A cam bearing lubrication structure for an internal combustion engine includes a cylinder head having a cam bearing region, a plug hole for an ignition plug and a plug tube fitted liquid-tight therein. The cam bearing lubrication structure includes an outer periphery oil path bypassing along an outer peripheral face of the plug tube, a main lubricating oil passage extending through the plug hole and formed to connect to the outer periphery oil path and a guide passage formed in and through the cam bearing region to connect a sliding face of the cam bearing region from the outer periphery oil path and supplying lubricating oil to a sliding face of the cam bearing region and a camshaft. In addition, a lubricating oil supplying structure is provided for a valve apparatus for further increasing the oil supply amount to achieve a further increase in the speed of the engine.

1. Field of the Invention
The present invention relates to a lubrication structure to a camshaft of a valve mechanism of an internal combustion engine and to a lubricating oil supplying structure for a valve apparatus of an internal combustion engine.
2. Description of Background Art
In a lubrication path of lubricating oil for camshafts wherein intake and exhaust cams for opening and closing intake and exhaust valves of a valve mechanism of an internal combustion engine are provided, a main lubricating oil passage is provided in a cylinder head. The main lubricating oil passage extends in parallel to and is positioned between an intake camshaft and an exhaust camshaft. Lubricating oil is supplied from an oil pump to the main lubricating oil passage. Since the main lubricating oil passage is disposed between the intake camshaft and the exhaust camshaft, a plug hole in which an ignition plug is fitted is formed for each cylinder between the intake camshaft and the exhaust camshaft and crosses with and divides the main lubricating oil passage. Therefore, an annular tubular member is inserted in the plug hole and mounted liquid-tight in the plug hole above and below the main lubricating oil passage to form a bypassing oil passage on an outer periphery of the plug tube such that the main lubricating oil passage is connected to the oil passage.
Further, a guide passage is formed on the downstream side of the main lubricating oil passage through a communication passage and an extension passage and extends in an upward and downward direction toward a bearing region positioned at an axial end of each camshaft so as to lubricate the bearing region. In addition, although at least a plurality of bearing regions for each camshaft are provided at different locations, if it is tried to provide an oil passage such as a communication passage, an extension passage or a guide passage formed independently of each other at each bearing region, then it is necessary to consider the arrangement space for the oil passages or the workability of a cylinder head. Therefore, there is the possibility that this may cause an increase in the size of the cylinder head. Thus, it is desired to provide a cam bearing lubrication structure for an internal combustion engine that is easy to service while oil passages to different locations are reduced in length. See, for example, Japanese Patent No. 3198689.
As a lubricating oil supplying structure for a valve apparatus of an internal combustion engine, a lubricating oil supplying structure is available wherein a lubricating oil path along which oil is discharged toward a contact region between an adjust bolt and a valve stem from among sliding regions of a rocker arm is provided in the rocker arm. Conventionally, one of such lubricating oil supplying structures for a valve apparatus is disclosed, for example, in Japanese Patent No. 4220415. In the lubricating oil supplying structure for the valve apparatus disclosed in Japanese Patent No. 4220415, a lubrication passage is provided in a rocker arm shaft such that oil is supplied to a sliding face between the rocker arm shaft and a rocker arm from the lubrication passage. The oil supplied from the sliding face is injected from a lubricating oil passage provided in the rocker arm shaft to a contact region between an adjust bolt and a valve stem.
In Japanese Patent No. 4220415, the amount of oil supplied to an ejection port of each rocker arm when oil is branched and shunted to the rocker arm shaft decreases. Further, the lubrication oil to the ejection hole of each rocker arm becomes long. In addition, since part of the oil supplied to the sliding face between the adjust bolt and the valve stem is injected, there is a limit to the assurance of the supply amount of oil. Therefore, where a further fuel supply amount is demanded from an increase in the speed of rotation of an engine, it is necessary to improve the oiling system.
The present invention solves such a subject of the prior art, and it is an object of an embodiment of the present invention to provide a cam bearing lubrication structure wherein the space of an oil passage is prevented from increasing to miniaturize a cylinder head. Thus, miniaturization of an internal combustion engine is achieved while oil passages to bearings for intake and exhaust camshafts are reduced in length. In addition, servicing is facilitated and the fabrication cost is reduced.
In order to attain the object described above, according to an embodiment of the present invention, a cam bearing lubrication structure for an internal combustion engine includes a cylinder head having a cam bearing region on which a camshaft is supported for rotation, a plug hole in which an ignition plug supported on the cylinder head is accommodated such that an end thereof is exposed to a combustion chamber, and a plug tube having a cylindrical shape and fitted liquid-tight at upper and lower end portions thereof in the plug hole to separate the inside of the cylinder head and the plug hole from each other. The cam bearing lubrication structure for the internal combustion engine further includes an outer periphery oil path formed liquid-tight at the upper and lower end portions of the plug tube with respect to the plug hole and bypassing along an outer peripheral face of the plug tube. A main lubricating oil passage extends through the plug hole in the cylinder head and is formed so as to connect to the outer periphery oil path. A guide passage is formed in and through the cam bearing region so as to connect a sliding face of the cam bearing region from the outer periphery oil path and supplying lubricating oil to a sliding face of the cam bearing region and the camshaft.
According to an embodiment of the present invention, an outlet of the guide passage to the cam bearing region is provided on a semicircular face at the plug hole side with respect to the center of rotation of the camshaft.
According to an embodiment of the present invention, the cam bearing region is configured from a plurality of divisional halves. A threaded hole, provided between the camshaft and the plug hole and used for a fastening member which couples the divisional half, is formed such that the guide passage extends therethrough. The threaded hole is sealed by the fastening member.
According to an embodiment of the present invention, the cam bearing region is configured from divisional upper and lower halves with the guide passage being formed by working in such a manner so as to be inclined with respect to a mating plane of the upper and lower halves toward the plug hole.
According to an embodiment of the present invention, the cylinder head has a plurality of camshafts provided thereon sandwiching the plug hole therebetween with a pair of guide passages being formed for each of the cam bearing regions.
According to an embodiment of the present invention, a protuberance is provided at a position below an upper end face of the plug tube and between the position of an inlet of the guide passage in such a manner as to protrude annularly from an outer periphery of the plug tube.
According to an embodiment of the present invention, a holder unit is disposed at an upper end face of the upper end portion of the plug tube so as to closely contact with the upper end face to fix the plug tube from coming off from above with an annular seal member interposed therebetween.
According to an embodiment of the present invention, the cam bearing region is configured from upper and lower halves formed as upper and lower divisional portions, and the holder unit is configured integrally with the upper half.
According to an embodiment of the present invention, the upper and lower end portions of the plug tube are fitted liquid-tight in the plug hole to form the outer periphery oil path. The guide passage is formed from the outer periphery oil path in such a manner so as to connect the cam bearing region. Consequently, oil is directly supplied from the outer periphery oil path to the cam bearing region through the guide passage. Thus, the oil passage to the cam bearing region can be reduced in length, and as a result, it is possible to reduce the size of the cylinder head to achieve miniaturization of the internal combustion engine.
According to an embodiment of the present invention, the outlet of the guide passage from the outer periphery oil path is provided on the semicircular face of the cam bearing region at the plug hole side. Therefore, it is possible to reduce the length of the guide passage to the utmost and reduce the time for oil supply to the cam bearing region after the internal combustion engine is started up.
According to an embodiment of the present invention, the guide passage is formed so as to extend through the threaded hole between the camshaft and the plug hole, and the guide passage is sealed by the fastening member. Therefore, in comparison with an alternative case in which the guide passage is formed bypassing the threaded hole, the guide passage can be connected in the shortest length, and it is possible to reduce the working cost.
According to an embodiment of the present invention, the cam bearing is formed from upper and lower halves, and when the guide passage is formed by working from the bearing formed as the two divisional upper and lower portions, by working the cam bearing region obliquely, the working procedure can be carried out readily.
According to an embodiment of the present invention, the supply of oil to the cam bearing regions at the opposite sides sandwiching the plug hole can be carried out from the outer periphery oil path of the common plug hole. Thus, the oil supply path can be simplified.
According to an embodiment of the present invention, the annular protuberance is provided on the outer periphery of the plug tube at a position above the inlet of the guide passage. Therefore, the flow of oil, which has flowed from below into and flowed upwardly in the outer periphery oil path into the inlet of the guide passage, can be promoted to facilitate the supply of the oil into the guide passage.
According to an embodiment of the present invention, the upper end face of the plug tube, which configures part of the outer periphery oil path, is fixed from coming off from above by the holder unit through the annular seal member. Therefore, the plug tube which is acted upon by hydraulic pressure and is likely to come off can be suppressed with certainty.
According to an embodiment of the present invention, the cam bearing region is configured from the upper and lower halves formed as upward and downward divisional portions. When the holder unit is provided, by forming the holder unit integrally with the upper half of the cam bearing region a reduction in the number of parts can be anticipated. Thus, a reduction in the fabrication cost can be anticipated.
In addition, it is an object of an embodiment of the present invention to provide a lubricating oil supplying structure for a valve apparatus of an internal combustion engine wherein the oil supplying amount is further increased in accordance with an increase in the speed of rotation of the engine.
According to an embodiment of the present invention, a lubricating oil supplying structure for a valve apparatus of an internal combustion engine having a cylinder head which supports camshafts for rotation thereon includes, for each pair of engine valves for intake and exhaust, rocker arms supported at pivotally supporting base portions thereof for rocking motion by rocker arm shafts. The rocker arms are interposed between valve stem axial ends of the engine valves and cam faces of the camshafts to allow contact therebetween. Pressing force from the cam faces acting upon the rocking arms is transmitted to the valve stems to open and close the engine valves. The lubricating oil supplying structure for the valve apparatus includes an oil passage provided in the cylinder head along an axial direction of the camshafts and formed from a single passage at a position lower than the rocker arm shafts between the intake and exhaust valves. A pair of oil injection oil paths is formed so as to be directed independently for the individual rocker arms from the oil passage.
According to an embodiment of the present invention, valve stem pressing portions are formed at locations at which the rocker arms contact with the valve stems side in a continuous relationship to lower faces of the rocking arms of the rocker arms. The direction in which the oil injection oil paths are directed to the rocker arms is directed toward the lower faces of the rocking arms.
According to an embodiment of the present invention, the lower face of the rocker arm is formed wherein a curved recessed portion is the lowest portion toward the valve stem pressing portion.
According to an embodiment of the present invention, clearance adjustment members for adjusting gaps between the valve stem axial ends and the rocker arms are formed exchangeably as separate members between the valve stems and the valve stem pressing portions of the rocker arms.
According to an embodiment of the present invention, the oil passage is provided in a protuberance protruding from a lower face of a connecting bottom wall which interconnects lower portions of a pair of support walls which are provided on the cylinder head and support the opposite axial ends of the rocker arm shaft.
According to an embodiment of the present invention, the camshafts are configured independently as an intake camshaft and an exhaust camshaft and disposed at a position above the rocker arms, and sliding portions between the rocker arms and the cam faces are provided on upper faces of the rocker arms.
According to an embodiment of the present invention, the rocker arm shafts are disposed between the intake and exhaust camshafts such that the sliding portions of the rocker arms are disposed so as to be directed outwardly relative to each other. The rocker arm shafts are disposed at heightwise positions different from each other with reference to an extension line of the cylinder center axis. The oil passage is disposed in an offset relationship to the rocker arm shaft disposed at the higher position.
According to an embodiment of the present invention, a cylinder of the internal combustion engine is mounted in an inclined relationship with respect to the vertical direction such that, in a state in which the internal combustion engine is mounted on a vehicle. A tip end of the rocker arm disposed on one of the two rocker arm shafts, which is disposed at the higher position, is directed obliquely upwardly while a tip end of the rocker arm disposed on the other one of the two rocker arm shafts, which is disposed at the lower position, is directed obliquely downwardly. The oil injection oil path is formed such that the injection direction from the oil injection oil path to the valve stem pressing portion of that one of the rocker arms in which the oil passage is disposed in an offset relationship is directed to the tip end of the rocker arm. The oil injection oil path is formed such that the injection direction from the oil injection oil path to the valve stem pressing portion of the other rocker arm is directed to the pivotally supporting base portion of the rocker arm.
According to an embodiment of the present invention, the oil passage is formed from the single passage extending along the camshafts at a position lower than the rocker arm shafts between the intake and exhaust valves, and the paired oil injection oil paths are provided so as to be directed independently of the individual rocker arms from the oil passage. Therefore, while the path for the injection oil is reduced in length, oil is supplied from the single oil passage directly to the rocker arms, and oil to be supplied to the oil injection oil paths is supplied from the common oil passage. Consequently, it is possible to facilitate assurance of the amount of oil. Further, since the oil injection oil paths are provided from the single oil passage, space saving of the lubricating oil supplying structure can be anticipated. Thus, the fabrication cost can be reduced.
According to an embodiment of the present invention, the lower faces of the rocking arms of the rocker arms are formed in a continuous relationship to the valve stem pressing portions. Thus, the direction in which the oil injection oil paths are directed to the rocker arms is directed toward the lower faces of the rocking arms. Therefore, even if part of the injected oil does not directly reach the valve stem pressing portions, it flows along the lower faces of the rocking arms and is supplied to the valve stem pressing portions. Consequently, the oil supplying amount to the valve stem pressing portions can be increased.
According to an embodiment of the present invention, the lower face of the rocker arm is formed as a curved recessed portion which is the lowest portion toward the valve stem pressing portion. Therefore, oil sticking to the lower face can positively flow to the sliding portion side between the valve stem pressing portion and the valve stem axial end to collect the oil.
According to an embodiment of the present invention, the clearance adjustment members are formed as separate members between the valve stem pressing portions of the rocker arms and the valve stem axial ends. Therefore, the necessity for such a screw adjustment mechanism disposed at a tip end of a rocker arm as in a conventional technology is eliminated. Further, since the sliding faces of the valve stem pressing portions are configured from curved faces, it becomes possible to supply oil flowing along the lower faces of the rocker arms with certainty to the sliding faces of the valve stem pressing portions.
According to an embodiment of the present invention, the oil passage is provided in the connecting bottom wall of the paired support walls which support the opposite axial ends of the rocker arm shaft and this is provided in the protuberance protruding from the lower face. Therefore, the oil passage can be provided in the cylinder head. Thus, an increase in the size of the cylinder head in the heightwise direction can be suppressed.
According to an embodiment of the present invention, the sliding portions are provided on the upper faces of the rocker arms. Therefore, the injected oil can be supplied to the valve stem side end portions without being obstructed by cam lobes of the camshafts.
According to an embodiment of the present invention, where the intake and exhaust rocker arm shafts are disposed closely to each other, they are disposed differently from each other in the cylinder axial direction, and the oil passage is disposed in an offset relationship to the rocker arm shaft side disposed at the higher position. Therefore, the free space can be utilized effectively to compactly dispose the oil passage.
According to an embodiment of the present invention, the internal combustion engine is mounted on the vehicle such that the tip ends of the two rocker arms are directed obliquely upwardly and obliquely downwardly, and the oil injection oil path to the rocker arm disposed at the higher position is formed so as to be directed to the tip end of the rocker arm while the oil injection oil path to the rocker arm disposed at the lower position is formed so as to be directed to the pivotally supporting base portion of the rocker arm shaft. Therefore, even where it is difficult to direct an oil injection oil path directly to the tip end of the rocker arm, it is possible to allow oil to flow and be supplied to the tip end of the rocker arm from the pivotally supporting base portion of the rocker arm. Consequently, while a reduction of the length of the oil injection oil path is achieved, oil supply can be carried out with certainty.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Cam bearing lubrication structure for internal combustion engine


