Conformationally constrained compounds that mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins as well as their prodrugs are disclosed. Such reverse-turn mimetic structures and prodrugs have utility over a wide range of fields, including use as diagnostic and therapeutic agents. Libraries containing the reverse-turn mimetic structures of this invention are also disclosed as well as methods for screening the same to identify biologically active members. The invention also relates to the use of such compounds and prodrugs for inhibiting or treating disorders modulated by Wnt-signaling pathway, such as cancer, especially colorectal cancer, restenosis associated with angioplasty, polycystic kidney disease, aberrant angiogenesis disease, rheumatoid arthritis disease, tuberous sclerosis complex, Alzheimer's disease, excess hair growth or loss, or ulcerative colitis.

1. Field of the Invention
The present invention relates generally to reverse-turn mimetic structures and to a chemical library relating thereto. The invention also relates to applications in the treatment of medical conditions, e.g., cancer diseases, and pharmaceutical compositions comprising the mimetics.
2. Description of the Related Art
Random screening of molecules for possible activity as therapeutic agents has occurred for many years and resulted in a number of important drug discoveries. While advances in molecular biology and computational chemistry have led to increased interest in what has been termed "rational drug design", such techniques have not proven as fast or reliable as initially predicted. Thus, in recent years there has been a renewed interest and return to random drug screening. To this end, particular strides having been made in new technologies based on the development of combinatorial chemistry libraries, and the screening of such libraries in search for biologically active members.
In general, combinatorial chemistry libraries are simply a collection of molecules. Such libraries vary by the chemical species within the library, as well as the methods employed to both generate the library members and identify which members interact with biological targets of interest. While this field is still young, methods for generating and screening libraries have already become quite diverse and sophisticated. For example, a recent review of various combinatorial chemical libraries has identified a number of such techniques (Dolle, J. Com. Chem., 2(3): 383-433, 2000), including the use of both tagged and untagged library members (Janda, Proc. Natl. Acad. Sci. USA 91:10779-10785, 1994).
Initially, combinatorial chemistry libraries were generally limited to members of peptide or nucleotide origin. To this end, the techniques of Houghten et al. illustrate an example of what is termed a "dual-defined iterative" method to assemble soluble combinatorial peptide libraries via split synthesis techniques (Nature (London) 354:84-86, 1991; Biotechniques 13:412-421, 1992; Bioorg. Med. Chem. Lett. 3:405-412, 1993). By this technique, soluble peptide libraries containing tens of millions of members have been obtained. Such libraries have been shown to be effective in the identification of opioid peptides, such as methionine- and leucine-enkephalin (Dooley and Houghten, Life Sci. 52, 1509-1517, 1993), and a N-acylated peptide library has been used to identify acetalins, which are potent opioid antagonists (Dooley et al., Proc. Natl. Acad. Sci. USA 90:10811-10815, 1993. More recently, an all D-amino acid opioid peptide library has been constructed and screened for analgesic activity against the mu ("μ") opioid receptor (Dooley et al, Science 266:2019-2022, 1994).
While combinatorial libraries containing members of peptide and nucleotide origin are of significant value, there is still a need in the art for libraries containing members of different origin. For example, traditional peptide libraries to a large extent merely vary the amino acid sequence to generate library members. While it is well recognized that the secondary structures of peptides are important to biological activity, such peptide libraries do not impart a constrained secondary structure to its library members.
To this end, some researchers have cyclized peptides with disulfide bridges in an attempt to provide a more constrained secondary structure (Tumelty et al., J. Chem. Soc. 1067-68, 1994; Eichler et al., Peptide Res. 7:300-306, 1994). However, such cyclized peptides are generally still quite flexible and are poorly bioavailable, and thus have met with only limited success.
More recently, non-peptide compounds have been developed which more closely mimic the secondary structure of reverse-turns found in biologically active proteins or peptides. For example, U.S. Pat. No. 5,440,013 to Kahn and published PCT Applications Nos. WO94/03494, WO01/00210A1, and WO01/16135A2 to Kahn each disclose conformationally constrained, non-peptidic compounds, which mimic the three-dimensional structure of reverse-turns. In addition, U.S. Pat. No. 5,929,237 and its continuation-in-part U.S. Pat. No. 6,013,458, both to Kahn, disclose conformationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins. The synthesis and identification of conformationally constrained, reverse-turn mimetics and their application to diseases were well reviewed by Obrecht (Advances in Med. Chem., 4, 1-68, 1999).
While significant advances have been made in the synthesis and identification of conformationally constrained, reverse-turn mimetics, there remains a need in the art for small molecules which mimic the secondary structure of peptides. There is also a need in the art for libraries containing such members, as well as techniques for synthesizing and screening the library members against targets of interest, particularly biological targets, to identify bioactive library members.
The present invention also fulfills these needs, and provides further related advantages by providing confomationally constrained compounds which mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins.
Wnt signaling pathway regulates a variety of processes including cell growth, oncogenesis, and development (Moon et al., 1997, Trends Genet. 13, 157-162; Miller et al., 1999, Oncogene 18, 7860-7872; Nusse and Varmus, 1992, Cell 69, 1073-1087; Cadigan and Nusse, 1997, Genes Dev. 11, 3286-3305; Peifer and Polakis, 2000 Science 287, 1606-1609; Polakis 2000, Genes Dev. 14, 1837-1851). Wnt signaling pathway has been intensely studied in a variety of organisms. The activation of TCF4/β-catenin mediated transcription by Wnt signal transduction has been found to play a key role in its biological functions (Molenaar et al., 1996, Cell 86:391-399; Gat et al., 1998 Cell 95:605-614; Orford et al., 1999 J. Cell. Biol. 146:855-868; Bienz and Clevers, 2000, Cell 103:311-20).
In the absence of Wnt signals, tumor suppressor gene adenomatous polyposis coli (APC) simultaneously interacts with the serine kinase glycogen synthase kinase (GSK)-3β and β-catenin (Su et al., 1993, Science 262, 1734-1737: Yost et al., 1996 Genes Dev. 10, 1443-1454: Hayashi et al., 1997, Proc. Natl. Acad. Sci. USA, 94, 242-247: Sakanaka et al., 1998, Proc. Natl. Acad. Sci. USA, 95, 3020-3023: Sakanaka and William, 1999, J. Biol. Chem. 274, 14090-14093). Phosphorylation of APC by GSK-3β regulates the interaction of APC with β-catenin, which in turn may regulate the signaling function of β-catenin (B. Rubinfeld et al., Science 272, 1023, 1996). Wnt signaling stabilizes β-catenin allowing its translocation to the nucleus where it interacts with members of the lymphoid enhancer factor (LEF1)/T-cell factor (TCF4) family of transcription factors (Behrens et al., 1996 Nature 382, 638-642; Hsu et al., 1998, Mol. Cell. Biol. 18, 4807-4818; Roose et al., 1999 Science 285, 1923-1926).
Recently c-myc, a known oncogene, was shown to be a target gene for β-catenin/TCF4-mediated transcription (He et al., 1998 Science 281 1509-1512; Kolligs et al., 1999 Mol. Cell. Biol. 19, 5696-5706). Many other important genes, including cyclin D1, and metalloproteinase, which are also involved in oncogenesis, have been identified to be regulated by TCF4/bata-catenin transcriptional pathway (Crawford et al., 1999, Oncogene 18, 2883-2891; Shtutman et al., 1999, Proc. Natl. Acad. Sci. USA., 11, 5522-5527; Tetsu and McCormick, 1999 Nature, 398, 422-426).
Moreover, overexpression of several downstream mediators of Wnt signaling has been found to regulate apoptosis (Moris et al., 1996, Proc. Natl. Acad. Sci. USA, 93, 7950-7954; He et al., 1999, Cell 99, 335-345: Orford et al, 1999 J. Cell. Biol., 146, 855-868; Strovel and Sussman, 1999, Exp. Cell. Res., 253, 637-648). Overexpression of APC in human colorectal cancer cells induced apoptosis (Moris et al., 1996, Proc. Natl. Acad. Sci. USA. 93, 7950-7954), ectopic expression of β-catenin inhibited apoptosis associated with loss of attachment to extracellular matrix (Orford et al, 1999, J. Cell Biol. 146, 855-868). Inhibition of TCF4/β-catenin transcription by expression of dominant-negative mutant of TCF4 blocked Wnt-1-mediated cell survival and rendered cells sensitive to apoptotic stimuli such as anti-cancer agent (Shaoqiong Chen et al., 2001, J. Cell. Biol., 152, 1, 87-96) and APC mutation inhibits apoptosis by allowing constitutive survivin expression, a well-known anti-apoptotic protein (Tao Zhang et al., 2001, Cancer Research, 62, 8664-8667).
Although mutations in the Wnt gene have not been found in human cancer, a mutation in APC or β-catenin, as is the case in the majority of colorectal tumors, results in inappropriate activation of TCF4, overexpression of c-myc and production of neoplastic growth (Bubinfeld et al, 1997, Science, 275, 1790-1792; Morin et al, 1997, Science, 275, 1787-1790; Casa et al, 1999, Cell. Growth. Differ. 10, 369-376). The tumor suppressor gene (APC) is lost or inactivated in 85% of colorectal cancers and in a variety of other cancers as well (Kinzler and Vogelstein, 1996, Cell 87, 159-170). APC's principal role is that of a negative regulator of the Wnt signal transduction cascade. A center feature of this pathway involves the modulation of the stability and localization of a cytosolic pool of β-catenin by interaction with a large Axin-based complex that includes APC. This interaction results in phosphorylation of β-catenin thereby targeting it for degradation.
CREB binding proteins (CBP)/p300 were identified initially in protein interaction assays, first through its association with the transcription factor CREB (Chrivia et al, 1993, Nature, 365, 855-859) and later through its interaction with the adenoviral-transforming protein E1A (Stein et al., 1990, J. Viol., 64, 4421-4427; Eckner et al., 1994, Genes. Dev., 8, 869-884). CBP had a potential to participate in variety of cellular functions including transcriptional coactivator function (Shikama et al., 1997, Trends. Cell. Biol., 7, 230-236; Janknecht and Hunter, 1996, Nature, 383, 22-23). CBP/p300 potentiates β-catenin-mediated activation of the siamois promoter, a known Wnt target (Hecht et al, 2000, EMBO J. 19, 8, 1839-1850). β-catenin interacts directly with the CREB-binding domain of CBP and β-catenin synergizes with CBP to stimulate the transcriptional activation of TCF4/β-catenin (Ken-Ichi Takemaru and Randall T. Moon, 2000 J. Cell. Biol., 149, 2, 249-254).

