A method for increasing the accuracy and the types of data measurements of laser scanned dye stained cells, in a single sample, by means of multiple assays, utilizing cell positions as a factor in merging data measurements. Change in lasers, use of different cell dye stains and different treating reagents provide additional data regarding cells of the sample and fixing of cell positions in the first assay permits merging of the data obtained in subsequent assays.

A technique using fluorescent dyes for characterizing cells by flow cytometry (FCM) has been of considerable utility in immunohematology and cell biology. Another technique known as laser scanning cytometry (LSCM) has been developed to automatically measure laser excited fluorescence at multiple wavelengths and light scatter from cells on stationery slides (as opposed to a flow as in FCM) that have been treated with one or more fluorescent dyes in order to rapidly determine multiple cellular constituents and other features of the cells.
A laser scanning cytometer can use the methods perfected for FCM and has been shown to provide data equivalent to FCM for DNA analysis of aneuploid specimens, for immunophenotyping, and for analysis of cell proliferation and apoptosis. Because it is microscope based and measures cells on a slide and not in a flow chamber (as used in FCM), records position of each cell on the slide, and has higher resolution, it provides a number of benefits that may make it more suitable for pathology laboratories than FCM.
FCM has used fluorescent dyes to quantify cell constituents because fluorescence emissions are directly proportional to the mass of the constituent stained by the dye, if dye concentrations are low. Additionally, light scatter which has been useful to characterize cellular size and granularity occurs at a different wavelength than fluorescence and is easily separated from it in FCM. Automated fluorescence image analysis (FIA) in which a specimen is illuminated by an arc lamp or laser light source and is imaged at one or more wavelengths, using a CCD camera, has also been characterized for use in cell analysis.
The technologies of FIA, FCM and LSCM can be utilized to quantify cell constituents using fluorescence. Two of these, FCM and LSCM measure scatter as well as fluorescence. FIA, FCM, and LSCM each automatically measure fluorescence at multiple wavelengths of cells that have been treated with one or more fluorescent dyes in order to rapidly assay multiple cellular constituents. In FCM and LSCM, fluorescence and scatter result from interaction of the cells with a laser beam comparable in spot size to the cell. The laser optics is designed to produce a large depth of field with nearly collimated excitation to achieve accurate constituent measurements independent of cell position in the FCM stream or LSCM slide focus. In FIA the cells are uniformly illuminated, preferably by a mercury or xenon arc epi-illuminator. Fluorescence is imaged at high resolution and low depth of focus by a sensitive CCD camera. Commercial FIA, FCM and LSCM instruments provide feature values, for each event found, in standardized format computer list mode files.
In LSCM, the cells are measured and retained on a solid support such as a slide. In FCM, cells flow past the laser in a flow of cells which end in a waste container. The LSCM slide position and laser beam are moved under computer control to excite the cells. Since the position of the slide and laser beam is known to the computer, cell position on the slide is a measurement feature of LSCM but cell position cannot be a feature of FCM.
In LSCM, interactions of each cell and the laser are measured and recorded many times in a two dimensional pattern and features computed from these inter-actions are derived. In contrast, in FCM, properties of a single analog pulse are recorded as each cell flows past the laser focus.
With LSCM, because cells are prepared and measured on a slide, it is not necessary to provide single cell or nuclei only cell suspensions. Touch or needle biopsy specimens can be made as imprints or smears or tissue can be measured directly. Cytoplasmic as well as nuclear constituents can be characterized and centrifugations are not required and fewer cells may be lost. Preparations requiring amplification or specific fixatives can be employed without agglutination or cell clumping. The complete area encompassing a specimen is able to be scanned to allow all cells in a small specimen to be measured.
Since the absolute position on the slide of each measured cell's coordinates are recorded in the cell's list of features, the position feature can be used to relocate cells for visual observation or CCD camera image capture. Images may be included in reports or used for high resolution analysis of selected cells. Additionally, cells may be observed and categorized and their category used as values of a category feature for subsequent data analysis. Conversely, cells may be visually located and features of observed cells displayed. The position feature can be treated and displayed as any other feature and used for quality control of staining by displaying a fluorescence feature versus X or Y position.
The LSC.TM. laser scanning cytometer, available from CompuCyte Corporation, makes measurements on each cell at 0.5 micron spatial intervals. Features can be computed such as area, perimeter, the peak value found in the array, and texture, all of which give additional information useful in characterizing cells with fewer dyes and sensors. Constituents that are localized to regions of the cell such as probe spots in fluorescence in situ hybridization (FISH) preparations can be independently characterized yielding other features not obtainable with FCM. The total fluorescence, area, and peak fluorescence of the individual probe spots are used as laser scanning cytometer features allowing the laser scanning cytometer to more accurately count probe spots in cells of FISH specimens.
Cell contouring, i.e., outlining of the cell, is effected by presetting sensors to measure individual position pixel fluorescence values within the cell and to locate pixel positions within the cell where there is a predetermined drop-off of fluorescence value (threshhold value). A position having the predetermined drop-off is a boundary position, with the sum of such sites working to contour the cell.
A list of feature values is computed and stored in a PC computer disk data file for each cell found by the laserscanning cytometer. This list contains the following feature values:
For the sensor used for contouring:
1) The integrated value (the corrected sum of the pixel values in the data contour) equivalent to the FCM constituent value, PA1 2) The peak-value within the data contour, PA1 3) The area of the thresholding contour, PA1 4) The perimeter of the thresholding contour, PA1 5) The absolute slide position of the event's peak value, PA1 6) The computer clock time when the event was measured, PA1 7) The number of probe spots within the cell's data contour for FISH specimens, PA1 8) An annotation feature which the user adds as cells are relocated and visually observed, PA1 9) The structure of the data within the contour is analyzed to determine if the event represents a single or a multiple cell. Multiple cell events are tagged. PA1 1) The integrated value, PA1 2) The peak value within the data contour. PA1 1) The integrated value of all pixels in the probe contour, PA1 2) The area of the probe contour, PA1 3) The distance to the nearest probe spot. PA1 a) utilizing scanning means to examine the cell sample with initial examination parameters, while determining and recording the position of individual cells relative to the scanning means; PA1 b) utilizing the scanning means to examine the cell sample for each of the remainder of the multiple times and determining and recording the position of the individual cells relative to the scanning means during each of said remainder of the multiple times; PA1 c) using the recorded cell position of the individual cells from each of multiple examinations as a key to merge results obtained for individual cells having positions within predetermined deviation values. It is preferred, though not necessary, that the key also includes positions outside of predetermined overlapping distance values from adjacent cells.
For every other sensor:
For every probe spot during FISH applications:
As each specimen is run, the PC computer monitor screen shows a series of windows. Any number of windows containing scatter diagrams of any two features, or histograms of one feature can be displayed. These scattergrams or histograms can be related to the gating region of any other scattergrams or histograms so as to only display cells within the parent display's gating region. Any number of gating regions can be drawn using a mouse. In this way complex relationships involving any sets of features can be developed and used to display subsequent scattergrams or histograms compute a variety of statistics of cells within a region, including sub-population counts and distribution statistics, or to select events for relocation and visualization.
In both FCM and LSCM, it is desirable to simultaneously measure as many constitutents of individual cells as possible. For example, it is desirable to measure the total DNA of each cell simultaneously with two specific DNA sequences in which two fluorescence in situ hybridization probes are each bound to different fluorescent molecules or to simultaneously characterize DNA per cell, cell proliferation, and cell apoptosis. The number of constitutents that can be measured is limited since each laser used emits a single wavelength and can excite dyes to fluoresce only at wavelengths longer in wavelength than the excitation wavelength. Additionally, the excitation bands of many dyes are broad and have grossly different emission intensities and do not allow distinguishing multiple constituents, each stained with different constituent specific dyes. For example, the dye propidium iodide (PI), used to stain DNA, is used in LSCM for both finding and associating each cell's fluoresence digital data for analysis, as well as determining total DNA values per cell. PI is excited by an Argon ion laser and has a broad spectral distribution which does not allow any other dye excited by an Argon ion laser and emitting fluoresence at longer wavelengths than PI to be measured simultaneously with PI, limiting the number of cell constituents that can be measured. Another laser other than the Argon ion laser such as a red light emitting HeNe laser can be used to excite the fluoresence of longer wavelength emitting dyes such as CY3 and CY5 that can be conjugated to antibodies that will bind to specific DNA sequences or specific cell proteins. However, both lasers can not be used simultaneously in LSCM because the direct red light from the HeNe laser will interfere with the measurement of the Argon ion excited dyes since its wavelength is close the Argon ion excited dyes emission wavelength, and the Argon ion excited dyes emission will overlap the emission of the red laser excited dyes. It has therefore not been possible to distinguish more than one additional constituent when using dyes such as PI in a single LSCM assay.


