The present invention discloses a localized plasmon resonance sensing device and a fiber optic structure. The device comprises an optical fiber and a noble metal nanoparticle layer. The optical fiber has a plurality of notches, and such notches are located on the side surface of the optical fiber. The noble metal nanoparticle layer is located at the notch. As a result, when a light is launched into the optical fiber, a detecting unit can be used to detect a localized plasmon resonance signal which is generated by the interaction between the noble metal nanoparticle layer and the light.

1. Field of the Invention
The present invention relates to a localized plasmon resonance sensing device and a fiber optic structure; in particular, the present invention relates to a localized plasmon resonance sensing device and a fiber optic structure with an array of sensing regions.
2. Description of Related Art
A fiber optic sensor basically uses an optical fiber to guide light waves generated by a light source to a test area, and variations regarding to certain physical or chemical quantity in the test area, e.g., stress, strain, temperature, refraction index, molecular concentration, may cause changes in the characters of the light wave, therefore through analyses on such changes of light wave characters, it is possible to infer such variations regarding to the physical or chemical quantity. The sensor signal of the fiber optic sensor is barely subject to interferences from electromagnetic noises and magnetic fields when operated in a fiber optic mode, and other hazards in the local environment such as ionizing radiation can be effectively avoided as well; as such, it can be appropriately applied in hostile environments, like within a nuclear power plant. Additionally, one single optical fiber can be simultaneously used as a sensor and a signal transfer line, and the integral size of the fiber optic sensor is usually smaller than that of a conventional sensor together with the transfer line, so it is possible to be deployed in a region spatially tight or extremely challenging for reaching.
The fiber optic sensor employs light as the media for excitation and transmission, rather than usage of electric current or voltage, thus risks in electric shock can be avoided, and it is suitable for medical measurement applications. Fiber optic materials are corrosion-proof, well adapted for deep ocean engineering and applications in a chemically corrosive environment, and provide good biocompatibility as well. The glass optical fiber demonstrates better temperature tolerance than the metal strain gauge, whose long-term stability and fatigue lifecycle are both higher than the resistive stain gauge, accordingly fitting for surveillances in long duration of time. Since the optical fiber is originally applied in the field of long distance communication, relevant technologies in fiber optic sensor can be conveniently exploited from technologies in long distance telemetry. Furthermore, wavelength division multiplexing technology developed in optical communication also facilitates multi-point telemetry with one single optical fiber, so the fiber optic sensor now has been comprehensively used in various fields such as aviation, medication, chemistry, geotechnical engineering, civil engineering and so forth.
Please refer first to FIG. 1, wherein a diagram illustrating the basic structure of an optical fiber is shown. The optical fiber in essence is an optical waveguide of an axially symmetric cylindrical structure, and, radially from the axle to the outside, can be divided into three layers, respectively the core 11, the cladding 12 and the jacket 13. The core 11 and the cladding 12 are basic elements for light transfer in the optical fiber and core 11 has a higher refractive index than that of cladding 12. The jacket 13 acts as the protection layer against external environment.
The well-known principle of the fiber optic sensor is, for example, to measure a certain physical (chemical) quantity, it first relates one characteristic of light to the variation of such a physical (chemical) quantity, next performs measurements on the result caused by such a variation, then the magnitude of the physical (chemical) quantity to be measured can be indirectly inferred. Regarding to an example of measurement on a physical quantity, if it is now to measure the torsion of a piece of mechanical part, bending the optical fiber leads to escape of light energy from the core and energy loss, and higher torsion results in more significant light energy loss; in other words, light energy is subject to the variation of torsion. Accordingly, by placing the optical fiber optic onto the mechanical part, it is possible to measure the intensity of transmitted light through the optical fiber, indirectly inferring the torsion of the mechanical part sensed by the optical fiber; on the other hand, for an example of chemical value measurement, a gas can absorb light of a certain specific wavelength and the absorption is proportional to the concentration of the gas. Therefore, an appropriate light is guided by the optical fiber to the test area so as to allow part of the light to interact with the gas in the test area, and get analyzed at the other end of the optical fiber by the spectrum thereof for measurement of intensity attenuation at the particular light wavelength such that it is possible to infer the concentration of the gas. Herein the modulation of light characteristic accountable for the variation of the physical (chemical) quantity may occur inside the optical fiber optic or at the exterior of the optical fiber as well; modulation of different characteristics of light may be measured individually or interactively, wherein the modulation mechanism may comprise:
1. absorption modulation;
2. chromatic dispersion modulation;
3. scattering based modulation;
4. luminescence-fluorescence based modulation;
5. refractive index based modulation;
6. geometric effect based modulation;
7. interferometric and phase modulation;
8. wavelength modulation; and
9. Doppler's effect modulation.
In addition, according the location where the sensing modulation occurs, different modulation mechanisms can be categorized as three major types: (1) extrinsic type, (2) intrinsic type, and (3) evanescent type characterized between the aforementioned two types. For the extrinsic typed sensor, it means that light, after guided to the test area through the optical fiber, momentarily leaves the optical fiber and is modulated by the external environment, then coupled into the original optical fiber or another optical fiber, and transferred to a signal generator for signal interpretation, wherein the optical fiber acts simply as a signal transmission line without participating in sensing operations; in the intrinsic typed sensor, on the other hand, light wave basically remains in the optical fiber all the time, and modulation from external environment cause changes in the internal characteristics of the optical fiber, thereby affecting a certain feature of the light wave (e.g., wavelength); the evanescent sensor uses changes of light energy loss in the evanescent field of the optical fiber caused by modulation from external environment to determine the environmental parameter to be detected; although such type of sensor may similarly involve in part of the light energy leaving the fiber core like the extrinsic typed sensor, a difference exists in that the modulation mechanism acts inside the cladding of the optical fiber, and the optical fiber is not only used as a signal transmission line but a sensing component as well.
To meet the requirements on sensing operations, the desktop Fiber Optic-Localized Plasmon Resonance (FO-LPR) sensing platform and implanted FO-LPR sensing system are developed. The implanted FO-LPR sensing system can be used to directly measure variations of specific biological molecules inside a living body, then the optical fiber of a suitable size can be selected based on the size of the object (e.g., organ or tissue) subject to the implantation. For example, if the optical fiber having a core of larger size is applied to a small animal, or to some small organs or tissues in a human body, such a larger size fiber may undesirably cause damages to a certain extent to the living body itself during implantation; serious damage may jeopardize its life while minor damage can result in additional metabolites or inflammation reactions in the living body, thus interfering the results originally intended to be measured.

Localized plasmon resonance sensing device and fiber optic structure


A rechargeable battery, which can improve safety by maintaining a short-circuit state when the internal pressure of the rechargeable battery exceeds a critical pressure due to overcharge (or any other reason). In one embodiment, the rechargeable battery includes an electrode assembly, a case accommodating the electrode assembly, a cap assembly sealing the case and including a cap plate, and a short-circuit member including a first short-circuit plate coupled to the cap plate and a second short-circuit plate on a surface of the first short-circuit plate facing toward the electrode assembly and coupled to the cap plate.

1. Field
Embodiments of the present invention relate to a rechargeable battery.
2. Description of the Related Art
Unlike a primary battery that is incapable of being recharged, a rechargeable battery can be repeatedly charged and discharged. A low-capacity rechargeable battery having a single cell is used, for example, in small portable electronic apparatuses, such as mobile phones, and camcorders. A large-capacity rechargeable battery that includes a plurality of rechargeable cells connected in a pack shape is used, for example, as a power source for driving a motor of a hybrid electric vehicle and the like.
Rechargeable batteries are manufactured in various shapes, for example, a cylindrical shape and a prismatic shape. A rechargeable battery is typically constructed with an electrode assembly in which a positive electrode and a negative electrode with a separator interposed between the positive and negative electrodes, a case accommodating the electrode assembly, and a cap assembly having an electrode terminal in the case.
Meanwhile, the rechargeable battery may be subjected to ignition and/or explosion due to an increase in the internal pressure of the rechargeable battery when excessive heat is generated due to overcharge and/or when an electrolyte is decomposed. Accordingly, there is a need for a rechargeable battery constructed to have improved safety.


In one aspect, the invention provides methods for treating, inhibiting, alleviating or preventing fibrosis in a mammalian subject suffering, or at risk of developing a disease or disorder caused or exacerbated by fibrosis and/or inflammation. In one embodiment, the invention provides methods of treating a subject suffering from renal fibrosis. In one embodiment, the invention provides methods of reducing proteinuria in a subject suffering from a renal disease or condition associated with proteinuria. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.

