Polypeptides that can modulate SIRPα-CD47 functions and methods of use of the polypeptides are presented. In addition, polynucleotides that encode the polypeptides referred to above are presented. Further, pharmaceutical compositions to treat conditions are presented.

A variety of human diseases, in their active stages, are characterized by migration of large numbers of neutrophils (PMN) through tissues and across mucosal surfaces. For example, in inflammatory pulmonary diseases, such as bronchitis, cystic fibrosis and bronchiectasis, acute inflammation of the airway is characterized by infiltration of bronchial epithelium with neutrophils. In the urinary system, migration of PMN across tubular and transitional epithelium is associated with cystitis and pyelonephritis. In the gastrointestinal tract, active inflammatory disease characterized by migration of PMN across the epithelial lining is the hallmark of chronic and self-limited diseases such as ulcerative colitis, Crohn's disease and bacterial eriterocolitis. In these conditions, epithelial injury, disease activity and symptoms parallel PMN infiltration of the mucosa. (Hawker, et al., Gastroenterology, 79: 508, 1980; Weiland, et al., Am. Rev. Respir. Dis., 133: 218, 1986; Nusrat, et al., Gastroenterology, 113: 1489, 1997; Koyama, et al., Immunol., 147: 4293, 1991).
The emigration of circulating PMN from the blood stream to mucosal surfaces is an essential component of the acute inflammatory response and involves a complex and incompletely understood series of events. During this process, there are sequential, bi-directional interactions of PMN with endothelial cells, interstitial matrix and, under many conditions, epithelial cells. During the initial phases of recruitment, circulating PMN are activated by exposure to inflammatory mediators including complement fragments, cytokines such as IL-8 and tumor necrosis factor, and lipopolysaccharide leading to their microvascular sequestration and firm adhesion to the endothelium (Pober, et al., Transplantation, 50: 537, 1990; Luscinskas, et al., J. Immunol., 146: 1617, 1991; Smith, et al., J. Immunology, 72: 65, 1991). Sequestered PMN then migrate across the vascular endothelium, a process that involves sequential interactions between PMN integrins and endothelial cell adhesion molecules including ICAM and PECAM (Smith, et al., Semin. Hematol., 30:45, 1993; Smith, et al., J. Clin. Invest., 83: 2008, 1990; Springer, Nature, 346: 425, 1990; Muller, et al., J. Exp. Med., 178: 449, 1993). In the extravascular space, directed PMN migration depends on the presence of a chemotactic stimulus and interactions between extracellular matrix proteins and adhesion molecules. Chemotactic stimuli can be produced locally by activated cells or by external pathogens. For example, intestinal epithelial cells secrete the chemoattractant IL-8 in a basolaterally polarized manner as a response to many pathogens (McCormick, et al., J. Cell Biol., 131: 1599, 1995) which then serves to recruit PMN from the circulation to the sub-epithelial space. PMN migration across the epithelium is then directed towards bacterial-derived peptides such as fMLF and requires sequential adhesive and signaling interactions along the basolateral epithelial cell membrane (Parkos, Bioessays, 19: 865, 1997).
While many of the molecular steps involved in this complex process of transmigration are still undefined, it has been demonstrated that a transmembrane protein termed CD47 plays an important role in regulating PMN migration at the level of the endothelium, matrix and epithelium (Parkos, et al., J. Cell Biol., 132: 437, 1996; Cooper, et al., Proc Natl Acad Sci USA, 92: 3978, 1995). In particular, it has been shown that CD47 is a crucial component of the transepithelial migration response and that CD47-dependent events occur after β2 integrin-mediated neutrophil adhesion to the epithelium (Parkos, et al., J. Cell Biol., 132: 437, 1996). Recently it was reported that CD47 binds to another class of transmembrane Ig superfamily members called Signal Regulatory Proteins (SIRPs) (Jiang, et al., J. Biol. Chem., 274: 559, 1999; Seiffert, et al., Blood, 94: 3633, 1999). SIRP's have been implicated in both positive and negative signal transduction cascades in a variety of cell types. CD47 was first purified from human placenta in 1990 (Brown, et al., J. Cell Biol., 111: 2785, 1990), and the complete cDNA sequence was reported by Campbell (Campbell, et al., Cancer Res, 52: 5416, 1992) and Lindberg et al. (Lindberg, et al., J. Cell Biol, 123: 485, 1993) and is widely expressed in hematopoietic cells (e.g., erythrocytes, lymphocytes, platelets, monocytes and neutrophils) and other tissues (e.g., placenta, surface epithelia, liver and brain). The human CD47 gene has been mapped to chromosome 3, band q 13.1-q 13.2 and encodes a protein of 305 amino acids (isoform 2) with a predicted core polypeptide molecular weight of 35 kDa and four isoforms have been cloned and characterized (Campbell, et al., Cancer Res, 52: 5416, 1992; Lindberg, et al., J. Cell Biol., 123: 485, 1993; Reinhold, et al., Journal of Experimental Medicine, 185: 119-21, 1997). The primary sequence of CD47 predicts an N terminal extracellular domain that structurally belongs to the immunoglobulin variable-like (IgV) superfamily (Lindberg, et al., J. Cell Biol., 123: 485, 1996; Vaughn, et al., Neuron 16(2): 261-73, 1996) containing a disulfide bridge harboring several potential N-glycosylation sites. Several hydrophobic helices suggest three or five transmembrane segments. There is a short hydrophilic intracytoplasmic tail with four alternatively spliced forms that are expressed in a tissue-specific manner (Campbell, et al., Cancer Res, 52: 5416, 1992; Lindberg, et al., J. Cell Biol., 123: 485, 1993; Reinhold, et al., Journal of Experimental Medicine, 185: 1, 1997). Studies with several IgV superfamily proteins have shown that the IgV-like domain is important in cell surface adhesive functions (Vaughn, et al., Neuron 16(2): 261-73, 1996). Studies using depletion and chimeric constructs suggest that the extracellular IgV-like domain of CD47 is important for its ability to regulate β3 integrin avidity for immobilized vitronectin (Lindberg, et al., J. Cell Biol., 123: 485, 1996). Direct association between CD47 and β3 integrin was first demonstrated by coimmunoprecipitation experiments in placenta (Brown, et al., J. Cell Biol., 111: 2785, 1990). These findings have further been validated by studies using CD47 knock out mice who rapidly die of Escherichia coli peritonitis, a phenomenon directly correlated with a reduction in leukocyte activation in response to β3 integrin ligation (Lindberg, et al., J. Cell Biol., 123: 485, 1996).
CD47 has been shown to have a central role in PMN transepithelial migration (Parkos, et al., J. Cell Biol., 132: 437, 1996). A potent CD47-specific antibody (Ab), C5/D5, was identified that was capable of inhibiting PMN migration across vascular endothelium, collagen-coated filters and intestinal epithelium without inhibiting β2 integrin-mediated adhesion (Parkos, et al., J. Cell Biol., 132: 437, 1996). At the same time, it was shown that anti-CD47 also inhibited PMN migration across endothelial monolayers (Cooper, et al., Proc Natl Acad Sci USA, 92: 3978, 1995). Subsequent studies with CD47 knockout mice have confirmed the importance of CD47 in PMN migration in vivo suggesting that CD47 plays a role in regulating the rate of PMN recruitment to sites of infection. (Lindberg, et al., Science, 274: 795, 1996)