There is provided composite nano-particles comprising nano-crystal particles dispersed stably and individually in suspension in high concentration without mutual aggregation of the nano-particles. A determined amount of pure water or deionized water is poured into a reactor, into which is introduced nitrogen gas at rate of 300 cm3/min for a given time while agitating with a stirrer to remove dissolved oxygen in the pure water, allowing to stand in an atmosphere of nitrogen. Next, the inside of the reactor is maintained in an atmosphere of nitrogen and sodium citrate as a dispersion-stabilizing agent, an aqueous solution of MPS as a surface-modifying agent, an anion aqueous solution for co-precipitation as a nano-crystal and a cation aqueous solution are added, in that order. Then, an aqueous solution of sodium silicate is added to the reactor, which is then allowed to stand in the dark place in an atmosphere of nitrogen after agitation. At that time, a vitrification-inhibiting agent may be added in order to inhibit the growth of glass layer.

1. Field of the Invention
The present invention generally relates to a composite nano-particle in which each of more than two kinds of chemical species has a phase individually and forms a nano-sized particle and method for preparing the same and, more particularly relates to a nano-sized nano-particle for, for example a composite low energy electron exciting light emitting phosphor etc., composed of independent good dispersible particles, which is formed without coagulation of composite nano-particles in the process of production.
2. Discussion of Background
In recent years, it has been noted that a nano-crystal (nano-structure crystal) has unique optical characteristics in an ultrafine particle such as Si, Ge, etc. porous silicon, semiconductor of II-IV group element in the periodic table. The nano-structure crystal herein used means a crystal particle having a particle diameter of several nm (nano-meters) and often referred to as nano-crystal.
By the way, different types of phosphors are used in a display such as a television etc. A phosphor currently used for a display of a television etc. is synthesized by firing raw materials at high temperatures. The particle diameter of the phosphor thus synthesized is several micrometers (3-10 μm). On the other hand, in recent years, a low-profile display has been desired in the filed of television etc. and a lightweight flat display such as a plasma display (hereinafter referred to as PDP), field-emission-display (hereinafter referred to as FDD), electro-luminescence-display (hereinafter referred to as ELD) has received considerable attention.
When the above-described FED which has received particular attention is formed in low-profile, it is necessary to lower the voltage of electron beam. However, when such a phosphor having a particle diameter of several micrometers as above described is used in a low-profile display, sufficient emission can not be obtained because low voltage of electron beam. That is to say, such a low-profile display can not excite sufficiently a conventional phosphor.
A low energy electron exciting light emitting phosphor is generally used in a vacuum fluorescent display. Particularly, a nano-sized phosphor is suitable for an FED, a highly-refined thin-profile vacuum fluorescent display, etc.
On the other hand, a nano-crystal phosphor can excite the afore-mentioned phosphor with an electron beam irradiated by low voltage and to emit light. A phosphor which satisfies such requirements is exemplified by a II-IV group semiconductor having such a nano-structure crystal as above described.
Unexamined Patent Publication (Kokai) No. 10-310770 discloses a method of preparing a nano-sized phosphor by using co-precipitation. In such a conventional invention as disclosed in the publication, a nano-sized phosphor particle doped with an activating agent by a liquid phase reaction using co-precipitation is formed and simultaneously, an organic acid acrylic acid, methacrylic acid, etc. is added to the liquid phase reaction. Thereby, the surface of the afore-mentioned phosphor particle is coated with the organic acid and defects on the surface of the phosphor particle are decreased to make improvements in the emission efficiency possible.
Further, an activating agent is dispersed uniformly on a II-IV group semiconductor by the afore-mentioned liquid phase reaction using the co-precipitation method. According to such a prior art, the only organic acid is boned to ZnS:Mn via S—O bond added. Unexamined Patent Publication (Kokai) No. 10-310770 describes on pages 6 and 8 that when ZnS:Mn is bonded with an organic acid, it coats the surface of the phosphor particle and supplies energy required for light emission. Since, however, coating with only organic acid is performed is such a technique as described in Unexamined Patent Publication (Kokai) No. 10-310770, there is a problem in the stabilization.
Unexamined Patent Publication (Kokai) No. 2000-265166 discloses a phosphor which is formed by coating a nano-sized nano-crystal phosphor particle ZnS-Tb obtained by the liquid phase reaction using precipitation with a glass component. Such a glass component as described in the publication is a gel-like (—SiO—) n film obtained by polymerizing tetrakissilane in ethanol, ion-exchanged water and hydrochloric acid.
In such an invention as described in Unexamined Patent Publication (Kokai) No. 2000-265166, a nano-crystal phosphor or another composite nano-particle obtained by the liquid phase reaction using precipitation is reacted with a gel-like glass component, that is, coated directly with a gel-like (—SiO—) n film obtained by polymerizing tetrakissilane in ethanol, ion-exchanged water and hydrochloric acid, thereby improving the light emission efficiency in electron beam excitation emission.
However, a composite nano-particle the surface of which is coated with a glass component constituted by such a prior art aggregates, similarly to a conventional composite nano-particle. Therefore, original characteristics of nano-crystal can be hardly obtained.
Among the afore-mentioned nano-crystal, a semiconductor nano-crystal having a quantum size effect is situated in a transition region between a bulk semiconductor of mono-crystal or large particles and a molecule and shows characteristics different from them. Therefore, it has received considerable attention in a variety of fields.
In the case of a nano-crystal having specific characteristics for a crystal particle of a metal or insulator having a particle diameter of several nano-meters other than the above-described semiconductor nano-crystal, nano-crystal phosphor, a nano-crystal having excellent dispersibility is provided.
Tremendous research effort has been made on the optical characteristics of the afore-mentioned semiconductor nano-crystal toward the practical use for an optical material, phosphor material, photo-catalyst, etc. However, such a semiconductor nano-crystal has problems to be solved, that is to say, it is unstable compared with a bulk semiconductor and easy to be decomposed and degraded, control of particle diameter is hard because of the presence of particle distribution, synthetic method is hard or complicated, mass-production is hard, etc.
By the way, among the afore-mentioned semiconductor nano-crystals, a method of preparing a conventional nano-sized phosphor has such defects as described below. While a nano-sized phosphor particle can be easily synthesized by a general co-precipitation method of a prior art, nano-sized phosphor particles aggregate each other immediately in a reaction solution and the particle size of the nano-sized phosphor particle thus obtained is made apparently larger than Bohr diameter of ZnS. Therefore, there are problems that a group of thus aggregated phosphor particles is coated with an organic acid or glass component, and particle size is made larger furthermore, and the quantum size effect or quantum confined effect can not be sufficiently exerted.
Next, the afore-mentioned quantum size effect and quantum confined effect are explained in detail. Change in physical properties depending on size appears particularly in optical properties. Specifically, when the particle size of the nano-sized phosphor particle is made smaller than the effective Bohr diameter of ZnS, it is well known that its electron state is different from that of bulk semiconductor. That is to say, when a phosphor is a very small atomic group in the order of nano-meter, a band rank which must be continuous originally is discontinuous with an increase in number of atom, and consequently the energy of HOMO lowers, and the energy of LUMO rises. Therefore, a band gap increases and excitation energy also increases. These phenomena are called "quantum size effect."
When a phosphor absorbs an electron beam or light, it forms an electron and a hole in a band. While an electron and a hole move individually in a state of bulk, a pair of electron-hole (exciton) is formed stably because the electron and hole are confined in a very narrow space in a nano-particle. Thereby, the energy transportation efficiency to light emission, that is, the light emission quantum efficiency increases. These phenomena are called "quantum confined effect."
A combination of chemical species constituting a nano-crystal must be selected, depending on a specific objective. Such a combination is exemplified by [metal/oxide/sulfide] or [conductor/semiconductor/insulator]. For example, CdS/SiO2, CdS/CdSe, Au/SiO2, etc. are exemplified.

Composite nano-particle and method for preparing the same

Keio University Faculty of Science and Technology


Organopolysiloxanes containing a sulfide-containing organic group, a long-chain alkyl group, and a hydrolyzable group are novel. The organopolysiloxanes are effective for improving the shelf stability of epoxy resin compositions.

Organopolysiloxanes containing a mercapto group and a hydrolyzable group and their making methods are known in the art. For example, Patent Document 1 discloses a method of preparing an organopolysiloxane by hydrolytic condensation using a neutral fluorine compound as the catalyst. Patent Documents 2 and 3 disclose that organopolysiloxanes containing a mercapto and hydrolyzable group are used in coating compositions and rubber compositions. However, the compositions comprising an organopolysiloxane containing a mercapto and hydrolyzable group lack shelf stability because the mercapto group is active.
Also known are organopolysiloxanes containing a sulfide group and a hydrolyzable group and their making methods. For example, Patent Document 4 discloses an organopolysiloxane containing a sulfide and propyl group and a method of preparing the same.
However, organopolysiloxanes containing a sulfide-containing organic group, long-chain alkyl group, and hydrolyzable group are unknown.


