Neurotrophins having activities of multiple parental neurotrophins are described, as well as DNA for their production and pharmaceutical preparations thereof.

Many polypeptide growth factors mediate their biological responses by binding to and activating cell surface receptors with intrinsic tyrosine kinase activity. Upon ligand binding, these receptors become autophosphorylated on multiple tyrosine residues and subsequently associate with intracellular molecules important for signal transduction (Ullrich, 1990). However, little is known about the structural determinants of the specificity of ligand-receptor binding and how this interaction results in receptor activation and in the transduction of pleiotropic biological effects.
Recent work on the Trk family of tyrosine kinase receptors has established that these molecules constitute signal-transducing receptors for a family of structurally and functionally related neurotrophic factors collectively known as the neurotrophins. Most of our knowledge on neurotrophic factors comes from work on nerve growth factor (NGF), a 118 amino acid polypeptide that controls the maturation and survival of sympathetic neurons, as well as subpopulations of sensory and central neurons (Levi-Montalcini, 1968; Thoenen, 1980; Thoenen, 1987.) Other neurotrophins include brain-derived neurotrophic factor (BDNF) (Barde 1982; Leibrock, 1989); neurotrophin-3 (NT-3); (Hohn, 1990; Maisonpierre, 1990; Ernfors, 1990; Rosenthal, 1990); and neurotrophin-4 (NT-4); (Hallbook, 1991; Ip, 1992) also named neurotrophin-5 (NT-5); (Berkemeier, 1991). The ability of neurotrophins to promote survival of peripheral and central neurons during development and after neuronal damage has stimulated the interest in these molecules as potential therapeutic agents for the treatment of neurodegenerative diseases and nervous system injuries.
The neurotrophins show about 50% sequence identities and display both overlapping and specific sets of neurotrophic activities on peripheral and central neurons. For example, all neurotrophins, in various proportions, support the survival of neural crest-derived sensory neurons Thoenen, 1980; Lindsay, 1985; Hohn, 1990; Ip, 1992!. In contrast, survival of embryonic sympathetic neurons is supported only by NGF, while placode-derived sensory neurons are supported by BDNF and NT-3, but not by NGF Thoenen, 1980; Lindsay, 1985; Hohn, 1990!. This specificity is believed to be achieved in part by the selective interaction between the different neurotrophins and the members of the Trk family of tyrosine kinase receptors expressed on the surface of distinct neuronal populations. Thus, whereas NGF binds only to p140.sup.trk (herein called TrkA) Kaplan, 1991; Kaplan 1991a, Klein, 1991! BDNF and NT-4 interact exclusively with p145.sup.trkB (herein called TrkB) Soppet, 1991; Squinto, 1991; Klein, 1991b; Ip, 1992!, while NT-3 interacts with p145.sup.trkC (herein called TrkC) and to a lesser extent, also with TrkA and TrkB. Cordon-Cardo, 1991; Lambelle, 1991; Klein, 1991b; Squinto, 1991!.
Unlike Trk receptors, the low-affinity nerve growth factor receptor p75.sup.NGFR (herein called LNGFR) Radeke, 1987; Johnson, 1986! recognizes each of the neurotrophins with a similar affinity Rodriquez-Tebar, 1990; Ernfors, 1990; Hallbook, 1991; Rodriquez-Tebar, 1992!. Although LNGFR was initially postulated as a component of functional high-affinity NGF receptors (Hempstead, 1989; Hempstead, 1989! involved in mediating biological activity Hempstead, 1989; Yan, 1991!, emerging evidence disputes the direct role of this molecule in signal transduction Westcamp, 1991, Glass, 1991; Ibanez, 1992; Jing, 1992!.
Information on neurotrophin-receptor interactions has been obtained from studies of structure-function relationships and the design of neurotrophin mutants with altered properties. For example, in copending parent application Ser. No. 071847,369 filed on Mar. 6, 1992, now U.S. Pat. No. 5,349,055 entitled NEUROTROPHIC FACTORS HAVING ALTERED RECEPTOR BINDING SPECIFICITIES, which is incorporated by reference in its entirety herein, this approach was used to show that a positively charged interface in the NGF protein formed by Lys-32, Lys-34 and Lys-95 mediates the binding of NGF to LNGFR. NGF molecules mutated in these positions do not bind to LNGFR but retain binding to TrkA receptors and biological activity in cultures of primary neurons, thus demonstrating that TrkA alone is sufficient to mediate the biological activity of NGF in neuronal cells.
Most of the sequence variations among the neurotrophins occur in distinct regions, and initial studies using chimeric molecules between NGF and BDNF have shown that specific combinations of some of these variable sequences allow a broader spectrum of neurotrophic activities than those of the two wild type proteins (Ibanez, 1991; Suter, 1992). However, these studies did not identify specific receptor binding sites in the neurotrophins responsible for the observed differences in biological specificities.
The recent elucidation of the crystal structure of NGF has localized three quarters of the variable residues in three .beta.-hairpin loops and a reverse turn (McDonald, 1991). Other variable regions include part of a .beta.-strand and the amino (NH.sub.2) and carboxy (COOH) termini. The fact that most of the conserved amino acid residues in the neurotrophins play structural roles suggests that all four neurotrophins have very similar conformations, with individual differences restricted to the variable regions (McDonald, 1991). Surface loop regions are in general thought to be important for receptor binding of growth factors (Sclunegger, 1992; Daopin, 1992; Oefner, 1992). For example, in U.S. Pat. No. 5,134,121 issued on Jul. 28, 1992, agonists and antagonists of nerve growth factor are described which consist of peptides derived from the region between amino acid 26 and amino acid 40 of NGF.

DNA encoding multifunctional neurothrophic factors


An adjustable-length walking aid provides a hollow tubular body having a top and a bottom. A spring-biased gripper arm at the bottom is connected to a tension gripper actuator filament that is spooled around a flywheel spool. A lamp housed in the base of the body is connected to a power supply in the handle by a conductive filament that is also spooled around the flywheel. The tension on the gripper actuator and conductive filaments is maintained by the flywheel regardless of the length to which the cane is adjusted.

Implements to assist with walking are well known and often take the form of a cane with a handle at the top and skid-resistant cap at the bottom. Canes are useful to assist locomotion for those who, do to age or injury, for example, require or appreciate the stability that a cane provides for upright walking. As the baby boom generation ages, walking canes become increasingly important personal possessions.
In addition to mobility, the elderly may also appreciate help tools that help them pick and retrieve items. Walking canes that incorporate a gripper mechanism have been described previously, such as in U.S. Pat. No. 7,624,746, where a gripper mechanism for an adjustable length cane is operated by a cabling system house internally in the hollow cane.
Height-adjustable walking canes with a gripper mechanism and a light that can be switched on and off by the user have also been described, such as, for example, US Pat. Pub. No. US20110155195.
Despite the clever solutions provided in the above references, they have shortcomings. For example, a light at the base of the cane and an actuator mechanism near the handle is not provided for an adjustable-height cane, because they do not provide an adjustable length electrical conductor that maintains its tension when the length of the cane is changed.
Another shortcoming is the lack of selectively actuatable illumination sources that project light in more than one desired direction. For example, it would be useful to have a light that shines forward to illuminate the area into which a user is walking, as well as a light that shines downward or from the base of the cane, to illuminate the floor or under a table or chair so that a user can find something that may have fallen on the floor or under a table.
The present disclosure, accordingly, describes an adjustable-length walking cane with a gripper mechanism and more than one source of illumination.


A sliding bone support plate assembly comprises at least first and second plates which slide with respect to each other, varying the length of the plate assembly by plate-on-plate sliding after bone screws mount the plate assembly to vertebrae in a recipient. The plates comprise cooperating sliding structures which cooperate with each other to interconnect the plates to each other and to facilitate sliding movement of the plates with respect to each other. Such sliding accommodates varying the length of the plate assembly, and relieving stress which would otherwise be imposed on the plate assembly by post-procedural settling of respective vertebrae to which the plates are mounted without requiring any movement of a plate with respect to a bone to which that plate is mounted. The plate assembly is fabricated using bio-compatible, bio-stable materials which are safe for extended use in a living human, and which are not generally assimilated.

