The described invention provides methods and regimens for treating adverse consequences of a persistent and progressive myocardial injury-due to a vascular insufficiency that occurs early or late in a subject in need thereof, and progressive myocardial injury-preventing compositions that contain a chemotactic hematopoietic stem cell product, and, optionally, an additional active agent.

The Cardiac Cycle
The term "cardiac cycle" is used to refer to all or any of the mechanical events related to the coronary blood flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. Blood pressure increases and decreases throughout the cardiac cycle. The frequency of the cardiac cycle is the heart rate. Every single 'beat' of the heart involves five major stages: (1) "late diastole," which is when the semilunar valves close, the atrioventricular (Av) valves open and the whole heart is relaxed; (2) "atrial systole," which is when the myocardium of the left and right atria are contracting, AV valves open and blood flows from atrium to ventricle; (3) "isovolumic ventricular contraction," which is when the ventricles begin to contract, AV and semilunar valves close, and there is no change in volume; (4) "ventricular ejection," which is when the ventricles are empty but still contracting and the semilunar valves are open; and (5) "isovolumic ventricular relaxation," when pressure decreases, no blood is entering the ventricles, the ventricles stop contracting and begin to relax, and the semilunar valves are shut because blood in the aorta is pushing them shut. The cardiac cycle is coordinated by a series of electrical impulses that are produced by specialized heart cells found within the sino-atrial node and the atrioventricular node.
Coronary Blood Flow
The flow of blood through the coronary arteries is pulsatile, with characteristic phasic systolic and diastolic flow components. Systolic flow, which relates to the contraction or pumping phase of the heart cycle, has rapid, brief, retrograde responses. Diastolic flow, which relates to the relaxation or filling phase of the heart cycle, occurs during the relaxation phase after myocardial contraction, with an abrupt increase above systolic levels and a gradual decline parallel with that of aortic diastolic pressures. Intramural coronary blood volume changes during each heartbeat, with the myocardium accommodating the volume change brought about by muscular contraction. Coronary venous flow is out of phase with coronary arterial flow, occurring predominantly in systole and nearly absent during diastole.
For each heartbeat, blood pressure varies between systolic and diastolic pressures. The term "systolic pressure" refers to the peak pressure in the arteries, which occurs near the end of the cardiac cycle when the ventricles are contracting. The term "diastolic pressure" refers to the minimum pressure in the arteries, which occurs near the beginning of the cardiac cycle when the ventricles are filled with blood.
Coronary blood flow not only is phasic but also varies with the type of vessel and location in the myocardium. Coronary arterioles appear to have specialized regulatory elements along their length that operate "in series" in an integrated manner. A system of multiple functional "valves" permits fine control of the coronary circulation. The smallest arterioles dilate during metabolic stress, resulting in reduced microvascular resistance and increased myocardial perfusion. Stenosis or narrowing of a blood vessel produces resistance to blood flow related directly to the morphologic features of the stenosis. As the upstream arteriolar pressure decreases due to a fall in distending pressure across the stenosis, myogenic dilation of slightly larger arterioles upstream occurs and causes an additional decrease in resistance. Increased flow in the largest arterioles augments shear stress and triggers flow-mediated dilation, further reducing the resistance of this network.
The arterial and venous pulsatile flow characteristics of the heart are dependent on intramyocardial compliance. The term "compliance" refers to a measure of the tendency of a hollow organ to resist recoil toward its original dimensions upon removal of a distending or compressing force. The higher the compliance the more elastic the material. Compliance is calculated using the following equation, where ΔV is the change in volume, and ΔP is the change in pressure:C=ΔV/ΔP
The capacity of the heart as a reservoir is controlled by resistance arterioles to coronary vascular inflow. Outlet resistance is related to intramural cardiac veins. The intramyocardial capillary resistance influences both arterial and venous responses but predominantly acts in concert with outlet resistance.
Approximately 75% of total coronary resistance occurs in the arterial system, which comprises conductance (R1), prearteriolar (R2) and arteriolar and intramyocardial capillary vessels (R3). Normal epicardial coronary arteries in humans typically are 0.3 to 5 mm in diameter, and do not offer appreciable resistance to blood flow. Normally, large epicardial vessel resistance (R1) is trivial until atherosclerotic obstructions compromise the lumen. Precapillary arterioles (R2), 100 to 500 μm in size) are resistive vessels connecting epicardial to myocardial capillaries and are the principal controllers of coronary blood flow. They contribute approximately 25% to 35% of total coronary resistance. Distal precapillary arteriolar vessels (<100 μm in diameter), the main site of metabolic regulation of coronary blood flow, are responsible for 40-50% of coronary flow resistance. The dense network of about 4000 capillaries per square millimeter ensures that each myocyte is adjacent to a capillary. Capillaries are not uniformly patent (meaning open; affording free passage), because precapillary sphincters regulate flow according to the needs of the myocardium.
Several conditions, such as left ventricular hypertrophy, myocardial ischemia, or diabetes, can impair the microcirculatory resistance (R3), blunting the maximal absolute increase in coronary flow in times of increased oxygen demand.
Ischemia
The myocardium depends almost entirely on aerobic metabolism, since oxygen stores in the heart are meager. Myocardial oxygen supply rises and falls in response to the oxygen (energy) demands of the myocardium. The term "autoregulation" refers to the ability to maintain myocardial perfusion at constant levels in the face of changing driving forces. Autoregulation maintains coronary perfusion at relatively constant levels over a wide range of mean aortic pressure. When aortic pressure exceeds its upper or lower limits, coronary blood flow precipitously declines or increases proportionately.
The heart needs to be supplied with a sufficient quantity of oxygen to prevent underperfusion. When reduced perfusion pressure distal to stenoses is not compensated by autoregulatory dilation of the resistance vessels, ischemia, meaning a lack of blood supply and oxygen, occurs. Because the zone least supplied generally is the farthest out, ischemia generally appears in areas farthest away from the blood supply.
After total or near-total occlusion of a coronary artery, myocardial perfusion occurs by way of collaterals, meaning vascular channels that interconnect epicardial arteries. Collateral channels may form acutely or may preexist in an under-developed state before the appearance of coronary artery disease. Preexisting collaterals are thin-walled structures ranging in diameter from 20 μm to 200 μm, with a variable density among different species. Preexisting collaterals normally are closed and nonfunctional, because no pressure gradient exists to drive flow between the arteries they connect. After coronary occlusion, the distal pressure drops precipitously and preexisting collaterals open virtually instantly.
The term "myocardial ischemia" refers to a decrease in blood supply and oxygen to the cells of the myocardium. The development of myocardial ischemia has been attributed to two mechanisms: (1) increased myocardial oxygen demand, and (2) decreased myocardial perfusion and oxygen delivery. (Willerson, J. T. et al., J. Am. Coll. Cardiol. 8(1): 245-50 (1986)). Myocardial ischemia generally appears first and is more extensive in the subendocardial region, since these deeper myocardial layers are farthest from the blood supply, with greater need for oxygen.
Transient ischemia, hibernating myocardium, and myocardial infarction are clinically different conditions.
Transient Ischemia.
The term "transient ischemia" as used herein refers to a reversible (meaning that the myocytes survive the insult) narrowing of a coronary artery at rest or with exercise where there is no thrombus or plaque rupture but where blood supply cannot be met. Every time the heart's oxygen demand increases, an imbalance between oxygen demand and supply is created. Transient ischemia produces a cascade of events beginning with metabolic and biochemical alterations leading to impaired ventricular relaxation and diastolic dysfunction, impaired systolic function, and electrocardiographic abnormalities with ST segment alterations, followed by increased end-diastolic pressure with left ventricular dyssynchrony, hypokineses, akinesis, and dyskinesis, and lastly painful symptoms of angina. Even though ischemic myocytes experience physiological and metabolic changes within seconds of the cessation of coronary flow, resulting in T wave and sometimes ST segment abnormalities (but without serum enzyme elevation), no cell death results from the ischemia. Kloner, R. A. and Jennings, R B, Circulation 104: 2981-89 (2001). Once blood flow is re-established, a complete recovery of myocyte contractile function takes place.
Although angina pectoris (chest pain) may be a symptom of transient ischemia, by and large transient ischemia is silent (meaning ST-segment depression of at least 1 mm is present without associated symptoms, e.g., chest pain) in 79% of subjects. In most patients with stable angina, for example, physical effort or emotion, with a resultant increase in heart rate, blood pressure, or contractile state, or any combination thereof, increases myocardial oxygen demand without an adequate delivery in oxygen delivery through tightly narrowed (stenosed) coronary arteries. More than 40% of patients with stable angina treated with one or more antianginal drugs have frequent episodes of silent ischemia, which has been shown to predict a higher risk of coronary events and cardiac death. Deedwania, P C, Carbajal, E V, Arch. Intern. Med. 150: 2373-2382 (1991).
Chronic Myocardial Ischemia.
The term "chronic myocardial ischemia (CMI)" as used herein refers to a prolonged subacute or chronic state of myocardial ischemia due to narrowing of a coronary blood vessel in which the myocardium "hibernates", meaning that the myocardium downregulates or reduces its contractility, and hence its myocardial oxygen demand, to match reduced perfusion, thereby preserving cellular viability and preventing myocardial necrosis. This hibernating myocardium is capable of returning to normal or near-normal function on restoration of an adequate blood supply. Once coronary blood flow has been restored to normal or near normal and ischemia is resolved, however, the hibernating myocardium still does not contract. This flow-function mismatch resulting in a slow return of cardiac function after resolution of ischemia has been called stunning. The length of time for function to return is quite variable, ranging from days to months, and is dependent on a number of parameters, including the duration of the original ischemic insult, the severity of ischemia during the original insult, and the adequacy of the return of the arterial flow. A number of studies have provided evidence for inflammation in hibernating myocardium. Heusch, G. et al., Am. J. Physiol. Heart Circ. Physiol. 288: 984-99 (2005). A study conducted in a porcine model of myocardial hibernation in which the mean rest (left anterior descending coronary artery (LAD) coronary blood flow was reduced to about 60% of baseline for a period of 24 hours to four weeks, detected apoptotic myocytes in all experimental pigs in the hibernating regions supplied by the stenotic LAD, suggesting that functional downregulation may not be adequate to prevent gradual, ongoing myocyte death through apoptosis in hibernating myocardium. Chen, C, et al., J. Am. Coll. Cardiol. 30: 1407-12 (1997).
Acute Myocardial Infarction (AMI).