A system and method switches between an active call and a call on hold when handing off a mobile station (204) from a Wireless Local Area Network (WLAN) (202). A Handover Starting message is received from a mobile station. The Handover Starting message includes at least one first identifier. A Notification message is also received. The Notification message includes a second identifier. The at least one first identifier is compared to the second identifier and a handover of the mobile station (204) proceeds when a match is determined. Subsequently, the mobile station (204) switches from an active call to a call on hold.

Mobile stations that operate in Wireless Local Area Networks (WLANs) are often capable of engaging in multiple calls. For example, a first user at the mobile station may be engaged in an on-going voice call with a second user, another voice call from a third user may arrive at the mobile station of the first user, and the first voice call may be put on hold. After completing the call from the third user, the first user may switch back to the initial call (that had been placed on hold) and continue the first call with the second user.
Some WLANs are connected to other networks, such as a cellular networks or the Public Switched Telephone Network (PSTN). Mobile stations operate within WLANs and utilize various protocols and messages to communicate. In one example, some wireless systems use the Session Initiation Protocol (SIP) to enable communications between mobile stations. Specifically, certain messages such as SIP INVITE messages are exchanged between mobile stations to initiate and conduct communications between these devices.
Mobile stations are typically not stationary within WLANs or other networks. For example, if the mobile station is a dual mode cellular telephone, the phone typically moves within the WLAN and then between the WLAN and other networks. When the mobile station leaves the WLAN, it is handed off (or over) to the receiving network. Various messaging protocols and sequences have been developed to ensure that the transition occurs smoothly.
Previous systems, however, do not allow a user at a mobile station to switch between an active call and a call on hold while the user is handed out of the WLAN system. This inability to switch between calls when handing a mobile station out of the WLAN system results in unpredictability in service for users, potential lost calls, and user dissatisfaction with system performance.
Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and/or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments of the present invention. It will also be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein.

System and method of switching between calls when handing off a mobile station out of a WLAN


The present invention discloses a composition for improving internal circulation and delaying aging and application thereof, and the composition is prepared by Rosa roxburghii, Phyllanthus emblica, honey, walnut and Citrus limon as raw materials.

Aging refers to a progressive process that progressive hypofunction and decline of reserve capacity occur in functional activities of organs in human body with age after mature. It is mainly featured by lassitude, waist-leg weakness, amnesia, poor appetite and insomnia, short breath and tiredness, hair loss and loose tooth, intolerance of cold and cold limbs.
At present, there are different opinions on the occurrence mechanism of aging, modern medicine studies believe that aging correlates to the change of in-vivo oxyradicals, endocrine abnormality, brain damage, protein denaturation, inheritance and other factors; traditional Chinese medicine researchers and scholars believe that aging is mainly caused by kidney deficiency, deficiency of spleen and stomach, stagnation of Qi and blood, etc., and mainly manifested by decline of visceral functions, aging appearance and functional degeneration, functional decline of organs, tissues, limbs and bones, etc. In recent years, studies on the theory of aging caused by stagnation of Qi and blood based upon traditional Chinese medicine have been increasingly concerned by traditional Chinese medicine researchers and scholars at home and abroad, showing a theory of dissipative structure, namely: human body is regarded as a dissipative structure which is a system capable of keeping homeostasis in the course of material/energy exchange with the external environment, and when the system is in a stagnation status for a long time, it fails to achieve effect material/energy exchange to supplement the "substance" demanded by daily activities of our human body, thus causing continuous dissipation of nutrient substances, accumulation of hazardous substances, resulting in aging. Researches of modern traditional Chinese medicine show that there is a disturbance of blood circulation and microcirculation in human body with age, which is easy to form blood stasis, causing disturbance of Qi and blood circulation, failure of visceral nourishment and damage of gasification function; meanwhile, metabolites may be not discharged out of body freely and accumulated in body, causing body toxication, thus creating a vicious circle and accelerating aging.
With the gradual improvement of people's life, people's health-care consciousness has enhanced gradually, and moreover, with the social aging in recent years, the market requires 112q1q
increasingly high demand for the products capable of regulating internal circulation, improving body functions and delaying aging. Currently, the common anti-aging products are mainly precious Chinese herbal medicines and preparations thereof, such as: Ginseng Royal Jelly, Ginseng tablets, Panax quiquefolium tablets, Ophiocordyceps sinensis 5X, but these preparations have single effect and are expensive, moreover, the anti-aging effect is not significant.
Based upon this, with the guidance of the theory of the traditional Chinese medicine, and combined with decades of clinical research and medication experience, the inventor repeatedly optimizes and adjusts the recipe to obtain the composition of the present invention finally; the composition has the efficacy of dredging the channel, regulating Qi functions of visceral organs, expelling vivotoxins, supplementing human nutrition, improving internal circulation, enhancing body functions and delaying aging.

This patent is subject to a terminal disclaimer.

Composition for improving internal circulation and delaying aging and application thereof

GUIZHOU JIN QIAN FRUIT BIOTECHNOLOGY CO., LTD.


A vertical flow meter comprises a vertical barrel, an adjustment mechanism and an induction mechanism. The vertical barrel has a flow passage inside to house a vertical rod and a magnetic element coupling on the vertical rod. The adjustment mechanism straddles a holding plate and a scale plate that are located at two sides of the vertical barrel, and includes an adjustment portion at one side thereof, at least one adjustment member corresponding to a second elongate slot of the scale plate and fastening to the adjustment portion, a protrusive connection portion at another side opposite to the adjustment portion, and a connection plank connecting with the adjustment portion and protrusive connection portion. The induction mechanism is disposed at one side of the protrusive connection portion. Through magnetic attraction between the induction mechanism and the magnetic element, the adjustment mechanism can be moved upward or downward on the scale plate.

Many types of vertical flow meters are now available on the market. FIG. 1 illustrates an example that a vertical flow meter 1 is assembled with an upper flow tube 11 and a lower flow tube 12 for various types of liquids to flow through. The vertical flow meter 1 includes a holding plate 13 installed on the back side thereof with a guide slot 131 formed on the holding plate 13, and a screw fastener 141 run through the guide slot 131 to fasten an induction mechanism 14 to the holding plate 13. When the vertical flow meter 1 is in use, the back side of the vertical flow meter 1 and a wall surface 15 are very close and spaced from each other with only a small gap 16 which makes adjustment of position of the induction mechanism 14 difficult. To do the adjustment of the induction mechanism 14, first, the vertical flow meter 1 has to be detached, and the screw fastener 141 has to be unfastened. After the position of the induction means 14 has been adjusted, the screw fastener 141 has to be fastened again. Hence for the conventional vertical flow meter 1, adjustment of the position of the induction mechanism 14 is very inconvenient and time-consuming. There is still room for improvement.


The present invention relates to isoxazole derivatives, including pharmaceutical compositions and for the preparation of isoxazole derivatives. And more particularly the present invention provided a pharmaceutical composition of isoxazole derivatives for activation of Farnesoid X receptor (FXR, NR1H4).

