A system for electronically, managing, finding, and/or visualizing biomolecular interactions is described. A computer-implemented system of the invention has a database having a plurality of records. Each record contains a reference biomolecular interaction defined by a chemical graph and descriptive information from an external database. The information correlates the biomolecular interactions to records in the external batabase. The system has a user interface allowing a user to selectively view information regarding a biomolecular interaction.

A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by any one of the patent disclosure, as it appears in the Patent and Trademark files or records, but otherwise reserves all copyright rights whatsoever.
The present application includes and incorporates by reference a computer sequence listing appendix on a single compact disc and its duplicate, each compact disc was created on Oct. 23, 2003 and includes the files Appendix A.doc (96 kB) and Appendix B.doc (160 kB).
The invention relates to a system, methods and products for managing, finding, and/or displaying biomolecular interactions.
Technological advances and mounting interest have pushed proteins into the scientific spotlight. This growing field encompasses the study of proteins, both in structure and in function, contained in a proteomexe2x80x94the protein equivalent of a genome. Because of increased interest and technique automation (Mendelsohn et al., 1999), the rate of proteomic data production is growing in a similar fashion as that of genomics a decade ago. For example, mass spectrometers, gene chips, and two-hybrid systems have made cellular signaling pathway mapping faster and easier and consequently these are becoming large producers of data. Protein-protein interaction and more general biomolecule-biomolecule (protein-DNA, protein-RNA, protein-small molecule, etc.) interaction information is being generated and recorded in the literature. Lessons from the genomic era have taught us that large amounts of related data recorded in scientific journals soon becomes unmanageable. A well designed common data specification based on a model of the biological information is therefore required to describe and store biomolecular interaction data.
The present inventors have designed a data specification for the storage and management of biomolecular interaction and biochemical pathway data that possesses the following properties:
1. It describes the full complexity of the biological data, from simple binary interactions to large-scale molecular complexes and networks of pathways and interactions. It stores protein, DNA, RNA, and other molecules in full atomic detail, since character based sequence abstractions of biomolecules often miss important chemical features, such as methylation on DNA. This allows as much data as possible to be stored for scientific use in electronic form rather than in print.
2. It is easily computable. A computer can easily read, write, and traverse the specification. This facilitates maintenance of a database of such information, creation of advanced queries and querying tools and development of computer programs that use the information for data visualization, data mining, and visual data entry.
3. It is platform and database independent. Tools written for one platform can read data created on another platform directly. It handles the data structure without modification as well.
4. It is succinct and easy for humans to understand. Field to data correspondence is very clear and a human readable format of the specification is available.
The data structure was designed for a database referred to herein as xe2x80x9cBINDxe2x80x9d (Biomolecular Interaction Network Database). The data structure is written in a data specification language called Abstract Syntax Notation. 1 (ASN.1, also known as X.208 or ISO-8824) The U.S. National Center for Biotechnology Information (NCBI) uses ASN.1 to describe and store all of its biological and publication data and all of GenBank, MMDB and PubMed (Ostell and Kans, 1998). BIND inherits the NCBI data model, which provides a solid foundation for the BIND data specification through the use of mature NCBI data types that describe sequence, 3D structure, and publication reference information.
Although the specification is written in ASN.1, it is not restricted to this syntax. The data structures can be readily translated to other common data specification languages such as CORBA IDL (Object Management Group, 1996) or XML if the need arises. Aside from ASN.1, no other biological data specification is sufficiently rich in mature data types to use as a foundation for BIND without first building and testing those base data types.
The BIND data specification represents complex cellular pathway information efficiently in a computer. BIND defines three main data types: interactions, molecular complexes, and pathways. Each of these objects is composed of various component and descriptor objects that are either defined in the specification proper or inherited from the NCBI ASN.1 data specifications. For example, an interaction record contains, among other data objects, two BIND-objects. A BIND-object describes a molecule of any type and is itself defined using simpler sub-objects. Normally, a BIND-object describing a biopolymer sequence will store a simple link to a sequence database, such as GenBank (Benson et al., 1999). If, however, the sequence is not present in a public database, it can be fully represented using an embedded NCBI-Bioseq object. The NCBI-Bioseq object is how NCBI stores all of the sequences in GenBank and is a mature data structure. BIND also inherits the NCBI taxonomy model (also used and supported by EMBL, DDBJ and Swiss-Prot) and data, via an inherited NCBI-BioSource, and is designed so that interactions can be both inter- and intra-organismal. Sequence, structure, publication, taxonomy and small molecule databases provide a strong foundation for BIND.
Broadly stated, the present invention contemplates a system for electronically managing, finding, and/or visualizing biomolecular interactions comprising a computer system including at least one computer receiving data on biomolecular interactions from a plurality of providers and processing such data to create and maintain images and/or text defining biomolecular interactions, said computer system, in response to data requests, creating and transmitting to a plurality of end-users, the images and/or text defining biomolecular interactions.
In an embodiment, a system for electronically managing, finding, and/or visualizing biomolecular interactions is provided comprising:
(a) a maintenance entity for receiving data on biomolecular interactions from a plurality of providers and means for receiving and processing such data to create and maintain images and/or text defining biomolecular interactions; and
(b) one or more computer systems maintained by the maintenance entity and having means for creating and transmitting to a plurality of end-users the images and/or text defining biomolecular interactions.
The system is useful in managing, finding, and/or displaying biomolecular interactions including interactions involving proteins, nucleic acids (RNA, DNA), and ligands, molecular complexes, and signaling pathways. The interactions are defined both at the molecular and atomic levels and in particular they may be defined by chemical graphs.
The invention also provides a method for displaying on a computer screen information concerning biomolecular interactions comprising retrieving an image and/or text defining a biomolecular interaction from a system of the invention.
The present invention also provides a data structure stored in the memory of a computer the data structure having a plurality of records and each record containing a biomolecular interaction and information relating to the biomolecular interaction. In an embodiment the biomolecular interaction is identified by chemical graphs. The information in the data structure may be accessible by using indices which may represent selections of information from the chemical graphs.
The term xe2x80x9crecordxe2x80x9d used herein generally refers to a row in a database table. Each record contains one or more fields or attributes. A given record may be uniquely specified by one or a combination of fields or attributes known as the record""s primary key. A record of a biomolecular interaction as used herein is generally a record containing information identifying the biomolecular interaction as a chemical graph and a plurality of other attributes with information pertaining to the biomolecular interaction (e.g. information on the cellular place of interaction, experimental conditions used to observe the interaction, conserved sequence comment of molecules in the interaction if they are biological sequences, information on molecules in the interaction, description of metabolic and signaling pathways, cell cycle stages in which an interaction is involved, locations of binding sites on the molecules in an interaction, chemical actions mediated by the interactions, and chemical states of the molecules in the interaction).
The term xe2x80x9cchemical graphxe2x80x9d refers to a connectivity graph of all the atoms and bonds in a molecule in a biomolecular interaction. The graph may include three-dimensional coordinates.
The invention also provides a method for storing a representation of a biomolecular interaction in a memory of a computer system, the method executed on a computer system and comprising the steps of:
(a) identifying a chemical graph of a biomolecular interaction; and
(b) storing a record in a data structure of the invention.
The invention further provides a method for storing a representation of a biomolecular interaction in a memory of a computer system, the method executed on a computer system and comprising the steps of:
(a) identifying a chemical graph of a biomolecular interaction;
(b) generating one or more indices from information in the chemical graph; and
(c) storing a record in a data structure of the invention.
The invention still further provides a method for identifying a biomolecular interaction that is similar to a reference biomolecular interaction, the method executed on a computer and comprising the steps of:
(a) conducting a similarity search for each molecule in a test biomolecular interaction;
(b) screening the results of the similarity search preferably by selected taxonomy;
(c) assembling a putative biomolecular interaction to create a test record;
(d) accessing one or more records in a data structure stored in the memory, the data structure having a plurality of records, each of the records containing a reference biomolecular interaction and information relating to the reference biomolecular interaction; and
(e) matching the test record with each record in the data structure to produce a matching record containing a reference biomolecular interaction matching the test biomolecular interaction.
The similarity searches may be based for example on sequence similarity or identity, or similarities in molecular weights, pIs, mass fingerprinting data or mass spectrometric data, fragment-ion tag data, peptide masses from enzymatic digestion, fragment ion masses, isotope patterns, and sequence tag data. Standard tools available in the art for similarity searching and screening can be used. (For example, the following tools may be used BLAST BioScan, Fasta3, PropSearch, SAMBA, SAWTED, Scanps, FDF, ExPASY Proteomics Tools TagIdent: PeptIdent:ProteinProspector:MultiIdent: PeptideSearch:PROWL:Mascot:BioSCAN, Pro).
Another aspect of the invention provides a computer system for storing a representation of one or more biomolecular interactions in a memory in the computer system and for comparing one or more reference biomolecular interactions to a test biomolecular interaction, comprising:
(a) a database means stored in the memory representing one or more biomolecular interactions; each of the biomolecular interactions represented by a chemical graph; and
(b) a data structure means for storing a plurality of record means, each record means containing chemical graphs of the test biomolecular interaction.
The invention also provides a computer system comprising memory means, storage means, program means, and stored means for building virtual-models of biomolecular interactions in the computer system comprising:
(a) one or more libraries of reference biomolecular interactions that comprise any number of attributes or components of the biomolecular interaction which values are either being used to describe characteristics of the types of biomolecular interactions in the computer system, or values or data structures used by the program at runtime, or are to be used to more specifically describe characteristics of individual components of the biomolecular interaction that each instance of a type of biomolecular interaction is to represent, or characteristics of each instance of biomolecular interaction in the computer system; wherein the attributes have values of any type in the computer system or in a network accessible by the computer system;
(b) means for manipulating the biomolecular interaction by domain experts or program means comprising visual means for making the biomolecular interactions available through menus or palettes or programmatic means; and
(c) constructor means to create new instances from the definitions of the biomolecular interactions, and means to establish directional output-input links between complemenatary instances of the biomolecular interactions directly or through components.
Also provided is a computer system comprising:
(a) a database having a plurality of records, wherein each record contains a reference biomolecular interaction defined by a chemical graph and descriptive information from an external database which information correlates the biomolecular interactions to records in the external database; and
(b) a user interface allowing a user to selectively view information regarding a biomolecular interaction.
In an embodiment, a computer system is provided comprising:
(a) a database having a plurality of records, each of said records containing a reference biomolecular interaction defined by a chemical graph and descriptive information from an external database, which information correlates the biomolecular interactions to records in the external database;
(b) a processor in communication with said database and responsive to user input to access records in said database; and
(c) a user interface allowing a user to provide user input to said processor to selectively view information regarding a biomolecular interaction.
Still further the invention provides a database system comprising a plurality of internal records, the database comprising a plurality of records, wherein each record contains a biomolecular interaction defined by chemical graphs and descriptive information from an external database which information correlates the biomolecular interactions to records in the external database.
In an embodiment the external database is PubMed. The interface of the computer system may further comprise user selectable links to enable a user to access additional information for a biomolecular interaction. The links may comprise HTML links. Additionally provided is a method of using a computer system to present information, or a method of presenting information pertaining to records of biomolecular interactions in a database, the records containing information identifying the biomolecular interaction and defining the biomolecular interaction by chemical graphs, the method comprising:
(a) providing an interface for entering query information relating to a biomolecular interaction;
(b) locating data corresponding to the entered query information; and
(c) displaying the data corresponding to the entered query information.
In step (b) the data is located by examining records in the database.
The invention further provides a computer program product comprising a computer-usable medium having computer-readable program code embodied thereon relating to a plurality of records of biomolecular interactions, the records identifying the biomolecular interactions and defining chemical graphs of the biomolecular interactions, the computer program product comprising computer-readable program code for effecting the following steps within a computing system:
(a) providing an interface for entering query information relating to a biomolecular interaction;
(b) locating data corresponding to the entered query information; and
(c) displaying the data corresponding to the entered query information.
The invention contemplates a database storing data relating to biomolecular interactions comprising:
(a) first data types describing biomolecular interactions between chemical objects;
(b) second data types describing collections of biomolecular interactions; and
(c) third data types describing pathways between said collections of interactions.
The first data types may include objects for the chemical objects, each of the objects including at least one of a pointer to an external database describing the chemical object, a sequence, and a chemical graph. The first data types may be stored as records and further include objects identifying the biomolecular interactions and defining chemical graphs of the biomolecular interactions.
The second data types may include lists of identifications referencing the biomolecular interactions in the collections. The third data types may include objects for the chemical objects that can form networks of interactions. The networks of interactions may include metabolic pathways and cell signaling pathways. The third data types may additionally include sequences of identifications referencing biomolecular interactions that make up the pathways.
The systems and products of the present invention may be used to study and identify biomolecular interactions. Such information is of significant interest in pharmaceutical research, particularly to identify potential drugs and targets for drug development. The systems and products provide great power and flexibility in analyzing biomolecular interactions.