Another type of insult occurs during AMI. AMI is an abrupt change in the lumen of a coronary blood vessel which results in ischemic infarction, meaning that it continues until heart muscle dies. On gross inspection, myocardial infarction can be divided into two major types: transmural infarcts, in which the myocardial necrosis involves the full or nearly full thickness of the ventricular wall, and subendocardial (nontransmural) infarcts, in which the myocardial necrosis involves the subendocardium, the intramural myocardium, or both, without extending all the way through the ventricular wall to the epicardium. There often is total occlusion of the vessel with ST segment elevation because of thrombus formation within the lumen as a result of plaque rupture. The prolonged ischemic insult results in apoptotic and necrotic cardiomyocyte cell death. See Kajstura, J., et al., Lab Invest. 74: 86-107 (1996). Necrosis compromises the integrity of the sarcolemmal membrane and intracellular macromolecules such that serum cardiac markers, such as cardiac-specific troponins and enzymes, such as serum creatine kinase (CK), are released. In addition, the patient may have electrocardiogram (ECG) changes because of full thickness damage to the muscle. An ST-Elevation Myocardial Infarction (STEMI) is a larger injury than a non-ST-elevation myocardial infarction. ST-segment elevation and Q waves on the ECG, two features highly indicative of myocardial infarction, are seen in only about half of myocardial infarction cases on presentation.
AMI remains common with a reported annual incidence of 1.1 million cases in the United States alone (Antman, E. M., Braunwald, E., Acute Myocardial Infarction, in Principles of Internal Medicine, 15th Ed., Braunwald, E. et al., Eds., New York: McGraw-Hill (2001)). Preclinical and clinical data demonstrate that following a myocardial infarction, the acute loss of myocardial muscle cells and the accompanying peri-infarct border zone hypo-perfusion result in a cascade of events causing an immediate diminution of cardiac function, with the potential for long term persistence. The extent of myocardial cell loss is dependent on the duration of coronary artery occlusion, existing collateral coronary circulation and the condition of the cardiac microvasculature. Paul et al., Am. Heart J. 131: 710-15 (1996); Pfeffer, M. A., Braunwald, E., Circulation 81: 1161-72 (1990); Sheilban, I. e. al., J. Am. Coll. Cardiol. 38: 464-71 (2001); Braunwald E., Bristow, M. R., Circulation 102: IV-14-23 (2000); Rich et al., Am. J. Med. 92:7-13 (1992); Ren et al., J. Histochem. Cytochem. 49: 71-79 (2002); Hirai, T. et al., Circulation 79: 791-96 (1989); Ejiri, M. et al., J. Cardiology 20: 31-37 (1990). Because myocardial cells have virtually no ability to regenerate, myocardial infarction leads to permanent cardiac dysfunction due to contractile-muscle cell loss and replacement with nonfunctioning fibrotic scarring. Frangogiannis, N. G., et al., Cardiovascular Res. 53(1): 31-47 (2002). Moreover, compensatory hypertrophy of viable cardiac muscle leads to microvascular insufficiency that results in further demise in cardiac function by causing myocardial muscle hibernation and apoptosis of hypertrophied myocytes in the peri-infarct border zone.
Among survivors of myocardial infarction, residual cardiac function is influenced by the extent of ventricular remodeling (meaning changes in size, shape, and function, typically a progressive decline in function, of the heart after injury). Alterations in ventricular topography (meaning the shape, configuration, or morphology of a ventricle) occur in both infarcted and healthy cardiac tissue after myocardial infarction. Pfeffer, M. A., Braunwald, E., Circulation 81: 1161-72 (1990). Ventricular dilatation (meaning a stretching, enlarging or spreading out of the ventricle) causes a decrease in global cardiac function and is affected by the infarct size, infarct healing and ventricular wall stresses. Recent efforts to minimize remodeling have been successful by limiting infarct size through rapid reperfusion (meaning restoration of blood flow) using thromobolytic agents, and mechanical interventions, including, but not limited to, placement of a stent, along with reducing ventricular wall stresses by judicious use of pre-load therapies and proper after-load management. Id. Regardless of these interventions, a substantial percentage of patients experience clinically relevant and long-term cardiac dysfunction after myocardial infarction. Sheiban, I. et al., J. Am. Coll. Cardiol. 38: 464-71 (2001). Despite revascularization of the infarct related artery circulation and appropriate medical management to minimize ventricular wall stresses, a significant percentage of these patients experience ventricular remodeling, permanent cardiac dysfunction, and consequently remain at an increased lifetime risk of experiencing adverse cardiac events, including death. Paul et al., Am. Heart J. 131: 710-15 (1996); Pfeffer, M. A., Braunwald, E., Circulation 81: 1161-72 (1990).
At the cellular level, immediately following a myocardial infarction, transient generalized cardiac dysfunction uniformly occurs. In the setting of a brief (i.e., lasting three minutes to five minutes) coronary artery occlusion, energy metabolism is impaired, leading to demonstrable cardiac muscle dysfunction that can persist for up to 48 hours despite immediate reperfusion. This so-called "stunned myocardium phenomenon" occurs subsequent to or after reperfusion and is thought to be a result of reactive oxygen species. The process is transient and is not associated with an inflammatory response. Frangogiannis, N. G., et al., Cardiovascular Res. 53(1): 31-47 (2002). After successful revascularization, significant recovery from stunning occurs within three to four days, although complete recovery may take much longer. Boli, R., Prog. Cardiovascular Disease 40(6): 477-515 (1998); Sakata, K. et al., Ann. Nucleic Med. 8: 153-57 (1994); Wollert, K. C. et al., Lancet 364: 141-48 (2004).
Coronary artery occlusion of more significant duration, i.e., lasting more than five minutes, leads to myocardial ischemia (i.e. an insufficient blood flow to the heart's muscle mass) and is associated with a significant inflammatory response that begins immediately after reperfusion and can last for up to several weeks. Frangogiannis, N. G., et al., Cardiovascular Res. 53(1): 31-47 (2002); Frangogiannis, N. G. et al., Circulation 98: 687-798 (1998).
The inflammatory process following reperfusion is complex. Initially it contributes to myocardial damage but later leads to healing and scar formation. This complex process appears to occur in two phases. In the first so-called "hot" phase (within the first five days), reactive oxygen species (in the ischemic myocardial tissue) and complement activation generate a signal chemotactic for leukocytes (chemotaxis is the directed motion of a motile cell, organism or part towards environmental conditions it deems attractive and/or away from surroundings it finds repellent) and initiate a cytokine cascade. Lefer, D. J., Granger, D. N., Am. J. Med. 4:315-23 (2000); Frangogiannis, N. G., et al., Circulation 7:699-710 (1998). Mast cell degranulation, tumor necrosis factor alpha (TNFα) release, and increased interleukin-6 (IL-6), intercellular adhesion molecule 1 ("ICAM-1" or CD-54, a receptor typically expressed on endothelial cells and cells of the immune system), selectin (L, E and P) and integrin (CD11a, CD11b and CD18) expression all appear to contribute to neutrophil accumulation and degranulation in ischemic myocardium. Frangogiannis, N. G. et al., Circulation 7: 699-710 (1998), Kurrelmeyer, K. M, et al., Proc. Natl. Acad. Sci. USA. 10: 5456-61 (2000); Lasky, L. A., Science 258: 964-69 (1992); Ma, X. L., et al., Circulation 88(2): 649-58 (1993); Simpson, P. J. et al., J. Clin. Invest. 2: 624-29 (1998). Neutrophils contribute significantly to myocardial cell damage and death through microvascular obstruction and activation of neutrophil respiratory burst pathways after ligand-specific adhesion to cardiac myocytes. Entman, M. L., et al., J. Clin. Invest. 4: 1335-45 (1992). During the "hot" phase, angiogenesis is inhibited due to the release of angiostatic substances, including interferon gamma-inducible protein (IP 10). Frangogiannis, N. G., et al., FASEB J. 15: 1428-30 (2001).
In the second phase, the cardiac repair process begins (about day 6 to about day 14), which eventually leads to scar formation (about day 14 to about day 21) and subsequent ventricular remodeling (about day 21 to about day 90). Soon after reperfusion, monocytes infiltrate the infarcted myocardium. Attracted by complement (C5a), transforming growth factor B1 ("TGF-B1") and monocyte chemotactic protein 1 ("MCP-1"), monocytes differentiate into macrophages that initiate the healing process by scavenging dead tissue, regulating extracellular matrix metabolism, and inducing fibroblast proliferation. Birdshall, H. H., et al., Circulation 3: 684-92 (1997). Secretion of interleukin 10 (IL-10) by infiltrating lymphocytes also promotes healing by down-regulating inflammatory cytokines and influencing tissue remodeling. Frangogiannis, N. G. et al., J. Immunol. 5:2798-2808 (2000). Mast cells also appear to be involved in the later stages of myocardial repair by participating in the formation of fibrotic scar tissue. Stem Cell Factor (SCF) is a potent attractor of mast cells. SCF mRNA has been shown to be up-regulated in ischemic myocardial segments in a canine model of myocardial infarction and thus may contribute to mast cell accumulation at ischemic myocardial sites. Franigogiannis, N. G. et al., Circulation 98: 687-798 (1998). Mast cell products (including TGF-B, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and gelatinases A and B) induce fibroblast proliferation, influence extracellular matrix metabolism, and induce angiogenesis. Fang, K. C., et al., J. Immunol. 162: 5528-35 (1999); Takeshi, S., et al., Cardiology 93: 168-74 (2000).
Following a myocardial infarction, neoangiogenesis occurs after the "hot" phase of the inflammatory process subsides (about day 5) coincident with rising levels of VEGF (VEGF peaks at about day 7 and gradually subsides to baseline at about day 14 to about day 21). During this phase of the healing process, endothelial precursor cells (EPCs) are mobilized and recruited to the infarct site. Shinitani, S., et al., Circulation 103: 2776-79 (2001). Without being limited by theory, it has been suggested that the chemokine stromal cell derived factor-1 (SDF-1), which is the ligand for the CXCR-4 chemokine receptor expressed by CD34+ cells, also plays a role in horning of cells to areas of ischemic damage. Ceredini, D. I, et al., Nature Medicine 10: 858-63 (2004); Askari, A., et al., Lancet 362: 697-703 (2003); Yamaguchi, J. et al., Circulation 107: 1322-34 (2003). While it is known that SDF-1 plays a role in hematopoiesis and is involved in migration, homing and survival of hematopoietic progenitors, and while SDF-1 has been implicated in ischemic neovascularization in vivo by augmenting EPC recruitment to ischemic sites (Yamaguchi et al. Circulation 107:1322-1328 (2003), SDF-1's role in neoangiogenesis is not certain. There is suggestive evidence implicating SDF-1. For example, SDF-1 gene expression is upregulated during hypoxia, a deficiency of oxygen in the tissues, by hypoxia inducible factor-1. Furthermore, CD34+ cells are capable of homing to areas of ischemia, rich in SDF-1, including infarcted myocardium. Askari et al., Lancet 362: 697-703 (2003). Moreover, virtually all CD34+ CXCR-4+ cells co-express VEGF-2 and therefore migrate in response to VEGF as well as SDF-1. Peichev M., et al., Blood 95: 952-58 (2000). CD34+CXCR-4+VEGF-1 cells, once recruited, are capable of contributing to neoangiogenesis. Yamaguchi, J. et al., Circulation 107: 1322-34 (2003).
The Peri-Infarct Border Zone
The zone of dysfunctional myocardium produced by coronary artery occlusion extends beyond the infarct region to include a variable boundary of adjacent normal appearing tissue. (Hu, Q., et al., Am. J. Physiol. Heart Circ. Physiol. 291: H648-657 (2006)). This ischemic, but viable, perinfarct zone of tissue separates the central zone of progressive necrosis from surrounding normal myocardium. The peri-infarct zone does not correlate with enzymatic parameters of infarct size and is substantially larger in small infarcts. Stork, A., et al., European Radiol. 16(10): 2350-57 (2006).
Ischemia due to edema and compression of the blood vessels in the border zone may be very important to outcome after an AMI. It is known, for example, that after an AMI, transient ischemia occurs in the border zones, and that percutaneous coronary interventions, which open up the infarct-related artery, can adversely affect the health of the peri-infarct border zones. It has been suggested that intermediate levels of mean blood flow can exist as the result of admixture of peninsulas of ischemic tissue intermingled with regions of normally perfused myocardium at the border of an infarct. (Hu, Q., et al., Am. J. Physiol. Heart Circ Physiol. 291: H648-657 (2006)). However, the boundary of the intermingled coronary microvessels, which in dogs is no more than 3 mm in width, cannot explain the relatively broad region of dysfunctional myocardium surrounding an infarct. Murdock, R H, Jr., et al., Cir. Res. 52: 451-59 (1983); Buda, A J, et al., J. Am. Coll. Cardiol. 8: 150-58 (1986). Progressive dysfunction of this peri-infarct myocardium over time may contribute to the transition from compensated remodeling to progressive heart failure after an AMI.