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. FXR is highly expressed in the liver, intestine, kidney, adrenal glands, white adipose tissue and in induced during adipocyte differentiation in vitro. (Cariu B. et al., J. Biol. Chem., 2006, 16, 11039-11049).
Not only FXR regulates various physiological processed such as modulates regulated of bile acid (BA) regulation, lipids/glucose metabolism, inflammation/fibrosis, but recently it has also been linked to the pathology of FXR receptors.
This nuclear receptor is the intracellular bile acid f"sensor" and its major physiological role is to protect liver cells from the deleterious effect of bile acids (BA) overload. Intestine is the tissue expressing the first FXR target gene identified. Indeed IBAB-P is expressed in enterocytes and binds bile acids, thus limiting the free concentration of BA intracellularly and consequently their toxicity. (Makishima M, et al., Science, 1999, 284(5418), 1362-1365). FXR is highly expressed in the liver and regulates key genes involved in BA synthesis, metabolism and transport including CYP7A1, UGT2B4, BSEP, MDR3, MRP2, ASBT, NTCP, OST α and OST β in humans. One effect of FXR activation is down regulation of CYP7A1 and thus bile acid synthesis; this is accomplished through induction of SHP (Small Heterodimer Partner) which then represses CYP7A1 transcription (Claude T, et al., Arterioscler. Thromb. Vase. Biol., 2005, 25, 2020-2031). Altered expression or malfunction of these genes has been described in patients with cholestatic liver disease. FXR agonist 6-ethyl-chenodeoxycholic acid (6EtCDCA) was found to fully reverse the impairment of bile flow and to protect the hepatocytes against liver cell injury caused by the cytotoxic lithocholic acid. (Pelliciari R, et al., J. Med. Chem., 2002, 45(17), 3569-3572).
In the intestine, FXR also induces expression of SHP which represses transcription of the apical sodium dependent bile acid transporter (ASBT, SLC10A2) gene which encodes the height affinity apical sodium dependent bile acid transporter that mouse bile acids from the intestinal lumen into the enterocyte as part of the enterohepatic recycling of bile acids. (Li H, et al., Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 288, G60-G66). Ileal bile acid binding protein (IBABP) gene expression is also induced by FXR agonists in the enterocyte. (Grober J, et al., J. Biol. Chem., 1999, 274(42), 29759-29754). FXR seems to be also involved in paracrine and endocrine signaling by upregulation the expression of the cytokine Fibroblast Growth Factor 15 (rodents) or 19 (monkeys, humans). (Holt J, et al., Genes Dev., 2003, 17(13), 1581-1591; Inagaki T, et al., Cell Metab., 2005, 2(4), 217-225).
FXR activation has also been described to downregulate proinflammatory enzymes iNOS and COX-2, as well as migration of vascular smooth muscle cell migration. (Li Y T Y, et al., Arterioscler Thromb Vase Biol., 2007, 27(12), 2606-2611). FXR is also expressed in hepatic stellate cells (HSC) which play a role in deposition of extracellular matrix during the fibrotic process. Treatment of cultured HSCs with the FXR agonist 6-ethyl-chenodeoxycholic acid (6EtCDCA) results in decreased expression of fibrotic markers such as α-smooth muscle actin and α1(I) collagen. 6EtCDCA has also been reported to percent development and promote resolution of hepatic fibrosis in multiple rodent models of this disease. (Fiorucci S, et al., Gastroenterology, 2004, 127(5), 1497-1512; Fiorucci S, et al., J. Pharmacol. Exp. Ther., 2005, 314(2), 584-595).
The process of enterohepatic circulation of bile acids is also a major regulator of serum cholesterol homeostasis. After biosynthesis from cholesterol in the liver, bile acid (BA) are secreted with nile into the lumen of the small intestine to aid in the digestion and absorption of fat and fat-soluble vitamins, The ratio of different BA determines the hydrophilicity of the bile acid pool and its ability to solubilize cholesterol. FXR activation increases the hydrophilicity of the pool, decreasing the intestinal solubilization of cholesterol, effectively blocking its absorption. Recent report have shown that FXR opposed this effect in part by directly repressing the expression of HMGCoA reductase via a pathway involving SHP (Small Heterodimer Partner)  LRH1. (Datta S, et al., J. Biol. Chem., 2006, 281(2), 807-812).
According to subsequent studies, FXR activation affects Triglyceride (TG) metabolism via several pathways such as Sterol regulatory element-binding transcription factor 1 (SREBF1), apoC-III, apoC-II, syndecan-1 and the VLDL receptor. Recently new FXR modulator compounds show the ability to reduce both plasma triglyceride (TG) and cholesterol levels in normal and hyperlipidemic animal models (WO2007070796).
In addition, FXR agonist GW4064 or cholic acid treatment reduced plasma glucose levels and improved insulin sensitivity in three diabetic models (db/db, ob/ob and KK-A(y)mice) (Cariu B, et al., J. Biol. Chem., 2006, 281(16), 11039-11049 Zhang Y, et al., Proc. Natl. Acad. Sci., 2006, 103(4), 1006-1011; Ma K, et al., J. Clin. Invest., 2006, 116, 1102-1109). This demonstrates that FXR is involved in glucose metabolism.
Therefore, FXR activity has been implicated in variety of diseases, including, but not limited to disorder of bile acid homeostasis, inflammation/fibrosis and height levels of plasma triglyceride (TG)/cholesterol.
Conventionally known FXR agonists INT-747 (OCA) and EDP-305 are modified bile acid (BA), developed for the treatment of diseases caused by disorder of bile acid homeostasis such as Nonalcoholic fatty liver disease (NASH), Alcoholic disorders, Primary biliary cirrhosis (PBC), Primary sclerosing cholangitis (PSC) and caused clinical side effects for the accumulation of substances in the body.
Following, small molecule compounds such as FXR agonist were derived form GW4064, PX-102 (GS-9674)/PX-104 and Global Pharmaceutical Company published various patent with various derivatives (WO2000037077, WO2003015771, WO2004048349, WO2009012125, WO2009149795, WO2011020615, WO2013037482 and WO2016097933).
As FXR agonist has been progressed with respect to the prior published clinical literature, has a new mechanism of action for the treatment.
FXR agonist is development as target for variety treatment of diseases, including, but not limited to disorder of bile acid homeostasis, inflammation/fibrosis and height levels of plasma triglyceride (TG)/cholesterol so that worldwide attention is focused.
So The present invention is expected that patients with metabolic diseases, including, but not limited to cholestatic Liver Diseases, Organ Fibrosis and Liver Fibrosis, will be able to open a therapeutic field of new mechanism.

Isoxazole derivatives as nuclear receptor agonists and uses thereof


To provide a connector which is capable of reducing the possibility that a cover is removed due to a cause other than an operation of removing a card when the cover is in a locked position, even if a height of the connector is reduced. A cover 7 which covers an upper surface of an IC card 21 accommodated in an accommodating section 33 of a housing 3 is pivotally mounted on the housing. The cover 7 is formed by a cover main body 71 which is opposed to the upper surface of the IC card 21 accommodated in the housing 3, arm portions 74 and 74 which are connected to the cover main body 71, shaft portions 75 and 75 which are connected to the arm portions 74 and 74, respectively, and are pivotally supported by respective slots 321a formed in respective side plates 312 of the housing 3. The arm portions 74 and 74 are capable of being elastically deformed, and being brought into contact with opposite sides of the IC card 21 accommodated in the housing 3. The shaft portions 75 and 75 are inserted through the respective slots 312a and 312a from the accommodating section 33 of the housing 3.

Conventionally, there has been proposed a connector of this kind, comprising an insulator, contacts, and a cover (see Japanese Laid-Open Patent Publication (Kokai) No. 2006-85987).
The insulator includes an accommodating portion for accommodating a card, such as an IC card.
The contacts are held by the insulator.
The cover is pivotally mounted on the insulator. Further, the cover is capable of moving between a locked position and an open position along a longitudinal direction of the insulator. When the cover is in the locked position, the cover is locked to the insulator. When the cover is in the open position, the cover is unlocked from the insulator, and at the same time can be opened.
The cover is formed by blanking and bending a metal plate. The cover includes first and second card-holding portions for holding a card, a pair of arm portions, and a pair of shaft portions. A cross-section of each of the first and second card-holding portions is U-shaped. The pair of arm portions are each substantially leaf spring-shaped, and are each capable of being elastically deformed in a direction of a width of the card. The pair of shaft portions are each disposed on an inner surface of the respective arm portions (surface toward the card), and each protrude toward the card. The shaft portions are inserted into respective recesses formed in one end of the insulator from outside the insulator.
To mount the card in the connector, the cover is opened by sliding the cover to the open position, and the card is inserted into the first and second card-holding portions of the cover.
Thereafter, the cover is closed and is slid to the locked position.
When the cover reaches the locked position, contact portions of the contacts are brought into contact with pads of the card. As a result, the card is electrically connected to the connector.
To remove the card from the connector, it is only necessary to perform the above-mentioned mounting operation in reverse order.
In this connector, since the arm portions are capable of being elastically deformed in the width direction of the card, it is possible to insert and remove the shaft portions of the cover into and from the recesses of the insulator, so that it is possible to mount and remove the cover to and from the insulator with ease.


The invention relates to a filter circuit and a method for making a filter circuit comprising at least one gyrator core section (GCi) having four inverters mutually connected in a loop configuration between a pair of input terminals (ixe2x80x941; ixe2x80x942) and a pair of output terminals (oxe2x80x941; oxe2x80x942). At least one common mode feedback section (CMIi, CMOi) is provided between the pair of input terminals and/or the pair of output terminals. The common mode feedback section comprises two series connections respectively formed by an inverter and a short-sectioned inverter connected antiparallelly between the input terminals or the output terminals. The inverters may be constituted by a MOS, CMOS or BiCMOS or bipolar transistor. According to the invention, the channel region dimensions of the transistors of the gyrator core section and/or the common mode feedback section are selected such that the relationship g*Cxe2x89xa7gm*cm is fulfilled, where g is the effective conductive loading of the gyrator core section terminals, C is the effective capacitive loading of the gyrator core section terminals, gm is the effective gyration constant of the gyrator core section, and cm is the effective transcapacitance of the gyrator core section.