The present invention relates to devices for the fixation and/or support of bones. In particular, the present invention relates to bone support plate assemblies for the fixation and/or support of bones of the spinal column, thus spinal plate assemblies. The plate assemblies of the present invention have particular application in situations where compressional or "settling" forces, as well as torsional and flexing forces on a spinal plate, which supports "fixed" vertebrae, cause significant stressing, and potential failure of the spinal plate and/or plate components.
Vertebral fixation has become a common approach to treating spinal disorders, fractures, and the like, and for fusion of vertebrae at the time such fixation is instituted. Namely, one or more vertebrae are fixed in position relative to one or more other vertebrae above, e.g. toward the head from, and/or below, e.g. toward the coccyx from, the vertebrae being fixed. Generally, a spinal plate is the device of choice used for mechanically supporting such vertebral fixation. A typical spinal plate includes a plate having a plurality of bone support apertures therethrough. A plurality of fasteners, i.e., bone screws, are generally positioned into and through respective bone support apertures of the plate to secure the spinal plate to bone, such as to respective upper and lower supporting adjacent spinal vertebrae. The screws are fastened to the respective support vertebrae to secure the spinal plate to the respective vertebrae. In general, such plate and screw assemblies can be utilized for e.g. anterior fixation of the e.g. cervical, lumbar, and/or thoracic portions of the spine.
The basis of anterior fixation or plating is to approach the spine from an anterior or anterio-lateral direction, and to use the screws to solidly mount the spinal plate to the affected vertebrae. In some instances, in addition to the application of a spinal plate, graft material may be incorporated into the procedure in an attempt to permanently fuse together adjacent vertebrae. The graft material can be e.g. of bone grafts obtained from bones of the recipient or from another individual.
A first common and undesirable result associated with use of conventional such spinal plates is the tendency of the bone screws to "back out," or pull away from the bone into which they are fixed. This problem occurs primarily as a result of the normal torsional and bending motions of the human body and spine as the recipient/patient goes about routine daily activities. This is a particularly important problem because, as the screws become loose and pull away from the bone, the heads of the screws can rise above the surface of the spinal plate and can even work their way completely out of the bone. While this condition can cause extreme discomfort for the recipient, this condition can also create a number of potentially serious physiological problems given the significant amount of nervous and vascular structures located at or near the potential locations of anterior spinal plate fixations.
A number of designs have been proposed in attempts to prevent screws from pulling away from the bone and/or to prevent the screws from backing out or pulling away from the surface of the spinal plate. Such mechanisms used to prevent bone screws from pulling out of bones include cams which engage and lock the screws, and the use of expanding head screws which expand outwardly when adequate force is applied thereto to engage the holes in the spinal plate. All of these designs have detriments including potential for breakage or requiring particular precision and alignment in their application in order to work correctly. Additionally, loose components and accessories of spinal plates which address the "backing-out" problem can get dropped and/or misplaced while the vertebral fixation surgical procedure is taking place, prolonging and complicating the procedure as well as creating substantial risk of harm to the recipient.
A second common result associated with use of such spinal plates is the tendency of the vertebrae being "fixed" to settle after the spinal plate affixation procedure. Such settling of the "fixed" vertebrae relative to each other is a response to the normal loading of the spine as the recipient/patient carries on routine daily activities. Such settling of the "fixed" vertebrae adds compression forces to the above-listed forces which cause the bone screws to "back out" or pull away from the bone into which they were fixed. Zdeblick et al (U.S. Pat. No. 5,324,290) attempted to address the problem of compression forces in the context of treating vertebral burst fractures, but fails to provide any functional means to prevent the screws pulling away as a result of torsional and flexing forces. Zdeblick et al also fails to provide any structure in the plate assembly which relieves the stress imposed on the plate by the vertebral settling.
My U.S. Pat. No. 6,503,250 teaches use of slot-shaped apertures which enables longitudinal translation of the bone screws in the slot-shaped apertures with respect to the plate in cooperation with post-procedural settling of the vertebrae. Such translation of the bone screws requires that the bone screws not be locked to the plate, and is accompanied by movement of the bone screws with respect to the plate, along the longitudinal axes of the slots, typically along the longitudinal axis of the plate. Such settling of the bones, such movement of the bone screws with respect to the plate, is also accompanied by movement of the plate with respect to one or more of the vertebrae to which the plate is mounted. Such movement of the plate with respect to the bone can, in some instances, have undesirable consequences.
Therefore, it is an object of the invention to provide spinal plate assemblies which accommodate rigid bone-to-bone fixation and provide bone support for such fixation, such as e.g. adjacent or second adjacent vertebrae, while allowing post-procedural compression between the respective bones, e.g. post procedural bone-to-bone movement, without requiring any movement of any bone screw in a slot-shaped aperture with respect to the respective plate.
It is a further object of the invention to provide spinal plate assemblies wherein the bone screws do not need to move with respect to the plate assembly in order for stress, potentially imposed on the plate assembly by post-procedural settling of the vertebrae, to be relieved or avoided.
Yet a further object of the invention is to provide spinal plate assemblies having first and second sliding plates which are adapted and configured to provide plate-on-plate sliding of the first and second plates, with respect to each other, in order to relieve a substantial portion of the stress which would otherwise be imposed on the respective plate assembly by post-procedural vertebral settling.
Still a further object of the invention is to provide spinal plate assemblies which accommodate bone-to-bone settling while providing bone support for such fixation, while accommodating post procedural compression between the respective bones, and while maintaining rigid, unmoving fixation between the plate and the respective bones/vertebrae.
It is a further object of the invention to provide bone support plate assemblies, e.g. spinal plate assemblies, which accommodate bone-to-bone settling while providing bone support for such fixation, while accommodating post procedural compression between the respective bones, without requiring, or enabling, any movement of any plate with respect to a bone to which such plate is mounted.


Materials immunoreactive with parathyroid hormone-related protein (PTH-rp) are used in the invention method to prevent and treat cancer metastasis to bone and cancer cell growth in bone as well as osteolysis and symptomatic sequelae thereof. Antibodies with human characteristics are included in the invention for application of the invention method to human subjects.

