases the club's moment of inertia, which is a measurement of the club's resistance to torque, for example the torque resulting from an off-center hit. These clubs are easier to hit than blades and muscle backs, and are therefore usable by less-skilled and beginner golfers.
Other known golf clubs achieve a desired balance or moment of inertia by adding a weight to the club. These clubs typically add a weight member to the bottom surface of the sole, in the center thereof.

Multi-piece golf club head with improved inertia


A microprocessor chip having a selectable size cache. The selection is accomplished by cache size logic fabricated on the chip. The cache size logic includes a cache size logic register with output select lines that are set by the designer. The select lines control the output of multiplexors that communicate either a "0" or the contents of selected bits of a virtual address register which receives the virtual address from the CPU to either a tag field register or an address field register.

1. Field of the Invention
This invention relates generally to microprocessor chips having caches and, more particularly, to microprocessor chips having a selectable size cache.
2. Discussion of the Related Art
A cache memory is a small, fast memory which is designed to store the most frequently accessed words from a larger, slower memory. The concept of a memory hierarchy with a cache as part of the hierarchy has been associated with the computer art from the earliest discussions of computer design. The idea of a memory hierarchy, with memory speed and memory size being the tradeoff, was discussed in John von Neumann's report on the design of the EDVAC (Electronic Discrete Variable Automatic Computer), which was written in the mid-1940s. The necessity for a cache with faster memory became more apparent because of the competition for the communication channel, which has become known as the "von Neumann bottleneck." This bottleneck and the inherent slowness of large memory components such as disk or tape drives became even more critical in the early 1960s when CPU (central processing unit) speeds could exceed memory speeds by a factor of 10. This factor has become even more critical as CPU speeds have increased by orders of magnitude over the increase in speed of memory since the 1960s.
Early studies and efforts to increase the speed and performance of computers revealed a principle that applied to computer programs called the principle of locality which has enhanced the need for caches and the value of caches in the design and operation of computers. The principle of locality states that programs access a relatively small portion of their address space at any instant of time. There are two different types of locality: (1) temporal locality (locality in time) which states that if an item is referenced, it will tend to be referenced again soon and (2) spatial locality (locality in space) which states that if an item is referenced, items in memory with close addresses will tend to be referenced soon. The design, implementation, and use of a memory hierarchy takes advantage of the principle of locality. A major consideration in the design of a memory hierarchy is that the fastest memories are more expensive per bit than the slower memories. Main memory is implemented using DRAM (dynamic random access memory) chips, while levels closer to the CPU, such as caches, use SRAM (static random access memory) chips. DRAM is less costly per bit than SRAM; however, it is substantially slower. The price difference arises because DRAM uses fewer transistors per bit of memory and, thus, DRAMs are less expensive to manufacture. Another factor in the design of memory systems is that SRAM use more silicon area for the same memory capacity.
Because of the differences in cost and access time, it is advantageous to implement a computer architecture with the memory built as a hierarchy of levels with the faster memory close to the microprocessor and the slower, less expensive memory further away from the microprocessor. The goal has been to present the users with as much memory as possible in the least expensive technology, while providing the speed required by the application. This tradeoff between cost and speed and, thus, performance is one of the major considerations in computer system design.
The three major technologies used to construct memory hierarchies are SRAM, DRAM, and magnetic disk. The access time and price per bit vary widely among these technologies as the table below indicates (using values typical for 1993):
______________________________________ Memory Typical access Technology time $ per MByte ______________________________________ SRAM 8-35 ns $100-$400 DRAM 90-120 ns $25-$50 Magnetic Disk 10,000,000-20,000,000 ns $1-$2 ______________________________________
It is clear from an examination of the values in the above table that a computer system design that incorporates unneeded or underutilized SRAM in a cache has a higher cost than required. On the other hand, too little SRAM in a cache will provide a lower cost device but at the expense of speed. It has been the tendency in the prior art to design a computer system with a microprocessor having a standard cache sized to meet the needs of a broad spectrum of users without regard to the specific use for which the microprocessor is to be used. Generic designs were used since design costs are high. But a microprocessor designed with a standard cache size is difficult to effectively fit into a price-performance requirement for a given application or a market. On the other hand, it is too expensive, in terms of design and development costs, to design a separate microprocessor for each price-performance demand of the market. Since the performance of a microprocessor depends upon the cache size and cache parameters, it is desirable to be able to produce microprocessors of varying levels of performance and size from the same basic design without the associated high cost of each individual new design effort.
What is needed is a design which will allow the designer to select a cache size which is optimum, in terms of a mix between cost and performance, for a target market. The designer should be able to consider factors such as the size of application programs that will likely be used, the number of different application programs that will likely be used, the necessity for speed, and the cost constraints of the system. The optimum solution would be for the designer to be able to change the cache size by making minimal changes to a basic design in order to easily create a new version of the basic design.

Microprocessor with a fixed cache size selected from a predesigned set of sizes


Embodiments relate to an implantable cardiac system and methods, including a housing, electronic circuitry for controlling one or more of power management, processing unit, information memory and management circuit, sensing and simulation output and how these operate. The system also includes diagnosis and treatment software for diagnosing health issues, diagnosing mechanical issues, determining therapy output and manage patient health indicators over time, a power supply system including at least one rechargeable battery, a recharging system, an alarm (or alert) system to inform patient of energy level and integrity of system, communication circuitry, one or more electrodes for delivering therapeutic signal to a heart and one or more electrodes for from delivering electrocardiogram signal from the heart to the electronic circuitry, and body orientation determination, in various aspects.

