A topical, non-prescription formulation of essential oils combined with skin permeation enhancers for the clinical treatment of plantar fasciitis in humans. The formulation may exclude black pepper essential oil. The present compositions and methods relate to a method for treating a disorder chosen from plantar fasciitis, bursitis, or arthritis in humans in a patient in need thereof, comprising administering to the patient compositions having a therapeutically effective amount of a combination of isoprenoidal essential oils, for example, Tea Tree Oil and Clove Bud Oil, in combination with a skin permeation enhancer, such as DMSO, the administration comprising contacting an affected area of skin of the patient with the composition.

Plantar fasciitis is the most common cause of heel pain presenting to the outpatient clinic, and 10% of the population may present with heel pain over the course of their lives. Between 4% and 7% of people have heel pain at any given time and about 80% of these cases are due to plantar fasciitis. Plantar fasciitis is diagnosed on the basis of a history of pain on taking the first few steps in the morning, worsening pain with weight-bearing, and pain and tenderness to palpation over the medial calcaneal tubercle. Patients may have decreased ankle dorsiflexion secondary to a tight Achilles tendon. Up to one third of patients with plantar fasciitis will present with bilateral symptoms.
Etiology
Plantar fasciitis is multifactorial in etiology. Intrinsic factors include age, excessive foot pronation, obesity and limited ankle dorsiflexion. Extrinsic factors include occupational prolonged weight-bearing, inappropriate shoe wear, and rapid increases in activity level. These factors combine to create a pathologic overload of the plantar fascia at the calcaneal insertion, causing microtears in the fascia that subsequently lead to perifascial edema and increasing heel pad thickness.
As microtears within the fascia increase in size and become symptomatic, inflexibility of the posterior structures of the foot, combined with weakness of the plantar flexors during the pushoff phase of the gait cycle, alters the normal biomechanics of the foot, creating an environment of decreased efficiency of force absorption and production. The decrease in force absorption contributes to the overload of the plantar fascia and increasing degenerative changes, which include collagen necrosis, angiofibroblastic hyperplasia, chondroid metaplasia and matrix calcification. Plantar fasciitis can also be associated with various forms of arthritis, but in approximately 85% of cases there are no known systemic factors.
In runners, plantar fasciitis is primarily believed to be an overuse injury combined with training errors, training surfaces, biomechanical alignment and muscle dysfunction and inflexibility. For example, excessive pronation of the foot leads to increased tension on the plantar fascia during the stance phase of running. In athletes who are just beginning their training programs, the lower limb muscles may have yet to develop the necessary strength and flexibility, and shock absorption can be negatively affected.
Epidemiology
Ten percent of people in the United States may present with heel pain over the course of their lives, with 83% of these patients being active working adults between the ages of 25 and 65 years old. A recent survey of members of the American Podiatric Medical Association revealed that plantar fasciitis/heel pain was the most prevalent condition being treated in podiatric clinics. Within the current literature, prevalence rates of plantar fasciitis among a population of runners have been shown to be as high as 22%
The association of plantar fasciitis with increasing age is consistent with the histopathological findings of degenerative and inflammatory changes within the plantar fascia. These findings support the hypothesis that plantar fasciitis is secondary to repetitive microtrauma caused by prolonged weight-bearing activities. The constant overload inhibits the normal repair process, resulting in collagen degeneration, which causes both structural changes and perifascial edema. These changes in turn lead to a thicker heel pad, which has been shown to be associated with pain in individuals with plantar fasciitis.