Despite a growing number of reports of different functions of CD47 (Parkos, et al., J. Cell Biol., 132: 437, 1996; Jiang, et al., J. Cell Biol., 274: 559, 1999; Lindberg, et al., J. Cell Biol., 134: 1313, 1996; Ticchioni, et al., Journal of Immunology, 158: 677, 1997; Waclavicek, et al., Journal of Immunology, 159: 5345, 1997; Gao, et al., J. Cell Biol., 135: 533, 1996; Furusawa, et al., J. Biol. Chem., 123: 101, 1998; Frazier, et al., J. Biol. Chem., 274: 8554, 1999; Chung, et al., J. Biol. Chem., 272: 14740, 1997; Chung, et al., Blood, 94: 642, 1999), the mechanism by which CD47 regulates PAN migration is not known. In other cell systems, CD47 has been shown to functionally and physically associate with β3 and β1 integrins (Brown, et al., J. Cell Biol., 111: 2785, 1990; Lindberg, et al., J. Cell Biol., 134:1313, 1996; Frazier, et al., J. Biol. Chem., 274: 8554, 1999; Blystone, et al., J. Cell Biol., 130: 745, 1995; Lindberg, et al., J. Cell Biol., 123: 485, 1996). However, others have not been able to detect a direct association of CD47 with β1, β2, and β3 integrins in PMN and observe no significant effect on PMN transepithelial migration in the presence of a panel of functionally inhibitory mAbs against β3 integrin or β1 integrin (Liu, et al., J. Biol. Chem., 276: 40156). CD47 has also been shown to bind to the C-terminal cell binding domain of thrombospondin1 (Gao, et al., J. Biol. Chem., 271: 21, 1996), but this interaction does not modulate PMN migration (Liu, et al., J. Biol. Chem., 276: 40156, 2001). Recent in vitro studies have suggested that CD47 regulates the rate of PMN migration (Liu, et al., J. Biol. Chem., 276: 40156, 2001). In that study it was found that anti-CD47 mAbs delayed PMN migration across both T84 epithelial monolayers and matrix-coated permeable filters towards the chemoattractant fMLF. However, despite delayed transmigration, the numbers of PMN migrating across were not affected by the presence of anti-CD47 antibodies. This finding is consistent with studies with CD47 knock-out mice (Lindberg, et al., Science, 274: 795, 1996) suggesting that, although CD47 deficient PMN can eventually migrate to sites of infection, the delayed response resulted in enhanced mortality.
As indicated above, surface Ig superfamily member SIRPα (also termed SIRPα1; P84, Bit, SHPS-1 and MFR) (Jiang, et al., J. Biol. Chem., 274: 559, 1999; Seiffert, et al., Blood, 94: 3633, 1999; Vernon-Wilson, et al., European Journal of Immunology, 30: 2130, 2000; Kharitonenkov, et al., Nature, 386: 181, 1997; Han, et al., J. Biol. Chem., 275: 3798, 2000; Brumell, et al., J. Biol. Chem., 272: 875, 1997) was reported to bind to CD47. SIRPs are a family of transmembrane glycoproteins expressed in a variety of tissues (Kharitonenkov, et al., Nature, 386: 181, 1997). However, within these tissues, SIRPs are only selectively expressed in certain cell types (Adams, et al., Journal of Immunology, 161: 1853, 1998). In mice, SIRPs (termed SHPS-1) are richly expressed in hematopoietic cells including macrophages and myeloid cells, but not in T and B cells (Veillette, et al., J. Biol. Chem., 273: 22719, 1998). In humans, SIRPs are expressed in monocytes, granulocytes, dendritic cells and CD34+CD38−CD133+bone marrow stem/progenitor cells but not in lymphocytes (Seiffert, et al., Blood, 94: 3633, 1999; Seiffert, et al., Blood, 97: 2741, 2001). Through cDNA library screening, multiple homologous sequences that account for at least 15 additional SIRP members have been reported (Kharitonenkov, et al., Nature, 386: 181, 1997).
Primary structural analysis indicates that SIRPs all share common structural motifs that comprise a single transmembrane segment and an N-terminal extracellular domain that contains three Ig-like loops connected by three pairs of disulfide bonds. Therefore, SIRPs structurally belong to the Ig superfamily. The C-terminal intracellular domain, on the other hand, structurally separates two subfamilies of SIRPs termed SIRPα and SIRPβ (Kharitonenkov, et al., Nature, 386: 181, 1997). SIRPα has a long intracellular domain containing four tyrosine residues that form two immunoreceptor tyrosine-based inhibitory motifs (ITIM), while SIRPβ contains a basic lysine residue followed by a short intracellular tail that serves as a receptor for DAP12, a protein with an immunoreceptor tyrosine-based activation motif (Kharitonenkov, et al., Nature, 386: 181, 1997; Seiffert, et al., Blood, 97: 2741, 2001).
Similar to other ITIM domain containing proteins such as CD3, TCRξ, FcRγ, and BCR (Tomasello, et al., Seminars in Immunology, 12: 139, 2000; Vivier, et al., Immunology Today, 18: 286, 1997), SIRPα has been shown to play an important role in regulating cellular responses to a wide variety of different stimuli. For example, treatment of tissue-cultured cells with growth factors (including PDGF and EGF), growth hormone, insulin, CSF, LPA, etc., has been shown to induce phosphorylation of tyrosines on the intracellular ITINI domain of SIRPα resulting in binding to SH2 domain containing tyrosine phosphatase-1 or 2 (SHP-1 and 2) (Kharitonenkov, et al., Nature, 386:181, 1997; Veillette, et al., J. Biol. Chem., 273: 22719, 1998; Timms, et al., Molecular & Cellular Biology, 18: 3838, 1998). SIRPα binding to SHP-1 or SHP-2 has been shown to deliver positive or negative signals that regulate a variety of cellular functions, respectively (Kharitonenkov, et al., Nature, 386:181, 1997; Stofega, et al., J. Biol. Chem., 275: 28222, 2000; Stofega, et al., J. Biol. Chem., 273: 7112, 1998).
As mentioned above, there are recent reports of SIRPα1 as an extracellular ligand for CD47. These findings are important in that no membrane protein receptor has been described for either SIRP or CD47. CD47-SIRPα interactions have been implicated in a number of cellular functions, including the regulation of neutrophil migration, memory formation, macrophage multinucleation, B cell aggregation, T cell activation, dendritic cell maturation and function, and red blood cell self-recognition in mice, (Kharitonenkov, et al., Nature, 386: 181, 1997; Han, et al., J. Biol. Chem., 275: 37984, 2000; Chang, et al., Learning & Memory, 6: 448, 1999; Oldenborg, et al., Science, 288: 2051, 2000; Tanaka, et al., Journal of Immunology, 167(5): 2547-54, 2001; Liu, et al., v 277(12): 10028-36, 2002; Avice, et. al., Journal of Immunology, 167(5): 2459-68, 2001; Blazar, et al., Journal of Experimental Medicine, 194(4):541-9, 2001; Seiffert, et al., Blood, 97(9): 2741-9, 2001; Oldenborg, et al., Journal of Experimental Medicine, 193(7): 855-62, 2001; Pettersen, Apoptosis, 5(4): 299-306, 2000; Han, et al., J. Biol. Chem., 275(48): 37984-92, 2000; Demeure, et al., Journal of Immunology, 164(4): 2193-9, 2000; Armant, et al., Journal of Experimental Medicine, 190(8): 1175-82, 1999; Jiang, et al., J. Biol. Chem., 274(2): 559-62, 1999; Lee, et al., European Journal of Neuroscience, 12(3): 1105-12, 2000; and Chang, et al., Learning & Memory, 6(5): 448-57, 1999) although the mechanisms remain undefined.
Thus, a heretofore unaddressed need exists in the industry to modulate the interaction between CD47 and SIRPα.