Chronic kidney diseases affect more than 20 million people in the United States (Drawz P. et al., Anm Intern Med 162(11); ITC 1-16, 2015). Glomerulonephropathies (GNs), including IgAN and MN are kidney diseases in which the glomeruli are damaged and frequently lead to end-stage renal disease and dialysis. Several types of primary GNs exist, the most common being IgAN. Many of these patients have persistent renal inflammation and progressive deterioration. Often these patients are treated with corticosteroids or immunosuppressive agents, which have many serious long-term adverse consequences. Many patients continue to deteriorate even on these treatments. No treatments are approved for the treatment of IgAN or MN.
IgA Nephropathy
Immunoglobulin A nephropathy (IgAN) is an autoimmune kidney disease resulting in intrarenal inflammation and kidney injury. IgAN is the most common primary glomerular disease globally. With an annual incidence of approximately 2.5 per 100,000, it is estimated that 1 in 1400 persons in the U.S. will develop IgAN. As many as 40% of patients with IgAN will develop end-stage renal disease (ESRD). Patients typically present with microscopic hematuria with mild to moderate proteinuria and variable levels of renal insufficiency (Wyatt R. J., et al., N Engl J Med 368(25):2402-14, 2013). Clinical markers such as impaired kidney function, sustained hypertension, and heavy proteinuria (over 1 g per day) are associated with poor prognosis (Goto M et al., Nephrol Dial Transplant 24(10):3068-74, 2009; Berthoux F. et al., J Am Soc Nephrol 22(4):752-61, 2011). Proteinuria is the strongest prognostic factor independent of other risk factors in multiple large observational studies and prospective trials (Coppo R. et al., J Nephrol 18(5):503-12, 2005; Reich H. N., et al., J Am Soc Nephrol 18(12):3177-83, 2007). It is estimated that 15-20% of patients reach ESRD within 10 years of disease onset if left untreated (D'Amico G., Am J Kidney Dis 36(2):227-37, 2000).
The diagnostic hallmark of IgAN is the predominance of IgA deposits, alone or with IgG, IgM, or both, in the glomerular mesangium. In IgAN, renal biopsies reveal glomerular deposition of mannan-binding lectin (MBL), a key recognition molecule for activation of MASP-2, the effector enzyme of the complement system's lectin pathway. Glomerular MBL deposits, usually co-localized with IgA and indicating complement activation, and high levels of urinary MBL are associated with an unfavorable prognosis in IgAN, with these patients demonstrating more severe histological changes and mesangial proliferation than patients without MBL deposition or high levels of urinary MBL (Matsuda M. et al., Nephron 80(4):408-13, 1998; Liu L L et al., Clin Exp Immunol 169(2): 148-155, 2012; Roos A. et al., J Am Soc Nephrol 17(6): 1724-34, 2006; Liu L L et al., Clin Exp Immunol 174(1):152-60, 2013). Remission rates also are substantially lower for patients with MBL deposition (Liu L L et al., Clin Erp Immunol 174(1):152-60, 2013).
Current therapy for IgAN includes blood pressure control and, frequently, corticosteroids and/or other immunosuppressive agents, such as cyclophosphamide, azathioprine, or mycofenolate mofetil, for severe disease (e.g., crescentic IgAN). The Kidney Disease Improving Global Outcomes (KDIGO) Guidelines for Glomerulonephritis (Int. Soc ofNephrol 2(2):139-274, 2012) recommend that corticosteroids should be administered to patients with proteinuria of greater than or equal to 1 g/day, with a usual treatment duration of 6 months. However, even with aggressive immunosuppressive treatment, which is associated with serious long-term sequelae, some patients have progressive deterioration of renal function. There is no approved treatment for IgAN, and even with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to control blood pressure, increased proteinuria persists in some patients. None of these treatments have been shown to stop or even slow the progression of IgAN in patients who are at risk for rapid progression of the disease.
Membranous Nephropathy
The annual incidence of membranous nephropathy (MN) is approximately 10-12 per 1,000,000. Patients with MN can have a variable clinical course, but approximately 25% will develop end-stage renal disease.
Membranous nephropathy is an immune-mediated glomerular disease and one of the most common causes of the nephrotic syndrome in adults. The disease is characterized by the formation of immune deposits, primarily IgG4, on the outer aspect of the glomerular basement membrane, which contain podocyte antigens and antibodies specific to those antigens, resulting in complement activation. Initial manifestations of MN are related to the nephrotic syndrome: proteinuria, hypoalbuminemia, hyperlipidemia, and edema.
Although MN may spontaneously remit without treatment, as many as one third of patients demonstrate progressive loss of kidney function and progress to ESRD at a median of 5 years after diagnosis. Often, corticosteroids are used to treat MN and there is a need to develop alternative therapies. Additionally, patients determined to be at moderate risk for progression, based on severity of proteinuria, are treated with prednisone in conjunction with cyclophosphamide or a calcinuerin inhibitor, and these two treatments together are often associated with severe systemic adverse effects.
Methods:
Two Phase 1 clinicial trials carried out in healthy volunteers have demonstrated that both intravenous and subcutaneous dosing of a MASP-2 inhibitory antibody, OMS646, resulted in sustained lectin pathway inhibition.
This Example describes interim results from an ongoing Phase 2, uncontrolled, multicenter study of a MASP-2 inhibitory antibody, OMS646, in subjects with IgAN and MN. Inclusion criteria require that all patients in this study, regardless of renal disease subtype, have been maintained on a stable dose of corticosteroids for at least 12 weeks prior to study enrollment (i.e., the patients are steroid-dependent). The study is a single-arm pilot study with 12 weeks of treatment and a 6-week follow-up period.
Approximately four subjects are planned to be enrolled per disease. The study is designed to evaluate whether OMS646 may improve renal function (e.g., improve proteinuria) and decrease corticosteroid needs in subjects with IgAN and MN. To date, 2 patients with IgA nephropathy and 2 patients with membranous nephropathy have completed treatment in the study.
At study entry each subject must have high levels of protein in the urine despite ongoing treatment with a stable corticosteroid dose. These criteria select for patients who are unlikely to spontaneously improve during the study period.
The subjects were age ≥18 at screening and were only included in the study if they had a diagnosis of one of the following: IgAN diagnosed on kidney biopsy or primary MN diagnosed on kidney biopsy. The enrolled patients also had to meet all of the following inclusion criteria:
(1) have average urine albumin/creatinine ratio >0.6 from three samples collected consecutively and daily prior to each of 2 visits during the screening period;
(2) have been on >10 mg of prednisone or equivalent dose for at least 12 weeks prior to screening visit 1;
(3) if on immunosuppressive treatment (e.g., cyclophosphamide, mycophenolate mofetil), have been on a stable dose for at least 2 months prior to Screening Visit 1 with no expected change in the dose for the study duration;
(4) have an estimated glomerular filtration rate (eGFR)≥30 mL/min/1.73 m2 calculated by the MDRD equation1; 1MDRD Equation: eGFR (mL/min/1.73 m2)=175×(SCr)−1.154×(Age)−0.203×(0.742 if female)×(1.212 if African American). Note: SCr=Serum Creatinine measurement should be mg/dL.
(5) are on a physician-directed, stable, optimized treatment with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) and have a systolic blood pressure of <150 mmHg and a diastolic blood pressure of <90 mmHg at rest:
(6) have not used belimumab, eculizumab or rituzimab within 6 months of screening visit 1; and
(7) do not have a history of renal transplant.
The monoclonal antibody used in this study, OMS646, is a fully human IgG4 monoclonal antibody that binds to and inhibits human MASP-2. MASP-2 is the effector enzyme of the lectin pathway. As demonstrated in Example 12, OMS646 avidly binds to recombinant MASP-2 (apparent equilibrium dissociation constant in the range of 100 μM) and exhibits greater than 5,000-fold selectivity over the homologous proteins C1s, C1r, and MASP-1. In functional assays, OMS646 inhibits the human lectin pathway with nanomolar potency (concentration leading to 50% inhibition [IC50] of approximately 3 nM) but has no significant effect on the classical pathway. OMS646 administered either by intravenous (IV) or subcutaneous (SC) injection to mice, non-human primates, and humans resulted in high plasma concentrations that were associated with suppression of lectin pathway activation in an ex vivo assay.
In this study, the OMS646 drug substance was provided at a concentration of 100 mg/mL, which was further diluted for IV administration. The appropriate calculated volume of OMS646 100 mg/mL injection solution was withdrawn from the vial using a syringe for dose preparation. The infusion bag was administered within four hours of preparation.
The study consists of screening (28 days), treatment (12 weeks) and follow-up (6 weeks) periods, as shown in the Study Design Schematic below.