It has long been understood that morbidity and mortality caused by cancer, especially in view of the fact that surgical techniques are readily available, are due to more-or-less systemic sequelae of the original multiplication of the cancer cells. Metastasis of an original tumor to additional locations, the destruction of target locations as a direct or indirect result of this metastasis, cachexia, hypercalcemia, and other symptomologies characterize the course of the malignancy. The mechanisms whereby these sequelae occur are believed to involve a variety of cytokines, growth factors, and cell adhesion molecules, among other factors. It is entirely unknown, however, how cancers dissolve bone in bone metastases since at present, the only cells known to be able to dissolve bone are osteoclasts. It is not known how metastasized cancer dissolves bone in order to accommodate the growth of the cancer.
One of many factors which is known to play a role in at least some of these processes is parathyroid hormone-related protein (PTH-rp). Due to its similarity to PTH, it has been recognized as a mediator of humoral hypercalcemia of malignancy (HHM). In this role, PTH-rp secreted by the tumor is circulated through the blood and is associated with hypercalcemia, an index of bone resorption. PTH-rp has been shown to be the cause of systemic bone resorption and calcium reabsorption from urine at the tubule. Both of these result in a systemic elevation of blood calcium levels. This factor has been described in connection with HHM in U.S. Pat. No. 5,116,952. This patent also describes preparation of anti-PTH-rp antibodies using peptide subunits of the partially sequenced protein. This protein has also been called adenylate cyclase stimulating factor (ACSF) in U.S. Pat. No. 5,312,810 and humoral hypercalcemic factor (hHCF) in U.S. Pat. No. 5,114,843. The association of PTH-rp with HHM is also described by Yates, A. J. P. et al., J Clin Invest (1988) 81:932-938. Japanese application A4-228089, published Aug. 18, 1992 describes recombinant production of anti-PTH-rp antibodies, including murine/human chimeras. This application also discloses animal studies demonstrating that either murine or chimeric monoclonal antibodies directed to PTH-rp ameliorate the effects of HHM in a model system where HHM is caused by either systemically infusing PTH-rp into mice peritoneally or by implanting PTH-rp-producing prostate cancer cell lines in nude mice.
PTH-rp has been purified from human lung cancer, breast cancer and renal cell carcinoma. Although PTH-rp was originally found associated with tumor cells, it is also present widely in normal tissue. The gene encoding PTH-rp was cloned and expressed by Suva, L. J. et al. Science (1987) 237:893-895. PTH-rp has been shown to bind to PTH receptors (Abou-Samra, A. et al. Proc Natl Acad Sci USA (1992) 89:2732-2736) and has activities similar to PTH (Horiuchi, N. et al. Science (1987) 23:1566-1568). It has been shown to stimulate adenylate cyclase in renal and bone systems, increase tubular reabsorption of calcium, decrease renal phosphate uptake and stimulate 1.alpha.-hydroxylase. Thus, it is logical that where PTH-rp is circulating, inhibitors of the PTH-like action of PTH-rp would interfere with these biological events, including calcium reabsorption from urine to blood at the kidney tubules and systemic bone resorption. However, PTH/PTH-rp receptors are not found on osteoclasts. Either such receptors have been resistant to characterization or to the extent that PTH-rp may be found to affect osteoclasts, the effect may be exerted by some unknown mechanism, for example by effecting the secretion of unknown mediators from osteoblasts (which are known to have PTH/PTH-rp receptors). There is no available evidence to connect PTH-rp to bone resorption mediated by osteoclasts.
PTH-rp also has properties that are not shared by PTH, including regulation of placental calcium transport as summarized in a review by Mallette, L. E. Endocrine Rev (1991) 12:110-117. Of particular relevance with respect to the invention herein is that PTH-rp has also been associated with the establishment of bone metastasis in breast cancer (Powell, G. J. Cancer Res (1991) 51:3059-3061; Southby, J. et al. Cancer Res (1990) 50:7710-7716). The data provided in these disclosures show only the association of PTH-rp with bone metastasis of breast cancer, but no causal relationships are implied. PTH-rp has been considered as a possible autocrine factor for a limited number of tumors (Burton, P. B. J. et al. Biochem Biophys Res Com (1990) 167:1134-1138; Li, X. et al. Cancer Res (1993) 53:2980-2986).
Thus, the precise role of PTH-rp in mediating the effects of a primary cancer is not well understood. Not only are there additional factors which also participate in the progress of this condition, the production of PTH-rp is believed affected by additional factors such as prolactin, glucocorticoids, epidermal growth factor, TGF-.alpha., TGF-.beta., estrogen, "stretch," and even extracellular calcium concentration. The presence of additional factors is particularly important and adds to the uncertainty of the mechanism. Factors such as IL-1, IL-6, IL-11, M-CSF and GM-CSF in particular have been considered important in bone resorption. In a report by Sasaki, A. et al. J Bone Min Res (1994) 9 Supp 1:S 294, B 257, it is demonstrated that administration of recombinant human IL-1.alpha. into calvaria of nude mice attracted metastasis of cancer calls that had been inoculated into the left ventricle, while other bones of the same animal which did not receive IL-1.alpha. did not show cancer metastasis. Gilles, J. et al. ibid. S 337, B 433, suggest that IL-6 markedly potentiates the effects of bone resorbing factors on osteoclastic bone resorption and that IL-6 production in bone is important both in cytokine-mediated bone resorption and in those disease states where cytokine-mediated bone resorption is potentially involved, such as estrogen-related bone loss, myeloma and Paget's Disease. It has also been shown that transgenic mice that are modified to comprise an IL-6 gene knockout show reduced bone loss in models for osteoporosis. It has been confirmed that osteoclasts have receptors for IL-6 and IL-11. Osteoclasts treated with M-CSF and GM-CSF show accelerated maturation in culture. Transgenic mice that have genetic deficiencies in the M-CSF gene also exhibit a condition mimicking osteoporosis and this condition can be treated by injection of M-CSF. Thus, a multiplicity of factors are known which appear to play a major role in local bone resorption and/or osteoclast activation.
Sato, K. et al. J Bone Min Res (1993) 8:849-860 describe results obtained in a murine model of HHM wherein the affected mice were administered a monoclonal murine antibody obtained from immortalized spleen cells of mice injected with a peptide representing amino acid positions 1-34 of PTH-rp. Passive immunization resulted in decreases in serum calcium concentration in these hypercalcemic nude mice that had been transplanted with human PTH-rp-producing tumors. These tumors were implanted in nonbone tissue to provide a model for HHM. The authors suggest that if a human counterpart to this antibody could be obtained, it might be used in treatment where malignancy-associated hypercalcemia is due to PTH-rp. (Sato, K. et al. use the term "malignancy-associated hypercalcemia" in this paper; it is synonymous with HHM.) In this model, elevated levels of PTH-rp are maintained in the blood which are, evidently, mitigated by the administration of anti-PTH-rp antibodies. Similar studies were conducted by Kukreja, S. C. J Clin Invest (1988) 82:1798-1802 and showed that polyclonal anti-PTH-rp antibodies suppress hypercalcemia in a human tumor model of HHM. This is the first disclosure of any therapeutic effect of anti-PTH-rp on HHM. The relevance of this model is verified by the finding of Tashjian, A. H. et al. J Exp Med (1964) 119:467 that 15% of 147 hypercalcemic breast cancer patients exhibited no bone metastases.
Hypercalcemia may also be caused by osteolysis of bone through the mediation of osteoclasts. Mundy, G. R. J Clin Invest (1988) 82:1-6 describes increased osteoclastic bone resorption in areas surrounding breast cancer metastases. In addition, breast cancer cells have been shown to resorb bone directly in vitro (Eilon, G. & Mundy G. R., Nature (1978) 276:726-728.
Kohno, N. et al. Surgery Today, Japan J Surg (1993) 4:215-220 reported studies performed on immobilized sections of surgically removed breast cancers using an anti-PTH-rp antibody also prepared by immunizing mice with the first 34 amino acids of PTH-rp. The antibody bound to 57% of the tumors; it bound to 83% of the tumors derived from patients who developed skeletal metastases but only 38% in those who either developed lung metastases or no metastases at all. These authors conclude that their results suggest that PTH-rp-positive tumors have an affinity to bone. However, the observations related only to the staining of cancer tissues by anti-PTH-rp and are not quantitative. Thus, the results do not show a causal relationship between the presence of PTH-rp and any acceleration of bone metastasis or growth enhancers. An equally plausible explanation is that PTH-rp is an effect rather than a cause of metastasis, cancer growth and/or osteolysis.
The present inventors have developed a model of human breast cell cancer metastasis to bone that results in osteolysis. Nakai, M. et al. Cancer Res (1992) 52:5395-5399; Sasakai, A. et al. J Bone Min Res (1993) 8 (Supp 1):No. 92. Tumor cells introduced into the left cardiac ventricle of nude mice can be shown to cause osteolytic lesions that can be seen by x-ray examination and that can be confirmed histologically. A375 melanoma cells and the human breast cancer cell line MDA231 have been used in this model. Using this model, it was demonstrated that bone metastasis could be prevented by a synthetic antagonist to laminin.
This model has also been used to demonstrate in vivo the metastatic nature of human neuroblastoma cells as described in an abstract by Yoneda, T. et al. J Bone Min Res (1994) 9 (Supp 1):S 293, B 225. Six weeks after inoculation with the neuroblastoma cells, x-rays showed lesions in the tibiae that were both osteolytic and osteoblastic, but there was no hypercalcemia or cachexia. Thus, cancer metastasis of the bone is clearly a complex situation which can generate both osteoblasts and osteoclasts and is not always associated with systemic disorders such as hypercalcemia or cachexia. Histologic examination showed that neuroblastoma cells occupied the bone marrow cavity, and there were numerous bone resorbing osteoclasts (which have not been demonstrated to exhibit PTH/PTH-rp receptors) on endosteal bone surfaces. Culture supernatants of the tumor cells stimulated bone resorption in organ cultures of fetal rat long bones and increased proliferation of osteoblastic osteosarcoma cells, which promote bone formation. The culture media contained significant levels of PTH-rp and high levels of IL-6. It is known that osteoclasts have IL-6 receptors.
The present inventors have also demonstrated that the number of osteolytic lesions is increased by enhancing PTH-rp expression of the MDA231 cells used in the model, but not diminished by MDA231 cells transfected with an antisense PTH-rp construct. Overexpressing clones were obtained by transfecting MDA231 cells with cDNA encoding human prepro PTH-rp; clones having diminished production of this peptide were obtained by transfecting the cell line with an antisense construct. A clone showing elevated PTH-rp expression (100 pM/24 hours) produced 16.3.+-.3.8 lesions radiographically at 3 weeks as compared with the antisense construct which secreted less than 0.3 pM/24 hours which produced only 7.6.+-.0.22 lesions. The number of lesions in mice administered unmodified MDA231 cells which produce 1.6-8.4 pM/24 hours PTH-rp is similar to the number of lesions in mice administered the MDA231 cells modified to contain the antisense construct, which produces less PTH-rp. No plasma concentrations of PTH-rp were detectable in any of the mice used in these studies; hypercalcemia was minimal and present only in mice harboring the PTH-rp-enhanced MDA231 cells. The present inventors have also shown that PTH-rp concentrations in serum-free media conditioned by MDA231 cells were increased two-fold when the cells were cultured on an extracellular matrix produced by bone cells. These results were reported by Guise, T. A. et al. J Bone Min Res (1994) 9 (Supp 1):S 128, No. 30.
It has now been found that antibodies specific for PTH-rp are affective in inhibiting metastasis and ameliorating the effects of malignant cells localized in bone. This provides an effective pharmacological approach to treatment.

Method to ameliorate osteolysis and metastasis


A joggled structural element includes two wings with a small thickness and a great thickness. Slopes made in a joggle of the structural element are computed as a function of each of the thicknesses of the wings. Thus, the joggled structural element comprises a shallow slope in the joggle on the side having the wing of great thickness and a steep slope in the joggle on the side having the wing of small thickness. A method is also disclosed implementing an anvil and a punch. This method can be used to make joggled structural elements.

1. Field of the Invention
The invention relates to a method to joggle a structural element and a structural element joggled according to this method. Joggling a structural element comprises joggling such a structural element so as to create an offset between two of its parts. In the context of the invention, the structural element to be joggled is a beam with any section whatsoever comprising, in its profile, a strut and wings at the two ends of this strut. The invention is aimed at reducing a length in the offset given by a joggling operation. The present invention can be applied to special advantage, but not exclusively, in the field of aeronautics.
A joggled structural element is generally used to strengthen a link between two parts, such as two parts of an aircraft that are not aligned with each other.
2. Description of the Prior Art
FIG. 1 shows a view of such a prior art joggled structural element 100. This structural element herein has an I-shaped section that could have any section whatsoever, such as a C-shaped or U-shaped section. This structural element 100 has a first wing 101, a second wing 102, and a strut 103. The first wing 101 has a thickness E1 and the second wing 102 has a thickness E2. This joggled structural element 100 is used to set up or reinforce a link between a part 121 and a part 122.
The first wing 101 and the second wing 102 are each deployed in a plane that forms a non-zero angle with a plane of the strut 103, itself located in the plane of the FIG. 1. In a particular embodiment, these wings 101 and 102 are each deployed in a plane that is perpendicular to a plane of the strut 103. There is a linking joggle 104 between a first part 105 and a second part 106 of the structural element. This joggle 104 corresponds to the part of the structural element 100 that is bent. This joggle 104 gives an offset between the first part 105 and the second part. 106. The offset extends in the plane of the strut 103 of the structural element with an offset height H measured along a direction perpendicular to the plane of the wings 101 and 102, and with an offset length L measured in a direction parallel to the planes of the strut 103 and of the wings 101 and 102.
This length L is computed as a function of a thickness of a wing. In one exemplary embodiment, for structural elements comprising wings 101 and 102 with equal thicknesses E1 and E2, the length L is on the whole equal to six times the thickness of a wing. This ratio between the thickness of a wing and the length L varies as a function of the material out of which the structural element is made. The length L is as short as possible but cannot be reduced as much as is desired. Indeed, the proportion of six times the thickness of the wing is a constraint that cannot be flouted without a risk of deterioration of the structural element.
In the prior art, when the thicknesses E1 and E2 of the wings 101 and 102 are different, the length L is computed from the thickness of the bigger of the two wings. In FIG. 1, the length L is therefore equal to six times the thickness E1 of the thick wing 101. In its joggle 104, the structural element 100 therefore has identical slopes on both sides of the wings 103 and 104.
The fact that the slopes are identical raises a problem. Indeed, the joggled structural element 100 is used to strengthen a link between two parts 121 and 122 having a difference in level. A space 130 depending on the length L can be seen between the parts 121 and 122 and the structural element 100. Since the length L of the offset given by the joggle is very great, the space 130 between the parts and the structural element is great. At the position of such a space 130, the joggled structural elements of the prior art therefore do not optimally participate in strengthening the link between the parts 121 and 122.
It is an object of the invention to resolve this problem of excessive space 130 between the structural element 100 and the parts 121 and 122.

