The image forming apparatus comprises: an object liquid deposition device which deposits an object liquid containing coloring material onto a recording medium; a treatment liquid deposition device which deposits a treatment liquid that insolubilizes the coloring material onto the recording medium; and a control device which controls the treatment liquid deposition device in such a manner that volume of the treatment liquid deposited in a high-density region on the recording medium where volume per prescribed surface area of the object liquid deposited on the recording medium is high, is less than volume of the treatment liquid deposited in a low-density region on the recording medium where the volume per prescribed surface area of the object liquid deposited on the recording medium is low.

1. Field of the Invention
The present invention relates to an image forming method and an image forming apparatus, and more particularly, to technology for insolubilizing the coloring material contained in an object liquid, such as ink, by means of a prescribed treatment liquid.
2. Description of the Related Art
In recent years, inkjet recording apparatuses (inkjet printers) have become widespread as image forming apparatuses for printing images. An inkjet recording apparatus prints a desired image by ejecting ink droplets from an inkjet recording head, onto a recording medium, such as recording paper, while moving the recording medium and the inkjet recording head relatively with respect to each other.
In an inkjet recording apparatus, in order to avoid bleeding and obtain a clean image, desirably, the coloring material contained in the ink is fixed rapidly onto the recording medium. In view of these circumstances, various technologies have been proposed for rapidly fixing the coloring material onto the recording medium, by insolubilizing the coloring material in ink deposited onto the recording medium by means of a prescribed treatment liquid.
Japanese Patent Application Publication No. 2005-119115 discloses an inkjet recording apparatus in which the deposition volume of a reactive liquid per unit surface area of a recording medium is varied in accordance with the differential between the landing times of the reactive liquid and the ink on the recording medium, and the reactive volume of the reactive liquid and the reactive volume of the colored ink are set to be approximately the same. Japanese Patent Application Publication No. 8-72229 discloses an inkjet recording apparatus in which a low-resolution mode using ink only, and a high-resolution mode using ink and treatment liquid are used.
In an image forming apparatus such as an inkjet recording apparatus, desirably, the diameter of the dots formed on the recording medium by the ink droplets is adjusted in accordance with the desired density. For example, in a high-density region, in order to form an image of high density, it is desirable to prevent the appearance of white background color by increasing the dot diameter. On the other hand, in a low-density region, it is desirable to improve the image granularity by making the dot diameter sufficiently small.
However, in the inkjet recording apparatus according to Japanese Patent Application Publication No. 2005-119115, since the reactive volume of the reaction liquid and the reactive volume of the colored ink are approximately the same, then the diameter of the ink dots is virtually uniform. Consequently, it is difficult to actively change the ink dot diameter. If the dot diameter is made relatively small, for example, then in the high-density region, it is difficult to make mutually adjacent ink dots contact each other, thus making white background color liable to appear. On the other hand, if the ink dot diameter is made relatively large, then it is difficult to ensure good image granularity. In this way, in the inkjet recording apparatus described in Japanese Patent Application Publication No. 2005-119115, it is difficult to satisfy both "improvement in the image granularity in the low-density region" and "prevention of the appearance of white background color in the high-density region", in an efficient manner.
Furthermore, the inkjet recording apparatus according to Japanese Patent Application Publication No. 8-72229 is disadvantageous in terms of the "improving the granularity of the image in the low-density region", since the treatment liquid is not used in low-resolution mode, and therefore, it is difficult to make the dot diameter sufficiently small. On the other hand, in the high-resolution mode, a fixed volume of the treatment liquid is used and the dot diameter may be made too small, which is disadvantageous in terms of the "preventing the occurrence of background white color in the high-density region".
Therefore, the technology for achieving both the "improvement of image granularity in the low-density region" and the "preventing the occurrence of background white color in the high-density region", in an efficient manner, have been expected.

Image forming method and image forming apparatus using treatment liquid


A method and system for labeling data in a networked environment. The method and system comprise determining if a label should be added to a portion of data having an associated first header. If so, a second header is constructed containing a label. The second header is indicated in a reference in the first header. The label contains at least one attribute of the data. The second header is attached to the first header. The portion of data is then transmitted, along with the headers. In one embodiment, the second header may contain credential information related to the data portion.

1. Field of the Invention
The present invention relates to the field of inter-networked devices. Specifically, an embodiment of the present invention relates to a method and system of labeling data to transfer data attributes along with the data.
2. Background Art
Estimates of the worldwide damage caused by malware (e.g., viruses, trojan horses, etc.) exceed $1 trillion per year in wasted effort to repair problems, reconstruct damaged data, etc. Trusted operating systems take a proactive approach to the problem by providing strong security features and assurances in accordance with formally stated requirements. They provide a trusted computing base built from the ground up for the purpose of enforcing a security policy (e.g., the set of rules that determine who accesses what and how). The trustworthiness comes from the guarantee, to a certain level of assurance, that all accesses to objects by subjects from software running on the trusted computing base are controlled and cannot compromise the protection mechanisms of the trusted computing base.
Multilevel security is being increasingly considered outside the traditional governmental and military circles, as it has the potential to meet emerging information technology security needs, when combined with other technologies. In order to guarantee that information is protected to a certain level of assurance, multilevel secure operating systems enforce a set of mandatory access control (MAC) rules that can be evaluated according to predefined criteria.
In order to enforce those access controls across a network, routing needs to be controlled so as to select specific network links in accordance with the security policy. Also, hosts need to retrieve the security attributes of data coming from the network and to communicate those of their own processes to remote hosts.
Information in a Multilevel-Secure Operating System, such as Trusted Solaris™, is assigned a label. The label contains attributes used to enforce the access controls required by a security policy. However, the label may be used for purposes other than security. The label of a process (e.g., program) may represent the credentials (e.g., owner, clearance, and privileges) or other attributes of that process. The label of an object (e.g., file, device, etc.) may represent the sensitivity (e.g., confidential, secret, public, engineering use only, etc.), the integrity, or other attributes of the data.
Implicit labeling is one way of labeling information. A conventional implicit labeling scheme is dedicating an IPsec (Internet Protocol Security) security association for each sensitivity level. However, implicit labeling has numerous shortcomings. First, scalability is limited when using implicit labeling. Implicitly binding security attributes to a security association may be sufficient when the set of values (e.g., sensitivity levels) is small. However, some attributes have a multitude of sensitivity levels. Thus, there needs to be a separate security association for each combination.
Another shortcoming of implicit labeling is the cost of establishing the security establishment. For example, an IPsec security association may be able to scale down to selectively protect a single socket (one connection/liaison). However, due to the cost of establishing the security association (including the key exchange), it is more efficient to aggregate the flows by broader selectors, such as host or subnet addresses or transport level port numbers.
A further shortcoming of implicit labeling is the inherent difficulty of using the implicit information to route data packets. For example, a router will not necessarily be a member of the security association. Unless the router is a member, it will not know the security attributes of the packets and hence is unable to route based on the attributes.
Explicit labeling is another way of labeling information. One conventional method using explicit labeling is an Internet Protocol Version 4 (IPv4) Security Option. However, this method was designed for only a small number of possible labels that are generally not well suited for commercial applications. Furthermore, emerging standards are making IPv4 antiquated.
Therefore, a problem with conventional methods of labeling information is scalability. Another problem with conventional methods is efficiency. Still another problem with conventional methods is not being able to use the labeling information to route data. A further problem is that some methods lack commercial applicability and are becoming antiquated.

Method and system for labeling data in a communications system


Antisense compounds, compositions and methods are provided for modulating the expression of connective tissue growth factor. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding connective tissue growth factor. Methods of using these compounds for modulation of connective tissue growth factor expression and for treatment of diseases associated with expression of connective tissue growth factor are provided.