The invention relates to a filter circuit consisting of at least one filter stage in which amplifier-like circuits such as integrators and/or gyrators are employed to emulate the impedance of inductors. The invention also relates to a method for making (designing) such filter circuit.
The invention in particular addresses the problem how complex (higher order) filters can be designed such that the actual filter characteristics obtained in the practically realized filter circuit coincide with the theoretically designed filter characteristics. The invention also addresses the problem how such complex (e.g. higher order) filters can be designed such that they are stable.
As shown in FIG. 1, typically a filter circuit consists of a plurality of filter stages FST1 . . . FSTi wherein the first filter stage FST1 is driven by a source, e.g. a current source CS and a source impedance SI, and the output of the last filter stage FSTi is terminated with an output impedance OI. As is well known to the skilled person the filter transfer function is essentially a polynomial consisting of a plurality of poles and zeros in the complex plane. Depending as to whether the individual filter stages FSTi are a filter stage of first order or higher order, a desired filter function and thus a desired filter characteristic can be obtained.
Hereinafter, it is assumed that each filter stage FSTi consists of a single transistor or gyrator. However, of course the invention is not restricted to each filter stage being of the said types but also higher order filter stages may be used.
Depending on the desired filter transfer function, each filter stage is realized by coils, resistors and capacitors. For example, on-chip filters are normally restricted to resistor/capacitor filter stages, except at very high frequencies where on-chip coils of a few nH may be employed. In such passive filter realizations (i.e. no active circuitry is employed in the filter stages FSTi) it therefore depends on how accurate or whether at all coils (more particular the coil impedance) can be realized by a passive coil construction.
As is also well known to the skilled person in the art of filter design, active on-chip filters are often used to circumvent the coil restrictions in passive filter circuits. In such active filters amplifier-like circuitry is used to emulate the impedance of the inductors. That is, the coils are replaced by an active circuit. For continuous-time filters such amplifier-like circuits typically consist of integrators or gyrators and for discrete-time circuits (digital filters) integrators are used for emulating the coils impedance.
Continuous-time filters implemented with integrators typically employ such elements in loops and these loops. Two integrators in a loop actually form a gyrator. If the forward and backward integrators have the same gain characteristics they form a passive gyrator and if they do not have the same gain characteristics they form an active (or asymmetric) gyrator. FIG. 2 shows a typical block diagram of a gyrator and its equivalent circuit diagram. The input voltage V1 and the output voltage V2 are linked via the gyration constant gm* as I1=xe2x88x92gm*V2 and I2=gm*V1. Thus, the gyrator shown in FIG. 2 consists of a positive transconductance gm* and a negative transconductance xe2x88x92gm*.
FIG. 3 shows a typical realization of the gyrator in FIG. 2 employing at least one common mode feedback section CMIi, CMOi and a gyrator core section GCi. As shown in FIG. 3, the negative transconductance xe2x88x92gm* is typically formed by employing differential signals and crossing one pair of wires. That is, the gyrator core section GCi comprises four inverters GI1i-GI4i mutually connected in a loop configuration between a pair of input terminals i_1; i_2 and a pair of output terminals o_1; o_2. The common mode feedback section CMIi, CMOi is connected between the pair of input terminals and/or the pair of output terminals and comprises two series connections respectively formed by an inverter CMI1, CMO1 and a short-circuited inverter CMI2, CMO2 connected antiparallely between said input terminals or said output terminals. It should be noted that one of the input or output common mode feedback sections CMIi, CMOi is sufficient for realizing the positive transconductance gm* and that one gyrator core section GCi is sufficient for realizing the negative transconductance xe2x88x92gm.
However, independent as to how the actual inverters are realized (by MOS, CMOS, BiCMOS or bipolar transistors), the crossing of the wires results in a loop through the four inverters GI1i, GI2i, GI3i, GI4i. FIG. 4 shows the realization of the inverters in FIG. 3 using two CMOS transistors T1 (e.g. NMOS) and T2 (e.g. PMOS) whose drains D and gates G are connected with the respective sources connected to ground. Similarly, the short-sectioned inverters would correspond to the circuit configuration shown in FIG. 4 with the input In and the output Out connected together.
Furthermore, gyrators realized by differential amplifier circuitry are possible, as shown in FIGS. 5a, 5b. FIG. 5a shows on the left-hand side the symbol for a transconductor realized by a differential amplifier and on right-hand side the inverter solution for such a differential type amplifier in CMOS technology is shown. Two inverters I1, I2 (e.g. having a circuit configuration as shown in FIG. 4) are respectively connected to a first and second current source CS1, CS2 which are biased by bias voltages bias1, bias2.
FIG. 5b shows the gyrator core section GCi of FIG. 3 using a differential transconductor configuration as in FIG. 5a. As shown on the left-hand side in FIG. 5b two differential transconductors DA1, DA2 are provided in a feedback loop and therefore, using the circuit configuration in FIG. 5a, this leads to a structure similar to that shown in FIG. 3, namely loop-like circuits in the gyrator core section GCi.
In FIG. 5b the circuit configuration of FIG. 5a is contained twice leading to two first current sources CS1, CS12 and to second current sources CS21, CS22, to first inverters I11, I12 and to second inverters I21, I22.
It should be noted that any gyrator configuration as shown in FIGS. 3, 4, 5 may be used for the filter circuit according to the invention as will be described below. That is, the present invention is not restricted to any particular gyrator constructions. However, any gyrator construction would lead to the loop-like circuit of the gyrator core section GCi as shown in FIG. 3. The only difference is that for the differential amplifier gyrator shown in FIG. 5b no common mode feedback is needed because in the differential transconductor a high CMRR (Common Mode Rejection Ratio) exists.
As explained above, the loop-like configuration of the gyrator leads to a stability problem and the stability analysis of the gyrator- and integrator-based filters is the same since the integrators are parts of gyrator loops. An analysis of the gyrators is thus valid for the integrator configuration as well.
The stability of filter circuits comprising a gyrator construction as shown in FIG. 3 has been studied by B. Nauta: xe2x80x9cA CMOS transconductance-C filter technique for very high frequencies in IEEE Journal of Solid-State Circuits, SC-27, pages 142-153, February 1992xe2x80x9d. In this prior art document the stability of the circuit in FIG. 3 (hereinafter called the Nauta cell) was conducted by assuming a MOS or CMOS transistor realization of the integrators in FIG. 3. As is well known to the skilled person in the field of transistor technology, each MOS or CMOS transistor has a channel region of a particular dimension and the time needed for transporting carriers through this channel (between the source and drain) will influence the switching properties of the CMOS or MOS transistor.
In a PhD thesis which is the basis for the afore-mentioned IEEE paper, Nauta presented a number of simple filters and complex intermediate-frequency (IF) filters. The filter structures of lower order did work well but the more complex ones (higher order filters) had a very poor frequency response. In particular, the measured filter characteristics deviated from the theoretically expected filter characteristic to more than 10 dB. Furthermore, stability problems occurred and for making the filter circuits stable a separate Q-tuning circuit (separate supply voltage for the ballast inverters in the common mode feedback network) was used to enable an external adjustment. Basically, the adding of ballast devices or the sizing of the inverters in the common mode feedback sections reduces the dependence of the filter circuit on the output conductance of the filter and thus leads to more stable filter characteristics. Whilst Nauta achieved to make the filter stable by the adding of the Q-tuning circuits, the filter characteristics significantly deviated from the expected behavior. Thus, obviously merely adding ballast inverters in the common mode feedback network is not sufficient to keep stability and achieve the desired filter characteristic. Furthermore, each individual gyrator would require a separate Q-tuning loop.
Lower-order filters comprising Nauta cells do work because the external terminations provide a sufficient loading of the gyrator to make it stable. On the other hand, higher-order filters tend to have internal nodes that do not get sufficient loading to make the filter stable.
Thus, no complex active continuous-time on-chip MOS filter has been successfully fabricated in products due to the unreliability of the gyrator cell in terms of stability and the only workable examples are limited to lower-order filters or cascades of low-order filters (with inferior sensitivity characteristics).
Therefore, as explained above, the object of the present invention is to provide a filter circuit comprising at least one filter stage including at least one gyrator and a method for making such a filter circuit such that the filter circuit is stable also when higher-order filter stages are used and such that the practically obtained filter characteristic matches the theoretically expected filter characteristic.
This object is solved by the filter circuit (claim 11) consisting of at least one filter stage which comprises: a gyrator core section having four inverters mutually connected in a loop configuration between a pair of input terminals and a pair of output terminals; at least one common mode feedback section connected between the pair of input terminals and/or the pair of output terminals and comprising two series connections respectively formed by an inverter and a short-sectioned inverter connected antiparallely between said input terminals or said output terminals; each of said inverters being constituted by at least one MOS, CMOS or BiCMOS transistor having a gate, drain, source and a channel region between said drain and source; wherein the channel region dimensions of the transistors of the gyrator core section and/or the common mode feedback section are selected such that the following relationship is fulfilled: g*Cxe2x89xa7gm*cm where:
g: effective conductive loading of the gyrator core section terminals; C: effective capacitive loading of the gyrator core section terminals; gm: effective gyrating constant of the gyrator core section; and cm: effective transcapacitance of the gyrator core section.
Furthermore, this object is also solved by a method (claim 1) for making a filter circuit consisting of at least one filter stage which comprises the following steps:
providing said at least one filter stage with a gyrator core section having four inverters mutually connected in a loop configuration between a pair of input terminals and a pair of output terminals; and providing at least one common mode feedback section connected between the pair of input terminals and/or the pair of output terminals and comprising two series connections respectively formed by an inverter and a short-sectioned inverter connected antiparallely between said input terminals or said output terminals; each of said inverters being constituted by at least one MOS, CMOS or BiCMOS transistor having a gate, drain, source and a channel region between said drain and source; including the following step: selecting the channel region dimensions of the transistors of the gyrator core section and/or the common mode feedback section such that the following relationship is fulfilled:
g*Cxe2x89xa7gm*cm where: g: effective conductive loading of the gyrator core section terminals; C: effective capacitive loading of the gyrator core section terminals; gm: effective gyrating constant of the gyrator core section; and cm: effective transcapacitance of the gyrator core section.
Furthermore, the object is solved by a method for making a filter circuit consisting of at least one filter stage FSTi which comprises the following steps:
providing S1 said at least one filter stage FSTi with a gyrator core section GCi having four inverters I1, I12, I22, I21 mutually connected in a feedback loop between a pair of input terminals i_1, i_2 and a pair of output terminals o_1, o_2; wherein the inverters are arranged as a differential transconductor configuration, such that a first and second inverter I11, I21 are respectively provided between the first input and first output terminal i_1; o_2 and the second input terminal and the second output terminal i_2; o_2; each of said inverters being constituted by at least one MOS, CMOS or BiCMOS transistor having a gate G, drain D, source S and a channel region CH between said drain D and source S;
selecting S4 the general region dimensions CL, CB of the transistors of the gyrator core section such that the following relationship is fulfilled: g*Cxe2x89xa7gm*cm
where: g: effective conductive loading of the gyrator core section terminals; C: effective capacitive loading of the gyrator core section terminals; gm: effective gyrating constant of the gyrator core section; and cm: effective transcapacitance of the gyrator core section.
Furthermore, this object is solved by a filter circuit consisting of at least one filter stage FSTi, which comprises:
at least one filter stage FSTi with a gyrator core section GCi having four inverters I1, I12, I22, I21 mutually connected in a feedback loop between a pair of input terminals i_1; i_2 and a pair of output terminals o_1; o_2; wherein the inverters are arranged as a differential transconductor configuration, such that a first and second inverter I11, I21 are respectively provided between the first input and first output terminal i_1; o_1 and the second input terminal and the second output terminal i_2; o_2; each of said inverters being constituted by at least one MOS, CMOS or BiCMOS transistor having a gate G, drain D, source S and a channel region CH between said drain D and source S; the general region dimensions CL, CB of the transistors of the gyrator core section being selected such that the following relationship is fulfilled: g*Cxe2x89xa7gm*cm
where: g: effective conductive loading of the gyrator core section terminals; C: effective capacitive loading of the gyrator core section terminals; gm: effective gyrating constant of the gyrator core section; and cm: effective transcapacitance of the gyrator core section. According to the invention the problem was discovered that the channel delay of the transistor structures used in the gyrator circuits actually make the circuit unstable and causes the deviation from the actual filter characteristic from the expected theoretical filter characteristic. According to the invention it was realized that the non-quasi-static behavior of the channel charge does indeed add a parasitic pole in the transconductance of the device. This extra pole or delay makes the gyrator unstable and therefore must be designed properly. Whenever the channel delay becomes significant, it is therefore necessary to design the channel region dimension such that g*Cxe2x89xa7gm*cm is fulfilled. It is also not necessary to add Q-tuning to the ballast inverters in the common mode feedback network. If the channel region dimensions of the MOS transistors are designed to fulfill this condition also higher-order filters with excellent filter characteristics can be provided.
According to a first aspect of the invention the channel region dimensions are changed differently in the gyrator core section and in said common mode feedback section. The channel region dimensions of the common mode feedback section transistors can be kept constant and the channel region length of the gyrator core section can be reduced whereby the transadmittance of the respective transistor is changed. Thus, the devices are shortened such that the open-circuit voltage gain of the devices is low enough not to cause instability.
According to a second aspect of the invention the channel region dimensions of the common mode feedback section transistors are kept constant and the channel region length and the channel region width of the gyrator core section is reduced wherein the transmittance of the respective transistor is kept constant such that the resonance frequency of the core section {overscore (xcfx89)}Tcore is larger than the resonance frequency of the filter circuit {overscore (xcfx89)}Ofilter. Therefore, the gyrator-core devices can be scaled down such that their delay becomes insignificant.
According to a third aspect of the invention, when the channel region dimensions have been designed such that the overall filter fulfills g*Cxe2x89xa7gm*cm, additional ballast inverters can be added to the common mode feedback section. Essentially, the channel region width of the transistors of the common mode ballast inverters in the common mode feedback section is increased. That is, the CM ballast inverter channel region is widened and one must discriminate here between the CM ballast inverter connected to one terminal (CMI2 and CMO2) whose width is actually increased and the CM inverters connected between terminals (CMI1, CMO1) whose width can be kept constant.
Preferably, the channel length of the CM inverters (CMI1 and/or CMO1) can be made longer (even though this may be inferior to widening CMx2) as this will create a similar gain imbalance.
According to a fourth aspect of the invention, the aforementioned stability criteria and further stability criteria discussed hereinafter can be employed for a filter circuit which is formed by a differential transconductor configuration in a feedback loop without additional common mode feedback sections.
The above-mentioned schemes are applicable to symmetrical and asymmetrical realizations of the inverters.
Further advantageous embodiments and improvements of the invention can be taken from the dependent claims. Furthermore, it should be noted that the invention is not restricted to the embodiments and examples described hereinafter and that further embodiments of the invention may comprise features which have been described separately in the claims and in the description. Hereinafter, embodiments of the invention will be described with reference to the drawings.