Reverse-turn mimetics and method relating thereto


An electric damper which does not transmit unbalance wheel vibration to a vehicle body is provided. A low-pass cutoff frequency setting unit and a high-pass cutoff frequency setting unit respectively set the cutoff frequencies for band-stop filters to a frequency band corresponding to unbalance wheel vibration based on a signal indicating a vehicle speed from a vehicle speed sensor, and a function as a band-stop filter comprising a low-pass filter computation unit, a high-pass filter computation unit and an adder is computed for a displacement rate of the vertical motion of a wheel calculated by a differentiating unit in a damper control unit. A damper control amount computation unit calculates a control amount of controlling an electric motor for a motor-driven damper based on the calculated filtered displacement rate, and outputs a control signal to a motor driving unit through a driving circuit output unit.

1. Field of the Invention
The present invention relates to an electric damper for a vehicle suspension device.
2. Description of the Related Art
JP 2007-276571 A discloses a technology relating to an electric damper (motor-driven damper device) for a vehicle suspension device having a rack and pinion mechanism. Moreover, JP 2005-256921A discloses a technology of detecting a vertical acceleration parts on the spring of a vehicle using an acceleration sensor provided right above each wheel to detect the vertical acceleration, acquiring the power spectrum distribution of the vertical acceleration, reading out a power spectrum in a frequency region relating to goodness/poorness of the ride comfort, and changing the cutoff frequency of a low-pass filter in accordance with the sum of the spectra, thereby controlling the damper characteristic.
According to JP 2005-256921A, however, if the electric damper is set to have a characteristic with a high damping force, i.e., a characteristic for a sporty vehicle that a ride comfort is hard, wheel vibrations (hereinafter, "unbalance wheel vibration") caused due to the unbalance of a wheel are transmitted to a vehicle body on the spring, so that a driver feels uncomfortable vibrations.
It is possible to reduce transmission of the unbalance wheel vibration to the vehicle body by setting the damping force in a high frequency region low. However, setting the damping force to vertical vibration of a wheel low is not desirable since vehicles having a ride comfort set to a hard characteristic are generally sporty vehicles, and the ride comfort is set hard to drive the vehicle with the driving characteristic being emphasized while acquiring road-surface information from vibrations from a road surface. Because the unbalance wheel vibration is not good for transmitting road-surface information, but the unbalance wheel vibration obscures road-surface information, so that the unbalance wheel vibration is not desirable for sporty vehicles.
The present invention is made to overcome the foregoing problem, and it is an object to provide an electric damper that does not transmit unbalance wheel vibration to a vehicle body to realize comfort driving.


A direct current stabilization power supply apparatus, comprising: an output control device which generates a voltage corresponding to a drive current given and outputs it as an output voltage; a direct current stabilization portion which gives the drive current to the output control device to equalize a comparison voltage corresponding to the output voltage with a predetermined reference voltage and makes the output control device generate a desired output voltage; and a drive current limitation portion which monitors the comparison voltage and lowers the drive current according to a drop in the comparison voltage, wherein, when the comparison voltage is equal to or lower than a predetermined threshold voltage, the drive current limitation portion carries out an operation to hold the drive current at a predetermined lower-limit current value, or an operation to clamp a lower-limit value of the comparison voltage at a predetermined voltage value. Accordingly, even if the output voltage becomes a negative voltage, it is possible to secure a suitable drive current.

1. Field of the Invention
The present invention relates to a direct current stabilization power supply apparatus which has an output short-circuit protection function.
2. Description of the Related Art
Conventionally, there are many direct current stabilization power supply apparatuses disclosed which have a protection function to protect an output transistor from a large current or a high power besides a regulator function to drive and control the output transistor to generate and output a desired output voltage. Among such direct current stabilization power supply apparatuses, there are many power supply apparatuses in which a correlation between an output voltage Vo and a drive current Ido shows a fold-back type drooping characteristic. In such a direct current stabilization power supply apparatus, when the output voltage drops, the drive current is limited according to the fold-back type drooping characteristic.
Here, a graph illustrating a general fold-back type drooping characteristic is shown in FIG. 12. As the graph shows, when the output voltage drops, the drive current is limited according to the fold-back type drooping characteristic. Conventionally, there is a problem that when the power supply apparatus is turned on with the output voltage being a negative voltage, the drive current becomes 0 and the output voltage cannot be boosted. However, JP-A-2004-348216 proposes an improvement measure to this problem.
According to this improvement proposition, a correlation between the output voltage and the drive current has a fold-back type drooping characteristic shown in FIG. 13, and a drive current flows at the time of turning on the power supply apparatus even if the output voltage is a negative voltage. Accordingly, the output voltage starts up according to the fold-back type drooping characteristic shown in FIG. 13, and the problem mentioned above is eliminated. As another document on the prior art, besides the patent document mentioned above, there is JP-A-2005-251130.
In the power supply apparatus mentioned above, when lowering the drive current to curb heat quantity at the time of shot-circuit (Vo=0 V), it is necessary to drop, for example, a voltage that is clamped at the time of short-circuit to a negative voltage. However, by dropping the clamped voltage, the fold-back type drooping characteristic in the power supply apparatus becomes substantially the same as the antecedent fold-back type drooping characteristic, and the dive current can become 0 at a small negative voltage.
Besides, if the drive current at the time of short-circuit is excessively lowered, the drive current can become 0 even at a relatively low negative voltage (e.g, −0.1 V) because of temperature changes and differences in circuit-device characteristics. Accordingly, because it becomes hard to secure a stable operation at the time of turning on the power supply apparatus, it is not desirable to excessively lower the drive current at the time of shirt-circuit.

Direct current stabilization power supply


An interlock assembly for a circuit breaker prevents inadvertent installation or removal of the circuit breaker from a circuit breaker panel while current is flowing. The interlock assembly cooperates with the circuit breaker panel to physically prevent the circuit breaker from being inserted into the circuit breaker panel until the circuit breaker is put into a tripped state. Likewise, the interlock assembly cooperates with the circuit breaker panel to physically prevent the circuit breaker from being taken out of the circuit breaker panel until the circuit breaker is put into a tripped state. This ensures that the circuit breaker will not be inadvertently installed or removed from the circuit breaker panel while current can immediately flow or is flowing through the circuit breaker.