System for electronically managing, finding, and/or displaying biomolecular interactions


A method wherein the separability between a polyether phase and a water phase is improved when a water-soluble compound is extracted and removed from a polyether containing the water-soluble compound with water is provided. The method comprises producing a polyether including a step of extracting and removing a water-soluble compound from a polyether containing the water-soluble compound with water, wherein the step includes at least an operation of separating a water phase from a polyether phase at a temperature of 50° C.

Various types of polymeric substances such as polyethers have been industrially produced. Usually, these polymeric substances are produced by purifying a polymeric substance containing impurities (crude polymeric substance) to remove the impurities.
Examples of the impurities contained in such a crude polymeric substance include metal compounds derived from an alkali metal compound and a double metal cyanide complex, and specific examples thereof include the following compounds:    (1) In producing a hydroxyl-group-containing polyether by allowing an alkylene oxide to react with an initiator, a double metal cyanide complex catalyst is used as a catalyst. This catalyst remains in the resulting polymeric substance without change or as a modified decomposition product.    (2) When an oxyalkylene polymer such as polypropylene oxide is produced by addition polymerization of an alkylene oxide, an alkali metal compound such as sodium hydroxide or potassium hydroxide is used as a catalyst. This alkali metal compound remains in the resulting polymeric substance without change or as a salt.    (3) When a functional-group-containing polymer such as an oxyalkylene polymer or a diene polymer that has a hydroxyl group or a carboxyl group is allowed to react with a halogen-containing compound such as epichlorohydrin or allyl chloride to produce a polymer having another functional group, an alkali metal compound such as sodium hydroxide or potassium hydroxide is used as a catalyst. This alkali metal compound remains in the resulting polymeric substance without change or as a salt.
In addition to the above cases, there are many crude polymeric substances contaminated with a metal compound such as an alkaline earth metal compound or a transition metal compound.
Since such a metal compound remaining in a polymeric substance causes various problems, the metal compound is preferably minimized. For example, when the polymeric substance is used in further reaction, the metal compound may affect the reaction rate or the reaction yield. Therefore, the metal compound must be sufficiently removed. More specifically, when methyldimethoxysilane or the like is allowed to react with an allyl-group-terminated polyether in the presence of a platinum-containing catalyst, a metal compound remaining due to insufficient removal significantly decreases the reaction rate.
In general, impurities are often removed by, for example, a treatment with an adsorbent or a method including neutralization, filtration, and subsequent extraction with water.
Among these, the treatment with an adsorbent is disadvantageous in that the treatment is not suitable for treating a large amount of metal compound and that the type of usable adsorbent is limited when the metal compound is a salt.
The method including filtration is disadvantageous in that crystals of neutralized salts must be enlarged and that the salts are dissolved in water when water is present.
Because of these problems and other reasons, a method of extraction separation is suitable for many cases.
The method of extraction separation is a method of sufficiently bringing a crude polymeric substance into contact with water to transfer a metal compound in the form of a water-soluble salt to the water, and then separating the water from the polymeric substance. Hitherto, it has been believed that when vigorous agitation is performed in order to satisfactorily bring a crude polymeric substance into contact with water, the system easily becomes an emulsion state because of the presence of the polymeric substance (Patent Documents 1 and 2). In particular, Patent Document 2 describes as follows: "Since polyethers produced in the presence of a double-metal cyanide complex catalyst are emulsified with water very easily, it is extremely difficult to remove the catalyst by an extraction method". Accordingly, it may take a long time for the subsequent separation of water from the polymeric substance or a huge apparatus may be required. On the other hand, when the agitation is moderately performed to prevent emulsification, the metal compound is not satisfactorily extracted. Consequently, it is necessary to establish a technique that satisfies incompatible conditions, namely, a technique in which the extraction efficiency is increased and the separability is also increased. Furthermore, such an extraction method using water cannot be used for polymeric substances having high hydrophilicity. Even in hydrophobic polymeric substances, when a trace of hydrophilic impurities is contained in starting materials, emulsification occurs extremely easily. Accordingly, the application of such an extraction method is significantly limited for industrial use. It is desirable to establish a production method including a versatile purification method that can be used for not only unsaturated-group-containing polyethers but also high-molecular-weight polyethers having the above properties.
An example of a disclosed method is a method including centrifugal separation to actively promote oil-water separation (Patent Document 3). As an apparatus used for a general method of extraction separation, a spray tower; a continuous countercurrent extraction tower, such as a stirring-type tower, and a reciprocating-type tower; and a centrifugal separator are used and disclosed (Patent Documents 1 and 3). These unexamined patent applications provide a method in which a polyether, which is a polymer, and water are agitated in a high-speed-agitation-type agitation tank equipped with impellers, and the water phase is then separated from the polyether phase in a centrifugal separator or a countercurrent contact-type agitation tower or using a filter. However, in these methods, in order to increase the extraction efficiency, an agitation tank for high-speed agitation and an expensive centrifugal separator or a filter must be used. It is believed that this is a problem to be solved.
Furthermore, when a polyalkylene oxide is produced by ring-opening polymerization of an alkylene oxide having three or more carbon atoms, such as propylene oxide, and an initiator contains a polymer of ethylene oxide or the monomer contains ethylene oxide as an impurity, these components increase the hydrophilicity of the resulting polymer, and thus it may be significantly difficult to perform extraction separation with water. In order to prevent this problem, it is necessary to strictly control the content of the polymer of ethylene oxide in the initiator and the content of ethylene oxide in the monomer.    Patent Document 1: Japanese Unexamined Patent Application Publication No. 2002-249580    Patent Document 2: Japanese Unexamined Patent Application Publication No. 8-231707    Patent Document 3: Japanese Unexamined Patent Application Publication No. 1-294733