A catalyst monitoring system is provided for monitoring catalyst efficiency in a catalytic converter of a motor vehicle. The catalyst monitoring system includes a catalyst monitor receiving electrical signals indicative of oxygen in the exhaust gas from a first oxygen sensor positioned between the vehicle's engine and the catalytic converter and a second oxygen sensor positioned downstream from the catalytic converter. Each of these input signals are filtered in the catalyst monitor such that a particular range of frequencies that encapsulate information regarding catalyst efficiency are passed. The filtered signals are then used to establish an amplitude ratio between the downstream oxygen signal and the upstream oxygen signal, such that the algorithm output linearly correlates to catalyst efficiency of the catalytic converter. Digital signal filtering is preferably implemented using a finite impulse response bandpass filter, a full-wave rectifier, a low pass filter, a sampler and a signal normalizer. A means for detecting a stabilized output signal may optionally be used in conjunction with the catalyst monitor.

1. Field of the Invention
The present invention relates generally to catalyst monitoring in a motor vehicle and, more particularly, to a method and apparatus for monitoring catalyst efficiency in a catalytic converter based on frequency characteristics of the catalyst as measured by oxygen sensors.
2. Discussion
Catalytic converters are used to reduce major air pollutants, such as hydrocarbons (HC), carbon monoxide (CO) and oxides of nitrogen (NO.sub.x), contained in the exhaust gas from an internal combustion engine of a motor vehicle. Each converter contains catalysts that produce a heated chemical reaction that transforms noxious pollutants into less harmful carbon dioxide (CO.sub.2) and water (H.sub.2 O) vapors. The catalytic converter is integrated downstream from the vehicle's engine into the vehicle's exhaust system. The effectiveness of reducing pollutants by a catalytic converter is highly dependent on the temperature and total gas throughput which, in turn, depends on the operational states and conditions of the internal combustion engine. Over time, catalyst efficiency degrades and thus decreases the capacity of the converter to convert toxic material. Government environmental regulations require continued reductions in vehicle emissions as well as accurate monitoring of various components of the emission system.
Therefore, it would be desirable to provide a non-intrusive method for monitoring catalytic converter efficiencies that is not dependent on any special vehicle operating conditions. In this way, catalyst monitoring can be performed under steady-state and transient vehicle operating conditions. Catalyst monitoring should linearly correlate its algorithm output to catalyst efficiency. In addition, it should be performed with minimal processing requirements and no additional sensors or circuitry as provided by a typical motor vehicle.