Polynucleotides and polypeptides relating to the modulation of SIRPα-CD47


An implantable cardiac stimulation device and associated method perform an automatic calibration procedure for evaluating whether automatic capture verification can be recommended. The calibration procedure calculates and displays a number of variables for use by a medical practitioner in programming automatic capture operating parameters. An average paced depolarization integral (PDI) is determined from the cardiac signals following delivery of multiple stimulation pulse below and above capture threshold such that both pure lead polarization signals and evoked response signals may be analyzed. From the paced depolarization integral data, a capture threshold, a stimulation response curve, a minimum evoked response, a maximum lead polarization, an evoked response sensitivity, an evoked response safety margin, and a polarization safety margin are determined. Based on these variables, the calibration procedure determines if automatic capture verification can be recommended. If so, the stimulation device calculates a capture detection threshold. The automatic capture verification recommendation and the estimated calibration variables are displayed.

The present invention relates to an implantable cardiac stimulation system using an automatic capture feature. More specifically, the present invention relates to an implantable cardiac stimulation system in which an external programmer controls an automatic capture calibration routine and displays pertinent information regarding the feasibility of performing automatic capture.
Implantable cardiac stimulating devices including pacemakers, cardioverters and defibrillators, detect and treat incidents of cardiac arrhythmias. Such devices are coupled to a patient""s heart through transvenous leads that are used to sense electrical signals from the heart and deliver both low voltage and high voltage electrical therapy to the heart. The device circuitry generally includes sensing circuitry for sensing cardiac electrical activities in order to detect intrinsic electrical depolarizations of the cardiac tissue that cause contraction of the respective heart chambers.
In the atria, detection of a P-wave indicates atrial contraction, and in the ventricles detection of an R-wave, also known as a QRS complex, indicates ventricular contraction. If detection of an intrinsic P-wave or an R-wave does not occur within a given interval of time, generally referred to as the xe2x80x9cescape interval,xe2x80x9d the heart rate is determined as being too slow. A stimulation pulse is then generated by the pacemaker circuitry and delivered to the appropriate heart chamber at the end of the escape interval in order to stimulate the muscle tissue of the heart to contract, thus maintaining a minimum heart rate. The duration of the escape interval corresponds to some base pacing rate, for example an escape interval of 1,200 msec would maintain a base pacing rate of 50 heart beats per minute.
The electrical depolarization caused by the delivery of a stimulation pulse is known as an xe2x80x9cevoked response.xe2x80x9d An evoked response will only occur when the stimulating pulse is of sufficient energy to cause depolarization of the cardiac tissue, a condition known as xe2x80x9ccapture.xe2x80x9d The minimum stimulating energy required to capture a chamber of the heart is known as xe2x80x9cthreshold.xe2x80x9d
Modern pacemakers often include a feature known as xe2x80x9cautomatic capture.xe2x80x9d When the automatic capture feature is implemented, the pacemaker circuitry detects the evoked response following the delivery of a stimulation pulse in order to verify that capture has occurred. If no evoked response is detected, the stimulation pulse may have been of insufficient energy to capture the heart; therefore, a high-energy back-up pulse is quickly delivered to the heart in order to maintain the desired heart rate. A threshold detection algorithm is then invoked in order to re-determine what minimum energy is required to capture the heart.
The stimulating pulse energy is automatically adjusted to this new threshold value plus some safety margin. As long as an evoked response is detected following a stimulation pulse, that is, as long as capture is verified, pacing will continue at the set pulse energy.
Hence, the automatic capture feature improves pacemaker performance in at least two ways: 1) it verifies that the stimulation therapy delivered has been effective in causing the heart chamber activation, and 2) it improves battery energy longevity by determining the lowest stimulation energy needed to effectively capture the heart.
However, one problem with capture detection is that the signal sensed by the ventricular and/or atrial sensing circuits immediately following the application of a stimulation pulse may not be an evoked response. Rather, it may be noise, either electrical noise caused, for example, by electromagnetic interference (EMI), or myocardial noise caused by random myocardial or other muscle contractions (muscle xe2x80x9ctwitchingxe2x80x9d). Alternatively, the signal sensed by the ventricular and/or atrial sensing circuits may be a natural R-wave or P-wave that just happens to occur immediately following the application of a non-capturing stimulation pulse.
Another problematic condition is xe2x80x9cfusionxe2x80x9d. Fusion occurs when a pacing pulse is delivered such that the evoked response occurs coincidentally with an intrinsic depolarization. The evoked signal may be absent or altered preventing correct capture detection by the pacemaker""s capture detection algorithm. A loss of capture may be indicated when capture is in fact present, which is an undesirable situation that will cause the pacemaker to unnecessarily deliver a high-energy back-up pacing pulse and to invoke the threshold testing function in a chamber of the heart. Frequent delivery of back-up pacing pulses or execution of threshold tests defeats the purpose of the energy-saving features of autocapture. If fusion continues during a threshold test, the pacing energy output may be driven to a maximum level, quickly depleting the battery energy.
The incidence of fusion can be particularly problematic in patients with intermittent or intact atrio-ventricular conduction being treated by dual chamber pacing. In dual chamber pacing, both atrial and ventricular activity are monitored. A P-wave detected in the atria is followed by an AV/PV interval which is the desired delay between an atrial depolarization and a ventricular depolarization. If an intrinsic R-wave is not detected prior to expiration of the AV/PV delay, a Vpulse is delivered to pace the ventricles. Since the AV conduction time may vary, an intrinsically conducted R-wave may occur at different times and therefore may occur approximately the same time that a ventricular pacing pulse is delivered. Furthermore, the AV/PV interval may be programmed inappropriately leading to increased likelihood of fusion events. Fusion masquerading as loss of capture will cause the pacemaker to initiate frequent threshold tests and may drive the pacemaker to its maximum pacing output.
Yet another signal that interferes with the detection of an evoked response is associated with lead electrode polarization. Lead electrode polarization is caused by electrochemical reactions that occur at the lead/tissue interface due to the application of the electrical stimulation pulse across such interface. The lead polarization signal is a complex function of the lead materials, lead geometry, tissue impedance, stimulation energy, and many other variables.
The evoked response is monitored within 3 to 80 msec of the stimulation pulse. During the early portion of this time, the lead polarization signal voltage is still relatively high. In order to minimize lead polarization voltage, low polarization materials can be used in manufacturing the electrode. Still, since the evoked response and polarization signal occur simultaneously, if the polarization signal is very high, it may not be possible to reliably detect an evoked response. The result may be a false positive detection of the evoked response. Such false positive detection leads to a false capture indication, which, in turn, can lead to missed heartbeats, a highly undesirable situation.
Variation in the lead polarization signal can be significant from patient to patient depending on implanted lead configurations and other factors. Therefore, calibration methods are generally required to determine a threshold for detecting the evoked response and distinguishing it from the lead polarization signal.
Different parameters or characteristics of the evoked response have been proposed in automatic capture calibration and automatic capture detection schemes, including impedance change, voltage differential (dV/dt), signal polarity reversal, and peak negative amplitude.
Typically, evoked response sensing occurs between the tip and ring of a bipolar lead connected to the device sensing circuits. The evoked response may also be monitored by sensing between the ring electrode and device housing. In either event, a bipolar pacing lead has generally been required in order to detect the evoked response. These configurations have been selected since they reduce the likelihood of false positive capture detection. Such reduction is achieved by selecting a feature in the bipolar evoked response that is not strongly expressed in the polarization artifact. Alternatively, in the ring-case configuration, one of the pacing electrodes may be removed from the sensing circuit, thereby reducing the sensed polarization signal. This implies that these automatic capture schemes will not work with unipolar pacing leads.
Thus, in patients having unipolar leads implanted in conjunction with a cardiac stimulation device, the ability to reliably employ the automatic capture feature has been heretofore limited.
It would thus be desirable to provide the cardiac stimulation system with an automatic calibration routine that evaluates variables associated with the lead polarization signal and the evoked response signal, and, based on this evaluation, determines whether or not the automatic capture feature is recommended for a particular patient. In addition, it would be desirable to report these calibration variables to the physician to allow him or her to make informed decisions in enabling or disabling the automatic capture feature and, when enabled, to make an informed decision in selecting appropriate automatic capture operating parameters.
The present invention addresses this and other needs by providing an implantable cardiac stimulation system with an automatic capture calibration feature capable of automatically evaluating whether the automatic capture can be reliably performed using a unipolar electrode configuration, and further calculating and reporting calibration variables that can be used by a medical practitioner in programming automatic capture parameters. It should be understood that the calibration procedure of the present invention can alternatively be performed using leads with bipolar or multipolar electrode configurations.
The implementation of this calibration procedure in an external programmer in communication with an implanted stimulation device allows thorough testing and evaluation of stimulation response signals, and gives the opportunity to display pertinent information regarding the feasibility of the automatic capture feature to the physician.
The automatic calibration procedure of the present invention, which employs the xe2x80x9cpaced depolarization integral method calibrationxe2x80x9d or xe2x80x9cPDI-method calibrationxe2x80x9d, can be executed by an external programmer controlling certain operations of an implanted cardiac stimulation device. The calibration procedure includes the following steps: 1) automatic gain adjustment and fusion avoidance adjustment; 2) paced depolarization integral data collection and table creation; 3) capture threshold determination and stimulation response curve slope determination; 4) automatic capture recommendation and failure conditions reporting; and 5) reporting of calibration variable estimations.
When the automatic calibration procedure is initiated, the external programmer first adjusts the gain of the sensing circuit (or circuits) of the implanted stimulation device to achieve a desired maximum magnitude of sampled signals. If necessary, the programmer also recommends adjustment of pacer timing parameters in order to minimize the likelihood of fusion, such as increasing the base rate of the pacemaker, or shortening the AV and or PV intervals.
The programmer then collects data relating to the lead polarization signal and the evoked response signal following the delivery of a stimulation pulse by integrating a sampled cardiac EGM signal. In so doing, the programmer triggers the implanted stimulation device to deliver a given number of stimulation pulses at a several pulse amplitude settings over a specified range, including both supra-capture threshold amplitudes and sub-capture threshold amplitudes. The sensed cardiac signal is integrated in order to obtain the paced depolarization integral (or PDI) associated with each stimulation pulse. The values of the integrals obtained for a given number of stimulating pulses at each pulse amplitude are statistically evaluated, and the results are stored in memory. If inappropriate or insufficient results are obtained during this data collection and analysis, the physician is alerted that the calibration procedure cannot be run.
Based on the paced depolarization integral data collected, the capture threshold is determined, and the slope of the stimulation response curve (pulse amplitude versus paced depolarization integral) is calculated. Based on further mathematical analysis of the paced depolarization integral data, which in essence determines the margin for safely discriminating an evoked response signal from a lead polarization signal, the activation of the automatic capture feature would be determined to be either xe2x80x98recommendedxe2x80x99 or xe2x80x98not recommended.xe2x80x99
For either condition, a set of calibration variables are calculated and displayed, including minimum and maximum evoked response amplitudes, maximum polarization signal amplitude, evoked response sensitivity, and evoked response safety margin. Having this information, the medical practitioner can make informed decisions in programming the automatic capture feature of an implantable cardiac stimulation device.
Thus, one feature of the present invention is a calibration procedure that is executed by an external programmer controlling certain operations of the implanted stimulation device. Another feature of the present invention included in this calibration procedure is the ability to make gain adjustments or fusion avoidance adjustments to improve the ability of the calibration procedure in collecting sufficient and appropriate data.
A further feature of the present invention is the ability to sample and digitize a cardiac stimulation response signal. Yet another feature of the present invention is a method for integrating the sampled stimulation response signal during a defined response time window and relative to an integration baseline in order to obtain a paced depolarization integral.
Still another feature of the present invention is the performance of mathematical and statistical analyses of the paced depolarization integral data in order to determine the capture threshold and by what margin automatic capture can be reliably performed. A further feature is the calculation of estimations of certain variables pertinent to the performance of automatic capture. Another feature is a method for displaying calibration procedure failure conditions, an automatic capture recommendation, and automatic capture variable estimations.

Implantable cardiac stimulation system and method for automatic capture verification calibration


A semiconductor device of a multilayer structure comprising semiconductor materials of different properties manufactured by using at least a step of epitaxially forming a semiconductor material layer on a substrate and a passivation film layer thereover, a step of introducing impurities into specific portions of the epitaxially formed semiconductor material layer and a step of removing the passivation film layer formed directly above the epitaxially formed semiconductor material layer within an epitaxial device and then applying epitaxial growing. Impurities introduced additionally to specific portions of the layer inside are substantially eliminated at the boundary adjacent the layer above the region introduced with impurities and the properties of the thus-produced semiconductors vary abruptly at the boundary between the layer in which the impurities are introduced and the layer thereabove. The material used for the passivation film layer comprises one that can be epitaxially formed and easily removed at a temperature and in a atmosphere under which the epitaxially formed layer below the passivation film are not decomposed or evaporized.