In the course of studies of platelet-derived growth factor (PDGF) isoforms, a novel, cysteine-rich mitogenic peptide secreted by human vascular endothelial cells and related to the v-src-induced immediate early gene product CEF-10 was identified. An anti-PDGF antibody was used to screen a human umbilical vein endothelial cell (HUVEC) expression library, and the gene encoding this novel mitogen was named connective tissue growth factor (CTGF). The connective tissue growth factor protein was shown to stimulate DNA synthesis and promote chemotaxis of fibroblasts (Bradham et al., J. Cell Biol., 1991, 114, 1285-1294).
Connective tissue growth factor (CTGF; also known as ctgrofact, fibroblast inducible secreted protein, fisp-12, NOV2, insulin-like growth factor-binding protein-related protein 2, IGFBP-rP2, IGFBP-8, HBGF-0.8, Hcs24, and ecogenin) is a member of the CCN(CTGF/CYR61/NOV) family of modular proteins, named for the first family members identified, connective tissue growth factor, cysteine-rich (CYR61), and nephroblastoma overexpressed (NOV), but the family also includes the proteins ELM-1 (expressed in low-metastatic cells), WISP-3 (Wnt-1-induced secreted protein), and COP-1 (WISP-2). CCN proteins have been found to be secreted, extracellular matrix-associated proteins that regulate cellular processes such as adhesion, migration, mitogenesis, differentiation, survival, angiogenesis, atherosclerosis, chondrogenesis, wound healing, tumorigenesis, and vascular and fibrotic diseases like scleroderma (Lau and Lam, Exp. Cell Res., 1999, 248, 44-57).
In most cases, a single 2.4-kilobase connective tissue growth factor transcript has been reported in expression studies, although 3.5- and 7-kilobase transcripts have been reported in glioblastoma cells. Connective tissue growth factor is expressed in fibroblasts during normal differentiation processes that involve extracellular matrix (ECM) production and remodeling, such as embryogenesis and uterine decidualization following implantation. Connective tissue growth factor is also frequently overexpressed in fibrotic skin disorders such as systemic sclerosis, localized skin sclerosis, keloids, scar tissue, eosinophilic fasciitis, nodular fasciitis, and Dupuytren's contracture. Connective tissue growth factor mRNA or protein levels are elevated in fibrotic lesions of major organs and tissues including the liver, kidney, lung, cardiovascular system, pancreas, bowel, eye, and gingiva. In mammary, pancreatic and fibrohistiocytic tumors characterized by significant connective tissue involvement, connective tissue growth factor is overexpressed in the stromal compartment. In many cases, connective tissue growth factor expression is linked spatially and temporally to the profibrogenic cytokine transforming growth factor-beta (TGF-β) (Moussad and Brigstock, Mol. Genet. Metab., 2000, 71, 276-292).
Connective tissue growth factor has been mapped to human chromosomal region 6q23.1, proximal to the c-myb gene, and chromosomal abnormalities involving this region have been associated with human tumors, such as Wilms' tumor (Martinerie et al., Oncogene, 1992, 7, 2529-2534).
Tumors with significant fibrotic and vascular components exhibit increased connective tissue growth factor expression, and connective tissue growth factor may be involved in the pathogenesis of pediatric myofibroblastic tumors. Of 12 pediatric tumors examined, all showed moderate to intense connective tissue growth factor expression in tumor cells and/or endothelial cells of the associated vasculature (Kasaragod et al., Pediatr. Dev. Pathol., 2001, 4, 37-45).
Connective tissue growth factor mRNA is also specifically upregulated in malignant human leukemic lymphoblasts from children with acute lymphoblastic leukemia (ALL) (Vorwerk et al., Br. J. Cancer, 2000, 83, 756-760), and both mRNA and protein levels are upregulated by TGF-beta in Hs578T human breast cancer cells in a dose-dependent manner, indicating that connective tissue growth factor is an important neuroendocrine factor and a critical downstream effector of TGF-beta (Yang et al., J. Clin. Endocrinol. Metab., 1998, 83, 2593-2596).
Based on a region of amino acid homology to insulin-like growth factor (IGF) binding proteins (IGFBPs), connective tissue growth factor was hypothesized to regulate cell growth through IGF. Recombinant human connective tissue growth factor was expressed in a baculoviral system and demonstrated to bind to IGF in vitro with low affinity, and thus, connective tissue growth factor was identified as a member of the IGFBP superfamily, and was given the name IGFBP-8 (Kim et al., Proc. Natl. Acad. Sci. U.S.A., 1997, 94, 12981-12986).
The role of connective tissue growth factor has been investigated in a transgenic mouse. Transgenic mice overproducing the connective tissue growth factor protein under control of the collagen promoter could develop and their embryonic and neonatal growth were normal, but they displayed dwarfism within a few months of birth, bone density was decreased compared with normal mice, male testes were much smaller than normal and fertility was affected. These results indicate that the effects of overexpression of connective tissue growth factor affects endochondral ossification, and may also regulate embryonic development of the testes (Nakanishi et al., Biochem. Biophys. Res. Commun., 2001, 281, 678-681).
In cultured 22-day fetal rat calvarial osteoblasts, cortisol stimulates transcription of connective tissue growth factor in a time- and dose-dependent manner, and cyclohexamide did not preclude this effect, indicating that this upregulation was not protein synthesis dependent. Glucocorticoids have complex effects on bone, some due to direct regulation of specific genes expressed by osteoblasts, and some indirect, mediated by locally produced growth factors or their binding proteins. IGFs have important stimulatory effects on bone formation, but glucocorticoids inhibit expression of IGFs. Because connective tissue growth factor binds to IGF, its increased expression could modulate the effect of cortisol on bone (Pereira et al., Am. J. Physiol. Endocrinol. Metab., 2000, 279, E570-576).
Connective tissue growth factor may be regulated not only at the level of transcription, but also by proteolytic degradation, but this varies with cell type. In large vessel bovine endothelial cells, cyclic AMP (cAMP) was found to increase expression of intact connective tissue growth factor protein by inhibiting degradation, whereas TGF-beta stimulated neither mRNA nor protein levels. In microvessel cells, TGF-beta stimulates an increase in connective tissue growth factor mRNA and both TGF-beta and cAMP stimulated proteolytic degradation, and these differences may have an effect on angiogenesis and wound healing (Boes et al., Endocrinology, 1999, 140, 1575-1580).
Purified murine connective tissue growth factor promotes the adhesion of primary human dermal microvascular endothelial cells (HMVECs) and of platelets through integrin receptors αvβ3 and αIIbβ3, respectively, suggesting its involvement in cell adhesion signaling, hemostasis and thrombosis (Babic et al., Mol. Cell. Biol., 1999, 19, 2958-2966; Jedsadayanmata et al., J. Biol. Chem., 1999, 274, 24321-24327). Connective tissue growth factor also stimulates migration of HMVECs in culture through an integrin receptor α3β3− dependent mechanism. Furthermore, connective tissue growth factor can promote survival of HMVECs plated onto laminin but deprived of growth factors, a condition that otherwise induces apoptosis. In vivo, connective tissue growth factor induces neovascularization in rat corneal micropocket implants. Thus, connective tissue growth factor is an angiogenic inducer, and may play a role in adhesion, migration, and survival of endothelial cells during blood vessel growth, perhaps by delivering an antiapoptotic signal via its interaction with integrin αvβ3 (Babic et al., Mol. Cell. Biol., 1999, 19, 2958-2966).
In contrast, connective tissue growth factor may negatively regulate growth of human prostate cells. Connective tissue growth factor expression is upregulated during senescence of normal human prostate epithelial cells (HPECs), and connective tissue growth factor is responsive to growth regulators such as all-trans retinoic acid (atRA), supporting a growth-regulatory role of connective tissue growth factor in prostatic epithelium (Lopez-Bermejo et al., Endocrinology, 2000, 141, 4072-4080).
Expansion of ECM with fibrosis occurs in many tissues as part of the end-organ complications of diabetes (i.e. diabetic nephropathy), and advanced glycosylation end products (AGE) are implicated as one causitive factor in diabetic tissue fibrosis. In addition to being a potent inducer of ECM synthesis and angiogenesis, connective tissue growth factor is increased in tissues from rodent models of diabetes. AGE treatment of primary cultures of CRL-2097 and CRL-1474 nonfetal human dermal fibroblasts resulted in an increase in steady state levels of connective tissue growth factor mRNA as well as protein levels in conditioned medium and cell-associated connective tissue growth factor, while other IGFBP-related proteins were not upregulated by AGE. Thus, AGE upregulates the profibrotic and proangiogenic protein connective tissue growth factor, which may play a role in diabetic complications (Twigg et al., Endocrinology, 2001, 142, 1760-1769).
Diabetic nephropathy is a syndrome occurring in people with diabetes mellitus and characterized by albuminuria, hypertension, and progressive renal insufficiency. Diabetic nephropathy is a common complication in patients with either type 1 or type 2 diabetes mellitus and is recognized to cause severe morbidity and mortality. Structural hallmarks of advanced diabetic nephropathy are glomerulosclerosis and tubulointerstitial fibrosis leading to kidney failure. Current therapies include ACE inhibitors and angiotensin II receptor blockers, both of which are not justified for blanket use among all newly diagnosed patients since only 30-40% will develop progressive renal disease and the long term side effects of these drugs are unknown.
In addition to the need for safe and effective treatments for diabetes is a need for a reliable method to accurately predict, at early stages of disease, which diabetic patients will develop nephropathy and progress to kidney failure. Persistent microalbuminuria is regarded as a predictor of established vascular damage and an indicator of incipient nephropathy. Studies of renal biopsies from patients with type 1 diabetic nephropathy demonstrate an increase in expression of CTGF in renal tissue exhibiting microalbuminuria and nephropathy, relative to normal control tissues (Adler et al., Kidney Int., 2001, 60, 2330-2336), suggesting CTGF is not only a mediator of diabetic nephropathy, but could be used as a marker for the development of disease (Riser et al., Kidney Int., 2003, 64, 451-458).
In a murine lung fibrosis model, an increase in connective tissue growth factor mRNA expression is also induced by bleomycin, a known lung fibrogenic agent (Lasky et al., Am. J. Physiol., 1998, 275, L365-371), as well as in bronchoalveolar lavage cells from patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis, in comparison to healthy nonsmoking control subjects, indicating that connective tissue growth factor is involved in the fibroproliferative response to injury (Allen et al., Am. J. Respir. Cell Mol. Biol., 1999, 21, 693-700). Similarly, in an experimental model of proliferative glomerulonephritis, connective tissue growth factor mRNA expression was strongly increased in extracapillary and mesangial proliferative lesions and in areas of periglomerular fibrosis. The early glomerular connective tissue growth factor overexpression coincided with a striking upregulation of TGF-β proteins, and the kinetics of connective tissue growth factor expression strongly suggest a role in glomerular repair, possibly downstream of TGF-beta in this model of transient renal injury (Ito et al., J. Am. Soc. Nephrol., 2001, 12, 472-484).
