A molecular sensor (10) comprises a flow path (12) configured for flowing a solution (28) potentially containing a target molecule (26). A source of polarized light (16) is provided and a detector (18) arranged to receive light from the source after it has passed through the flow path. A sensor element (19) is provided comprising a scaffold moiety (20) with a high aspect ratio disposed, in use, within the flow path and a receptor moiety (24), for the target molecule, attached to the scaffold moiety. A method for sensing a target molecule in a flowing solution is also described.

By their nature, organisms contain many complex molecules and molecular assemblies. Some of the most important molecules and assemblies are large and have high aspect ratios (i.e. one axis significantly greater in length than any other). It is known to use an optical apparatus to specifically detect these high aspect ratio molecules. Such an apparatus relies on the way these long molecules interact with polarised light (i.e. light with an electric field established in one direction only).
The phenomenon being exploited in the above apparatus is known as dichroism. The incident light may be either linearly polarised, giving rise to linear dichroism (LD), or circularly polarised, giving rise to circular dichroism (CD). LD is the property exhibited by some molecular structures whereby linearly polarised light is differentially absorbed along two orthogonal axes. CD relates to the difference in absorption of left and right circularly polarised light. A molecule that is capable of selective light absorption is known as a chromophore. Dichroic molecules, i.e. those that exhibit dichroic properties, are a particular type of chromophore. Examples of dichroic materials are certain natural crystals, stretched polymers, and other non-isotropic molecules. Biomolecules contain a wide range of chromophores (including aromatic side chains, nucleotides and peptide backbones).
In order to be able to observe a dichroic effect, it is necessary that the chromophores be aligned, or at least partially aligned, with respect to the incident polarised light beams. This requirement has the advantage of allowing the extraction of data only from aligned molecules in a milieu of unaligned molecules. However, this requirement has, to date, also limited the application of the above technique, primarily, to the study of large molecules with high aspect ratios, since these are easily alignable. A molecule is considered to have a high aspect ratio if one axis is substantially longer than the other. Suitable molecules may be in the shape of a rod, a disc or a cruciform. Depending upon the stiffness of the molecule, an aspect ratio of 100:1 may be sufficient to facilitate alignment but an aspect ratio of greater than 1000:1 is preferable. Some examples of moieties of interest that have been successfully aligned include linear biomolecules in the form of DNA, fibrous proteins and membranes (including membrane proteins) (Marrington R, Small E, Rodger A, Dafforn T R, Addinall S G, "FtsZ fiber bundling is triggered by a conformational change in bound GTP" J Biol Chem 2004; 279(47):48821-48829; Dafforn T R, Rajendra J, Halsall D J, Serpell L C, Rodger A, "Protein fiber linear dichroism for structure determination and kinetics in a low-volume, low-wavelength couvette flow cell" Biophys J 2004; 86(1 Pt 1):404-410; Dafforn T R, Rodger A, "Linear dichroism of biomolecules: which way is up?" Curr Opin Struct Biol 2004; 14(5):541-546; Halsall D J, Rodger A, Dafforn T R, "Linear dichroism for the detection of single base pair mutations" Chem Commun (Camb) 2001 (23):2410-2411).
A particularly convenient method for aligning such molecules is to create a solution including the molecules and then to flow the solution. Due to the elongate nature of the molecules, alignment arises as a result of shear forces generated by the flow, making the sample suitable for exhibiting the effect of linear dichroism.
In a known apparatus, once the molecules of interest have been aligned, linearly polarised light is directed through the solution from a direction substantially perpendicular to the axes of the aligned molecules. Absorption of light occurs within a molecule because, at a particular wavelength, the electric field of radiation urges the electrons in the molecule in a particular direction. When several molecules are similarly aligned, the electrons in each are all characterised by the same preferred net displacement direction. LD is a measure of the difference of absorbance of the incident light between two orthogonal polarisations. Varying the wavelength of the incident light and detecting the light emerging from the sample, allows a spectrum to be obtained which illustrates the absorbance of the sample with respect to wavelength.
An LD spectrum of a molecule provides information on the chromophores that are present including the orientation of the chromophores (and hence molecular conformation) and the orientation of the chromophores with respect to the axes of polarization. This information is important in understanding the structure of the molecule. Note that LD is a measurement of a sample's bulk property. The strength of the absorbance can be used to quantify the number of target molecules that are present in the sample. In addition, since LD is extremely sensitive to changes in alignment, an anomaly in the structure of a molecule may be detected. For example, LD can detect the distortion caused by a single mismatched hydrogen bond in a 1300 bp (base pair) fragment of DNA.
Furthermore, LD is extremely sensitive to the formation of a complex since the binding of an aligned molecule to a second molecule has the following two measurable effects.                1) The shape of the aligning moiety is altered and this results in its alignment also being altered, which leads to a change in the observed LD spectrum.        2) The second molecule itself becomes aligned by virtue of its attachment to the aligned molecule. This leads to the generation of an LD signal for the previously unaligned chromophores of the second molecule. Thus, information on the structure of the complex can be obtained.
Both of the above effects result in detectable phenomena that can be used to detect the formation of complexes. Not only can structural information be gleamed regarding the nature of the complex but the affinity of the interaction can also be determined.
Unfortunately, most molecules do not have a high aspect ratio and instead have shapes more closely related to spheres, with aspect ratios of less than approximately 5:1. In order to align these molecules it is necessary to link the target molecule to a receptor that itself has a high aspect ratio. This method of alignment has been achieved and has been applied to studies of ligands (e.g. cisplatin) that bind to naturally alignable receptors (e.g. DNA). However, this method is also limited in its application since only those molecules that bind to naturally alignable receptors can be studied.
It is therefore an aim of the present invention to expand the application of dichroic analysis.


A test chip performs measurements to evaluate the performances of interconnects. In particular, the statistical failure distribution, the electromigration and the leakage current are measured. An algorithm detects a via failure at any of the available n metal layers. The test chip includes a ROM memory array. The vias to be measured are formed in the columns of the array. Via or contact failures are detected by forcing a predetermined current through both an array column and a reference column. The failure analysis is obtained by comparing the resulting voltage drops.

In accordance with the well-known "Moore's law", first formulated in 1965 [1], [2], integration density has doubled approximately every 18 months during the last 25 years. The related Technology Roadmap for Semiconductors (TRS) predicts, for microprocessors, that the number of transistors per chip will be about a billion in 2010 [3], [4].
The main reason of such a trend is an endless feature size reduction. In this scenario, the realization of electrical interconnections (contacts and vias), also referred to as interconnects, becomes more and more critical, and represents a limit to the scaling-down trend.
In particular, as circuit complexity increases (e.g., realization of complete systems on a chip or SOC), the number of interconnects also increases. The shrinking of transistor dimensions forces interconnect sizes to shrink as well (to fully exploit the increase in circuit density obtained with the feature size reduction). Moreover, for any chip, the electric performance depends on the behavior of all devices: transistors, capacitors, resistors, and interconnects as well.
Interconnects suffer from several possible types of failure. Most critical are the so-called "open-failures" at the contact and at the via level. An open-failure may signify a chip failure (this is generally the case of logic and memory chips). Of course, the larger the number of interconnects, the higher is the probability of having a chip failure due to interconnect failures.
Several phenomena can cause a failure across an interconnect, the most usual being a process fault (open-failure at time zero) and electromigration (failure during operation) [5]-[7]. The probability of both mechanisms of failure is inversely proportional to the size of contacts and vias. For the above reasons, in modern processing, manufacturing yield and circuit reliability become increasingly dependent on interconnects.
Of course, the basic requirements of interconnects are low resistance, stability during the fabrication process, and reliability during operation. Furthermore, interconnects (in particular, contacts and vias) must show a good adhesion to the underlying layer. So far, aluminium (or an aluminium-based alloy) has been the most used conductor to form interconnects in integrated silicon technology.
Aluminium (Al) processes have evolved to improve interconnect yield and reliability. The biggest problem in Al interconnects is represented by electromigration, which arises in the presence of an excessively high current density. At present, copper (Cu) is emerging as the leading conductor for interconnects due to its lower resistivity (1.7 μΩ·cm vs. 2.7 μΩ·cm) and its better immunity to electromigration.
In addition, the use of copper interconnects allows thinner and more closely spaced wires than Al-based technologies. Nevertheless, it must be pointed out that copper has several disadvantages. Above all, copper is more difficult to etch, thus requiring manufacturers to adopt new process steps. Moreover, it must be encapsulated with barrier materials for reliable integration with existing backend oxide dielectrics.
Several phenomena must be investigated to settle copper-based interconnect technology. For instance, in the presence of an electric field at temperatures as low as 150° C., positive Cu ions drift rapidly through silicon dioxide, thus degrading field isolation (by inducing dielectric leakage) and even active devices.
Furthermore, due to the continuous current density increase, electromigration and new process failures of vias and contacts represent a very critical issue. The dependence of these failures on the C/V aspect ratio must be analyzed. Some mechanisms for copper via failure have been reported [8]. One or more small voids can be present in the metallic copper that forms the via. The voids can join and migrate to the bottom of the via through either electromigration or, more critically, thermal-stress migration, thus opening the connection between the via and the barrier over the underlying metal layer. In some cases, thermal stress can be so great that the via metal tears away from the barrier material, thus forming a void and opening the connection.
A further possible drawback in scaled-down devices is represented by the leakage current between adjacent metal lines (belonging either to the same level or to different levels). As mentioned above, the use of copper can lead to oxide contamination. The ensuing leakage current can both contribute to increase the power consumption and decrease manufacturing yield. This aspect also needs also to be experimentally analyzed.
For the above reasons, to improve the performance of interconnects (to be more specific, of contacts and vias) it is fundamentally mandatory to use a test chip able to experimentally evaluate their behavior. Moreover, because of the many metal layers that are used in modern processes, the test system should be able to detect open-failures between any pair of adjacent metal levels of the test chip. Indeed, it would be desirable to obtain the statistical failure distribution for any different via level, so as to be able to improve the manufacturing process at every step.
Due to the statistical nature of failures, a large amount of experimental data is needed. The time to perform all the necessary measurements should be kept as low as possible. The above requirements represent a key design constraint for any suitable test device [9], [10]. Furthermore, to reduce testing time and cost, it would be desirable to have a test chip that allows all the above measurements. To improve the fabrication process, a detailed physical analysis of the detected failures must eventually be carried out. Because the number of failures is relatively small, the location of any failed element should be exactly determined.