An optical transmitter comprising:                (i) an electrical switch;        (ii) a laser array comprising a plurality of tunable laser elements; and        (iii) an Optical Spectrum Reshaper (OSR) used to reshape the output pulses from the laser elements in the laser array;

The quality and performance of a digital transmitter is determined by the distance over which the transmitted digital signal can propagate without severe distortions. This is typically characterized as the distance over which a dispersion penalty reaches a level of ˜1 dB. A standard 10 Gb/s optical digital transmitter, such as an externally modulated optical source (e.g., a laser), can transmit up to a distance of ˜50 km in standard single mode fiber, at 1550 nm, before the dispersion penalty reaches the level of ˜1 dB. This distance is typically called the dispersion limit. The dispersion limit is determined by the fundamental assumption that the digital signal is transform-limited, i.e., the signal has no time-varying phase across its bits and the signal has a bit period of 100 ps, or 1/(bit rate) for a 10 Gb/s optical digital transmitter.
Three types of optical transmitters are currently in use in prior art fiber optic transmission systems:
(i) Directly Modulated Laser (DML) transmitters;
(ii) Electroabsorption Modulated Laser (EML) transmitters; and
(iii) externally modulated Mach Zhender (MZ) transmitters.
For transmissions in standard single mode fiber, at 10 Gb/s and 1550 nm, it has generally been assumed that MZ and EML transmitters can achieve the longest reach, typically reaching 80 km. Using a special coding scheme, generally referred to as phase shaped duobinary transmission, MZ transmitters can reach 200 km. On the other hand, DML transmitters generally reach <5 km because their inherent time dependent chirp causes severe distortion of the signal after this <5 km distance.
Azna LLC of Wilmington, Massachusetts has recently developed a novel line of CML transmitters which can exceed the aforementioned <5 km transmission limit of conventional DML transmitters. By way of example but not limitation, various novel DML systems for long-reach optical data transmission (e.g., >80 km at 10 Gb/s) through optical fibers in single mode fiber are disclosed in the eight (8) above-identified U.S. patent applications (which patent applications are hereby incorporated herein by reference). The CML transmitter associated with these novel systems is sometimes referred to by Azna LLC as a Chirp Managed Laser (CML)™. In these new CML systems, a Frequency Modulated (FM) source (e.g., a laser) and an optical spectrum reshaper (e.g., a filter) which uses the frequency modulation to increase the amplitude modulated signal and compensate for dispersion in the transmission fiber. In one novel CML embodiment, the frequency modulated source may comprise a Directly Modulated Laser (DML). The Optical Spectrum Reshaper (OSR), sometimes referred to as a frequency discriminator, can be formed by an appropriate optical element that has a wavelength-dependent transmission function (e.g., a filter). The OSR can be adapted to convert frequency modulation to amplitude modulation.
A wavelength tunable laser source is of great interest in Wavelength Division Multiplexing (WDM) systems in which a number of different laser wavelengths are used to simultaneously transmit multiple channels of digital information through an optical fiber. This is because a single wavelength tunable laser can be used to generate the light signal needed for any one of the different channels, thereby greatly simplifying equipment maintenance and inventory considerations.
In the prior art, tunable lasers are typically externally modulated devices which use lithium niobate or InP Mach Zehnder modulators. The signals generated by these externally modulated optical transmitters require a relatively high drive voltage. In addition, the dispersion distance of these external modulators can be limited: for example, these external modulators typically have a dispersion limit of <80 km, at 10 Gbps at 1550 nm, in standard Single Mode Fiber (SMF).

Widely tunable, dispersion tolerant transmitter

Abstract: wherein the electrical switch takes an input electrical digital signal and selectively directs it to a specific laser element in the DFB laser array.


The invention relates to a self-closing valve for the dispensing of flowable media from a container comprising a curved membrane, a support segment, a connecting wall as well as a slitting provided in said membrane.