A method detects anomalies in time series data by comparing universal features extracted from testing time series data with the universal features acquired from training time series data to determine a score. The universal features characterize trajectory components of the time series data and stochastic components of the time series data. Then, an anomaly is detected if the anomaly score is above a threshold.

Time series data can be generated and analyzed for a number of applications. For example, automatic equipment monitoring can avoid costly repairs. This can be clone by analyzing time series data acquired by sensors on or near the equipment to detect anomalies that may indicate that maintenance or repair of the equipment is needed.
As shown in FIGS. 1A and 1B for typical schochastic and multivariate time series data, most prior methods for detecting anomalies simply determine values outside of a normal operating range 101.
For examples, one method assumes that multivariate time series can be modeled locally as a vector autoregressive (AR) model, see Bay et al., "A Framework for Discovering Anomalous Regimes in Multivariate Time-Series Data with Local Models," Technical Report, Center for the Study of Language and Information, Stanford University, 2004. That method first learns a distribution of AR model parameters for each time window of the training data. During testing, for each time window, the AR Model parameters are estimated and the probability of these parameters are determined from the previously learned probability distribution. The distribution learned by that method uses a restrictive autoregressive assumption. That method works well time series data with a random stochastic components.
Most methods focus on a single type of time series data for a particular application. There are very few methods that attempt a more general solution to the problem of anomaly detection in time series data.
U.S. Pat. No. 7,716,011, "Strategies for identifying anomalies in time-series data," is a model-based approach that fits spline segments to time-series data, see FIG. 1C. That method computes changes in the spline parameters and uses L1 distances between the splines to detect anomalies, and L2 distances to measure normal operation. This method works well on time series with a smooth trajectory.

Method for detecting anomalies in a time series data with trajectory and stochastic components

Mitsubishi Electric Research Laboratories, Inc.


The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in the periplasm of gram negative bacteria and mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display.

1. Field of the Invention
The present invention relates generally to the field of protein engineering. More particularly, it concerns improved methods for the screening of combinatorial libraries of polypeptides to allow isolation of ligand binding polypeptides.
2. Description of Related Art
The isolation of polypeptides that either bind to ligands with high affinity and specificity or catalyze the enzymatic conversion of a reactant (substrate) into a desired product is a key process in biotechnology. Ligand-binding polypeptides, including proteins and enzymes with a desired substrate specificity can be isolated from large libraries of mutants, provided that a suitable screening method is available. Small protein libraries composed of 103–105 distinct mutants can be screened by first growing each clone separately and then using a conventional assay for detecting clones that exhibit specific binding. For example, individual clones expressing different protein mutants can be grown in microtiter well plates or separate colonies on semisolid media such as agar plates. To detect binding the cells are lysed to release the proteins and the lysates are transferred to nylon filters, which are then probed using radiolabeled or fluorescently labeled ligands (DeWildt et al. 2000). However, even with robotic automation and digital image systems for detecting binding in high density arrays, it is not feasible to screen large libraries consisting of tens of millions or billions of clones. The screening of libraries of that size is required for the de novo isolation of enzymes or protein binders that have affinities in the subnanomolar range.
The screening of very large protein libraries has been accomplished by a variety of techniques that rely on the display of proteins on the surface of viruses or cells (Ladner et al. 1993). The underlying premise of display technologies is that proteins engineered to be anchored on the external surface of biological particles (i.e., cells or viruses) are directly accessible for binding to ligands without the need for lysing the cells. Viruses or cells displaying proteins with affinity for a ligand can be isolated in a variety of ways including sequential adsorption/desorption form immobilized ligand, by magnetic separations or by flow cytometry (Ladner et al. 1993, U.S. Pat. No. 5,223,409, Ladner et al. 1998, U.S. Pat. No. 5,837,500, Georgiou et al. 1997, Shusta et al. 1999).
The most widely used display technology for protein library screening applications is phage display. Phage display is a well-established and powerful technique for the discovery of proteins that bind to specific ligands and for the engineering of binding affinity and specificity (Rodi and Makowski, 1999). In phage display, a gene of interest is fused in-frame to phage genes encoding surface-exposed proteins, most commonly pIII. The gene fusions are translated into chimeric proteins in which the two domains fold independently. Phage displaying a protein with binding affinity for a ligand can be readily enriched by selective adsorption onto immobilized ligand, a process known as "panning". The bound phage is desorbed from the surface, usually by acid elution, and amplified through infection of E. coli cells. Usually, 4–6 rounds of panning and amplification are sufficient to select for phage displaying specific polypeptides, even from very large libraries with diversities up to 1010. Several variations of phage display for the rapid enrichment of clones displaying tightly binding polypeptides have been developed (Duenas and Borrebaeck, 1994; Malmborg et al., 1996; Kjaer et al., 1998; Burioni et al., 1998; Levitan, 1998; Mutuberria et al., 1999; Johns et al., 2000).
One of the most significant applications of phage display technology has been the isolation of high affinity antibodies (Dall'Acqua and Carter, 1998; Hudson et al., 1998; Hoogenboom et al., 1998; Maynard and Georgiou, 2000). Very large and structurally diverse libraries of scFv or FAB fragments have been constructed and have been used successfully for the in vitro isolation of antibodies to a multitude of both synthetic and natural antigens (Griffiths et al., 1994; Vaughan et al., 1996; Sheets et al., 1998; Pini et al., 1998; de Haard et al., 1999; Knappik et al., 2000; Sblattero and Bradbury, 2000). Antibody fragments with improved affinity or specificity can be isolated from libraries in which a chosen antibody had been subjected to mutagenesis of either the CDRs or of the entire gene CDRs (Hawkins et al., 1992; Low et al., 1996; Thompson et al., 1996; Chowdhury and Pastan, 1999). Finally, the expression characteristics of scFv, notorious for their poor solubility, have also been improved by phage display of mutant libraries (Deng et al., 1994; Coia et al., 1997).
However, several spectacular successes notwithstanding, the screening of phage-displayed libraries can be complicated by a number of factors. First, phage display imposes minimal selection for proper expression in bacteria by virtue of the low expression levels of antibody fragment gene III fusion necessary to allow phage assembly and yet sustain cell growth (Krebber et al., 1996, 1997). As a result, the clones isolated after several rounds of panning are frequently difficult to produce on a preparative scale in E. coli. Second, although phage displayed proteins may bind a ligand, in some cases their un-fused soluble counterparts may not (Griep et al., 1999). Third, the isolation of ligand-binding proteins and more specifically antibodies having high binding affinities can be complicated by avidity effects by virtue of the need for gene III protein to be present at around 5 copies per virion to complete phage assembly. Even with systems that result in predominantly monovalent protein display, there is nearly always a small fraction of clones that contain multiple copies of the protein. Such clones bind to the immobilized surface more tightly and are enriched relative to monovalent phage with higher affinities (Deng et al., 1995; MacKenzie et al., 1996, 1998). Fourth, theoretical analysis aside (Levitan, 1998), panning is still a "black box" process in that the effects of experimental conditions, for example the stringency of washing steps to remove weakly or non-specifically bound phage, can only be determined by trial and error based on the final outcome of the experiment. Finally, even though pIII and to a lesser extent the other proteins of the phage coat are generally tolerant to the fusion of heterologous polypeptides, the need to be incorporated into the phage biogenesis process imposes biological constraints that can limit library diversity. Therefore, there is a great need in the art for techniques capable of overcoming these limitations.
Protein libraries have also been displayed on the surface of bacteria, fungi, or higher cells. Cell displayed libraries are typically screened by flow cytometry (Georgiou et al. 1997, Daugherty et al. 2000). However, just as in phage display, the protein has to be engineered for expression on the outer cell surface. This imposes several potential limitations. For example, the requirement for display of the protein on the surface of a cell imposes biological constraints that limit the diversity of the proteins and protein mutants that can be screened. Also, complex proteins consisting of several polypeptide chains cannot be readily displayed on the surface of bacteria, filamentous phages or yeast. As such, there is a great need in the art for technology which circumvents all the above limitations and provides an entirety novel means for the screening of very large polypeptide libraries.

This patent is subject to a terminal disclaimer.