Analysis of the quality of contacts and vias in multi-metal fabrication processes of semiconductor devices, method and test chip architecture


An in vivo assay to measure anchorage-independent growth and phenotypic stability of a certain cell population comprising subcutaneous or intramuscular injection in a mammal of a cell suspension of articular chondrocytes in an iso-osmotic liquid, the same suspension comprising articular chondrocytes in an amount equivalent to at least 1×106 chondrocytes as applied to immune-deficient mice. The outcome is linked to molecular markers. The present invention further relates to DNA chips and diagnostic tools comprising the latter to predict the outcome of ACT. Antibodies raised against positive and negative markers of chondrocyte stability can also be used for quality control on the chondrocytes. Therapeutical compositions comprising stable chondrocytes are very useful for tissue repair.

Cartilage is a tissue composed by a cellular component, chondrocytes, and by an extra-cellular matrix typically rich in collagen type II and highly sulphated high molecular weight proteoglycan aggregates. The latter property confers cartilage its peculiar histochemical characteristics that are: strong staining with Alcian blue at low pH (from 0.2 to 2.5) and metachromacy with Toluidine blue and Safranin O. The abundance of type II collagen, link protein, and proteoglycan aggrecan, along with the presence of minor collagens such as type IX and type XI collagen are hallmarks of cartilage tissue.
In post-natal mammals, cartilage contributes to the structure of several organs and systems like the articular surface of diarthrodial joints and other joint-associated structures (such as menisci), the ear, the nose, the larynx, the trachea, the bronchi, structures of the heart valves, part of the costae, synchondroses, entheses etc. In some of the mentioned locations (e.g. entheses, the annulus fibrosus of the intervertebral disks, in the menisci, insertion of ligaments etc.) for the abundance of collagens (mostly type I collagen) and the peculiar distribution of the fibrous bundles it is called fibrocartilage. In other locations (e.g. the pinna of the ear, epiglottis etc.) it is particularly rich in elastin and it is called elastic cartilage. In all the other structures, for its semi-transparent, clear aspect it is called hyaline cartilage.
During embryogenesis cartilage has a role in the development of long bones. Mesenchymal cells aggregate and differentiate to form cartilage anlagen, which provide the mold of the future long bones. These cartilage templates in development evolve, undergo endochondral bone formation through a cascade of events including chondrocyte hypertrophy, vascular invasion, mineralization, and are eventually replaced by bone except for a thin layer at the extremities of the bone elements that will differentiate into the articular surface of diarthrodial joints. In these locations cartilage tissue remains hyaline for all the life-span of the individual. With ageing, articular cartilage is well known to undergo a process of senescence, affecting its mechanical properties and its intrinsic resilience.
Joint surface defects can be the result of various aetiologies such as inflammatory processes, neoplasias, post-traumatic and degenerative events etc. Whatever the cause, the mechanisms of repair and of subsequent evolution are largely common.
Osteochondral (or full-thickness) articular surface defects include damage to the articular cartilage, the underlying subchondral bone tissue, and the calcified layer of cartilage located between the articular cartilage and the subchondral bone. They typically arise during severe trauma of the joint or during the late stages of degenerative joint diseases, e.g. during osteoarthritis. These lesions disrupt the congruence between the joint surfaces and therefore can lead to OA, which can be painful and severely limit the joint function. Osteochondral defects can rely on an extrinsic mechanism for repair. Extrinsic healing uses mesenchymal elements from subchondral bone to participate in the formation of new connective tissue. The repair tissue, however, often consists of fibrocartilage or fibrous tissue. This scar tissue does not share the same biomechanical properties as hyaline cartilage and eventually degenerates with the development of osteoarthritis.
Superficial or partial-thickness injuries of the articular cartilage that do not penetrate the subchondral bone can only rely on an intrinsic mechanism for repair. Chondrocytes adjacent to the injured surfaces proliferate and increase the deposition of extracellular matrix. Despite these attempts at repair, there is no appreciable increase in the bulk of cartilage matrix and the repair process is rarely effective in healing the defects. Although initially sometimes painless, partial-thickness defects often degenerate into osteoarthritis of the involved joint.
Repair of articular cartilage defects with suspensions of chondrocytes has been carried out in a variety of animal models (Brittberg et al. (1996) Clin. Orthop. (326):270-83) and is now employed in humans (Brittberg et al. N Engl J Med. 1994 Oct. 6; 331(14):889-95). Autologous chondrocytes obtained from an unaffected area of the joint are released, expanded in vitro in the presence of autologous serum and subsequently injected under a periosteal flap sutured to cover the cartilage defect. This procedure has led to a proven at least symptomatic amelioration. This conceptually promising approach has still wide margins for improvement, since it is known that in vitro expansion of chondrocytes results, after a limited number of cell divisions, in a loss of their phenotypic stability (as defined by the ability of chondrocytes to form hyaline cartilage in vivo) making the cell suspension to be injected unreliable.
Three alternative approaches have been developed in an attempt to improve the success rate in treating mammalian articular cartilage defects. In the first approach, synthetic carrier matrices are impregnated with allogeneic chondrocytes and then implanted into the cartilage defect where they hopefully produce and secrete components of the extracellular matrix to form articular cartilage at the site of the defect. A variety of synthetic carrier matrices have been used to date and include three-dimensional collagen gels (e.g. U.S. Pat. No. 4,846,835), reconstituted fibrin-thrombin gels (e.g. U.S. Pat. Nos. 4,642,120; 5,053,050 and 4,904,259), synthetic polymer matrices containing polyanhydride, polyorthoester, polyglycolic acid and copolymers thereof (U.S. Pat. No. 5,041,138), and hyaluronic acid-based polymers. Once a mitotically expanded population of chondrocytes is obtained, the cells can be implanted either back into the same subject from which their parent cells were originally derived (autologous implantation), or into a different subject (heterologous implantation). In addition, heterologous implantation may use chondrocytes obtained from a related or unrelated individual of the same species (allogeneic), or from a different species (xenogeneic). Alternatively, chondrocytes may be obtained from an established, long-term cell line that is either allogeneic or xenogeneic.
The introduction of non-autologous materials into a patient, however, may stimulate an undesirable immune response directed against the implanted material, leading to potential rejection of the newly-formed and engrafted cartilage tissue. In addition, heterologous implantation risks the transmission to the subject of infectious agent(s) present in the tissue or cell line. Neo-cartilage may be formed around the periphery of the implant thereby preventing integration of the implant into the cartilage defect. Monitoring the formation and development of the resulting synthetic cartilage in situ is difficult to perform and usually involves an arthroscopic or open joint examination. Furthermore, implants containing synthetic polymer components may be unsuitable for repairing large cartilage defects since polymer hydrolysis in situ inhibits the formation of cartilage and/or its integration into the defect.
In the second approach, the defect is filled with a biocompatible, biodegradable matrix containing chemotactic and mitogenic growth factors to stimulate the influx of chondrocyte progenitor cells into the matrix in situ. The matrices optimally contain pores of sufficient dimensions to permit the influx into, and proliferation of the chondrocyte progenitor within the matrix. The matrix also may contain differentiating growth factors to stimulate the differentiation of chondrocyte progenitor cells into chondrocytes which in turn hopefully secrete extracellular matrix components to form cartilage at the site of the defect in situ (e.g. U.S. Pat. Nos. 5,206,023 and 5,270,300 and EP-A-530,804). This approach however results in problems similar to those associated with the first approach hereinabove. Furthermore there is no data so far that articular cartilage contains chondrocytic progenitors available for partial thickness defect repair.
In the third approach, chondrocytes may be cultured and expanded in vitro thereby to form synthetic cartilage-like material that is implanted subsequently into the cartilage defect. This has the advantage over the previous methods in that the development of the synthetic cartilage material may be monitored, through morphological, biochemical, and molecular characterisation, prior to implantation. Chondrogenic cells may be expanded in either an anchorage-dependent or an anchorage-independent culture system. In the latter, chondrogenic cells may be cultured as colonies within an agarose gel. Heretofore, only small pieces of cartilage tissue of undefined shape have been prepared using this manner. Furthermore, the resulting cartilage remains embedded within a gel matrix making it less suitable for implantation into mammals. Alternatively, in another anchorage-independent method, chondrocytes may be cultured as colonies in suspension culture. However the resulting particles containing synthetic cartilage-like material are usually small and of undefined shape, and do not integrate with each other and with the surrounding cartilage within the defect. This makes them unsuitable for implantation and repair of a predetermined articular cartilage defect.
In the anchorage-dependent method, primary cultures of chondrogenic cells isolated from primary tissue are grown as monolayer attached to the surface of a cell culture flask (e.g. U.S. Pat. No. 4,356,261). The primary cells derived directly from explant tissue remain capable of producing and secreting extracellular components characteristic of natural cartilage, specifically type II collagen and sulphated proteoglycans. However, it is well known that during in vitro expansion as monolayers, chondrocytes dedifferentiate and lose their ability to form hyaline cartilage in vivo. Until now it has not been possible to prepare large patches of articular cartilage from small pieces of biopsy tissue using the anchorage-dependent procedures of U.S. Pat. No. 4,356,261.
In order to solve the above problems, U.S. Pat. No. 5,723,331 provides a method for preparing in vitro large quantities of synthetic cartilage from small samples of biopsy tissue which, based on the discovery that chondrogenic cells may be isolated from a variety of tissues, e.g. pre-existing cartilage, perichondrial tissue or bone marrow, and expanded in vitro prior to cartilage formation, includes first seeding denuded (i.e. isolated from an enzymatically or mechanically disaggregated tissue) chondrogenic cells, proliferated ex vivo, into a pre-shaped well having a cell contacting, cell adhesive surface, and then culturing the proliferated chondrogenic cells in the well for a time sufficient to permit the cells to secrete an extracellular matrix thereby to form a three-dimensional, multi cell-layered patch of synthetic cartilage. This approach does not yield an optimal integration between the implant and the surrounding cartilage. Thus far there is no evidence on the phenotypic stability of cells in such preparations.