Increasing heel pad thickness leads to a loss of heel pad elasticity; both of these factors are associated with increasing age and increasing body mass index (BMI). The decrease in elasticity of the fascia seen with increasing age is associated with a decrease in shock absorbing capabilities, which may be a result of the degenerative fascia's inability to resist normal tensile loads. It is this decrease in shock absorbing capability that is believed to cause the pain associated with plantar fasciitis.
In order to determine epidemiological risk factors and the current incidence of plantar fasciitis within a population of individuals with a high level of physical activity, one study (see, Scher, D. L., Belmont, P. J. Jr, Bear, R, et al., "The Incidence of Plantar Fasciitis in the United States Military," J. Bone Joint Surg. Am., 2009; 91(12):2867-2872, which is incorporated in its entirety herein by reference) accessed a database from the United States Armed Forces. The United States Armed Forces represent a physically active population of ethnically diverse male and female service members with generally high occupational demands. In this comprehensive study, female subjects, when compared with male subjects, were twice as likely to develop plantar fasciitis as their male counterparts. These findings are based on incidence rates, but tend to correlate with prevalence data seen within the existing literature. The overall incidence of plantar fasciitis in the military population was 10.55 per 1,000 person-years. Members of the Army and Marines were more likely to get plantar fasciitis than those in the Air Force.
Increased body weight and increased BMI have been shown to be significant risk factors for plantar fasciitis. Subjects with a BMI of more than 30 being over 5.6 times as likely to get plantar fasciitis compared to someone with a BMI less than 25.
Another study, (see, Riddle, D. L., Pulisic. M., Pidcoe, P., and Johnson, R. E., "Risk Factors for Plantar Fasciitis: A Matched Case-Control Study," J. Bone Joint Surg. Am., 2003; 85(5):872-877, which is incorporated in its entirety herein by reference) hypothesized that reduced ankle dorsiflexion is the most important risk factor for the development of plantar fasciitis, as the greater the limitation in ankle dorsiflexion, the greater the amount of compensatory foot pronation and therefore the higher level of loading on the plantar fascia.
Another study (see, Scott, G., Menz, H. B., and Newcombe, L., "Age-Related Differences in Foot Structure and Function," Gait Posture, 2007; 26(1):68-75, which is incorporated in its entirety herein by reference) found that older patients (mean age 80.2) had reduced ankle range of motion compared with younger patients (mean age 20.9). Other studies have shown an exponential relationship between decreasing ankle dorsiflexion and the risk of developing plantar fasciitis has been found, with individuals who have 0° of dorsiflexion or less having an odds ratio of 23.3 (95% confidence interval, 4.3 to 124.4). Foot pronation alone, for example, as measured by the Foot Posture Index (see, Redmond, A. C., Crosbie, J., and Ouvrier, R. A., "Development and Validation of a Novel Rating System for Scoring Standing Foot Posture: the Foot Posture Index," Clin. Biomech., 2006; 21(1):89-98, which is incorporated in its entirety herein by reference) has also been shown to be significantly greater in patients with chronic plantar heel pain.
In addition to these intrinsic factors, various extrinsic factors have been related to the development of plantar fasciitis. Several studies have shown an association between work-related prolonged weight-bearing and plantar fasciitis. For example, in some case series (see, e.g., Lapidus, P. W. and Guidotti, F. P., "Painful Heel: Report of 323 Patients with 364 Painful Heels," Clin. Orthop. Relat. Res., 1965; 39:178-186, which is incorporated in its entirety herein by reference) patient population included a predominance of occupations that necessitate continual standing or walking, such as waiters, maids, and kitchen workers. In addition, each heel strike during running causes compression of the heel pad up to 200% of body weight.
Therefore, in individuals who may not have adequate muscle strength or flexibility, and therefore have decreased shock-absorbing capabilities, the initiation of a new training program can exacerbate overloading of the plantar fascia. Increases in tensile loading, seen with new increases in running intensity or frequency and changes in general footwear have been associated with overloads of the plantar fascia leading to microtears.
Other drawbacks and issues with existing treatments for planar fasciitis also exist.