Combinatorial protein library screening by periplasmic expression

The Board of Regents of The University of Texas System


The present invention provides a piperidine compound represented by Formula (I)

Prostaglandin D2 (PGD2) is the inflammatory mediator produced and released in the largest amount by mast cells activated by crosslinking of an allergen with the immunoglobulin E on the cells (Non-patent Literature (NPL) 1), and is considered to play an important role in causing allergic symptoms. PGD2 is detected at a high concentration in an asthmatic's bronchoalveolar lavage fluid (Non-patent Literature (NPL) 2), and it was reported that bronchoconstriction induced by PGD2 inhalation was more clearly observed in asthmatic patients than in healthy subjects (Non-patent Literature (NPL) 3).
On the other hand, synthases that generate PGD2 are referred to as prostaglandin D synthases, which has been classified into two distinct types: hematopoietic prostaglandin D synthase and lipocalin-type prostaglandin D synthase. PGD2 participates in the onset and exacerbation of various diseases, including allergies, and in the regulatory mechanisms of the body. Therefore, pharmaceutical preparations that can improve abnormal production of PGD2 are considered to be very effective for the treatment of various diseases.
Human hematopoietic prostaglandin D synthases (H-PGDS) are mainly distributed throughout the placenta, lung, fetus liver, lymph node, brain, heart, thymus, bone marrow, and spleen. Moreover, at the cellular level, they are reported to be expressed in microglial cells in the brain; megakaryocytes; many like antigen-presenting cells such as Langerhans cells in the skin, Kupffer cells in the liver, macrophages, and dendritic cells; mast cells; and Th2 cells.
Moreover, from the fact that H-PGDS are highly expressed in mast cells or inflammatory cells in the nasal mucosa of allergic rhinitis patients, or in nasal polyps of chronic sinusitis patients, it is thought that PGD2 generated by H-PGDS plays an important role in the onset and exacerbation of allergic diseases, such as asthma, rhinosinusitis, dermatitis, and chronic obstructive pulmonary disease (Non-patent Literature (NPL) 4). Further, the expression of H-PGDS is observed in the necrosed part of skeletal muscle, in which the expression of H-PGDS is generally detected (Non-patent Literature (NPL) 5). For this reason, it is suggested that PGD2 generated by H-PGDS participates in diseases accompanied by tissue damage, such as muscular dystrophy, amyotrophic lateral sclerosis, multiple sclerosis, inflammatory colitis, rheumatoid arthritis, and chronic obstructive arterial disease.
Therefore, an H-PGDS inhibitor is expected to find application as a pharmaceutical preparation that is useful as an agent for preventing and/or treating diseases, such as allergic disease and inflammatory disease in which PGD2 generated by H-PGDS or the metabolite participates, muscle necrosis, and traumatic brain injury.
There are some reports on an H-PGDS inhibitor (for example, Patent Literature (PTL) 1 and 2). Patent Literature (PTL) 3 discloses an H-PGDS inhibitor having a structure similar to that of the compound of the present invention. In addition, piperidine compounds have been widely studied as useful pharmacological agents in addition to H-PGDS inhibitors.
Patent Literature (PTL) 4 discloses, as a hedgehog signaling inhibitor, a piperazine compound having a furylcarbonyl piperazine structure.
Patent Literature (PTL) 5 discloses a wide range of piperazine compounds as compounds that interact with potassium channels.

Prostaglandin D synthase inhibitory piperidine compounds

Abstract: (wherein X1, X2, X2, A, B and N are as defined in the Description); or a salt thereof.


There is disclosed an apparatus for controlling the capacity of a hydraulic motor (5) in a hydraulically driven motor vehicle, which comprises: a hydraulic pump (2) adapted to be driven by an engine (1) having a variable rotation speed; the hydraulic motor of a variable capacity type adapted to be rotated by a discharge pressure fluid from the hydraulic motor for driving a traveling body that constitutes the motor vehicle allowed to travel; a capacity control section for reducing the capacity of the hydraulic motor when the rotation speed of the engine is increased and for increasing the capacity of the hydraulic motor when the rotation speed of the engine is reduced, the capacity control section having a variable operation rate and being operable at a variety of positions among a maximum capacity position, an intermediate capacity position and a minimum capacity position; and an operation rate control unit for accelerating the operation rate of the capacity control section when it is operating at a position between the maximum capacity position and the intermediate capacity position mentioned above and for decelerating the above mentioned operation rate when the capacity control section is operating at a position between the intermediate capacity position and the minimum capacity position mentioned above.

There has hitherto been known a hydraulically driven motor vehicle in which a hydraulic pump is driven by an engine and a hydraulic motor is rotated by a discharge pressure fluid from the hydraulic pump for driving a traveling body that constitutes the motor vehicle caused to travel with the hydraulic motor. In order to allow such a hydraulically driven motor vehicle to be accelerated and decelerated, the hydraulic motor has commonly been designed to be of a variable capacity type in which for the purpose of the vehicle acceleration the hydraulic motor is accelerated by increasing the capacity thereof and for the purpose of the vehicle deceleration the hydraulic motor is decelerated by reducing the capacity thereof.
As disclosed, for example, in Japanese Unexamined Patent Publication No. Sho 62-255658, it has been known that the capacity of a hydraulic pump can be gradually reduced by permitting an operating member for increasing and decreasing the capacity thereof to be operated in a direction in which the capacity is reduced and the capacity of the hydraulic pump can be swiftly increased by permitting the operating member to be operated in a direction in which the capacity is increased, thereby effecting a gradual deceleration of a motor vehicle while enhancing an ability thereof to swiftly accelerate itself.
It has also been known that a hydraulically driven motor vehicle having a hydraulic motor of variable capacity type can be provided with a servo cylinder assembly and a servo valve which are designed to control the capacity thereof in accordance with the pump pressure of a hydraulic pump and the rotation speed of an engine, in which the capacity of the hydraulic motor is reduced when the rotation speed of the engine is increased (when the vehicle is to be accelerated) to increase the rotation rate of the hydraulic motor and the capacity of the hydraulic motor is increased when the rotation rate of the engine is reduced (when the vehicle is to be decelerated) to reduce the rate of rotation of the hydraulic motor.
And, where it is desirable to change the capacity of the hydraulic motor in such a manner, it has been found that as in the case in which the capacity of the hydraulic pump is varied as described previously, not only is the ability to accelerate enhanced but also it is possible to decelerate gradually, by rapidly reducing the capacity of the hydraulic motor when the rotation speed of the engine has been increased whereas by gradually increasing the capacity of the hydraulic motor when the rotation speed of the engine has been reduced.
It has been found, however, that whereas the former system noted previously as disclosed in the Japanese Unexamined Patent Publication Sho No. 62-255658 in which the capacity of the hydraulic pump is controlled without regard to the pump pressure and the engine rotational speed makes it possible to control how to change the capacity variably as regards the directions in which it is increased and reduced, the latter system as described above in which a combination of the servo cylinder assembly and the servo valve is employed to control the capacity in accordance with the pump pressure and the engine rotational speed is not able, as it is, to control how to change the capacity variably with respect to the directions in which it is increased and decreased as in the former system.
For this reason, a measure has typically been taken in the prior art, in which a circuit for interconnecting the servo valve and the servo cylinder chambers is provided with a slow return valve whereby the speed of the servo piston at which it is displaced in a direction in which the capacity is reduced is accelerated whereas the speed of the servo piston at which it is displaced in a direction in which the capacity is increased is decelerated, thus making it possible to enhance the ability to accelerate quickly and to decelerate slowly.
It may be noted that it is preferred for the change in speed of a motor vehicle to be smaller when it is to be accelerated while it is traveling at a given speed, to be greater when it is being started from a stop, to be smaller initially when the traveling motor vehicle is being decelerated at an initial period of its deceleration, and to be greater immediately before it comes to a stop (at a final period of its deceleration).
It is also noted that in a case where a slow return valve is provided as described previously, the speed of the servo piston at which it is displaced in the direction in which the capacity is reduced will be a given value that can be preset independently of any particular position of the servo piston, as shown by the line A in FIG. 1 of the drawings attached hereto. Likewise, the speed of the servo piston at which it is displaced in the direction in which the capacity is increased will then be a constant value that can be established independently of any specific position of the servo piston, as shown by the line B in FIG. 1.
Noting in this way the fact that where a slow return valve is employed, a speed of displacement of the servo piston is rendered constant independently of its position as shown by the lines A and B in FIG. 1, it has been the prior art practice to improve as a whole both the acceleration and deceleration characteristics by adopting as the acceleration characteristic the one that can be seen intermediate between one settable in a traveling period and one settable in a starting period and as the deceleration characteristic the one that can be found intermediate between one in an initial deceleration period and one settable in a final deceleration period, as noted above. It has now been discovered that such a measure as it is cannot give rise to a fully satisfactory entire acceleration and deceleration performance for the hydraulically driven motor vehicle.
With the above described problem taken into account, it is an object of the present invention to provide an apparatus for controlling the capacity of a hydraulic motor in a hydraulically driven motor vehicle, that is capable of giving rise to a fully satisfactory entire acceleration and deceleration performance for the motor vehicle by permitting the change in speed thereof to be smaller while it is traveling, to be greater while it is being accelerated in a period in which it is started, to be smaller in an initial period of its deceleration, and to be increased in a final period of the deceleration.

Capacity control device for a hydraulic motor for a hydraulically driven vehicle


An electric component mounting unit for an air-conditioned garment, which is used in combination with a garment body having a fan opening and which is mounted on a body, includes a fan which takes air from outside into the garment body, a mounter which mounts the fan on the body, and a fan attacher which attaches the fan to the mounter. The fan includes a fan-side linker which links the fan with the fan opening.