Circuit breakers provide automatic power interruption to an electrical load when fault conditions occur, such as an overload current or a short circuit. A circuit breaker is typically deployed on a line conductor between a load and a current source, usually an electric main. The current source provides current over the line conductor through the circuit breaker and to the load, which is typically also connected to ground or neutral. A neutral conductor provides a return path from the load through the circuit breaker and back to the current source.
A typical circuit breaker has a load terminal for connecting the circuit breaker to the load and a line terminal for connecting the circuit breaker to the line conductor. A braided wire conductor carries current from the line terminal to one side of a trip unit. The other side of the trip unit is connected to the load terminal by an electrical contact that provides a path for current to flow through the circuit breaker. The trip unit typically includes an armature having an opening therein for engaging and holding a latch of the trip unit. During normal operation, the armature remains in the latched position and current is allowed to flow through the circuit breaker. When a fault condition occurs, the armature is moved to the unlatched position, tripping the circuit breaker and interrupting the flow of current.
In most residential and commercial establishments, the circuit breakers are installed in a circuit breaker panel that serves as a central distribution point for the various loads in the establishments. The circuit breaker panel typically has a plurality of compartments and the circuit breakers are plugged or otherwise installed in the panel by pressing or inserting them into the compartments. Each compartment typically includes a bracket, guides, openings, and/or other means for receiving and engaging the circuit breaker.
Occasionally, it may be necessary to unplug a circuit breaker from the circuit breaker panel. For example, the circuit breaker may need to be removed for servicing or maintenance, or it may need to be replaced with another circuit breaker with a different current rating due to new load requirements. Preferably the circuit breaker panel is de-energized before the circuit breaker is removed, but in some situations it is not feasible to de-energize the panel. In these situations, it is prudent to ensure the circuit breaker is in the tripped state so current is not flowing at the time the circuit breaker is removed from the panel. If the circuit breaker is inadvertently removed while current is flowing, arcing may occur, potentially leading to electrical shock, arc flash, load damage, or other hazardous event. For the same reasons, it is equally important to ensure the circuit breaker is in the tripped state during installation so the circuit breaker is not inadvertently plugged in while current is able to immediately flow through it.
Accordingly, a need exists for an improved circuit breaker that addresses the above and other problems, and particularly a circuit breaker with a mechanism that prevents the circuit breaker from being inadvertently installed or removed while current can immediately flow or is flowing through the circuit breaker.

Panel board to circuit breaker positive retention interlock


Method for determining geometric characteristics of a hydraulic fracture includes performing a baseline seismic survey for a geological formation. A velocity model is created by combining results of the baseline seismic survey and additional geoscientific information, and seismic properties of the geologic formation are evaluated. At least one strong flat lithological reflector disposed below a planned fracture is identified. A numerical model of elastic wave propagation in the geologic formation with a fracture with given properties is created. Hydraulic fracturing is performed and after fracturing when the fracture is maintained open and pressurized seismic surveys are performed. The fracture's dimensions and shape are determined by comparing the first and the second reflected and refracted seismic signals and solving an inverse problem with the use of the numerical model.

Formation hydraulic fracturing is a well-known method for enhancing hydrocarbons' production from a well by means of fracture generation. A high-viscosity fluid, also referred to as the hydraulic fracturing fluid containing a propping agent (proppant) is injected into a formation to create a fracture in the production interval and fill the fracture with the proppant. For the efficient use the fracture must be located inside the production interval and must not protrude into the adjacent strata as well as be of sufficient length and width. Therefore, obtaining reliable information about hydraulic fractures is, therefore, crucial for optimizing their design and efficient planning of the fields operation.
Nowadays the geometry of fractures is determined using various technologies and methods. Most wide-known are passive seismic methods (the so-called hydraulic fracture visualization) ensuring the evaluation of the spatial orientation of a fracture and its length during the hydraulic fracture activities and based on recording and locating of micro-seismic events generated by cracking of the rock near the edges of propagating fracture. The shape characterization has some intrinsic uncertainty, because the scatter of natural microseismic events around the fractured zone can be large compared to typical fracture width. The method does not always work: due to low emission amplitudes or high attenuation registered signal may be low compared to a noise level. Hydraulic fracture monitoring activities using passive seismics methods are very seriously restricted by the fact that they require a second observation well located within reasonably small distance from the main treatment well. Small distance is required to ensure registration of relatively weak microseimic events, whose amplitude mostly depends on in-situ properties and state of the rock and is out of operator's control. The second well is required, because it is difficult to deploy acquisition string simultaneously with the hydraulic fracturing treatment involving high pressure pumping, which may be very noisy.
Hydraulic fracture seismics using an active seismic source are also known. They may provide a higher (compared with the passive seismics methods) amplitude of the registered useful signal. Thus, U.S. Pat. No. 5,574,218 suggests a method for determining a length and an azimuth of a hydraulic fracture after it has been formed without the need for positioning sensors at subsurface locations by performing two or more subsequent surface seismic acquisitions. The method comprises performing a baseline seismic survey to determine a seismic response of the undisturbed formation followed by one or more seismic surveys when the fracture is still open and under pressure; studying the differences in seismic responses enables to determine the fracture length and azimuth. A seismic source and seismic receivers' array are positioned at substantially equal distances from the treatment well with this distance being equal to approximately one-half of the depth of the layer to be fractured. The method described is not efficient for hydraulic fracture characterization, because, apparently, it aims at registration of the differential signal diffracted from the fracture in upward direction, which will have small amplitude.
In WO 99/04292, it is suggested to detect horizontal and vertical edges of a fracture by identifying a boundary between unaffected and shadowed direct raypaths, when acquisition string and a source are on the opposite sides of the open hydraulic fracture and by distinguishing the raypaths reflected from the fracture from raypaths transmitted in the reservoir on the same side from the fractures as the seismic source. In both cases the detection of the fracture edges is done by detecting absence or presence of an S-component signal completely shadowed or reflected by the open fluid-filled fracture. This method is aimed at the detection of the strongest component of the seismic disturbance introduced by the hydraulic fracture when it is maintained in open condition, this disturbance is the share shadowing by the fracture due to zero elastic shear modulus in the fracture fluid. The described method has very high requirements to the field development diagram and plan, especially as far as the well trajectory is concerned. The method requires several dedicated observation wells, preferably, located within 100 m distance from the treatment well which need to be stopped from production during the survey; to detect shadowed or reflected rays the seismic sensors should be positioned below the fracture. Finding such wells occasionally has quite low chance for success, it is more likely that getting such wells would require costly dedicated drilling program, because typically wells are not drilled far below the production depth.


The invention discloses a sensor for 360-degree magnetic field angle measurement. It comprises multiple GMR (or MTJ) stripes with identical geometries except for their orientations. These are used as the building blocks for a pair of Wheatstone bridges that signal the direction of magnetization of their environment. The design greatly enhances sensitivity within GMR stripes and does not require an additional Hall sensor in order to cover the full 360 degree measurement range.