Composition and method for treating plantar fasciitis in humans


In a communication device for carrying out communications according to an Echonet protocol on a network of a prescribed network layer protocol, a prescribed bit sequence value of a network layer address or a datalink layer address of the communication device is set as a candidate for an Echonet address to be used in the Echonet protocol. Then, an inquiry packet for inquiring whether the prescribed bit sequence value is identical to the Echonet address used by each other communication device or not is transmitted, and the prescribed bit sequence value is determined as the Echonet address of the communication device when the prescribed bit sequence value is judged as not identical to any of Echonet addresses used by the other communication devices.

1. Field of the Invention
The present invention relates to a communication device and a communication control method for carrying out communications according to a control protocol such as Echonet on a network using a network layer protocol such as IP (Internet Protocol).
2. Description of the Related Art
In recent years, the information home electronics have been developing rapidly. This field encompasses a wide variety of devices such as home appliances, AV home electronics, information devices or mobile devices such as PCs, etc., and various applications utilizing the digital technology have been proposed for each device.
One such application is the use of a home network. The home network is a network technology developed for a network inside the home, for interconnecting various information home electronics mentioned above.
As this home network technology, the Internet technology has been attracting much attentions recently. For example, many applications that are attractive to the home network users such as those of music distribution, home page viewing, e-mails, etc., have been developed and the number of users is steadily increasing.
On the other hand, one exemplary application of the home network is a facility related network, or the use of the home network for the home automation. It is possible to connect air conditioners, lights, home appliances, etc., to the home network and carry out applications such as device state monitoring, remote controlling, etc.
In Japan, the Echonet is expected to be the de facto standard for this facility related network. The Echonet defines commands, protocols, objects, API, etc. for controlling facility related devices (home appliances, etc.) on various physical media such as electric power lines, twisted pair lines, etc. Further details of the Echonet can be found in documents disclosed at the URL "http://www.echonet.gr.jp", for example. The Echonet is standardized by a consortium founded mainly by several Japanese electronics companies, which has already issued the specification version 1, and the commercial application is about to start.
The Echonet has its own address system, so that there is a need for a mechanism to use the address system of the Echonet on the address system of the Internet. To this end, it is necessary to account for things that have not been accounted so far, such as the determination of a correspondence relationship between the Echonet address and the Internet address. This is done by the Echonet address initialization procedure.
In the case of determining the Echonet address, it can be expected that an Echonet address server for determining the Echonet address may not necessarily exist, so that there is a need to provide a mechanism for determining the Echonet address independently. An example of such a mechanism is that in which "a candidate value for the Echonet address is selected and broadcasted on the local network to check the address overlap". In this mechanism, there is a possibility for a loop of "selecting a tentative address value→checking→discovering overlap→going back to start" to take some time. For this reason, there can be cases where the own Echonet address cannot be determined during some period of time after the activation.
In particular, in the case of implementing this mechanism on the radio scheme such as Bluetooth, because the Bluetooth has a limitation that the number of nodes (the number of slaves) that can actively carry out communications simultaneously is limited to be less than or equal to seven, there is a possibility for the above loop to require much time, especially in view of the fact that the above loop utilizes the broadcast processing.

Communication device and communication control method using efficient Echonet address determination scheme


In an abnormal condition detecting system, an electronic control unit determines that a condition for carrying out a process for detecting an abnormal condition of an electric motor and/or electric supply lines for the motor is satisfied, when a position of a control valve is at its initial closed position. Then, the electronic control unit stops supply of the electrical power to the electric motor, to start a detection of the abnormal condition (electrical disconnection) in the motor and/or the electric supply lines.

An exhaust gas recirculation apparatus (an EGR apparatus) is known in the art as an engine control system, in which an amount of recirculation gas (re-circulated exhaust gas) is controlled to reduce nitrogen oxides (NOx) contained in the exhaust gas from an engine. In the EGR apparatus, an EGR valve is provided in an exhaust gas recirculation pipe, and the EGR valve is driven by an electric motor to control the amount of the re-circulated exhaust gas. When any malfunction occurs in the EGR valve, the control for the amount of re-circulated exhaust gas can not be carried out. Accordingly, it is necessary to detect an abnormal condition, such as an electrical disconnection, a condition in which an output from the motor is fixed, and so on.
In Japanese Patent Publication No. H5-168284, an abnormal condition detecting device is disclosed, according to which a power supply from a motor driving circuit to a motor is stopped and an abnormal condition is detected based on a voltage behavior immediately after the stop of the power supply. When the motor is in the abnormal condition (e.g. the motor can not be rotated), a flyback voltage is generated shortly after the power supply to the motor is cut off. On the other hand, when the motor is in the normal condition, no flyback voltage is generated and instead the voltage is gradually increased as the rotational speed of the motor is decreased. The abnormal condition is detected based on such a difference of the above voltage behavior, that is, a transient change of the voltage during the power supply to the motor is stopped.
In the above prior art, it is necessary to temporally stop the power supply from the motor driving circuit to the motor in order to detect the abnormal condition in the motor of the EGR apparatus, or in power supply lines of a wire harness electrically connecting the motor driving circuit with the motor.
The EGR valve may be moved to its initial position (e.g. a fully closed position), when the power supply to the motor is stopped, even when the period of such power supply stop is short. In the case that the valve position was at its half-opened or full-opened position just before the power supply to the motor is cut off, the EGR valve may be quickly moved to its initial closing position due to the cut-off of the power supply.
If the power supply to the motor is even temporally stopped for the purpose of detecting the abnormal condition of the EGR apparatus, the operation for the EGR control can not be temporally performed. This would result in deterioration of exhaust gas and/or drivability and a generation of noise to be caused by a rapid movement of the EGR valve to its valve closing position.