Disclosed and claimed in U.S. Pat. No. 5,876,730 is a substantially pure or isolated polypeptide characterized as having an amino acid sequence corresponding to the carboxy terminal amino acids of a connective tissue growth factor (CTGF) protein, wherein the polypeptide has an amino acid sequence beginning at amino acid residue 247 or 248 from the N-terminus of connective tissue growth factor, an isolated polynucleotide sequence encoding the connective tissue growth factor polypeptide, a recombinant expression vector which contains said polynucleotide, a host cell containing said expression vector, and a pharmaceutical composition comprising a therapeutically effective amount of connective tissue growth factor polypeptide in a pharmaceutically acceptable carrier. Antisense oligonucleotides are generally disclosed (Brigstock and Harding, 1999).
Disclosed and claimed in U.S. Pat. Nos. 5,783,187; 5,585,270; 6,232,064; 6,150,101; 6,069,006 and PCT Publication WO 00/35936 are an isolated polynucleotide encoding the connective tissue growth factor polypeptide, expression vectors, host cells stably transformed or transfected with said vectors; an isolated polynucleotide comprising 5′ untranslated regulatory nucleotide sequences isolated from upstream of connective tissue growth factor, wherein said untranslated regulatory nucleotide sequences comprises a transcriptional and translational initiation region and wherein said sequence is a TGF-beta responsive element; an isolated nucleic acid construct comprising a non-coding regulatory sequence isolated upstream from a connective tissue growth factor (CTGF) gene, wherein said non-coding regulatory sequence is operably associated with a nucleic acid sequence which expresses a protein of interest or antisense RNA, wherein said nucleic acid sequence is heterologous to said non-coding sequence; and a fragment of connective tissue growth factor (CTGF) polypeptide having the ability to induce ECM synthesis, collagen synthesis and/or myofibroblast differentiation, comprising an amino acid sequence encoded by at least exon 2 or exon 3 of said polypeptide. Further claimed is a method for identifying a composition which affects TGF-beta-induced connective tissue growth factor expression, and a method of diagnosing a pathological state in a subject suspected of having a pathology selected from the group consisting of fibrotic disease and atherosclerosis, the method comprising obtaining a sample suspected of containing connective tissue growth factor, whereby detecting a difference in the level of connective tissue growth factor in the sample from the subject as compared to the level of connective tissue growth factor in the normal standard sample is diagnostic of a pathology characterized by a cell proliferative disorder associated with connective tissue growth factor in the subject. Further claimed is a method for ameliorating a cell proliferative disorder associated with connective tissue growth factor, comprising administering to a subject having said disorder, at the site of the disorder, a composition comprising a therapeutically effective amount of an antibody or fragment thereof that binds to connective tissue growth factor, wherein said antibody or fragment thereof does not bind to PDGF. Antisense oligonucleotides are generally disclosed (Grotendorst, 2000; Grotendorst and Bradham, 2001; Grotendorst and Bradham, 2000; Grotendorst and Bradham, 1996; Grotendorst and Bradham, 1998; Grotendorst and Bradham, 2000).
Disclosed and claimed in PCT Publication WO 99/66959 is a device for promoting neuronal regeneration, comprising a gene activated matrix comprising a biocompatible matrix and at least one neuronal therapeutic encoding agent having an operably linked promoter device, wherein the neuronal therapeutic encoding agent encodes an inhibitor of neuronal cell growth, and wherein the inhibitor of neuronal cell growth is selected from the group consisting of NFB42, TGF-beta, connective tissue growth factor (CTGF), and macrophage migration inhibitory factor (MIF), and wherein the neuronal therapeutic encoding agent is selected from the group consisting of a nucleic acid molecule, a vector, an antisense nucleic acid molecule and a ribozyme (Baird et al., 1999).
Disclosed and claimed in PCT Publication WO 00/27868 is a substantially pure connective tissue growth factor polypeptide or functional fragments thereof, an isolated polynucleotide sequence encoding said polypeptide, said polynucleotide sequence wherein T can also be U, a nucleic acid sequence complementary to said polynucleotide sequence, and fragments of said sequences that are at least 15 bases in length and that will hybridize to DNA which encodes the amino acid sequence of the connective tissue growth factor protein under moderate to highly stringent conditions. Further claimed is an expression vector including said polynucleotide, a host cell stably transformed with said vector, an antibody that binds to said polypeptide, and a method for producing said polypeptide. Further claimed is a method for inhibiting the expression of connective tissue growth factor in a cell comprising contacting the cell with a polynucleotide which binds to a target nucleic acid in the cell, wherein the polynucleotide inhibits the expression of connective tissue growth factor in the cell, wherein the polynucleotide is an antisense polynucleotide, as well as a kit for the detection of connective tissue growth factor expression comprising a carrier means being compartmentalized to receive one or more containers, comprising at least one container containing at least one antisense oligonucleotide that binds to connective tissue growth factor (Schmidt et al., 2000).
Disclosed and claimed in PCT Publication WO 00/13706 is a method for treating or preventing fibrosis, the method comprising administering to a subject in need an effective amount of an agent that modulates, regulates or inhibits the expression or activity of connective tissue growth factor or fragments thereof, and wherein the agent is an antibody, an antisense oligonucleotide, or a small molecule. The method is directed to treating kidney fibrosis and associated renal disorders, in particular, complications associated with diabetes and hypertension (Riser and Denichili, 2000).
Disclosed and claimed in PCT Publication WO 01/29217 is an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from a group comprising NOV1, NOV2 (connective tissue growth factor), and NOV3, a mature form or variant of an amino acid sequence selected from said group, as well as a nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from said group as well as mature and variant forms or fragments of said polypeptides, and the complement of said nucleic acid molecule. Antisense oligonucleotides are generally disclosed (Prayaga et al., 2001).
There are currently no known therapeutic agents that effectively inhibit the synthesis of connective tissue growth factor and to date, but investigative strategies aimed at modulating connective tissue growth factor function have involved the use of sodium butyrate (NaB), function blocking antibodies and antisense oligonucleotides.
NaB is a dietary micronutrient. Dietary factors are believed to play an important role in both the development and prevention of human cancers, including breast carcinoma. NaB is a major end product of digestion of dietary starch and fiber, and is a potent growth inhibitor that initiates cell differentiation of many cell types in vitro. NaB exerts its biological effects, in part, as a histone deacetylase inhibitor in mammary epithelial cells, induces apoptotic cell death in Hs578T estrogen-non-responsive human breast cancer cells, and can activate different genes involved in cell cycle arrest depending on cell type. NaB specifically upregulates the expression of connective tissue growth factor in a dose-dependent manner, stimulating an increase in both mRNA and protein levels in both cancerous and non-cancerous mammary cells (Tsubaki et al., J. Endocrinol., 2001, 169, 97-110).
TGF-beta has the unique ability to stimulate growth of normal fibroblasts in soft agar, a property of transformed cells. Connective tissue growth factor cannot induce this anchorage-independent growth normal rat kidney (NRK) fibroblasts, but connective tissue growth factor synthesis and action are essential for TGF-β-induced anchorage-independence. Antibodies to connective tissue growth factor specifically blocked TGF-beta-induced anchorage-independent growth, and NRK fibroblasts transformed with a construct expressing the connective tissue growth factor gene in the antisense orientation were not responsive to TGF-beta in the anchorage-independent growth assay (Kothapalli et al., Cell Growth. Differ., 1997, 8, 61-68). These CTGF-antisense expressing NRK cells were also used to show that TGF-beta-stimulated collagen synthesis is mediated by connective tissue growth factor, indicating that connective tissue growth factor may be a useful target for antifibrotic therapies (Duncan et al., Faseb J., 1999, 13, 1774-1786).
The 3′-untranslated region (UTR) of the human connective tissue growth factor cDNA bears several consensus sequences for regulatory elements. When the 3′-UTR was fused downstream of a reporter gene, it was found to act as a strong cis-acting repressive element, and the antisense 3′-UTR had a similar, but stronger effect. (Kubota et al., FEBS Lett., 1999, 450, 84-88). Comparison of the human and mouse connective tissue growth factor 3′-UTRs revealed a conserved small segment of 91 bases. This region was amplified by RT-PCR from NIH3T3 mouse fibroblasts and used to make a chimeric fusion construct for analysis of its repressive effects. The mouse connective tissue growth factor 3′-UTR in either the sense or the antisense orientation had a strong repressive effect on transcription of the reporter gene, indicating an orientation independence of this regulatory element (Kondo et al., Biochem. Biophys. Res. Commun., 2000, 278, 119-124).
A phosphorothioate antisense oligonucleotide, 16 nucleotides in length and targeted to the translation initiation start site, was used to inhibit expression of connective tissue growth factor and suppress proliferation and migration of bovine aorta vascular endothelial cells in culture (Shimo et al., J. Biochem. (Tokyo), 1998, 124, 130-140). This antisense oligonucleotide was also used to show that connective tissue growth factor induces apoptosis in MCF-7 human breast cancer cells and that TGF-beta-induced apoptosis is mediated, in part, by connective tissue growth factor (Hishikawa et al., J. Biol. Chem., 1999, 274, 37461-37466). The same antisense oligonucleotide was also found to inhibit the TGF-beta-mediated activation of caspase 3 and thus to inhibit induction of TGF-beta-mediated apoptosis in human aortic smooth muscle cells (HASC) (Hishikawa et al., Eur. J. Pharmacol., 1999, 385, 287-290). This antisense oligonucleotide was also used to block connective tissue growth factor expression and demonstrate that high blood pressure upregulates expression of connective tissue growth factor in mesangial cells, which in turn enhances ECM protein production and induces apoptosis, contributing to the remodeling of mesangium and ultimately glomerulosclerosis (Hishikawa et al., J. Biol. Chem., 2001, 276, 16797-16803).
Consequently, there remains a long felt need for additional agents capable of effectively inhibiting connective tissue growth factor function.
Antisense technology is emerging as an effective means for reducing the expression of specific gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of connective tissue growth factor expression.
The present invention provides compositions and methods for modulating connective tissue growth factor expression in cells and in vivo.