The present invention relates to a self-closing valve for the dispensing of flowable media from a container.
There are a number of liquid and fluidized products which are sold to consumers in such containers.
These fluids include, for example, cleansing and personal care products for the human body such as liquid soaps, shower gels, shampoos, skin oils, etc. Another group of such products are foods and condiments such as ketchup, mustard, honey and the like. A third group of these products are utilitarian fluids such as, for example, oils used for technical purposes, etc.
What all these cited products have in common is that the consumer dispenses them from their containers in relatively small quantities.
Conventional containers have a closure cap screwed onto the container neck for this purpose. To dispense the liquid, the container is tilted and the liquid discharged. Depending on the viscosity of the liquid and its intended use, there are a number of different designs, for example small end openings in flexible containers which are squeezed inward to dispense the liquid.
There are numerous proposals within the patent literature for configuring such a container closure having a self-closing valve. This type of valve has the advantage that the user doesn""t have to remove the closure cap each time liquid is to be dispensed.
Yet the demands placed on a self-closing closure are very high. The closure must operate simply because otherwise there would be no advantage over conventional screw closures, and on the other hand it has to exhibit an adequate seal for its respective intended use.
A container closure having a self-closing valve is proposed in EPA 0 545 678 in which a curved membrane is employed which is connected to a retaining lip by means of a connecting wall. The connecting wall is arranged between the membrane and the retaining lip such that it extends in a rolling motion to open the membrane, exerting an opening force on said membrane and inducing it to open.
Starting from this prior art, the present invention puts forth the task of providing a self-closing valve with good opening and sealing qualities which is of small dimensions, which can be inserted into a simply-designed closure cap, and which is easy and economical to produce.
This task is inventively solved by the object of claim 1.
Further embodiments of the present invention comprise the subject matter of the subclaims.
The inventive solution provides for a self-closing valve which, on one hand, opens reliably when pressure is applied to the container in the dispensing position and yet which, on the other hand, closes in a reliable and sealed fashion.
The valve according to the present invention comprises an annular connecting wall which is arranged substantially perpendicular to the longitudinal axis of the container closure or, in other words, which is substantially parallel to the plane in which the closure membrane extends. The membrane is hereby acceded moveability by means of a hinge-like design between the dividing wall and the membrane side wall, yielding what comes close to a flexibly slack suspension of the membrane, and thus preventing the transferring of torque from the dividing wall to the membrane and vice-versa.
The present invention provides for a curved membrane, its curve being directed toward the container interior in the closed position. When the container is squeezed while inverted, meaning when the valve is underneath, an excess pressure is created in the container and the membrane bulges outwardly, whereby slits in the membranes then open, allowing the passage of the fluid.
The membrane and the slits are mated to one another such that upon the membrane""s outward deformation, elastic resilient forces build up in the membrane which, upon depressurization, induce the valve to close.
The membrane and the connecting wall are preferably designed to be rotationally symmetric. In such an embodiment, the support segment is likewise preferably configured to be rotationally symmetric.
The membrane is preferably configured such that it has an approximate semi-spherical shape in the static position. However, the term xe2x80x9csemi-sphericalxe2x80x9d is meant here solely as an indication of the general fundamental design and is not to be considered as an exact geometric definition of the membrane""s form.
The membrane is provided with slits so that it can open.
Particularly in the case of a rotationally symmetric membrane, four or five slits can be provided which in each case extend outwardly from the axis of rotation; i.e. toward the connecting wall.
According to a preferred embodiment of the present invention, one slit is provided which will then extend radially across the axis of rotation.
It is however especially preferred for the membrane to be provided with three slits. In a rotationally symmetric design to the membrane, these slits are arranged such that they extend radially outwardly from the axis of rotation. The slits are preferably disposed at the same angular distance from one another, which amounts to an angle of 120xc2x0.
The use of three slits has particular advantages.
A slitted design having three, four or five slits divides the membrane into a corresponding number of pointed flaps. After deformation and opening, these flaps must be returned to their original position again so that their sectional edges will precisely position against one another. A slight offsetting of the flaps will lead to said flaps, particularly in the area of their tips, riding up over one another, preventing said flaps from having a fully sealed contact.
This kind of problem cannot arise in the case of just one centric alit since the type of flaps as described above are not formed.
The particularly preferred structuring having three slits is based on the knowledge that such flaps, when provided at angles of 120xc2x0, offer far greater protection against lateral displacements and offsettings than flaps provided at just 90xc2x0 or less.
In accordance with another, especially preferred embodiment of the present invention which is as suited for one, but also preferably for three, four, five or more slits, a slit design incorporates at least one material bridge within said slit.
Said material bridge(s) functions like an elastic draw spring within the elastic membrane, pulling the slits back together upon reclosing.
As will be explained in more detail subsequently, such a design provides for a closure which has a strong closing force despite having a low opening force and which induces a reliable guiding of the closure flaps so that their respective side faces will position against one another.
The connecting wall may be configured as a thicker wall, resulting in a very stable supporting of the membrane relative a closure cap. It is, however, also possible to configure the connecting wall in a thinner fashion.
In the case of a thick-walled and thus rigid connecting wall, it is particularly preferred that the membrane and the connecting wall are decoupled as regards torque; i.e. that membrane movement is affected as little as possible by the forces and especially by the torque which could be transmitted from the connecting wall to the membrane.
This condition is yielded by a hinge-like connection between the connecting wall and the membrane. Such a hinge can be produced in various different ways. Especially preferred is a thin segment arranged in the area of connection between the connecting wall and the membrane and which rotates about the membrane when same is of rotationally symmetric design. In order to enhance the hinge effect, said thin segment is preferably of S-shape in cross-section.
As described above, the contact surface between connecting wall and membrane is preferably configured in such a manner that especially no torque will be transmitted from the connecting wall to the membrane. In accordance with a preferential design, this contact surface can also be realized with the use of inhomogeneous material in this area, meaning, for example, that another material is used in this area or that the properties of the material are appropriately controlled so as to attain the desired diminishing of the ability to transfer torque.
The valve according to the present invention may be manufactured from any material which exhibits the appropriate properties for the elastic deformation and the elastic resilient strength.
It is particularly preferable to manufacture the membrane and/or the connecting wall from a silicone material. It is furthermore possible to manufacture the membrane and/or the connecting wall from a thermoplastic elastomer. When so doing, the connecting wall, the support segment and the membrane are all preferably of the same material and form a valve body.
Especially preferred is the reinforcing of the self-closing valve""s support segment with synthetic means, a plastic ring in the case of a rotationally symmetric design to the valve, which in contrast to the material of the connecting wall and the membrane, is made from a rigid and, where applicable, also more economical synthetic material.
In accordance with a preferred embodiment, a reinforcing ring made of a harder plastic is molded onto the support segment. When so doing, it is preferable that the plastic ring is manufactured in a separate prior manufacturing step from that of the self-closing valve and that a plurality of openings are provided on said reinforcing ring into which the valve material can penetrate during the molding process so that a deep, lasting and moreover reasonably-priced connection is created between the reinforcing ring and the valve body.
It is preferred to use polyamide as the material for the reinforcing ring.
The injection molding process may be especially preferably designed such that the polyamide ring and the silicone membrane are molded directly subsequent one another and in particular in a manner in which the polyamide is first injected into the injecting tool, the injecting tool is then subsequently opened and brought to another cavity arrangement with the silicone then being injected into this other cavity.
When an injection is made simultaneously to a second or, as preferred, to several valves, the polyamide material for the producing of the ring is then in turn injected into a number of second cavities.
Thus a first sequence phase ensues in which only polyamide rings are injected and then the polyamide rings are respectively molded in a phase of simultaneous injection of silicone to said previously-molded polyamide rings so as to then result in one, respectively the total number of valves being molded in one respective sequence phase.
It must be noted that such an approach is not limited to polyamide and silicone materials but rather can also be realized with other materials, thermoplastic elastomers, etc.
The terms xe2x80x9cfluid,xe2x80x9d xe2x80x9cliquidsxe2x80x9d and xe2x80x9cmediumxe2x80x9d or xe2x80x9cflowable mediumxe2x80x9d as used in the present description are to be understood as all substances having a viscosity which allows for their being discharged from a container, if necessary by means of an additional exertion of pressure, regardless of whether said viscosity is dynamic or kinematic. Hence these terms include not only such substances which flow on their own such as, for example, watery substances, but also substances which may only flow when pressure is applied to them such as, for example, greasy or pasty substances.
In accordance with a first preferential use, the closure is used for food products and those food products of the group comprising the following foods: vegetable and fruit juices and other drinks, seasoning sauces of all types such as soy sauce and the like, viscous seasonings such as mustard, ketchup, mayonnaise and viscous foods such as honey, jellies, jams, and milk products like milk, condensed milk, cream, etc.
It is furthermore preferred to employ the valve in the packaging of personal care and cleansing products such as liquid or pasty soap, shower gels, skin oils, sun tanning or blocking preparations, shampoos, hair colorants, skin creams, deodorants, etc.
Use of the valve is additionally preferred with other cleaning and care products such as dishwashing liquids, universal cleaning agents, shoe creams, polishes, stain removers, liquid detergents and the like.
Use of the closure is also preferred for pharmaceutical products and preferably for products which are consumed in small quantities such as, for example, eye drops, nose drops, disinfectants, and all types of pharmaceutical products regardless of whether they are for internal or external usage.
A further preferential use is that with technical products such as, for example, paints, varnishes, solvents, lubricants and other technical chemical and substance mixtures.


The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

The design of covalent diabodies is based on the single chain Fv construct (scFv) (Holliger et al. (1993) "'Diabodies': Small Bivalent And Bispecific Antibody Fragments," Proc. Natl. Acad. Sci. USA 90:6444-6448; herein incorporated by reference in its entirety). In an intact, unmodified IgG, the VL and VH domains are located on separate polypeptide chains, i.e., the light chain and the heavy chain, respectively. Interaction of an antibody light chain and an antibody heavy chain and, in particular, interaction of VL and VH domains forms one of the epitope binding sites of the antibody. In contrast, the scFv construct comprises a VL and VH domain of an antibody contained in a single polypeptide chain wherein the domains are separated by a flexible linker of sufficient length to allow self-assembly of the two domains into a functional epitope binding site. Where self assembly of the is impossible due to a linker of insufficient length (less than about 12 amino acid residues), two of the scFv constructs interact with each other to form a bivalent molecule, the VL of one chain associating with the VH of the other (reviewed in Marvin et al. (2005) "Recombinant Approaches To IgG-Like Bispecific Antibodies," Acta Pharmacol. Sin. 26:649-658). Moreover, addition of a cysteine residue to the c-terminus of the construct has been show to allow disulfide bonding of the polypeptide chains, stabilizing the resulting dimer without interfering with the binding characteristics of the bivalent molecule (see e.g., Olafsen et al. (2004) "Covalent Disulfide-Linked Anti-CEA Diabody Allows Site-Specific Conjugation And Radiolabeling For Tumor Targeting Applications," Prot. Engr. Des. Sel. 17:21-27). Further, where VL and VH domains of differing specificity are selected, not only a bivalent, but also a bispecific molecule may be constructed.
Bivalent diabodies have wide ranging applications including therapy and immunodiagnosis. Bivalency allows for great flexibility in the design and engineering of diabody in various applications, providing enhanced avidity to multimeric antigens, the cross-linking of differing antigens, and directed targeting to specific cell types relying on the presence of both target antigens. Due to their increased valency, low dissociation rates and rapid clearance from the circulation (for diabodies of small size, at or below ˜50 kDa), diabody molecules known in the art have also shown particular use in the filed of tumor imaging (Fitzgerald et al. (1997) "Improved Tumour Targeting By Disulphide Stabilized Diabodies Expressed In Pichia pastoris," Protein Eng. 10:1221). Of particular importance is the cross linking of differing cells, for example the cross linking of cytotoxic T cells to tumor cells (Staerz et al. (1985) "Hybrid Antibodies Can Target Sites For Attack By T Cells," Nature 314:628-631, and Holliger et al. (1996) "Specific Killing Of Lymphoma Cells By Cytotoxic T-Cells Mediated By A Bispecific Diabody," Protein Eng. 9:299-305). Diabody epitope binding domains may also be directed to a surface determinant of any immune effector cell such as CD3, CD16, CD32, or CD64, which are expressed on T lymphocytes, natural killer (NK) cells or other mononuclear cells. In many studies, diabody binding to effector cell determinants, e.g., Fcγ receptors (FcγR), was also found to activate the effector cell (Holliger et al. (1996) "Specific Killing Of Lymphoma Cells By Cytotoxic T-Cells Mediated By A Bispecific Diabody," Protein Eng. 9:299-305; Holliger et al. (1999) "Carcinoembryonic Antigen (CEA)-Specific T-cell Activation In Colon Carcinoma Induced By Anti-CD3×Anti-CEA Bispecific Diabodies And B7×Anti-CEA Bispecific Fusion Proteins," Cancer Res. 59:2909-2916). Normally, effector cell activation is triggered by the binding of an antigen bound antibody to an effector cell via Fc-FcγR interaction; thus, in this regard, diabody molecules of the invention may exhibit Ig-like functionality independent of whether they comprise an Fc domain (e.g., as assayed in any efferctor function assay known in the art or exemplified herein (e.g., ADCC assay)). By cross-linking tumor and effector cells, the diabody not only brings the effector cell within the proximity of the tumor cells but leads to effective tumor killing (see e.g., Cao et al. (2003) "Bispecific Antibody Conjugates In Therapeutics," Adv. Drug. Deliv. Rev. 55:171-197, hereby incorporated by reference herein in its entirety).