Heart Failure
Heart failure is a complex clinical syndrome that arises secondary to abnormalities of cardiac structure and/or function that impair the ability of the left ventricle to fill or eject blood. See Hunt, S. J. Am. Coll. Cardiol. 46: e1-e82 (2005). It is a progressive condition where the heart muscle weakens and cannot pump blood efficiently. Patients may be categorized as having heart failure with depressed ejection fraction ("EF")(referred to as "systolic failure"), or having heart failure with a normal EF or heart failure with a preserved EF (referred to as "diastolic failure"). Patients may have significant abnormalities of left ventricle (LV) contraction and relaxation and yet have no symptoms, in which case they are referred to as having "asymptomatic heart failure". When a patient with chronic heart failure deteriorates, the patient is referred to as having "decompensated heart failure", or, if the symptoms arise abruptly, as having "acute decompensated heart failure".
The various diagnostic criteria used to determine the presence of heart failure are shown in the following Table (V. L. Roger, Intl. J. Environ. Res. Public Health 7(4): 1807-30 (2010)):
European SocietyGothenburg Score4Framingham1Boston2of Cardiology3 nCriteria/method of assessmentMAJORCATEGORY I:1. Symptoms ofCARDIAC SCORECRITERIA:Historyheart failure (at restHistory of heartSelf-ParoxysmalRest dyspneaor during exercise)disease (1-2 pts)reportnocturnal dyspnea(4 pts)andAngina (1-2 pts)Self-or orthopneaOrthopnea (4 pts)2. ObjectivereportNeck veinParoxysmalevidence of cardiacEdema (1 pt)Self-distensionnocturnaldysfunction (at rest)reportRalesdyspnea (3 pts)andNocturnal DyspneaSelf-CardiomegalyDyspnea on3. Response to(1 pt)reportAcute pulmonarywalking on leveltreatment directedRales (1 pt)Physicaledema S3 gallop(2 pts)towards heart failureexamIncreased venousDyspnea on(in cases whereAtrial fibrillationECGpressure ≧16 cmclimbing (1 pt)diagnosis is in(1 pt)waterCATEGORYdoubt).PULMONARY SCORECirc. time ≧25 secII: PhysicalCriteria 1 and 2History of ChronicSelf-Hepatojugularexaminationshould be fulfilled inbronchitis/asthmareportrefluxHeart rateall cases(1-2 pts)MINORabnormality (1-Cough, phlegm, orSelf-CRITERIA:2 pts)wheezing (1 pt)reportAnkle edemaJugular venousRhonchi (2 pts)PhysicalNight coughpressureexamDyspnea onelevation (1-2Cardiac and pulmonary score areexertionpts)calculated and used toHepatomegalyLung cracklesdifferentiate Cardiac formPleural effusion(1-2 pts)pulmonary dyspneaVital capacityWheezing (3 pts)decreased ⅓Third heartfrom maximumsound (3 pts)Tachycardia rateCATEGORYof ≧120/min)III: ChestMAJOR ORradiographyMINORAlveolarCRITERION:pulmonaryWeight loss ≧4.5edema (4 pts)kg in 5 days inInterstitialresponse topulmonarytreatmentedema (3 pts)HEARTBilateral pleuralFAILURE:effusions (3 pts)present with 2Cardiothoracicmajor or 1 majorratio ≧0.50 (3and 2 minorpts)criteriaUpper-zone flowredistribution (2pts)HEARTFAILURE:Definite 8-12pts, possible 5-7 pts, unlikely 4pts or less1McKee P A, Castelli W P, McNamara P M, Kannel W B. The natural history of congestive heart failure: the Framingham study. N. Engl. J. Med. 285: 1441-1446 (1971)2Carlson K J, Lee D C Goroll A H, Lehy M, Johnson R A, an analysis of physicians' reasons for prescribing long-term digitalis therapy in outpatients. J. Chronic Dis. 38: 733-39 (1985)3Guidelines for the diagnosis of heart failure The Task Force on Heart Failure of the European Society of Cardiology. Eur. Heart J. 16: 741-751 (1995)4Eriksson H, Caidahl K, Larsson B, Ohlson L O, Welin L, Wilhelmsen L, Svardsudd K. Cardiac and pulmonary causes of dyspnoea-validation of a scoring test for clinical-epidemiological use: the Study of Men Born in 1913. Eur. Heart J. 8: 1007-1014 (1987)[
The prognosis of heart failure is poor with reported survival estimates of 50% at 5 years and 10% at 10 years; left ventricular dysfunction is associated with an increase in the risk of sudden death. Id.
To date, no ideal therapy exists for preventing the long term adverse consequences of vascular insufficiency, particularly vascular insufficiency after myocardial infarction. Large vessel revascularization (meaning the successful placement of a stent) is insufficient in addressing increased demands posed by compensatory myocardial hypertrophy. As a result, infarct extension and fibrous replacement commonly occur, regardless of large vessel revascularization, appropriate medical management of ventricular wall stresses, and potential natural, albeit suboptimal, CD34+ cell-mediated neoangiogenesis (one of theories relating to the underlying cause of myocardial infarction is that the ability to mobilize these cells may be biologically limited).
Intense interest has developed in evaluating the ability of endothelial and myocardial precursor cells to limit damage to the myocardium after infarction and to limit or prevent ventricular remodeling. Significant preclinical data and some clinical data demonstrate the safety and potential of cell therapy using a variety of cell precursors (particularly hematopoietic cells) to contribute to neoangiogenesis, limited cardiac myogenesis (principally by fusion), and muscle preservation in the myocardial infarct zone. See, e.g., Jackson, et al., J. Clin. Invest. 107: 1395-1402 (2001); Edelberg, J. M., et al., Cir. Res. 90: e89-e93 (2002); Schichinger, V. et al., New Engl. J. Med. 355 (12): 1210-21 (2006) (using bone marrow-derived progenitor cells); Assmus, B. et al., New Engl. J. Med. 355 (12) 1222-32 (2006) (using bone marrow-derived progenitor cells), but see Lunde, K. et al., New Eng. J. Med. 355 (12): 1199-209 (2006) (using bone marrow-derived progenitor cells).
Bone marrow consists of a variety of precursor and mature cell types, including hematopoietic cells (the precursors of mature blood cells) and stromal cells (the precursors of a broad spectrum of connective tissue cells), both of which appear to be capable of differentiating into other cell types. Wang, J. S. et al., J. Thorac. Cardiovasc. Surg. 122: 699-705 (2001); Tomita, S. et al., Circulation 100 (Suppl. II): 247-256 (1999); Saito, T. et al., Tissue Eng. 1: 327-43 (1995). Unmodified (i.e., not fractionated) marrow or blood-derived cells have been used in several clinical studies, for example, Hamano, K. et al., Japan Cir. J. 65: 845-47 (2001); Strauer, B. E., et al., Circulation 106: 1913-18 (2002); Assmus, et al., Circulation 106: 3009-3017 (2002); Dobert, N. et al., Eur. J. Nuel. Med. Mol. Imaging, 8: 1146-51 (2004); Wollert, K. C. et al., Lancet 364: 141-48 (2004). Since the mononuclear fraction of bone marrow contains stromal cells, hematopoietic precursors, and endothelial precursors, the relative contribution of each of these populations to the observed effects, if any, remains unknown.
CD34 is a hematopoietic stem cell antigen selectively expressed on hematopoietic stem and progenitor cells derived from human bone marrow, blood and fetal liver. Yin et al., Blood 90: 5002-5012 (1997); Miaglia, S. et al., Blood 90: 5013-21 (1997). Cells that express CD34 are termed CD34+. Stromal cells do not express CD34 and are therefore termed CD34−. CD34+ cells isolated from human blood may be capable of differentiating into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. See Yeh, et al., Circulation 108: 2070-73 (2003). CD34+ cells represent approximately 1% of bone marrow derived nucleated cells; CD34 antigen also is expressed by immature endothelial cell precursors (mature endothelial cells do not express CD34). Peichev, M. et al., Blood 95: 952-58 (2000). In vitro, CD34+ cells derived from adult bone marrow give rise to a majority of the granulocyte/macrophage progenitor cells (CFU-GM), some colony-forming units-mixed (CFU-Mix) and a minor population of primitive erythroid progenitor cells (burst forming units, erythrocytes or BFU-E). Yeh, et al., Circulation 108: 2070-73 (2003). CD34+ cells also may have the potential to differentiate into, or to contribute to, the development of new myocardial muscle, albeit at low frequency.
Techniques have been developed using immunomagnetic bead separation to isolate a highly purified and viable population of CD34+ cells from bone narrow mononuclear cells. See U.S. Pat. Nos. 5,536,475, 5,035,994, 5,130,144, 4,965,205, the contents of each of which is incorporated herein by reference. Two clinical studies support the clinical application of bone marrow derived CD34+ cells after myocardial infarction. See C. Stamm, et al., Lancet 361: 45-46 (2003); Herenstein, B. et al., Blood Supplement, Abs. 2696 (2004).
Animal Models
Peripheral artery disease (PAD), also called peripheral vascular disease (PVD), is modeled by the hind limb model of ischemia in which the femoral artery of the mouse is tied off to simulate peripheral artery disease. PAD, which commonly affects the arteries supplying the leg and includes all diseases caused by the obstruction of large arteries in the arms and legs, can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. Restriction of blood flow due to arterial stenosis or occlusion often leads patients to complain of muscle pain on walking (intermittent claudication). Any further reduction in blood flow causes ischemic pain at rest. This condition is called chronic limb ischemia, meaning the demand for oxygen cannot be sustained when resting. Ulceration and gangrene may then supervene in the toes, which are the furthest away from the blood supply, and can result in loss of the involved limb if not treated.
Therapies for limb ischemia have the goals of collateral development and blood supply replenishment. Bone marrow derived CD34+ mononuclear cells have been tested in such hindlimb ischemia models, but the hindlimb ischemia model does not model what takes place in the heart. A preferred therapy after AMI would stop cells from dying during recovery that leads to reverse remodeling and failure, or replace the dying cells with cardiomyocytes.
The closest animal model, the pig model, is not a good model of human disease because (i) all experiments generally are done in nonatherosclerotic animals, (ii) the animals are not treated with angioplasty, (iii) normal pigs do not embolize blood vessels; (iv) circulation of the pig is not exactly the same as human; and (iv) the peri-infarct border zone may not be the same.
A marginal improvement in angina symptoms recently was reported when CD34+ cells were mobilized with G-CSF, apheresed after 5 days, and then injected into an ischemic area of the heart based on Noga mapping. [Northwestern University (2009, Apr. 1). Adult Stem Cell Injections May Reduce Pain And Improve Walking In Severe Angina Patients. ScienceDaily. Retrieved Oct. 21, 2010, from http://www.sciencedaily.com-/releases/2009/03/090330091706.htm] Data from a phase I trial conducted by the present inventors has provided evidence that subjects treated with at least 10×106 isolated autologous CD34+ hematopoietic stem cells containing a subpopulation of at least 0.5×106 potent CD34+ cells expressing CXCR-4 and having CXCR-4 mediated chemotactic activity (n=9) experienced significant improvement in resting perfusion rates at 6 months compared to subjects receiving 5 million cells (n=6) and control (n=15), as measured by the SPECT Total Severity Score (−256 versus +13, p=0.01). U.S. Patent Applications 61/169,850 and 61/119,552, incorporated herein by reference.
The described invention is a therapy for preventing the long-term adverse consequences of vascular insufficiency, particularly vascular insufficiency that produces expansion of the myocardial infarct area after an AMI progressing to heart failure. It is proposed that administration of a potent dose of a nonexpanded, isolated population of autologous mononuclear cells enriched for CD34+ cells, which further contain a subpopulation of potent CD34+ cells expressing CXCR-4 and having CXCR-4-mediated chemotactic activity administered early or late after occurrence of an AMI can result in a reduction in major adverse cardiac events, including, but not limited to, premature death, recurrent myocardial infarction, the development of congestive heart failure, significant arrhythmias, and acute coronary syndrome, and the worsening of congestive heart failure, significant arrhythmias, and acute coronary syndrome.