The use of mesenchymal cells has also been proposed for cartilage repair. Mesenchymal cells are a potential alternative source of cartilage-producing cells. They are generally recognised as pluripotent cells capable of dividing many times to produce progeny cells that can eventually give rise to many tissues, including skeletal tissues such as cartilage, bone, tendon, ligament, marrow stroma and connective tissue. By definition, they can undergo many more divisions. Chondro/osteoprogenitor cells, which are bipotent with the ability to differentiate into cartilage or bone, were isolated from bone marrow (e.g. in U.S. Pat. No. 5,226,914), and subsequently from muscle, heart and granulation tissue. Pluripotency is demonstrated using different culture conditions and adding more or less specific inducers, which elicit differentiation of the stem cells into chondrocytes (cartilage), osteoblasts (bone), myotubes (muscle), adipocytes (fat).
It would be highly desirable to have progenitor cells which are easily obtained such as by muscle biopsy, cultured to yield large numbers, and can be used as a source of chondrocytes or osteoblasts or myocytes. However, the same pluripotency that makes them attractive, conveys the risk of metaplastic differentiation. In other words there is the risk that they could differentiate in an undesired direction (e.g. bone or fat within a cartilage defect). In U.S. Pat. Nos. 5,226,914 and 5,197,985 the cells were absorbed into porous ceramic blocks and implanted, yielded primarily bone. However, U.S. Pat. No. 5,906,934 discloses that under very specific conditions mesenchymal stem cells in a suitable polymeric carrier (such as polyglycolic acid mesh) implanted into a cartilage and/or bone defect will differentiate to form cartilage and/or bone, as appropriate. Also U.S. Pat. No. 5,919,702 discloses chondrocyte progenitor cells isolated from umbilical cord sources, e.g. from Wharton's jelly, and cultured so as to give rise to chondrocytes that can produce cartilage tissue. Also in another attempt to avoid the drawbacks of current cartilage and bone repair techniques which cause bleeding and involve the use of mechanically weak non self-derived material, U.S. Pat. No. 5,866,415 suggests treating cartilage or bone defects with a biological material obtained by attaching in vitro cartilage or bone forming cells to a periosteum of sufficient size to accommodate the defect.
WO/96/41523 and WO96/41620 describe the use of FGFR3 as a marker for mesenchymal skeletal progenitor cells. Such cells do not show a stable phenotype. To initiate differentiation of these cells factors may be added to the cells or in situ, for example an FGF9 antagonist. As indicated above the use of progenitor cells for implantation in the body is counter-indicated due to the danger of metaplastic differentiation.
Transforming growth factor-beta ("TGF-β") refers to a family of related dimeric proteins which regulate the growth and differentiation of many cell types. Members of this family include TGF-β1, TGF-β2, TGF-β3, TGF-β4, TGF-β5, morphogenic proteins ("MP") such as MP-121 and MP-52, inhibins/activins (such as disclosed in EP-A-222,491), osteogenic proteins ("OP"), bone morphogenetic proteins (hereinafter denoted "BMP"), growth/differentiation factors ("GDF") such as GDF-1, GDF-3, GDF-9 and Nodal. TGF-β was first characterised for its effects on cell proliferation. It both stimulated the anchorage-independent growth of rat kidney fibroblasts and inhibited the growth of monkey kidney cells. TGF-β family members have been shown to have many diverse biological effects, e.g. they regulate bone formation, induce rat muscle cells to produce cartilage-specific macromolecules, inhibit the growth of early haematopoietic progenitor cells, T cells, B cells, mouse keratinocytes, and several human cancer cell lines. TGF-β family members increase the synthesis and secretion of collagen and fibronectin, accelerate healing of incisional wounds, suppress casein synthesis in mouse mammary explants, inhibit DNA synthesis in rat liver epithelial cells, stimulate the production of bFGF binding proteoglycans, modulate phosphorylation of the epidermal growth factor ("EGF") receptor and proliferation of epidermoid carcinoma cells and can lead to apoptosis in uterine epithelial cells, cultured hepatocytes and regressing liver. TGF-β's can mediate cardio-protection against reperfusion injury by inhibiting neutrophil adherence to endothelium and protect against experimental autoimmune diseases in mice. On the whole, proteins of the TGF-β family are multifunctional, active growth factors and also have related biological activities such as chemotactic attraction of cells, promotion of cell differentiation and tissue-inducing capabilities. Differences in their structure and in their affinity for receptors lead to considerable variations in their exact biological function.
In contrast to the foregoing reports of the ability of TGF-β to induce the production of cartilage-specific macromolecules in muscle cells and chondrocytes, TGF-β was found to act synergistically with fibroblast growth factor to inhibit the synthesis of collagen type II by chicken sternal chondrocytes and in rat chondrocytes. In fact, TGF-β, has emerged as the prototypical inhibitor of the proliferation of most normal cell types in vitro as well as in vivo, exhibiting a remarkable diversity of biological activity. TGF-β1 has been purified from human and porcine blood platelets and recombinant TGF-β1 is currently available.
Among the sub-family of BMPs, the structures of BMP-1 through BMP-15 have previously been elucidated. The unique inductive activities of these proteins, along with their presence in bone, suggests that they are important regulators of bone repair processes and may be involved in the normal maintenance of bone tissue. Recently, the BMP-12-related subfamily of proteins, including BMP-13 and MP52 (see e.g. WO93/16099 and U.S. Pat. No. 5,658,882), was shown to be useful in compositions for the induction of tendon/ligament-like tissue formation and repair. U.S. Pat. No. 5,902,785 discloses that BMP-12 related proteins are particularly effective for the induction of cartilaginous tissue and that BMP-9 is useful for increasing proteoglycan matrix synthesis and therefore for the maintenance of cartilaginous tissue. It also describes compositions comprising a BMP-12 related protein and additionally including one or more TGF-β superfamily member proven to be osteogenic, preferably BMP-2, -4, -5, -6 and/or BMP-7 as useful for the regeneration of multiple tissue types (for example at the interface or junction between tissues) and especially useful for the treatment of articular cartilage, in which the articular surface, cartilage, subchondral bone and/or tidemark interface between cartilage and bone need to be repaired. The same patent further describes compositions comprising a BMP-12 related protein together with a protein useful for the maintenance of chondrocytes or cartilaginous tissue such as BMP-9, the said compositions being especially useful for the induction and maintenance of cartilaginous tissue at a site in need of cartilage repair such as an articular cartilage defect.
WO96/14335 discloses, using mRNA prepared from newborn articular cartilage, the isolation of two members of the BMP family, designated Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1, CDMP-2). Storm et al. (1994) in Nature 368, 639-43 and Chang et al. (1994) in J.Biol.Chem. 269, 28227-34 independently established that CDMP-1 mapped close to the brachypodism locus on chromosome 2 in mice and might be involved in the brachypodism phenotype. Also the expression patterns of CDMP's suggests an important role for these genes in joint morphogenesis. WO98/59035 also discloses a method of maintaining a cartilaginous phenotype in chondrocytes in vitro, comprising culturing the chondrocytes in serum-free medium containing a CDMP and/or BMP.
Table 1 summarises the BMP subfamily members according to Reddi A H, Nature Biotechnol. 1998, 16:247-52.
TABLE 1The BMP family in mammalsBMPBMPsubfamilyGeneric namedesignationBMP 2/4BMP-2ABMP-2BMP-2BBMP-4BMP 3OsteogeninBMP-3Growth/differentiation factor 10BMP-3BOp-1/BMP-7BMP-5BMP-5Vegetal related-1 (Vgr-1)BMP-6Osteogenic Protein-1 (Op-1)BMP-7Osteogenic Protein-2 (Op-2)BMP-8Osteogenic Protein-3 (Op-3)BMP-8BGrowth/differentiation factor 2 (GDF-2)BMP-9BMP-10BMP-10Growth/differentiation factor 11 (GDF-11)BMP-11GDF-5, 6, 7Growth/differentiation factor 7 (GDF-7) orBMP-12cartilage-derived morphogenic protein-3(CDMP-3)Growth/differentiation factor 6 (GDF-6) orBMP-13cartilage-derived morphogenic protein-2(CDMP-2)Growth/differentiation factor 5 (GDF-5) orBMP-14cartilage-derived morphogenic protein-1(CDMP-1)BMP-15BMP-15
Other families of growth factors have been shown to play a role in cartilage formation/differentiation. Among them the fibroblast growth factors (FGFs) are a family of polypeptide growth factors involved in a variety of activities. One of their receptors, FGF receptor 3 (FGFR-3) (Keegan K. et al., 1991 Proc. Nat. Acad. Sci. 88: 1095-99), is known to play a crucial role in chondrogenesis. Point mutations in the fgfr3 gene resulting in a ligand-independent constitutively active protein (which means that the FGF signalling is always active also in the absence of the ligand) cause skeletal abnormalities as achondroplasia and thanatophoric dysplasia.
As already outlined above, although autologous chondrocyte transplantation ("ACT") is becoming a widely accepted technique for repair of joint surface defects ("JSD") it still presents some drawbacks. More in detail, this procedure implies in vitro expansion—in the presence of autologous serum—of autologous chondrocytes obtained from an uninvolved area of the joint surface, followed by the implantation of the chondrocyte suspension under a periosteal flap sutured to seal the joint surface defect. Cell expansion is necessary to obtain from a small cartilage biopsy a number of cells sufficient to repair the cartilage defect. Expansion in monolayer result in the loss of phenotypic traits in chondrocytes (Benya and Shaffer. 1982, Cell 30:215-24). To date, however, it is not known how far it is possible to expand chondrocytes without hampering their phenotypic stability and therefore their capacity to form stable hyaline cartilage in vivo, resistant to vascular invasion and endochondral bone formation. Other factors that can affect the capacity of chondrocytes to form cartilage in vivo are the culture conditions, and several factors dependent on the donor such as age and pre-existing joint or systemic diseases. At the end of cell expansion the chondrocyte population is composed of some cells that retain their phenotypic stability, and others that still can proliferate but will not anymore contribute to cartilage repair. To obtain a consistent cell suspension for ACT, it is desirable to determine which is the actual capacity of the cells to form cartilage in vivo and, if necessary, to select stable chondrocytes within the expanded cell population. The importance of this issue is underscored by the large variability in the quality of the repair tissue obtained in a large series (Peterson et al. Clin Orthop [374], 212-234. 2000.) consisting of a range going from hyaline-like cartilage to fibrocartilage to no signs of repair.
Chondrocytes are the only normal skeletal cells known to grow anchorage-independent in agarose cultures (Benya and Shaffer. 1982, Cell 30:215-224). This culture system allows a recovery of some of the phenotypic traits that are lost with expansion in monolayer (Benya and Shaffer. 1982, Cell 30:215-224). The expression of type 2 collagen and the capacity to grow and rescue phenotypic traits in agarose culture, are good assays to evaluate chondrocyte differentiation and the potential to differentiate respectively. However they do not measure the capacity of chondrocytes to form cartilage in vivo.