This patent is subject to a terminal disclaimer.


A substantially 100% active aqueous solution of one or more phosphonocarboxylic acids and one or more hydroxides, wherein the solution has a slightly alkaline pH. In an alternate embodiment, a dry, free flowing mixture comprising one or more phosphonocarboxylic acids, calcium chloride fines which, on average, are a dihydrate, and hydroxide is disclosed.

Hydroxyphosphonocarboxylic acids have been used as corrosion inhibitors in rust inhibition systems. For example, the use of such inhibitors, either alone or in combination with other inhibitors such as chromates, is discussed in U.S. Pat. Nos. 4,847,017; 4,052,160; 3,933,427; and 4,057,511.
A problem with the use of phosphonocarboxylic acids, including hydroxyphosphonocarboxylic acids, is that they are extremely acidic by nature. Further, these compounds tend to be corrosive and a potential hazard.
In addition, a further problem which has been encountered in preparing phosphonocarboxylic acid solutions is that some of the phosphonocarboxylic acid may be deactivated during the preparation of the solution and accordingly not available for use in the inhibition system.

Preparation of salt solutions of phosphonocarboxylic acids


A web is formed between two wire loops (13, 14), in a wire section of a paper or board machine, in connection with which dewatering elements (12, 17, 15, 28) are placed and in which water is drained from a stock suspension from between the two wires (13, 14). In the region of a twin-wire zone, a suction roll (15) is placed within one wire loop and a suction box (16) having a curved surface is situated in opposed relationship with the suction roll (15) on the wire loop. After the suction box (16), the web is guided, due to the effect of a vacuum of the suction roll (15), forwards on the surface of the wire loop of the suction roll (15).

The invention relates to an arrangement for a wire section of a paper or board machine, in which a web is formed between two wire loops, in connection with which dewatering elements are placed and in which water is drained from a stock suspension from between said two wires.
In paper or board machines, stock is passed from a headbox to a forming section, i.e. a wire section, in which water is removed from the stock and a web is formed. In the forming section, or the wire section, different types of formers are used in which water is drained from the web usually between two wires.
As known in the prior art, in the manufacture of paper and board webs, a stock is thus prepared first for the headbox, and fibre material, fillers, and fines and additives are mixed with said stock. The stock system mixes the fibres and fillers as well as fines and additives, if any, to form a stock that is as homogeneous as possible in order to be fed to the headbox of a paper or board machine. The headbox spreads the stock suspension produced evenly to the forming section, i.e. the wire section, where dewatering and the couching of the web begin.
Several different types of wire sections, or formers, in themselves known to a person skilled in the art, are known in the prior art: fourdrinier formers, hybrid formers and gap formers. A board machine may comprise several wire units. In forming sections, water is removed by means of forming rolls, suction rolls and by means of blade shoes or the equivalent, which blade shoes typically have several vacuum chambers, so that the use of vacuum makes pressure pulses more effective. Loadable blades are generally placed on the opposite side of the web to assist dewatering by producing shear forces in the suspension within the web, which shear forces break up fibre flocs, thus improving the forming of the web. After that, the fibrous web in formers is generally passed onto a suction roll, which further removes water from the web, after which the web is generally passed to a press section. In connection with the suction roll, water guide plates or water collecting plates have generally been used for recovering the exiting water. This has led to asymmetric dewatering to some extent and it has not been possible to regulate the distribution of dewatering in this arrangement to improve asymmetry.
EP patent 912798 (corresponding FI patent application 965277) discloses a suction box in a paper machine and a method in a suction box of a paper machine. This document describes a suction box in which a vacuum chamber deck or a set of blades in an equivalent position forms a curved support surface for a wire at least in a running situation. In this kind of suction box, the friction between the wire and the blades or between the wire and the deck is very small. This document describes the use of a suction box placed on a wire run between two rolls, in which connection the suction box enables the run of the wire to be curved, and the use of the box at a wire guide roll, over which wire guide roll two wires are running, so that the run of the wire on the side of the box can be made curved by means of the suction box.
FI patent 106730 discloses an arrangement in the wet end of a paper machine for transferring a web from a forming section to a press section. The forming section comprises a twin-wire zone defined mutually by an upper wire loop and a lower wire loop, after which the web is arranged to follow the upper wire at the point at which the web is transferred from the underside of the upper wire onto the top side of a fabric situated in the press section. At the end of the twin-wire zone there is a suction box within the upper wire loop and, in opposed relationship with the suction box, an open roll within the lower wire loop, the suction box having a deck which is curved at least in a running situation such that the tension of the upper wire reduces the normal force caused by the vacuum of the suction box between the wire and the deck, and which suction box can be provided with a vacuum which keeps the web at the suction box mainly apart from the roll and from the lower wire while adhering to the underside of the upper wire and conforming to the curved shape of the deck of the suction box. Members are arranged in connection with the suction box and/or the roll for making the web follow the lower wire in a break situation to conduct it to the broke handling system. In the arrangement disclosed here, the web continues to travel on the surface of the wire on the side of the suction box.

Arrangement for a wire section of a paper or board machine


A balloon display unit is provided to display a single balloon on the end of a stick. These display units can be secured to display bases to provide a balloon display. A balloon display unit includes a balloon and a balloon pedestal, which includes a base and a balloon stick receiving structure extending from the base. The balloon stick receiving structure can received sticks of varying inner and outer diameters. The balloon display includes a display base that receives one or more of the balloon display units.

Due to an increased demand for helium, it is becoming difficult to offer helium-filled balloons at prices agreeable to potential balloon consumers. Only a small percentage of the global helium supply is purchased for use in filing balloons, while a much larger percentage (and rising) is purchased for use in other applications, such as cooling the magnets of Magnetic Resonance Imaging (MRI) machines. The MRI industry and others industries willing and capable of purchasing helium at high prices are beginning to drive helium prices beyond what the balloon industry can bear.
As helium prices increase, helium-filled balloon prices increase, and helium-filled balloon demand decreases. Because the lighter-than-air characteristics of a helium-filled balloon are important to the balloon consumer, a suitable substitute should simulate some of the floating, bobbing and weaving characteristics of lighter-than-air balloons. To help simulate some of the characteristics mentioned above of lighter-than-air balloons, the non-helium-filled balloon's can be attached to and held upright by a stick such that the balloon and the stick can be carried around by an individual or set up for a more stationary display, much like a balloon on a string might be carried around or secured to something stationary for display. Therefore there exists a need in the art for a more universal balloon weight (or balloon display) and method that permits a balloon stick and a balloon weight to be used for any given display and display concept.

Fillable balloon weight and balloon pedestal display


A medium is transferred and loaded to a media tray provided with a media processing unit which is operable to perform information processing on the medium, by using a transfer arm of a media transfer mechanism. A distance from a surface of the medium loaded on the media tray to a reference position of the transfer arm is acquired. A difference between the acquired distance and a predetermined distance from a reference surface of the media tray to the reference position of the transfer arm is calculated. It is determined that a double transfer of the medium to the media tray occurs when the calculated difference is larger than a predetermined threshold value.