Compositions and methods for treating progressive myocardial injury due to a vascular insufficiency


The present invention provides a membrane carrier 3 for a test kit of detecting a target substance in a liquid sample, comprising at least one flow path 2 transporting the liquid sample, wherein a microstructure producing capillary action for transporting the liquid sample is formed at a bottom of the flow path 2, and the microstructure is provided to change along a transport direction d of the liquid sample.

Recently, Point of Care Test (POCT) reagents using, for example, antigen-antibody reactions for determining contraction of infectious diseases, pregnancy, blood sugar level and the like have attracted attention. The POCT reagents have such characteristics as capability of determination of test results in a short time, simple operation and low cost. By virtue of these characteristics, the POCT reagents are frequently used in, for example, medical examinations at the stage of mild symptoms and regular medical examinations and used as an important examination tool in home medical care which is expected to expand from now on.
In most POCT reagents, determination is made by introducing a liquid sample such as blood in a test kit and detecting a predetermined target substance contained in the liquid sample. As a method for detecting a predetermined target substance from a liquid sample, immunochromatography is frequently used. The immunochromatography is a technique for detecting a substance by delivering a liquid drop onto a membrane carrier of a test kit, allowing the liquid drop to move on the membrane carrier, allowing a target substance to bind to a label and the resultant to further bind specifically to a substance (hereinafter referred to as a detection substance) immobilized in the test kit to produce a color or weight change, and detecting the change. The detection substance may be called also as a reagent.
As a technique for detecting a target substance, a technique for detecting a color change produced by using colored latex particles, fluorescent latex particles, metallic colloidal particles and the like as a label by an optical measuring apparatus such as an absorbance measuring apparatus is well known.
As the POCT reagent for optically determining a color change, lateral flow type kit using a nitrocellulose membrane is often used (Patent Literature 1). The nitrocellulose membrane has many micropores having a diameter of about several Lm and a liquid sample moves through the micropores with the help of capillary force.
However, the nitrocellulose membrane, which is derived from a natural product, has pores not uniform in size and arrangement. Because of this, the flow rate of a liquid sample varies depending on the membranes. If the flow rate varies, the time taken for detecting a target substance varies, with the result that a wrong determination: "binding was not detected" may be made before the target substance binds.
In order to overcome the above problem, a technique for artificially producing a micro flow-path is devised (Patent Literatures 2 to 6). If this technique is used, a membrane carrier having a uniform structure can be prepared, with the result that the possibility of wrong determination: "binding was not detected" made before the target substance binds, can be reduced.

Membrane carrier for liquid sample test kit, liquid sample test kit, and method for producing liquid sample test kit


A jury selection system for efficient jury selection using a jury board demarcated with a grid that mimics a jury seating arrangement. The jury selection system further comprises a primary tag to record a juror's information to be placed in the demarcated space on the board that corresponds with the juror's actual seat number. The primary tag has a primary tag indicator to indicate that the tag is a primary tag. A supplemental tag is provided if more information is recorded to be placed on top of the primary tag. The supplemental tag has a cut out to align with the primary tag indicator so that the primary tag can be identified when the supplemental tag is placed on top of the primary tag. Peremptory tags may be used to keep track of peremptory challenges.