This patent is subject to a terminal disclaimer.

In vivo assay and molecular markers for testing the phenotypic stability of cell populations, and selected cell populations for autologous transplantation


A keyboard includes a main body and a support in the main body. The main body includes a bottom defining two slots and two opposite sidewalls each defining a receiving hole. The slots communicate with the receiving holes, respectively. The support includes a rotation member, two driving members and two connecting members received in the two slots, respectively. Each connecting member includes a first arm and a second arm, wherein two ends of the first arm are rotatably connected to the rotation member and the second arm, respectively, the second arm is further rotatably connected to one of the driving members, and the second arm moves together with the one of the two driving members, causing the connecting ends of the first arm and the second arm to extend out of one of the two slots.

1. Technical Field
The present disclosure relates to keyboards and, particularly, to a keyboard with multi-angle support.
2. Description of Related Art
A keyboard usually includes a pair of supports for supporting the keyboard at an angle to be more comfortable for a user. The supports can usually be folded into the keyboard when not in use, pulled out to different positions according to user preference. The limited number of positions are not enough to satisfy users' needs.

Hong Fu Jin Precision Industry (ShenZhen) Co., Ltd.


A method and system for implementing a document processor and re-aggregator is described herein. A document is divided into one or more sections and formatting is removed. A condensed document is generated that includes one or more links to the one or more sections. The condensed document is transmitted to a mobile device to be displayed for a user. The user may choose to download one or more of the sections by selecting one or more of the links. Once downloaded, a section may be modified by the user. The one or more modified sections may be transmitted from the mobile device. The one or more modified sections may then be re-aggregated with the unmodified sections to form a revised document.

An increasing number of mobile devices, such as cell phones and pocket PCs, are giving users the ability to read and edit documents. However, the ability to read and edit these documents is constrained by the limited screen size available on the mobile device. Furthermore, downloading a large document that may include graphs, images, embedded audio and/or video is a challenge. Not only may it take a long time to download a large document but the download may also be constrained by the storage limitations of the mobile device.


A drum brake has two sets of braking linings. The drum brake includes a brake plate and a brake drum. An additional cylinder is mounted on an outer periphery of the brake plate. The additional cylinder is actuated by hydraulic oil on depression of an additional brake pedal provided proximate to a clutch pedal of the car. A further brake lining is provided around an outer periphery of the brake drum. On depression of the additional brake pedal, the brake lining engages with the outer surface of the brake drum to provide additional stopping capability.

The present invention relates to improved drum brake, particularly to an improved drum brake having two sets of brake linings to enhance the brake effect or to act as an auxiliary brake system when the brake pedal controlled by the right foot of a driver is broken in an emergency situation.
Conventionally, a drum brake for a car which is controlled by a brake pedal comprises a brake plate and a brake drum. Two brake shoes and a cylinder actuated by hydraulic oil on depression of the brake pedal are mounted on an inner side of the brake plate. A first brake lining is mounted on the brake shoe for engaging with an inner surface of the brake drum to provide the brake effect.
Car accidents usually occur due to a short stopping distance or brake system failure. In such circumstances, the driver is unable to stop the car immediately and collision inadvertently occurs. The present invention intends to provide a drum brake in which an additional brake lining is provided around an outer surface of the brake drum together with an additional brake pedal installed proximate to the clutch pedal to aid in shortening the stopping distance of a car.


Methods and systems are provided for routing incoming customer service requests directly to the most appropriate destination within a call center without requiring customer knowledge of a specific telephone number or extension to call and without requiring the customer to select from a series of menus. The receiving location or inbound call center accepts a voice call from a customer. The incoming voice call includes an associated data stream. This data stream is processed by the inbound call center and is used to route the call to the appropriate destination or customer service representative, for example a specific person, a department, a subsidiary, an individual either working within a facility or working outside the facility, a subcontractor and combinations thereof. Additional functionality is provided by including additional data, e.g. data in addition to routing data, along with voice data.