Within the screening period and before the first OMS646 dose, consented subjects provided three urine samples (collected once daily) on each of two three-consecutive-day periods to establish baseline values of the urine albumin-to-creatinine ratio. Following the screening period, eligible subjects received OMS646 4 mg/kg IV once weekly for 12 weeks (treatment period). There was a 6-week follow-up period after the last dose of OMS646.
During the initial 4 weeks of treatment with OMS646, subjects were maintained on their stable pre-study dose of corticosteroids. At the end of the initial 4-weeks of the 12-week treatment period, subjects underwent corticosteroid taper (i.e., the corticosteroid dose was reduced), if tolerated, over 4 weeks, followed by 4 weeks during which the resultant corticosteroid dose was maintained. The target was a taper ≤6 mg prednisone (or equivalent dose) daily. Over this period, the taper was discontinued in subjects who had deterioration of renal function, as determined by the investigator. Subjects were treated with OMS646 through the corticosteroid taper and through the full 12 weeks of treatment. The patients were then followed for an additional 6 weeks after their last treatment. The taper of corticosteroids and OMS646 treatment permitted assessment of whether OMS646 allowed for a decrease in the dose of corticosteroid required to maintain stable renal function.
The key efficacy measures in this study are the change in urine albumin-to-creatinine ratio (uACR) and 24-hour protein levels from baseline to 12 weeks. Measurement of urinary protein or albumin is routinely used to assess kidney involvement and persistent high levels of urinary protein correlates with renal disease progression. The uACR is used clinically to assess proteinuria.
Efficacy Analyses
The analysis value for uACR is defined as the average of all the values obtained for a time point. The planned number of uACRs is three at each scheduled time point. The baseline value of the uACR is defined as the average of the analysis values at the two screening visits.
Results:
FIG. 40 graphically illustrates the uACRin two IgAN patients during the course of a twelve week study with weekly treatment with 4 mg/kg MASP-2 inhibitory antibody (OMS646). As shown in FIG. 40, the change from baseline is statistically significant at time point "a" (p=0.003); time point "b" (p=0.007) and a time point "c" (p=0.033) by the untransformed analysis. TABLE 12 provides the 24-hour urine-protein data for the two IgAN patients treated with OMS646.
TABLE 1224-hour Urine Protein (mg/day) in OMS646-treated IgAN PatientsPatient #1Patient #2Time of Sample(mg/24 hours)(mg/24 hours)MeanBaseline387624373156Day 8517834551119p = 0.017
As shown in FIG. 40 and TABLE 12, the patients with IgAN demonstrated a clinically and statistically significant improvement in kidney function over the course of the study. There were statistically significant decreases in both uACR (see FIG. 40) and 24-hour urine protein concentration (see TABLE 12). As shown in the uACR data in FIG. 40, the mean baseline uACR was 1264 mg/g and reached 525 mg/g at the end of treatment (p=0.011) decreasing to 128 mg/g at the end of the follow-up period. As further shown in FIG. 40, the treatment effect was maintained throughout the follow-up period. Measures of 24-hour urine protein excretion tracked uACRs, with a mean reduction from 3156 mg/24 hours to 1119 mg/24 hours (p=0.017). Treatment effects across the two patients were highly consistent. Both patients experienced reductions of approximately 2000 mg/day and both achieved a partial remission (defined as greater than 50 percent reduction in 24-hour urine protein excretion and/or resultant protein exertion less than 1000 mg/day; complete remission defined as protein excretion less than 300 mg/day). The magnitude of the 24-hour proteinuria reductions in both IgA nephropathy patients is associated with a significant improvement in renal survival. Both IgA nephropathy patients were also able to taper their steroids substantially, each reducing the daily dose to ≤5 mg (60 mg to 0 mg; 30 mg to 5 mg).
The two MN patients also demonstrated reductions in uACR during treatment with OMS646. One MN patient had a decrease in uACR from 1003 mg/g to 69 mg/g and maintained this low level throughout the follow-up period. The other MN patient had a decrease in uACR from 1323 mg/g to 673 mg/g, with a variable course after treatment. The first MN patient showed a marked reduction in 24-hour urine protein level (10,771 mg/24 hours at baseline to 325 mg/24 hours on Day 85), achieving partial and nearly complete remission, while the other remained essentially unchanged (4272 mg/24 hours at baseline to 4502 mg/24 on Day 85). Steroids were tapered in the two MN patients from 30 mg to 15 mg and from 10 mg to 5 mg.
In summary, consistent improvements in renal function were observed in IgAN and MN subjects treated with the MASP-2 inhibitory antibody OMS646. The effects of OMS646 treatment in the patients with IgAN are robust and consistent, suggesting a strong efficacy signal. These effects are supported by the results in MN patients. The time course and magnitude of the uACR changes during treatment were consistent between all four patients with IgAN and MN. No significant safety concerns have been observed. Patients in this study represent a difficult-to-treat group and a therapeutic effect in these patients is believed to be predictive of efficacy with a MASP-2 inhibitory antibody, such as OMS646, in IgAN and MN patients, such as patients suffering from steroid-dependent IgAN and MN (i.e., patients undergoing treatment with a stable corticosteroid dose prior to treatment with a MASP-2 inhibitory antibody), including those at risk for rapid progression to end-stage renal disease.
In accordance with the foregoing, in one embodiment, the invention provides a method of treating a human subject suffering from IgAN or MN comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody effective to inhibit MASP-2-dependent complement activation. In one embodiment, the method comprises administering to the human subject suffering from IgAN or MN an amount of a MASP-2 inhibitory antibody sufficient to improve renal function (e.g., improve proteinuria). In one embodiment, the subject is suffering from steroid-dependent IgAN. In one embodiment, the subject is suffering from steroid-dependent MN. In one embodiment, the MASP-2 inhibitory antibody is administered to the subject suffering from steroid-dependent IgAN or steroid-dependent MN in an amount sufficient to improve renal function and/or decrease corticosteroid dosage in said subject.
In one embodiment, the method further comprises identifying a human subject suffering from steroid-dependent IgAN prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody effective to inhibit MASP-2-dependent complement activation.
In one embodiment, the method further comprises identifying a human subject suffering from steroid-dependent MN prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody effective to inhibit MASP-2-dependent complement activation.
In accordance with any of the disclosed embodiments herein, the MASP-2 inhibitory antibody exhibits at least one or more of the following characteristics: said antibody binds human MASP-2 with a KD of 10 nM or less, said antibody binds an epitope in the CCP1 domain of MASP-2, said antibody inhibits C3b deposition in an in vitro assay in 1% human serum at an IC50 of 10 nM or less, said antibody inhibits C3b deposition in 90% human serum with an IC50 of 30 nM or less, wherein the antibody is an antibody fragment selected from the group consisting of Fv, Fab, Fab′, F(ab)2 and F(ab′)2, wherein the antibody is a single-chain molecule, wherein said antibody is an IgG2 molecule, wherein said antibody is an IgG1 molecule, wherein said antibody is an IgG4 molecule, wherein the IgG4 molecule comprises a S228P mutation. In one embodiment, the antibody binds to MASP-2 and selectively inhibits the lectin pathway and does not substantially inhibit the classical pathway (i.e., inhibits the lectin pathway while leaving the classical complement pathway intact).
In one embodiment, the MASP-2 inhibitory antibody is administered in an amount effective to improve at least one or more clinical parameters associated renal function, such as an improvement in proteinuria (e.g., a decrease in uACR and/or a decrease in 24-hour urine protein concentration, such as greater than 20 percent reduction in 24-hour urine protein excretion, or such as greater than 30 percent reduction in 24-hour urine protein excretion, or such as greater than 40 percent reduction in 24-hour urine protein excretion, or such as greater than 50 percent reduction in 24-hour urine protein excretion).
In some embodiments, the method comprises administering a MASP-2 inhibitory antibody to a subject suffering from IgAN (such as steroid-dependent IgAN), via a catheter (e.g., intravenously) for a first time period (e.g., at least one day to a week or two weeks or three weeks or four weeks or longer) followed by administering a MASP-2 inhibitory antibody to the subject subcutaneously for a second time period (e.g., a chronic phase of at least two weeks or longer).
In some embodiments, the method comprises administering a MASP-2 inhibitory agent to a subject suffering from MN (such as steroid-dependent MN), via a catheter (e.g., intravenously) for a first time period (e.g., at least one day to a week or two weeks or three weeks or four weeks or longer) followed by administering a MASP-2 inhibitory antibody to the subject subcutaneously for a second time period (e.g., a chronic phase of at least two weeks or longer).
In some embodiments, the method comprises administering a MASP-2 inhibitory antibody to a subject suffering from IgAN (such as steroid-dependent IgAN) or MN (such as steroid-dependent MN) either intravenously, intramuscularly, or subcutaneously. Treatment may be chronic and administered daily to monthly, but preferably at least every two weeks, or at least once a week, such as twice a week or three times a week.
In one embodiment, the method comprises treating a subject suffering from IgAN (such as steroid-dependent IgAN) or MN (such as steroid-dependent MN) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen binding fragment thereof, comprising a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3 of the amino acid sequence set forth as SEQ ID NO:67 and a light-chain variable region comprising CDR-L1, CDR-L2 and CDR-L3 of the amino acid sequence set forth as SEQ ID NQ:69. In some embodiments, the composition comprises a MASP-2 inhibitory antibody comprising (a) a heavy-chain variable region comprising: i) a heavy-chain CDR-H1 comprising the amino acid sequence from 31-35 of SEQ ID NO:67; and ii) a heavy-chain CDR-H2 comprising the amino acid sequence from 50-65 of SEQ ID NO:67; and iii) a heavy-chain CDR-H3 comprising the amino acid sequence from 95-107 of SEQ ID NO:67 and b) a light-chain variable region comprising: i) a light-chain CDR-L1 comprising the amino acid sequence from 24-34 of SEQ ID NO:69; and ii) a light-chain CDR-L2 comprising the amino acid sequence from 50-56 of SEQ ID NO:69; and iii) a light-chain CDR-L3 comprising the amino acid sequence from 89-97 of SEQ ID NO:69, or (II) a variant thereof comprising a heavy-chain variable region with at least 90% identity to SEQ ID NO:67 (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity to SEQ ID NO:67) and a light-chain variable region with at least 90% identity (e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity to SEQ ID NO:69.
In some embodiments, the method comprises administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen binding fragment thereof, comprising a heavy-chain variable region comprising the amino acid sequence set forth as SEQ ID NO:67 and a light-chain variable region comprising the amino acid sequence set forth as SEQ ID NO:69.
In some embodiments, the method comprises administering to the subject a composition comprising a MASP-2 inhibitory antibody, or antigen binding fragment thereof, that specifically recognizes at least part of an epitope on human MASP-2 recognized by reference antibody OMS646 comprising a heavy-chain variable region as set forth in SEQ ID NO:67 and a light-chain variable region as set forth in SEQ ID NO:69.
In some embodiments, the method comprises administering to a subject suffering from, or at risk for developing IgAN (such as steroid-dependent IgAN) or MN (such as steroid-dependent MN), a composition comprising a MASP-2 inhibitory antibody, or antigen binding fragment thereof comprising a heavy-chain variable region comprising the amino acid sequence set forth as SEQ ID NO:67 and a light-chain variable region comprising the amino acid sequence set forth as SEQ ID NO:69 in a dosage from 1 mg/kg to 10 mg/kg (i.e., 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg or 10 mg/kg) at least once weekly (such as at least twice weekly or at least three times weekly) for a period of at least 3 weeks, or for at least 4 weeks, or for at least 5 weeks, or for at least 6 weeks, or for at least 7 weeks, or for at least 8 weeks, or for at least 9 weeks, or for at least 10 weeks, or for at least 11 weeks, or for at least 12 weeks.

Methods for inhibiting fibrosis in a subject in need thereof


An X-ray diagnosis apparatus includes a display-image creating unit that creates a display image from three-dimensional medical image data such that a display image of three-dimensional medical image data substantially matches up with an anatomical structure on an acquired image by the X-ray diagnosis apparatus. Moreover, the X-ray diagnosis apparatus includes a display-image changing unit that changes a display image so as to maintain consistency of an anatomical structure in accordance with change in acquiring conditions by the X-ray diagnosis apparatus. Furthermore, the X-ray diagnosis apparatus includes a display unit that displays a display image that is at least one of created and changed by at least one of the display-image creating unit and the display-image changing unit.