In recent years, air-conditioned garment for cooling the body has been put into practice and has been rapidly becoming common. As illustrated in FIG. 35A and FIG. 35B, a conventional air-conditioned garment 101 includes a garment body 110 sewn with a material that does not breathe well, two fans 140, 140 attached at a lower back part of the garment body 110, a power supply (not shown) for supplying electric power to the two fans 140, 140 and power cables (not shown) for electrically connecting the power supply with the two fans 140, 140.
When the fans 140 are turned on, a large amount of air is taken into the garment body 110 through the fans 140. The pressure of the taken air automatically forms an air pathway between the garment body 110 and the body or an underwear, and the taken air flows upward in the formed air pathway along the surface of the body or underwear and is discharged to the outside, for example, through a neck opening or sleeve openings. The neck opening and sleeve openings serve as air discharging portions 130.
The air evaporates sweat from the body while flowing in the air pathway between the garment body 110 and the body or underwear, and the body is cooled by the heat of vaporization (e.g. see Patent Document 1).
Such conventional air-conditioned garment 101 is designed in various ways so that it can bear the weight of the fans 140 and that the fans 140 do not come off from the garment body 110 even when the fans 140 are subjected to a pressure in different directions.
For example, a garment body 110 of typical air-conditioned garment 101 is made of a fabric material. The fans 140 easily come off by a small force since such fabric is stretchable. To avoid this, attaching holes for the fans 140 are specially processed. For example, a plastic reinforcing plate is sewn on the fabric so that the fabric is not teared by the weight of the fans 140 and can securely fix the fans 140.

Electric component mounting unit for air-conditioned garment, and air-conditioned garment


In order to protect a delicate photo-detector from high-intensity optical radiation such as from a laser, a device for limiting power to the detector is interposed between the radiation and detector. This device has two embodiments and is made such that high-intensity radiation is totally reflected. In the absence of high-intensity radiation, total reflection is frustrated, and desired radiation passes to the detector. Both embodiments use two prisms with parallel surfaces skewed to incident radiation and with a slightly absorbant optical material between the surfaces. Desired radiation normally passes through the prisms and the material to the detector. In one embodiment, the material is a liquid which vaporizes in response to high-intensity radiation, and in the other embodiment, the material expands and pushes the prisms apart. In either case, transmission of radiation halts, and the radiation is totally reflected by a prism skewed surface.

This invention is in the field of protective devices for photo-detectors, and is particularly concerned with protecting such detectors against laser countermeasures. The types of detectors being protected include image intensifiers, television camera tubes, infrared detectors, and the human eye. Of these, the human eye requires the greatest protection because of its low damage threshold. Various techniques have been used and suggested for use against laser (or other possibly damaging radiations, such as sunlight). The main techniques used are fast-acting shutters (mechanical or electro-optical) and interference filters (absorbing or reflecting).
Unfortunately, these techniques have disadvantages which make them unusable for some detectors. Specifically, shutters require relatively long times to open and close, compared to the rise time of a pulsed laser. Interference filters, in order to block the spectra of various lasers, must be individually made for each threatening laser, and stacked in front of the detector being protected. For detection of low-level light, such stacked filters present unacceptable attenuations. The instant invention overcomes these disadvantages; it is fast acting and relatively non-attenuating in its unactivated mode.

Frustrated total internal reflection optical power limiter

The United States of America as represented by the Secretary of the Army


Methods for increasing the amount of cenospheres in a fly ash sample are disclosed. The cenospheres are obtained in a dry state by using air as the “fluid” media for separation. In one version, the invention is a two step process, that is, screen by size followed by density separation such as in a fluidizing vertical column by density. In another version of the invention, the separation by density is followed by screening by size. Additional cycles can improve purity as defined by concentration of cenospheres.

1. Field of the Invention
This invention relates to a method for increasing the amount of cenospheres in a fly ash sample.
2. Description of the Related Art
Coal fired boilers are widely used to generate steam for producing electricity. A common form of boiler uses a pulverized coal that is injected into a furnace. The process of burning coal in a boiler produces fly ash. Some of the recovered fly ash is commercially usable in concrete, concrete products, cement production, sewage sludge stabilization, pavement base materials, lightweight aggregate, reinforced plastics, and other miscellaneous purposes. The remaining fly ash must generally be disposed of by landfilling since it has no commercial value. It is well known that landfill space is rapidly dwindling in many regions and that the construction of new landfills is very costly. Therefore, much effort has been directed at finding uses for fly ash so that the fly ash does not need to be landfilled.
The composition of fly ash can vary depending on the composition of coal that generated the fly ash. Therefore, material specifications have been developed for fly ash that is to be used in specific applications. For example, fly ash that is used as a filler in concrete should meet the specifications described in American Society for Testing and Materials, "Standard Specification for Fly Ash and Raw or Calcined Natural Pozzolan for Use as a Mineral Admixture in Portland Cement Concrete", Designation: C 618. This ASTM specification indicates that fly ash particles are made largely of silicon dioxide, aluminum oxide and iron oxide. The particles in fly ash have different types of structures. Some particles in fly ash are solid. Other particles in fly ash are hollow and are called cenospheres. A cenosphere is a lightweight, inert, hollow sphere filled with inert air or gas. Cenospheres are hard and rigid, light, waterproof and insulative. Due to the hollow structure, cenospheres have lower density (e.g., some cenospheres have a density below 1 g/cc) as compared to solid fly ash particles. Cenospheres have traditionally been reported to represent about 1-3% by weight of the total fly ash produced.
In the composite materials field, there is increasing interest in ultra light energy-absorbing materials and structures which incorporate hollow particles. Accordingly, cenospheres have been added to polymers and there is growing interest in incorporating them in metals. Fine and sized cenospheres can be sold at attractive prices to this segment of industry providing syntactic foams and cellular solids. In addition, there is a growing market for fine solid microspheres to produce reinforced polymers, metals and ceramics.
Methods are known for recovering cenospheres from fly ash. In one method, cenospheres lighter than water are skimmed off of ash ponds (as many cenospheres float due to their lower density), dried and sold for use. U.S. Pat. No. 4,652,433 describes another method in which fly ash is screened into a coarse fraction and a fine fraction, and cenospheres are removed from the coarse fraction by mixing the coarse fraction with water such that the cenospheres float on the water and are removed by skimming. However, these processes do have disadvantages. For example, these methods only collect cenospheres with a density of less than 1.0 g/cc as only cenospheres of these densities float on water. Also, the fly ash that is produced from burning subbituminous western coal includes significant amounts of calcium compounds. For example, this fly ash may include 10% or more lime. These high calcium fly ashes (such as ASTM C 618 Class C fly ash) have cementitious properties and therefore, when mixed with water these fly ashes rapidly harden and the remainder cannot then be used for other purposes such as a cementitious material in the production of concrete. In the case of Class F fly ash, a dry method also provides the advantage of not expending energy to dry the remainder after separation of cenospheres for other uses. Another disadvantage is that, many cenospheres are entrapped in agglomerated and/or hardened masses before flotation occurs. Furthermore, the known methods for recovering cenospheres from fly ash do not allow for recovery of cenospheres of controlled sizes and densities. As a result, the properties of polymeric composites including cenospheres have not been optimized due to lack of availability of cenospheres of controlled sizes and densities.
Thus, there is a need for a method for recovering cenospheres from fly ash that has cementitious properties. There is also a need for a method for recovering cenospheres of narrow size ranges and densities from fly ash.


A dual disconnect differential assembly for four-wheel drive (4WD) vehicle is disclosed. This disconnect differential assembly connects both output shafts of a differential assembly (and correspondingly both axle shafts which are driven by the respective output shafts) simultaneously. The dual differential assembly herein also disconnects both output shafts simultaneously. A clutch mechanism associated with the two differential side gears (which may be otherwise conventional) and with annular driven gears which are in driving engagement with respective output shafts, is provided for simultaneous connection and simultaneous disconnection of the output shafts. The dual disconnect differential assembly herein is simple, compact, and reliable. It overcomes the disadvantages associated with single axle disconnect mechanisms presently in use. It also provides a simpler, more compact, and more reliable dual disconnect differential mechanism than any such mechanism presently known.

Four-wheel drive vehicles which are operable in either a two-wheel drive mode or a four-wheel drive mode have gained widespread popularity. Axle disconnect mechanisms, or differential disconnect mechanisms or assemblies for such vehicles are known.
Commonly used disconnect mechanisms for four-wheel drive vehicles disconnect only one of the two output shafts on an axle assembly which is driven part time. This causes the pinion gears and the side gears of the differential to rotate due to back driving, although the differential case remains stationary. This is not compatible with speed-sensitive limited slip differentials. Also, single axle disconnect mechanisms may cause noise and wear and poor fuel economy due to rotation of the differential components while the vehicle is in two-wheel drive mode.
Various dual disconnect differential assemblies or mechanisms have been proposed. These mechanisms in general have a number of moving parts, are fairly complex, and would be suitable only for installation on relatively wide vehicles because of the space required. None has achieved commercial acceptance.