Various businesses handle a large volume of phone calls from clients or customers. To facilitate the processing of this large volume of phone calls, many businesses utilize technologies such as call centers and automated call routing equipment. In general, each call center contains the equipment and personnel necessary to manage and to process a large volume of inbound or outbound calls. Inbound call centers provide support for incoming sales and for customer service requests. For example, inbound call centers receive calls from customers looking to obtain information about the goods or services that a company sells, to purchase those goods or services, to manage their accounts and to obtain assistance. The same arrangement of equipment in a given call center, however, can be used as either an inbound call center or an outbound call center.
The problems associated with call routing inbound calls increase as the customer service functions are divided and distributed among an increasing number of departments and representatives. Therefore, customers experience increasing difficulty in identifying the correct customer service group—by having to locate a telephone number associated with that group, for example. The difficulty in identifying the proper service group includes identifying the department providing a particular service, e.g. the Radiology Department at the local hospital, or identifying the person that is on duty or that is currently performing a particular function, e.g. the consultant on duty, the officer of the day, the acting manager or the pediatrician on call.
Inbound call centers typically contain an automatic call distributor (ACD) to handle incoming calls and to provide the desired routing. For example, the ACD connects calls to a sales representative, a customer service representative or a help desk operator, among others. The ACD also facilitates automated routing of incoming calls to prompt the caller to select one or more menu choices and to place calls that cannot be answered immediately into a hold queue until the next appropriate agent becomes available. The hold queue provides the caller with music, advertising or periodic barge-in messages updating the caller on the current queue status. Reponses to the menu choices facilitate routing of the call through the call center in the most appropriate way.
The routing and queuing provided by the ACD was historically handled by a live human operator. For example, a customer would call a customer service number and would be connected with the live operator. The caller would describe the nature of the issue or service desired, for example by saying, "I have a question about my bill," or "The item I ordered hasn't arrived yet." The live operator would determine the customer's needs, route the call accordingly and provide verbal assurance to the customer that the call is being handled by providing responses such as, "You need to speak with our sales department. One moment, please, while I connect you."
The use of ACD has provided companies with a more efficient method of handling and distributing incoming customer requests, particularly as the number of these requests grows. In general, ACD systems prompt callers through a multitude of levels of menus. Customer input is provided by selecting numbers, letters and symbols on the customer premises equipment (CPE) in response to recorded prompts from the ACD. Examples of these prompts include "Press 1 for new orders, press 2 to check on the status of an existing order, press 3 for additional options, press the pound sign to repeat these options." These automated systems often require callers to pass through several levels of menu selections, listening to all options and figuring out which one best applies. As the number of options increases, it is increasingly difficult for a customer to keep track of the various options. If a customer progresses through many levels and is inadvertently disconnected, that customer must reconnect and step through all of the menus again. In addition, callers are often not presented with any options for speaking directly with a live operator.
Recent technological advances provide for the use of voice recognition systems to facilitate customer routing and menu selection. These systems, however, do not eliminate the need to progress through various menus levels. In addition, voice recognition systems provide additional problems including an inability to understand all spoken responses. With these limitations, ACD's can create a customer service interface that is slow and frustrating and that produces a negative response in customers, which is not a desired reaction for purposes of customer service.
Therefore, a need exists for systems and methods that provide for automated and efficient routing of incoming customer service requests to call centers in a more customer-friendly environment.

International Business Machines Corporation


Disclosed therein is an automatic transmission lever assembly having a shift-lock cam having an electromagnet. The automatic transmission lever assembly includes: a base bracket fixed to a frame of a vehicle; a rod; a rotating member joined to a lower end of the rod, the rotating member rotating on a predetermined shaft according to a movement of the rod for changing a transmission mode and having a locking portion formed at a position corresponding to a shift-lock; a shift-lock cam having a permanent magnet, the shift-lock cam being caught to the locking portion at a shift-lock position and being rotatable on the shaft; and an electromagnet provided at a position facing the permanent magnet, wherein when a brake signal is transferred, electric current flows to the electromagnet, so that the shift-lock cam is operated in a direction to be released from the locking portion.

1. Field of the Invention
The present invention relates to an automatic transmission lever assembly for a vehicle. More particularly, the present invention relates to an automatic transmission lever assembly having a shift-lock cam having an electromagnet.
2. Background Art
In general, a lever assembly arranged near a driver's seat of a vehicle for manipulating an automatic transmission has various types of movement traces, such as a straight lever type that a lever moves in a straight line, a gate lever type that the lever moves in a zigzag form, a manual transmission mode type, and so on. An automatic transmission lever includes a shift-lock device, which enables the vehicle to change gear to a neighboring gear from a specific gear only when the driver steps the brake in order to prevent sudden acceleration incidents. For instance, when the transmission lever moves from a P gear, which is a parking gear, to a D gear, which is a driving gear, or moves from an N gear, which is a neutral gear, to an R gear, which is a reverse gear, the transmission lever can move only when the driver steps the brake.
The shift-lock device according to a prior art has a structure that a solenoid pulls a shift-lock cam to rotate the lever assembly when the driver steps the brake and the lever assembly returns to its original position by a return spring disposed inside the solenoid when the driver releases the brake. However, the shift-lock device according to the prior art has a problem in that the solenoid produces noise and vibration when the solenoid is actuated.

Automatic transmission lever assembly having shift-lock cam using electromagnet


A door gasket is shown for sealing between confronting surfaces. The gasket has a base for mounting to one confronting surface and a deforming section which protrudes outwardly for contacting the second surface. A wire extends through the base parallel to the axis of the gasket member. The deforming section includes a bottom wall, a vertical wall and a slanting wall which are integrally formed with the base and interconnected to define a right triangular exterior which produces improved sealing characteristics.

1. Field of the Invention.
This invention relates in general to gaskets that seal between confronting surfaces, and in particular to a gasket for sealing between the confronting surfaces of an appliance door.
2. Description of the Prior Art.
Various gasket configurations are known in the art for sealing between the confronting surfaces of oven doors, refrigerator doors, automobile doors and the like. For instance, household ovens have gaskets located between the oven door and the frame of the oven for cushioning and sealing the heat within. Many of these gaskets are formed of silicone rubber so as to resist temperature degradation and to extend the useful life of the gasket. The prior art oven door gaskets are typically comprised of straight, elongated pieces, each for one side of the oven. Usually, there are three pieces provided, one for the top, and one for each side, with the corners having small gaps between each straight piece. Normally, the pieces contain flat metal strips that extend all or part of the length of the gaskets for removably clipping the gaskets to apertures in the frame of the oven. This allows the gaskets to be removed for cleaning.
U.S. Pat. No. 4,538,381, to Vogel, issued Sept. 3, 1985, and assigned to the assignee of the present invention, shows a continuously extruded gasket with a tubular section which protrudes outwardly from a base. A ductile wire passes along the entire length of the base and allows the gasket to be bent into a rectangular shape for mounting on the oven door.
In spite of the above improvements, I have found that door gaskets of oval, round, square or rectangular cross-sectional shape tend to pucker or distort when bent, thereby forming potential leak paths due to unequal compression requirements, allowing heat to leak from the sealed enclosure. This is a particular problem for an oven door gasket formed of a continuously extruded length of material which is bent into a rectangular shape to fit the door opening.
A need exists for an improved door gasket for sealing between two confronting surfaces which can be bent into a 90.degree. corner which does not pucker or distort in the corner to form a potential leak path.
A need also exists for such a door gasket having a profile which allows the bending distortion at the 90.degree. corner to be absorbed in other portions of the profile than the sealing portions thereof.
A need also exists for such a door gasket which provides improved sealing characteristics at lower degrees of compression than prior art gaskets.


A buffer for varying data access speed. Combining the buffer with a memory such as a double data rate synchronous dynamic random access memory, the data transmission rate of a memory system can be enhanced. The buffer is coupled with a control chip set and several memory modules to provide functions of data analysis and assembly to satisfy a two-way data transmission interface and to obtain a higher data transmission rate. The buffer also has the function of isolating the electric connection between two sides. A single signal interface from a memory module can be converted to a complementary source synchronous signal by the buffer, so that a high-speed data transmission can be achieved. A memory system can apply several of such buffers to achieve an even higher data transmission speed.

1. Field of the Invention
The invention relates in general to a buffer in a memory access system. More particularly, the invention relates to a buffer in a motherboard used for enhancing data access speed of memories.
2. Description of the Related Art
In recent years, dynamic random access memory (DRAM) has evolved from the earliest non-synchronous dynamic random access memory (DRAM) to enhance data out (EDO) dynamic random access memory, and further to the currently widely applied synchronous dynamic random access memory (SDRAM). Each transmutation provides a great enhancement in access speed of the memory system. Most of the high-speed buses employ a source synchronous design such as the AGP Bus, the double data rate dynamic random access memory (DDR DRAM), and the RAMBUS. In addition, as a high data transmission speed requires a set of complementary data strobe signals, combination of the source synchronous design and provision of a set of complementary data strobe signals have become a leading trend in memory system design.
The market for dynamic random access memory system is still enormous. Generally speaking, a macro-revolution of this product takes three to five years. Thus, the speed of performance enhancement for a memory system relative to the growth of data transmission between microprocessor and storage device or microprocessor and graphic apparatus is slow. Especially in the use of the Internet, where a significant amount of data transmission is required, the inferior memory bandwidth seriously degrades the sensory enjoyment of the users.
FIG. 1 is a block diagram showing a conventional memory system on a mother board. The control chip set 100 is directly coupled to a memory module 140. The control chip set 100 and the memory module 140 use the same system clock as the reference for data transmission speed. Being limited by the current dynamic random access memory, the control chip set 100 has to lower the speed of the read/write instruction and data transmission to complete the data read/write operation with a transmission speed allowed by the memory system.
The invention provides an apparatus for varying data access speed, so that the current standard dynamic random access memory system can have a multiple data transmission rate. In one embodiment of the invention, a buffer is provided. The buffer is coupled between a control chip set and several memory modules to disassemble the write data sent from the control chip set to the memory modules and to assemble the read data sent from the memory modules to the control chip set.
The invention provides an apparatus for varying data access speed. A single memory read/write interface sent from a memory is converted into a high speed complementary signal of source synchronous design.
The above apparatus can also isolate the electric connection between the control chip set and the memory module. The modulization of the system design is thus more flexible. For example, the consideration of sequence in layout design is easier.
The above apparatus can also reduce the pin counts with the bandwidth that maintains or increases data transmission speed. Therefore, the fabrication cost can be reduced, or the input/output (I/O) pins can be reserved for other applications.
In one embodiment of the invention, a buffer varying data access speed is provided. The buffer includes a phase lock loop circuit, a control chip set data I/O interface, a memory data I/O interface, a first-in-first-out (FIFO) memory from the control chip set to the memory, a FIFO memory from the memory to the control chip set, and a control signal generator. The phase lock loop circuit is responsible for generating various clock signals required for the buffer. The buffer is coupled to the control chip set and the memory modules. The write data from the control chip set is received by the FIFO memory from the control chip set to the memory. Thereby, the write data is disassembled and transmitted to the memory modules by the memory data I/O interface. The FIFO memory from the memory to the control chip set is responsible for receiving the read data from the memory modules. Once assembled by control chip set data I/O interface, the read data is then transmitted to the control chip set. The control signal generator generates proper read/write control and I/O control, so that the data transmission speed at the control chip set can be a multiple of the data transmission speed at the memory as expected. Alternatively, the phase lock loop circuit can be omitted by supplying the clock signals directly from the system.
With the above buffer, a respective memory module can be assembled to enhance the performance of the memory system to match data transmission speed of the microprocessor or other I/O interface.
Both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