1. Field of the Invention
This invention concerns a semiconductor device such as a bipolar transistor (hereinafter simply referred to as BT) which is manufactured by using a multilayer structure material formed through the epitaxy of semiconductor materials of different properties and which is useful as an ultrahigh frequency and ultrahigh speed transistor and, particularly a heterojunction bipolar transistor (hereinafter simply referred as HBT) a semiconductor laser and a light emitting diode, as well as a method of manufacturing same.
2. Description of the Prior Art
High speed operation factors f.sub.t and f.sub.m for BT are represented as: ##EQU1## where .tau.e (emitter depletion layer transit time)=re(Cbc+Ceb+Cpb),
.tau.b (base trainsit time)=Wb.sup.2 /nDb, PA1 .tau.c (collector depletion layer transit time)=Wc/2Vs, .tau.cc (collector depletion layer charging time)=(Ree+Rc).(Cbc+Cpc), PA1 Rb: base resistance, PA1 Cbc: base-collector capacitance, PA1 Ceb: base-emitter capacitance, PA1 Cpb: base layer parasitic capacitance, PA1 Cpc: collector layer parasitic capacitance, PA1 Wb: base layer thickness, PA1 Db: base layer diffusion coefficient, PA1 Wc: collector depletion layer thickness, PA1 Vs: collector transit speed, PA1 Ree: emitter contact resistance, and PA1 Rc: collector resistance.
As can be seen from the formulas, it is important in a BT to decrease the junction capacitance such as the Cbc and Ceb, the base layer thickness, the ohmic contact resistance and the base resistance in order to increase f.sub.t and f.sub.m. Above all, it is important to decrease the base resistance Rb and Cbc in order to increase the f.sub.m. In view of the above, attempts have been made for reducing the size of transistors.
In an HBT using a semiconductor material as an emitter having a band gap larger than that of the base, since the leaks of positive holes from the base to the emitter is suppressed (in the case of npn type), the base can be doped to a higher extent, while the emitter and the collector can be doped to a lower extent contrary to an ordinary BT. Since this can reduce the base resistance Rb which is important for increasing the operation speed and the frequency of the transistor, it is advantageous for the increase of the factor f.sub.m. Further, in the usual bipolar transistor, Cbc and Ceb are represented as a product of the factors Ceb (n, h), Cbc (n, h) of the junction capacitance depending on the doping and the junction areas Aeb, Abc. Since the emitter and the collector are doped at a low concentration while the base is doped at a high concentration in the heterojunction bipolar transistor, Ceb (n, h) and Cbc (n, h) are dependent only on the doping of the emitter and the collector and Ceb and Cbc are represented as: EQU Ceb.varies..sqroot.Ne.multidot.Aeb Cbc.varies..sqroot.Nc.multidot.Abc
Accordingly, since Ceb and Cbc are made smaller in an HBT by reason of the hetero-structure as compared with the usual BT, .tau.e and .tau.cc are made smaller to provide an advantage for the increase of f.sub.t. Further, since the Cbc is made smaller, it provides an advantage in that f.sub.m is increased coupled with a decrease in Rb. For making the HBT operation speed higher, it is important to optimize the device structure in addition to the optimization of the hetero-structure itself. A normal structure in which the emitter is situated above and an inverted type in which the collector is situated above are fundamentally possible in the usual BT as the well as HBT (H. Kroemer: "Hetero-structure Bipolar Transistors and Integrated Circuits" Proc. IEEE, vol. 70, p. 13, 1982). In the normal type, it is advantageous to decrease the size of the emitter for making the Ceb smaller. In addition, if the collector can be made smaller by making the periphery of the collector semi-insulating, a remarkable increase in the f.sub.t, f.sub.m is possible since the Cbc can be made smaller (P. M. Asbeck, et al. "GaAs/(Ga,Al)As Heterojunction Bipolar Transistors with Buried Oxygen Inplanted Isolation Layers", IEEE, EDL-5, p. 311 (1984)). Further, in a inverted structure, since the collector is situated above, it is essentially advantageous to reduce the size of the collector for reducing the Cbc. Further, since the Ceb is reduced if the periphery of the emitter can be semi-insulated, f.sub.t and, accordingly, f.sub.m can be increased. It has been attempted, for such an objective, to fabricate semiconductor materials of different properties into a multi-layer structure suitable for the manufacture of BT through an epitaxy and then making the periphery of the collector at a specific portion inside of the multilayer structure semi-insulating by ion inplantation from above (P. M. Asbeck, et al. "GaAs/(Ga,Al)As Heterojunction Bipolar Transistors with Burried Oxygen Inplanted Isolation Layers", IEEE, EDL-5, p. 311 (1984)).
However, introduction of impurities into the specific portion inside of the multilayer structure from above by means of ion implantation or diffusion is not desirable as it produces undesired effects on the transistor characteristics. This is because the introduced impurities form a distribution in the direction of the depth and the impurities are distributed above the specific portion requiring the introduction of the impurities and the crystals are inevitably injured due to the great amount of impurities passed therethrough.

Method of manufacturing semiconductor device

Matsushita Electric Industrial Co., Ltd.


A concentrating photovoltaic module comprising: a lightguide member having at least one exit face and a plurality of entrance faces; and at least one solar cell placed immediately after the exit face of the lightguide member; wherein the lightguide member is comprised of a light transmissive, solid medium having no refractive-index-discontinuity portion and a surface of the lightguide member is smooth and wherein the lightguide member makes sunbeams incident on the plurality of entrance faces, totally reflected on side faces, and emergent from the exit face, whereby the sunbeams can be concentrated on the solar cell with high efficiency.