The legal system has been set up so that peers can determine the outcome of a dispute. These peers are supposed to form an impartial jury panel. However, due to the natural biases and life circumstances of people, one party may not necessarily receive a fair trial if the first 12 jurors were automatically seated without question. Therefore, the jury selection process is an important process is determining the fairness of the trial and maintaining impartiality of the jury.
During the jury selection process, counsel for both sides are allowed to ask each individual juror questions to determine the impartiality of the juror and the juror's ability to appropriately apply the laws to the facts of the case. This process is customarily referred to as "Voir Dire" which has a French origin and means "to speak the truth." This process requires the attorneys and their staff to keep track of questions, answers, and their assessment of each prospect of juror. Oftentimes, notes are scribbled and passed around amongst a number of people. Notes on one juror can get mixed up with notes for another juror, or the notes can simply get lost. Watching an attorney fumble around with his notes can have a negative impact on the jurors as well as the client.
For the foregoing reasons there is a need for a jury selection system that allows the attorneys keep an organized record of the questions asked, the answers provided, and the assessment of each juror in order to keep the jury selection process efficient and effective.


A silica-based coating film having a low dielectric constant not exceeding 2.5 can be formed on the surface of a substrate to serve as a planarizing layer or an interlayer insulating layer by coating the surface with a unique coating solution containing a hydrolysis-condensation product of a polyalkoxy silane compound such as tetraethoxy silane and monomethyl trimethoxy silane, which is formed by the hydrolysis of a polyalkoxy silane in the presence of a basic catalyst such as ammonia in an alcohol solvent in a relatively low concentration followed by replacement of the alcohol solvent with an aprotic polar solvent such as N-methyl pyrrolidone, followed by drying and baking at 350 to 800° C.

The present invention relates to a silica-based coating film on a substrate surface and a coating solution for the formation of a silica-based coating film on a substrate surface. More particularly, the invention relates to a silica-based coating film having a low dielectric constant formed on a substrate surface in the manufacturing process of various kinds of semiconductor devices to serve as a planarizing layer, interlayer insulating layer and the like as well as to a coating solution containing a specific hydrolysis-condensation product of a hydrolyzable silane compound for the formation of a silica-based coating film.
It is conventional in the manufacturing process of semiconductor devices that, when a planarizing layer or interlayer insulating layer has to be formed, a silica-based coating film is formed on the substrate surface to serve for the purpose. Several methods are utilized for the formation of such a silica-based coating film on a substrate surface including the chemical vapor-phase deposition (CVD) method, coating method by the use of a coating solution and others.
The CVD method, when applied to the formation of a silica-based coating film, is conducted by using a specialized apparatus in which silica optionally doped with phosphorus or boron is vapor-deposited to grow a silica-based coating film on the substrate surface. In the solution-coating method for the formation of a silica-based coating film, on the other hand, the surface of a substrate is coated with a coating solution containing a partial hydrolysis-condensation product of an alkoxy silane compound dissolved in an organic solvent followed by baking of the coating layer to complete the silica-based coating film, in which the hydrolysis-condensation reaction of the alkoxy silane compound in an organic solvent is performed usually in the presence of an acidic catalyst.
One of the serious problems in the electronic information-processing technology in recent years is that, along with the increasing trend of semiconductor devices toward a higher and higher degree of multiplication of multilayered pattern structure and fineness of patterning, a delay is caused in the signal transmission not to allow high velocity working of ULSIs. A large number of proposals have been made for a solution of this problem including an idea to employ a dielectric material of a low dielectric constant for the interlayer insulating layer.
For example, a proposal is made for an insulating film of silica doped with fluorine, referred to as an SiOF film hereinafter, as formed by the CVD method. One of the problems in the SiOF film is the expensiveness of the CVD apparatus therefor resulting in high costs. In addition, the SiOF film contains a Si—F linkage having high reactivity which reacts with water in the atmosphere to form an Si—OH linkage having an effect of increasing the dielectric constant of the film. Accordingly, the dielectric constant of SiOF films can rarely be lower than about 3.3.
In the solution-coating method for the formation of a silica-based coating film, proposals are made for the use of methyl polysiloxanes and hydrogen silsesquioxanes having a relatively low dielectric constant, such as a hydrolysis-condensation product of a dimethyl alkoxy silane and methyl silsesquioxane, as the film-forming constituent in the coating solution. The dielectric constant of the films consisting of a methyl polysiloxane and hydrogen silsesquioxane, however, can be about 2.8 and 3.3, respectively, at the lowest and a dielectric film having a dielectric constant lower than 2.8 can hardly be obtained. Accordingly, the solution-coating method by using these coating solutions cannot meet the requirements in the modern semiconductor devices for a lower and lower dielectric constant of the silica-based coating films.
It is a known technology that a poly(methylsilsesquioxane) powder as a filler for use in synthetic resins and rubbers and coating compositions are prepared from a polyalkoxy silane compound by conducting the hydrolysis-condensation reaction thereof in the presence of a basic catalyst (see, for example, Japanese Patent Kokai 54-72300 and 2-209927 for the powder and Japanese Patent Kokai 2-627 for the coating composition). No proposals have been made heretofore, however, on the application of such a technology to hydrolyze a polyalkoxy silane compound in the presence of a basic or alkaline catalyst for the preparation of a coating solution which can be used for the formation of a silica-based coating film on a substrate surface in the manufacturing process of semiconductor devices.
A method is disclosed in Japanese Patent Kokai 5-125187 for the preparation of a poly(organosilsesquioxane) having an extremely high molecular weight by promoting condensation of a low-degree hydrolysis-condensation product of a trialkoxy silane compound in the presence of an alkaline catalyst. Further, a proposal is made for the formation of a silica-based coating film having a low dielectric constant by using a coating solution obtained by conducting the hydrolysis treatment of an alkoxy silane compound in two steps including the first step in which the hydrolysis reaction is conducted in the presence of an alkaline catalyst to give a low-degree hydrolysis product which is further hydrolyzed in the second step in the presence of an acidic catalyst. The above described methods, however, are defective due to the low stability of the silica-based coating films obtained thereby and, even if the problem of stability is set aside, due to the dielectric constant of the coating films not low enough which is 3.8 at the lowest to be much higher than the target value of 2.5 desirable in the manufacture of semiconductor devices.

Silica-based coating film on substrate and coating solution therefor


A method, equipment and system for policy control. The method includes: a trusted Wireless Local Area Network (WLAN) access gateway receiving Quality of Service (QoS) information from a 3GPP core network, and sending the QoS information to an Access Controller (AC) or a Broadband Network Gateway (BNG); the AC or the BNG or other fixed network access devices performing admission control and/or resource allocation according to the QoS information. In the technical solution, the interface configuration and policy configuration are performed for the WLAN access gateway in the fixed mobile convergence scenario, thereby the policy control is implemented in the fixed mobile convergence scenario.

The present FIG. 1 is a schematic diagram of a composition framework of EPS (Evolved Packet System) of 3GPP (3rd Generation Partnership Project). As shown in FIG. 1, the EPS network framework in a non-roaming scenario includes: E-UTRAN (Evolved Universal Terrestrial Radio Access Network), MME (Mobility Management Entity), S-GW (Serving Gateway), PDN GW (also called as P-GW, Packet Data Network Gateway), HSS (Home Subscriber Server), PCRF (Policy and Charging Rules Function) entities and other supporting nodes.
Wherein, the PCRF is a core of the PCC (Policy and Charging Control), and is responsible for formulating policy strategy and charging rules. The PCRF provides network controlling rules based on service data stream, and the network controlling includes service data stream detection, gating control, QoS (Quality of Service) control and charging rules based on data stream and so on. The PCRF sends the policy and charging rules formulated by itself to the PCEF (Policy and Charging Enforcement Function) for enforcement. Meanwhile, the PCRF is also required to ensure that the rules are coincident with the subscribers' subscription information. The basis for the PCRF to formulate policy and charging rules includes: acquiring service-related information from AF (Application Function); acquiring subscribers' subscription information of policy and charging control from SPR (Subscription Profile Repository); and acquiring bearer-related network information from PCEF.
The EPS supports communication with non-3GPP systems, and the EPS communicates with non-3GPP systems through S2a/b/c interfaces, using a P-GW as an anchor between 3GPP systems and non-3GPP systems. As shown in FIG. 1, non-3GPP systems are classified into trusted non-3GPP IP access and untrusted non-3GPP IP access. The trusted non-3GPP IP access can be connected with a P-GW through an S2a interface directly; the untrusted non-3GPP IP access is required to connect with P-GW through ePDG (Evolved Packet Data Gateway), where an interface between an ePDG and a P-GW is an S2B interface, and signaling and data between UE (User Equipment) and ePDG are encrypted for protection with IPSec (Internet Protocol Security). The S2c interface provides control and mobility support related to the user side between UE and P-GW, and the mobility management protocol supported by the S2c interface is DSMIPv6 (Mobile IPv6 Support for Dual Stack Hosts and Routers).
With the development of network technology, many operators begin to concern FMC (Fixed Mobile Convergence), and research on the connection and communication between 3GPP and BBF. In the scenario that subscribers access the mobile core network through BBF, it needs to ensure the QoS of the data in the whole transmission path (data may be transmitted through fixed network and mobile network). In the related art, the QoS is ensured by interacting with BPCF (Broadband Policy Control Framework) in the BBF access through PCRF. BPCF is the policy control framework of BBF access. For the resource request message of PCRF, BPCF performs, according to the network policy, subscription information and so on of the BBF access, resource admission control or forwards the resource request message to other network elements of the BBF access network (such as BNG (Broadband Network Gateway)), and then other network elements perform the resource admission control (i.e. other network elements are entrusted to perform resource admission control). For example, when a UE accesses the 3GPP core network through WLAN (Wireless Local Area Network), PCRF needs to interact with BPCF when performing QoS authorization in order to ensure a demand for a total bandwidth for visiting services by all the UEs accessing through WLAN accessing line being not larger than the bandwidth of the line (such as the subscription bandwidth or the largest physical agent supported by the line), thus the BBF access network performs resource admission control.
At present, one important scenario of studying interconnection and intercommunication between 3GPP and BBF is: a scenario of a 3GPP UE accessing the EPS through the WLAN of BBF. Many operators think that WLAN can be taken as a trusted non-3GPP system, thereby the problem of interconnection and intercommunication for UE accessing EPS through the trusted WLAN has been attached importance gradually and on the start of research. FIG. 2 is a schematic diagram of the framework for a UE accessing an EPC (Evolved Packet Core) network through WLAN in the related art, wherein, one logic network element of the WLAN interconnects with P-GW of 3GPP through an S2a interface, and the S2a interface supports GTP (Generic Tunneling Protocol)/PMIP (Proxy Mobile IP).
In the related art, to make AC (Access Controller)/BNG (Broadband Network Gateway) support S2a interface, all AC/BNG devices are required to upgrade, which will seriously impacts the present network.
In order to solve the problem, in the related art, it proposes to introduce a WLAN access network (such as TWAG′ (Trusted WLAN Access Gateway) as shown in FIG. 3), by this way, accessing the 3GPP network can be implemented without need of upgrading the AC/BNG devices on a large scale, as a result, upgrading and modification for the present network are lessened. In that framework, TWAG′ is added to WLAN, which is responsible for the intercommunication of the control plane messages and user plane data between WLAN and EPC network. Wherein, TWAG′ can be deployed alone, and can also be integrated in BSG (Broadband Service Gateway). In that framework, the related critical interfaces and functions thereof are described as follows:
Interface C: is an interface between TWAG′ and BBF AAA (Authentication, Authorization and Accounting). That interface is used to forward the authentication message sent by BNG or BBF AAA, and the authentication success message sent by BBF AAA can be used to trigger the establishment of GTP/PMIP tunnel between TWAG′ and P-GW of the EPC network.
Interface D: is an interface between TWAG′ and BNG. That interface is used to forward authentication message sent by BNG or DHCP (Dynamic Host Configuration Protocol) message, and subscriber data etc.
However, there is still no solution of implementing policy control in the network framework as shown in FIG. 3.