Method to joggle a structural element and structural element joggled according to this method


A method of processing an open asynchronous application service event and an open web service gateway implementing the method are provided. The open web service gateway includes: a plurality of SCFs (service capability features) operatively connected to an application service through a web service interface, receives an event registration request from the application service, and notifies an event occurring in a network to the application service; and an event broker registering the registration-requested based on a predetermined policy in correspondence with the SCFs, when the registration-requested event received from the application service is an asynchronous event, and notifies an occurrence of the event in the network to the SCFs according to a registered priority of the event. Accordingly, an asynchronous event is registered and notified based on a predetermined policy, so that it is possible to prevent event registration conflict between the SCFs and between the application services and to maximize network operation efficiency.

1. Field of the Invention
The present invention relates to a method of processing an open asynchronous application service event and an open web service gateway implementing the method, and more particularly, to a method of processing an open asynchronous application service event capable of registering and notifying an asynchronous event based on a predetermined policy and an open web service gateway implementing the method. This work was supported by the IT R&D program of MIC/IITA [Project No. 2005-S-056-02, Project Name: Development of Open API and Service Platform Technologies].
2. Description of the Related Art
In general, in an open system, an open web service gateway provides a standard web service application programming interface (API), so that a third party service provider can easily generate a service without knowledge of low layers of a network. In addition, the open web service gateway provides functions such as presence information notification, terminal state notification, terminal location notification, call notification, and SMS message transmission in units of service capability feature (SCF).
The open web service gateway provides an interface to an application service which is to use the SCF, so that the application service can invoke the API in a web service format. Operations for processing the API that is invoked by the application service are divided into synchronous and asynchronous operations according to functions of the SCF.
The asynchronous operation is performed to notify presence, terminal state, terminal location, call, or other events which occur in the network.
In addition, before the event notification, the application service needs register event conditions in advance by using the API provided from the open web service gateway.
More specifically, in the asynchronous operation, the application service registers a specific event in the open web service gateway in advance. When the registered event occurs in the network, the SCF associated with the event notifies the generation of the event to the application service.
However, in a conventional event registration procedure, an event having the same event condition may be registered by a plurality of application services. In this case, event notification conflict occurs.
Therefore, according to a feature of an application service or an event, the application service is designed to be invoked one time per event. Otherwise, different events are designed to be sequentially notified to different application services. However, in event registration logic, the event notification conditions are not considered.
Therefore, in a case where, the registered event is generated from a plurality of the application services without any arbitration, unpredicted event notification may be performed, so that conflict of event notification between application services or between SCFs in the open web service gateway may occur. Accordingly, there is a need for a method and apparatus capable of preventing the event notification conflict.

Method of processing open asynchronous application service event and open web service gateway implementing the same

Electronics and Telecommunications Research Institute


A radiometer and a method for indicating water content and water content change caused by water and/or liquid water are disclosed. According to the method, changes of noise temperature values are observed by receiving microwave electromagnetic radiation at a medium frequency. This medium frequency is considerably below the lowest absorption resonance (approximately 22 GHz) of water molecules. At least one noise temperature value is set as reference value, and noise temperature changes are compared with the reference level.

The essential atmospheric agents for microwave radiometry are oxygen and water vapor. The atmospheric oxygen and water vapor emit on a cloudless sky thermal noise and provide the so called clear sky radiometric brightness temperature T.sub.sky. Inspected from the ground, the atmospheric brightness temperature at clear weather is a function of both frequency and elevation. The frequency dependence is due to the resonant absorption/emission spectrum of water and oxygen molecules. Due to the atmospheric pressure the spectral lines are spread on a broader frequency range. The lowest spectral line of the water molecule absorption/emission resonance is at approx. 22 GHz frequency (FIG. 6a). The elevation angle dependence of the clear sky brightness temperature results from geometry. The transmission path length of the layer formed on the ground by the atmosphere is considerably shorter in the zenith direction than closer to the horizon (FIG. 6b). The radiometric brightness temperature of the atmosphere is to a certain extent dependent on the amount of effective agent in the radiometer beam, at clear sky on the so called effective path length of the inspection direction. The clear sky brightness temperature in zenith direction is thus considerably lower than close to the horizon (FIG. 6a).
Water is present in the atmosphere in water vapor and liquid form and as ice in clouds and rains. Atmospheric water content changes: air humidity, clouds and rain occur in the microwave region as changes in the sky brightness temperature.
Atmospheric property observations with a radiometric scanner and rain indication with a rain detector are presented as examples of the fields of embodiment of the method and device according to the invention.
Atmospheric and ground properties have been measured by microwave radiometers both from satellites (weather and remote sensing satellites) and from the ground.
Atmospheric microwave radiometric measurements from the ground have been utilized for example, in meteorological applications, in measurements relating to interferometric and electromagnetic wave propagation studies, e.g.:
i) the U.S. Pat. No. 4,873,481 PA1 ii) Measurement of atmospheric water vapor with microwave radiometry; S. Elgered et al./Chalmers University of Technology, Sweden, PA1 iii) Utilization of the radiometry method in a satellite connection propagation study; T. Kokkila, thesis for diploma, University of Technology 1988, PA1 iv) Correction of satellite beacon propagation data using radiometer measurements; Stutzman, Haidara, Reklus, IEEE Proceedings.-Microwaves. Antennas. Propagation, Vol 141 No.1 Feb 1994, PA1 v) Use of radiometers in atmospheric attenuation measurements Allnut, Pratt, Stutzman, Snider IEEE Proceedings.- Microwaves. Antennas. Propagation, Vol 141 No.5 Oct 1994.
The measuring device used in the above references are radiometers of Dicke-type (i, ii, iii) and a total output radiometer (iv, v). The radiometers are multichannel or connected to a measuring system utilizing radiometric measurements was to determine atmospheric properties by brightness temperature absolute values. The measuring of the brightness temperature absolute values requires stabilization of the radiometer amplification, measuring result calibration, accurate knowledge of the antenna side lobe properties and ambient radiation properties. The stabilization of the radiometer amplification is based on the construction principle (Dicke) or on a regular reference load measurement (total output radiometry). Calibration of the measuring results can be implemented by known objects giving hot/cold-brightness temperatures or by artificial loads, for example, by placing before the radiometer antenna input a piece of space cloth having the ambient temperature and alternately a piece of space cloth cooled with e.g. liquid nitrogen. The side lobe properties of the antenna can be estimated by measuring the antenna beam figure at used frequencies. The ambient radiation properties can be estimated by known radiation properties of the ground. Based on this and the above mentioned references, the determination of the atmospheric brightness temperature absolute values requires complicated equipment, `scientific instruments` as well as difficult and expensive measurement systems.
The atmospheric weather phenomenons can be also observed by a radar. The effect transmitted by the radar scatters from the water drops thus revealing possible water containing objects. Use of the radar requires a transmitter/receiver equipment. The curvature of the ground causes a shadow region, which restricts the operation range of the radar. The currently used rain indicating detectors are based on the observation of some electric property change in the detector component caused by the rain (rain drops or snow flakes), for example, the capacitance or breakdown voltage. The mechanical constructions of these detectors are due to their operation principle open and therefore sensitive to malfunctions caused by fouling and require regular service.
One rain detector application area is the automatic control of, for example the heating systems of satellite earth station antenna reflectors. The wet snow gathered on the earth station antenna surfaces attenuates the signal and turns the antenna beam away from the satellite direction thus reducing the capacity of the antenna. The rain detectors function in connection with outdoor temperature detectors, controlling the reflector heating into function when it rains at the temperature area of approx. -5.degree.-+5.degree. C. At higher temperatures the reflector snow melts by itself and at lower temperatures there is the risk that the melted snow freezes to the antenna constructions. Dry frozen snow has also a smaller effect than wet snow.
In addition to the above mentioned mechanical construction disadvantages, the present rain detectors in the satellite earth station heating control system have the deficiency that they in certain conditions do not observe the problems caused by snow gathered on the antenna surface. Frozen snowfall (for example, 10.degree. C.) and its gathering on the reflector surface does not switch on the heating control system. The warming of the gathered frozen snow when the weather becomes warmer or the sun has warmed the reflector surface increases the liquid water content of the snow. The melting of the gathered frozen snow on the antenna surface might cause long breaks or quality deteriorations in the telecommunication for several days after the snowing.


It is disclosed that a color separation optical system improves color reproducibility by obtaining a characteristic which approximates an ideal spectral characteristic in view of influence of polarization separation caused according to the magnitude of an incidence angle. In the color separation optical system, a curve representing a characteristic of a green-reflecting dichroic film DG has a shape along the characteristic curve representing an ideal spectral characteristic corresponding to green light. Further, the characteristic of the blue-reflecting dichroic film DB is associated with that of the green-reflecting dichroic film DG. A part, in which the transmittance of the blue-reflecting dichroic film DB changes from a low transmittance to a high transmittance, in the transmittance characteristic curve representing the characteristic of the blue-reflecting dichroic film DB is included in a predetermined wavelength region associated with the characteristic of the green-reflecting dichroic film DG.