Methods for substantially improved detection and analysis in nucleic acid hybridization assays are described. The methods provide the reliable estimation of background signal which derives primarily from nonspecific hybridization. The invention is useful in chemical, biological, medical and diagnostic techniques, as well as for drug discovery.

In nucleic acid sequencing and analysis, there is a growing emphasis on the use of high density arrays of immobilized nucleic acid probes. Such arrays can be prepared by massively parallel schemes, e.g., using the selective photomask techniques described in U.S. Pat. No. 5,143,854. Arrays constructed in this manner are typically formed in a planar area of between about 4-100 mm2, and can have densities of up to several hundred thousand or more distinct array members per cm2.
In use, an array surface is contacted with one or more analytes under conditions that promote specific, high-affinity binding of the analyte molecules to one or more of the array members (probes). The goal of the procedure is to identify one or more position-addressable members of the array which bind to the analyte as a method of detecting analyte molecule(s). Typically, the analyte is labeled with a detectable label such as a fluorescent tag, to indicate the one or more array regions where analyte binding to the array occurs. A variety of biological and/or chemical compounds have been used as hybridization probes in the above-described arrays. See, generally, Wetmur, J. (1991) Crit Rev Biochem and Mol Bio 26:227.
For example, such arrays can be used to perform nucleic acid hybridization assays. Generally, in such a hybridization assay, labeled single-stranded analyte nucleic acid (e.g. polynucleotide target) is hybridized to a complementary single-stranded nucleic acid probe. The complementary nucleic acid probe binds the labeled target and the presence of the target polynucleotide of interest is detected.
A common drawback of nucleic acid hybridization assays is the presence of signals which are generated due to an undesirable interaction of various components used in a given assay, i.e. signal generated by entities other than due to hybridization of the analyte and the specified complementary probes, such as signal generated from (i) the reporter, i.e. a signal arising from the label itself when it is not attached to the target, such as a signal generated from a fluorescent dye used in labeling the target; (ii) the non-reporter, i.e. a signal generated from the substrate or other assay components, and (iii) signal generated due to non-specific binding of probes to labeled entities other than their specific target molecules, i.e. binding not related to hybridization of the analyte and the complementary probes. Background signal generated from any of these mechanisms will add to the total signal measured. Uncorrected signal containing background signal results in an overestimation of the "real" signal, which can lead to "false positive" results. Thus, the background signal needs to be estimated accurately and subtracted from the total signal of a hybridization assay to yield the "real" signal.
However, accurate estimation of the background signal is complicated. Underestimation of the background signal will result in an overestimation of the "real" signal, which can yield "false positive" results. Conversely, overestimation of the background signal will result in an underestimation of the "real" signal, which can yield "false negative" results. Thus, background overestimation will negatively impact the lowest concentration of the target that can be reliably detected. An accurate estimate of the background signal is thus needed to generate accurate results.
A common approach to correcting background signal in arrays is to evaluate the portion of the array that is outside of the probe features. However, the background correction problem is particularly complex for measurements made using arrays of nucleic acid hybridization probes, because background may vary as a function of location on the surface. Furthermore, the local properties of the surface that contains bound nucleic acid probes may be very different from the surrounding surface that does not contain bound probes. The "local background signal" is the signal generated from the portion of the array outside of the probe feature area. The signal from the local background immediately adjacent to a given feature is subtracted from the total signal of that feature to correct for background and to yield the "real" signal. Alternatively, the local background signal from the entire array can be evaluated and a single value (e.g. an average local background signal or the minimum local background signal) can be calculated to correct all features of that array. This is referred to as the "global background signal". The choice of an appropriate background correction method depends critically upon which of these two influences, i.e., local background or modification of surface properties by covalently bound nucleic acid probes, is judged to most strongly influence background signal in the array regions containing covalently bound probe molecules.
The use of local or global background correction methods are problematic. The properties of the array surface outside the features may differ from the properties of the array surface within the features. These differences can result in different levels of non-reporter signal or different levels of reporter non-specific binding. Thus, the observed signal from the local background or estimated from a global background calculation may result in an inaccurate estimation of the background signal within the feature. Additionally, the probes themselves may generate a portion of the background signal. For example, the bases or phosphodiester linkages of the probes may (i) produce non-reporter signal, (ii) bind to components which produce non-reporter signal, or (iii) non-specifically bind the reporter. Therefore, in these cases, using local background will underestimate the true background signal that should be subtracted.
Representative methods for resolving the problem of interfering background signals in nucleic acid hybridization assays are described in U.S. Pat. Nos. 4,868,105; 5,124,246; 5,563,034; and 5,681,702; WO 98/24933; Chen Y., et al., Journal of Biomedical Optics (1997) 2:364-374; and DeRisi J. L. et al. (1997) Science 278:680-686. Existing methods generally correct for background signal by subtracting either the local or global background. However, these methods do not involve surface-bound nucleic acid probes, and in some cases background estimates obtained from local or global sampling of nonprobe regions overestimate background in regions that contain probes. Background overestimation negatively impacts the lowest dose of the target that can be reliably detected by an array involving a nucleic acid hybridization assay.
Therefore, there is a need for reliable methods for estimating background signal from probe-containing regions in hybridization arrays.

Arrays comprising background features that provide for a measure of a non-specific binding and methods for using the same


A polishing apparatus includes a polishing pad for polishing a wafer and a polishing head for holding the wafer. The polishing head includes a retainer ring, a membrane sheet, and a head body. The retainer ring retains the wafer in a horizontal direction. The membrane sheet depresses the wafer to the polishing pad. The head body supports the retainer ring and the membrane sheet. The retainer ring includes a fixed retainer ring and a released retainer ring. The released retainer ring is interposed between the inner periphery of the fixed retainer ring and the periphery of the wafer to retain the wafer in the horizontal direction.

1. Field of the Invention
The present invention relates to a polishing apparatus. More particularly, the invention relates to a polishing apparatus that is suitable for use in the chemical mechanical polishing (CMP) process performed in manufacturing semiconductor devices.
2. Description of the Related Art
In recent years, the integration density of semiconductor devices has increased, making it possible to form a multilayer interconnection structure in each semiconductor device. To manufacture a semiconductor device having the multilayer interconnection structure, each layer of the multilayer interconnections should have so flat a surface that projections and depressions, if any, may fall within the focal depth of the light source used in photolithography. The CMP process is employed to impart such a flat surface to the each film.
FIG. 5 shows a polishing apparatus 100 designed for use in the CMP process. The polishing apparatus 100 includes a polishing pad 11 that has a circular polishing surface 11a. On the polishing surface 11a, a wafer 12 is mounted, and a polishing head 13 is positioned thereon to sandwich the wafer 12 between the same and the polishing surface 11a. The polishing head 13 includes a head body 14, a retainer ring 16, and a membrane sheet 17. The head body 14 is of a disc shape The membrane sheet 17 has a diameter substantially equal to the diameter of the wafer 12, contacts the rear surface of the wafer 12, and is disposed below the head body 14. The retainer ring 16 is disposed to surround the wafer 12 and the membrane sheet 17. The bottom of the head body 14 and the membrane sheet 17 define a closed space 18. High-pressure air is supplied into the closed space 18, whereby the wafer 12 is depressed toward the polishing pad 11.
The retainer ring 16 has a top surface secured to the bottom of the head body 14 and a bottom surface in contact with the polishing surface 11a of the polishing pad 11. FIG. 6 is a top plan view illustrating the positional relationship between the wafer 12 and the retainer ring 16. The retainer ring 16 contacts, at the inner periphery thereof, the periphery of the wafer 12 to retain the wafer 12 in a horizontal direction, i.e., in-plane direction of the wafer 12.
During polishing the wafer 12, the polishing pad 11 is rotated around the axis thereof, while slurry, i.e., polishing agent, is being supplied onto the center of the polishing surface 11a. The membrane sheet 17 depresses the rear surface of the wafer 12 retained within the retainer ring 16. The main surface of the wafer 12 is thereby depressed onto the polishing surface 11a. In this condition, the polishing head 13 is rotated around the axis thereof and moved back and forth in the radial direction of the polishing surface 11a, whereby the polishing head 13 polishes the main surface of the wafer 12 in the CMP process.
JP 2004-119495A and JP 2002-367941A, for example, describe apparatus similar to the polishing apparatus of FIG. 5 and a polishing method such as described above.
In the conventional polishing apparatus 100, the periphery of the membrane sheet 17 is aligned with the periphery of the wafer 12 as shown in FIG. 5. However, the membrane sheet 17 is deformed to bulge downwards, when high-pressure air is supplied into the closed space 18 to conduct the polishing. As a result, the periphery of the membrane sheet 17 is raised as is indicated by numeral 31 in FIG. 7. Inevitably, the pressure depressing the wafer 12 downwards will be decreased in the vicinity of the periphery of the wafer 12.
The decrease in the pressure depressing the wafer 12 downwards reduces the polishing rate during the CMP process to cause a non-uniform surface, i.e., a lager range of variation on the polished surface. This ultimately lowers the product yield in the manufacture of semiconductor devices. To solve this problem, the assigner of the present invention has a proposal as described in JP Patent Application No. 2006-136024 that the membrane sheet 17 should have a larger diameter than the wafer 12 so that the periphery of the membrane sheet 17 may not be raised and may not be brought into contact with the wafer 12 during the polishing process.