Buffer for varying data access speed and system applying the same


A method of controlling an image processing apparatus, and an image processing apparatus to carry-out the method. The edge pixels of a black character may be evaluated to improve visibility of edge pixels and to enhance the blackening of the edge pixels when the evaluated edge pixels are determined to be the actual edge pixels of the original image and to correct the edge pixels to be suitable for original background pixel values and to brighten the edge pixels when the evaluated edge pixels are determined to be the actual background pixels of an original image. The black character may be enhanced so that the actual black character becomes blacker and that the background pixels become brighter to improve the visibility of the black character. The black character may be distinguished from a scanned image, the print thickness of the distinguished black character may be controlled, and the black character having controlled print thickness may be printed out using only a K color.

1. Field of the Invention
The present general inventive concept relates generally to a method of controlling an image processing apparatus, and more particularly to a method of controlling an image processing apparatus to improve reduction quality of an image by improving visibility of a black character, and an apparatus to carry-out the method.
2. Description of the Related Art
In general, an image processing apparatus converts a document created by a user who wishes to perform printing through an application program or an image photographed by a user using a digital camera into coded data to print the data to a recording paper so that the user can see the data. Such an image processing apparatus typically includes a printer, a scanner, a copy machine, or a facsimile.
An image processing apparatus capable of performing color printing includes toners of various colors such as cyan, magenta, yellow, and black (CMYK). The color image is then printed out by combining colors of the toners.
After the color image is binarized, black pixels are expressed by a combination of the C, M, Y, and K colors, which may cause toner dispersion or noise around an edge of the color image during reproduction. Furthermore, when such a combination is used, the obtained black color is different from the original black color because the level of the obtained black color is lower than the level of the original black color. As a result, reproduction quality deteriorates.
For this reason, as disclosed in U.S. Pat. No. 6,937,756, the pixels that belong to a black line image are printed using the K color to enhance a black image. That is, a K channel is enhanced and C, M, and Y channels are suppressed in order to increase the black level.
However, when an input image is scanned, the edge pixels of a black character are commonly blurred. This means that only a part of the edge pixels are determined to be the edge pixels of the black character. As a result, the printed character and thin lines may appear thicker than the originals and/or may be printed out with lower resolution.

Image processing apparatus and control method the same


A control device for controlling a fuel injection in an internal combustion engine provided with a fuel injection valve has a driving portion supplying an electric power to a terminal of the fuel injection valve so as to drive the fuel injection valve to be opened; a current detecting portion detecting a drive current flowing through the fuel injection valve when the fuel injection valve is driven to be opened; a voltage detecting portion detecting a terminal voltage of the terminal of the fuel injection valve; a correction portion correcting the electric power supplied by the driving portion so that an actual value of the drive current detected by the current detecting portion agrees with a target value; a valve close detecting portion detecting a valve closing timing of the fuel injection valve based on the terminal voltage detected by the voltage detecting portion in a condition where the electric power supplied by the driving portion is corrected by the correction portion.

Conventionally, it is known that an opening of a fuel injection valve is detected based on a variation in electric current flowing through a solenoid of an electromagnetic fuel injection valve (refer to Patent Literature 1). In an electromagnetic valve shown in Patent Literature 1, an valve opening is detected based on a variation in solenoid current which is generated when an armature of a fuel injection valve is mechanically abuts on a stopper at a full-close position.
That is, if the armature does not mechanically abut on the stopper, the opening of the fuel injection valve cannot be detected. When a valve body of the fuel injection valve does not reach the full-close position at a partial lift injection, the opening of the fuel injection valve cannot be detected, so that a valve opening operation cannot be corrected.

Device for controlling fuel injection in internal combustion engine


Automated tests are scheduled for a telecommunication network. A time slot array is created and a subset of the time slots are marked as unavailable according to respective maintenance windows. A remainder of the time slots are marked as available. Trunk groups are sequentially selected for respectively scheduling the tests. A particular available time slot is identified in the array for both of the testing units corresponding to the respective trunk group. The slot is marked as unavailable and then each trunk circuit is sequentially selected within the respective trunk group. A respective test is designated for a selected trunk circuit during the particular time slot and a counter is incremented. A check is made whether the counter indicates that a number of the tests have been scheduled that fills a capacity of the testing units for running simultaneous tests. If the capacity is not filled, then the method repeats the designating step for a next selected trunk circuit using the particular time slot. Otherwise, a further time slot marked as available in the array for both of the testing units is found, the further time slot is marked as unavailable, and the designating step is repeated for a next selected trunk circuit using the further time slot.

The present invention relates in general to maintenance testing of telecommunications network equipment, and, more specifically, to scheduling of tests between large numbers of network nodes using test equipment having multiple channels for conducting a plurality of simultaneous tests.
In order to maintain a high level of quality of service in a telecommunications network, various standard equipment tests have been defined such as those in the Telcordia standard GR-822. In order to quickly identify all malfunctions that may compromise the quality of service, automated testing needs to be thorough and efficient so that all network resources are checked in the least amount of time. A typical telecommunications network has many functioning elements connected in a complex architecture. A nationwide long distance network, for example, may have about fifty switches interconnected by several thousand Intermachine Trunk (IMT) groups. Each IMT consists of many T1 spans (DS-1) and each DS-1 in turn contains 24 trunk circuits (DS-0). Tests that operate at the trunk circuit level (e.g., echo canceller testing) require many thousands of individual automated tests.
Testing units utilized in test the system are standalone devices capable of several different kinds of automated tests. Each testing unit is equipped with one or more T1 cards to handle multiple channels so that it can do many simultaneous tests. In a typical network, at least one respective testing unit is connected to each switch or other node through Automatic Trunk Routing (ATR). Most trunk circuit tests involve both switches connected by the DS-0 line and the individual testing units connected to the switches. Each test typically involves a test call being placed over the trunk circuit, which results in that trunk circuit being unavailable to carry any customer calls during the test. Therefore, tests are scheduled only during predefined "maintenance windows" coinciding with the least busy times for the network. Since switches may be in different geographic locations spanning different time zones, the maintenance windows may not start or end together at both ends of a particular trunk group.
Scheduling of automated tests should make full use of available testing resources. For example, the simultaneous testing capabilities of the testing units should be fully utilized. Scheduling should ensure that there are no conflicts in the assigned tasks. Even though testing may be occurring simultaneously on unrelated trunk groups, tests must be scheduled in such a way that a testing unit is not overloaded and is not directed to perform incompatible tasks. Scheduling must also be achieved in such a way that the ability of the network to meet quality of service performance during testing is not impaired. Due to the complexity of the network interactions and the large number of permutations of potential testing events, prior art scheduling techniques have failed to meet the foregoing goals. Prior art manual scheduling methods have only managed to test about 15% of a 50-switch long distance network in a two week time period. Testing of a full network would have taken even longer.

Scheduling of automated tests in a telecommunication system


A network learns capability information indicating whether a user equipment (UE) is capable of simultaneous and independent operation in multiple component carriers (CCs). The network configures a monitoring pattern for each of multiple CCs that are configured for the UE in dependence on the received capability information. The capability information derives from the UE's RF layout; if the UE is capable of such simultaneous and independent operation the network can assign for the CCs different monitoring patterns that are independent of one another and the UE will have no gaps where it cannot take or send a measurement. This knowledge is particularly useful if the CCs are frequency non-contiguous with one another. If the UE is not so capable, the network must assign monitoring patterns to that UE for all its configured CCs that are not independent of one another.