1. Technical Field
The present invention relates to a color separation optical system for separating incident light into a plurality of color light components, and to an image pickup apparatus having the color separation optical system.
2. Related Art
Generally, image pickup apparatuses, such as a television camera and a video camera, have color separation optical systems. FIG. 17 illustrates an example of the configuration of a color separation optical system. The color separation optical system 101 separates incident light L, which is incident thereon via a taking lens 102, into three color components that are a blue light component LB, a red light component LR, and a green light component LG. Image pickup devices 4B, 4R, and 4G, such as charge coupled devices (CCDs), respectively used for the light components LB, LR, and LG, into which incident light is separated by the color separation optical system 101, are disposed at places respectively corresponding to the color light components LB, LR, and LG. The color separation optical system 101 is referred to as a Philips type color separation optical system, and is provided with a first prism 110, a second prism 120, and a third prism 130, which are arranged along an optical axis Z1 in order from the side of incidence of light. The blue light component LB, the red light component LR, and the green light component LG are taken out by the first prism 110, the second prism 120, and the third prism 130, respectively.
A blue-reflecting dichroic film DB1 is formed on a reflection/transmission surface 111 of the first prism 110. A red-reflecting dichroic film DR1 is formed on a reflection/transmission surface 121 of the second prism 120. The first prism 110 and the second prism 120 are disposed so that the surface 111 of the first prism 110, on which the blue-reflecting dichroic film DB1 is formed, and a surface of the second prism 120, on which light is incident, are spaced by an air gap 110 AG and face each other. Further, a trimming filter 151 is provided on a surface of the first prism 110, from which light exits. A dichroic film 151A is formed on a surface of the trimming filter 151, from which light exits. Similarly, a trimming filter 152, on which a dichroic film 152A is formed, is provided on a surface of the second prism 120, from which light exits. A trimming filter 153, on which a dichroic film 153A is formed, is provided on a surface of the third prism 130, from which light exits. The trimming filters 151, 152, and 153 are provided in order to make the spectral characteristic of the color separation optical system approximate an ideal characteristic. The trimming filters 151, 152, and 153 have a role of shaping spectral characteristics represented by wavelength components, which are not sufficiently shaped by the blue-reflecting dichroic film DB1 and the red-reflecting dichroic film DR1.
FIG. 19 illustrates ideal spectral characteristics of a color imaging system, which respectively correspond to a red component (R-component), a blue component (B-component), and a green component (G-component). Incidentally, the ideal spectral characteristics illustrated in FIG. 19 are normalized so that the maximum value of each of the R-component, the B-component, and the C-component is 1. The "ideal spectral characteristic" can be obtained by converting the chromaticity coordinates of three primary colors of a color reproduction medium thereinto and performing a linear transformation of a color matching function in an XYZ color coordinate system. Incidentally, the "color reproduction medium" is a medium for reproduction (or display) of an image taken by an image pickup apparatus. The "color reproduction medium" is, e.g., a display apparatus such as a liquid crystal monitor and a projector. FIG. 18 illustrates an example of chromaticity coordinates of three primary colors R, G, and B for obtaining an ideal characteristic. Three primary colors R, G, and B determine a color range that can be reproduced by a color reproduction medium.
Ideal color reproduction can be achieved in a case where a characteristic, which is the same as an ideal characteristic as illustrated in FIG. 19, can be obtained using a color separation optical system 101 illustrated in FIG. 17. However, actually, it is difficult to obtain a characteristic which is completely the same as an ideal characteristic. Thus, a color separation optical system is designed to obtain a characteristic which approximates an ideal characteristic. The color separation optical system 101 is designed so that a characteristic, which approximates an ideal characteristic, is obtained by appropriately adjusting the dichroic films DB1 and DR1 respectively formed on the prisms and the dichroic films 151A, 152A, and 153A respectively formed on the trimming filters 151, 152, and 153. FIG. 20 illustrates an example of color separation optical system obtained by performing such a design.
FIG. 21 illustrates examples of the designs of the dichroic films DB1 and DR1 used in the color separation optical system 101. As illustrated in FIG. 21, films having characteristics, the wavelength-to-transmittance characteristic curves of which have steep leading edges or trailing edges as compared with those of the characteristic curves of the ideal characteristics illustrated in FIG. 19, are used as the dichroic films DB1 and DR1, respectively. Additionally, unnecessary wavelength components of light exiting from an exit surface of each of the prisms are cut off using the trimming filters 151, 152, and 153 on which the dichroic films 151A, 152A, and 153A are formed, respectively.
Thus, characteristics are arranged using various trimming filters in the color separation optical system. For example, Patent Document 1 (JP-A-2005-208256) has proposed a method for improving color reproducibility by increasing the luminance level of a fresh color using a trimming filter which has a special spectral transmission characteristic. In addition, another method is known, which arranges a transmission characteristic by disposing a half mirror on a bonding surface between the second prism 120 and the third prism 130, instead of the dichroic film DR1, and providing dichroic films having transmission characteristics, which approximate ideal characteristics, as the trimming filters 152 and 153. FIG. 22 illustrates a spectral characteristic of a color separation optical system, which is made by a special arrangement to approximate an ideal characteristic.
However, the color separation optical system using a trimming filter provided with a dichroic film on an exit surface of a prism has a wavelength range, in which a reflectance is high in some wavelengths, as a characteristic of the dichroic film. Consequently, the above color separation optical system has problems in that multiple reflections occur between the dichroic surface and an imaging surface and result in occurrence of ghost flare, and that picture quality is degraded. FIG. 23 illustrates multiple reflections occurring at the side of an exit surface of the third prism 130, from which green light LG is taken out, in the color separation optical system 101, by way of example. As illustrated in FIG. 23, the image pickup device 4G has an imaging surface 401G, a cover glass 402, and an extraction electrode 403. For example, a part of green light LG passing through the trimming filter 153 for green light is reflected by the imaging surface 401G. Then, the return light reflected therefrom is reflected by the dichroic film 153A provided on the trimming filter 153 according to the wavelength selectivity characteristic of the dichroic film 153A. Thus, multiple reflection light 160 is generated to thereby cause ghost flare. Accordingly, hitherto, it is difficult to implement an imaging system having an ideal spectral characteristic, which reduces ghost flare.
Further, although FIG. 17 illustrates the Philips type color separation optical system 101 in which the first prism 110 and the second prism 120 are disposed by interposing the air gap 110 AG therebetween, particularly, a gapless type color separation optical system, which is provided without the air gap 110AG therebetween, has a problem in that polarization separation is liable to occur at a reflection dichroic surface. FIG. 24 illustrates an example of the configuration of the gapless type color separation optical system 101A. The gapless type color separation optical system 101A shown in FIG. 24 differs from the Philips type color separation optical system 101 illustrated in FIG. 17 in the order in which the color components are taken out therefrom. The color separation optical system 101A is configured so that green light LG, blue light LB, and red light LR are respectively taken out by the first prism 110, the second prism 120, and the third prism 130, respectively. In the color separation optical system 101A, a green-reflecting dichroic film DG1 adapted to reflect green light LG and to transmit blue light LB and red light LR is formed on a reflection/transmission surface 111 of the first prism 110. Moreover, a blue-reflecting dichroic film DB1 adapted to reflect blue light LB and to transmit red light LR is formed on a reflection/transmission surface 121 of the second prism 120. The surface 111 of the first prism 110, on which the green-reflecting dichroic film DG1 is provided, and an incidence surface of the second prism 120, on which light is incident, are closely attached to each other without providing an air gap therebetween.
In the case of such a gapless type color separation optical system 101A, an incidence angle θ of incidence of light on the reflection dichroic surface (blue-reflecting dichroic film DB1) of the second prism 120 increases, as compared with the Philips type color separation optical system 101. In a case where the incidence angle θ increases, a phenomenon called a "polarization separation" occurs at the blue-reflecting dichroic film DB1. Thus, as is understood from an example of a transmission characteristic curve illustrated in FIG. 25, in the blue-reflecting dichroic film DB1, a wavelength width W100 required to change the transmittance of the film DB1 from a low transmittance band to a high transmittance band has a tendency to increase in a case where the transmittance is assumed to be an average of the transmittance of P-polarized light and that of S-polarized light. It is considered to be necessary for obtaining an ideal spectral characteristic to set the wavelength width W100 in an appropriate wavelength range.
The invention is accomplished in view of such problems. An object of the invention is to provide a color separation optical system and an image pickup apparatus, which are enabled to improve color reproducibility by obtaining a characteristic which approximates an ideal spectral characteristic in view of influence of polarization separation caused according to the magnitude of an incidence angle.

This patent is subject to a terminal disclaimer.

Color separation optical system and image pickup apparatus


Certain embodiments of the present invention provide a method for performing diagnostics in a medical imaging system during the normal operating mode of the imaging system including firing a diagnostic vector with a probe, collecting signal data based at least in part on the diagnostic vector, and processing the signal data to determine a diagnostic status. The diagnostic status indicates an operating condition of at least one component of the medical imaging system.