Polishing apparatus including separate retainer rings


The present invention relates to elastomeric compounds having a high filler content additionally containing 1 to 400% by weight of resin of microsilica as a modifier to improve the processability. Thereafter, the invention relates to a method for production of elastomeric compounds having a high filler content, wherein microsilica is added to the elastomeric compounds in an amount of 1 to 400% by weight of resin as a modifier to improve processability.

It is well known to produce elastomeric compounds such as those used in seals, gaskets, tyres, cables and other articles made from rubber using ingredients like fillers, plastizisers, antioxidants, curatives and others. All these compound ingredients are used to receive certain properties of the final article or are necessary during the manufacturing. But some of these substances do influence each other leading to detrimental effects on physical properties or on processing behaviour. Functional fillers, for instance some carbon blacks and precipitated silicas, are used to improve hardness, tensile strength, tear resistance and other desired properties, but they also, especially at high filler loadings, increase compound viscosity leading to poor processability and scorch safety. This has to be balanced out by the incorporation of plastizisers and/or process aids. Plastizisers and process aids have, however, a negative influence on physical properties, including fire performance and they can "bloom out". So far no material is known that could overcome the processing difficulties of elastomeric resin compositions with high filler loading, and still maintaining the desired physical properties.
It is very difficult to give a precise definition of "high filler loading" as it depends very much on the polymer used and on the application of the final compound. However, generally if the filler content of a highly filled elastomeric compounds is increased, the viscosity will increase to a level where the processability of the compounds will be strongly reduced. The amount of fillers in highly filled resins can thus, depending on the polymer, vary from about 15 to about 500% by weight of resin.
It is known to use microsilica as semi-reinforcing filler in elastomers replacing for instance MT (medium thermal)—black or calcium silicate fillers. In these instances microsilica has always been used as a replacement to obtain a less costly elastomer having the same strength. Thus the total filler loading has never been increased when using microsilica as a semi-reinforcing filler.

Highly filled elastomeric resin compositions with added microsilica for processability


A method for fabricating a semiconductor structure having a high-strained crystalline layer with a low crystal defect density is disclosed. The structure includes a substrate having a first material comprising germanium or a Group(III)-Group(V)-semiconductor or alloy thereof. In addition, a crystalline epitaxial first layer, comprising a graded buffer layer and a substantially relaxed layer, is provided. The buffer layer is sufficiently relaxed to provide relaxation of the substantially relaxed layer deposited thereon. A further layer may be provided on the first layer, and the transfer of at least the further layer is facilitated by providing a weakened zone in the first layer.

The present invention relates to a semiconductor structure having a strained crystalline layer formed on a single crystal substrate or on an insulator and further to a method for fabricating such a semiconductor structure.
Strained, thin semiconductor layers, such as silicon layers, have enhanced electron and hole mobility characteristics which are advantageous for improving speed or decreasing power requirements of electronic devices. Because their use can lead to high performance devices having high speed and low power consumption, such layers are of interest in nearly all parts of microelectronics.
Strain in silicon layers can be induced, for instance, by growing a thin silicon layer on a relaxed SiGe layer with a high concentration of germanium. Because silicon is the smaller atom, the stress between silicon and such a SiGe layer increases gradually with increasing Ge concentration, and more favorable strain values can be achieved when the germanium concentration of the SiGe layer is as large as possible.
U.S. Published Application No. 2002/0084000 A1 discloses a method and a semiconductor structure for growing a GeSi layer with a gradually increasing germanium content on a silicon substrate up to a germanium content of about 50%. Increasing germanium content of the graded GeSi layer causes cracks and a high number of threading dislocations to occur in the layer. In order to remove a cross-hatch pattern on the surface of the GeSi layer, a surface planarization step such as a Chemical Mechanical Polishing is applied to the GeSi surface. The planarization step prevents the continued roughening of the surface and leads to dislocation blocking as grading continues, and the germanium content of the GeSi is further increased until a pure Ge layer results on the top of the structure.
International Publication No. WO 02/15244 A2 describes a method and a semiconductor structure that provides a SiGe buffer layer that serves as a seed layer for a strained silicon film. A SiGe layer is deposited on a single crystal silicon wafer, wherein the germanium concentration is gradually increased up to 25% germanium. Then, a relaxed SiGe cap layer is deposited, having a final Ge composition of 25%. The process of growing a relaxed SiGe layer is very complex. The growth generates a very high density of misfit dislocations and a cross-hatch pattern of the SiGe layer. Furthermore, the above method is limited to a germanium content below 40% when a crystal defect density below 104 cm−2 is targeted.
Strained semiconductor layers can also be effectively used if they are transferred on an insulator layer, resulting in a SOI (silicon-on-insulator)-type structure, whose benefits are commonly known in microelectronics and micromechanics.
A publication by Cheng et al. at the 2001 IEEE International SOI Conference called "SiGe-on-Insulator (SGOI): Substrate Preparation and MOSFET Fabrication for Electron Mobility Evaluation" describes a method for fabricating a SiGe-on-insulator structure. A graded SiGe layer was grown on a single crystalline silicon donor wafer. During SiGe growth, the germanium content was gradually increased until a germanium concentration of about 25% was reached. A relaxed SiGe layer was then grown on the graded SiGe layer, and hydrogen ions were implanted into the relaxed SiGe layer, forming a weakened zone in the relaxed SiGe layer. The implanted structure was then bonded with an oxidized silicon wafer. After annealing, the bonded structure was split into two parts along the weakened zone resulting in the SiGe-on-insulator structure and a residual structure. A strained silicon layer was then grown on the SiGe layer resulting in a Si-on-SiGe-on-insulator structure.
This resulting structure, however, has a critical disadvantage in that the strain of the strained silicon layer on top of the SiGe layer cannot be increased to a value of commercial importance. This is due to the limited germanium content of the SiGe layer which cannot be increased over 25% without risking formation of a high dislocation density in the SiGe layer, which considerably influences the electronic characteristics of the strained silicon layer.
The present invention addresses these problems of the prior art, by providing a commercially useful high-strained silicon layer with a low defect density on a single crystal substrate as well as on an insulator.

Semiconductor structure for providing strained crystalline layer on insulator and method for fabricating same

S.O.I.Tec Silicon on Insulator Technologies S.A.


A method for making a multilayer golf ball including a solid center having a center hardness, a plurality of laminates cut into a plurality of shapes formed around the center to create an inner ball, and a cover formed around the inner ball, wherein the plurality of layers can include at least a first layer having a hardness greater than the center hardness and a second layer having a hardness greater than the first layer hardness, and optionally a third layer disposed between the first and the second layers having a hardness greater than the first layer hardness.

Golf ball manufacturers constantly strive to construct golf balls with a balance of good "feel," distance, and durability. Adjusting the construction of the ball, e.g., multilayer, and/or the composition of the individual layers, e.g., high flexural modulus material in an intermediate layer, allows golf ball manufacturers to tweak ball properties to obtain the desired balance of golf ball properties.
Golf balls today can be of varied construction, e.g., two piece balls, three piece balls, the latter including wound balls. The difference in play characteristics resulting from these different types of constructions can be quite significant.
Generally, golf balls have been classified as solid or wound balls. Solid, balls having a two piece construction, typically an crosslinked rubber core, e.g., polybutadiene crosslinked with zinc diacrylate and/or similar crosslinking agents, encased by a blended cover, e.g., ionomer resins, are generally most popular with the average recreational golfer. The combination of the core and cover materials provide a "hard" ball that is virtually indestructible by golfers and one that imparts a high initial velocity to the ball, resulting in improved distance. Because the materials of which the ball is formed are very rigid, two piece balls have a hard "feel" when struck with a club. Likewise, due to their hardness, these balls have a relatively low spin rate which provides greater distance.
Wound balls are generally constructed from a liquid or solid center surrounded by tensioned elastomeric material and covered with a durable cover material, e.g., ionomer resin, or a softer cover material, e.g., balata or polyurethane. Wound balls are generally thought of as performance golf balls and have good resiliency, desirable spin characteristics, and feel when struck by a golf club. However, wound balls are generally difficult to manufacture when compared to solid golf balls.
The prior art includes a variety of golf balls that have been designed to provide particular playing characteristics. These characteristics are generally the initial velocity and spin of the golf ball, which can be optimized for various types of players. For instance, certain players prefer a ball that has a high spin rate in order to control and stop the golf ball. Other players prefer a ball that has a low spin rate and high resiliency to maximize distance. Generally, a golf ball having a hard core and a soft cover will have a high spin rate. Conversely, a golf ball having a hard cover and a soft core will have a low spin rate. Golf balls having a hard core and a hard cover generally have very high resiliency for distance, but are hard feeling and difficult to control around the greens. A number of patents, for example, have been issued which are directed towards directed towards improving the carry distance of conventional two piece balls by altering the typical single layer core and single cover layer construction to provide a multi-layer ball, e.g., a dual cover layer, dual core layer, and/or a ball having an intermediate layer disposed between the cover and the core. U.S. Pat. Nos. 4,863,167, 5,184,828, and 4,714,253 are examples of such multilayer golf balls.
In addition, there are a number of patents directed to improving the spin, click and feel of solid balls while maintaining the distance provided by the solid construction golf balls. U.S. Pat. Nos. 5,072,944, 4,625,964, 4,650,193, and 4,848,770 disclose a golf ball having a rubber core and intermediate layer, e.g., polybutadiene, surrounded by a cover. U.S. Pat. Nos. 5,253,871, 5,681,898, 5,439,227, 5,556,098 are directed to golf balls having intermediate layers using a variety of materials other than polybutadiene.
Further, there are also several patents which are directed to golf balls having multiple cover layers. U.S. Pat. Nos. 4,431,193, 5,314,187, 4,919,434 are examples of such patents.
It would be advantageous to provide a golf ball having a core, a plurality of solid intermediate layers, and a cover, wherein the materials included in the intermediate layers are the same or different, resulting in a golf ball having improved physical properties.