The present invention discloses a single chip solution for a GMR (giant magneto-resistance) or MTJ (magnetic tunneling junction)-based sensor with a full 360-degree range capability for magnetic field measurement. This design greatly enhances sensitivity relative to prior art devices. It does not require an additional Hall sensor in order to provide a full 360 degree range of measurement. It may be implemented using either a GMR (giant magneto-resistance) or an MTJ (magnetic tunnel junction) device, which terms we will use inter-changeably in the description that follows.
As illustrated in FIG. 1, a GMR structure is deposited as a multi-layer structure starting with a seed-layer(11)/AFM(12)/AP2(13)/Ru(14)/AP1(15)/Cu(16)/free layer(17)/capping layer(18), where a ferromagnetic sub-layer AP2, non-magnetic spacer Ru and a ferromagnetic reference sub-layer AP1 form an anti-parallel synthetic pinned layer. In an MTJ structure, the Cu layer just below the free layer is replaced by an insulating tunnel barrier layer, (typically AlOx). The synthetic layer is further pinned by anti-ferromagnetic layer (AFM). The pinning field, or exchange anisotropy, is related to the exchange coupling between an antiferromagnetic (AFM) layer and a ferromagnetic sub-layer (AP2) [2].
In a conventional angle sensor, the sensing elements are four long AMR (anisotropic magneto-resistance) [1] stripes oriented in a diamond shape with the ends connected together by metallization to form a Wheatstone bridge, as shown in FIG. 2. The top and bottom connections of the four identical elements are given a direct current stimulus in the form of a supply voltage (Vs), with the remaining side connections to be measured as ΔV. With no magnetic field present, the side contacts should be at the same voltage. To have the elements' magnetization directions align with an externally applied magnetic field, the latter must be large enough to saturate the permalloy material.
With the AMR elements connected in this fashion to form the Wheatstone bridge, the side contacts will produce a different voltage (ΔV) as a function of the supply voltage, MR ratio, and the angle; which is the angle between the element current flow and element magnetization (M). One set of this bridge only provides a measurement of angles ranging from −45 degree to +45 degree. Combined with a second bridge which is oriented 45-degree in rotation from the first set, a wide range of angles, from −90 degree and +90 degrees, can be measured.
In this prior art design, due to the characteristic of the AMR effect, one of the AMR Wheatstone bridges only detects within a 90-degree angle range while two AMR Wheatstone bridges with 45-degrees orientation difference only allow measurement over a 180-degree angle range. In order to measure a full 360-degree angle, an additional Hall sensor must be used in combination with the two Wheatstone bridges.

Magnetic field angle sensor with GMR or MTJ elements


A non-neurotoxin, arginine residue-containing non-naturally occurring lytic peptide comprising a sequence of amino acid residues in sufficient number and arrangement to confer lytic activity to the peptide, wherein the guanido groups of the arginine residues and the .alpha.-amino group of the N-terminal amino acid are sufficiently glyoxylated to impart enhanced tryptic, chymotryptic, and aminopeptidase digestion resistance to the peptide. The compositions of the invention are suitable for in vivo administration. A method of-making the same, to impart enhanced tryptic digestion resistance thereto, comprising glyoxylating the guanido groups of the arginine residues and the .alpha.-- amino group of the N-terminal amino acid with glyoxa containing buffer for sufficient time and at sufficient conditions to glyoxylate the side chain and .alpha.-amino groups to sufficient extent to confer enhanced proteolytic digestion resistance to the peptide.

1. Field of the Invention
The present invention relates to glyoxylation-stabilized, arginine-containing synthetic lytic peptide compositions with enhanced resistance to proteolytic digestion, and to methods of making the same.
2. Description of Related Art
Naturally occurring amphipathic lytic peptides play an important if not critical role as immunological agents in insects and have some, albeit secondary, defense functions in a range of other animals. The function of these peptides is to destroy prokaryotic and other non-host cells by disrupting the cell membrane and promoting cell lysis. Common features of these naturally occurring amphipathic, lytic peptides include an overall basic charge, a small size (23-39 amino acid residues), and the ability to form amphipathic .alpha.-helices. Several types of amphipathic lytic peptides have been identified: cecropins (described in U.S. Pat. Nos. 4,355,104 and 4,520,016 to Hultmark et al.), defensins, sarcotoxins, melittin, and magainins (described in U.S. Pat. No. 4,810,777 to Zasloff). Each of these peptide types is distinguished by sequence and secondary structure characteristics.
Several hypotheses have been suggested for the mechanism of action of the lytic peptides: disruption of the membrane lipid bilayer by the amphipathic .alpha.-helix portion of the lytic peptide; lytic peptide formation of ion channels, which results in osmotically induced cytolysis; lytic peptide promotion of protein aggregation, which results in ion channel formation; and lytic peptide-induced release of phospholipids. Whatever the mechanism of lytic peptide-induced membrane damage, an ordered secondary conformation such as an .alpha.-amphipathic helix and positive charge density are features that appear to participate in the function of the lytic peptides.
Active analogs of naturally occurring lytic peptides have been produced and tested in vitro against a variety of prokaryotic and eukaryotic cell types (see for example Arrowood, M. J., et al. J. Protozool. 38: 161s [1991]; Jaynes, J. M., et al. FASEB J. 2: 2878 [1988]), including: gram positive and gram negative bacteria, fungi, yeast, envelope viruses, virus-infected eukaryotic cells, and neoplastic or transformed mammalian cells. The results from these studies indicate that many of the synthetic lytic peptide analogs have similar or higher levels of lytic activity for many different types of cells, compared to the naturally occurring forms. In addition, the peptide concentration required to lyse microbial pathogens such as-protozoans, yeast, and bacteria does not lyse normal mammalian cells.
The specificity of the lytic action depends upon the sequence and structure of the peptide, the concentration of the peptide, and the type of membrane with which it interacts. Jaynes et aL Peptide Research 2: 157 (1989) discuss the altered cytoskeletal characteristics of transformed or neoplastic mammalian cells that make them susceptible to lysis by the peptides. In these experiments, normal, human non-transformed cells remained unaffected at a given peptide concentration while transformed cells were lysed; however, when normal cells were treated with the cytoskeletal inhibitors cytochalasin D or colchicine, sensitivity to lysis increased. The experiments show that the action of lytic peptides on normal mammalian cells is limited. This resistance to lysis was most probably due to the well-developed cytoskeletal network of normal cells. In contrast, transformed cell lines which have well-known cytoskeletal deficiencies were sensitive to lysis. Because of differences in cellular sensitivity to lysis, amphipathic peptide concentration can be manipulated to effect lysis of one cell type but not another at the same locus.
Synthetic lytic peptide analogs can also act as agents of eukaryotic cell proliferation. Peptides that promote lysis of transformed cells will, at lower concentrations. promote cell proliferation in some cell types. This stimulatory activity is thought to depend on the channel-forming capability of the peptides, which somehow stimulates nutrient uptake, calcium influx or metabolite release, thereby stimulating cell proliferation (see Jaynes, J. M. Drug News & Perspectives 3: 69 [1990]; and Reed, W. A. et al. Molecular Reproduction and Development 31: 106 [1992]). Thus, at a given concentration, these peptides stimulate or create channels that can be beneficial to the normal mammalian cell in a benign environment where it is not important to exclude toxic compounds.
The synthetic lytic peptide analogs typically contain as few as 12 and as many as 40 amino acid residues. A phenylalanine residue is often positioned at the amino terminus of the protein to provide an aromatic moiety analogous to the tryptophan residue located near the amino terminus of natural cecropins and a UV-absorbing moiety with which to monitor the purification of the synthetic peptide. The basis for the design of these lytic peptide analogs is that an amphipathic peptide of minimal length and containing overall positive charge density effects lytic activity. Peptides that have the structural motif of a .beta.-pleated sheet and overall positive charge density can also effect lytic activity.
As discussed in the preceding paragraph, in vitro laboratory tests of the lytic peptide analogs have been successful. However, the use of the lytic peptide analogs in vivo could be considerably limited in circumstances where proteases may digest the peptide analogs before sufficient pathogen cell lysis has occurred. In particular, the high concentration of positively charged amino acids such as lysine and arginine make the synthetic peptides susceptible to tryptic digestion. The secondary conformation of the peptides sequesters the hydrophobic amino acid residues, thus shielding them from interaction with proteases such as chymotrypsin, which hydrolyzes peptides at bulky or aromatic amino acid residues. This proteolytic susceptibility is a general problem for peptides and proteins when used in vivo. Many techniques are suitable for stabilizing proteins for in vitro use but are not appropriate for in vivo or oral administration to humans and animals.
Several studies teach that chemical modification of arginine residues has been used to study structure-function relationships in a variety of naturally occurring proteins and their substrates. For example, Busby et al., Arch. Biochem. Biophys 177: 552 (1976) teach that chemical modification of arginine residues with 1,2-cyclohexanedione can be used to study the essential nature of arginine residues in the maintenance of biological activity. This report states that the arginine residues in the test protein, plasma .alpha.-1 anti-trypsin, do not participate in the catalytic reaction.
Lin et al., Biochim. et Biophys. Acta 1159: 255 (1992) teach that .alpha.-bungarotoxin, a long-chain neurotoxin containing three arginine residues, can be derivatized on the arginine residues using either 1,2-cyclohexanedione or p-hydroxylphenylglyoxal. The effect of arginine modification on biological activity was tested by examining the binding activity of the modified toxin to the nicotinic acetylcholine receptor. None of the modified arginine residues were essential for binding to the receptor, however, the modification resulted in diminution of lethality and binding affinity. Thus, the article relates only to binding characteristics and biological activity of a modified neurotoxin and does not address enhanced proteolytic resistance of the protein.
Patthy et al., J. Biol. Chem. 250: 557 (1975) and J. Biol. Chem. 250: 565 (1975) teach that modification of arginine residues in lysozyme using 2,3-butanedione, phenylglyoxal or glyoxal showed that lysozyme retained biological activity.
Accordingly, it would be a significant advance in the art to provide a method of producing chemically modified physiologically active lytic peptides that have enhanced resistance to proteolysis.
It would be particularly desirable to provide a method of producing such peptides so that the modified peptides have enhanced proteolytic stability and retain their physiological activity for in viva applications against pathogenic microbial organisms such as bacteria, yeast, fungi, and protozoans; neoplastic or transformed cells; envelope viruses; and virally-infected cells.
These and other objects and advantages will be more fully apparent from the ensuing disclosure and claims.