The present invention generally relates to medical imaging. In particular, the present invention relates to systems and methods for proactive detection of imaging chain problems during normal system operation.
Imaging systems encompass a variety of imaging modalities, such as x-ray systems, computerized tomography (CT) systems, ultrasound (US) systems, electron beam tomography (EBT) systems, magnetic resonance (MR) systems, and the like. Imaging systems generate images of an object, such as a patient. The images may be generated, for example, through exposure to an energy source or wave. For example, ultrasound beams may travel into a patient and produce echo signals reflected from bone and tissue inside the patient. As another example, an x-ray source may be used to generate x-rays that pass through an object. The x-rays may be partially absorbed by the object and an image may be generated based on the energy that passes through the object.
The generated images may be used for many purposes. For instance, internal defects in an object may be detected. Additionally, changes in internal structure or alignment may be determined. Fluid flow within an object may also be represented. Furthermore, the images may show the presence or absence of structures in an object.
The images generated by medical imaging systems may be used to assist a physician in making an accurate diagnosis. For example, a physician may use one or more images to visually identify a lesion or other anomalous structure in a patient. As another example, a physician may compare images taken over a series of patient visits to examine the evolution of a structure and/or to evaluate the effectiveness of a treatment. That is, the physician may examine morphological changes, such as changes in size and/or shape, of a lesion to evaluate its characteristics and/or the effectiveness of therapy.
In an ultrasound imaging system, for example, a sequence of beams or sound waves is generated by a probe. The transmitted waves are reflected or scattered from the object being scanned. Some of the waves may only be partially reflected. The reflected signals are received by the probe. The received signals are then read out from the probe and processed to create a digital image.
The ultrasound beams generated by an ultrasound imaging system are based on a scan sequence. The scan sequence includes a series of vectors that specify the parameters of the beam to be generated by the probe. The parameters may include amplitude and direction, for example. The vectors may be based on the kind of image desired and/or an scanning mode. For example, in a B-mode image, the scan sequence may specify a series of vectors to fan the beam through a plane to generate a two-dimensional image. As another example, a pulsed wave mode may be used for examining blood flow. A scan sequence may include and/or mix different kinds of vectors. For example, a scan sequence may include 100 B-mode beams mixed with 86 color beams.
Another type of vector that may be included in a scan sequence is a "junk" or "conditioning" vector. A junk vector may be used to set up initial conditions for subsequent vectors and/or when switching modes. A junk vector may be fired when it is desirable for a subsequent vector to have acoustic energy in tissue, for example. For example, in a sequence of color firings 0 through 10, a junk vector may be added to the sequence at firing −1, yielding the same side-effects regarding acoustic energy in the tissue for the actual color firings.
The reflected signals from the beams are received by the ultrasound probe. The reflected signals are then processed by the imaging chain of the ultrasound system. That is, the signals are read out of the transducer of the probe and then processed to generate one or more images.
Current medical imaging systems, such as ultrasound systems, may include system diagnostics that reside on the system for assessing problems with imaging performance. Such diagnostic systems are passive. That is, a field service person and/or operator must manually invoke the diagnostics. For example, a field service engineer may manually invoke one or more diagnostic checks either in person or remotely. Running these diagnostics results in downtime for the users of the system. In other words, while the diagnostic system is being utilized, the imaging system cannot be used for its normal operations. Thus, it is highly desirable to have an active system-health monitoring capability that runs when the system is being used for normal operations.
Certain aspects of an imaging system may be easily monitored. For example, power supply voltages, system temperatures, or the data error rates of a network connection may be relatively simple to check the status of. However, current systems are unable to actively monitor the status of the image chain. That is, failures, errors, and/or artifacts in the imaging chain that may be indicative of larger or developing system failures are not easily monitored in current systems. Thus, it is highly desirable to be able to actively monitor the status of the image chain.
Therefore, there is a need for an active system-health monitoring capability that runs when the system is being used for normal operations. In addition, there is a need for the ability to actively monitor the status of the image chain. Thus, there is a need for systems and methods for proactive detection of imaging chain problems during normal system operation.

Systems and methods for proactive detection of imaging chain problems during normal system operation


Techniques for power gating. A first on-die router has an output port to receive data from a switching fabric. The output port is placed in a power-gated state if there is no activity in the output port for a current cycle and no messages are to be received by the output port during a subsequent cycle. A second on-die router has an input port coupled with the output port of the first on-die router. The input port is placed in a power-gated state if an input port buffer is empty and the output port is not active. Power-gating of the input port and the output port are independent of each other.

On-die routers are typically designed with a pipelined architecture and the general trend is to reduce the pipeline depth for better performance. However, when power gating is applied to a router design, the performance typically suffers due to wake up delay when the power-gated functional blocks in the router are being activated. In these short-pipeline routers the performance impact from the wake up delay can be significant.
Typical on-die router designs assume a specific number of cycles of wake up delay and designers attempt to minimize the impact on performance by managing the power gating frequency and wake up/shut down strategies. However, these approaches have tradeoffs between power savings and performance decrease, preventing optimal operation.

Reduced wake up delay for on-die routers


Methods and system for sub-ambient pressure control for column head pressure in gas chromatography (GC) systems. The GC system includes an inlet and a capillary column connected to the inlet. The inlet includes a valve that regulates an inlet pressure and pressure sensor that measures the inlet pressure and outputs a signal that indicates a measured inlet pressure. The GC system also includes an inlet-pressure set-point that can be set to a negative pressure set-point representing a pressure below ambient pressure, the negative pressure set-point driving the valve to change the inlet pressure until the measured inlet pressure equals the negative pressure set-point.

In a typical Gas Chromatography (GC) system, a capillary column is connected from the inlet of the GC to a Mass Spectrometer (MS). GC-MS systems are operated in a vacuum outlet condition. When the GC-MS system is operated in this vacuum outlet condition, the optimum pressure at the inlet to the column can be very low. Theoretically, the optimum inlet pressure should be set so low that it would go negative relative to ambient pressure.
Electronic pressure control is common in current GCs. Pressure set-points are entered in gauge pressures (pressure relative to ambient pressure) using the electronic pressure control. Unfortunately, existing electronic pressure controllers in GCs do not allow negative pressure (relative to ambient pressure) set-points. Consequently, it is necessary in existing GC-MS systems to maintain a positive inlet gauge pressure set-point and a resultant positive inlet pressure. Column flow in the capillary column is proportional (i.e., a squared relationship) to the inlet pressure when the GC-MS system is operated in a vacuum outlet condition. As a result, maintaining a positive inlet gauge pressure causes a higher column flow than is actually desired. As shown by the Van Deemter-plot in FIG. 1, the higher column flow, measured as an average linear velocity, above a certain level results in a reduced efficiency (lower HETP=greater efficiency) for mass spectrometry. FIG. 1 shows that for the specified column, conditions, and chemical (carrier gas), an average linear velocity of between approximately 20–30 cm/sec results in the greatest efficiency.

Method and system for sub-ambient pressure control for column head pressure in gas chromatography systems


The invention relates to quaternary ammonium multi-dentate mono-, bis-, tris- and tetrakis-phosphonate compounds, processes for preparing quaternary ammonium multi-dentate mono-, bis-, tris- and tetrakis-phosphonate compounds, antimicrobial coating compositions comprising quaternary ammonium multi-dentate mono-, bis-, tris- and tetrakis-phosphonate compounds and method of treating a surface with said compositions to provide a durable, antimicrobial-treated surface.

Bacterial infections in hospital environments are spread by two different ways: external contamination or in vivo contamination from implants. Patients can develop external infections through contact with surfaces such as door handles, pens, telephones, health care workers uniforms ("HCWU"), stethoscopes, or sterile packaging that have been colonized by microorganisms. Hospital-acquired infections ("HAI") from contact with pathogenic microorganisms affect approximately 2 million people and result in more than 100,000 deaths in the U.S.A. each year. Such infections require 10-20 days of additional patient hospitalization, costing the already strained U.S. health-care systems approximately $25,000-30,000 per infection totaling billions of dollars per year.
The second route for bacteria to infect patients is through hospital invasive support equipment such as intravascular lines and implanted medical devices such as artificial prosthetics, cardiovascular implants and urinary catheters. Implant associated infections ("IAI") occur in more than one million patients and cost an estimated $3 billion in the U.S. per year. For example, approximately 10-50% of patients with implanted catheters run the risk of developing urinary tract infections ("UTI") resulting in additional healthcare costs. The rise in the frequency and severity of HAI's and IAI's can be attributed to decreased antibiotic efficacy against drug-resistant strains of pathogens found in surface biofilms.
Biofilm formation involves three phases beginning with the initial reversible adhesion of bacteria on a surface through polysaccharides and adhesion proteins on the bacterial membrane (phase I). Under appropriate conditions, bacteria subsequently firmly attach to a surface (phase II), followed by the secretion of a protective polymeric matrix (biofilm, phase III) in which the bacteria typically show a marked increase in resistance to antibiotics, compared to none-adherent bacteria. As a result, once the infection occurs, it becomes difficult to treat. Thus, strategies that prevent bacterial contamination or destroy adsorbed microorganisms that lead to biofilm formation are actively sought.
In order to prevent the formation of biofilm, strategies have been employed in the past to make surfaces inhospitable to bacteria. For example, small molecule monolayers or polymer thin films either "grafted to" or "grown from" a surface have been widely used to prepare antimicrobial surfaces and clothing. These prior art monolayers or polymer coatings include, for example, non-biofouling coatings which are passive strategies that rely on preventing bacterial adhesion with hydrophobic or zwitterionic thin films, but do not kill the approaching bacteria. A second class of antibacterial thin films kills microbes on contact either by releasing a biocidal agent or immobilizing a biocidal agent. A third class of antibacterial thin films utilize a combination strategy of including a non-biofouling and biocidal component into the coating.
Organophosphorus Antimicrobial Surfaces Based on Monolayers
The first quaternary ammonium phosphonate compounds (phosphonate quats) were disclosed in the early 1950's in U.S. Pat. No. 2,774,786 and Dutch patent NL 79189 for use as synthetic detergents. In the patents syntheses, the final product could only be isolated as a sodium salt of the phosphobetaine after hydrolysis of the phosphonate ester with HCl followed by treatment with NaHCO3. In a similar synthesis Germanaud et al., (Bulletin de la Societe Chimique de France, 1988, 4, 699-704) published the isolation of the phosphonate quats as betaines by purification on an anion exchange resin. The products disclosed in the patents were not spectrally characterized and were used as is, while Germanaud's purification was costly and the product wasn't isolated as a phosphonic acid.
Phosphonate monolayers for the antimicrobial treatment of surfaces have been shown to be advantageous over self-assembled monolayers (SAMs) of thiols and silanes in terms of durability, long-term stability and surface coverage, especially on titanium and stainless steel. Thiol-based SAM's lack substrate specificity (mainly reserved for gold surfaces) and long-term stability needed for biomedical applications, (i.e. implants). Over time, the thiol-based SAM's become oxidized to sulfonates, which lack affinity for gold and become displaced from the surface.
In comparison to silane based SAM's on metal oxide surfaces, phosphonate based SAM's are advantageous because they resist hydrolysis under physiological conditions and higher surface coverage can be obtained without harsh acid surface pretreatment (to increase the OH content). Siloxanes are also known to be unstable and are easily hydrolyzed under physiological conditions.
Both active and passive strategies to prevent biofilm formation have been described with both mono- and bis-phosphonate monolayers. Examples for active surfaces include contact killing monolayers employing immobilized quaternary ammonium salts and the antibiotic daptomycin. Passive strategies have been described employing hydrophobic perfluorinated bisphosphonates on stainless steel, silicon, and titanium oxidize surfaces for anticorrosion applications.
U.S. Pat. No. 4,101,654 teaches phosphonate-pendant nitrogen heterocyclic compounds that are quaternized by alkyl halides and their use as corrosion inhibitor compounds.
U.S. Pat. No. 4,420,399 teaches phosphonate-quaternary ammonium compounds having a methylene group linking the phosphorus and nitrogen atoms and their use as corrosion inhibitor compounds.
U.S. Pat. No. 4,962,073 teaches porous surfaces treated with phosphoric acid esters.
U.S. Pat. No. 5,770,586 teaches phosphonate/phosphoric acid-quaternary ammonium compounds for use as dental care ingredients and for bone density treatment.
U.S. Pat. No. 5,888,405 teaches methods of inhibiting bacteria from adhering to submerged surfaces using amino-phosphonic acid compounds.
U.S. Patent Application Publication No. 2002/0023573 teaches phosphonate, phosphate and phosphinate compounds linked to mineral oxide surfaces through the oxygen atoms of the phosphorus moieties.
U.S. Patent Application Publication No. 2002/0128150 teaches phosphonate, phosphate and phosphinate sulfur compounds linked to mineral oxide surfaces through the oxygen atoms of the phosphorus moieties.
PCT Application Publication WO 2007/080291 teaches bisphosphonate-amines and quaternary ammonium compounds, their preparation and attachment to metal and metal-oxide surfaces and testing for antibacterial activity.
PCT Application Publication WO 2008/017721 teaches bisphosphonate-amines and quaternary ammonium compounds, their preparation and attachment to silicon and metal surfaces and cell proliferation testing.
U.S. Patent Application Publication No. 2008/0220037 teaches bisphosphonic acid compounds having pendant oxygen, sulfur or at least two quaternary ammonium functional groups, their preparation and treatment of mineral and metal surfaces and antibacterial or biofilm formation testing.
Guerro G et al., Pathologic Biologie, 2009, 57, 36-43 teaches surfaces modified with materials such as phosphonate quaternary ammonium compounds and phosphonate silver coatings, and their bacterial adhesion and inhibition properties.
Queffelec C et al., Chemical Reviews, 2012, 112(7), 3777-3807 teaches phosphonic acids and esters, their synthesis and modification of surfaces using functionalized phosphonic acids and esters. The functional groups include heterocycles, amino groups and larger organic molecules.
Thus, there has been a long-felt need for a durable and environmentally safe antimicrobial metal or mineral surface treatment and a process to manufacture the same.