1. Field of the Invention
The present invention relates to an X-ray diagnosis apparatus.
2. Description of the Related Art
Recently, an X-ray diagnosis apparatus is used during a treatment as well as during an examination. For example, according to a coil embolization that is an intervention treatment for a head aneurysm, a filling state of a coil is an important factor that leads to a successful treatment. For this reason, to begin with, during an examination, an operator of the X-ray diagnosis apparatus carries out rotational imaging of a head of a subject by using the X-ray diagnosis apparatus, thereby specifying the shape and the position of an aneurysm from acquired three-dimensional blood-vessel image data. During a treatment, the operator then performs imaging while changing an imaging angle, or performs imaging from several directions by using an X-ray diagnosis apparatus of a bi plane type, and confirms a filling state of a coil from taken X-ray images.
However, because an aneurysm is small, usually 10 millimeters or smaller, an operator often performs imaging by enlarging a field of view of the imaging during a treatment; if the imaging angle is changed, a region of interest of the subject may be sometimes dislocated from the field of view (dislocated from an effective image reception area of a detector) in some cases. In such case, to find the region of interest, the operator reduces the scale of image enlargement at first so as to observe a wider region, and while observing a radioscopic image by further radiating X-rays onto the subject, the operator adjusts imaging positions (for example, the angle of a supporting device, the position of the supporting device, the position of a couch, and the height of the couch), and arranges the region of interest to the center of the field of view so as to observe the region of interest easily. After that, to observe the region of interest easily, the operator again performs a fine adjustment of the scale of image enlargement and the imaging positions while observing a radioscopic image by radiating X-rays onto the subject. Moreover, when using the X-ray diagnosis apparatus of the bi plane type during a treatment, the operator needs to position the region of interest of the subject at the center of the field of view by repeating the same procedure as described above as an initial setting, and to perform a fine adjustment to make the scale of image enlargement and the imaging positions more suitable for the treatment.
For this reason, conventionally a technology has been disclosed that the operator specifies the position of a region of interest by imaging the subject from a plurality of directions such that the specified position comes to the center of rotation of a C-arm of the X-ray diagnosis apparatus. A technology of specifying the position of a region of interest on a three-dimensional image is also disclosed (for example, JP-A 2001-204718 (KOKAI), and JP-A 2002-136507 (KOKAI)).
However, the conventional technologies described above have a problem that operation efficiency is decreased. Precisely, according to JP-A 2001-204718 (KOKAI), the position of a region of interest needs to be specified by performing imaging from at least two directions; and according to JP-A 2002-136507 (KOKAI), the position of a region of interest needs to be specified on a three-dimensional image. However, such specifying operations are not included in a clinical work flow, consequently produce additional time and effort onto the operator, and reduce operation efficiency. In addition, only specifying a region of interest to come to the center of a field of view is not enough to carry out a treatment, and a fine adjustment of the scale of image enlargement and imaging positions need to be further performed while confirming a radioscopic image by radiating X-rays onto the subject, still there is radiation exposure during the fine adjustment that is irrelevant to the essence of the treatment.

X-ray diagnosis apparatus for creating a display image from three-dimensional medical image data


The method of the present invention involves a Twenty-One game, in which, in addition to his normal wager, a player will have the option of making an additional wager that becomes part of, and makes the player eligible to win, the progressive jackpot. If the player's Twenty-One hand comprises a particular, predetermined arrangement of cards, the player will win all, or part of, the amount showing on the progressive jackpot. In a Twenty-One game using any number of decks of cards, the predetermined winning arrangements of cards preferred in the present invention are an Ace, Two, Three, Four and Five suited; a Two, Three, Four and Five suited; a Four, Five and Six suited; a Four, Five and Six unsuited; an Ace-Jack suited; and optionally any Blackjack suited and any Blackjack unsuited. In a Twenty-One game that utilizes a six deck shoe, an alternative predetermined winning arrangements of cards preferred in the present invention are Five Three's unsuited; Three Five's suited; a Four, Five and Six suited; a Four, Five and Six unsuited and an Ace-Jack suited.

U.S. Pat. No. 4,861,041 describes a method and apparatus for progressive jackpot gaming in which a separate bet is utilized in a Twenty-One game. As described in that patent, a player may make an additional wager to be eligible to participate in a separate progressive jackpot. If during the play of the normal Twenty-One game the player achieves a predetermined arrangement of cards, the player wins all or part of the progressive jackpot amount.
In a preferred embodiment of the invention as described in U.S. Pat. No. 4,861,041, the predetermined arrangement of cards that results in winning hands and the respective payoff amounts from the progressive jackpot in a Twenty-One game were as follows:
______________________________________ Winning Hand Amount of Jackpot ______________________________________ Four 5's and an Ace 100% Ace, two, three, four, 4% five and six Six, seven and eight 100 tokens of same suit Three 7's 50 tokens ______________________________________
In practice, however, it became apparent that this predetermined arrangement of cards as the winning hands affected the play of the normal Twenty-One game. If a player were attempting to achieve one of the winning jackpot arrangements, the player may have to make card selection, or "hit," decisions during the play of the Twenty-One game that would be detrimental to his chances of winning the normal Twenty-One game. For example, if "Four Fives and an Ace" wins 100% of the progressive jackpot, a player holding two Fives and an Ace (a hand count of 21) would have to take a "hit" if the player were attempting to win the progressive jackpot amount. Since a 21 hand count is a very strong hand in Twenty-One, a player taking a hit on a hand of two Fives and an Ace would be risking a hand count that at worst would result in a tie, or "push," with the dealer.
It is an object of the present invention to provide predetermined arrangements of cards that constitute winning hands for the progressive jackpot component of a Twenty-One game where the predetermined arrangement of cards does not affect the play of the normal Twenty-One game.
It is a feature of the present invention that a predetermined arrangements of cards that constitute winning hands for the progressive jackpot component of a Twenty-One game (such as an Ace, Two, Three, Four and Five suited; a Two, Three, Four and Five suited; a Four, Five and Six suited; a Four, Five and Six unsuited; an Ace-Jack suited; any Blackjack Suited and any Blackjack, which are the preferred predetermined arrangements of cards when any number of decks are used) are selected so that the predetermined arrangement of cards does not affect the play of the normal Twenty-One game.
It is another feature of the present invention that a predetermined arrangements of cards that constitute winning hands for the progressive jackpot component of a Twenty-One game (such as Five Three's unsuited; Three Five's suited; a Four, Five and Six suited; a Four, Five and Six unsuited and an Ace-Jack suited, which are the preferred predetermined arrangements of cards when a six deck show is used) are selected so that the predetermined arrangement of cards does not affect the play of the normal Twenty-One game.
It is an advantage of the present invention that a player may attempt to achieve one of the predetermined arrangement of cards that will win all or part of the progressive jackpot component of the normal Twenty-One game without affecting the normal play of the Twenty-One game.

Method of progressive jackpot twenty-one


A transceiver system allows for simultaneous operation of transmit and receive modes, even in shared path configurations, by temporarily making the receiver insensitive to transmitter energy and by modifying standard readout technology to rapidly dissipate any transmitter energy deposited onto the receiver's detector elements. The entirely electronic technique alerts the receiver to the imminent emission of each transmitter pulse. This alert opens a gate voltage switch in the readout and prevents energy that is present on the detector from being passed to the readout integrator. As soon as the transmitter pulse has passed and any charges it generated on the detector have been dissipated, the switch is automatically closed and the receiver is again fully active. Since this on/off switching happens automatically and rapidly it can operate independently from, and have very little impact on the receiver. Furthermore, it levies absolutely no limitations whatsoever on the operation of the transmitter.

When transmitters radiate high intensity electromagnetic waves in close proximity to associated receivers with high sensitivities, these receivers can often be saturated, damaged or otherwise affected in a negative manner by the outgoing transmitter energy. This energy leaks, scatters or reflects back into the receiver.
In the electro-optical and infrared (EO/IR) regimes, this problem has conventionally been handled in one of several ways. Each of the following prior art methods may incur the operational penalties described below.
For split path architectures, the hardware for the transmit and receive functions, their optics and apertures, are physically separated. This approach necessarily takes up more physical space since the design must accommodate separate optical paths for the transmit and receive functions. Furthermore, it may imply harsh mechanical tolerances in order to guarantee that both paths continue to remain co-boresighted.
For baffles, barriers or blocks that prevent transmitter energy from scattering or reflecting back into the receiver field of view (FoV) are installed. This approach may alleviate some of the tolerances imparted on the split path design described above, but it also creates two separate, albeit coaxial, channels. This feature may also make auto-boresighting or operational alignment checks impossible. The inability to perform these functions may levy strict alignment and tolerance constraints of its own. Lastly, these baffles may physically occlude portions of the receiver aperture, and therefore lower overall sensitivity.
For spectral filtering, the transmitter wavelength is chosen to reside completely outside of the receiver spectral bandpass or within the blocking band of a notch filter that will sufficiently attenuate the transmitter intensity. This approach is unworkable, by definition, for active tracking systems because the recevier needs to be sensitive to transmitter radiation. It is the illumination of distant objects with transmitter light that the receiver needs to see in the first place.
In passive tracking systems, spectral filtering is possible, but no auto-boresighting or self-alignment checks can be performed. Again, the inability to perform these functions may levy strict alignment and tolerance constraints.
For shuttering, some mechanical means like an iris is employed to temporarily block the receiver FoV while the transmitter emits each pulse. The utility of this approach may be limited by the speed of the physical mechanism as well as its reliability. Mechanical shuttering may be roughly a thousand to a million times slower than the electronic techniques described herein. This speed may be acceptable in some applications but is unacceptable for others.
Finally, for frame dumping, nothing is done to prevent the blinding saturation effects. Instead, receiver frames that have been corrupted by the presence of unwanted transmitter energy are merely ignored. This approach may be used in systems that range gate or in systems that transmit once and then receive many frames. Tracking systems, however, generally require the continual update coordinates derived from receiver frames and therefore do not have the luxury of throwing away data frames.
A method of electronic signal blanking in optical transceivers that overcomes the disadvantages of the prior art is therefore needed.