Modified arginine containing lytic peptides and method of making the same by glyoxylation


An inventive engine valve assembly may comprise a rotatable shaft having a fluid passageway extending therethrough, preferably in a direction orthogonal to the longitudinal axis of the shaft. The shaft may be positioned such that the fluid passageway is in communication with an engine cylinder during selected portions of shaft rotation. The shaft may be arranged to rotate with the crankshaft. When used as an intake valve, the valve may be arranged to allow fluid communication with the cylinder during an intake stroke. When used as an exhaust valve, the valve may be arranged to allow fluid communication with the cylinder during an exhaust stroke.

This invention relates generally to engines, such as internal combustion engines, and more specifically to an intake and/or exhaust valve assembly and timing system for an engine.
Internal combustion engines are generally known. Many engines utilize at least one intake valve and at least one exhaust valve per cylinder. The valves are typically spring-loaded or biased in a normally closed configuration and are opened through a mechanical interaction with a camshaft.
The maximum engine speed or upper RPM limit in some engines may be controlled by the intake and exhaust valves and the related valve train. Inertia of the valve assemblies during the alternative movements can prevent the valves from opening or closing appropriately at high engine speeds, such as above redline.
Traditional valve assemblies may also substantially reduce the rated power output of the engine, as engine power must be used to operate the valve systems, which may include rotating camshafts, actuating rocker arms, compressing valve springs and actuating the moving mass of the valve and valve stem.
Further, traditional valve assemblies generally include many moving parts that may wear and eventually fail.
It would be desirable for an engine valve assembly to have fewer moving parts than traditional valve assemblies. It would further be desirable for an engine valve assembly to be capable of very high speed operation, and thus not limit the maximum speed of engine operation.
All US patents and applications and all other published documents mentioned anywhere in this application are incorporated herein by reference in their entirety.
Without limiting the scope of the invention a brief summary of some of the claimed embodiments of the invention is set forth below. Additional details of the summarized embodiments of the invention and/or additional embodiments of the invention may be found in the Detailed Description of the Invention below.
A brief abstract of the technical disclosure in the specification is provided as well only for the purposes of complying with 37 C.F.R. 1.72. The abstract is not intended to be used for interpreting the scope of the claims.


The invention for the nanocompatibilizer composed of a nanoclay and a compatibilizer prepared through a melt blending process is disclosed. The enhanced mechanical properties stemming from the increased compatibility for metallocene polyethylene/starch blends are attained with the addition of the nanocompatibilizer, in comparison with neat compatibilizer, which signified the role of nanocompatibilizer in the derived nanocomposites.

1. Field of the Invention
The invention relates to a method for forming composite materials, more particularly to a method for forming polymer-blend nanocomposites using a nanocompatibilizer.
2. Description of the Prior Art
Due to the rising consciousness on the environmental protection, the development of various biodegradable polymers has been received much attention by the industry in recent years, especially the biodegradable polymers applied in the packaging industry. However, the price of biodegradable polymers is usually quite high, and the mechanical properties such as tearing resistance etc. are inferior to the conventional packaging materials, such as polyethylene (PE). Therefore, for a biodegradable polymer to be commercialized successfully, it should be prepared through a blending process. In particular, the starch-based biodegradable polymers are widely studied due to the relatively low price of raw starch materials. However, there is quite a lot of moisture sensitivity problem for these starch-based biodegradable polymers, which in turn may affect their mechanical properties by some parameters. To better understand this behavior, nonpolar metallocene catalyzed polyolefin elastomer (mPE) was selected to blend with starch as an illustrative system for the current invention.
Furthermore, because different polymers show different properties, two kinds of polymers are often blended together to obtain a required property, which is a conventional way to produce the commercialized products. In general, the compatibility of different polymers is usually not good, thus a compatibilizer is often added to improve the compatibility of different polymers. Specifically, a clay-reinforced compatibilizer, termed nanocompatibilizer, was added to improve the interfacial strength of mPE/starch blends by exploiting the concept of nanocomposites.
In 1988, Toyota Company in Japan issued Nylon 6/clay nanocomposite patent (U.S. Pat. No. 4,739,007) at the first time. The organic alkyl ammonium was used to exchange the cations of silicate within the inorganic clay gallery, and to modify the hydrophilic clay into hydrophobic nanoclay. With the addition of modified clay during the in-situ polymerization of Nylon 6, the heat distortion temperature and mechanical properties of pristine Nylon 6 were improved significantly. Especially the above-mentioned efficacy could be reached by adding only a small amount of clay (about 3 to 5%), which was different from the conventional composite with high loading of inorganic substance (about 20%). It became the earliest commercialized nanocomposites.
Moreover, in 1992 Toyota Company cooperated with the Ube company to improve the modification technique of nanoclay. The Nylon 6 monomer, ω-caprolactam, was grafted to Na+ type Montmorillonite nanoclay directly. Then it was polymerized to form the exfoliated type Nylon 6/clay nanocomposite (U.S. Pat. No. 5,102,948). The tensile strength, tensile modulus, flexural modulus and heat distortion temperature etc. were increased significantly. Additionally, the dimensional stability, gas barrier property and flame retardant property etc. were much better than those of conventional Nylon 6 composites.
To exploit the uniqueness of nanoclay, in U.S. Pat. No. 6,339,121, Rafailovich et al. used the modified nanoclay as a compatibilizer for incompatible polymers. The patent pointed out that the organic modified nanoclay could be added into polymer blends, in order to improve the compatibility between two incompatible polymers, and to develop a more homogeneous system as well. However, this kind of system must be annealed at high temperatures for a day to promote the compatibility of incompatible polymers.
Upon searching and reviewing the prior art, the patented invention of relevant technology is still insufficient, and there is little research and development on any relevant technology, so more efforts should be made in the industry in the future.
Upon assessing the technological development of the prior art, although polymer/clay nanocomposites have established a milestone for major technological development in recent years, in fact the performance/cost ratio should be considered carefully in future applications. Therefore, up to date only a few nanocomposite systems are commercialized successfully.

Polymer blend nanocomposites using nanocompatibilizer and method of manufacture thereof


A system and method for generating a patient-specific organ model is provided. The method may include receiving ultrasound images of an organ and probe position data corresponding with each of the ultrasound images. The method may include receiving identification of landmarks in the ultrasound images corresponding with pre-defined landmarks of a generic geometric organ model. The method may include automatically identifying surface points of the organ in the ultrasound images. The method may include generating a patient-specific ultrasound point cloud of the organ based on the received identification of the landmarks, the automatically identified surface points of the organ, and the probe position data. The method may include registering a point cloud of the generic geometric model to the patient-specific ultrasound point cloud to create a patient-specific organ model. The method may include presenting the patient-specific organ model at a display system.

Ultrasound imaging is a medical imaging technique for imaging organs and soft tissues in a human body. Ultrasound imaging uses real time, non-invasive high frequency sound waves to produce a two-dimensional (2D) image and/or a three-dimensional (3D) image.
Traditionally, documentation of ultrasound examinations has been limited to still image snapshots of representative structures. These still image snapshots typically have limited value for re-evaluating an examination or comparing with older examinations. Still images also make it difficult to determine whether a lesion has appeared since a previous examination. Instead, doctors may be left to rely on whether the lesion was mentioned in the previous report. Such low levels of confidence are incompatible with the demands of diagnostic imaging modalities.
Due to some of the difficulties associated with ultrasound imaging, other imaging modalities such as computed tomography (CT) and magnetic resonance (MR) imaging modalities may be used to perform various examinations, such as liver volume measurements and studies tracking disease progression over time. CT and MR imaging modalities, however, are more expensive and invasive than ultrasound imaging. For example, CT examinations expose patients to radiation and both CT and MR examinations may use a contrast injection that may be harmful to patients with renal challenges.
Further limitations and disadvantages of conventional and traditional approaches will become apparent to one of skill in the art, through comparison of such systems with some aspects of the present disclosure as set forth in the remainder of the present application with reference to the drawings.