The present invention relates to a media processing apparatus that performs a predetermined process on media, such as CDs and DVDs and a controlling method of the same.
In recent years, disc dubbing apparatuses that write data on a plurality of media (information recording media), such as blank CDs (compact discs) or DVDs (digital versatile discs) and media processing apparatuses, such as CD/DVD publishers, that perform a data writing process and a label printing process to create media and publish the media have been used. As this type of media processing apparatus, an apparatus has been proposed which includes a drive that writes data on a medium, a printer that performs printing on a label surface of the medium, and a media transfer mechanism that holds the medium and transfers it to the driver and the printer (for example, see Patent Document 1).
Further, as a media take-out apparatus (disc take-out apparatus) that sequentially takes out a plurality of discs stored in a stacked state and transfers the media to a predetermined place, an apparatus has been proposed which includes: a disc lift mechanism that holds a plurality of discs in a stacked state and lifts up the discs; a disc detecting unit that detects the disc; a disc lift control unit that stops the operation of the disc lift mechanism when the disc detecting unit detects the top of the stacked discs; and a transfer mechanism that sequentially takes out the uppermost disc of the stacked discs from the disc lift mechanism and transfers it to a predetermined place, and in which the disc lift control unit controls the disc lift mechanism to be dropped a predetermined distance from the position where the disc lift mechanism stops due to the detection of the stacked discs by the disc detecting unit, and the disc detecting unit detects the thickness of the disc that is taken out and lifted up from the dropped position by the transfer mechanism (for example, see Patent Document 2).
The disc take-out apparatus disclosed in Patent Document 2 stops the stacked discs once, with an upper end of the stacked discs at a predetermined position where the disc detecting unit detects the discs, and then drops the discs by a predetermined distance. In addition, when the transfer mechanism takes out the uppermost disc of the stacked discs one by one at the dropped position and transfers the discs to a predetermined place, the transfer mechanism lifts up the disc once such that the disc detecting unit detects the disc, and then transfers the disc to a predetermined place. Therefore, when the transfer mechanism stops the stacked discs at a predetermined position, the disc detecting unit detects the upper end of the stacked discs. When the transfer mechanism transfers the uppermost disc, the disc detecting unit detects the thickness of the transferred disc to determine whether one disc or a plurality of discs are taken out.    Patent Document 1: Japanese Patent Publication No. 2006-202379A    Patent Document 2: Japanese Patent Publication No. 2005-44392A
The apparatus disclosed in Patent Document 2 prevents the double transfer of media when taking out one of a plurality of stacked media and transferring the medium. However, if the double transfer of the media occurs, a unit receiving the transferred medium is incapable of detecting the double transfer of the media. In the media processing apparatus disclosed in Patent Document 1, two or more media are transferred to a drive that writes data on media or a printer that performs printing on the label surfaces of media, the media interfere with a write head of the drive or a printer head of the printer, which results in the damage of an internal mechanism.

Media processing apparatus and controlling method of the same


A manufacturing method of the present invention includes the steps of: preparing a pre-line forming member having no face line; and cutting the pre-line forming member using a cutter 12 to form the face line on the pre-line forming member. The cutter 8 has a tip part having a cutting surface. The cutting surface has a recessed curved surface c4. An edge of the face line 8 is cut by the recessed curved surface c4. Preferably, the step of cutting is carried out by axial rotation of the cutter 8. Preferably, the cutting surface has a plane part c5 formed on an upper side of the recessed curved surface c4. Preferably, the upper side plane part c5 is perpendicular to a rotation axis rz of the cutter 12. Preferably, the cutting surface has a conical surface Fc formed on a lower side of the recessed curved surface c4.

1. Field of the Invention
The present invention relates to a manufacturing method of a golf club head having face lines.
2. Description of the Related Art
Face lines are formed on many golf club heads. The face lines can contribute to an increase in the backspin rate (backspin amount) of a hitting ball. The face lines can suppress fluctuation in the backspin rate.
As a forming method of the face lines, press processing and cut processing (machining) have been known. Japanese Patent Application Laid-Open No. 2003-199851 (US2003/126734A1) discloses face lines formed by the press processing. Japanese Patent Application Laid-Open No. 2008-206984 (US2007/0149312A1) discloses face lines formed by the cut processing (machining). Japanese Patent Application Laid-Open No. 2008-206984 describes that a roundness is applied to an edge of a groove by deburring the groove, and that the deburring is attained by a wire brush, a file, or blasting.


A braking control system comprising a first source of pressurized fluid (82a), a second source of pressurized fluid (82b), a modulator (70), a brake actuator (10), and a plurality of valves (84, 94, 96, 98), the modulator (70) having a supply inlet (72) which may be connected to either of the sources of pressurized fluid via a first fluid flow line which extends between a first one of the valves (84) and the supply inlet (72), and a control inlet (78) which may be connected to either of the sources of pressurized fluid via a second fluid flow line and a second one of the valves (94), a delivery port (74) which is connected an inlet (11) of the actuator (10), and an exhaust outlet (76) which vents to a low pressure region, the modulator (70) being operable to move between a build position in which flow of fluid from the supply inlet (72) to the delivery port (74) is permitted while flow of fluid through the exhaust outlet (76) is substantially prevented, and an exhaust position in which flow of fluid between the delivery port (74) and the exhaust outlet (76) is permitted, while flow of fluid through the supply inlet (72) is substantially prevented, wherein a portion of the fluid flow line connecting the second source of pressurized fluid (82b, 90) to the first valve (84) also provides a proportion of the connection between the second source of pressurized fluid (82b, 90) and the second valve (94).

In electronic braking systems for heavy goods vehicles, it is a legal requirement to provide failure redundancy in the brake system so that, in the event of a failure in the brake system, the driver is able to stop the vehicle in a reasonable distance. In an electronically controlled brake system for a heavy goods vehicle, this redundancy commonly takes the form of providing two pneumatic back-up circuits in addition to the normal electronic control to maintain braking capability in the event of an electrical power failure and/or the loss of a pneumatic reservoir. In order to achieve this, it is necessary to provide pneumatic connections between at least two separate pressurised fluid reservoirs and the arrangement of valves used to control supply of pressurised fluid to a brake actuator. It is advantageous to minimise the number of pipes used to provide the required back-up facility, particularly if the arrangement of valves is mounted adjacent the brake actuator in a wheel mounted unit, whilst the reservoir is mounted centrally on the chassis of the vehicle.


A rubber shear spring add-on assembly for the leaf spring of an automotive vehicle, the rubber shear spring add-on assembly being connected between the rear end of the leaf spring and the frame, the rubber shear spring add-on assembly including a spring carrier assembly mounting the rear end of the leaf spring, a hanger assembly mounted on the frame member and a rubber shear spring mounted between the hanger assembly and the spring carrier assembly which is mounted on the rear end of the leaf spring.

The present invention relates to a rubber shear spring add-on assembly for a leaf spring and a method relating thereto.
Certain vehicles have leaf springs for the rear wheels. However, many times these springs are too stiff for the load that is to be carried by the vehicle. In the past, insofar as known, if springs of lesser stiffness were required, it was necessary to replace the stiff leaf springs with leaf springs which were less stiff. This involved the expense of purchasing the less stiff springs and the labor involved in replacing the original stiff springs. In addition, the original stiff springs usually went to waste. It is with overcoming the foregoing deficiency of the prior art that the present invention is concerned.

Rubber shear spring add-on assembly for leaf spring and method relating thereto


The invention concerns the method to produce an EPROM or EEPROM type integrated memory cell on a semiconductor substrate. The cell comprises memory points, electrically insulated from each other, each memory point comprising a source (4), a drain (6), a floating gate (350), a control grid (38), a channel (5) situated under the floating gate (350), the source (4) and the drain (6) being situated on both sides of the floating (350), the floating gates of each memory point being laterally distant and insulated along a first direction (X) from one or two other floating gates, the production of the cell comprising a stage for embodying lateral insulations (320) of the floating gates along the first direction (X), then a stage for embodying the actual floating gates (350), which makes it possible to obtain insulations between submicronic floating gates.. Application for the embodiment of integrated memory cells.