A method of forming contact openings in a semiconductor device including providing a semiconducting substrate; forming an etch stop layer on said semiconducting substrate; forming a dielectric layer on said etch stop layer; forming a bottom anti-reflective coating (BARC) on said dielectric layer; forming and patterning a mask on said BARC layer; and, forming at least a first contact opening exposing said etch stop layer by a first etching process.

Etching of openings for forming electrical interconnects in the semiconductor processing industry is becoming more demanding as device sizes shrink. For example, as device sizes shrink to 0.15 microns and lower, the profiles of electrical contact holes can affect increasingly stringent electrical operating design requirements of integrated circuits.
There are a wide variety of variables that affect the anisotropicity of etching profiles in etching contact openings with an aspect ratio from about 3 to about 6. For example as the aspect ratio increases, the phenomenon of etch stop may occur where there is a build-up of fluoropolymers created during the plasma etching process along the sidewalls in the bottom of the etched opening which can degrade anisotropicity, effectively resulting in a cessation of anisotropic etching and the degradation of etching profiles. A degradation of etching profiles where the upper portion of the contact opening has a larger diameter may adversely affect both electrical resistance and capacitance of the integrated circuit.
While the formation of semiconductor devices of the prior art where device sizes have been relatively larger with a wider window for electrical property variations have had correspondingly greater room for variation in etching profiles and a greater tolerance for non-selective etching processes, increasingly stringent design requirements require an increasingly greater level of accuracy in forming electrical contacts.
For example, in ultra low power devices, for example a static random access memory device (SRAM), which require periodic refresh signals to retain stored data, the ratio of standby current (Isb) to drive current (Idr) is a critical design parameter in low power devices to enable proper functioning. For example, in creating an SRAM device it is frequently desirable to have an etch stop layer in an reactive ion etching (RIE) process to form contact openings since the relative depth of different contact openings in an etching process may vary, requiring an effective etch stop layer to prevent premature etch through.
One problem according to prior art RIE etching processes deals with the sufficient selectivity of etch stop layers. For example, forming contact openings including sufficient etch stop layer etching resistance to prevent premature etch-through, while maintaining sufficient etching selectivity in a subsequent etching process to avoid contact opening enlargement at an upper portion of the contact opening, is difficult to achieve according to the design requirements required, for example for 0.15 micron low power SRAM devices.
There is therefore a need in the semiconductor manufacturing art for an improved method to form sub-micron semiconductor devices including an anisotropic etching process such that anisotropically etched contact openings are formed with improved etching profiles to satisfy electrical design constraints.
It is therefore an object of the invention to provide an improved method to form sub-micron semiconductor devices including an anisotropic etching process such that anisotropically etched contact openings are formed with improved etching profiles to satisfy electrical design constraints as well as overcoming other shortcomings in the prior art.