1. Field of the Invention
The present invention relates to a concentrating photovoltaic module and a concentrating photovoltaic power generating system.
2. Related Background Art
Attention has been focused heretofore on the photovoltaic power generating systems utilizing the solar cell modules as an energy source being safe for and no strain on the environment, but emphasis is recently being shifted to development of inexpensive solar cell modules with higher efficiency, in order to make them competitive over the conventional power generating means such as the thermal power generation and others even from the economical aspect.
From this respect, attention is recently being given to a concentrating photovoltaic module and a concentrating photovoltaic power generating system consisting of the concentrating photovoltaic module and a sun tracking device. In the ordinary photovoltaic power generating systems the solar cell module itself is fixed at a certain position, but the relation between Sun and Earth varies with time as a matter of course. Therefore, the fixed solar cell module can be located at the best angle relative to the sun only for a moment, and can be said to receive the solar energy at inappropriate angles during other periods of time. This can not apply only to directions of the sun (so called hour angles) from the solar cell module side but also to seasonal change of the sun route (declination change). In addition, the reflectance on the surface of the solar cell module also increases as the angle of incidence of sunbeams deviates from a normal to the solar cell module. The light receiving angle of the solar cell module is thus also inappropriate in this respect, which causes loss. Such loss is considered to sum up even to 20 to 30% of the energy to be received otherwise.
In order to eliminate the inappropriateness of the light receiving angle, the solar cell module needs to be always maintained at the best angle to the sun. This idea leads to a scheme of the photovoltaic power generating system of a sun tracking type and the tracking of the sun is expected to increase the electric power generated per year by 25% to 40%.
The concentrating photovoltaic power generating systems of the sun tracking type are also under research similarly toward reduction of unit cost of power generation. Since the concentrating photovoltaic power generating systems allow great saving of solar cells, which are most expensive among the components of the concentrating photovoltaic modules constituting the photovoltaic power generating systems, it becomes feasible to implement extremely great cost reduction.
As generally mentioned, generated voltage increases with increase in light intensity, so as to increase the rate of output energy to input energy, i.e., conversion efficiency. This results in yielding a greater output when compared with a configuration wherein solar cells are spread over the same area.
In order to draw this effect satisfactorily, it is necessary to construct the concentrating photovoltaic power generating system capable of concentrating light at a high magnification. This system requires the concentrating photovoltaic module having an optical system for efficiently concentrating the sunbeams.
A conventional means for concentrating the sunbeams is one as shown in FIG. 17 wherein a solar cell 204 is located at a position approximately coincident with the focal length of Fresnel lens 201 and parallel to the Fresnel lens 201, so as to concentrate sunbeams 107 impinging on the Fresnel lens 201, onto the solar cell 204.
In this method, however, spherical aberration, chromatic aberration, etc. of the Fresnel lens 201 makes it harder to concentrate the sunbeams 107 at a point with decrease in the F-number (=focal length÷aperture) of the Fresnel lens 201, which decreases light concentration efficiency. As a result, the focal length of the Fresnel lens 201 was not allowed to be decreased much. For this reason, the conventional concentrating photovoltaic modules increased their thickness, weight, and cost as compared with the flat panel type solar cell modules, and the tracking device for making the concentrating photovoltaic module track the sun also had to be constructed in large scale in consideration of tracking performance, wind endurance, and so on.
Taking the above into consideration, Japanese Patent Application Laid-Open No. 7-231111 suggests an example in which the entire module is compactified by subdividing (or downsizing) a concentrating lens. This is the example in which both the concentrating optical elements and solar cells are reduced to shorten the focal length while maintaining the F-number, as against the conventional concentrating photovoltaic modules. In this example, however, the number of solar cells increased with decrease of the size, so as to raise problems of decrease in efficiency due to a voltage drop in a series configuration of the solar cells, and increase of manufacturing cost.
U.S. Pat. No. 5,089,055 suggests an example in which a plurality of concentrating optical elements and a plurality of optical fibers are used to guide the sunbeams onto one solar cell. However, when exit faces of the optical fibers were directly arrayed in front of the solar cell, unevenness in quantity of light (hereinafter referred to as xe2x80x9clight quantity unevennessxe2x80x9d) among the individual optical fibers directly resulted in light quantity unevenness on the solar cell, which reduced the efficiency of the solar cell. In order to eliminate the light quantity unevenness in the individual optical fibers, it was necessary to use sufficiently long optical fibers. Since the permissible angle range of incidence of sunbeams was narrow on the input faces of the optical fibers, it was necessary to increase the F-number of the concentrating optical elements.
The expression xe2x80x9clight quantity unevenness on a solar cellxe2x80x9d as herein employed is intended to mean a state such that portions with strong light and portions with weak light are generated on the solar cell, which results in that the portions with strong light and the portions with weak light have optimal operating points different from each other, whereby the optimal operating point is shifted. Thus, there are cases where the shifted optimal operating point may be a value lower than an optimal operating voltage to be obtained with uniform light quantity, thereby lowering the conversion efficiency. Further, there are also cases where the light quantity unevenness may cause partial temperature rise to break the solar cell.
The above U.S. patent also describes an example wherein the plurality of optical fibers are once guided to a tubular light pipe, the sunbeams are mixed by making use of internal reflection inside the light pipe, and the mixed light is guided to the solar cell. However, since the light pipe has a different refractive index from that of the optical fibers, reflection loss occurs at the interface between them. There also occurs transmission loss, because the sunbeams are transmitted through the reflection inside the light pipe. Namely, aluminum or silver commonly used as a reflecting material of internal reflectors has the reflectance of 85 to 95% (in the visible region). While the sunbeams are guided to the solar cell through several reflections on the internal reflector, the energy of sunbeams decreases every reflection on the internal reflector, which posed a problem that the sunbeams were unable to be efficiently guided to the solar cell. It was also necessary to take deterioration of the reflecting material or the like into consideration.
The spherical aberration and chromatic aberration of the aforementioned Fresnel lens 201 hindered uniform irradiation of the solar cell 204 with the concentrated sunbeams 107 to cause degradation of efficiency of the solar cell 204 and increase of temperature at only local areas in certain cases, which resulted in damaging the solar cell 204. When the solar cell 204 was of multiple junction structure (in which a plurality of pn junctions made of several different materials were stacked in the traveling direction of light), the chromatic aberration caused dispersion of spectral distribution on the solar cell 204, resulting in greatly decreasing the conversion efficiency of the solar cell 204.
The expression xe2x80x9cdispersion of spectral distributionxe2x80x9d as herein employed is intended to mean one caused by chromatic aberration or the like, specifically a state such that dispersion depending on locations is generated in spectral distribution on a solar cell, thereby generating locations with more light of longer wavelengths or locations with more light of shorter wavelengths as compared to ordinary spectral distribution.
Since the Fresnel lenses generally used had the merits of smaller thickness, lighter weight, and lower cost than spherical (or aspherical) lenses having the same focal length, they have commonly been used, but they had lower concentration efficiencies than the spherical lenses, because a spherical surface (or an aspherical surface) was approximated by an uneven surface.
Each of a Fresnel lens with an uneven surface on the photoreceptive surface side (which will be referred to hereinafter as a front convex Fresnel lens) and a Fresnel lens with an uneven surface on the opposite side to the photoreceptive surface (which will be referred to hereinafter as a back convex Fresnel lens) had both merits and demerits, but they both were inferior to the spherical lenses (aspherical lenses).
Namely, while it was preferable to use the front convex Fresnel lens with small coma (a characteristic capable of guiding even sunbeams off the normal direction to the Fresnel lens to the solar cell) in consideration of relief of tracking accuracy of the tracking device, relief of forming accuracy of the concentrating photovoltaic module, utilization of circumsolar radiation, etc., dust was easier to build up on the photoreceptive surface and reflection loss occurred at uneven portions without provision of a sufficient focal length in the case of the front convex Fresnel lens, as compared with the back convex Fresnel lens.
Neither of the above-stated methods succeeded in efficiently concentrating the sunbeams on the solar cell without light quantity unevenness and dispersion of spectral distribution (hereinafter referred to as xe2x80x9cspectral distribution dispersionxe2x80x9d) and, particularly, in providing a compact and inexpensive concentrating photovoltaic module.
An object of the present invention is to concentrate the sunbeams on the solar cell without light quantity unevenness and spectral distribution dispersion and with high efficiency. Another object of the invention is to provide a compact, lightweight, inexpensive concentrating photovoltaic module, and a concentrating photovoltaic power generating system comprising the concentrating photovoltaic module and a tracking device.
The present invention was accomplished on the basis of the above-discussed recognition.
A concentrating photovoltaic module according to the present invention is a concentrating photovoltaic module comprising: a lightguide member having at least one exit face and a plurality of entrance faces; and at least one solar cell positioned immediately after the exit face of the lightguide member; wherein the lightguide member is comprised of a light transmissive, solid medium having no refractive-index-discontinuity portion and a surface of the lightguide member is smooth, and wherein the lightguide member makes sunbeams incident on the plurality of entrance faces, totally reflected on side faces, and emergent from the exit face. This allows the sunbeams with different characteristics (light quantity and spectral distributions) incident on all the entrance faces in the concentrating photovoltaic module to be combined and to be guided in a reduced state of light quantity unevenness and spectral distribution dispersion to the solar cell with high efficiency.
Namely, the sunbeams with different characteristics incident from all the entrance faces of the lightguide member each are repeatedly totally reflected on the smooth side faces of the lightguide member to be mixed, and thereafter they are together mixed in the same area inside the lightguide member. It is thus feasible to guide the sunbeams in the reduced state of light quantity unevenness and spectral distribution dispersion to the solar cell and thus to prevent the degradation of efficiency of the solar cell due to the light quantity unevenness and spectral distribution dispersion. The expression xe2x80x9chaving no refractive-index-discontinuity portionxe2x80x9d stated herein refers to the refractive index being almost single; specifically, dispersion is preferably within 1% and more preferably within 0.5%. More preferably, it refers to the refractive index being single (though inevitable dispersion in fabrication is permitted).
Other features and effects of the present invention will be described below in detail with reference to the drawings.

Concentrating photovoltaic module and concentrating photovoltaic power generating system


An orthodontic device which may be used for treating Class II malocclusions including one or more rotational joints having a movable axis of rotation and an extension assembly having at least two reciprocating rods. Advantageously, the device may be elasticated or an unelasticated and may, with minimal reconfiguration, be used for further treatment, for example by being reversed.

Orthodontic appliances for treating Class II and III malocclusions include various types. Some of these appliances connect near a lower molar with the distal end connected to a strand near the upper canine. However, such appliances suffer from the disadvantage that they are unsightly. It is preferable, therefore, to attach the appliances between the lower and upper molars, as this reduces the visibility of the appliance.
The devices which attach between the upper and lower molars include two types: elasticated and non-elasticated. The elasticated type includes a spring or elasticated material to provide a biasing force. An example of such a device is disclosed in WO 2016/085606. However, such elasticated devices suffer from the disadvantage that the spring or elasticated material provides an inconstant biasing force over time due to degradation. Furthermore, a spring can impose significant discomfort for the patient.
Non-elasticated orthodontic devices for treating Class II and III malocclusions are known, such as that disclosed in US 2007/0224567, but this device, and similar devices disclosed in the art, suffer from the disadvantage that they are rigid and therefore do not accommodate the natural movements of the lower jaw, which can also lead to significant discomfort.
A further significant disadvantage of known unelasticated molar-to-molar devices lies in their overall length. It is desirable to reduce the length for mechanical and cosmetic reasons, but it is essential that these devices still provide the required leverage to treat the specific malocclusion.


A vessel support and plate which allows the user to carry a plate, napkin, and drinking vessel in one hand. The assembly includes a drinking vessel support member [23], a napkin holding member [25], a plate member [22] and a mechanism to grasp the assembly [24]. The vessel support member [23] has a recess [60] to receive the base of a drinking vessel [95, 97]. This recess has a mouth [63] extending from its periphery to its center [66], allowing the supporting member to cradle stemware by its bowl, with the stem suspended therefrom. A tilted grip member [24] attached to the plate allows the user to hold the device with minimal effort. A bulge [46] cooperating with the grip member on the bottom surface [44] of the plate allows the user to comfortably cradle the plate in the palm of the hand. The assembly further includes a member to detachably receive a napkin [25].

Formal dining occasions are often preceded by receptions, at which hors d'oeurves and appetizers are served along with drinks while guests greet one another and converse.
This activity is conducted in a similar fashion at business receptions, buffets, as well as at informal picnics and barbeques.
The service of food and drinks to people who have no formal seating arrangement presents the problem of handling: 1) a plate holding food; 2) a drink; 3) a napkin; 4) a utensil; 5) a proper handshake when greeting another guest. In this situation, with a standard plate and drinking glass, the user would have both hands busy, and would need to carefully manipulate these items to free a hand for any other use, such as a handshake. As discussed further below, this problem has been addressed to a varying degree of satisfaction.