Method and system for creating and utilizing a patient-specific organ model from ultrasound image data


An apparatus and method for using audible tones generated by a vehicle driver's use of a tone actuator in a vehicle. The vehicle generates an audible tone which is capable of being heard by the driver as well as being received by a processor in the vehicle, the processor accessing a memory table correlating each distinct tone with a distinct vehicle control function. The processor outputs a signal to select the vehicle control function corresponding to the generated tone.

The present disclosure is related to vehicle control systems and, more particularly, to vehicle control systems using audible sounds.
Voice recognition systems have been devised to allow a control system to take pre-determined actions in response to receiving a particular spoken voice command. In the vehicle field, such voice commands can be used to control the audio system of the vehicle as well as to communicate externally of the vehicle.
However, vehicles are produced throughout the world and thus use voice commands in the language spoken in a particular country. This requires different sound recognition interfaces and may not address dialects or languages spoken by only a small percentage of the people in a country.
US Patent publication US 2012/0229253 discloses a sound activated wireless vehicle door unlock device which is capable of unlocking the vehicle door locks in response to a pre-determined series of knocks or tones issued by the vehicle user.
U.S. Pat. No. 6,148,251 discloses vehicle control systems using voice or tone commands. This system converts the tones generated by tone generators when a steering wheel mounted push buttons are actuated. The tones are only electrical frequencies which are superimposed over the signal frequency sent from the steering wheel controller to the vehicle controller which then decodes the frequency to take the indicated vehicle function action. This system, however, does not generate audible tones which the vehicle driver can hear.
It is known that vehicle drivers, particularly drivers with many years of driving experience, frequently become bored or distracted while driving for a considerable length of time, particularly on highways.
It would be useful to provide an audible recognition system for controlling selected vehicle functions which can also alleviate driver boredom and distraction.


A force sensor assembly includes a force sensor, a first support member, a threaded portion, an opening made in the first support member, a nut, a restricting member and a spacer. The nut is screwed onto the threaded portion which is inserted through the opening. The restricting member is provided between the force sensor and the nut. The spacer, which is provided between the force sensor and the nut, is deformable in a direction of its thickness. The shape of the spacer is adapted to avoid interference with the restricting member. Before the nut is tightened onto the threaded portion, a summation of thickness for the first support member and the spacer is adapted to be not less than a height of the restricting member. The nut is tightened up with a predetermined fastening torque until the spacer deforms so that the nut strikes the restricting member.

The present invention relates to a force sensor assembly, and more particularly relates to a force sensor assembly, which is able to provide accurate measurement of a force.
An air bag system is mounted on a vehicle so as to provide safety for a passenger in case of a collision. A sensor is installed in a side seat in order to control the air bag system. A force sensor is typically selected for this sensor, which is able to measure the weight of a passenger when he is seated on the seat. This force sensor, which detects a seated passenger, generates a signal for controlling inflation of the air bag system. The control includes a case where a system prevents an air bag from inflating if the system determines that a passenger is a child, and another case where a system adjusts speed of inflation of an air bag according to the weight of a passenger, for example.
Patent document 1 discloses a technique associated with a force sensor assembly. This technique employs an upper rail, on which a seat cushion frame is disposed, is slidably supported on a seat track. The seat frame and upper rail have respective through holes, which are aligned with each other. A nut is tightened onto a threaded portion of the force sensor, which is inserted through the through holes. When a passenger is seated on a seat, the seat cushion frame pivots relative to the upper rail, increasing a distance between the seat cushion frame and the upper rail. This produces a tensile force acting on the threaded portion. In this way, the force sensor detects the force. The technique described above, which requires a mechanism that allows the seat cushion frame to pivot relative to the upper rail, inevitably renders the assembly complex.
Accordingly, it may be preferable in terms of simplification to place another type of sensor, which senses a compressive force acting downward instead, between a seat cushion frame and an upper rail, as disclosed in patent document 2.    Patent document 1: 2000-203324 (paragraphs 0024, 0029, FIG. 3)    Patent document 2: U.S. Pat. No. 3,268,128 (08-005475) (paragraphs 0013 to 0017, FIG. 1)
However, because the force sensor assembly disclosed in the patent document 2 requires that tightening of a nut onto the threaded portion does not have an adverse effect on the force sensor, it will be necessary to introduce more complex operation for tightening the nut. If an excessive torque is imposed on the nut, for example, it will affect adversely the force sensor to provide less accuracy due to a tensile stress axially acting on the threaded portion. In addition, because an origin of the force sensor is shifted, an available range for detecting a force will be narrowed, which leads to difficulty in implementing highly accurate detection.
There is also another problem that decreases accuracy for detection. It may be that the excessive torque induces torsion about an axis of the force sensor.
On the other hand, when tightening is carried out paying attention to an effect on the force sensor, it may possibly occur that the torque falls short to create looseness between the seat cushion frame and the upper rail, which is a cause for incomplete fastening.
A force sensor assembly disclosed in the patent document 1, which is secured to a seat frame and a sliding frame, tends to suffer preload when it is mounted. There are several causes for this preload, such as an error in parallelism of the sliding frame, variation in dimensions for a sensor mounting area of the seat frame which is created during its fabrication and a displacement of mounting position of a seat onto a vehicle body. In this case, distortion caused by the preload in the force sensor may add up to a false detection including the distortion in addition to the true weight of a passenger, or may create a measurement error due to deterioration of accuracy of the force sensor.


A porous composite metal oxide, including a mixture of first ultrafine particles containing alumina and second ultrafine particles containing zirconia, wherein the first ultrafine particles and the second ultrafine particles are uniformly dispersed in such a way as to satisfy a condition that standard deviations of content ratios (% by mass) of all metal elements contained in the porous composite metal oxide at 0.1% by mass or more are each 10 or less, the standard deviations being obtained by measuring content ratios of the metal elements at 100 measurement points within a minute analysis region of 20 nm square by energy dispersive X-ray spectroscopy using a scanning transmission electron microscope equipped with a spherical aberration correction function.

Various catalysts have so far been developed as catalysts for purification of exhaust gas with which noxious substances emitted from an internal combustion engine of an automobile or the like are treated for purification. For example, as a three-way catalyst which oxidizes CO and HC in exhaust gas and simultaneously reduces NOx therein for purification, a catalyst has widely been known in which a noble metal such as platinum or rhodium is supported on a catalyst support made of alumina, silica, zirconia, titania, and the like.
Meanwhile, as a method for producing such a catalyst support made of a composite metal oxide, the so-called coprecipitation method or the so-called hydrothermal synthesis method is generally employed. Specifically, in the coprecipitation method, an alkali is added to a solution containing multiple metal ion species, and thereby a supersaturation state where the ion concentration product in the solution is higher than the solubility product is achieved. As a result, insoluble salts of multiple kinds of metals precipitate and deposit simultaneously. Meanwhile, the hydrothermal synthesis method is a synthesis method conducted in the presence of hot water at high temperature and high pressure.
For example, International Application Japanese-Phase Publication No. 2008-526660 (Patent Literature 1) discloses a method for the formation of a composite hydroxide or oxide as a method for forming a composite hydroxide or oxide containing alumina and zirconia, and optionally containing at least one kind selected from ceria, lanthana, praseodymia, samaria, yttria, and other rare earth oxides. This method for the formation of a composite hydroxide or oxide comprising the steps of: preparing an aqueous metal salt solution consisting of water-soluble salts of metals corresponding to metals in the aforementioned composite oxide; and forming a hydroxide precipitate slurry by combining the aqueous metal salt solution with an aqueous solution of a caustic alkali in a reaction vessel with agitation at a pH greater than 8.5 to precipitate out all the metal species.
Meanwhile, Japanese Unexamined Patent Application Publication No. 2002-211908 (Patent Literature 2), which was applied by the same applicants as those of the present application, discloses a composite oxide powder produced by a method comprising: from an aqueous solution or a water-containing solution in which a cerium compound and a compound of at least one metal selected from Al, Ti and Si are dissolved, allowing the formation of a precipitate of a precursor of cerium oxide and a precursor of an oxide of the at least one metal selected from Al, Ti and Si or a compound of these precursors; aging the precipitate in a suspension state where the aqueous solution or the water-containing solution serves as a dispersant or in a state where water is sufficiently present in a system; and then calcining the precipitate. Patent Literature 2 states that, in such a composite oxide powder, ceria, and the oxide of the at least one metal selected from alumina, titania, and silica are dispersed on the no scale, and that when microanalysis on a non-overlapped single particle is carried out by means of EDS using a FE-STEM with a beam of 5-nm diameter, Ce and the at least one metal selected from Al, Ti, and Si are detected at composition ratios in ±20% of their respective feed composition ratios at 90% or more of analytical points.
However, the composite metal oxide is obtained by the so-called coprecipitation method in the invention described in each of these Patent Literatures. Such a composite metal oxide prepared by the conventional coprecipitation method or the conventional hydrothermal synthesis method has a limitation on improvement in the uniformly of the metal oxide, and a limitation on improvement in heat resistance. Accordingly, a catalyst obtained by using such a composite metal oxide as a support is not necessarily satisfactory because of its limitations on improvement in the catalytic activities and the durability thereof at high temperature.