Antisense modulation of connective tissue growth factor expression


A toilet ramp serving as a movable device for supporting and transporting a toilet bowl once it is lifted off from a floor comprises a body of a rectangular shape having a opening at each of the two opposite sides for inspecting and removing a wax seal underneath the toilet bowl, a circular opening at the top of the ramp for providing access to the wax seal from the openings of the sides, and an adjustable handle on the front side of the ramp.

This invention relates to a method which will allow you to do repairs on said bowls and floor repairs in a matter of placing the said bowl off the floor and out of your way while repairing the plumbing problem. This particular ramp will allow you to clean the bacterial wax seal without tilting the said bowl.
Several modifications and design considerations for the toilet ramp might prove to be of interest to the developer. For instance, consideration might be given to a version that is made of plastic Or fiberglass and wood.
The design parameters for this product are amenable to current production processes and tooling, and the materials specified are commonly available on the commercial level. Due to the toilet ramp very simple components, it should be no problem to produce from any technical standpoint, and existing assembly lines could be easily adapted for its speedy manufacture, well as explore possible variations and modifications to further improve the design of the product.


A method and arrangement for recovering lithium carbonate from a raw material containing lithium, which method comprises pulping (1) the raw material containing lithium in the presence of water and sodium carbonate for producing a slurry containing lithium from the raw material containing lithium. After pulping the lithium-containing slurry is leached (2) for dissolving the lithium in the solution thus producing a solution containing lithium carbonate. After pulping and leaching the method comprises carbonating (3) the solution containing lithium carbonate by using carbon dioxide under atmospheric conditions for producing a solution containing lithium bicarbonate and separating (4) the solids form the solution. The solution containing lithium bicarbonate is purified (5) to produce a purified solution containing lithium bicarbonate, and recovering by crystallizing (6) lithium carbonate from the purified lithium bicarbonate-containing solution.

US 2004/0005267 A1 discloses a method for making low sodium lithium carbonate from lithium containing brine. In the method a mother liquor containing carbonate from a prior precipitation step is added to brine to precipitate magnesium as magnesium carbonate; a solution of CaO and sodium carbonate is added to remove calcium and residual magnesium; lithium carbonate is precipitated from the purified brine by adding soda ash solution; the resultant solution is filtered to obtain solid lithium carbonate; an aqueous slurry of lithium carbonate is prepared in a reactor equipped with an inlet for introducing carbon dioxide gas into said aqueous slurry to form an aqueous lithium bicarbonate solution, said aqueous lithium bicarbonate solution is passed through filter and optionally through ion exchange column for further calcium and magnesium removal; said filtered lithium bicarbonate solution is introduced into a second reactor and adjusted to from 60 to 100° C. to precipitate ultra-pure lithium carbonate.
WO 2011/082444 A1 discloses a process for the production of lithium carbonate, the process comprises: calcining an alpha-spodumene ore or concentrate to produce beta-spodumene, sulphating at elevated temperature, passing the sulphated beta-spodumene to a leach step in which lithium sulphate is leached in water. The pregnant leach solution is passed to a series of impurity removal steps in which iron, alumina, silicates and magnesium are removed, adding sodium carbonate to the product for precipitating calcium, then ion exchanging for removing residual calcium, magnesium and other multivalent cations. The purified product is passed to lithium carbonate precipitation. The publication also discloses passing the precipitated lithium carbonate to a bicarbonate circuit, the bicarbonate circuit comprising digestion with carbon dioxide to produce bicarbonate intermediate and subsequent crystallisation to produce a lithium carbonate product.
Olivier, C. A and Nenninger, E. H, Continuous Process for the production of lithium carbonate, CIM Bulletin, July 1979, disclose a process for soda leaching of spodumene concentrate and carbonating under high pressure.
Galaxy Resources Limited has published a media release in November 2008 relating to preliminary test work to produce battery grade lithium carbonate using a 'Soda Ash' processing technique.


Disclosed is a method for providing services on online geometric correction using, in which information related with GCP (Ground Control Point) used for correcting geometric distortion of an image collected by an aircraft or a satellite are transmitted online through Internet network, thereby allowing a user at a remote place to perform geometric correction or ortho-rectification. In the geometric correction process, the image information related with the GCP is provided but the precise geographic coordinate of the GCP itself is not provided to thereby maintain the secretion of detailed geographic information.

1. Field of the Invention
The present invention relates to a method for providing services on online geometric correction using ground control point (hereinafter referred to as 'GCP') chips, and more particularly, to a method allowing a correction equation for ortho-rectification and geometric correction of an object image to be calculated with hiding a precise geometric coordinate of GCP when online providing services on GCP chip image and supplementary information, which are used for geometric distortion correction of aerial photograph or satellite image, through Internet network in a client/server manner.
2. Description of the Related Art
In general, a conventional technology for performing geometric correction using a GCP chip image has a basic concept of providing entire GCP-relating information as one data unit such as a GCP chip image, a precise geographic coordinate, related supplementary information and the like listed in a user computer or a GCP server. Additionally, the conventional technology uses the provided GCP information to search a corresponding point of the GCP at an object image such that a correction formula necessary for geometric correction or ortho-rectification is calculated, and the correction formula is used to correct the object image.
Similarly, as a technology for building the GCP information as the GCP chip image, there are "A STUDY OF MANAGEMENT SYSTEM OF THE GROUND CONTROL POINT DATABASE FOR ROCSAT-2 REMOTE SENSING IMAGES" disclosed in "Proceedings of ACRS 2002" on November 2002, "AUTOMATION OF PRECISE ORTHO-RECTIFICATION OF LANDSAT TM-IMAGES" disclosed in "Proceedings of the 41st SICE Annual Conference" in 2002, "AUTOMATIC SATELLITE IMAGE REGISTRATION BY COMBINATION OF MATCHING AND RAMDOM SAMPLE CONSENSUS" disclosed in "IEEE Transactions on Geoscience and Remote Sensing" on May 2003, and the like.
Further, as a technology for pursuing a convenience in correcting the object image by using the GCP information, there are Korean Patent Application No.: 1019970065942 entitled "SEMIAUTOMATIC ON-LINE GEOGRAPHIC CORRECTION METHOD" filed on 4 Dec. 1997, Korean Patent Application No.: 1020000027857 entitled "MAP MANUFACTURING METHOD USING IMAGE DATA OF SATELLITE" filed on 23rd MAY 2000, Korean Patent Application No.: 1020010067944 entitled "PARAMETER CONVERTING APPARATUS AND METHOD FOR IMAGE MATCHING" filed on 1st Nov. 2001, Korean Patent Application No.: 1020010084871 entitle "SENSOR MODELING METHOD OF SATELLITE IMAGE" filed on 26 Dec. 2001 and the like.
Further, as a technology for serving geographic information through an internet network, there are Korean Patent Application No.: 1020000028182 entitled "METHOD FOR SERVING GEOGRAPHIC INFORMATION USING INTERNET NETWORK" filed on 24th May 2000 and the like.
Similarly, when one looks into a technology disclosed in a prior art or treatise, a conventional method is a method for building and serving the GCP-relating information as a database to only a limited user allowed to access precise coordinate information of the GCP in a network environment separated from an external, or for allowing a GCP database to be retained within a user's computer listing the object image. In case that the precise geographic coordinate of the GCP cannot be opened to the public due to limitations by security regulation for regulating limitations to opening of geographic information to the public, it is impossible for many and unspecified persons to share the GCP-relating information. Accordingly, the conventional method continues to have a drawback in that all users should build respective GCP databases adaptive to purposes of themselves. Further, the conventional method has a drawback in that it is impossible for the GCP relating information to be opened to the public to share and reuse information.