Drinking vessel support means and plate assembly


Disclosed is a therapeutic agent for the treatment of peripheral circulatory disorders that contains as the effective ingredient a dibenzoxazepin derivative of the following formula or a pharmaceutically acceptable salt thereof: ##STR1## where R.sub.1 is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; R.sub.2 is a hydrogen atom or a lower alkyl group; and A signifies the group ##STR2## (where R.sub.3 is a hydrogen atom, a lower alkyl group, an optionally substituted phenyl group or a styryl group). Also, disclosed is a method for treatment of peripheral circulatory disorders by administering the compound of the formula (I) or a pharmaceutically acceptable salt thereof to a patient suffering from such disorders.

a. Field of the Invention
The present invention relates to a therapeutic agent for the treatment of peripheral circulatory disorders that contains as the effective ingredient a dibenzoxazepin derivative of the following formula or a pharmaceutically acceptable salt thereof: ##STR3## where R.sub.1 is a hydrogen atom, a halogen atom, a lower group or a lower alkoxy group; R.sub.2 is a hydrogen atom or a lower alkyl group; and A signifies the group ##STR4## (where R.sub.3 is a hydrogen atom, a lower alkyl group, an optionally substituted phenyl group or a styryl group).
b. Description of the Prior Art
The compounds of formula (I) were previously synthesized by the present inventors and their utility as medicines was seen to manifest not only by their ability to decrease lipids and peroxylipids, lower the blood sugar level and inhibit platelet aggregation (as shown in Japanese Patent Public Disclosure No. 166180/1981) but also by their ability to provide enhanced memory (as shown in Japanese Patent Public Disclosure No. 144319/1983).

Dibenzoxazepine compounds useful in the treatment of cerebral vasospasm or its sequela


A description processing device has: a receiving unit which receives a behavior level description; a label-name generating unit which generates a label name; a label disposing unit which disposes a top label statement; an extracting unit which extracts an extracted label statement, a variable-name generating unit which generates a variable name; a replacing unit which replaces a statement immediately below the top label statement to the extracted label statement by a column of a conditional executable statement and an operation/assignment statement and replaces a jump statement for jumping to the extracted label statement by a column of an operation/assignment statement and a jump statement for jumping to the top label; a control unit which repeats the extraction, the generation of a new variable name, and the replacement; an inserting unit which inserts an operation/assignment statement; and an output unit which outputs the behavior level description.

1. Field of the Invention
The present invention relates to a description processing device and a description processing method suitable for increasing parallelism by converting a behavior level description for designing an electronic circuit, and a recording medium recording program for realizing them on a computer.
2. Description of the Related Art
Because of advance in computer techniques, designing, analysis, evaluation, etc. of semiconductor integrated circuits has been commonly carried out by using a Computer-Aided Design (CAD) system having a behavioral synthesis tool and a logic synthesis tool. For example, Unexamined Japanese Patent Application KOKAI Publication No. 2007-272671 discloses a circuit design supporting system having a behavioral synthesis tool and a logic synthesis tool.
When a semiconductor integrated circuit is to be designed by using the circuit design supporting system, first, a designer prepares a behavior level description including the information necessary for hardware implementation of bit width, etc. of an input port and variables.
Next, by using the behavioral synthesis tool, the designer converts the behavior level description to a Register Transfer Level (RTL) description expressing the logics, which are to be implemented, by registers and logic functions between the registers. Then, the designer converts the RTL description to logic circuits of the gate level by using the logic synthesis tool.
In such design of an electronic circuit, techniques of increasing parallelism by speculatively calculating conditional expressions of conditional branching, THEN part, and ELSE part have been disclosed in, for example, Unexamined Japanese Patent Application KOKAI Publication No. H5-334391, Unexamined Japanese Patent Application KOKAI Publication No. H5-334466, and "Global Scheduling Independent of Control Dependencies based on Condition Vectors," by Kazutoshi Wakabayashi and Hiroshi Tanaka, Proc. of 29th ACM/IEEE Design Automation Conference, pp 112 to 115, 1992, 6 (referred to as "Non-Patent Literature 1").
Even when a label statement declaring a label which is a jump destination of a jump statement is present, there is a demand to constitute a high-speed electronic circuit by applying the techniques disclosed in Non-Patent Literature 1 and increasing parallelism by, for example, deleting or moving the label statement by parallelizing statements in the vicinity of the statement.

Description processing device, description processing method, and recording medium


A slider, the sliding performance, i.e., sealing performance of which is improved, without a decline in the combination strength of the grain boundaries and the abrasion resistance, by including 2-10%, more preferably 3-8%, by weight of free carbon in a slider composed of a high density silicon carbide sintered compact the relative density of which is not less than 95%.

1. Field of the Invention
This invention relates to a slider for use in mechanical seals, bearings, valve seats, etc. under severe atmospheric conditions, and more particularly to a high performance slider of silicon carbide sintered compact of which the friction coefficient is reduced in addition to improving the lubrication property, mechanical strength, abrasion resistance, etc. 2. Prior Art
A high-density silicon carbide sintered compact (hereinafter referred to as "SiC sintered compact") has long been known for its excellent property such as excellent resistance to heat, abrasion and corrosion, etc, and is one of the useful ceramics used, for example in gas turbines. In particular the SiC sintered compact has already been put in practical use as sliders for mechanical sealing and is now considered one of the high performance slider materials with the aforementioned excellent property.
With an increasing demand for highly effective seals, bearings, etc. under, the background of remarkable technological, development of a higher sealing performance is now required in mechanical seals, a higher lubricating performance in bearings and a higher sliding performance in sliders composed of SiC sintered compact.
Looking at known SiC sintered compacts actually used, they are obtained, for example, by a step of admixing a fixed amount of boron compound and/or aluminum compound, each serving as a sintering accelerator, with a fixed amount of carbon serving as a sintering aid, a step of molding into a compact, and a step of sintering the compact at a high temperature of not lower than 2000.degree. C. under an inert atmosphere. However, free carbon is found not only on the surface of the SiC sintered compact but also at grain boundaries thereof due to a sublimate decomposition reaction of SiC itself at the sintering step. As a result, there exists crystal grains of SiC and grain boundaries of carbon on the surface of high-density SiC sintered compact used for mechanical sealing. In other words, there is a segregation of carbon at fine cavities on the surface of the compact.
As is well known, carbon has a lipophilic property as well as relatively high hydrophilic property, and therefore it is usually possible for a high-density SiC sintered compact having the aforementioned microscopic carbon on the surface (i.e. sliding surface) to exhibit a high performance as a slider for mechanical sealing of fluid under a fluid lubrication. Due to a high temperature or a high viscosity produced in the liquid to be sealed, however, it is sometimes very difficult to stabilize a fluid lubrication film formed on the sliding surface in the case of a high-density SiC sintered compact of the aforementioned composition, and as a result, there is the possibility of abnormal abrasion or increase on of the friction coefficient on the sliding surface occurring which would cause thereby a decline in the sealing performance.
Accordingly, in the case of a slider composed of such a high-density SiC sintered compact, it is necessary to increase carbon content in order to improve stabilization of the fluid lubrication film on the sliding surface. But when free carbon (fc) is excessively increased in the SiC sintered compact, there exists a problem in that a desired dense packing (i.e., high density) of the sintered compact is not gained due to the increase of the carbon crystal structures a and as a result the combination strength of the grain boundaries is considerably lowered a eventually declining the abrasion resistance to be exhibited by the slider.

Slider composed of a high-density silicon carbide sintered compact


A sewing machine and is connected to an external environment device having a display such that additional pattern information transmitted to the external environment device may be confirmed at the display irrespectively of internal and external information, the sewing machine having a memory for storing data which may be rewritten therein and an information input/output device for inputting and outputting external information into and from the memory such that the sewing machine may be operated under control of the external information while machine control information is outputted through the information input/output device.