Porous composite metal oxide, catalyst using the same, and methods for producing the porous composite metal oxide and the catalyst


An optical head includes a fixed part, a movable part movably held by a plurality of wires fixed on the fixed part, and magnets fixed to the fixed part. The movable part includes a movable-part housing, a heatsink held by the movable-part housing, a light emitting element and a light receiving element both mounted on the heatsink, magnets provided to both sides of the movable-part housing to contact the heatsink, an objective lens held by the movable-part housing to allow an emitted laser beam from the light emitting element to focus, and a diffraction grating provided between the objective lens and the light emitting element and between the objective lens and the light receiving element. The gap between each coil and the adjacent magnet is filled with ferrofluid having a higher thermal conductivity than the atmosphere.

(1) Field of the Invention
The present invention relates to an optical head comprising a light emitting element such as a laser diode, for example, an optical head for reading data recorded on an optical recording medium such as a CD or a DVD and recording data on an optical recording medium.
(2) Description of Related Art
In recent years, information technology devices utilizing light emitting elements such as laser diodes have advanced remarkably. Such information technology devices include optical disk drives capable of recording data on an optical disk by laser light and reading the recorded data therefrom. An optical head is an extremely important component of such an optical disk drive, because its performance determines that of the optical disk drive. In order to realize high-speed recording and cost reduction of the optical disk drives, various attempts have been made. In the optical disk drive, the optical head records data by modulating laser light and applying the modulated laser light to an optical disk, detects return light from an optical disk to which laser light is applied and thereby converts data recorded on the optical disk into electrical signals.
An optical system of a conventional optical head is composed of a light emitting element (for example, a semiconductor laser diode), a light receiving element (for example, photodiode), an objective lens, a collimator lens, a diffraction grating, and so on. In the conventional optical head of such a structure, the following technique is typically employed (see Japanese Unexamined Patent Publication No. 10-177733). Only a lens holding means holding the objective lens is allowed to follow an optical disk, an emitted laser beam from the light emitting element is focused on a predetermined site of the recording surface of the optical disk, and the reflected beam from the recording surface is then guided to the light receiving element by the diffraction grating. However, this technique principally has the following two problems. The first problem is that the movement of the objective lens causes a difference between the principal ray of the emitted laser beam and the optical axis of the objective lens, leading to coma aberration. The second problem is that since the optical components are arranged separately into a component in the lens holding means that can follow the optical disk and components in a fixed part that does not follow the optical disk, the number of optical components increases, leading to difficulty in downsizing the optical head.
To cope with these problems, for example, there is suggested an optical head structure in which a an objective lens, a light emitting element and a light receiving element are mounted in the same housing and are made together movable in the focusing and tracking directions (see, for example, Japanese Unexamined Patent Publication No. 8-287499). Such an optical head in which a light emitting element and a light receiving element are mounted in the same housing and which has a mechanism that drives them together in the focusing and tracking directions is hereinafter referred to as an "optical-system-integrated optical head". According to the structure of the optical-system-integrated optical head, the positional relationship among the objective lens, the light emitting element and the light receiving element does not change at all during tracking and focusing motions. This can prevent the above-mentioned coma aberration from occurring and reduce the number of optical components.
FIG. 9 is a cross-sectional view showing the structure of the conventional integrated (optical head. As shown in this figure, the conventional optical head 1000 comprises a lens holding means (housing) 1010, and the lens holding means 1010 and a heatsink (radiating plate) 1011 are integrally molded. Furthermore, the lens holding means 1010 is mounted internally with a light emitting element 1001, a light receiving element 1002, a diffraction grating 1003, a quarter-wave plate 1004, a reflecting mirror 1005, and an objective lens 1006. The light emitting element 1001 and the light receiving element 1002 are mounted on the heatsink 1011. The lens holding means 1010 is mounted externally with a movable-part-driving coil (magnetic circuit) 1007, which is fixed in an optical disk drive by an elastic supporting member (not shown). The movable-part-driving coil 1007 allows a slight movement of a moveable part which consists of the lens holding means 1010 and so on (hereinafter, referred to as an "actuator motion").
An emitted laser beam from the light emitting element 1001 in the horizontal direction (the lateral direction in FIG. 9) passes through the diffraction grating 1003 and the quarter-wave plate 1004 and thereafter is reflected by the reflecting mirror 1005 in the generally vertical direction (the upright direction in FIG. 9). The emitted laser beam reflected by the reflecting mirror 1005 is focused on a predetermined site of an optical disk 1050. The focused emitted laser beam is reflected as a laser beam having an intensity distribution corresponding to recording/site information on the optical disk 1050. This reflected laser beam again passes through the objective lens 1006 and is then reflected by the reflecting mirror 1005. The laser beam reflected by the reflecting mirror 1005 passes through the quarter-wave plate 1004. Thereafter, it is diffracted and guided to the light receiving element 1002 by the diffraction grating 1003. The intensity distribution of the reflected laser beam is detected by the light receiving element 1002 and then converted into electrical signals by a photoelectric conversion device or the like. An arithmetic circuit (not shown) calculates a tracking error signal and a focus error signal based on these electrical signals. A predetermined power variation is applied to the movable-part-driving coil 1007 based on these error signals, thereby causing electromagnetic action. In this way, the lens holding means 1010 can be moved such that the emitted laser beam is always focused on a predetermined site of the optical disk 1050. Furthermore, the optical disk drive reads data recorded in the optical disk 1050 by detecting the intensity of the reflected laser beam from a predetermined site on the optical disk 1050. The intensity distribution is detected by the light receiving element 1002.
On the other hand, a large amount of Joule heat is produced during the actuation of the light emitting element 1001 and the light receiving element 1002. This Joule heat degrades the characteristics of the light emitting element 1001 and the light receiving element 1002 themselves. Therefore, in the optical head, a heat dissipating structure must be formed in the movable part to dissipate the produced heat. Thus, in the conventional optical-system-integrated optical head, the light emitting element 1001 and the light receiving element 1002 are mounted on the heatsink 1011 and a contact area between the heatsink 1011 and the atmosphere is increased. In this manner, heat generated in the light emitting element 1001 and the light receiving element 1002 is released into the atmosphere.

Matsushita Electric Industrial Co., Ltd.


A method of socket design and fabrication for Below-the-Knee (BK) amputees that utilizes manual measurements. This method, known as BK by Measurement, utilizes a manual measurement procedure where predetermined points are identified and measurements are taken of a patient's residual limb. These measurements are recorded and thereafter entered into a software package enabling customization by the fabrication facility. Prosthetic components fabricated in accordance with the present invention provide a custom fit, while not relying on more expensive digital imaging technology. The invention also provides a method and associated system for recording and retrieving fabrication and/or fitting data associated with a prosthetic component for use with a particular patient, which can include affixing to the prosthetic component a strip debossed with indicia unique to the particular patient or prosthetic component.