Method for providing services on online geometric correction using GCP chips

Electronics and Telecommunications Research Institute


Methods, systems, and articles of manufacture are disclosed for creating posed models. In various embodiments, deformations resulting from posing a model can be represented in a set of training poses. The sets of training poses for the model and a desired target pose (e.g., a simulated or sculpted pose) can be used to create a final pose for the model. Arbitrary deformer activation weights can be determined by projecting a target pose onto the set of training poses. The deformer activation weights can be applied to one or more deformers to approximate the desired pose.

This disclosure relates to computer-generated imagery (CGI) and computer-aided animation. More specifically, this disclosure relates to optimizing the performance of arbitrary deformers such that they can be executed in a reasonable time without consuming undue computing resources in CGI and computer-aided animation.
With the wide-spread availability of computers, computer graphics artists and animators can rely upon computers to assist in production process for creating animations and computer-generated imagery (CGI). This may include using computers to have physical models be represented by virtual models in computer memory. Typically, two-dimensional (2D) or three-dimensional (3D) computer-aided animation combines 2D/3D models of objects and programmed movement of one or more of the models. In 3D computer animation, the first step is typically the object modeling process. Objects can be sculpted much like real clay or plaster, working from general forms to specific details, for example, with various sculpting tools. Models may then be constructed, for example, out of geometrical vertices, faces, and edges in a 3D coordinate system to represent the objects. These virtual models can then be manipulated using computers to, for example, simulate physics, design aesthetic actions such as poses or other deformations, crate lighting, coloring and paint, or the like, of characters or other elements of a computer animation display.
Pixar is one of the pioneering companies in the computer-generated imagery (CGI) and computer-aided animation industry. Pixar is more widely known as Pixar Animation Studios, the creators of animated features such as "Toy Story" (1995) and "Toy Story 2" (1999), "A Bugs Life" (1998), "Monsters, Inc." (2001), "Finding Nemo" (2003), "The Incredibles" (2004), "Cars" (2006), "Ratatouille" (2007), and others. In addition to creating animated features, Pixar develops computing platforms and tools specially designed for computer-aided animation and CGI. One such example is now known as PhotoRealistic RenderMan, or PRMan for short. PRMan is a photorealistic RenderMan-compliant rendering software system based on the RenderMan Interface Specification (RISpec) which is Pixar's technical specification for a standard communications protocol (or interface) between 3D computer graphics programs and rendering programs. PRMan is produced by Pixar and used to render their in-house 3D animated movie productions. It is also available as a commercial product licensed to third parties, sold as part of a bundle called RenderMan Pro Server, a RenderMan-compliant rendering software system developed by Pixar based on their own interface specification. Other examples include tools and plug-ins for programs such as the AUTODESK MAYA high-end 3D computer graphics software package from AutoDesk, Inc. of San Rafael, Calif.
One core functional aspect of PRMan can include the use of a "rendering engine" to convert geometric and/or mathematical descriptions of objects into images. This process is known in the industry as "rendering." For movies, other animated features, shorts, and special effects, a user (e.g., a skilled computer graphics artist) can specify the geometric or mathematical description of objects to be used in the rendered image or animation sequence, such as characters, props, background, or the like. In some instances, the geometric description of the objects may include a number of animation control variables (avars) and values for the avars. An animator may also pose the objects within the image or sequence and specify motions and positions of the objects over time to create an animation.
As such, the production of CGI and computer-aided animation may involve the extensive use of various computer graphics techniques to produce a visually appealing image from the geometric description of an object that may be used to convey an essential element of a story or provide a desired special effect. One of the challenges in creating these visually appealing images is the can be the balancing of a desire for a highly-detailed image of a character or other object with the practical issues involved in allocating the resources (both human and computational) required to produce those visually appealing images.
A realistic looking character model is often extremely complex, having millions of surface elements and hundreds or thousands of attributes. Due to the complexity involved with animating such models, animation tools often rely on armatures and animation variables to define character animation. For example, an armature may be a "stick figure" representing a character's pose, or bodily position. By moving armature segments, which are the "sticks" of the "stick figure," an armature can be manipulated into a desired pose. As an armature is posed by an animator, animation tools may modify an associated character model so that the bodily attitude of a character roughly mirrors that of the armature.
Animation variables can be another way of defining a character animation of a complex character model. Animation variables can include parameters for functions that modify the appearance of a character model. Animation variables and their associated functions can be used to abstract complicated modifications to a character model to a relatively simple control. Animation variables and their associated functions may manipulate armature segments, thereby altering the appearance of a character model indirectly, or manipulate a character model directly, bypassing the armature.
Functions associated with animation variables, referred to as model components, can be used to create a variety of realistic and artistic effects. For example, model components can be used to create layers of bones, muscle, and fat beneath the surface of a character model, so that the surface or skin of a character model deforms either realistically or as desired as it is posed. Model components can also be used to simulate the movement of non-rigid features, such as hair and cloth. In addition to replicating specific physical phenomena, model components can be used to manipulate a character model according to an algorithm or procedure, such as sculpted shapes, metaballs, and physics simulations.
Model components can be extremely complex and therefore time-consuming to execute. To create artistically effective character animation, an animator may often create a rough version of a scene and then repeatedly fine-tune a character animation to create desired drama and expression of the final scene. The time needed to execute model components as animators pose and repose character models can hinder the efficiency of the animator during this artistic process. In one worst case, an animator may be forced to use simplified "stand-in" character models to create the initial animation, and then wait to see the resulting animation with the final character model. In this situation, the animator is essentially working blind and can only guess at the final result. Conversely, the additional computing resources needed to process model components in a reasonable time, if even possible, substantially increases the costs of creating animation.
Accordingly, what is desired is to solve one or more of the problems relating to optimizing the performance of model components such that they can be executed in a reasonable time without consuming undue computing resources, some of which may be discussed herein. Additionally, what is desired is to reduce some of the drawbacks relating to optimize any type of model component, regardless of its function or complexity, some of which may be discussed herein.


According to an aspect of the present invention, there is provided a sintered electroconductive oxide containing a perovskite phase of perovskite-type crystal structure represented by the composition formula: M1aM2bM3cAldCreOf where M1 is at least one of elements of group 3A other than La; M2 is at least one of elements of group 2A; M3 is at least one of elements of groups 4A, 5A, 6A, 7A and 8 other than Cr; and a, b, c, d, e and f satisfy the following conditional expressions:0.600≦a≦1.000;0≦b≦0.400;0.150≦c<0.600;0.400≦d≦0.800;0<e≦0.050;0<e/(c+e)≧0.18; and2.80≦f≦3.30.With the use of this conductive oxide sintered body, it becomes possible to carry out proper temperature measurements over the temperature range from a low temperature of −40° C. to a high temperature of 900° C. or higher.

Sintered electroconductive oxides having electrical conductivity and changing in resistance (specific resistance) with changes in temperature, thermistor elements using the sintered electroconductive oxides and temperature sensors using the thermistor elements are conventionally known.
Patent Document 1 discloses a sintered material for a thermistor element, which consists of Sr, Y, Mn, Al, Fe and O and has a crystal phase of a perovskite type oxide, a crystal phase of a garnet type oxide and a crystal phase of at least either a Sr—Al oxide or a Sr—Fe oxide, to enable temperature measurements over the range of 300° C. to 1000° C.
Patent Document 2 discloses a sintered electroconductive oxide material for a thermistor element, which has a composition of M1aM2bM3cM4dO3 where a, b, c and d satisfy given conditional expressions, to show a suitable specific resistance over the range of room temperature to 1000° C.
Patent Document 3 discloses a thermistor element formed with a mixed sintered material (MM′)O3.AOx of a composite perovskite type oxide (MM′)O3 and a metal oxide AOx.
Patent Document 1: Japanese Laid-Open Patent Publication No. 2004-221519
Patent Document 2: Japanese Laid-Open Patent Publication No. 2003-183075
Patent Document 3: Japanese Laid-Open Patent Publication No. 2001-143907
One use of a thermistor element is as a temperature sensor designed to detect the temperature of an exhaust gas from an automotive engine such as internal combustion engine. For protection of DPF and NOx reduction catalyst, there has recently been a demand for the thermistor element to enable temperature measurements in a high temperature range of around 900° C. There has also been a demand for the thermistor element to enable temperature measurements in a low temperature range e.g. under an engine starting or key-on state for detection of temperature sensor failure (wire break) in OBD systems (On-Board Diagnostic systems). It is especially demanded that the thermistor element be capable of carrying out temperature measurements even at a temperature of −40° C. since there may be a case where the engine starting temperature becomes below the freezing point in cold climates.
However, each of the sintered materials of Patent Documents 1 and 2 have a temperature gradient value (B-value) of about 4000 K or higher so as to show a suitable resistance change over the range of room temperature or not lower than 300° C. to 1000° C. (See e.g. TABLE 6 of Patent Document 2.) The thermistor elements using these sintered materials have a large temperature gradient value (B-value) and become too high in resistance at a low temperature of −40° C. This results in difficulty determining the resistance values of the thermistor elements and enabling temperature measurements.
The thermistor element of Patent Document 3 shows a resistance of 110Ω to 100 kΩ in the temperature range of room temperature to 1000° C. so that the temperature gradient coefficient β (corresponding to B-value) of the thermistor element can be maintained within the suitable range of 2200 to 2480 K. (See e.g. TABLE 1 of Patent Document 2.) No consideration is however given to the relationship between the metal constituent M or M′ of the composite perovskite type oxide (MM′)O3 and the metal constituent A of the metal oxide AOx. Depending on the combination of the metal element M or M′ and the metal element A and the compounding ratio of these constituents, there arises a possibility that the composite perovskite type oxide (MM′)O3 and the metal oxide AOx react with each other to form an unexpected by-product or that the metal element A replaces the constituent element of the composite perovskite type oxide (MM′)O3 to cause a change in composition. This deteriorates various characteristics of the thermistor element (sintered material) such as high-temperature composition stability (heat resistance).