The healthy heart produces regular, synchronized contractions. Rhythmic contractions of the heart are normally controlled by the sinoatrial (SA) node, which is a group of specialized cells located in the upper right atrium. The SA node is the normal pacemaker of the heart, typically initiating 60-100 heartbeats per minute. When the SA node is pacing the heart normally, the heart is said to be in normal sinus rhythm.
If the heart's electrical activity becomes uncoordinated or irregular, the heart is denoted to be arrhythmic. Cardiac arrhythmia impairs cardiac efficiency and may be a potential life-threatening event. Cardiac arrhythmias have a number of etiological sources, including tissue damage due to myocardial infarction, infection, or degradation of the heart's ability to generate or synchronize the electrical impulses that coordinate contractions.
Bradycardia occurs when the heart rhythm is too slow. This condition may be caused, for example, by impaired function of the SA node, denoted sick sinus syndrome, or by delayed propagation or blockage of the electrical impulse between the atria and ventricles. Bradycardia produces a heart rate that is too slow to maintain adequate circulation.
When the heart rate is too rapid, the condition is denoted tachyarrythmia. Tachyarrythmia may have its origin in either the atria or the ventricles. Tachyarrythmias occurring in the atria of the heart, for example, include atrial fibrillation and atrial flutter. Both conditions are characterized by rapid contractions of the atria. Besides being hemodynamically inefficient, the rapid contractions of the atria may also adversely affect the ventricular rate.
Ventricular tachyarrythmia occurs, for example, when electrical activity arises in the ventricular myocardium at a rate more rapid than the normal sinus rhythm. Ventricular tachyarrythmia includes ventricular tachycardia and ventricular fibrillation. Ventricular tachycardia may quickly degenerate into ventricular fibrillation. Ventricular fibrillation is a condition denoted by extremely rapid, uncoordinated electrical activity within the ventricular tissue. The rapid and erratic excitation of the ventricular tissue prevents synchronized contractions and impairs the heart's ability to effectively pump blood to the body, which is a fatal condition unless the heart is returned to sinus rhythm within a few minutes.
Implantable cardiac rhythm management systems have been used as an effective treatment for patients with serious arrhythmias. These systems typically include one or more leads and circuitry to sense signals from one or more interior and/or exterior surfaces of the heart. Such systems also include circuitry for generating electrical pulses that are applied to cardiac tissue at one or more interior and/or exterior surfaces of the heart. For example, leads extending into the patient's heart are connected to electrodes that contact the myocardium for sensing the heart's electrical signals and for delivering pulses to the heart in accordance with various therapies for treating arrhythmias.
In late 1980s, studies identified groups of patients that could benefit from the use of implantable cardiac defibrillators (ICDs). Implantation of ICDs became the medical standard of care for those patients determined to have the indicated level of health risks.
Over time, post market studies have identified a large group of patients who would meet the determined risk levels, but will not receive benefits from these devices in the immediate years. Therefore, such patients would receive an ICD and the device would stay in the body for a long time without ever firing or shocking the patient's heart. The current devices are designed to address complex arrhythmias and implantation of them in the initial group of patients is deemed as unnecessary, and economically irresponsible. Thousands of patients are given devices that treat more than they are at risk for, as the current devices on the market are developed to treat and handle a multitude of cardiac conditions. Additionally, the devices require a specialist to implant and often need a programmer or consultant to initially program the device.
ICDs are utilized more frequently as prophylactic devices for treatment of sudden cardiac death (SCD). In addition to implantable devices, automated external defibrillators (AEDs) are also effective in treatment of SCD but require administration of the therapy by an outside agent (such as a bystander). As long as the AED treatment is given to the patient within the first 2-3 minutes from the onset of the event, the patient will likely have a positive response to the treatment. Studies have shown that more than 75% of the SCDs occur at home and over half occur in the bedroom. Patients at risk of SCD are often alone and asleep and would need their safety product nearby and not rely on the help of a third party.


A pressurization device is described mobilizing gravity to mobilize seawater and to employ a weight (56) for gravitionally applying a force to and thereby pressurizing an enclosed pocket (58) of seawater, resulting in low energy utilisation. Energy is further recovered from the flow of pressurized seawater that is supplied to the desalination system (20), resulting in a mechanically robust and energy efficient pressurization system.

Fluids, or water in particular, are pressurised for a multitude of applications. One such application is in a desalination system using a reverse osmosis (RO) process for producing potable water. Seawater and brackish water are often used in the RO process. However, the seawater from a water source, for example the sea, has to be highly pressurised before it is supplied to the desalination system for the RO process to be performed.
High pressure pumps, for example displacement pumps, are conventionally used for drawing the seawater from the water source, pressurising the drawn seawater by compressing the seawater within a volume and supplying the pressurised seawater to the desalination system. However, the energy consumption of each of these pumps is high which results in high operating costs. Systems using these high pressure pumps require a variation of components to reduce water supply pulsation and prevent over-pressurisation of downstream pipes for conveying pressurised seawater.
There is hence a need for a pressurisation system for addressing the deficiencies of high pressure pumps.