Starting in the early 1990s, many Orthotic and Prosthetic (O&P) care professionals saw trends that pointed to a rapid increase in the population of amputees due mainly to longer life spans of existing amputees and an increasing number of people facing risk factors that lead to amputations. Those trends led to the desire for computer-aided design and manufacturing (CAD/CAM) to help the practitioners reduce time spent on patient care, while increasing the quality of that care. Before CAD/CAM became commonplace in the industry, practitioners relied on labor-intensive methods involving plaster casts and heavy plaster models that resulted in patients often waiting weeks for new sockets.
Vendors providing CAD/CAM worked with practitioners to develop effective systems and methods for socket sizing. Popular CAD software available today requires the use of scanning devices to digitize patient residual limb dimensions. These devices include rotating digitizers, tactile tracing pens, laser scanners, and digital cameras. Such devices, while often creating a highly accurate digital representation of the residual limb, could potentially create errors undetectable and out of the control of the practitioner. In addition, the costs involved with using CAD devices are often prohibitive, especially when calculating the high costs in dollars and time spent learning the CAD design techniques.
Thus, there is a need in the art to provide lower cost alternatives to prosthesis fitting practitioners, while continuing to utilize software in designing prosthetic components to be custom fabricated. This need, along with others, is satisfied by the present invention.

Method and associated system for recording and retrieving fabrication and/or fitting data associated with a prosthetic component


This invention relates to a resin composition having high impact strength at low temperatures, comprising a polyamide, a graft copolymer obtained by graft polymerizing a monomer mixture of an aromatic vinyl monomer and a vinyl cyanide monomer to a conjugated diene rubber, a copolymer comprising an aromatic vinyl monomer, a vinyl cyanide monomer and other vinyl monomer copolymerizable with the aromatic vinyl monomer and the vinyl cyanide monomer, a modified hydrogenated block copolymer comprising a conjugated diene rubber and styrene or its derivatives to which has been grafted an unsaturated carboxylic acid or an unsaturated carboxylic anhydride, a copolymer comprising an aromatic vinyl monomer, a maleimide monomer, an unsaturated carboxylic acid or an unsaturated carboxylic anhydride, and other vinyl monomer copolymerizable with the aromatic vinyl monomer, and a graft copolymer obtained by graft polymerizing a maleic anhydride to an ethylene-propylene rubber.

Polyamide resins have excellent abrasion resistance, electrical properties, mechanical strength and chemical resistance. Therefore, their molded products have been used for various mechanical parts as engineering plastics. However, they have drawbacks such as large water absorbance, low impact resistance, particularly low notched impact strength. Further, they also have drawbacks that they are inferior in heat resistance under a high load or in moldability because they are crystalline resins.
Since the polyamide resins have such drawbacks, their use as engineering plastics is limited, and in some cases, their excellent properties can not be adequately utilized.
Among the conventional resin compositions composed of a polyamide resin and a styrene-type polymer, there has been no resin material which has not only excellent properties of both resins but also excellent impact resistance at a low temperature.
In this point of view, U.S. Pat. No. 4,987,185 to Aoki et al discloses a resin composition capable of providing a molded product having excellent heat resistance and impact resistance, particularly, remarkably improved impact resistance at a low temperature, by blending a certain specific copolymer containing an .alpha.,.beta.-unsaturated dicarboxylic anhydride monomer component to a resin mixture comprising a polyamide resin and a certain specific rubber-modified styrene graft copolymer.
The U.S. patent discloses an impact resistant thermoplastic resin composition having a notched Izod impact strength of at least 73 kg.cndot.cm/cm as measured at 23.degree. C. and a notched Izod impact strength of at least 44 kg.cndot.cm/cm as measured at -20.degree. C. As shown in FIG. 1 of the U.S. patent, the notched Izod impact strength is rapidly reduced below -20.degree. C.
U.S. Pat. No. 4,429,076 to Saito et al discloses a thermoplastic polymer composition comprising (a) a component A consisting of modified block copolymers and the ionically crosslinked products of the modified block copolymer with one metal ion, (b) a component B of polyamides, polyurethanes, vinylalcohol polymers, polyacrylates, polymethacrylates, chlorinated hydrocarbon polymers or ionomers, and optionally (c) styrene polymer and olefin polymer to improve processability. Although the polymer composition employs a modified block copolymer, the polymer composition is not for a polymer composition having excellent impact strength at low temperatures.
It is an object of the present invention to provide a resin composition capable of providing a molded article having remarkably improved impact strength at a low temperature to about -30.degree. C., by adding a hydrogenated block copolymer to which has been grafted by an unsaturated carboxylic acid or an unsaturated carboxylic anhydride, and an aromatic vinyl copolymer containing a maleimide together, to the base resin of the present invention.

Thermoplastic resin composition with high impact strength at low temperatures


A propulsion system for a watercraft includes an upwardly inclined drive shaft to improve acceleration. The upwardly inclined orientation of the impeller shaft, and thus a similar orientation of the discharge stream exiting the jet propulsion system, causes the bow of the watercraft to ride out of the water when the watercraft is planing. The watercraft thus has less surface contact with the water, and travels faster.

1. Field of the Invention
The present invention relates in general to a watercraft, and in particular to a propulsion system for a watercraft.
2. Description of Related Art
Personal watercraft have become popular in recent years. Jet propulsion units commonly power these type of watercraft and include a motor driven impeller. The impeller operates within a water duct of the jet propulsion unit. The impeller draws in water through a water intake opening on the underside of the watercraft's hull and into the intake duct. The impeller thence compresses the water and forces it through a stationary discharge nozzle to form a jet of water. This water jet propels the watercraft.
A steering nozzle mates with the discharge end of the discharge nozzle and redirects the water jet stream for steering movement of the watercraft. For this purpose, the steering nozzle commonly rotates about at least a vertical axis and is controlled by a handlebar assembly of the watercraft.
Prior watercraft designs have attempted to minimize the vertical distance between the impeller and the water inlet opening in order to improve the performance of the jet propulsion unit. Pump inefficiencies can result when a substantial portion of the impeller's work goes to drawing water up into the water duct, as opposed to using more of that energy to increase the pressure of the water flowing into the discharge nozzle. The vertical rise of the intake duct therefore has generally been kept small by placing the impeller close to the hull underside. In this position, an impeller shaft, which drives the impeller, often slopes downward in a fore-to-aft direction. The resulting water stream exiting the discharge nozzle projects downward into the body of water in which the watercraft is operated.


A pillow has a lower surface with forward and rearward edges spaced by a length of about 9 inches coupled by perpendicular lateral side edges spaced by a width and an arcuate upper surface with a forward section formed with a radius of curvature of about 5 inches and a rearward section formed with a radius of curvature of about 15 inches. The pillow has a maximum height between the upper and lower surfaces of about 2.5 inches. The upper surface has a high point closer to the forward edge than the rearward edge. Between 40 and 45 percent of the length of the pillow is forward of the high point and 55 and 60 percent of the length of the pillow is rearward of the high point. Similarly configured planar side surfaces of the pillow have a curved upper edge and a lower edge co-extensive with the side edges of the lower surface. The method of exercising uses the pillow as a fulcrum to support a user while lifting one portion of the user's body.

1. Field of the Invention
The present invention relates to an exercise support system and more particularly pertains to providing a fulcrum about which a user's body pivots while bending between a lowered orientation and a raised orientation.
2. Description of the Prior Art
The use of exercise support systems of known designs and configurations is known in the prior art. More specifically, exercise support systems of known designs and configurations previously devised and utilized for the purpose of supporting a user while exercising are known to consist basically of familiar, expected, and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which has been developed for the fulfillment of countless objectives and requirements.
By way of example, U.S. Pat. No. 5,611,765 issued Mar. 18, 1997 to Koch relates to an Exercise Device. Also, U.S. Pat. No. 5,584,786 issued Dec. 17, 1996 to Almeda relates to An Abdominal Exercise Device. While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not describe an exercise support system that allows providing a fulcrum about which a user's body pivots while bending between a lowered orientation and a raised orientation.
In this respect, the exercise support system according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in doing so provides an apparatus of a preferred size and shape and resilience about which a user's body pivots while bending between a lowered orientation and a raised orientation.
Therefore, it can be appreciated that there exists a continuing need for a new and improved exercise support system about which a user's body moves while bending between a lowered orientation and a raised orientation. In this regard, the present invention substantially fulfills this need.