Method, apparatus and system for policy control


A method and system for processing messages received by a message storage system. The message storage system receives a message. The type of the message received is then determined. The message is then scanned for user specified content based upon the type of message. If the user specified content is found, message handling rules are applied to the message.

This invention relates to messaging systems. More particularly, this invention relates to a process for sorting messages received by the messaging system for a user. Still more particularly, this invention relates to a messaging system that all types of incoming messages for a user specified content and handling incoming messages containing the user specified content in a user specified manner.
1. Problem
Today, it is common for a user to have a message storage system that stores multiple types of messages for the user in a user mailbox. For example, calls to the user are forwarded by a switch to the messaging system when the user is unavailable and e-mails to the user may be forwarded by a server to the same messaging system. It is common for such system to store telephone messages, e-mails, faxes and other types of messages.
Sometimes a user is expecting a message from another person and does not know what type of message the person will send. For example, a salesman may be expecting an order from a customer. The customer may call the salesman, send an e-mail or fax an order request. Since the expected order may come in any type of message, it would be desirable for an agent operating the message system to be able to scan all messages regardless of type to detect the desired message when the message is received and to handle the message in a user specified manner. For example, it may forward a telephone message to another telephone or may page the user when the desired message is received.
2. Solution
The above and other problems are solved and an advance in the art is made by a messaging system that processes messages based upon user specified content. An advantage of this messaging system is that multiple types of messages may be processed looking for user specified content. This assures that a message including the specified content are handled in a desired manner. For example, a user is assured to receive a message including a contract which may come in an e-mail or as a fax.
In accordance with this invention, a messaging system or processor that is connected to the messaging system executes applications that provide a message agent that manages the storage of messages by the message storage system. The message agent receives a message for a user. The message agents then determine which type of message was received. The message is then scanned for user specified content based upon the type of message received. If user specified content is contained in the message, message handling rules are applied to the message.
Before a process in accordance with this invention is performed, the message agent may determine whether a user has provided user specified content. If the user has not provided user specified content, the message is stored in a conventional manner like all other messages received. This allows a user to choose when the processes in accordance with this invention are implemented.
If a message contains user specified content, the message agent may determine whether a rule is activated for the type of message received. If a rule is activated for the type of message received, the rule is applied to the message. Otherwise, the message is stored in a conventional manner. This allows the user to select only those certain types of messages to handle with priority. If the message does not contain user specified content, the message agent stores the message in a conventional manner.
The user may input user specified content. The user specified content is received by the message agent. The message agent then converts the user specified content into a format of each type of message that may be scanned. The rules for handling each type of message are received from the user. The rules may be received in the following manner. The message agent receives a type of message to handle from the user. The message agent then prompts the user for a message handling rule and receives a rule for handling that type of message from the user.

Message forwarding of multiple types of messages based upon a criteria


The present invention relates to a method for mid-span branching of optical fiber cable which makes the mid-span branching possible without excess length of the optical fiber cable by forming main branching part and sub branching part for branched cores to be taken out from an existing main cable. It is an object of the present invention to provide a method for mid-span branching that provides marginal length of the existing main cable from which the branch cable branches off without the excess length of cables. To accomplish the above object of the present invention, there is provided a method for mid-span branching of optical fiber cable, comprising the steps of: setting an existing main cable and a branch cable; unsheathing main branched part and sub branched part of the main cable with preserved part; choosing and cutting branched cores with preserved cores remaining uncut; connecting the first branched cores to first branching cores to make temporary connection; pulling out the temporary connection to the sub branched part through the preserved part; and splicing the first branched cores and the first branching cores at the sub branched part, and splicing the second branched cores and second branching cores at the main branching part, second branching cores in the branch cable.

The present invention relates to a method for. mid-span branching of optical fiber cable network and more specifically to a method for mid-span branching of optical fiber cable which makes the mid-span branching possible without excess length of the optical fiber cable.
In general, optical fiber cables are installed in the networks of loop distribution, star distribution, or other distribution in consideration of economy and reliability of installation, and flexibility to quantitative change of and diversification of service.
By the loop distribution, as shown in FIG. 1A, the excess length of cables for mid-span branching is ensured beforehand in the manholes or on the poles 1, 2, 3, 4, 5, 6 which are, when the cables are initially installed, the anticipated points for branching. When the demand for the cores arises in the middle of service, branch cable is installed from the point of demand for the cores to the point of the loop distribution network for branching. Also, the branched cores of existing main cable in the network are spliced with the branching cores of the branch cable. Thus the network is of the loop-shape.
By the star distribution, as shown in FIG. 1B, the excess length of cables for mid-span branching is ensured beforehand in the manholes or on the poles 1, 2, 3, 4 which are, when the cables are initially installed, the anticipated points for branching. When the demand for the cores arises in the middle of service, branch cable is installed from the point of demand for the cores to the point of the star distribution network for branching. Also, the branched cores of existing main cable in the network are spliced with the branching cores of the branch cable. Thus the network is of the star-shape.
In branching of the optical fiber network described above, there have been provided methods for access-point branching by which branch cable is branched from the network at the point of access to the point of demand for the cores, and for mid-span branching by which branch cable is branched from the network, not at the point of access but at the mid-point of the network cable, to the point of demand for the cores.
In the method for mid-span branching, to avoid tension on the branching part, the excess length of the cables must be ensured for the minimum length of core of the optical fiber cable for the distance from the branching part to branching device, response to demand for re-access in the case of access-failure, malfunction, operational needs, and etc.
Because the prior arts need the excess length of cables as mentioned above, as shown in FIG. 2A, existing main cable 20 is pulled out from the conduit line 10 in the manhole 1 that is the position of mid-span branching, supported by supporter 30, and the slack loop of cable is assumed. Thus the excess length of the cables is ensured. The cores of the existing main cable 20 and the branch cable 40 are placed in the manhole 1.
As shown in FIG. 2B, the excess length of cables is fastened on the prop 31. Branching part 100 is formed by unsheathing predetermined portions of the loop for the cores of the cable to be taken out. Splice closure is installed at the unsheathed part.
In the case where the excess length of cables either can""t be or isn""t ensured in the manhole that is supposed to be the position of mid-span branching, as shown in FIG. 3, branch cable 40 is installed in the manhole 2 adjacent to the manhole 1 which is supposed to be the position of mid-span branching. The splice closure 50 is disjointed and the branch cable 40 is branched from the existing main cable 20, which is the access point branching method. Herein, for the mid-span branching to be completed, at most 500 meters of the branch cable is necessary.
Due to the long excess length of the cable for mid-span branching of prior arts described above, however, there are several problems listed below on usability, workability, and economy in efficient installation of the network.
Firstly, the excess length of cables is generally endured excessively because workers cannot decide exact points of branching when initial installation of the cables. Also, there are the cases when extra branch cables are installed to the access point of the loop/star distribution network because of the lack of the excess length of cables at the points of mid-span branching. Thus, the cost of installation or branching is excessively high.
Secondly, in the case of decision of the incorrect points for branching, ensured excess length of cables must be pulled to the points of mid-span branching or extra branch cables are installed to the points where the excess length of cables has been already endured. Thus the cost for extra installation occurs.
Thirdly, the ensured excess length of cables is of such length that preserved cores are accommodated in the splice closure, which may reduce workability.
Fourthly, unsheathing the slack loop of excess length of the cables takes long time.
Fifthly, the splice closure must have the room for, at least, the allowable radius of curvature of unit of cores with hardened Polybutadien Terephthalate (PBTP), unit of cores having preserved cores. So it is hard to put the unit of cores in order in the splice closure, which reduces reliability of cores of the preserved unit having the cores in operation.
Sixthly, the cables in the manhole cannot be put in order due to the ensured excess length of cables, which may reduce workability. The ensured excess length of cables on the poles also reduces the reliability and a fine view.
It is, therefore, an object of the present invention to provide a method for mid-span branching that provides marginal length of the existing main cable from which the branch cable branches off without the excess length of cables that forms a slack loop.
To accomplish the above object of the present invention, there is provided a method for mid-span branching of optical fiber cable without excess length of cables, comprising the steps of: setting an existing main cable and a branch cable; unsheathing main branched part and sub branched part of the main cable with preserved part formed between the main branched part and the sub branched part; choosing and cutting branched cores with preserved cores remaining uncut at the main branched part, the branched cores having first branched cores and second branched cores; connecting the first branched cores to first branching cores to make temporary connection, first branching cores in the branch cable; pulling out the temporary connection to the sub branched part through the preserved part; and splicing the first branched cores and the first branching cores at the sub branched part, and splicing the second branched cores and second branching cores at the main branching part, second branching cores in the branch cable.
In accordance with another aspect of the present invention, there is provided a method for mid-span branching of optical fiber cable, comprising the steps of: setting an existing main cable and a branch cable; unsheathing main branched part and sub branched part of the main cable with preserved part formed between the main branched part and the sub branched part; choosing and cutting branched cores with preserved cores remaining uncut at the main branched part, the branched cores having first branched cores and second branched cores; pulling out the first branched cores to the sub branched part through the preserved part; setting hollow member above the preserved part; pulling out first branching cores to the sub branched part through the hollow member, first branching cores in the branch cable; and splicing the first branched cores and the first branching cores at the sub branched part and splicing the second branched cores and second branching cores at the main branched part, second branching cores in the branch cable.
Also, in accordance with another aspect of the present invention, there is provided a method for mid-span branching of optical fiber cable, comprising the steps of: setting an existing main cable and a branch cable; unsheathing main branched part and sub branched part of the main cable, preserved part formed between the main branched part and the sub branched part; choosing and cutting branched cores with preserved cores remaining uncut at the main branched part, the branched cores having first branched cores and second branched cores; pulling out the first branched cores to the sub branched part through the preserved part; aligning end of the branch cable with end of the sub branched part; unsheathing main branching part and sub branching part of the branch cable with second preserved part formed between the main branching part and the sub branching part, main branching part and sub branching part of the branch cable corresponding respectively to the main branched part and the sub branched part of the main cable; pulling out second branching cores to the main branching part through the second preserved part, second branching cores in the branch cable; and splicing the first branched cores and first branching cores at the sub branched part and splicing the second branched cores and the second branching cores at the main branched part, first branching cores in the branch cable.