This section is intended to provide a background or context to the invention that is recited in the claims. The description herein may include concepts that could be pursued, but are not necessarily ones that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, what is described in this section is not prior art to the description and claims in this application and is not admitted to be prior art by inclusion in this section.
The following abbreviations that may be found in the specification and/or the drawing figures are defined as follows:    3GPP third generation partnership project    BB baseband    BW bandwidth    CA carrier aggregation    CC component carrier    CQI channel quality indicator    DL downlink (eNB to UE direction)    DRX discontinuous reception    eNB EUTRAN Node B (evolved Node B/base station)    E-UTRAN evolved UTRAN (LTE)    HARQ hybrid Automatic retransmission request    LTE long term evolution    LTE-A LTE-advanced    MAC medium access control    PCC primary CC    PDCCH physical downlink control channel    PDSCH physical downlink shared channel    PUSCH physical uplink shared channel    RF radio frequency    RRC radio resource control    RSRP reference signal received power    RSRQ reference signal received quality    SCC secondary CC    UE user equipment    UL uplink (UE to eNB direction)    UTRAN universal terrestrial radio access network
In the E-UTRAN system, LTE Release 8 is completed, the LTE Release 9 is being standardized, and the LTE Release 10 is currently under development within the 3GPP. In LTE the downlink access technique is orthogonal frequency multiple division access OFDMA, and the uplink access technique is single carrier, frequency division multiple access SC-FDMA. These access techniques are expected to continue in LTE Release 10.
FIG. 1 shows the overall architecture of the E-UTRAN system. The EUTRAN system includes eNBs, providing the EUTRA user plane and control plane (RRC) protocol terminations towards the UE. The eNBs are interconnected with each other by means of an X2 interface. The eNBs are also connected by means of an S1 interface to an evolved packet core, more specifically to a MME and to a Serving Gateway. The S1 interface supports a many to many relationship between mobility management entities MMEs/Serving Gateways and the eNBs.
In LTE Release 8/9 there are discontinuous reception DRX periods during which a mobile terminal/UE is allowed to power down (sleep or idle mode) to conserve power and the network knows not to send transmissions to it. Other active periods are synchronized to this DRX period. For example FIG. 2 gives a general overview of the DRX concept in E-UTRAN for a single mobile terminal. The PDCCH gives resource allocations to multiple mobile terminals for resources in the UL and DL shared channels, shown as PDSCH and PUSCH. More than one consecutive PDCCH may be used (the duty cycle or 'on-duration'), but the overall schedule repeats after each DRX.
The UEs synchronize to the PDSCH and aligns to the RRC-Connected/idle mode DRX of the eNB in order to receive possible resource allocations/paging messages from network. One of the parameters needed in RRC-Connected/idle mode terminal is the RRC-Connected/idle mode DRX period so that the UE and eNB have synchronized resource allocation/paging occasions defined by the DRX schedule during which the eNB can send resource allocations or a page to the UE, which tunes to listen at those times.
Though described in view of LTE or E-UTRAN, many current wireless systems use the DRX concept and can benefit from these teachings, as will future systems that employ discontinuous reception at the mobile equipment. For example, the GERAN system uses a paging period (see for example 3GPP TS 45.002) and legacy UTRAN (3G) uses paging and idle mode DRX and continuous packet connectivity (CPC) in the connected mode (see for example 3GPP TS 25.331 and TS 25.304).
LTE-A will likely be part of LTE Release 10 which is to include bandwidth extensions beyond 20 MHz, among other changes. This bandwidth extension is to be done via carrier aggregation (CA), in which several component carriers (at least one of which is Release 8 compatible) are aggregated together to form a system bandwidth. This is shown by example at FIG. 3 in which there are five CCs aggregated to form one larger LTE-A bandwidth of 100 MHz. Future LTE-A terminals could potentially receive/transmit on multiple CCs at the same time to give the eNB greater scheduling flexibility while increasing data throughput.
In LTE-Advanced, multiple DL and/or UL CCs may be configured/activated for one UE. There are two levels of handling CCs: the UE may be configured with basic CC information via RRC signaling, and following configuration the different CCs can be activated and deactivated using MAC level signaling. MAC level signaling (activation and deactivation of CCs) was introduced in order to enable potential UE power savings.
An activated CC is one for which the UE is required to monitor the PDCCH for potential allocations, as well as perform CQI measurements and other procedures set forth in LTE Release 8. The UE does not need to monitor the PDCCH of a deactivated or inactive CC, nor is it required to perform CQI measurements on such a deactivated CC. It follows that in order that the UE to conserve power from having a CC-activation and CC-deactivation command, the UE measurement performance requirements for deactivated CCs has to be different than those that apply for activated CCs. By example, such a CC-activation or deactivation command can be at the MAC level or the RRC level, or possibly at the L1 level in certain embodiments.
As currently set forth at 3GPP TS 36.300 (v9.3.0) sec 12.1 "Carrier Aggregation" (as changed by CR document R2-102645, 3GPP TSG-RAN WG2 Meeting #69, Beijing, China; 12-16 Apr. 2010), if a UE is configured with more than one CC the same DRX operation applies to all configured and activated CCs, so there is identical active time for PDCCH monitoring. The PCC is from a primary cell and is always active; all other configured CCs are termed SCCs which may be from a secondary cell and at any given time any of those SCCs may be active or inactive for the UE for which they are configured. CR document R2-102645 is attached as Appendix A to the priority document U.S. 61/330,621.
A problem arises when the status of a configured CC is changed, for example from deactivated to activated (and also vice versa). The UE needs to tune from the first CC (PCC or some other CC which has remained active) to the newly activated second CC in order to monitor the PDCCH, measure it and report on that second CC. An additional problem occurs when measurements have to be performed on an intra-band deactivated CC (that is, contiguous in frequency with the other CC which remains active) in that still the UE needs to re-tune its radio to the frequency of the other contiguous-band CC. During the time the UE is tuned or needs to re-tune its receiver to receive and measure the other CC, there is a gap during which the UE's DRX pattern for a first CC causes the network to expect that the UE is actively listening to that first CC when in fact the UE is re-tuning in order to measure the other CC.
Embodiments of this invention are directed to how DRX and/or measurement reporting is applied on CC's of a CA system that are actively used by the UE. Currently for LTE-A it is assumed that the DRX cycle will be common to all CCs. At International publication WO/2009/120124, entitled "DRX FUNCTIONALITY IN MULTI-CARRIER WIRELESS NETWORKS", when there is a gap such as might arise from using a common DRX across multiple CCs, the network sends override commands to disable or to modify the DRX cycles of certain CCs, which this publication appears to characterize as providing independent DRX on the respective CCs.

Monitoring pattern separation between component carriers based on user equipment RF layout


An optical device comprises an optical head and a package containing the optical head and having pins led outside. A V-groove is formed in one side of a glass substrate. On the other side, the glass substrate is secured to the base of the package. A PD array and the pins are electrically interconnected through a gold electrode pattern formed on a mounting face of a submount, through holes, electrode pads formed on the top of the submount, and wires.