Electronic signal blanking in optical transceivers

BAE Systems Information and Electronic Systems Integration Inc.


A set-top box is connectable to a digital video recorder that includes at least one recorder interface that supports connection of the digital video recorder to the set-top box, and a disk that stores a selected video segment. The digital video recorder has a video data stream manager that, in response to a real-time video signal, provides a first video stream to store the selected video segment on the disk, and that, in response to a command from the set-top box that initiates a playback interval, receives a second video stream based on the selected video segment stored on the disk to generate a recorded video signal. The digital video recorder is configured to (a) continuously receive the real-time video signal from the set-top box, and (b) provide the recorded video signal to the set-top box during the playback interval. The set-top box includes a video input interface that receives a broadcast signal to generate the real-time video signal, and a video output interface that provides an output video data stream to a display device. The set-top box further includes a microprocessor that recognizes connection of the digital video recorder to the set-top box, and that, in response to user input, generates the command that initiates the playback interval. The set-top box further includes at least one auxiliary interface that supports connection of the set-top box to the recorder interface of the digital video recorder, the auxiliary interface continuously providing the real-time video signal to the digital video recorder subsequent to the microprocessor recognizing connection of the digital video recorder to the set-top box. The set-top box further includes a multiplexer, coupled to the video output interface and the microprocessor. The multiplexer selects the real-time video signal during a real-time interval and selects the recorded video signal during the playback interval to generate the output video data stream that is provided to the display device.

1. Field of the Invention
The present invention relates to information storage and display systems utilizing rotating storage drives, and more particularly, to video recording systems that record video data streams.
2. Description of the Related Art
Digital video recorders provide the capability of concurrently recording incoming streaming video data using hard disk drive technology and playing back previously recorded video data. As currently available, a digital video recorder receives incoming streaming video data from the output interface of a standard set-top box configured to receive the broadcast signals from a multiple-service operator (MSO), such as a cable provider, and the output of the digital video recorder is transmitted directly to a display device, such as a television. Such standard set-top boxes typically have only one input interface and one output interface. In response to commands from the user, the digital video recorder transmits to the display device either the incoming streaming video data from the output of the set-top box or the previously recorded video data.
Because currently available digital video recorders receive their input from the standard output interfaces of currently available set-top boxes, such digital video recorders require numerous components which are duplicates of components already utilized by the set-top boxes. For example, in order to view digital broadcast channels using a standard television, a set-top box must convert the input digital broadcast channels into output video signals which conform to a standard format for composite video, such as the National Television Standards Committee (NTSC) standard. This standard output format is generated by various components in the set-top box, such as a transport demultiplexer (xe2x80x9cDEMUXxe2x80x9d), an MPEG decoder, and an NTSC encoder. Additionally, the output from the set-top box may contain information from an on-screen display module. This information may represent programming information. The information may also list specialty capabilities such as picture-in-picture, which the user can enable. A digital video recorder compatible with such a configuration must convert the NTSC composite video received from the set-top box back into digital form for storage, and then reconvert again to NTSC composite video to play back the stored video signals. Therefore, just as the set-top box did, the digital video recorder requires a transport DEMUX, an MPEG decoder, and an NTSC encoder, which effectively duplicate components and functions of the set-top box.
Similarly, currently available digital video recorders also include a standard input interface that receives the output from the set-top box, and a modem that is configured to receive electronic program guide information from the MSO. Both the input interface and the modem of the digital video recorder duplicate components or functions found in currently available set-top boxes.
There is, therefore, a need to provide the capabilities of currently available digital video recorders and set-top boxes, while also enabling the reduction of the redundancy of functions and components among these digital video recorders and settop boxes.
The present invention may be regarded as a set-top box connectable to a digital video recorder that includes at least one recorder interface that supports connection of the digital video recorder to the set-top box, and a disk that stores a selected video segment. The digital video recorder has a video data stream manager that, in response to a real-time video signal, provides a first video stream to store the selected video segment on the disk, and that, in response to a command from the set-top box that initiates a playback interval, receives a second video stream based on the selected video segment stored on the disk to generate a recorded video signal. The digital video recorder is configured to (a) continuously receive the real-time video signal from the set-top box, and (b) provide the recorded video signal to the set-top box during the playback interval. The set-top box comprises a video input interface that receives a broadcast signal to generate the real-time video signal, and a video output interface that provides an output video data stream to a display device. The set-top box further comprises a microprocessor that recognizes connection of the digital video recorder to the set-top box, and that, in response to user input, generates the command that initiates the playback interval. The set-top box further comprises at least one auxiliary interface that supports connection of the set-top box to the at least one recorder interface of the digital video recorder, the at least one auxiliary interface continuously providing the real-time video signal to the digital video recorder subsequent to the microprocessor recognizing connection of the digital video recorder to the set-top box. The set-top box further comprises a multiplexer, coupled to the video output interface and the microprocessor, which selects the real-time video signal during a real-time interval and selects the recorded video signal during the playback interval to generate the output video data stream that is provided to the display device.

SET-TOP BOX CONNECTABLE TO A DIGITAL VIDEO RECORDER VIA AN AUXILIARY INTERFACE AND SELECTS BETWEEN A RECORDED VIDEO SIGNAL RECEIVED FROM THE DIGITAL VIDEO RECORDER AND A REAL-TIME VIDEO SIGNAL TO PROVIDE VIDEO DATA STREAM TO A DISPLAY DEVICE


This invention relates to novel compositions of botulinum toxin that can be applied topically for various therapeutic, aesthetic and/or cosmetic purposes. The compositions may include botulinum toxin complexes, wherein the amounts of hemagglutinin, non-toxin non-hemagglutinin and/or exogenous albumin are selectively and independently reduced compared to conventional commercially available botulinum toxin. The compositions may further contain molecules that are not native to botulinum toxin and that bind non-covalently to the botulinum toxin complexes, thereby acting as skin-tropic “adhesion molecules” to improve the ability of the toxin complexes to adhere to and to penetrate the skin epithelium. The compositions have an improved safety profile compared to existing botulinum-containing compositions that are injected subcutaneously. Methods for the use of such compositions are also contemplated by this invention.