Method for mid-span branching of optical fiber cable


A system for mounting a lead assembly on a construction machine including a set of leads having a driver that is slidably mounted to the set of leads. The system further includes at least one lifting component for engaging the driver and moving the driver on the leads, and a pivotable mounting assembly mounted to the set of leads and adapted to adjust the position of the set of leads. Moreover there is a quick connecting portion adapted to engage the pivotable mounting assembly and the construction machine so as to allow for the quick engagement and disengagement of the construction machine from the set of leads.

Different types of construction conditions often require different types of equipment to be able to accurately and properly prepare foundations for future construction. Typically this type of construction may be achieved by pile driving, screw piling, drilling or by auger for example. In general foundations are often pilings that are used to support the structure being built. The type of piling required and the depth that the piling must be driven into the earth will also depend on the type of structure being built. With large structures, the pilings by necessity are large to provide sufficient support and have to be driven through the earth and underlying bedrock with a great deal of force. Traditionally in the construction industry, the pile driving of these large pilings has been performed by mounting a pile driver to a crane. This requires the costly and time consuming transportation of a crane to the construction site as well as the engagement of a qualified crane operator. Typical pile drivers include a hammer mounted to a frame or leads and have a ram that engages the pile with a downward force. For accurate driving of the pilings and avoidance of damage to the frame, there has to be a proper alignment of the leads relative the piling being driven. In other construction operations leads are often mounted to a crane so as to operate a drilling system, auger system or screw pile.
Prior art lead attachment mechanisms for pile drivers and the like have been devised to address some of the noted problems. For example United States Pub. Patent Appln No. 2005/0247461 was filed on May 6, 2004 by Cardoso and relates to a construction equipment attachment for driving an object, such as a timber piles, steel piles, pipe piles, steel sheet piles, h-beam and the like. The attachment includes a hammer slidably coupled to a lead, a lead mounting assembly and a hydraulic actuator coupled to the lead and the lead mounting assembly. The hydraulic actuator is adapted to control the orientation of the lead relative to the lead mounting assembly.
U.S. Pat. No. 6,715,564 which issued on Apr. 6, 2004 to Buckland relates to a drilling rig having a boom supporting a leader. The leader is pivotally attached to the boom and is moveable between a generally upright orientation and a generally horizontal orientation for the purposes of transportation by a vehicle. Hydraulic rams cause linear movement of the leader relative to the boom while the hydraulic ram causes tilting of the boom about a generally horizontally axis.
U.S. Pub. Patent No. 2006/0213676 which was filed on Mar. 7, 2006 for Jinnings et al, relates to a pile driver including an apparatus for allowing relative movement between a hammer and a boom of an excavator. The apparatus includes a mounting plate mounted to the boom that inter-fits with and is slidable with respect to a frame rail mounted to the hammer. In operation, the hammer is placed on top of a pile and, as the pile is driven downwardly, the hammer follows the pile down.
U.S. Pat. No. 5,375,664 which issued on Dec. 27, 1994 to McDowell et al relates to a hydraulic pile driver including a backhoe, a lead, a vibratory hydraulic hammer, and a winch, for driving pin pile or needle pile into the ground. The lead is limited in height, as is the backhoe in size, so that the pile driver can be used within the interiors of many building structures. The vibratory hydraulic hammer operates at a rate greater than 400 blows per minute and generates a force greater than 100 foot-pounds.
U.S. Pat. No. 5,551,519 which issued on Sep. 3, 1996 to Pach relates to a device for driving piles, preferably poles, into a foundation. The device for ramming pole foundations limits idle times between ramming operations and takes the form of a self-propelled rail-road or dual purpose vehicle that can be driven on rails laid on a ballast or over a road surface and the vehicle can swivel over 360° with a top in relation to the undercarriage, with an operation cabin, a counter weight and a hoisting arm being arranged on the noted top, with a turning and tilting unit being provided at a free end of the hoisting arm, with a leader having a rammer mounted in a guiding unit, wherein, in the working position, the leader stands vertically and the top is turned 90° with respect to the direction of the rails and, when the ramming operation is finished, the leader is centrally clamped by the guiding unit and is turned 90° by the turning and tilting unit, with the leader and rammer then being shouldered by the hoisting arm and the device can thus be driven to the next ramming position.
U.S. Pat. No. 5,944,452 which issued on Aug. 31, 1999 to Reinert, Sr. relates to a heavy duty mobile metal foundation installation apparatus and method which includes a push-it carriage movably supported through controllable positioning to push a metal foundation into the ground by hydraulic cylinders pushing against a header frame held and secured in adjustable positions on a heavy duty mobile push-it tower. The heavy duty mobile push-it tower and metal foundation holder and push-it carriage mounted on the heavy duty tower are attached to a track roller frame tractor structure. The push-it tower is attached to the track roller frame tractor structure by a hydraulically activated tractor boom arm, a pivot point on the tower, and a hydraulic cylinder for rotating and positioning the tower about the pivot attachment point.
Thus a system for mounting a lead attachment assembly which allows for the timely and cost effective mounting of a lead attachment assembly for the operation of a pile driver or the like to an excavator with the ability to adjust the alignment and the positioning of the lead assembly and therefore the pile driver for example is desirable.


Methods and apparatus are disclosed that enable a Home Agent to be dynamically assigned to a mobile node. A Mobility Agent supporting Mobile IP enables a mobile node to be registered with either the Mobility Agent or another “local” Home Agent, by receiving a registration request packet from the Mobile Node indicating that a key to be shared by the Mobile Node and an agent with which the Mobile Node is registering is requested. In addition, the agent with which the Mobile Node is registering (e.g., local Home Agent) may be assigned. For instance, a local Home Agent may be assigned if load balancing among multiple Home Agents is desired. A key to be shared by the Mobile Node and the agent with which the Mobile Node is registering is obtained. The key to be shared by the Mobile Node and the agent with which the Mobile Node is registering is then stored. A registration reply packet is then sent to the mobile node including the key to be shared by the Mobile Node and the agent with which the Mobile Node is registering. The mobile node may then re-register with the agent (e.g., local Home Agent) using the key.