1. Field of the Invention
The present invention relates to an optical device including an optical fiber array having one or more optical fibers, and more particularly to an optical device suitable for use in monitoring signal light while the light is propagated through an optical fiber.
2. Description of the Related Art
With the recent development of wavelength multiplex communications using fiber amplifiers, it has become customary to monitor the amounts of light at respective wavelengths with photodiodes (PD), in order to adjust the amounts of light, and then amplify them with amplifiers.
Various methods are known for monitoring amounts of light at respective wavelengths. Since the optical fibers need to be coupled to respective monitoring devices, the monitoring devices alone are of considerable size.
Therefore, there has been a demand for smaller highly packed monitoring devices. For monitoring signal light, it is customary for the monitoring device to extract a portion of the signal light. It is desirable for monitoring devices to be able to monitor signal light without significantly attenuating the signal light.
Heretofore, a technique disclosed in Japanese Laid-Open Patent Publication No. 2001-264594, for example, has been proposed in the art. According to the disclosed technique, an optical fiber is placed in a V-shaped groove defined in a glass substrate, and thereafter, a parallel groove is formed in the glass substrate obliquely to an optical axis of the optical fiber. Then, a light reflecting base (optical member) is inserted into the parallel groove, with the gap filled with an ultraviolet-curable resin (adhesive).
From the signal light that is propagated through the optical fiber, a light component (reflected light) thereof, which is reflected by the light reflecting base, is extracted out of the cladding of the optical fiber. The signal light can be monitored by detecting the reflected light using a photodetector (PD), for example.
If PDs are disposed on the optical fibers, then since most of the optical fibers used are made up from single-core optical fibers, PDs in metal packages are often employed (see, for example, Japanese Laid-Open Patent Publication No. 10-300936, Japanese Laid-Open Patent Publication No. 11-133255, and PCT International Patent Publication No. WO97/06458). This is because single-core optical fibers pose less space limitations, and several PDs in metal packages are already available on the market and have proven satisfactory as to cost and reliability.
However, it is difficult to use PDs in metal packages in combination with multiple-core optical fibers. In particular, if optical fibers are required to be installed at a high density, e.g., at a pitch of 250 μm, then it is necessary to employ a photodiode array (PD array) comprising a plurality of bare photodiodes.
Generally, electric signals from a PD array are output through a package having a plurality of pins.
According to major conventional structures, electrodes are mounted on an upper surface of a V-groove substrate to which an optical fiber array is fixed, or on an upper surface of an optical waveguide that is optically coupled to such a V-groove substrate, and interconnections are connected to a package or the like through the electrodes (see, for example, Japanese Laid-Open Patent Publication No. 7-104146, Japanese Laid-Open Patent Publication No. 2-15203, PCT International Publication No. WO97/06458, and Japanese Laid-Open Patent Publication No. 7-159658).
One common problem is that, since the electrodes are mounted on the upper surface of the V-groove substrate or on the upper surface of the optical waveguide, there are limitations imposed on the interconnections connected (wire bonding) to the PD array, the mounted configuration of the PD array, etc.
In view of the interconnections connected to the package, e.g., wire bonding to the pins of the package, since the wires cannot be too long, the interconnections on the upper surface of the V-groove substrate or on the upper surface of the optical waveguide need to be positioned closely to the pins. This means that the V-groove substrate or the optical waveguide itself needs to be positioned closely to the pins, and the V-groove substrate or the optical waveguide thereby has its width unduly increased. As a result, the cost for such devices is increased.
In addition, it is necessary that the electrodes be formed in relative positional alignment with the V-groove substrate or the optical waveguide. However, a tedious and time-consuming procedure is required to form the electrodes in such a manner.
Furthermore, because the electrodes are mounted on the V-groove substrate after V-shaped grooves are formed therein, or the electrodes are mounted on a completed optical waveguide substrate of the optical waveguide, if the electrodes are defective, then the V-groove substrate or the optical waveguide substrate also becomes defective, resulting in a reduction in yield.
One problem inherent in V-groove substrates, particularly V-groove substrates of glass, is that their surfaces are often ground and do not have a mirror finish. Highly packed interconnections on such rough surfaces are unfavorable from the viewpoints of characteristics and reliability. The surface of a V-groove surface is ground before V-shaped grooves are formed therein because of the need for parallelism between a cutting machine for forming the V-shaped grooves and the machined surface of the substrate. After the surface of the substrate is ground by a surface grinding machine or the like, it is machined to form V-shape grooves therein.
Many conventional arrangements have been disclosed in which, rather than electrodes disposed on the surface of a V-groove substrate or an optical waveguide, the PD array itself is disposed on optical fibers (see, for example, PCT International Publication No. WO97/06458, Japanese Laid-Open Patent Publication No. 63-191111, Japanese Laid-Open Patent Publication No. 2000-249874, and Japanese Laid-Open Patent Publication No. 3-103804). Most of these publications, directed to such conventional arrangements, disclose nothing about interconnections to be connected after the installation of the PD array. Generally, interconnections may be connected to the package via another wiring board disposed between the PD array and the optical fiber array, or by direct wire bonding from the PD array.
Connecting interconnections via another wiring board is troublesome in that the other wiring board must be newly installed (positioned and bonded), after the PD array has been installed, and then the interconnections thereto are connected. Direct wire bonding from the PD array requires considerably long bonding wires, and is not sufficiently reliable. Further, it is highly difficult to perform direct wire bonding because complex interconnections must be directly connected from the PD array, which comprises highly packed photodiodes.
For positioning the PD array, it is the general practice to align the PD array while output currents therefrom are confirmed. According to both of the above processes, since a probe is directly applied to the PD array at this stage, this complicates the positioning process, making it a highly difficult task to perform.
A process involving the connection of interconnections to a PD array is disclosed in Japanese Laid-Open Patent Publication No. 2002-182051, for example. According to the disclosed process, a PD array has a portion installed on a submount and another portion (active layer portion) positioned within an optical path of reflected light, with an adhesive interposed therebetween. That is, a portion of the PD array other than the active layer is installed on the submount, because any obstructions positioned within the optical path leading to the active layer portion of the PD array tend to prevent the assembly from functioning properly as a monitor.
However, in the above structure, when stresses are generated by shrinkage of the adhesive as it is cured, or when dimensional changes thereof occur as it is thermally expanded, the PD array suffers strain stresses, since the PD array itself possesses a moment fulcrum. When such strain stresses are applied to the PD array, the characteristics of the PD array are adversely affected, by an increase in dark current, etc.
The submount supports the PD array thereon and has interconnections formed on its surface. If the submount experiences warpage, however, then the interconnections thereon may become unreliable, and a dark current may be produced by the PD array. Therefore, to avoid such warpage, the submount needs to have a thickness of at least 0.5 mm. Consequently, the distance between the optical fiber array and the PD array cannot be reduced to less than 0.5 mm, resulting in a loss of reflected light and increased crosstalk. In addition, the required distance between the optical fiber array and the PD array poses limitations on efforts to reduce the size of the entire assembly and increase the monitoring capability thereof.


A regulating unit for a hot and cold water mixing valve includes a pressure responsive part having a piston slide 60, and a temperature responsive part which is influenced by a thermostat 45 and which includes a regulating valve body 50 which is axially moveable and optionally included in an insert which can be screwed into the mixing valve. The regulating valve body and the piston slide are mutually concentrical and one of these two components is received at least partially in the other.

The present invention relates to a mixer valve regulating unit.
A regulating unit of this kind can be used with different types of mixing valves. The provision in the regulating unit of a pressure responsive component which functions to equalize any difference in pressure that may occur between the hot and the cold water delivered to the regulating unit is a highly important criterion, since a drop in pressure will often occur in practice in one of the delivery pipes as a result, for instance, of the introduction of hot or cold water into a branch pipe connected to the water supply system. A pressure responsive component of this kind will therewith compensate for any differences in pressure that may occur and will ensure that flows of equal magnitude will be delivered to the temperature responsive part of the valve, which is necessary in order to obtain water which has the temperature to which the mixing valve has been set.
The space available in a mixing valve is limited, however, and it is therefore important that a regulating unit which is provided with a pressure equalizing or pressure balancing component has a compact construction.
Furthermore, the regulating unit should preferably have a simple and reliable construction and be capable of being readily serviced, such that the moveable components of the regulating unit can be easily removed from the mixing valve for maintenance purposes or for replacement purposes.
When dimensioning the components of the regulating unit, it must also be remembered that the mixing valve of the kind to which the present invention relates will often require the provision of one or more check valves, or non-return valves, which function to prevent water flowing from at least the hot water side to the cold water side of the system.
SE,B,7403239-2 (Publication No. 383,404) (Vargarda) describes and illustrates a mixing valve which is provided with a temperature controlling knob and which is also pressure controlled, i.e. adapted to equalize variations in pressure of the hot and cold water delivered to the valve. This mixing valve, however, lacks a thermostat part, and the quantity of water delivered is controlled by means of a handle located adjacent a temperature control knob. Consequently, it is not possible to control temperature accurately with this known mixing valve, which lacks the provision of a thermostat control.
SE,B,7409845-0 (Publication No. 406.968) (Pont-a-Mousson) describes and illustrates an insert in the mixer housing formed in a mixing tap. The insert is provided with a temperature control unit and is also intended to function as a flow control valve and has a temperature control knob located adjacent a flow control knob.
The mixing valve insert is rotationally symmetrical about its longitudinal axis and one end of the insert can be screwed into a mixing housing. The insert, however, lacks pressure equalizing means and will function unsatisfactorily in the event of pressure surges in the distribution system.
SE,B,7705979-8 (Publication No. 432,649) (Oras) describes and illustrates an equalizing device intended for mixer valves which is located upstream of the actual mixing valve, seen in the flow direction of the water, and includes a slide which forms adjustable throughflow openings for hot and cold water/respectively, said slide being moved axially in reverse directions to respective water pressures, such as to adjust the areas of the throughflow openings. The slide is connected mechanically to a thermoelement which functions to move the slide in response to water temperature, such as to control the amounts of hot and cold water delivered to the valve.
In this case, the same slide is used both for pressure compensation and temperature control. This would seem impossible to achieve successfully in practice, and in actual fact this construction is a so-called desk invented product which will never function successfully in practice. As with other known mixing valves, the mixing valve taught by this publication has the drawback that the thermostat is located in the region of the temperature control body--it is actually incorporated in the temperature control body in the construction described--which means that the thermostat part will detect a temperature other than the final mixing temperature, which impairs the properties of the mixing valve, i.e. the valve is not as effective as would be desired.

Mixer valve regulating unit, and a regulating unit piston slide


A vehicle approach warning system is disclosed. The vehicle approach warning system includes: an in-vehicle communication apparatus to be mounted to a vehicle, the in-vehicle communication apparatus being configured to wirelessly transmit vehicle travel data to surroundings of the vehicle; and a portable warning terminal to be carried by a pedestrian, the portable warning terminal being configured to give, in response to receiving the vehicle travel data wirelessly transmitted from the in-vehicle communication apparatus, a warning about approach of the vehicle to the pedestrian in a way other than auditory stimulation if electric field strength at a time of receiving the vehicle travel data is larger than a threshold.

1. Field of the Invention
The present invention relates to a vehicle approach warning system, a portable warning terminal, and an in-vehicle communication apparatus.
2. Description of Related Art
Japanese Unexamined Patent Application Publication No. 2007-182195 discloses an alarm system that enables a hearing-impaired person to notice the presence of an alarm horn sound when a vehicle emits the alarm horn sound. Specifically, when the vehicle emits the alarm horn sound, an in-vehicle communication apparatus transmits a warning radio wave to the surroundings. When a portable warning terminal carried by the hearing-impaired person receives this warning radio wave, the portable warning terminal vibrates a vibrator or emits warning-colored light.
The inventors of the present application have found out the followings. A situation requiring a person to be warned is not limited to only a time when a vehicle sounds an alarm horn. For example, when a vehicle approaches a person from his or her back, the person may not notice the approach of the vehicle if the person is hearing-impaired or if the traveling sound of the vehicle is small. In this situation, a driver of the vehicle possibly assumes that the person is noticing the traveling sound of the vehicle and is walking with care. The driver may not sound an alarm horn.

Vehicle approach warning system, portable warning terminal and in-vehicle communication apparatus