Method of making a golf ball with a multi-layer core


The invention concerns the use of at least one protein extract of the Moringa genus plant seeds and a cosmetic and/or pharmaceutical composition containing at least one such extract. More particularly, the invention concerns the use of a protein extract of the Moringa genus plant seeds belonging to the Moringaceae family, as active principle, on its own or combined with at least another active principle, for preparing a cosmetic and/or pharmaceutical composition for topical use on the skin and/or skin appendages.

The present invention relates to the field of cosmetology and dermatology, more particularly cosmetics for the care of the skin and nails and hair, and has for its object the use, for cosmetic, dermatologic and/or pharmaceutical applications, of at least one proteic extract of seeds of a plant of the genus Moringa, as well as a cosmetic and/or pharmaceutical composition containing at least one such extract.
The genus Moringa comprises some 14 species of plants (of which particularly Moringa peregrina, M. aptera, M. concanensis, M. drouhardii, M. hildebrandtii, M. longituba), among which Moringa pterygosperma (synonym: Moringa oleifera) is the best known.
It is a tree that grows rapidly and which adapts very well to variable conditions, spread throughout the tropics, in Asia, Africa and South America. The fruits are 30 to 50 cm long, hanging like drumsticks, from which comes the English name xe2x80x9cdrumstick treexe2x80x9d, and its green pods are used as vegetables throughout the world. As a result, the seeds are rarely left to ripen for the production of oil.
The different parts of the tree (leaves, roots, root bark, flowers, seeds) are used in traditional medicine in the countries where it is found.
The seeds of Moringa are characterized by the presence of an oil whose content varies between 21 and 53% according to the species and maturity of the seeds.
For the species Moringa oleifera, the contents mentioned in the literature range from 21 to 34%.
The comparison of the oils of the seeds of Moringa oleifera, Mr. peregrina, M. concanensis and M. drouhardii show a very similar fatty acid content, these oils all having a very high content of oleic acid (71 to 78%) and saturated fatty acids.
Behenic acid (C22H44 O2) is the saturated fatty acid typical of Moringa oil (content 2.6 to 4.7%).
Because of its excellent stability against oxidation and its good properties as a perfume fixative, Moringa oil, also called Behen or Ben oil, was in ancient civilizations the oil most used by the producers of unguents for cosmetic and religious uses.
This oil was used by cosmetic formulators until the nineteenth century and its use has been recently xe2x80x9crediscoveredxe2x80x9d.
In addition to their oil content, Moringa seeds have recently claimed the attention of researchers because they are used conventionally for the clarification of water and thus have an economic potential for the treatment and purification of water in developing countries.
It has moreover been shown that the seeds of six species of Moringa that are the most frequent and cultivated contain flocculent compounds.
The compounds responsible for this activity have been isolated and identified: they are compounds of proteic nature (see particularly the articles: xe2x80x9cIsolation and characterization of a flocculating protein from Moringa oleifera lamxe2x80x9d, by U. Gassenschmidt, K. D. Jany, B. Tausche and H. R. Niebergall, Biochimica and biophysics acta, 1243:477-481, 1995xe2x80x94xe2x80x9cActive agents and mechanism of coagulation of turbid waters using Moringa oleiferaxe2x80x9d, of A. Ndabigengesere, K. Subba Narasiah and B. G. Talbot, Water research, 29, 2:703-710, 1995).
From delipidated flour of Moringa oleifera seeds, these proteins have been extracted in a buffered aqueous medium, then isolated by cation exchange chromatography.
These flocculent proteins are eluted with an NaCl gradient and are constituted by three active fractions called MO1, MO2, and MO3.
A second chromatographic step permits separating MO2 into three new active fractions called (MO2.1, MO2.2 and MO2.3).
With PAGE electrophoresis under non-denaturing conditions, MO2.1, MO2.2 seem to be homogeneous whilst MO2.3 is constituted by several proteins.
However, with SDS-PAGE, two bands corresponding to the PM 6.5 kDa and 7 kDa are observed for the proteins MO2.1 and MO2.2, which thus would be dimers.
Isoelectrofocalization shows that the isoelectric point of these flocculent proteins is 10.
The amino acid composition of MO2.1 has been determined and shows that this protein contains 60 amino acids with a high content of glutamine (15 residues), arginine (7 residues) and proline (7 residues), the end terminal being blocked by a pyroglutamate function.
The inventors of the present invention have discovered in an unexpected and surprising manner, that the proteic extracts of Moringa seeds, known for their turbid water clarifying properties, also have new and original properties whose beneficial effects on the skin and nails and hair, associated with very high tolerance, renders them directly usable in care cosmetology and in pharmacology, in particular for dermatological applications.
Thus, the principal object of the present invention consists in the use of at least one proteic fraction extracted from seeds of a plant of the genus Moringa belonging to the family of the Moringaceae, as the active principal, alone or in association with at least one other active principal, for the preparation of a cosmetic and/or pharmaceutical composition for topical application for the skin and/or the nails and hair.
The new properties of these proteic extracts flow directly from their particular nature and properties, particularly their basic isoelectric point and their flocculent capacity.
There have particularly been noted an emollient effect, conditioning and hydrating effects because of the great substantivity and chelating effects, rendering them suitable in the field of anti-pollution activity.
According to a preferred embodiment of the invention, the proteic fraction or fractions consist in one or more extracts of the plant Moringa oleifera, this or these proteic fraction or fractions containing, based on the dry extract, a protein content comprised between 0.01% and 100% by weight, preferably of about 45% by weight.
Preferably, the proteic fraction or fractions is or are extracted with water or an aqueous solution, particularly saline solutions at different pHs, as the case may be by means of an ultrasonic generator.
Thus, the proteic fraction or fractions is or are constituted by one or more aqueous extracts, saline medium extracts with different pHs, or a buffered medium of whole or decorticated seeds, partially or totally delipitized, by a proteic concentrate, by purified proteins or by a mixture of at least two of the mentioned constituents and having an isoelectric point greater than 7, preferably comprised between 8 and 12.
The proteic fraction or fractions utilized as active principal are preferably obtained by:
precipitation at the isoelectric point at a pH comprised between 8 and 12
ion exchange chromatography.
an extraction process selected from the group formed by affinity chromatography, gel filtration, ultrafiltration, solvent precipitation, of salts such as ammonium sulfate or the like or else by precipitation with the aid of organic polymers or by temperature variation.
Moreover, it has been determined that, in the case of precipitation at the isoelectric point, obtaining the proteic fraction or fractions is promoted by a temperature below ambient temperature, particularly by a temperature of about +4xc2x0 C.

Use of at least one protein extract of the moringa genus plant seeds and corresponding cosmetic and/or pharmacological composition

Laboratoires Serobiologiques (Societe Anonyme)


Techniques, devices, and systems for receiving, from a mobile device, a request associated with a subscriber information module (SIM) are described herein. At least one of the mobile device, the SIM, or a communication identifier can be determined. A query can be transmitted, based on a difference between a first time associated with the query and a second time associated with a previous query meeting or exceeding a threshold amount of time. An action can be performed based on the query information being associated with the malicious activity information.

A subscriber identity module (SIM) is a component of a user equipment (UE) that can store data, such as a unique serial number associated with the SIM, an international mobile subscriber identity (IMSI) number, security authentication data, contact data, capability data, service data, and/or the like. In some examples, a SIM can be an integrated circuit (e.g., a "SIM card") that can be inserted and removed from a UE. In some examples, a SIM can be an embedded-SIM (eSIM), which can be a programmable SIM that is embedded directly into a UE. In some examples, user accounts associated with SIMs are vulnerable to fraudulent attacks. As a result, malicious actors can obtain access to the user accounts, perform SIM swaps, and/or obtain private access codes. This can result in undesirable disclosure of information, detrimental utilization of user accounts, and/or unauthorized transfers of funds.

Automated security control using log information