Sintered electroconductive oxide, thermister element using sintered electroconductive oxide, and temperature sensor using thermister element


A crystalline form of an alkyl benzene sulfonyl urea compound that is useful as an oral antidiabetics is disclosed. Specifically, the compound is a hydrochloride salt of N-(3-(2-(4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide of the following formula I. A pharmaceutical composition containing the compound is also disclosed:

The compound of Formula 1 below, whose compound name is N-(3-(2-(4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide is disclosed in PCT application WO 2011/162515. The compound has a selective inhibitory activity for a mutant epidermal growth factor receptor tyrosine kinase.

Additionally, the above reference discloses the method for preparing the compound of Formula 1.
However, the compound of Formula 1 prepared in the above cited reference was prepared as an amorphous solid, which is a form generally less suitable for large-scale production of pharmaceutical drugs. In addition, the rather poor solubility of the compound of Formula 1 obtainable by the method in the above cited reference left room for improvement.
Accordingly, there is a need for suitable solid forms, preferably crystalline forms, of the compound of Formula 1 that can fully comply with the strict requirements and details thereof regarding pharmaceutical solid forms and formulations while having improved water solubility.
One sort of solid forms are salt forms of active ingredients, e.g. acid addition salts of basic active ingredients obtainable by reaction with acids. It is a challenging endeavor to identify suitable salt forms with appropriate solid state properties as there are many salt formers and potentially several polymorphs for each salt form. The present inventors have discovered that hydrochloride salts of the compound of Formula 1, especially the crystalline forms thereof, have excellent overall physicochemical characteristics required pharmaceutically including, for example, enabling long-term stable maintenance without requiring particular storage conditions, etc., while having excellent water-solubility, thereby completing the present invention.

Crystalline forms of hydrochloride salts of thienopyrimidine compound


A method for testing a partially fabricated wafer is provided that comprises the following steps: providing a plurality of selectable devices under test (DUT) overlying a substrate of the wafer; biasing a second structure located in proximity to the DUT to have a first electrical state such that a first equivalent test structure is formed; determining a first parasitic parameter associated with the first equivalent test structure by applying a signal to the DUT while the second structure is in the first electrical state and measuring a response that is indicative of the first parameter; biasing the second structure to have a second electrical state such that a second equivalent test structure is formed; and determining a second parasitic parameter associated with the second equivalent test structure by applying a signal to the DUT while the second structure is in the second electrical state and measuring a response that is indicative of the second parameter.

A critical part of semiconductor manufacturing and design is the testing of integrated circuits. Before the functionality tests at the end of processing, additional testing for process monitoring is also useful. Testing for process monitoring uses special test structures which are not part of the integrated circuit's functionality. Process monitoring helps to detect problems that may cause reliability problems in the field, helps to optimize the process for maximum yield, and helps to catch any process deviations before too much work-in-process is wasted.
Typical electrical test structures for in-process testing are long series-connected chains of similar elements (to test for excessive resistance or open circuits). The test structure will also include two or more "probe pads," which are flat metal surface that electrical connection can be made to them in the test lab. These test structures are manufactured at the same time as the functional circuitry, using the same process steps, but are specially designed to test particular process parameters. (For example, to test for specific contact resistance a chain of thousands of series-connected contacts might be created.) A large variety of test structures are used by process engineers to test various process stages and device portions.
A "wafer" is a flat disk of semiconductor material on which integrated circuits are made by micro-fabrication techniques. After fabrication is complete, the wafer will be separated into rectangular "dice," each of which is the electronics portion of one integrated circuit. The dice will be packaged to provide the end-product integrated circuits. Typically one wafer will provide dozens or hundreds of dice.
When the dice are separated, some of the wafer surface between them is wasted. This space is known as "scribelines," since the dice were formerly separated by scribing and fracturing; now that diamond sawing has replaced scribing, these spaces are also known as "saw streets."
Test structures are placed within the scribelines of the wafer (and in other places), typically once or more per photolithographic field. Typical scribeline test structures are individually connected to corresponding probe pads, also located in the scribelines. Since the area within the scribelines is densely occupied, the size and number of probe pads is critical. However, probe pad size has not scaled as fast as other process steps, and the space available within the scribelines is very limited. Placing multiple test structures and probe pads for those test structures within this limited area becomes difficult in many processes, and limits the testing of the wafer fabrication process. Limits to the testing capability lead to less reliable integrated circuits.
Scribeline widths are typically less than a tenth of a millimeter. Probe pads are typically made just small enough to fit within the scribeline. These dimensions can be expected to change over time, in dependence on wafer fabrication and separation technologies; but the key point is that each probe pad occupies a very significant fraction of the limited available scribeline area.
Since each probe pad nearly fills the width of a scribeline, the layout of test structures in the scribelines is often somewhat one-dimensional. That is, a test structure in the scribelines can be allowed to take up nearly the entire width of the scribeline, and extended along the scribeline as far as necessary.
Some space in the corners of the dice themselves is typically also allocated for test patterns, but again the available area is limited. Typically several to several tens of test structures can fit into each corner of a die.
Some space for test structures is also available along the edge of the wafer, where the grid of square or rectangular dice meets the unusable width of the rounded edge. While these spaces are relatively large, they are far from the important central areas of the wafer. Thus test structures in the edge-of-wafer corners cannot provide sufficiently close monitoring of process variation, including spatial variation across the wafer.
One basic tool for process monitoring is the use of pilot wafers. Some manufacturers will start several pilot or dummy wafers for each wafer that will produce actual chips. While some use of pilot wafers will always be common (e.g. at the head of each lot), every pilot wafer start takes the place of a wafer full of salable chips. Thus to the extent that sufficient process monitoring can be done using on-chip test and monitoring structures, this is greatly preferable to use of pilot wafers. Dummy wafers, on the other hand, are used to ensure that equipment has stabilized, e.g. when a bulk furnace is being ramped up or when a wet processing station has been refilled. Use of such dummy wafers is not motivated by process monitoring needs, and hence would not appear to be subject to trade-off against on-wafer test structures.
U.S. Pat. publication 20020047724, entitled "Multi-state test structures and methods," describes a selection capability that radically increases the number of test structures per probe pad. By adding a test selector to the test structure, multiple test structures are multiplexed to one (or more) probe pads. Selection of which test structure is to be accessed from a given probe pad is preferably performed entirely by control of the voltage applied across the probe pads. In one class of embodiments, the applied voltage directly determines which test structure will be accessed. In another class of embodiments, modulation of the applied voltage controls sequential logic that selects one of multiple test structures for access.
In the past, circuit delay has been due mostly to transistors. Today, the dominant source of delay in circuits such as ASICs and microprocessors is metal interconnect. FIG. 1 is a schematic diagram of a prior art charge-based capacitance measurement (CBCM) structure for measuring parasitic capacitance. A paper entitled "An On-Chip, Attofarad Interconnect Charge-Based Capacitance Measurement (CBCM) Technique," Proc. of IEDM 1996, pp. 69–72, discloses an improved test structure for performing CBCM that included an on-chip signal generator and an entirely new measurement scheme as well. The resolution limit of the methodology is estimated to be 0.01 fF, hence making it more than adequate for characterizing parasitic interconnect capacitances.
In this paper, a test structure is disclosed that comprises a pair of NMOS and PMOS transistors connected in a "pseudo" inverter configuration two form two inverters 100, 101. Inverter 100 is a reference inverter used to achieve the highest resolution. Inverter 100 is identical to inverter 101 in every manner except that it does not include the target capacitance to be characterized. Inverter 101 is connected to the target device that is to be measured. For example, in FIG. 1 the target device consists of level 2 metal line 111 and level 1 metal line 112 that form an intersection at 110. This structure is used to measure the resulting interconnect capacitance between the two lines. The reference inverter is connected to metal 1 line 113 that is the same configuration as line 112, but does not contain the metal 1 to metal 2 overlap capacitance that is to be measured.
FIG. 2 is a timing diagram illustrating non-overlapping clock signals used by the prior art CBCM structure of FIG. 1. The V1 and V2 signals of FIG. 1 consist of two non-overlapping signals shown in FIG. 2. These signals can be either generated off-chip or on chip. The purpose of these non-overlapping waveforms is to ensure that only one of the two transistors in each test structure inverter is conducting current at any given time. Thus, short-circuit current from Vdd to ground is eliminated. When the PMOS transistor turns on, it will draw charge from Vdd to charge up the target interconnect capacitance.
This amount of charge will then be subsequently discharged through the NMOS transistor into ground. An ammeter can be placed at the source of the PMOSFET (or, alternatively at the source of the NMOSFET) to measure this charging current. The actual waveform of this charging current is of no consequence; only its DC or average current value needs to be measured. DC current can be easily obtained from any modern current meter. The difference between the two DC current values in FIG. 1 is used to extract the target interconnect capacitance as shown by equations 1 and 2 below.I−Iref=Inet  (1)C=Inet/Vdd*F  (2)
CBCM can be used in conjunction with simulation at early process development stages to provide designers with accurate parasitic interconnect capacitances; including metal to substrate, interwire, and interlayer capacitances, as discussed in a paper entitled "Investigation of Interconnect Capacitance using Charge-Based Capacitance Measurement (CBCM) Technique and 3-Dimensional Simulation", IEEE JSSC, pp. 449–453, March 1998. However, this paper teaches that several test structures must be utilized to decouple vertical and horizontal capacitive components from the total capacitance.
Therefore, there is still a need in the art for a way to increase the efficiency of space usage for test structures within the scribelines of an integrated circuit process.