1. Field of the Invention
The present invention relates to Mobile IP network technology. More particularly, the present invention relates to enabling dynamic Home Agent assignment in Mobile IP.
2. Description of the Related Art
Mobile IP is a protocol which allows laptop computers or other mobile computer units (referred to as "Mobile Nodes" herein) to roam between various sub-networks at various locations—while maintaining internet and/or WAN connectivity. Without Mobile IP or related protocol, a Mobile Node would be unable to stay connected while roaming through various sub-networks. This is because the IP address required for any node to communicate over the internet is location specific. Each IP address has a field that specifies the particular sub-network on which the node resides. If a user desires to take a computer which is normally attached to one node and roam with it so that it passes through different sub-networks, it cannot use its home base IP address. As a result, a business person traveling across the country cannot merely roam with his or her computer across geographically disparate network segments or wireless nodes while remaining connected over the internet. This is not an acceptable state-of-affairs in the age of portable computational devices.
To address this problem, the Mobile IP protocol has been developed and implemented. An implementation of Mobile IP is described in RFC 2002 of the IP Routing for Wireless/Mobile Hosts Working Group, C. Perkins, Ed., October 1996. Mobile IP is also described in the text "Mobile IP Unplugged" by J. Solomon, Prentice Hall. Both of these references are incorporated herein by reference in their entireties and for all purposes.
The Mobile IP process and environment are illustrated in FIG. 1. As shown there, a Mobile IP environment 2 includes the internet (or a WAN) 4 over which a Mobile Node 6 can communicate remotely via mediation by a Home Agent 8 and a Foreign Agent 10. Typically, the Home Agent and Foreign Agent are routers or other network connection devices performing appropriate Mobile IP functions as implemented by software, hardware, and/or firmware. A particular Mobile Node (e.g., a laptop computer) plugged into its home network segment connects with the internet through its designated Home Agent. When the Mobile Node roams, it communicates via the internet through an available Foreign Agent. Presumably, there are many Foreign Agents available at geographically disparate locations to allow wide spread internet connection via the Mobile IP protocol. Note that it is also possible for the Mobile Node to register directly with its Home Agent.
As shown in FIG. 1, Mobile Node 6 normally resides on (or is "based at") a network segment 12 which allows its network entities to communicate over the internet 4 through Home Agent 8 (an appropriately configured router denoted R2). Note that Home Agent 8 need not directly connect to the internet. For example, as shown in FIG. 1, it may be connected through another router (a router R1 in this case). Router R1 may, in turn, connect one or more other routers (e.g., a router R3) with the internet.
Now, suppose that Mobile Node 6 is removed from its home base network segment 12 and roams to a remote network segment 14. Network segment 14 may include various other nodes such as a PC 16. The nodes on network segment 14 communicate with the internet through a router which doubles as Foreign Agent 10. Mobile Node 6 may identify Foreign Agent 10 through various agent solicitations and agent advertisements which form part of the Mobile IP protocol. When Mobile Node 6 engages with network segment 14, it composes a registration request for the Home Agent 8 to bind the Mobile Node's current location with its home location. Foreign Agent 10 then relays the registration request to Home Agent 8 (as indicated by the dotted line "Registration"). During the registration process, the Home Agent and the Mobile Node 6 may then negotiate the conditions of the Mobile Node's attachment to Foreign Agent 10. For example, the Mobile Node 6 may request a registration lifetime of 5 hours, but the Home Agent 8 may grant only a 3 hour period. Therefore, the attachment may be limited to a period of time. When the negotiation is successfully completed, Home Agent 8 updates an internal "mobility binding table" which links the Mobile Node's current location via its care-of address (e.g., a collocated care-of address or the Foreign Agent's IP address) to the identity (e.g., home address) of Mobile Node 6. Further, if the Mobile Node 6 registered via a Foreign Agent, the Foreign Agent 10 updates an internal "visitor table" which specifies the Mobile Node address, Home Agent address, etc. In effect, the Mobile Node's home base IP address (associated with segment 12) has been binded to the care-of address such as the Foreign Agent's IP address (associated with segment 14).
Now, suppose that Mobile Node 6 wishes to send a message to a Correspondent Node 18 from its new location. An output message from the Mobile Node is then packetized and forwarded through Foreign Agent 10 over the internet 4 to Correspondent Node 18 (as indicated by the dotted line "packet from MN") according to a standard Internet Protocol. If Correspondent Node 18 wishes to send a message to Mobile Node—whether in reply to a message from the Mobile Node or for any other reason—it addresses that message to the IP address of Mobile Node 6 on sub-network 12. The packets of that message are then forwarded over the internet 4 and to router R1 and ultimately to Home Agent 8 as indicated by the dotted line ("packet to MN(1)"). From its mobility binding table, Home Agent 8 recognizes that Mobile Node 6 is no longer attached to network segment 12. It then encapsulates the packets from Correspondent Node 18 (which are addressed to Mobile Node 6 on network segment 12) according to a Mobile IP protocol and forwards these encapsulated packets to a "care of" address for Mobile Node 6 as shown by the dotted line ("packet to MN(2)"). The care-of address may be, for example, the IP address of Foreign Agent 10. Foreign Agent 10 then strips the encapsulation and forwards the message to Mobile Node 6 on sub-network 14. The packet forwarding mechanism implemented by the Home and Foreign Agents is often referred to as "tunneling."
As indicated above, each mobile node has a designated Home Agent. As specified in RFC 2002, a mobile node is pre-configured with information identifying its Home Agent. In addition, both the mobile node and its Home Agent are also pre-configured with a shared key and Security Parameter Index (SPI) for the shared key, commonly referred to as a security association. Similarly, each Home Agent is pre-configured with information identifying mobile nodes that it supports as well as the corresponding security associations. In this manner, a mobile node is "anchored" to a specific Home Agent to enable it to subsequently register with that Home Agent and receive messages via that Home Agent from Correspondent Nodes.
There are various disadvantages associated with the pre-assignment of a specific Home Agent to a mobile node. For instance, the mobile node may be a cell phone that has been activated on the West Coast, and will therefore be assigned a Home Agent on the West Coast. However, the user of that cell phone may wish to travel to the East Coast. When the mobile node roams to a Foreign Agent, that Foreign Agent will therefore be on the East Coast. As a result, the communication path between the mobile node, located on the East Coast, and its pre-assigned Home Agent, located on the West Coast, is unnecessarily long.
Another disadvantage with pre-assignment of a specific Home Agent to each mobile node is the non-dynamic nature of such pre-assignments. As described above, each mobile node and Home Agent must be pre-configured with specific information anchoring each mobile node to a specific Home Agent. This requires the configuration information to be known ahead of time as well as manually configured for each device. Thus, even when there are multiple Home Agents on a single home network, since each Home Agent must be statically configured, it is impossible to dynamically distribute registration requests among the Home Agents. It would therefore be beneficial if a "lightly loaded" Home Agent could share the load of a "heavily loaded" Home Agent.
In view of the above, it would be desirable if a Home Agent could be dynamically assigned in Mobile IP.

Methods and apparatus for dynamic home agent assignment in mobile IP


An apparatus and method for powering headphone electronics over a standard audio signal cable without interfering with the normal audio transmission or playback of transmitted audio signals. A software application resides on a cell/smart phone or other mobile device that combines the nominal audio output of such a mobile device, like music or spoken word, with a high frequency audio signal to produce a dual component signal. The high frequency component is decoded and rectified outside of the mobile device, either in a connector or on the structure of the headphones themselves, to produce a direct current (“DC”) that powers the headphones. The music or other audible signal component transferred over the audio cable is decoded in parallel and sent to the headphone speakers for normal playback. The invention provides an alternative power source to headphone electronics such as active noise cancelling headphones over the audio cable.

Noise cancelling and white noise generating headphones have become popular in the last 10 years for actively controlling the output of headphone sound. In particular, noisy environments, such as airplane travel environments, demand active control over audio output in headphones in order to dynamically adjust to varied user environments. However, actively controlling headphone output requires electronics powered within the headphone system. Currently, such electronics cannot be powered by the audio signal that is received by the headphones without unacceptable degradation of the audio signal so such headphones incorporate either a separate power supply, necessitating a separate power wire, or a good set of batteries.
Batteries in headphones add weight and either must be replaced with new batteries or replaced with freshly recharged batteries. Some headphones have attempted to reduce the weight of battery load by using smaller batteries, but this necessitates more frequent chargings, and less available power. And while having a separate power line for headphones is possible, the additional wire is usually unacceptable to the user.
In concert with the advent of powered and active headphones, cell phones and mobile devices, like the iPad and iPod, have become much more powerful, both computationally and in battery strength. Applications can now be written for these platforms in a matter of days with reliable outcomes. Moreover, the dominant music source for music entertainment today is a user's mobile phone, or similar mobile device. Coincidentally, the protocol or format for outputting music through an audio port in a phone or mobile device is standardized. In other words, even though some variation in diameter still exits for mobile device audio ports, the pin configuration and electrical design specifications are universally accepted.
Hence, what is needed is a system and method for using the standardized audio output port in mobile electronics, such as a cell phone, to transfer power to a pair of audio headphones without interfering with the primary purpose of those headphones—for faithful reproduction of music and other audio signals coming from the mobile device.

Headphone power system using high frequency signal conversion


This invention is a method of memory saving in compressed video decoding. For each group of pictures the method determines whether less than the maximum number N reference frames are needed for decoding. If so, then a memory is configuring for the needed number M reference frames less than N. If not, the memory is configured for N reference frames. The group of pictures is decoding the group of pictures using the configured number of reference frames.

A typical H.264 universal decoder implementation needs a high dual data rate (DDR) memory footprint. This is primarily due to the large amount of memory needed for storing reference frames and co-located macroblock information required for decoding bidirectionally predicted (B) frame macroblocks. This is a big problem especially for High Definition (HD) decoding due to the large frame size.
A H.264 decoder typically requires multiple frames to be stored in a decoded picture buffer (DPB) as reference frames. The decoder may require up to N frames depending on the resolution. In addition many frames worth of macroblock information have to be stored in the DDR memory. These are co-located macroblock information needed to decode B macroblocks. This macroblock information typically needs to store 208 bytes for each macroblock.
According to the H.264 standard, five current decoded frames are need as reference frames for HD of 1920 pixels by 1080 pixels. The amount of memory needed for padded reference buffers and co-located macroblock information buffers is (4+1)*[((1920+64)*(1088+96)*1.5)+(8160*208)] or 24.9 Mbytes. Differing numbers of frame buffers is applicable for other pixel size resolutions. For example, for D1 resolution (720 pixels by 480 pixels) the maximum number of frame buffers is six. For CIF resolution (352 pixels by 288 pixels) the maximum number of frame buffers is 16.
This is a huge amount of memory. Many systems will not have this much free memory. This problem also becomes more severe in multichannel systems, where this large amount of memory needs to be allocated for each channel. This will demand a huge amount of DDR. Typical H264 decoder implementations need this memory regardless of the application or the type of streams/group of pictures (GOP) structures used.

Method for low memory footprint compressed video decoding