Phosphorus functional antimicrobial coatings for metal surfaces


A pixel electrode structure including a first electrode and a second electrode is provided. The first electrode has a first stripe electrode extended along a first direction and pleural first branch electrodes connected to the first strip electrode. The first branch electrodes include pleural first branch domain electrodes extended along a second direction and pleural second branch domain electrodes extended along a third direction substantially perpendicular to the second direction. The second electrode has a second stripe electrode extended along the first direction and pleural second branch electrodes connected to the second stripe electrode. The second branch electrodes include pleural third branch domain electrodes extended along the second direction and pleural fourth branch domain electrodes extended along the third direction. The first and the third branch domain electrodes are alternated to each other. The second and the fourth branch domain electrodes are alternated to each other.

1. Field of the Invention
The invention relates in general to a liquid crystal display, and more particularly to a multi-domain horizontal alignment (MHA) liquid crystal display panel and a pixel electrode structure thereof.
2. Description of the Related Art
Having the features of low voltage operation, no radiation, light weight and small size, the liquid crystal display (LCD) has gradually replaced the conventional cathode ray tube (CRT) display and become a mainstream product in the display market.
However, the liquid crystal display still encounters some problems such as the viewing angle being too narrow and the liquid crystal response time being too long. Therefore, how to enlarge the viewing angle and shorten the response time are prominent tasks for the industries. Currently, several solutions for wide-viewing angle LCD such as multi-domain vertical alignment (MVA) LCD, in-plane switching (IPS) LCD and fringe field switching (FFS) LCD are already provided. The IPS LCD generates a lateral electric field between the pixel electrode and the common electrode to drive the liquid crystal molecules to twist horizontally. The multi-domain horizontal alignment (MHA) LCD makes the liquid crystal molecules arranged in multiple directions to obtain pleural domains with different polarizing angles to increase the viewing angle of the LCD. Due to the restriction in electrode pattern, the liquid crystal molecules located between two adjacent domains are not driven by the electric field to twist. Consequently, the transmittance in the domain boundary region may easily deteriorate and image contrast is low.

Liquid crystal display panel and pixel electrode structure thereof


A conference condition file is used to check whether at least one stored conference condition is met, which indicates a condition regarding a participant's setup of and/or participation in the telecommunication conference. If at least one condition is met then the conference is set up or the participant is added to the conference.