This patent is subject to a terminal disclaimer.

Method for capacitance measurement in silicon


Methods for diagnosing and treating prostate cancer are disclosed. In practicing the method, a subject's body-fluid sample is assayed for GPC3 protein, and the GPC3 level observed is used in determining whether the subject has an elevated GPC3 level associated with prostate cancer. Patients with such elevated levels may be treated, in accordance with the invention, with a variety of GPC3-related immunotherapy agents.

Prostate cancer is the most common malignant cancer in North American men. It is estimated that approximately 200,000 new cases and 31,500 prostate cancer-related deaths will occur in the United States annually. Prostate cancer is now the second leading cause of cancer death in men, exceeded only by lung cancer. It accounts for 29% of all male cancers and 11% of male cancer-related deaths.
Currently, the FDA has approved serum PSA (prostate-specific antigen) for use as a prostate cancer screening laboratory test. Like many serum tumor markers, PSA is produced by both normal and cancerous glands. In men with prostate cancer, the serum levels can be elevated with both localized and advanced or disseminated disease. PSA levels are generally proportional to the volume of the cancer. Because there is a significant overlap between PSA levels found in cancer and benign prostatic hyperplasia, it is important to obtain sequential levels in low or borderline elevated values.
The introduction of free PSA (fPSA) testing has introduced a greater level of specificity in identifying early prostate cancer. In 1998, the FDA approved fPSA testing as a diagnostic aid for men with total PSA values between 4.0-10.0 ng/mL. This has often been the diagnostic gray zone for total PSA testing and fPSA may aid in the stratification. In general, at any free PSA level, the more enlarged the prostate, the more likely the prostate may be cancerous. However, these tests remain qualitative at best, and more reliable types of detection, and means for staging the cancer treatment, are needed.
Prostate cancer, like other forms of cancer, is caused by genetic aberrations, i.e., mutations. In the mutant cells the normal balance between the factors that promote and restrain growth is disrupted, and as a result, these mutant cells proliferate continuously—the hallmark of tumor cells. Mutations can arise spontaneously or by external factors such as chemical mutagens, radiation, or viral integration, which inserts extra-genomic DNA that may or may not contain an oncogene. A cellular gene can be modified by point mutation, insertion and frame shift (including truncation), (functional) deletion (including silencing), or translocation, which sometimes can result in gene fusion. In this way protooncogenes can become oncogenes, which promote proliferation, and tumor suppressor genes can become inactivated, also inducing tumor growth. Any combination of the above-mentioned changes in DNA can contribute to tumor formation. The consequences of these changes may or may not be held in check by the immune system (immune surveillance).
One protein whose expression has been implicated in certain cancers is the Glypican 3 protein, or GPC3, a heparin sulfate proteoglycan anchored to the cell membrane via glycosylphosphatidylinositol (1). The protein has a molecular weight of 65.6 kDa and the polypeptide chain has 580 amino acid residues. The heparin sulfate chain of the proteoglycans interacts with heparin-binding growth factors and thus serves as a co-receptor in cell signaling (2), although GPC3 might bind also in a different way (3). In embryonic development, GPC3 modulates BMP and EGF-mediated effects during renal branching morphogenesis (4). It also controls cellular responses to BMP4 in limb patterning and skeletal development (5). Except for weak expression in bronchiolar epithelial cells, GPC3 is not expressed in systemic organs (6). Because its expression is decreased in lung adenocarcinoma (7, 8), human gastric cancer (9), ovarian cancer cell lines (10, 11), mesotheliomas (10, 11), and breast tumors (12), GPC3 may function as a tumor suppressor. But because its mRNA and protein expression is increased in hepatocellular carcinomas (13-15), colorectal malignancies (16), and embryonal tumors (17) as compared to normal tissue, GPC3 is also considered an onco(fetal) protein. For hepatocarcinoma, GPC3 is a promising diagnostic marker (6). It is also known that in these cancers, GPC3 modulates FGF2 and BMP-7 signaling (18), and promotes growth by stimulating canonical Wnt signaling (3).
In more than 80% of melanoma and melanocytic nevus, both GPC3 mRNA and protein are expressed (19). Interestingly, GPC3 protein is found in sera from 40% of melanoma patients but not in sera from subjects with large congenital melanocytic nevus and from healthy donors. GPC3 expression disappeared in sera from one third of the patients after surgical removal of the melanoma (19).
Heretofore, there has been no demonstrated link between changes in GPC3 levels and prostate cancer. Such a link could have a number of important diagnostic and therapeutic applications. In accordance with the present invention, it has now been discovered that (i) GPC3 levels increase significantly in prostate cancer cells, and (ii) this increase can be measured the ductile fluid and blood-fluid sample of patients.

Methods for screening for prostate cancer


The present invention relates to an electrolyte additive comprising a salt of an anion with K+ or Na+, the anion being derived from a nitrogen atom-containing compound, and a lithium-containing compound for forming a coating film. In addition, the present invention provides a lithium salt, a non-aqueous organic solvent, and the electrolyte additive. The present invention relates to a lithium secondary battery which includes a cathode employing a cathode active material, an anode employing an anode active material, a separator interposed between the cathode and the anode, and the non-aqueous electrolyte.

In accordance with the recent development of the information and communication industry, electronic devices are becoming smaller, lighter, thinner, and more portable. As a result, there is a growing demand for high energy densification of batteries used as power sources for these electronic devices. As lithium secondary batteries are best able to meet such demand, research thereon is being actively conducted.
Lithium secondary batteries include a cathode, an anode, an electrolyte providing a pathway for the movement of lithium ions between the cathode and the anode, and a separator. Electrical energy is generated by oxidation and reduction reactions when lithium ions are intercalated and de-intercalated at the cathode and anode.
Lithium secondary batteries have an average discharge voltage of about 3.6 to 3.7 V, presenting an advantage in that the discharge voltage thereof is higher than other alkaline batteries and nickel-cadmium batteries. In order to achieve such a high driving voltage, an electrolyte composition which is electrochemically stable at a charge-discharge voltage range of 0 to 4.2V is required.
At the time of initial charging of a lithium secondary battery, lithium ions generated from a cathode active material such as a lithium metal oxide, or the like, migrate to an anode active material such as a graphite-based material, or the like, and are intercalated between layers of the anode active material. Herein, since lithium is highly reactive, it reacts with an electrolyte and the carbon composing the anode active material on the surface of the anode active material (such as a graphite-based material), thereby resulting in the production of a compound such as Li2CO3, LiO2, or LiOH. These compounds form a solid electrolyte interface (SEI) film on the surface of the anode active material.
The SEI film acts as an ion tunnel and allows only lithium ions to pass through. Since the SEI film has the effect of an ion tunnel, an organic solvent molecule with a high molecular weight moving together with the lithium ions in the electrolyte is inserted between the layers of the anode active material to prevent the anode structure from being destroyed. Therefore, it is possible to prevent contact between the electrolyte and the anode active material, and thus degradation of the electrolyte does not occur and the amount of lithium ions in the electrolyte is reversibly maintained, thereby enabling the charge/discharge to be maintained stably.
In the related art, it is difficult to expect to achieve an improvement in the lifetime characteristics of lithium secondary batteries since an uneven SEI film is formed in the case of employing conventional electrolytes or electrolyte additives. Further, even when the electrolyte includes an electrolyte additive, if the amount of the electrolyte additive is not able to be adjusted to a required amount, problems have been encountered in which the electrolyte additive causes degradation of a cathode surface or an oxidation reaction of the electrolyte during high temperature or high voltage reactions, ultimately resulting in an increase in the irreversible capacity loss of the secondary battery, with deterioration of the lifetime characteristics.
Patent Literature: KR 2009-0026203

Electrolyte additive and lithium secondary battery comprising the same


A method and system is provided that allows a well-behaved program to execute more quickly than dynamically typed programming languages did in the past, thereby allowing a the dynamically typed language to be competitive with static declarative programming languages. A method includes converting lines of source code representing functions to byte-codes representing functions, selecting a subsequence of the byte-codes based on the byte-codes and the dynamic run-time properties of program variables, generating processor instructions in a compiler for the subsequence, and interpreting the byte-codes not contained in the subsequence.