1. Field of the Invention
The present invention relates to a sewing machine and the system thereof, and more particularly relates to operating the sewing machine under control of external information while machine control information is outputted.
2. Prior Art
According to the conventional sewing machine, a pattern to be stitched is optionally selected among a plurality of different patterns in reference to the pattern data or indication data which are stored in the sewing machine. It has been proposed that an external memory having pattern data stored therein is removably connected to the sewing machine so as to stitch new patterns. However, as the external memory has no indicating means such as a display, the machine user can not know the contents of the memory until the same is connected to the sewing machine. Further, the machine user has to know the contents of the internal and/or external memories at a limited area of display which is arranged in a limited space of the sewing machine frame and often fails to show thereat a sufficient amount of information as required by the user. Further, it has been proposed to read out the pattern data from a plurality of external memories, capacity of which is limited respectively, so as to form a pattern in combination of different patterns. In this case, at most two memories are allowed to be connected to the sewing machine. It has, therefore, been very troublesome to exchange the external memories in case the patterns to be combined are stored in many memories, for example, in more than four memories. Further, as an external environment means, a computer has been proposed to be connected to the sewing machine. This is, however, to simply give instructions on the basis of data and is not a part of sewing machine system for cooperating with the sewing machine. Namely, the computer fails to renew and indicate the content of control for the sewing machine.
The invention has been provided to eliminate the defects and disadvantages of the prior art. It is, therefore, a primary object of the invention to provide an external environment means having a display and connected to a sewing machine so as to enable a machine user to visually confirm, besides the limited area of machine frame, the information stored in the external memories as well as in the sewing machine and the information to be newly added.
It is another object of the invention to operate the sewing machine under control of the confirmed information which is transferred into a memory of the sewing machine.
It is another object of the invention to enable a machine user to visually confirm and memorize the contents of a plurality of external memories indicated at the display of the external environment means.
It is another object of the invention to provide an information input/output means for storing the external data stored in a plurality of external memories into a memory of a sewing machine.
It is another object of the invention to provide another information input/output means which may be connected to the first mentioned information input/output means during operation of the sewing machine so as to supply further new information to the sewing machine.
It is another object of the invention to control the information inputted and outputted by the information input/output means with the specific information specified by a user or machine operator.
It is another object of the invention to make the specific information include a plurality of information specified by a plurality of users or machine operators.
It is another object of the invention to specify the information inputted and outputted by said information input/output means in connection with the contents of stitching operation.
It is another object of the invention to specify the information inputted and outputted by said information input/output means in connection with a pattern or patterns to be stitched.
It is another object of the invention to provide a sewing machine system for renewing the data.
It is another object of the invention to provide a net work as an external environment so as to enable the machine user to obtain new information at a real time.
The other objects and advantages of the invention will be apparent in the detailed description of the invention.
For attaining the objects, the invention substantially comprises a vertically reciprocating needle and a mechanism for moving a work relative to the needle to form stitches on the work, the sewing machine comprising a first memory having pattern data and indication data stored therein, the pattern data and indication data being selectively recoverable, a second memory having a control system of a sewing machine stored therein, a third memory for storing at least one of pattern data, indication data and control data which may be rewritten therein, an information input/output means for inputting and outputting external information into and from the third memory, so that the sewing machine may be operated under control of external information while machine control information is outputted through the information input/output-means.
Further, the invention comprises a vertically reciprocating needle and a mechanism for moving a work relative to the needle to form stitches on the work, the sewing machine comprising a first memory having pattern data and indication data stored therein, said pattern data and indication data being selectively recoverable, a second memory having a control system of sewing machine stored therein, a third memory for storing at least one of pattern data, indication data and control data and data set by a user or machine operator which may be rewritten therein, an information input/output means for inputting and outputting external information into and from the third memory, so that the sewing machine may be operated under control of external information while machine control information is outputted through the information input/output means.
Further, the invention comprises a vertically reciprocating needle and a mechanism for moving a work relative to the needle to form stitches on the work, said sewing machine comprising a first memory having pattern data and indication data stored therein, the pattern data and indication data being selectively recoverable, a second memory having a control system of sewing machine stored therein, a third memory for storing at least one of pattern data, indication data and control data and data set by a user or machine operator, which may be rewritten therein, an information input/output means for inputting and outputting external information into and from the third memory, so that the sewing machine may be operated under control of external information while the data set by a user or machine operator is outputted through the information input/output means.
Further, the invention comprises a sewing machine having a vertically reciprocating needle and a mechanism for moving a work relative to the needle to form stitches on the work and an external environment means for maintaining the control environment of said sewing machine and giving instructions while exchanging information with said sewing machine, the sewing machine including a first memory having pattern data and indication data stored therein, the pattern data and indication data being selectively recoverable, a second memory having a control system of sewing machine stored therein, a third memory for storing at least one of pattern data, indication data and control data which may be rewritten therein, an information input/output means for inputting and outputting external information into and from the third memory, so that the sewing machine may be operated under control of external information, and so that the external environment means may output the control information from said third memory through the information input/output means.


The present disclosure provides a panel display optimization method, a display panel, and a storage medium. The panel display optimization method includes a region acquisition step, an adjustment step, and a high-low gray level step. The present disclosure is used to make processing coefficients of high-low gray levels of pixels to be processed having farther boundaries be greater according to distances from the pixels to be processed to the boundaries of a first pixel region, a second pixel region, and a third pixel region, that is, according to forward transitional spaces and backward transitional spaces to adjust the processing coefficients of the high-low gray levels. This further reduces graininess of the panel and improves visual quality of the panel after performing high-low gray level processing on adjusted pixels.

In current technology, in order to achieve objectives of low cost and high transmittance, 4-domain pixel is the best layout of sub-pixels. However, panels with 4-domain pixels have a problem of serious color shift at wide viewing angles. An improved algorithm at wide viewing angles is developed to improve the color shift at wide viewing angles by substituting original image data (as shown in FIG. 1) with a pair of high and low gray levels (high-low, HL).
Technical problem: introduction of HL gray levels causes a problem of graininess (as shown in FIG. 2) after images are processed. In order to reduce graininess, color detection functions are developed subsequently, and the functions reduce a certain degree of graininess by detecting colors and selectively performing HL processing in image regions. When a detected region requiring HL gray level processing is narrower in a horizontal direction, the graininess shown will appear, which is very abrupt and seriously affects visual effects of panels.
Therefore, the present disclosure provides a panel display optimization method, a display panel, and a storage medium to reduce the problem of graininess when performing high-low gray level processing, thereby improving display effects of display panels.

Panel display optimization method, display panel, and storage medium

TCL China Star Optoelectronics Technology Co. Ltd.


A bootstrap capacitor detecting circuit includes a current source, for providing a discharging current; a first switch, for conducting connection between a system voltage and a bootstrap voltage node according to a power-on-reset signal, to charge the bootstrap voltage node; a second switch, for conducting connection between a current source and the bootstrap voltage node according to the power-on-reset signal, to discharge the bootstrap voltage node; and a detecting unit, for determining whether a bootstrap capacitor is connected normally according to a bootstrap voltage of the bootstrap voltage node after the current source discharges the bootstrap voltage node.

1. Field of the Invention
The present invention relates to a bootstrap capacitor detecting circuit and a bootstrap DC-DC converter, and more particularly, to a bootstrap capacitor detecting circuit and the bootstrap DC-DC converter thereof capable of discharging a bootstrap voltage node and then determining whether a bootstrap capacitor is connected normally according to whether a bootstrap voltage is significantly reduced.
2. Description of the Prior Art
Power supply devices play important roles in the modern information technology. Among all the power supply devices, DC-DC converters have been widely used, and are mainly utilized for providing a stable output voltage for electronic elements.
In short, please refer to FIG. 1, which is a schematic diagram of a conventional bootstrap DC-DC converter 10. As shown in FIG. 1, when a clock signal VCLF is with logic high to trigger a set terminal S of an SR flip-flop 100, the SR flip-flop 100 continues to output a control signal CON in logic high to a pre-driving unit 102. Therefore, the pre-driving unit 102 controls an upper gate driving unit 104 and a lower gate driving unit 106 to output an upper gate control signal UG and a lower gate control signal LG accordingly, such that the upper gate switch 108 is turned on and the lower gate switch 110 is turned off, to output an inductance current IL and a corresponding output voltage VOUT for a loading RLOAD. Then, when a feedback voltage VF (a divided voltage from the output voltage VOUT) exceeds a reference voltage VREF, an error amplifier 112 outputs an error signal EAO to indicate a pulse width modulation (PWM) control loop 114 to reset a reset terminal R of the SR flip-flop 100, such that the SR flip-flog 100 outputs the control signal CON in logic low. Therefore, the pre-driving unit 102 turns off the upper gate switch 108 and turns on the lower gate switch 110 accordingly until the clock signal VCLK switches to another logic high to trigger the set terminal S of the SR flip-flop 100. Then, the above operations are repeated.
When the lower gate control signal LG is with logic high such that the lower gate switch 110 is turned on, a switch 116 (including a body diode 118) conducts connection between a system voltage PVCC and a bootstrap capacitor CBOOT to charge the bootstrap capacitor CBOOT. Therefore, when the control signal CON is with logic high to turn on the upper gate switch 108, a driving voltage of the upper gate driving unit 104 is high enough to turn on the upper gate switch 108, wherein a bootstrap voltage VBOOT of a bootstrap voltage node BOOT, which is coupled to an input terminal of a driving voltage of the upper gate driving unit 104, is an input voltage VIN plus a voltage across the bootstrap capacitor CBOOT (i.e., the system voltage PVCC), and the drain-source voltage of the upper gate switch 108 is the bootstrap voltage VBOOT. The operation of the bootstrap DC-DC converter 10 is well-known for those skilled in the art, and hence the details are omitted herein.
For this structure, if the bootstrap capacitor CBOOT is not connected normally during the manufacturing process (such as false welding or lose efficacy, that is, the bootstrap capacitor CBOOT is ineffective, causing the system voltage PVCC to charge parasitic capacitor), the upper gate driving unit 104 can not be effectively driven by the bootstrap voltage VBOOT to completely turn on the upper gate switch 108. Therefore, when the upper gate switch 108 outputs the inductance current IL, the upper gate switch 108 could be burned out due to large power. Thus, there is a need for improvement of the prior art.

Bootstrap capacitor detecting circuit and bootstrap DC-DC converter thereof


A personal watercraft designed to advance suitably in a forward direction, to prevent an influence of side waves, and to incline to the turning center side when being steered by an operator from a forward direction to a turned direction. The personal watercraft includes a keel provided at a middle portion in the widthwise direction of the bottom of the body and extending from the bow to the stern. The keel is formed in an arc in the widthwise direction of the body. The keel is configured such that, at the rear half portion of the body, the center of the arc of the keel substantially coincides with the position G of the center of gravity of the body. On the other hand, at the front half portion of the body, the radius R2 of the arc of the keel gradually decreases in the forward direction.