An integrated memory is an integrated circuit comprising an actual memory section called a memory cell formed of several electrically interconnected memory points, as well as peripheral circuits serving to control the memory points.
The sole object of the invention is to produce the actual memory section.
The most modern memory cells allowing for the storing of 10 bits have surface areas of from 20 to 25 .mu.m2 in 1.2 .mu.m technology, namely in which the smallest tapes and spaces measure 1.2 .mu.m. The surface area of a memory is thus about 14 to 17 times that of the elementary square of a lithograph (1200.times.1200 nm2).
FIG. 1 diagrammatically shows a perspective view of a known EPROM type memory cell, namely a memory cell electrically programmable solely on reading and erasable by ultraviolet radiation.
As represented on FIG. 1, a memory point is formed of a transistor comprising a source 4, a channel 5 and a drain 6, all embodied in a monocrystalline silicon semi-conductive substrate 8; the source and the drain present conductivities opposite those of the substrate.
The transistor also includes a grid nonconductor 10, generally silicon oxide, on which stacked are a first grid 12 and a second grid 14, both generally made of polycrystalline silicon doped with phosphorus. These two grids are separated by a fine insulating layer 16 generally made of silicon oxide.
The first grid 12 is a floating gate and the second grid 14 is the control grid of the memory point.
The memory point is electrically insulated from the other memory points and the peripheral control circuits of this point by means of a field oxide 18 embodied, for example, by the localized and superficial oxidation of the substrate through a mask of silicon nitride.
The entire memory cell is covered with a thick insulating layer 22, usually made of silicon oxide, in which the electric contact holes of the sources and drains, such as 24, are embodied. The electric connections between the sources and drains of the various memory points and/or the various peripheral control circuits are ensured by a conductive layer 26, generally made of aluminium and deposited on the nonconductive layer 22 and suitably engraved.
The electric connections between the control grids of the various memory points are defined at the same time as the control grids 14 and in the same polycrystalline silicon layer.
The applicant has encountered several technical problems in embodying these memory cells.
The first problem relates to integration density.
In fact, efforts are increasingly centered on finding a way to reduce the size of integrated circuits and especially of memories so as to increase their integration density. In currently known memories, efforts to resolve this problem have so far been centered solely on two factors for limiting reduction of the dimensions of the memory cell.
The first factor is the overlapping between the floating gate 12 and the field oxide 18; an overflowing X1 of the floating gate 12 above the field oxide 18 and an overflowing Y1 of the field oxide 18 with respect to the floating gate 12 are necessary owing to the inaccuracy of superimposing the various layers constituting the memory points and lithograph masks required for etching the various layers. These overflowings are respectively in the direction X of the lines of words (or grid connections) of the memory cell and in the direction Y of the channels of the memory points, said direction Y being perpendicular to the direction X.
The second factor is the need to provide insulating guards around the contact holes of the line of bits, namely around the contact holes of the drains of the memory points. One insulating guard X2 is provided in the direction X between the drain contact and the field oxide 18 and another insulating guard Y2 is provided in the direction Y between the drain contact and the grids 12 and 14.
As reduction of the lithographic dimensions is not generally accompanied by any proportional improvement as regards the accuracy of superpositions of different levels, especially of lithographic masks, the limitation factors mentioned above prove to be increasingly inhibitive as regards increasing the integration density of the memories.
Accordingly, a search is made to improve the methods for producing memory cells so as to obtain self-aligning or self-positioning in order to avoid overlapping between the floating gate and the field oxide and/or the insulating guards around the contact holes.
The second problem resides in the fact that the memory cells produced by conventional methods have small points marked by the reference P on FIG. 1. These points are localized at the level of the angles formed by the extreme edges of the grids and the interpoly nonconductor 16.
The third problem resides in the fact that the memory cells embodied by conventional methods have a structure which presents a large relief when it would be preferable to obtain a structure approximating a flat structure.


The package includes a substrate having an opening. A first die is mounted on the upper surface of the substrate. A second die is attached on the lower surface of the first die by epoxy. The first die is encapsulated by mold compound. A plurality of solder balls are mounted on the substrate to establish a thermal and electrical connection. The modified embodiment is also possible to use a conductive plate between the first and second dies. A further embodiment includes a multi-layer substrate. Apertures are respectively formed in the layers of the substrate and are enlarged from the layer under the uppermost layer to the lowermost layer. A first die is attached on the top surface of the uppermost layer of the multi-layer substrate and is electrically connected to the conductive traces by using bonding wires. A second die is attached on the lower surface of the uppermost layer of the substrate. Mold compound covers the first die and a cap is attached to the lower surface of the multi-layer substrate. Solder balls are arranged on the lower surface of the multi-layer substrate for communicating with external modules.

Integrated circuits manufactures are constantly striving to reduce semiconductor device sizes. With the rapid advances in wafer fabrication process technology, IC designers are always tempted to increase chip level integration at an ever faster pace. It has been the trend in integrated circuit (IC) technology to make small, high speed and high density devices. Thus, the density of semiconductor devices per unit area of silicon wafer is increased. It follows then that the semiconductor devices, such as transistors and capacitors, must be made smaller and smaller.
In recent years, there has existed a high interest of developing the ball grid array (BGA) package and assembly technology. It is because that the renewed desire in high density hybrid is driven by the requirement of larger numbers of electrical connections, the increasing clock rate of digital systems. However, a conventional lead frame package meets an obstacle to increase the number of the package's lead. Thus, the requirement of the operation speed is limited by such packages. The industry has moved away from the use of pins as connectors for the semiconductor package due to the aforesaid reason and the limitation on the input/output pins. As a result, solder ball have been used to meet the present and further demand, one of such solder ball electrical connection technologies is known as ball grid array (BGA) semiconductor package that is superior to pins. The BGA offers many advantages over conventional packages such as solder ball I/O and high speed due to a short path for signal transformation.
As well known in the art, the BGA package includes a substrate with a semiconductordie formed thereon. A plurality of bond pads are mounted to the top surface of the substrate. Gold wires are electrically connected these bond pads to a plurality of conductive traces formed on the substrate. The conductive traces each terminate with a pad where a solder ball is attached. Typically, an encapsulating material covers the die and the substrate for preventing the moisture. One of such BGA is disclosed in U.S. Pat. No. 5,640,047. In the package, solder balls 24, 25 are connected with a printed wiring board. The surface of the ground plane 22 is made of copper leaf that is covered by a second dielectric layer 26. The first and second outer connecting terminal lands 21, 23 that are exposed to atmosphere by means of flux. A semiconductor die 32 is mounted by using a conductive adhering agent 31. Electrode pads mounted on the die 32 are connected to the wire bonding portions 18.
A further BGA package is developed by Motorola, which can be seen in U.S. Pat. No. 5,583,377. The package 10 includes circuitized substrate 12 having a plurality of conductive traces 14 formed thereon. Conductive pads 16 are formed on the bottom surface of the substrate 12. The electrical signal is routed from the substrate 12 to the die 13 by using wires 19. The conductive pads 16 and solder balls 21 are formed in a matrix configuration for external signal accessing to the die 13. A plurality of vias 18 are extended through the substrate 12 for electrical coupling. The device 10 also has a heat sink 22 having a cavity for receiving the die 13.
However, none of the aforementioned packages can receive multiple semiconductor dies in the device. Thus, what is required is a package having multiple semiconductor dies receiving therein.


A multi-instruction switch for enhancing electrical insulation is provided. The multi-instruction switch includes a housing, a common pin and a switching pin set. The housing comprises an accommodating space which includes a conductive elastic plate moving back-and-forth and a support rack therein. The conductive elastic plate includes a normal connection section and a switching connection section. The support rack includes a limiting track. The common pin is normally in electrical contact with the normal connection section in the housing. The switching pin set includes a first pin having a contact section and a second pin having a trigger section. The limiting track includes a first insulation plate, a second insulation plate, and an insulation space between the first and second insulation plates. As such, the present invention enhances the insulation effect by the first and second insulation plates and the insulation space located at the limiting track.

Along with the miniaturization of various electronic devices, designs of electronic components correspondingly follow the miniaturization trend. FIG. 1 shows a switch element that controls an output signal. Referring to FIG. 1, a conventional switch element includes a switch housing, a common pin 1, an normally closed pin 2 and an normally open pin 3. The switch housing includes an accommodating space, an elastic plate 41 disposed in the accommodating space, and a support rack 42. The support rack 42 has a movement track 421 for the elastic plate 41 to move therein, and an insulation block 422 disposed in the movement track 421. The common pin 1 penetrates through the switch housing to extend into the accommodating space 41 to become electrically in contact with the elastic plate 41. The normally closed pin 2 is partially embedded in the support rack 42, and extends into the movement track 421 to abut against one side of the simulation block 421. The normally open pin 3 penetrates through the switch housing and is exposed in the movement track 421, with an exposed part abutting against the opposite side to the side abutted against by the normally closed pin 2. When the elastic plate 41 is pressed by an external force and thus moves in the movement track 421, the elastic plate 41, from the normally closed pin 2 originally in contact with, crosses the insulation block 422 to become in contact with the normally open pin 3.
As the conductive elastic plate 41 comes into contact with the normally closed pin 2 or the normally open pin 3 during up-and-down movements, a contact point is melted by an electric arc as a result of electric discharge. Thus, carbon residue is generated and scattered to the surroundings and even deposited on the insulation block 422. With long-term accumulation, the carbon residue forms a conductive layer that connects the normally closed pin 2 to the normally open pin 3. During a high-voltage test, the conductive layer electrically connects the normally closed pin 2 to the normally open pin 3 in a way that, the micro-switch not only becomes malfunctioning but also fails safety certification of higher amperage and an expected product yield rate.

Multi-instruction switch for enhancing electrical insulation


Some embodiments of the disclosure provide a brake mechanism, a power platform and a karting. The brake mechanism includes a brake assembly. The brake assembly is configured to be mounted on a vehicle frame, the brake assembly includes a brake pad, a position of the brake pad is adjustably configured, such that the brake pad has a first position and a second position. Herein, when the brake pad is located at the first position, the brake pad is configured to be in contact with a tire, and when the brake pad is located at the second position, the brake pad is separated from the tire.