The service called Push-to-Talk over Cellular (PoC) allows a user or sender to select one or more recipients and then, when he has pressed a special Push-to-Talk over Cellular key (PoC key), to transmit                speech        to a plurality of recipients simultaneously        using the half-duplex method, i.e., only the sender can speak and the recipients cannot interrupt him while he is speaking.
With this service, the voice data are usually already being distributed over the telecommunication network while the sender is speaking. This is also called "streaming." Thus, from the point of view of the user, Push-to-Talk over Cellular is similar to conventional CB radio, but with the extension that the sender is able to speak to recipients throughout the world who are able to be reached using the communications engineering of at least one telecommunication conference network, preferably a mobile radio telecommunication conference network. However, one prerequisite is that these recipients are also registered in the telecommunication network at the time at which the telecommunication link is set up, and in the case of a mobile radio communication network this means that they are registered, in other words that they are "online."
Push-to-Talk over Cellular has been specified in a first version in an industrial consortium and is described in Push-to-Talk over Cellular (PoC); Release 2.0. Further activities take place in the Open Mobile Alliance (OMA) and 3rd Generation Partnership Project (3GPP) standardization committee. Push-to-Talk over Cellular is implemented in the "packet switched domain" (PS domain, i.e., in the packet-switched domain of the telecommunication network; the communication network protocol used on the network layer level is the Internet Protocol (IP)).
For every Push-to-Talk over Cellular group session there is a central Push-to-Talk over Cellular server device, known as the controlling PoC server. During a PoC group session, the PoC client devices are linked to the controlling PoC server via a respective "participating server" associated with them. By way of example, the signaling communication link between a PoC client and a participating PoC server or between a participating PoC server and a controlling PoC server uses the IP Multimedia Subsystem (IMS), which uses the "Session Initiation Protocol" (SIP) as signaling communication protocol, as described in RFC 3261 "SIP: Session Initiation Protocol." The data transmission communication link between the PoC client and the participating PoC server or between the participating PoC server and the controlling PoC server uses the "Transport Protocol for Real Time Applications" (RTP).
Push-to-Talk currently has three different types of PoC groups (Push-to-Talk over Cellular groups), which are distinguished essentially by the structure of the PoC group session:                Ad-hoc PoC group session:        Before an ad-hoc PoC group session is set up, the initiator of the ad-hoc group session defines a list of PoC users, including their addresses, for example their telephone numbers, as an SIP-URL (Session Initiation Protocol Unique Resource Locator) or an SIP address as an SIP-URL.        In this connection, it should be noted that the list of PoC users may also comprise just one person. The list is included in the dispatch from the initiating PoC client to the controlling PoC server when the ad-hoc PoC group session is set up, and the controlling PoC server then invites all the PoC users contained in the list to join the ad-hoc PoC group session. Invited PoC users may accept, turn down or else ignore this invitation.        Prearranged PoC group session:        If one recurrently wishes to conduct a PoC group session with the same PoC users, a PoC user is able to define his own personal, fixed groups and to notify the controlling PoC of them. These are the "prearranged PoC groups."        By way of example, a PoC user can define his own prearranged PoC group "friends"' with the appropriate PoC users, including their address, for example a telephone number SIP-URL or an SIP address as an SIP-URL.        The prearranged PoC group is then allocated a dedicated group address, for example an SIP-URL. This group address is included in the dispatch from the initiating PoC client to the controlling PoC server when the prearranged PoC group session is set up, and the controlling PoC server then invites all the PoC users belonging to the prearranged PoC group to join this prearranged PoC group session. Invited PoC users may accept, turn down or else ignore this invitation.        Chat PoC group session:        Chat PoC groups are likewise firmly defined, known to the controlling PoC server and relate, by way of example, to a particular topic of discussion. With this type of PoC group, there is generally provision for a PoC user who is authorized to do so to dial into a chat PoC group session himself and then to be able to conduct a PoC group session with the other PoC users who are likewise taking part in this chat PoC group session as PoC participants.        This group session thus works in a similar manner to the provision made in a "chat room" on the Internet.
With Push-to-Talk over Cellular, there are thus two different options for a PoC user to be able to become a PoC participant in a PoC group session. Either he dials into a PoC group session (which is the usual way in the case of a chat PoC group session) or he accepts an invitation (which is the usual way in the case of an ad-hoc PoC group session or in the case of a prearranged PoC group session).
Internet Draft "A Session Initiation Protocol (SIP) Event Package for Conference State" discloses a "Session Status Notification" service, as a service feature (Feature) of Push-to-Talk over Cellular, which is used to inform a PoC user of the current status of the PoC group session. Such a status may include, by way of example, who is currently a PoC participant in the PoC group session. When a PoC user registers for such a service, he is thus aware at any time of how many and which PoC participants are currently taking part in a PoC group session. This optional service feature is implemented by the SIP extension SUBSCRIBE/NOTIFY, as described in RFC 3265 "Session Initiation Protocol (SIP)-Specific Event Notification."
If a PoC user wishes to take part in a discussion in a particular chat PoC group session, this PoC user may wish to take part only under certain conditions. By way of example, the PoC user may wish to take part in this chat PoC group session only if at least three people are already taking part in it, since he is of the opinion that the discussion cannot be of interest otherwise.
To be able to guarantee that such a condition is observed, the PoC user might register for the afore-mentioned service feature "Session Status Notification" and constantly, i.e., continuously, observe the current status regarding the chat PoC session of interest.
As soon as he establishes from the Session Status Notification messages transmitted to him that the condition that he himself has set, that is to say in this example that at least three PoC participants are already taking part in the PoC group session of interest, is met he enters the appropriate chat PoC group session.
A different scenario is conceivable with an ad-hoc PoC group session or with a prearranged PoC group session.
When the PoC user is invited to join such an ad-hoc PoC group session or a prearranged PoC group session, he might turn down the invitation at first because a condition that he has chosen and that he himself has set, for example that his boss should also already be taking part in this PoC group session, is not met. In that case, he subsequently observes the status of this PoC group session of interest, for example likewise by registering for the service feature "Session Status Notification," and dials into this PoC group session as soon as his boss is also taking part as a PoC participant in the PoC group session of interest.
One particular drawback of the two scenarios described above is that the PoC user himself must constantly observe the current status of a particular PoC group session and cannot request that he join a respective PoC group session that is of interest to him until the condition which he has set is met. Another drawback of the practices described above is that if the condition is never met then the user has wasted a large amount of time and energy in constantly observing the status of the corresponding PoC group session. It is also possible on the basis of the practices described above that, although the condition is met, the fact that the user has not noticed that the condition is met until at a late time means that he does not join the PoC group session until later or even until too late, and hence might not obtain information of interest to him that is distributed or interchanged in the PoC group session.
RFC 3311 "The Session Initiation Protocol (SIP) UPDATE Method" describes an SIP message UPDATE and RFC 2976 "The SIP INFO Method" describes an SIP message INFO.
RFC 2327 "SDP: Session Description Protocol" discloses the "Session Description Protocol" (SDP).
RFRC 3428 "Session Initiation Protocol (SIP) Extension for Instant Messaging" describes the SIP message MESSAGE.
The problems described above also arise in other telecommunication conferences, for example a telecommunication conference system on the Internet, which has been described in J. Rosenberg, A Framework for Conferencing with the Session Initiation Protocol, SIP Internet-Draft, IETF SIPPING Working Group: Draft-IETF-SIPPING-conferencing-framework-02, June, 2004, for example and is called "conferencing framework." On the basis of this telecommunication conference system, the standardization committee 3GPP also specifies the service IMS Conferencing.
Besides a method for controlling the access rights to multimedia telecommunication conference resources (also called floor control) and setting up conference rules (also called conference policy) the telecommunication conference system described in J. Rosenberg, A Framework for Conferencing With the Session Initiation Protocol, SIP Internet-Draft, IETF SIPPING Working Group: Draft-IETF-SIPPING-conferencing-framework-02 June 2004, also provides Session Initiation Protocol (SIP)-based procedures, inter alia for setting up, managing, entering and leaving telecommunication conferences. This system also contains methods for notifying the conference participants (also called Conference Notification Service) about specific information and events relating to the telecommunication conference. One of these notification methods is the aforementioned "Session Status Notification," for example. Within the telecommunication conference system, it is possible to interchange any types of media between the participants, and for this reason the telecommunication conference system is subsequently also referred to as a multimedia telecommunication conference system.
To define different rules, the multimedia telecommunication conference system described in J. Rosenberg, A Framework for Conferencing with the Session Initiation Protocol, SIP Internet-Draft, IETF SIPPING Working Group: Draft-IETF-SIPPING-conferencing-framework-02, June, 2004, defines the "Conference Policy Control Protocol" (CPCP), as described in H. Khartabil et al., The Conference Policy Control Protocol (CPCP), XCON, Internet Draft, IETF XCON Working Group: Draft IETF-XCON-CPCP-XCAP-01, July 2004.
US 2003/0153339 A1 describes a method in which a user sends a server a list of participants with the request to provide a conference involving the participants specified by the list of participants. In this case, the server checks, in particular, whether a conference involving the participants is already in existence and, if appropriate, adds the user to the conference retrospectively.
US 2004/0205212 A1 describes a method for forwarding service-related information to a network user. In this case, a terminal belonging to the network user requests event packets, and the network user is then informed about service configurations, for example.
US 2004/0199580 A1 describes a system for managing a conference in which a client application is used to configure a conference, a server unit manages the conference settings and configures a conference unit, so that the conference unit provides the conference at the scheduled time.

Method for automatically setting up and/or controlling a telecommunication conference


A silicone type cinnamic acid derivative which is a siloxane having at least one unit represented by the formula (I): ##STR1## and having the other units which may exist in the siloxane being represented by the formula: EQU O.sub.(4-m)/2 SiR.sub.m.sup.3. wherein R.sup.1 represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R.sup.2 is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom, O, X is an alkoxy group, n is an integer of 0 to 3, a is an integer of 2 or 3, R.sup.3 is an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, and m is an integer of 0 to 3.

1. Field of the Invention
The present invention relates to a novel silicone type cinnamic acid derivative and a method of preparing same, and to a novel UV-ray absorber and an external skin treatment agent.
More specifically, the present invention relates to a novel silicone type cinnamic acid derivative which can be dissolved in silicone oil, has an excellent water resistance and oil resistance, and has an UV-ray absorbing characteristic at wavelengths in the UV-B region, and to a novel external treatment agent having an excellent sunburn-prevention effect, useability, and prolonged cosmetic effects.
2. Description of the Related Art
As is well known, UV-rays cause various changes to the skin, and dermatologically, the acting wavelengths thereof are classified into long wavelength UV-rays of 400 to 320 nm, medium wavelength UV-rays of 320 to 290 nm, and short wavelength UV-rays shorter than 290 nm; called UV-A, UV-B, and UV-C, respectively.
Generally, most of the UV-rays to which humans are exposed are sunlight rays, and consist of UV-rays reaching the earth, i.e., UV-A and UV-B, and UV-rays absorbed in the ozone layer and not reaching the earth, i.e., UV-C. Of the UV-rays reaching the earth, UV-B rays cause erythema or blistering when irradiated on the skin at a certain dose or higher, and further, promote the forming of melamine in the skin, i.e., cause a darkening or dyeing of the skin.
Accordingly, protection of the skin from UV-B rays is very important from the viewpoint of preventing an accelerated aging of the skin and a generation or increase of splotching or freckling of the skin, and thus various UV-B absorbers to be used for this purpose have been developed.
Among existing UV-B absorbers, there are known PABA derivatives, cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, urocannic acid derivatives, benzophenone derivatives, and heterocyclic derivatives, and these UV-B absorbers are utilized exclusively by formulation in external treatment agents such as cosmetics and quasi-drugs.
As the external agent bases, silicone type bases with low molecular weights, such as dimethylpolysiloxane, are widely used, as is well known in the art, due to the excellent useability characteristics of such silicone type bases, e.g., a good extendability, plain feeling, and no stickiness, and an excellent function thereof in that they are not easily removed by sweat or water.
On the other hand, since sun-protection cosmetics in which UV-ray absorbers are formulated are used during hot summer, they are liable to be removed by excessive sweating or skin fat extrusions, and when these products are used at the beach or at a swimming pool, a problem arises in that they are removed when the skin is immersed in water. Therefore, there is obviously a need to enhance the cosmetic durability of these cosmetics, and accordingly, a silicone type base with a low molecular weight such as dimethylpolysiloxane, etc., is now widely used as the external treatment agent base, due in the most part to the properties possessed by silicone type bases; for example, a useability such as good spreadability, a plain feeling, no stickiness, and further, functional characteristics such as an excellent water resistance, oil resistance, and resistance to easy removal by sweat or water.
Nevertheless, existing UV-B absorbers have a remarkably low compatibility with or low solubility in silicone type bases, and accordingly, to formulate such UV-B absorbers in an external treatment agent having a silicone type base, an oily base must be added, and therefore, a drawback arises in that the useful properties of the silicon type base as described above are lost, and further, these compositions have an inferior water resistance and oil resistance.
Japanese Examined Patent Publication (Kokoku) No. 29866/1969, Japanese Unexamined patent Publications (Kokai) Nos. 58991/1985 and 108431/1985 disclose compositions having a UV-ray absorbability, but the chemical structures thereof include unsubstituted cinnamic acid as the basic skeleton, which has an absorption maximum wavelength on the UV-C side, in silicone oil, and thus the UV-B absorbability thereof is not satisfactory. FIG. 3 shows the UV absorption spectrum of 3-bis(trimethysiloxy)-methylsilyl-2-methylpropyl-cinnamate, from which it can be understood that this composition does not have an adequate wavelength region for a UV-B absorber.

Silicone type cinnamic acid derivative, preparation method thereof, UV-ray absorber, and external skin treatment agent