Skin protects the body's organs from external environmental threats and acts as a thermostat to maintain body temperature. It consists of several different layers, each with specialized functions. The major layers include the epidermis, the dermis and the hypodermis. The epidermis is a stratifying layer of epithelial cells that overlies the dermis, which consists of connective tissue. Both the epidermis and the dermis are further supported by the hypodermis, an internal layer of adipose tissue.
The epidermis, the topmost layer of skin, is only 0.1 to 1.5 millimeters thick (Inlander, Skin, New York, N.Y.: People's Medical Society, 1-7 (1998)). It consists of keratinocytes and is divided into several layers based on their state of differentiation. The epidermis can be further classified into the stratum corneum and the viable epidermis, which consists of the granular melphigian and basal cells. The stratum corneum is hygroscopic and requires at least 10% moisture by weight to maintain its flexibility and softness. The hygroscopicity is attributable in part to the water-holding capacity of keratin. When the horny layer loses its softness and flexibility it becomes rough and brittle, resulting in dry skin.
The dermis, which lies just beneath the epidermis, is 1.5 to 4 millimeters thick. It is the thickest of the three layers of the skin. In addition, the dermis is also home to most of the skin's structures, including sweat and oil glands (which secrete substances through openings in the skin called pores, or comedos), hair follicles, nerve endings, and blood and lymph vessels (Inlander, Skin, New York, N.Y.: People's Medical Society, 1-7 (1998)). However, the main components of the dermis are collagen and elastin.
The hypodermis is the deepest layer of the skin. It acts both as an insulator for body heat conservation and as a shock absorber for organ protection (Inlander, Skin, New York, N.Y.: People's Medical Society, 1-7 (1998)). In addition, the hypodermis also stores fat for energy reserves. The pH of skin is normally between 5 and 6. This acidity is due to the presence of amphoteric amino acids, lactic acid, and fatty acids from the secretions of the sebaceous glands. The term "acid mantle" refers to the presence of the water-soluble substances on most regions of the skin. The buffering capacity of the skin is due in part to these secretions stored in the skin's horny layer.
Wrinkles, one of the telltale signs of aging, can be caused by biochemical, histological, and physiologic changes that accumulate from environmental damage to the skin. (Benedetto, International Journal of Dermatology, 38:641-655 (1999)). In addition, there are other secondary factors that can cause characteristic folds, furrows, and creases of facial wrinkles (Stegman et al., The Skin of the Aging Face Cosmetic Dermatological Surgery, 2nd ed., St. Louis, Mo.: Mosby Year Book: 5-15 (1990)). These secondary factors include the constant pull of gravity, frequent and constant positional pressure on the skin (e.g., during sleep), and repeated facial movements caused by the contraction of facial muscles (Stegman et al., The Skin of the Aging Face Cosmetic Dermatological Surgery, 2nd ed., St. Louis, Mo.: Mosby Year Book: 5-15 (1990)).
Different techniques have been utilized in order to potentially mollify some of the signs of aging. These techniques range from facial moisturizers containing alpha hydroxy acids and retinol to surgical procedures and injections of neurotoxins. For example, in 1986, Jean and Alastair Carruthers, a husband and wife team consisting of an ocuplastic surgeon and a dermatologist, developed a method of using the type A form of botulinum toxin for treatment of movement-associated wrinkles in the glabella area (Schantz and Scott, In Lewis G E (Ed) Biomedical Aspects of Botulinum, New York: Academic Press, 143-150 (1981)). The Carruthers' use of the type A form of botulinum toxin for the treatment of wrinkles led to the seminal publication of this approach in 1992 (Schantz and Scott, In Lewis G E (Ed) Biomedical Aspects of Botulinum, New York: Academic Press, 143-150 (1981)). By 1994, the same team reported experiences with other movement-associated wrinkles on the face (Scott, Ophthalmol, 87:1044-1049 (1980)). This in turn led to the birth of the era of cosmetic treatment using the type A form of botulinum toxin.
Interestingly, the type A form of botulinum toxin is said to be the most lethal natural biological agent known to man. Spores of C. botulinum are found in soil and can grow in improperly sterilized and sealed food containers. Ingestion of the bacteria can cause botulism, which can be fatal. Botulinum toxin acts to produce paralysis of muscles by preventing synaptic transmission or release of acetylcholine across the neuromuscular junction, and is thought to act in other ways as well. Its action essentially blocks signals that normally would cause muscle spasms or contractions, resulting in paralysis. However, the muscle-paralyzing effects of botulinum toxin have been used for therapeutic effects. Controlled administration of botulinum toxin has been used to provide muscle paralysis to treat conditions, for example, neuromuscular disorders characterized by hyperactive skeletal muscles. Conditions that have been treated with botulinum toxin include hemifacial spasm, adult onset spasmodic torticollis, anal fissure, blepharospasm, cerebral palsy, cervical dystonia, migraine headaches, strabismus, temporomandibular joint disorder, and various types of muscle cramping and spasms. More recently the muscle-paralyzing effects of botulinum toxin have been taken advantage of in therapeutic and cosmetic facial applications such as treatment of wrinkles, frown lines, and other results of spasms or contractions of facial muscles.
In addition to the type A form of botulinum toxin, there are seven other serologically distinct forms of botulinum toxin that are also produced by the gram-positive bacteria Clostridium botulinum. Of these eight serologically distinct types of botulinum toxin, the seven that can cause paralysis have been designated botulinum toxin serotypes A, B, C (also known as C, D, E, F and G. Each of these is distinguished by neutralization with type-specific antibodies. The molecular weight of the botulinum toxin protein molecule, for all seven of these active botulinum toxin serotypes, is about 150 kD. The different serotypes of botulinum toxin vary in the animal species that they affect and in the severity and duration of the paralysis they evoke. For example, it has been determined that botulinum toxin type A is 500 times more potent than botulinum toxin type B, as measured by the rate of paralysis produced in rats. Additionally, botulinum toxin type B has been determined to be non-toxic in primates at a dose of 480 U/kg, about 12 times the primate LD50 for type A. Due to the molecule size and molecular structure of botulinum toxin, it cannot cross stratum corneum and the multiple layers of the underlying skin architecture.
As released by Clostridium botulinum bacteria, botulinum toxin is a component of a toxin complex containing the approximately 150 kD botulinum toxin protein molecule along with associated non-toxin proteins. These endogenous non-toxin proteins are believed to include a family of hemagglutinin proteins, as well as non-hemagglutinin protein. The non-toxin proteins are believed to stabilize the botulinum toxin molecule in the toxin complex and protect it against denaturation, for example, by digestive acids when toxin complex is ingested. Thus, the non-toxin proteins of the toxin complex protect the activity of the botulinum toxin and enhance systemic penetration, particularly when the toxin complex is administered via the gastrointestinal tract. More specifically, it is believed that some of the non-toxin proteins specifically enhance penetration across the gastrointestinal epithelium while other non-toxin proteins stabilize the botulinum toxin molecule in blood. Additionally, the presence of non-toxin proteins in the toxin complexes typically causes the toxin complexes to have molecular weights that are greater than that of the bare botulinum toxin molecule, which is about 150 kD, as previously noted. For example, Clostridium botulinum bacteria can produce botulinum type A toxin complexes that have molecular weights of about 900 kD, 500 kD or 300 kD. Interestingly, botulinum toxin types B and C are apparently produced as only a 700 kD or a 500 kD complex. Botulinum toxin type D is produced as both 300 kD and 500 kD complexes. Botulinum toxin types E and F are produced as only approximately 300 kD complexes.
To provide additional stability to botulinum toxin, the toxin complexes are often stabilized by combining them with exogenous stabilizers, (e.g., gelatin, polysaccharides, or most commonly additional albumin) during manufacturing. The stabilizers serve to bind and to stabilize toxin complexes in disparate environments, including those associated with manufacturing, transportation, storage, and administration.
Typically, the botulinum toxin is administered to patients by carefully controlled injections of compositions containing the botulinum toxin complex and albumin, but there are several problems associated with this approach. Not only are the injections painful, but they often must deliver enough toxin to create large subdermal wells of toxin locally around the injection sites, in order to achieve the desired therapeutic or cosmetic effect. Even worse, many injections may be required when the area to be treated is large. Moreover, because the injected toxin complexes contain non-toxin proteins and albumin that stabilize the botulinum toxin and increase the molecular weight of the toxin complex, the toxin complexes have a long half-life in the body, are slow to diffuse through tissue, and may cause an undesirable antigenic response in the patient. Also, since the non-toxin proteins and albumin stabilize the botulinum toxin in blood, the injections must be carefully placed so that they do not release a large amount of toxin into the bloodstream of the patient, which could lead to fatal systemic poisoning. Thus, injections typically must be performed precisely by highly trained medical professionals with a deep understanding of human anatomy.
In view of all of the problems discussed in the foregoing, it would be highly desirable to have a method of administering botulinum toxin that would be painless and require less toxin than conventional injection-based methods. Additionally, it would be highly desirable if such a method were to reduce the antigenicity and blood stability of the botulinum toxin, while increasing the diffusion rate of botulinum toxin complexes within the body, thereby making it safer to use botulinum toxin for various therapeutic, aesthetic and/or cosmetic purposes. It also would be desirable to have a method of administration that does not critically depend on precise injection of the botulinum toxin by a medical professional in order to achieve safe administration of the toxin.

Compositions and methods of topical application and transdermal delivery of botulinum toxins with reduced non-toxin proteins


Disclosed herein is a die assembly comprising a first attachment block having a passage, an inlet port and an exit port; where the passage is operative to transport a molten material from the inlet port to the outlet port; a die; and a conduit; where the conduit comprises a passage that is operative to transport the molten material from the first attachment block to an entry port of the die; where the die comprises a first outer tube; and an extrusion pin that comprises a post and fins; where the extrusion pin is located in the first outer tube using the fins and where the post extends from the fins in a direction away from the entry port of the die; and where the post comprises one or more passages; where at least of these passages open to the atmosphere to provide for pressure equalization; and a travelling template; the template being operative to contact an extrudate that emanates from the die and to transfer a texture to a surface of the extrudate by virtue of pressure applied by a guide tube to the extrudate via the travelling template.

Disclosed herein is a die for manufacturing catheters. More specifically, disclosed herein is a die that permits texturing outer surfaces of an elastomer while creating tubular pathways on the inside that permit the transfer of fluids to a patient.
Catheters are often used for inserting prosthetics into the body of a patient, for transferring fluids to various points in a body, or for removing fluids from various points in a body. Because catheters traverse various parts of the body, bacteria from one part of the body can be transferred to other parts of the body. Additionally, bacteria from outside the body can be transferred to various parts inside the body. It is desirable to prevent this bacterial transfer.
Surfaces that have patterns and other forms of texturing (hereinafter "texturing") can be advantageously used to minimize the adhesion of living organisms and other forms of non-living matter (e.g., ice, dust, dirt, and the like) to the surface. The texturing can have dimensions that are selected to specifically prevent the adhesion of specific living organisms or non-living matter on the surface, while at the same time encouraging the growth of other organisms or the adhesion of other types of non-living matter to the surface.
For example, in order to prevent the growth of certain types of living organisms the dimensions of the texturing may have to be in the nanometer or in the micrometer range, while for preventing the growth of certain other types of organisms, the dimensions of the texturing may have to be in the millimeter or centimeter range. In another example, in order to facilitate the growth of certain types of living organisms the dimensions of the texturing may have to be in the nanometer or in the micrometer range, while for facilitating the growth of certain other types of organisms, the dimensions of the texturing may have to be in the millimeter or centimeter range. Reproducing this texturing on surfaces that are large in size (e.g., of the area of several square centimeters) or on surfaces that have a complex shape (e.g., a non-planar surface that is circular or spherical) is difficult.
In order to traverse and reach various parts of the body, catheters are generally manufactured from flexible materials that have tubular pathways inside them. The tubular pathways allow for the manipulation of prosthetics inside the body. They also allow for fluid transfer to and from the body. This means that the catheter is generally manufactured from a flexible material (e.g., an elastomer). Manufacturing a catheter with multiple tubular pathways from a flexible material while at the same time disposing texturing on an outside surface of the catheter requires a special die.

Die for continuously manufacturing textured surfaces and methods of manufacture thereof


Disclosed relates a modular jack that can be manufactured simply with small size and reduce cross talk induced from the plug satisfactorily. The modular jack includes a housing for receiving a plug and an insert for electrically connecting to the plug. The insert includes first and second conductors of first to fourth signal pairs, the first and second conductors of the first, second and fourth signal pair [T1, R1], [T2 and R2] and [T4 and R4], adjacent to the first and second conductors of the third signal pair [T3 and R3], are intersected with each other in a multi-layered wiring structure to generate inductive cross talk having a reverse phase against cross talk that arises from the plug, thus canceling the cross talk. Besides, the first and second conductors of signal pair [T1, R1], [T2 and R2] and [T4 and R4] are arranged to make an angle of 90 degree at a crossing surface between the first and second conductors to minimize the inductive cross talk that occurs due to the crossing arrangement.