Two types of brake mechanisms, including a disk brake mechanism and a drum brake mechanism, are generally taken as a brake system structure of an electric vehicle known to inventors. Wherein, the disc brake mechanism includes brake pads fixed on two sides of a brake disc of a wheel respectively, a brake cylinder piston pushes the brake pads to clamp the brake disc on two sides, to achieve braking accordingly. The drum brake mechanism includes two arc brake pads provided in a drum cavity, and a brake cable pulls the two arc brake pads by making use of a lever principle to be in contact with an inner surface of a hub, to achieve frictional braking accordingly.

Brake mechanism, power platform and karting


A toner containing toner particles has a particular weight-average particle diameter, containing therein toner particles with another particle diameter in a predetermined number percentage of the number of the toner particles. A releasing agent contained in the toner particles has a particular endotherm ratio (Q/q), that is measured, using a differential scanning calorimeter (DSC), wherein q is the endotherm (.mu.V.multidot.min/mg) of the releasing agent contained in predetermined classified and sampled toner particles, assessed per unit amount of the sampled toner particles, and Q is the endotherm (.mu.V.multidot.min/mg) of the releasing agent contained in the toner particles of the toner in its entirety, assessed per unit amount of the toner particles. A method of producing the toner, and a method of forming images, using the toner, and a toner container or cartridge containing therein the toner are disclosed.

1. Field of the Invention
The present invention relates to a toner for developing latent electrostatic images to toner images, which toner has excellent anti-offset performance, fluidity and durability, a method for forming toner images using the toner, a method for producing the toner, and a toner container for containing therein the toner.
2. Discussion of Background
In electrophotography, a latent electrostatic image is formed on a photoconductor comprising a photo-conductive material, using various means, and the formed electrostatic image is then developed with a toner to a visible toner image, and when necessary, the developed visible toner image is then transferred to a sheet of paper or the like, and fixed thereto with the application of heat and/or pressure thereto, or using a vapor of a solvent, whereby a hard copy can be obtained.
As methods for developing the electrostatic image to the visible image, using the toner, there are known, for instance, magnetic brush development method, cascade development method, and powder cloud development method. In any of these development methods, the step of fixing the toner image to a transfer sheet is a very important step. In particular, when the toner image is thermally fixed, using heat rollers, the toner image in a fused state comes into contact with the surface of the heat rollers, so that a phenomenon that the toner image adheres to the surface of the heat rollers and is transferred thereto, that is, a so-called offset phenomenon, may take place. It is required that such offset phenomenon should be prevented from occurring.
Conventionally, in order to prevent the occurrence of the offset phenomenon, the surface of an image fixing roller is made of a material having excellent releasability with respect to the toner, such as silicone rubber or fluorine-based resin.
Furthermore, conventionally, in order to prevent the occurrence of the offset phenomenon more effectively, and also to prevent the fatigue of the surface of the image fixing roller, the surface of the image fixing roller is covered or coated with a thin layer of a liquid which has high releasability with respect to the toner, such as silicone oil or a fluorine-based oil, which may be referred to as the offset preventing liquid.
The above-mentioned method is extremely effective for preventing the occurrence of the offset phenomenon, but has a problem that an apparatus for supplying the offset preventing liquid to the image fixing roller is necessary, which makes the image fixing apparatus complicated in mechanism. Furthermore, the step of coating the surface of the image fixing roller with the oil has the risk of bringing about the problems that the surface layers of the image fixing roller are separated and accordingly the life of the image fixing roller is significantly shortened while in use.
Instead of using such an oil supplying apparatus, there has been proposed a method of supplying an offset preventing liquid from toner particles themselves in the course of the image fixing step with the application of heat and/or pressure thereto. More specifically, a releasing agent such as a low-molecular-weight polyethylene, or a low-molecular-weight polypropylene, is added to the toner particles and is caused to ooze from the toner particles at the image fixing step while heat and/or pressure is applied thereto as disclosed, for instance, in Japanese Laid-Open Patent Application 60-230663 and Japanese Laid-Open Patent Application 1-234858.
Such a toner that includes the releasing agent in the toner particles thereof is generally produced by uniformly mixing a binder resin, a coloring agent and the releasing agent, each in a powder-like state, fusing and kneading the mixture, pulverizing the kneaded mixture to prepare a pulverized material and classifying the pulverized material.
However, generally the releasing agent has a lower molecular weight and a less hardness than the binder resin has, so that at the above-mentioned pulverizing step, the pulverizing of the kneaded mixture takes place selectively either inside the releasing agent or at the interface between the releasing agent and the binder resin. As a result, the releasing agent tends to be exposed at the surface of the toner particles. The larger the particle size of the releasing agent in the kneaded mixture of the toner, the more conspicuously the above-mentioned tendency is developed due to the non-uniformity in the mechanical strength of the components in the kneaded mixture, while the smaller the particle size of the releasing agent in the kneaded mixture of the toner, the less the tendency is developed due to the increased uniformity in the mechanical strength of the components in the kneaded mixture. Such a releasing agent tends to be subjected to excessive pulverizing, so that that the particle size of the releasing agent tends to be more considerably decreased than that of the binder resin.
It is known that as the amount of the releasing agent exposed on the surface of the toner particles is increased, the releasing agent is released from the surface of the toner particles and adheres to the surface of carrier particles or a charging member, so that a so-called spent phenomenon takes place by which the charging performance of the carrier particles and that of the charging member are significantly lowered, as a result, the durability of the toner is markedly lowered.
It is also known that the presence of the above-mentioned releasing agent within the toner impairs the fluidity of the toner and/or the transfer performance of the toner to a transfer sheet.
The pulverizing of the toner particles at the interface between the binder resin and the releasing agent takes place not only in the course of the production of the toner, but also within a development unit in the course of the stirring of the toner. When such pulverizing takes place, the toner aggregates or the fluidity of the toner is lowered, so that proper development and image transfer cannot be carried out and image quality obtained is lowered.
In order to solve the above problem, the following proposals have been made, in which the state of the added releasing agent in the toner is controlled:
For example, in Japanese Laid-Open Patent Application 3-243956, there is proposed the use of a toner having a 200 to 5000 .ANG. average lattice length of a primary peak of a small angle X-ray scattering (SAXS); in Japanese Laid-Open Patent Application 3-296067, there is proposed a toner at a cross section of which there are formed island-sea structures composed of a binder polymer and polypropylene, with a maximum diameter in a major axis of island portions formed by the polypropylene being in a range of 200 to 3000 .ANG., and an average interval among the islands being 1 .mu.m or less; and in Japanese Laid-Open Patent Application 5-45925, there is proposed a toner comprising toner particles on the surface of which there is deposited a releasing agent with a particle size of 100 to 5000 .ANG., having a fusing initiation temperature--fusing termination temperature difference of 50.degree. C. or less, and a melting point of 60 to 180.degree. C.
In order to maintain the development performance and abrasion resistance of a photoconductor, there is proposed in Japanese Laid-Open Patent Application 5-197199 a toner on the surface of which there are dispersed polyolefin particles with a particle size of 0.01 to 0.5 .mu.m in an amount of 2 to 20%; in Japanese Laid-Open Patent Application 7-301951 a toner comprising a binder resin and a releasing agent with an SP value difference thereof being 1.5 or less; and in Japanese Laid-Open Patent Application 7-271095 a toner comprising a releasing agent with a crystallization degree in a range of 40 to 60% when the releasing agent is in the toner.
However, in any of the above prior art, the average values with respect to the overall characteristics of the toners are defined, but none of the prior art analyzes the state of the releasing agent in the toner particles with a smaller particle size than the average particle size of the toner particles, which smaller toner particles are in the range of 4 .mu.m or less, and cause problems mainly in the fluidity of the toner and also cause the spent phenomenon. As a matter of course, problems in connection with the fluidity of the toner and the spent phenomenon thereof have not sufficiently been solved by the prior art.
Japanese Laid-Open Patent Application 10-69125 discloses a toner for electrophotography comprising toner particles, each toner particle comprising a binder resin, a coloring agent, and a wax which serves as a releasing agent. In this reference, the content of the releasing agent is defined by the ratio of the content (w) of the wax in the toner particles with a volume mean diameter of 3 .mu.m to the content (W) of the wax in the entire toner particles of the toner with a volume mean diameter of 8 to 12 .mu.m as being 1.00 to 1.20, that is, w/W=1.00 to 1.20. However, this reference neither teaches nor suggests anything about the state of the releasing agent in the toner particles with the particle size in the range of 4 .mu.m or less, which mainly cause the problems with respect to the fluidity of the toner and also with respect to the spent phenomenon. Accordingly the problems are not effectively solved by the invention disclosed in this reference.
This reference does not specifically describe how to produce the toner, and the toners disclosed in the examples thereof cannot be produced even by the methods described in the examples.

Toner, method of producing the toner, image formation method using the toner, and toner container