Method for forming an improved low power SRAM contact

Taiwan Semiconductor Manufacturing Co., Ltd.


a resin composition for a powder coating comprising a polyester A, which does not substantially set to gel and has a hydroxyl value of at least 1,200 g eq/10.sup.6 g, a polyester B, which does not substantially set to gel and has a hydroxyl value of from 200 to 1,000 g eq/10.sup.6 g, and an inner blocked isocyanate hardener, wherein the weight ratio of polyester A to polyester B is from 70:30 to 10:90 and the difference (absolute value) in gel time between these polyesters A and B is at least 3 minutes.

Common examples of powder coatings include epoxy-series, acryl-series and polyester-series. It is well known that polyester-series powder coatings have well-balanced coating performance.
Powder coatings have been widely used in various fields including appliance, automobile and construction materials. In some cases, a glossy coated surface (specular gloss at 60.degree.: approximately 90 to 100%) is required for aesthetic purposes, while a mat (specular gloss at 60.degree.: approximately less than 30%) or semimat (specular gloss at 60.degree.: approximately 30 to 70%) may be required for other purposes.
Examples of conventional methods for preparing a powder coating capable of giving such a mat or semimat coating film include a method comprising adding a large amount of a pigment of coarse particles, and another method comprising dry-blending a polyester-series powder coating with an acryl-series powder coating.
However, the addition of a large amount of a pigment of coarse particles causes a deterioration in smoothness or a decrease in mechanical strength of the coating film. On the other hand, when using the method of dry-blending the two powder coatings, a mat or semimat powder coating cannot be obtained by a single step, which increases production cost. Furthermore, this method suffers from other problems including heterogeneity of the resulting blend and a change in the blending ratio during recovery and application.
In order to solve the above-mentioned problems, JP-A-64-1770 (the term "JP-A" as used herein means an "unexamined published Japanese patent application") proposes a resin composition for a powder coating comprising a polyester having a hydroxyl value of at least 1,200 g eq/10.sup.6 g, another polyester having a hydroxyl value of from 200 to 1,000 g eq/10.sup.6 g and a blocked isocyanate hardener wherein the difference in gel time between the two polyesters is at least 3 minutes.
In the case of a powder coating comprising this resin composition for a powder coating, however, a large amount of a di- or tri-functional blocked isocyanate hardener should be blended in order to control the functional value to a level almost equivalent with the hydroxyl value, since a polyester having a hydroxyl value of at least 1,200 g eq/10.sup.6 g is contained therein. As a result, there occur some troubles, for example, contamination of a stove or a material to be coated due to vaporization of a large amount of a blocking agent during the reaction between the polyester and the blocked isocyanate hardener and a weight loss of 10% or above.


The button apparatus is an apparatus provided for, for example, a vending machine and to be touched and pressed with the body of a user who wants to purchase a commodity from the vending machine. By pressing down the button apparatus, the user can purchase a required commodity from the vending machine. The button apparatus has a conductive pusher, an insulator, a switch, and a transceiver. A user wearing a wearable computer and a user's transceiver touches and presses down the pusher, to separately establish communication between the transceiver and the user's transceiver through the conductive pusher and the body of the user, as well as communication of providing a press signal.

1. Field of the Invention
The present invention relates to a button apparatus employing a transceiver used for data communication with, for example, a wearable computer. In particular, the present invention relates to a button apparatus employing a transceiver that transmits and receives information by inducing an electric field in an electric-field propagating medium according to information to be transmitted and by detecting an electric field induced in the electric-field propagating medium.
2. Description of Related Art
Reduced size and improved capabilities of portable terminals have brought attention to wearable computers. FIG. 1 shows examples of wearable computers put on and used by a human. In FIG. 1, the wearable computers 1a, 1b, and 1c are provided with transceivers 3a, 3b, and 3c, respectively, and are put on, for example, the arm, shoulder, and torso of a user, to communicate data among them. Transceivers 3d and 3e are installed on, for example, the wall and floor so that they can be touched with the tip of a hand or foot of the user, to enable the wearable computers 1a, 1b, and 1c to communicate with an external personal computer (PC) 5 through the transceivers 3d and 3e and cables.
Each of the transceivers 3 used for communication among the wearable computers 1 and between the wearable computers 1 and the PC 5 utilizes a signal detection technique based on electro-optic means employing laser beams and electro-optic crystals. Namely, the transceiver 3 induces an electric field in the body of the user serving as an electric-field propagating medium according to information to be transmitted and uses the induced electric field to communicate information (Japanese Unexamined Patent Application Publication No. 2001-352298).
Now, to purchase a commodity from, for example, a vending machine, one must carry money, insert the money into the vending machine, select a commodity, and thus purchase the commodity.
In this procedure of purchasing a commodity, one encounters a problem that he or she must take various steps until getting a required commodity. The steps include taking money out of a purse, inserting the money into a vending machine, selecting a commodity, picking up change, and the like.

Sales apparatus and method of transmitting and receiving merchandise information by electric field induced in human body

Nippon Telephone and Telegraph Corporation


A skewer assembly for use with a spiral meat slicing apparatus. The skewer assembly includes a base and a skewer connected thereto and extending therefrom. The skewer has an upper end, a lower end and a body portion therebetween. The body portion has a length and has a slot defined therethrough for at least a portion of the length of the body portion. The skewer may be inserted through a boneless cut of meat and the skewer assembly along with the meat product may be placed on a spiral meat slicing apparatus. Once the boneless cut of meat has been spiral sliced, the skewer assembly along with the meat product can be removed from the meat slicing apparatus. Prior to removing the skewer from the meat product, a knife can be inserted into the slot and can be moved along the slot to cut the meat product into two approximate halves through the portion of the meat which was not sliced by the circular slicing apparatus. Each half will have an unsliced portion that will hold the slices in the half of the meat product together.

The present invention relates to an apparatus for slicing a boneless cut of meat. More specifically, the invention relates to a skewer used to support a boneless cut of meat on a spiral meat slicer. The skewer has a slot therethrough which allows the meat product to be cut with a knife or other cutting blade while the skewer is inserted into the meat.
There are a number of devices available for spiral slicing boneless cuts of meat. U.S. Pat. Nos. 4,821,635 and 5,030,472 to Logan, Jr. et al., issued in April of 1989, and July of 1991, respectively, both of which are incorporated herein by reference disclose meat slicing apparatus for spiral slicing boneless cuts of meat. The Logan patents disclose a meat slicing apparatus that includes a meat spit between and upper and lower chucks to support the boneless cut of meat. When the meat rotates, the slicing blade is moved into slicing engagement with the meat. The blade moves vertically as the meat rotates to create the spiral slice. When slicing is complete, a central uncut core will remain around the spit. The central core allows the spiral sliced meat product to hold its shape and prevents the slices from separating from one another.
Another spiral slicing apparatus is shown in U.S. Pat. No. 5,251,543 to Brothers, issued Oct. 12, 1993, the details of which are incorporated herein by reference. That patent discloses a spiral slicing means that has an accessory adapted to be utilized with various spiral slicing machines. The accessory essentially comprises a skewer having a base and a movable stop member.
Although the apparatus in the aforementioned patents work well, it is sometimes desirable to cut the spiral sliced meat product into two separate halves. When doing so, it is desirable to cut the product into halves through the uncut center core so that the slices in each half will not separate from one another, and each half will maintain an aesthetically pleasing shape. None of the known apparatus disclose a method by which it can be insured that the sliced meat product can be cut precisely through the center core so that each half will have an uncut portion that holds the slices together and allows each half to maintain its shape. The present invention solves that problem.
The present invention is directed to a skewer apparatus which can be utilized with a wide variety of spiral meat slicers. The invention provides a method and apparatus for cutting a spiral sliced meat product into halves and insuring that the meat product is cut through the unsliced center core that will exist after the product has been spiral sliced.
The invention includes a skewer assembly comprised of a base and a skewer connected to and extending from the base. The skewer has a lower end portion, a body portion and an upper end portion. The upper end portion is preferably tapered to a point so that it can be easily inserted into a boneless meat product. The lower end is received and is connected to the base. The body portion has a length, and has a slot disposed therethrough for at least a portion of the length of the body portion. The slot is adapted to receive a knife or other cutting blade.
The operation of the invention simply comprises inserting an end of the skewer into a lower end of the meat product until the upper end portion of the skewer is exposed through the upper end of the meat product. The skewer must be inserted such that a portion of the slot is exposed at an end thereof, and preferably at the upper end of the meat product. The skewer assembly can then be placed on a spiral meat slicing apparatus. Once the boneless meat product is sliced, it can be removed from the apparatus and a knife or other cutting blade can be inserted into the exposed portion of the slot while the skewer is still inserted in the meat product. The knife can be moved along the length of the slot so that it will cut the meat product into halves. The cut will be through the unsliced center portion of the meat product since the cut will be made by the knife through the skewer. This insures that the two halves of the meat product will have an uncut portion which will hold the slices in each half together to provide not only for an aesthetically pleasing appearance but also for easier packaging.