1. Field of the Invention
The present invention relates to an electrical connector comprised of a modular jack and a plug, more particularly to a modular jack that can be manufactured simply with small size and reduce cross talk induced from the plug satisfactorily.
2. Description of the Related Art
Referring to FIG. 1, showing an electrical connector including a commonly available RJ45 type modular jack 1 and its associated plug 2, the modular jack 1 including a housing 11 and a substrate 12 mounted into the housing 11. Insert 13 is mounted on an end of the substrate 12 and a connecting terminal 14 for electrically connecting to an external cable on an opposite end of the substrate 12. Insert 13 includes connecter pins 13a and a body 13b. Connecter pins 13a penetrating the body 13b electrically connect to the substrate 12 at the rear of the body 13b. Besides, predetermined electrical paths are provided on the top and rear sides of the substrate 12, thus appropriately coupling the connecter pins 13a to the connecting terminal 14.
Plug 2 includes guide grooves 21, for guiding the connector pins 13a in a position corresponding to the connector pins 13a, and contacts, not depicted, electrically connected to a cable 22 in the guide grooves 21. Accordingly, when the plug 2 is inserted to the housing 11 of modular jack 1, the connecter pins 13a of modular jack 1 are electrically coupled to the contacts of plug 2.
Next, referring to FIGS. 2 and 3, there are provided four signal pairs comprised of conductors [R1 and T1], [R2 and T2], [R3 and T3], and [R4 and T4], respectively. In general, cross talk arises due to capacitive and inductive couplings between adjacent conductors, not between each of the signal pairs. Accordingly, adjacent conductors, which are not a single pair in themselves, are referred to as a cross-talking pair. That is, conductors [T1 and R3], [R3 and T2], [R2 and T3], and [T3 and R4] form cross-talking pairs, respectively.
Here, it is known that the cross talk induced within each of the cross-talking pairs [T1 and R3] and [T3 and R4] may be substantially cancelled by reverse phase capacitive coupling, a well-known method in the art. However, the inventor of the present invention has found that the cross talk which occurs within each of the cross-talking pairs [R3 and T2] and [R2 and T3] may not be sufficiently cancelled by the capacitive coupling. Thus, it is considered that the cross talk which arises within each of the cross-talking pairs [R3 and T2] and [R2 and T3] may be substantially affected by the inductive coupling rather than the capacitive coupling. In effect, the inventor has noted that a substantial amount of magnetic field is induced between the signal pair [T2 and R2] as shown in FIG. 3 with arrows.
Meanwhile, the induced magnetic filed generates electric current between the signal pairs, and the induced current corresponds to a noise signal against the original signal transmitted through the signal pair [T2 and R2]. Accordingly, it is necessary to provide a method for reducing cross talk induced from the modular jack 1 connected to the plug 2. Recently, there have been applied a method for forming a predetermined circuit on the substrate 12 of modular jack 1 to reduce cross talk. That is, the connector pins 13a are soldered on the substrate 12 where a predetermined circuit corresponding to the respective conductors of the connector pins 13a is formed. Here, it is necessary to consider electromagnetic variations, such as thickness and length of conductors, intervals between conductors, etc., in the circuit sufficiently to reduce the capacitive and inductive cross talk generated between adjacent conductors. However, since the size of substrate 12 is limited to the extent that it is inserted to the housing 11 of modular jack 1, it is required to design precisely the respective patterns corresponding to eight conductors, for example, on the small-sized substrate 12.
Besides, since the conventional modular jack 1 includes the substrate 12 for reducing cross talk as described above, it is necessary to have the additional connecting terminal 14 for electrically connecting to an external device, such as a communication cable or printed circuit board of communication equipment, etc., which has drawbacks in reducing the overall size of the modular jack to meet the recent trend of miniaturization of communication equipments, and simplifying the manufacturing process as well.
Accordingly, the present invention is directed to a modular jack that can be manufactured simply with small size and reduce cross talk induced from the plug satisfactorily.
To accomplish an object of the present invention, there is provided a modular jack, connected to a plug including first to fourth signal pairs having first and second conductors respectively, the second signal pair being placed between the first and second conductors of the third signal pair, the modular jack comprising a housing for receiving the plug; and an insert for electrically connecting to the plug, the insert, assembled with the housing, including first to fourth signal pairs having first and second conductors respectively, the respective conductors of the first, second and fourth signal pairs adjacent to the first and second conductors of the third signal pairs being arranged cross to each other.
To accomplish another object of the present invention, the insert includes connector pins, electrically connected to the first to fourth signal pairs of the plug, having first to fourth signal pairs, and first and second portions, bent rectangularly, for fixing the connector pins, the first portion forming an upper side of the housing and the second portion forming a lateral side of the housing.
To accomplish another object of the present invention, the insert includes a first insert, having first connector pins having first conductors of the first to fourth signal pairs, first and second bodies for fixing the first connector pins; and a second insert, having second connector pins having second conductors of the first to fourth signal pairs, third and fourth bodies for fixing the second connector pins, the first body of the first insert and the third body of the second insert forming the first portion of the insert, and the second body of the first insert and the fourth body of the second insert forming the second portion of the insert, thus forming a multi-layered wiring structure.
To accomplish another object of the present invention, the first portion of the insert includes shelves formed on both edges thereof and the second portion of the insert has lockers on both lateral sides thereof, and the housing includes guide bars formed on both sides of an upper part thereof for assembling slidably with the shelves, and locking grooves formed on both lateral sides thereof for receiving the lockers.
To accomplish another object of the present invention, the connector pins are bent on a front edge of the first portion of the insert, and the housing includes a first guide groove for guiding the connector pins bent on the front edge of the first portion of the insert and a second guide groove for guiding connector pins located on a rear edge of the second portion of the insert.
To accomplish another object of the present invention, the first and second conductors of the first, second and fourth signal pairs are intersected with each other in the first portion, and the first and second conductors of the first and second signal pairs are arranged adjacent to an outside of the insert, having a multi-layered wiring structure.
To accomplish another object of the present invention, the first and second conductors of the second signal pair are intersected with each other twice in the first portion.
To accomplish another object of the present invention, the first and second conductors of the first, second and fourth signal pairs are disposed to make an angle of 90 degree at a crossing surface between the first and second conductors.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.


An apparatus for capturing bottle necks in bottle filling installations includes a clip having clip arms. The clip arms are pivotable in a horizontal plane and mounted so as to be jointly pivotable in a horizontal plane about a pivot axis. The apparatus also includes an attachment for a magnet, and another magnet provided with the attachment and disposed on a side of the attachment such that the pivot axis is between the magnet and the clip arms, and a clip holding block configured to be secured onto a star and facing the clip and having a magnet. The magnet on the attachment and the magnet on the clip holding block are essentially opposite and spaced apart from each other by a distance that ensures horizontal pivoting movements of the clip.

There are very different developments of these types of clips. Thus, for example, DE 10 2006 012 020 shows a pair of clips, the two clip arms being pivotable into non-separated axes and the closing force being held in the closing position by means of a spring. As these types of spring elements frequently do not meet the demands for hygiene required in bottle filling installations, efforts are made to propose other closing mechanisms. Thus, in an expensive development, DE 10 2005 041 929 provides permanent magnets that support both the closing and the opening in different pairings. In this solution the permanent magnets are positioned outside the clip grabbing arms.
To support the opening force of the clips, one solution according to DE 20 2005 002 924 U or DE 10 2005 014 838 A provides that repelling magnets are positioned between the grabbing region of the clips and pivotal axes. In the case of these kinds of clips, there is a certain requirement for lateral yielding, as the participating elements are frequently driven by way of servo motors that do not always run in a precisely synchronous manner. This means that there can be a small misalignment, for example between a transfer star, a filling machine or the like. Small reference circles produce curve-shaped paths for the bottle into the grabbing means, wear and tear on the grabbing means and the transfer being improved by means of lateral flexibility.

Clip for capturing bottle necks, particularly of pet bottles


A handle for turning on and off a faucet has a push button release for removal of the handle from a stem of the faucet structure. Pressing down upon the push button causes a latch attached to the handle to disengage from a slot in the stem allowing removal of the handle. Following removal of the handle, the faucet structure and/or the handle can be repaired and/or cleaned if necessary. The original handle or a new replacement handle can then be quickly and easily put back into place by reengaging the latch on the handle with the slot in the stem.

1. Field of the Invention
The present invention relates generally to faucet structures, and more particularly, to a faucet handle apparatus which is easily removable from the rest of a faucet structure.
2. Description of the Prior Art
Faucet structures in the form of kitchen sink faucets, bathroom sink faucets, bath and shower faucets and valves, bidet valves as well as outdoor faucets and the like are well known in the art of water discharging devices. All of these and other faucet structures and/or water discharging devices have some type of handle for turning the water on and off such as the typical rotating handles generally used or levers which can be lifted and rotated or spindles which are also rotated. These handles are fastened to the stem of a faucet with a screw. Unfortunately, these screws often become rested or the threads on the screw become stripped. Both of these problems with the prior art faucet structures make it extremely difficult to remove the screw or the handle.
Prior art faucet handle structures are illustrated by the following U.S. Pat. Nos. 4,876,766; 4,796,329; and 4,065,216.
Although the foregoing body of prior art indicates it to be well known to use handles for turning faucets on and off, the provision of a more simple to remove device is not contemplated. Nor does the prior art described above teach or suggest a push button device on a faucet handle which may be used by individuals to quickly and easily remove the handle from the faucet structure. The foregoing disadvantages are overcome by the unique easily removable faucet handle of the present invention as will be made apparent from the following description thereof. Other advantages of the present invention over the prior art also will be rendered evident.