High-level programming languages typically process English-like programming statements in one of two ways. The first way is known as compilation. Compilers perform a translation of the high-level language into machine language before the program is run. The result of this process is a file of machine code that is directly executable by the machine.
A second way is known as interpretation. Interpreted software languages are not translated into a form that is directly readable by the computer but are, instead, processed as data by an interpreter.
Compiled languages are usually faster than interpreted languages, because an interpreter or a virtual machine must typically process each high-level program statement each time it is executed, while a compiler need only translate each program statement once, after which the computer may execute the resulting code directly. Interpreted languages, however, are often easier to use and more powerful than compiled languages and so are often used to write smaller programs in which speed of program execution is not as important as speed and ease of writing the program.
In any programming language, whether compiled or interpreted, a variable's type denotes what kind of values it contains. Example variable types are integer, floating point, and text string. When a variable is static, it means the type is fixed or bound at compile time, and cannot thereafter be changed. When a variable is dynamic, it means that the type is not fixed or bound until run time, and therefore can change repeatedly during the course of program execution. Thus, dynamic typing refers to the property that a variable can adopt a type and change that type according to run-time demands.
In programming, static typing often allows better error detection, more work at compile time and hence faster execution times, while dynamic typing often allows greater flexibility, and easier to write (for example, no declaration statements) programs.


A semiconductor module may include a system board including a top surface and a bottom surface, a module substrate provided on the top surface of the system board, a system semiconductor package mounted on the module substrate, and first and second power management semiconductor packages mounted on the module substrate. The first and second power management semiconductor packages may be spaced apart from each other in a first direction, which is parallel to a top surface of the module substrate, with the system semiconductor package interposed therebetween.

Example embodiments relate to a semiconductor module, and in particular, to a semiconductor module with a power management integrated circuit (PMIC).
A semiconductor package is configured to allow a semiconductor chip to be easily used as a part of an electronic product. The semiconductor package may include a printed circuit board (PCB) and a semiconductor chip, which is mounted on the PCB and is electrically connected to the PCB using bonding wires or bumps. Conventionally, a single power management chip may supply electric power to the semiconductor chip via the PCB.
As the operation speed and capacity of the semiconductor package increase, the power consumption of the semiconductor package may increase. Accordingly, it is important to stably supply an electric power to the semiconductor package.

Semiconductor module including multiple power management semiconductor packages


A system for delivering targeted content based on user behavior stores multiple behavior change models, generates a user record containing information regarding a user, selects a behavior change model from the multiple stored models based on the information in the user record, and delivers to the user targeted content based on the selected behavior change model, the targeted content being adapted to influence the user to change behavior according to the selected behavior change model.

Publishers face several key challenges in order to compete in today's digital environment. Users, advertisers, sponsors and content licensors require publishers to be able to deliver targeted information across multiple digital channels. In order to effectively serve users of its content, a publisher must be able to deliver the right content to the right audience at the right time. Content targeting is of value because it improves relevancy, saves time and reduces the effort required to deliver content to users. There is significant business value to publishers who develop the capability of delivering highly targeted content to a targeted audience and influence behavior.
Existing content databases from publishers have a legacy established over many years. Articles can be lengthy, consisting of 1000 or more words. Often the content has become outdated. It is a significant and expensive undertaking for a publisher to update large legacy content databases or change its data structure. Cost and effort considerations create significant barriers for publishers to adapt their legacy content to a rapidly changing and evolving digital world. To remain competitive publishers need to update and adapt content, as well as create new content types for multiple media channels such as web, mobile or social media. They must also be able to apply content targeting and behavior change models to enhance the user experience and create new business models.
To deliver a more robust digital experience that maximizes content value, publishers need to create more comprehensive and flexible content structures. Futhermore, publishers must deliver targeted content based on user behaviors, predictive behavior modeling, readiness to change mind-set and user profiles to maximize the value of content and the impact it can have.
To use a health example, a page of general health information is of low value since it is not targeted to any particular disease state. A page of content related to a specific disease (e.g. diabetes) is of medium value since it now targets a patient with diabetes. Going much further in the targeting and profiling chain, a page of content specific to a patient with diabetes, who is female, is taking medication and is ready to make a lifestyle change is of extremely high value. Moreover, the version of diabetes content delivered to a person who is ready to make a lifestyle change should be different than the diabetes content delivered to a diabetes patient who is not ready to make a lifestyle change. Publishers face many challenges to efficiently provide this level of content targeting and customization beyond the subject matter. They simply deliver diabetes content and do not consider more detailed targeting and behavior parameters. It is this additional detailed targeting around behavior models and more defined user profiles that will create a more valuable user experience and increase the value of a publisher's content.
In order to manage the complex task of organizing content databases, publishers will often use a content management system (CMS) or similar publishing system. CMS's can be effective in organizing content articles as documents. Each document, or content article, is generally stored as single block of text. Any attempt to insert targeted messages or advertisements into the editorial flow in the body of an article is done in a very clumsy manner. This creates a disconnect between the original article flow and the inserted element (these "insertions" are often done in the margins outside the boundaries of the text article or as advertisement boxes that break up an article flow). Within traditional publishing systems content articles, or documents, are tagged according to a subject matter or contextually organized based on key words within the document. In some cases publishers may employ semantic targeting of content, which is looking closer at the meaning and sense of the words in an article rather than just using key-words alone. Whether using subject, contextual or semantic methods, publishers can still only deliver associated content (or advertisements) based on a particular subject matter, key word or combination of key words. They do not provide content based on a detailed user behavior modeling or profiles. Since publishers using traditional content management systems store articles as single blocks of text they do not segment an article into components, or insert component content into the body of a text article. This approach diminishes the potential value of content, reduces readability qualities and limits the flexibility to distribute content across multiple media channels.

Automated system for delivery of targeted content based on behavior change models


A load carrier mountable upon a transporting vehicle having an extension member for positioning an article carried upon the load carrier away from the transporting vehicle. The extension member has a vehicle engaging end that is coupleable to the transporting vehicle and a supporting end substantially opposite the vehicle engaging end upon which an upwardly extending support assembly is connected. The support assembly has an upright post fixed to the extension member and an upright support member coupled to the extension member for relative pivotal movement between the upright post and the upright support member. A collar is slidingly engagable upon the upright support member for releasably securing the upright support member to the upright post thereby establishing a traveling orientation of the load carrier. The collar has a tightener for orienting the collar between an expanded configuration that permits relative sliding movement between the collar and the upwardly extending support assembly and a constricted configuration that prevents relative sliding movement between the collar and the upwardly extending support assembly.

Carriers for sporting equipment are well known in the industry and are used for transporting pieces of sport equipment to remote locations for use. One such instance is carriers for bicycles that mount upon passenger vehicles. A preferred location for mounting such racks is at the rear of the vehicle where the rack causes minimum distraction and does not obstruct a driver's view. Many vehicles have tailgates that lower and back windows that raise; examples of such vehicles are station wagons, pick-up trucks and many sport utility vehicles. It is also common for such vehicles to have trailer hitch receptacles or receivers located proximate to the bumper structure below these gates. A common configuration for such receivers is a rectangular receptacle intended for a balled assembly to be inserted and fixed therein. It is upon this balled assembly that a trailer may be hitched. When such a balled assembly is not needed, it may be removed in many designs. When removed, the rectangular receiver is vacant and often covered with a removable cap.
Sport rack carrier designers have taken advantage of the presence of such a receiver and designed sports racks to be mounted therein at times when the vehicle is not being used for towing purposes and the receiver is vacant. One particularly popular embodiment in such a rack is in the form of a bicycle carrier.
Such hitch mounted bicycle carriers are known in the industry. One example is found in U.S. Pat. No. 5,529,231 issued to Burgess for an Adjustable Car Carrier on Jun. 25, 1996. In that invention, an upright post is journalled to a horizontal extension to the hitch receiver. Typical carrier systems of known designs incorporate a hinged configuration so that the primary upright structure may be folded downward to facilitate the opening and closing of an adjacently located tailgate. During transport and travel, however, the carrier must be fixed in an upright orientation for proper carriage of the sports equipment resting thereon.
A common means for fixing the upright orientation and preventing outward folding of the upright member is a pinned locking mechanism. This pinned configuration provides a simple means for fixing relative movement between the two pieces of the carrier assembly, but it does not provide a particularly strong connection nor one that is rattle free. Furthermore, it is possible for these pinned connections to be inadvertently disengaged. As a result, the need for an improved system for securing a hinged member of such a hitch mounted rack and preventing its inadvertent disengagement has been recognized as desirable and the present invention has been designed in answer thereto.