Skewer assembly for supporting a boneless cut of meat on a spiral meat slicer


An apparatus and a method for changing the shape of seals is provided. The apparatus includes an elastomer member that applies force onto the seal to change the size of the seal. An embodiment of the invention includes returning the seal to its original diameter by deforming the elastomer that is positioned about at least a portion of the seal.

Seals, such as polytetrafluoroethylene (PTFE) seals, that are of a one-piece design having a continuous, unbroken, or cut section (similar to an o-ring) are commonly used for various sealing applications. Generally, the seals must be stretched over a mandrel or other similar device to properly position the seal into a groove on the outside diameter of the part to be sealed. Because of the physical properties of some materials, the seal stretches over time to a diameter greater than its original diameter. After stretching, the seal generally does not return to its original size. As a result, the seal is ineffective and is frequently discarded.
Prior art attempts to compress the seals to their original diameter have failed or at least have suffered from several deficiencies. For example, one common apparatus for returning seals to their original diameter utilizes a metal collet. As shown in FIGS. 1 and 2, a metal collet 5 is typically used to size seals. The metal collet 5 has segmented jaws spaced radially about the surface of the metal collet 5. Generally, force is applied to push the seal radially from the outside diameter inward to retract the seal to its original diameter. Essentially, the seal is "squeezed" to its original size and shape. However, these metal collets 5 are problematic for a number of reasons.
First, as shown in FIGS. 1-2, the metal collet 5 is typically made from a single continuous piece of spring-tempered steel. The metal collet 5 has relief cuts 6 (or kerfs) that permit steel sections 7 to move radially inward and outward with respect to the interior of the metal collet 5. Typically, the metal collet 5 is only designed to move a few thousandths of an inch. However, seals frequently expand more than a few thousandths of an inch from their original diameter. In such instances, the metal collet 5 is unable to return the seal to its original diameter. If the metal collet 5 is constructed so that it can expand further than a few thousandth of an inch, the metal collet 5 frequently fails due to material fatigue, which is not conducive to high volume manufacturing.
In addition, as the steel sections 7 move together, the kerfs 6 radially contract and are reduced from a gap of considerable size to a very narrow gap in order to squeeze the seals. However, the contraction of the kerfs 6 tends to pinch the seals resulting in damage and weakening of the seals. For example, the kerfs 6 compress the seal material between the gaps and frequently create witness lines and indentations along the seal that causes the seals to fail.
The metal collet 5 is a fixed geometry tool. In other words, the metal collet 5 has a fixed shape and is sized for one specific diameter. A fixed geometry tool, such as the metal collet 5, cannot accommodate the different compressability factors involved in sizing two or more differently sized seals. As a result, the metal collet 5 is not practical for sizing seals of varying diameters at the same time. The metal collet 5 is, instead, only designed to compress one type of seal and to compress the seal an amount equal to the range of movement of the metal collet 5.
Therefore, there is a need in the art for an improved apparatus and method for sizing seals. For example, there is a need in the art for an improved apparatus capable of sizing different sized seals with a single apparatus. In addition, there is a need in the art for an apparatus capable of sizing seals without risk of damage or weakening of the seals. There is also a need in the art for an apparatus for sizing seals that is capable of simultaneously sizing more than one type and sized seal.
Additional information will be set forth in the description which follows, and in part will be obvious from the description or may be learned by practice of the invention.


A system for monitoring digital content, including streaming media having one or more client test machines configured to receive and test digital content; one or more streaming servers configured to read content and provide the digital content to the client test machines; and one or more application servers configured to provide a test data file, having a URL to an item of the digital content, to the client test machines. The client test machines store the test results and transmit them to an application server for analysis. The application server may aggregate the information and sort the information via various categories of test results to pinpoint the location of potential points of failure along the path providing the digital content.

1. Field of the Invention
The present invention relates generally to systems and methods for monitoring delivery of digital content and, more particularly, to a method and system for allowing observation and diagnosis of the relative integrity of streaming content, including both the actual content and the infrastructure used to deliver the content, including a network, such as the Internet.
2. Description of Related Art
With the advent of the Internet and the World Wide Web and with advances in achieving ever increasing, affordable bandwidth, an industry has developed around the delivery of digital content, especially streaming media content. By way of example, streaming media may be used for any of a number of purposes, including entertainment, distance learning and corporate purposes. Entertainment companies stream movies, music, and sporting events, distance learning companies stream educational content, and corporations stream training materials, presentations and commercials.
Although some streaming media content providers may have relatively few items of content to provide, some content providers have hundreds, even thousands of content files. Storing and streaming this number of content files can be costly. Furthermore, streaming content requires a level of technical expertise often not found in companies focusing on creating content. Consequently, content creators and providers have turned to service providers to store and stream content on behalf of the content providers.
As more content providers turn to service providers for their streaming technology needs, service providers must manage more client accounts and greater numbers of content files. Furthermore, to maintain existing content provider clients and attract new clients, service providers must provide a content management system and delivery system that is reliable and is easy for the content providers to use.
Presently, there is no system that is capable of analyzing the relative integrity of a streaming media system. In general, as the number of users that use a system and the number of data files that are cataloged and indexed for use on a system increase, so too does the potential for poor performance. For example, too many users accessing a limited number of servers providing the streaming media creates a bottleneck that degrades the access time for each user. Similarly, a hardware conflict or malfunction on a particular server that provides streaming media content could seriously degrade system performance. Likewise, a path between the server and an individual user or a group of users could be damaged, either by accident or intentionally, thus degrading or even preventing access to the streaming media.
Accordingly, there remains a need for a system and method to diagnose the efficiency of a system that provides digital content, including streaming media, and identify potential points of failure or performance degradation within the system.

System and method for monitoring delivery of digital content, including streaming media


A protection structure of a motor for a cooling fan include a motor to which power source wire is connected for receiving electricity and a hub that is coupled to the motor and rotates. The hub includes: an outer portion along an outer peripheral surface of which blades are formed and on a center of which a center hole is formed; a center portion which is disposed at a middle of the center hole and to which is a rotations shaft of the motor is coupled; and a support member that couples the outer portion and the center portion. The support member is fractured physically to prevent overload to the motor and fire in advance. Furthermore, the power source wire is configured via the support member and thus is broken together when the support member is fractured to prevent unnecessary rotation of the motor.

1. Field of Invention
The present disclosure relates to a protection structure of a motor for a cooling-fan, and more particularly, to a protection structure of a motor for a cooling-fan, capable of protecting a motor by fracturing parts between a power source wire for applying power to the motor, blade and the motor when a restriction (between shroud) is occurred.
2. Description of Related Art
Generally, a radiator of a vehicle for cooling cooling-water heated in an engine vehicle is arranged at a front part of the vehicle to be cooled by a traveling-wind and further is provided with a plurality of wrinkles or cooling fins to have larger radiation area.
A cooling fan of the radiator increases cooling effect by forced ventilation through a rotation of a blade and is coupled to an engine with a pulley (fan belt type) for operation or is operated through a driving of an electric motor.
The cooling fan operated by the driving of the motor has been widely in a Front engine Front-wheel driving (FF) vehicle wherein it is operated in such a manner that a controller applies power to a motor when the cooling water is at a predetermined temperature or more.
Since the cooling fan using a motor can be arranged easily and operated promptly without warming and, prevent engine power loss without a coupling to a pulley, the cooling fan using a motor is used more widely than the fooling fan of a fan-belt type.
However, when the motor is restricted to be rotated while power source is applied thereto, fire may occur due to over load. Furthermore, there is a need to protect a motor of the cooling fan since the cooling fan is coupled to a radiator and disposed on a front part of a vehicle.
In more detail, as show in FIG. 1, a gap between a shroud and a blade is maintained at a range of 3-4 mm so that air is guided to be input smoothly. However, the blade is restricted to be rotated in case where snow or rain is infiltrated into the gap and frozen or foreign substance such as soil or stone are jammed therein.
The gap between the shroud and the blade may be increased in order to prevent the restriction but it may decrease wind amount.
The information disclosed in this Background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Protection structure of motor for cooling-fan