Receiver bandwidth is dynamically altered during operation (with respect to, for example, filter bandwidth and/or filter center frequency) as a function, at least in part, of communication resource allocation.

Communication systems are well known and comprise many types including land mobile radio, cellular radiotelephone, and personal communication systems to name a few. Within a communication system, transmissions are conducted between a transmitting device and a receiving device over a communication resource, commonly referred to as a communication channel. To date, the transmissions have typically consisted of voice signals. More recently, however, there has been rapidly growing interest in carrying other forms of signals, including high-speed packetized data signals that are suitable for video, audio, and other high bandwidth data applications.
Because of the increase in demand for data communications services, such as Internet services like access to the World Wide Web, the size of data messages and their frequency of transmission have increased and take longer to transfer on existing communication systems. New and/or proposed cellular radio systems, including those based on technologies such as time division multiplexing, frequency division multiplexing, and/or code division multiplexing, allow the data rate available to an individual mobile station to be changed on demand to better accommodate such needs as they arise. This is done in frequency division multiplexed/time division multiplexed systems by allocating a larger number of time division slots and/or carrier (or sub-carrier) frequencies per unit time to the particular user requiring greater throughput. In code division multiple access systems, a greater number of spreading codes are assigned to the user requiring greater throughput.
In such systems, one or more wideband frequency domain channels (having, for example, 50 KHz, 100 KHz, or 150 KHz bandwidths) are subdivided in time and/or code domains into smaller logical channels (some of which can be used for control purposes to dynamically inform the mobile station during operations of the logical channels to be used by the mobile stations). In many systems, the wideband frequency domain channel is first subdivided into narrower frequency domain sub-carriers, which sub-carriers are then similarly subdivided with respect to time and/or codes to yield the desired logical channels.
Unfortunately, when a mobile station, such as a cellular telephone handset, receives, for example, a wide-band time division multiple access (TDMA) transmission on a 100 KHz system, the mobile station is presently required to receive and decode the entire 100 KHz bandwidth of the wideband frequency domain channel to obtain and decode the desired data, regardless of whether the specific assignment for that mobile station only requires receipt of data as carried on a subset of the sub-carriers that constitute the wideband channel. Thus, even if the mobile station is assigned only 50 KHz of the total available bandwidth, the mobile station must nevertheless unnecessarily receive and decode the remaining bandwidth. This results in extra current drain and therefore reduced battery life for a portable device. These circumstances also significantly impact receiver sensitivity as noise contributions that correspond to reception and processing of the full bandwidth channel necessarily impact reception and processing of that portion of the full bandwidth channel that contains the data of interest.
Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are typically not depicted in order to facilitate a less obstructed view of these various embodiments of the present invention.


A level shifter circuit that properly operates even when the power supply voltage is unstable. A level shifter circuit includes a first level shifter unit, a second level shifter unit, and a latch unit. In the first level shifter unit, a transistor is connected to a power supply line to generate drive voltage that is lower than a first power supply voltage. The first level shifter unit outputs complementary signals from the drive voltage. The output of the first level shifter unit is provided to the second level shifter unit. The second level shifter unit converts a complementary signal to a signal having a second power supply voltage. Based on this signal, a signal of the latch unit is switched.

The present invention relates to a level shifter circuit for converting a voltage level in a semiconductor integrated circuit using a plurality of power supply voltages.
Power supply voltages for semiconductor integrated circuits have become lower to reduce power consumption. A semiconductor integrated circuit includes a plurality of circuit blocks having various functions and using various power supply voltages. Further, in a semiconductor integrated circuit, the signal level at an input/output terminal connected to an external device is determined in accordance with the characteristics of the connected device. Thus, power supply voltage that differs from that for internal circuits may become necessary.
Therefore, a semiconductor integrated circuit is supplied with a plurality of power supply voltages. A circuit unit, referred to as a level shifter, for converting signal levels is arranged on portions of a chip of the semiconductor integrated circuit where different power supply regions come into contact with one another (for example, refer to Japanese Laid-Open Patent Publication No. 2001-36398, first page and Japanese Laid-Open Patent Publication No. 2004-96616, FIG. 1). Japanese Laid-Open Patent Publication No. 2001-36398 describes a level shifter circuit including transistors (TP4 and TN4). Signals are input to the transistors to stop signal transmission when fluctuation occurs in the input to the level shifter circuit. Further, a latch circuit is used to stabilize an output signal by outputting a fixed potential that is dependent on an input signal held by the latch circuit.
Japanese Laid-Open Patent Publication No. 2004-96616 describes a level shifter circuit including an N-channel transistor (Mn8) connected between ground and the drains of N-channel transistors (Mn2 and Mn3) in a booster circuit. Low voltage power is applied to the gate of the N-channel transistor (MN8). A bus repeater is connected between the output terminal of the booster circuit and the input terminal of an inverter. When a low voltage power supply is grounded to reduce power supply, the N-channel transistor (Mn8) is deactivated. This prevents tunneling current from flowing in the booster circuit from a high voltage power supply to ground. Even if the potential at the gates of P-channel and N-channel transistors forming the booster circuit fluctuates, the bus repeater holds the output signal of the booster circuit immediately before such a fluctuation. This suppresses fluctuation of the output potential at the level shifter and prevents erroneous operations of circuits connected to the level shifter.
In a situation in which power is supplied to the output side, when power is not supplied to the input side or when power is about to be supplied to the input side, activation of the level shifter may transmit an erroneous signal to the output side. However, in the technique described in Japanese Laid-Open Patent Publication No. 2001-36398, the input side and the output side are separately operated. Thus, control is executed by an input from terminal (C). As a result, a mechanism for controlling the input of terminal (C) in accordance with the state of terminal (A) is necessary.
In the technique described in Japanese Laid-Open Patent Publication No. 2004-96616, a low voltage power supply (VCCL) controls the transistor (Mn8). Since there is not enough margin, the transistor (Mn8) may erroneously operate when the low voltage power supply (VCCL) becomes somewhat high. Thus, normal circuit operation cannot be guaranteed.


A capacitance measurement sensor, having a voltage subtractor that rejects common signals between the columns or rows of a touch sensor matrix depending on which are driven and which are being sensed, is described.

One type of touchpad operates by way of capacitance sensing utilizing capacitance sensors. The capacitance detected by a capacitance sensor changes as a function of the proximity of a conductive object to the sensor. The conductive object can be, for example, a stylus or a user's finger. In a touch-sensor device, a change in capacitance detected by each sensor in the X and Y dimensions of the sensor array due to the proximity or movement of a conductive object can be measured by a variety of methods. Regardless of the method, usually an electrical signal representative of the capacitance detected by each capacitive sensor is processed by a processing device, which in turn produces electrical or optical signals representative of the position of the conductive object in relation to the touch-sensor pad in the X and Y dimensions. A touch-sensor strip, slider, or button operates on the same capacitance-sensing principle.
A first type of touchpad is composed of a matrix of rows and columns. Within each row or column there are multiple sensor elements, however, all sensor pads within each row or column are coupled together and operate as one long sensor element. The number of touches a touchpad can detect is not the same as the resolution of the touchpad. For example, even though a touchpad may have the capability to detect two substantially simultaneous touches with an XY matrix, the touchpad cannot resolve the location of the two substantially simultaneous touches.
One way to resolve the location of a second touch is if the touches arrive sequentially in time. If both touches arrive or are detected substantially simultaneously, however, there is no way to resolve which of the two pairs of potential locations constitute "actual" touches, instead of invalid touches (e.g., "ghost" touches). Thus, the two-axis touchpads are configured to resolve only a location of a single touch. Similarly, touch screens are designed to detect the presence and location of a single touch.


Binary tree split mode coding is performed while encoding digital video image blocks using a quad tree plus binary tree coding. The quadtree split can be represented by some combinations of horizontal and vertical binary tree split. Blocks are constrained to be split down to a minimum block size and with certain split constraints such that some redundant tree structures are avoided. Redundant syntax in coding the binary tree split mode syntax element is removed to provide coding efficiency.

Aspects of the present embodiments aim at improved compression efficiency compared to existing video compression systems, such as ITU-T H.265 TELECOMMUNICATION STANDARDIZATION SECTOR OF ITU (10/2014), SERIES H: AUDIOVISUAL AND MULTIMEDIA SYSTEMS, Infrastructure of audiovisual services—Coding of moving video, High efficiency video coding, Recommendation ITU-T H.265, sometimes referred to as HEVC or simply H.265, and "Algorithm Description of Joint Exploration Test Model 3", Document JVET-C1001_v3, Joint Video Exploration Team (JVET) of ISO/IEC JTC1/SC29/WG11, 3rd meeting, 26 May-1 Jun. 2015, Geneva, for example.
Emerging video compression tools include a Coding Tree Unit representation in the compressed domain, in order to represent picture data in a more flexible way in the compressed domain. The advantage of this more flexible representation of the coding tree is that it provides increased compression efficiency compared to the CU/PU/TU (Coding Unit/Prediction Unit/Transform Unit) arrangement of the HEVC standard.
The Quad-Tree plus Binary-Tree (QTBT) coding tool provides this increased flexibility. It consists in a coding tree where coding units can be split both in a quad-tree and in a binary-tree fashion. Such coding tree representation of a Coding Tree Unit is illustrated in FIG. 1.
The quadtree split can be represented by some combinations of horizontal and vertical Binary-Tree splitting. The same partition shape can also be generated by applying the horizontal and vertical binary split in different orders. In order to avoid some redundant tree structures a split constraint is used (splitConstrain=Horizontal means a horizontal split is forbidden).
The Binary-Tree is limited by the MinBTSize parameter, which is the imposed minimum size (in width or height) on the blocks issued from binary-tree splitting.
The embodiments described herein propose to remove the redundant syntax in coding the Binary Tree Split Mode syntax element.

Method and apparatus for restricting binary-tree split mode coding and decoding

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