1. Field of the Invention
This invention relates to a personal watercraft which includes a saddle type seat extending in a forward and backward direction at a middle portion of a body, an operation handle member provided forwardly of the seat, and an arcuate keel provided at a middle portion of a bottom of the body.
2. Description of Background Art
One known example of a personal watercraft is a jet propulsion watercraft having a jet propeller mounted at a rear portion of a body and driven by an engine which takes in water from the bottom and jets the water rearwardly to propel the body.
This personal watercraft includes a keel provided at a middle portion of the bottom and extending forwardly and rearwardly (that is, from the bow to the stern).
FIG. 8 shows a sectional view of a conventional personal watercraft. The personal watercraft 100 is configured such that a keel 101 is formed in such a manner as to project downwardly so that it may project by a comparatively great amount downwardly from a middle portion of a bottom 102.
Since the keel 101 projects downwardly by a comparatively great amount, the straightforwardly advancing property of the personal watercraft 100 can be maintained suitably when it is propelled.
However, where the keel 101 projects downwardly by a comparatively great amount, for example, if the personal watercraft 100 is acted upon by a side wave while it glides, then the keel 101 is liable to be influenced by the side wave. Since the keel 101 is influenced by a side wave in this manner, the personal watercraft 100 tends to roll leftwardly or rightwardly.
An example of a personal watercraft which is not influenced by a side wave, is shown a xe2x80x9cPersonal Jet Propulsion Watercraftxe2x80x9d of the official gazette of Japanese Patent Publication No. Hei 6-96397. In the following, this personal watercraft is described in detail with reference to the succeeding figures (FIGS. 9 and 10) derived from FIGS. 1 and 4(A), respectively, shown in the official gazette. Note, however, that the reference numerals are re-numbered.
FIG. 9 is a sectional view showing a first example of a conventional personal watercraft which is less susceptible to being influenced by a side wave. The personal watercraft 110 is configured such that a keel 111 is formed flat so as not to project downwardly from a bottom 112.
According to this personal watercraft 110, even when it is acted upon by a side wave while it glides, the keel 111 is influenced comparatively little by a side wave. Therefore, the personal watercraft 110 does not roll leftwardly or rightwardly.
FIG. 10 is a plan view showing a second example of a conventional personal watercraft which is less susceptible to be influenced by a side wave. As a crew-member 115 of the personal watercraft 110 operates an operation handle member 116 as indicated by an arrow mark b, a steering nozzle (not shown) of a body rear portion 117 is swingably moved.
Consequently, a water jet 118 jetted from the steering nozzle is directed obliquely as indicated by an arrow mark c so that the personal watercraft 110 turns as indicated by an open arrow mark.
However, if the keel 111 is formed flat as not to be influenced by a side wave, then when the personal watercraft 110 is turned, the body is pushed by water from a sideward direction and the body tends to incline inwardly. However, since the bottom is formed flat, when the body begins to incline, the flat face of the body acts as resistance and the body is less likely to incline.
Therefore, it would be desirable to construct the personal watercraft 110 in such a manner that it could incline readily when the body begins to incline upon turning. With such a design, the personal watercraft 110 could be placed into a turning condition from a straightforwardly advancing condition, while maintaining a natural feeling for the operator, for example, similar to the natural feeling provided an operator of a motorcycle during a turning operation.
Therefore, the object of the present invention is to provide a personal watercraft which suitably assures a straightforwardly advancing property, and which also prevents the influence of a side wave, and inclines readily when the personal watercraft is turned.
In order to attain the object described above, according to the first aspect of the present invention, a personal watercraft is provided with a saddle type seat extending in a forward and backward direction at a middle portion of a deck of a body, an operation handle member provided forwardly of the seat, a pair of foot decks formed on the opposite sides of the seat, and a keel provided at a middle portion of a bottom of the body and extending from a bow to a stern. The keel extends in the forward and backward direction of the body and is formed in an arc. In addition, at a location rearward of the center of the body, the center of the arc of the keel substantially coincides with the height of the position of the center of gravity of the body.
At the portion of the body rearward of the center of the body, the center of the arc of the keel substantially coincides with the height of the position of the center of gravity of the body. Consequently, the radius of the arc of the keel can be made large. As the radius of the arc of the keel becomes large, the keel can be prevented from projecting downwardly by a great amount from the bottom. Since the projecting amount of the keel is suppressed in this manner, the keel is less likely to be influenced by a side wave so that the body can be prevented from rolling leftwardly or rightwardly by an influence of a side wave.
Further, since the center of the arc of the keel substantially coincides with the height of the position of the center of gravity of the body, when a crewmember performs a steering operation and the body turns its direction from a forwardly advancing direction to a turning direction and is pushed by water from a sideward direction, whereupon the body begins to incline toward the center of the turning movement, the body can incline around the height of the position of the center of gravity. Therefore, the body can incline readily when the watercraft turns.
Consequently, since the body can incline smoothly toward the center of the turning movement by a natural movement, the posture of the personal watercraft can smoothly change from an uprightly standing posture to an inclined posture when the watercraft is turned, providing an operator with the same sense as an operator of a motorcycle feels when the motorcycle turns.
According to a second aspect of the present invention, the radius of the arc of the keel gradually decreases forwardly at a location forward of the center of the body.
Since, at the portion of the body forward of the center of the body, the radius of the arc of the keel gradually decreases forwardly, the keel at the portion of the body forward of the center of the body can be made project by a comparatively great amount from the bottom.
Consequently, since the plowing property by the keel when the personal watercraft advances straightforwardly can be improved, when the personal watercraft is hit by a high wave during gliding thereof, the impact provided to the body can be kept low, and driving comfort can be maintained.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.


In a forming an electrical double-layer capacitor by combining a plurality of electrical double-layer capacitor cells, the electrical double-layer capacitor cells are formed not by being laminated in a vertical direction but by being arranged in a horizontal direction, thereby allowing a multiplicity of electrical double-layer capacity cells to be arranged even in the case of a narrow space if only there is a sufficient area.

1. Field of the Invention
The present invention relates to a structure for arranging large-capacity electrical double-layer capacitor cells within narrow confines of space.
2. Description of the Related Art
An electrical double-layer capacitor has a large capacity as compared with other types of capacitor and has hitherto been used as a power source for backup, or the like.
FIG. 6 illustrates a conventional electrical double-layer capacitor cell (hereinafter simply referred to as the cell in some cases). As shown, a cell C comprises the following components: a collecting electrode 1; a sealing material 2; two electrode layers 3; and a porous separator 4.
The sealing material 2 has a cylindrical configuration, and the porous separator 4 is disposed in a substantially central portion of its interior. The electrode layer 3 is filled on each opposite side of the porous separator 4, and the collecting electrode 1 is placed in such a manner as to cover the surface of the electrode layer 3 and the rim of the sealing material 2.
As the collecting electrode 1, an electrically conductive rubber sheet, for example, may be used, and as the sealing material 2, non electrically conductive rubber, for example, may be used. As the porous separator 4, a polypropylene porous film, for example, may be used. In addition, as the electrode layer 3, paste made by mixing activated carbon particles and dilute sulfuric acid may be used.
FIG. 7 illustrates a conventional electrical double-layer capacitor formed by combining a plurality of cells C having the above described arrangement. As shown, the electrical double-layer capacitor comprises the following components: a case 5; electrode plates 6, 7; terminals 6-1, 7-1; an insulating plate 8; reinforcing plates 9, 10; and the cells C.
The reinforcing plate 9 is connected to the electrode plate 6, while the reinforcing plate 10 is connected to the electrode plate 7 via the case 5. The terminal 6.1 is formed by cutting out a part of the electrode plate 6, while the terminal 7-1 is formed by cutting out a part of the electrode plate 7. The insulating plate 8 is inserted between the electrode plates 6 and 7 to provide insulation therebetween.
If the cells C are simply laminated, the contact resistance of activated carbon particles of the cells C is large, so that the internal resistance of the capacitor is large. Hence, it is common practice to calk the rim of the case 5 at the time of lamination so as to apply pressure to the laminated body, which reduces the aforementioned contact resistance, thereby rendering the internal resistance of the capacitor small.
In the above-described example, pressurization is conducted not at the stage of individual cells but after the lamination thereof. However, in some cases, pressurization processing is effected at the stage of individual cells.
FIG. 8 illustrates a cell of an electrical double-layer capacitor of a button type. As shown, this cell comprises the following components: collecting electrodes 11, 12; two electrode layers 13; a porous separator 14; a sealing material 15; and an insulating material 16.
The collecting electrode 12 is formed into a cylindrical configuration and accommodates therein the electrode layer 13, the porous separator 14, the sealing material 15, etc. This assembly is pressed with the collecting electrode 11 from thereabove, and the rim of the collecting electrode 12 is calked inwardly, thereby fabricating a cell. The calking force of the collecting electrode 12 provides the pressurizing force, thereby rendering the internal resistance small.
FIG. 9 shows an electrical double-layer capacitor in which button-type cells are laminated. In order to obtain a desired voltage, a necessary number of cells are laminated and are accommodated in an outer case 17. In this case, it suffices if electrical contact is secured, and there is no need to provide pressurization.
As described above, in conventional electrical double-layer capacitors, the cells C are disposed by being laminated.
It should be noted that, as a prior-art document concerning electrical double-layer capacitors, for example, Japanese Patent Laid-Open No. 2621/1981 is known.
However, there has been a problem in that if a request is made to install a large-capacity electrical double-layer capacitor within narrow confines of space, it is impossible to meet the request with the conventional way of laminating cells.
For instance, when it is desirous to install an electrical double-layer capacitor within narrow confines of space such as between a pair of inner and outer panels constituting a wall of an automobile, the conventional structure of lamination would result in an increased thickness for the capacitor, thereby making the installing impossible.

Structure for arranging electrical double-layer capacitor cells