Abnormal condition detecting system for engine


A method of making a set of labelled compounds by the use of a preferably particulate support, comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support. The steps are repeated several times, preferably to build up oligomer molecules carrying labels which identify the nature and position of a monomer unit of the oligomer, and which are releasable from the support. Preferred labels, which are releasable from the compounds by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. Also claimed are libraries of these labels and their use in assays and nucleic acid analysis methods.

This invention concerns reagents of the kind which comprise a product which is built up using stepwise reactions, often chemical reactions, and associated tag moieties which track the synthetic pathway and/or the reagents used. The product will often be an oligomer and the tags define the identity and position of at least one monomer residue in the oligomer. Such reagents are useful in assay methods in which they can generate much more information than can be generated by a simple labelled analyte. Sets and libraries of such reagents can be created by combinatorial chemistry and are valuable for screening large numbers of compound e.g. for biological activity. In preferred systems according to the invention, positively charged tag groups are generated for analysis by mass spectrometry by cleavage, e.g. photocleavage of neutral molecules.
WO 95/04160 describes a reagent which comprises:    a) an analyte moiety comprising at least two analyte residues, and linked to    b) a tag moiety comprising one or more reporter groups adapted for detection by mass spectrometry, wherein a reporter group designates an analyte residue, and the reporter group at each position of the tag moiety is chosen to designate an analyte residue at a defined position of the analyte moiety. A plurality of such reagents, each comprising a different analyte moiety, provides a library of reagents which may be used in assay methods involving a target substance. Analysis of the tag moieties indicates the nature of the analyte moiety bound to the target substance.
WO 94/08051 describes a system used to make simultaneously a library of all oligomers each attached to a bead. Any individual bead made by a split and mix process carries a unique chemical product, and this is true of each bead which goes through the same synthetic pathway. Two coupling steps are used at each point in the process: one step affects the synthon or ligand; the other alters the structure of a tag which is also carried on the bead. Tags are designed to identify the steps through which the bead has been taken.
It is an object of this invention to provide a set or library of labelled compounds which may be synthesised on a support and may be used either attached to or separated from that support.
In one aspect the invention provides a method of making a set of labelled compounds, by the use of a support and a set of labels, which method comprises the steps:    a) at least one first or intermediate step comprising dividing the support into lots, performing a different chemical reaction on each lot of the support so as either to modify that lot of the support or to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support, and    b) at least one intermediate or final step comprising dividing the support into lots, performing a different chemical reaction on each lot of the support, so as either to modify that lot of the support or to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, whereby each different label is linked to a chemical moiety coupled to the support in a different step and forms with that chemical moiety a labelled compound which is separable from the support, and combining the said lots of the support.
The method uses a support which is repeatedly divided into lots which are then recombined. The support may be a massive support e.g. a flat sheet or silicon chip or microtitre plate which is divided e.g. by masking into regions for performing the different chemical reactions. The support may be a polymeric material which is soluble in some solvents and not in others, and which is separated into lots or recombined e.g. by precipitation or dissolution. Most usually the support will be particulate, e.g. pins or fibres or capillaries or preferably beads. Derivatised beads for performing combinatorial chemistry by a split and mix strategy are commercially available and can be used here. A preferred particulate support comprises beads having cleavable linkers, wherein each cleavable linker has one group for defined chemical procedures e.g. oligomer synthesis and another group for labelling. By this means it is possible at the end of the synthesis, to recover the labelled chemical products e.g. oligomers into solution.
The method of the invention involves performing at least one step a) and at least one step b), most usually at least three steps in all. Each step involves performing a reaction, generally but not necessarily a chemical reaction. An example of such a reaction might be the removal of a protective group so as to leave a primary amine or hydroxyl or carboxylic acid group. Most usually, the chemical reaction involves coupling a chemical moiety to the support. The chemical moiety will usually be an organic chemical group, for example as described in WO 94/08051. While successive chemical moieties may be attached to the support through separate linkers, more usually, successive chemical moieties will be joined to each other to form a chain extending from the support. Preferably the chemical moieties are monomer units which are built up to form oligomer chains.
In a preferred method according to the invention, the set of labelled compounds is a library of ns labelled oligomers, where n is the number of different monomer units and s is the number of monomer units in each labelled oligomer, wherein step a) is performed once to couple a different monomer unit to each lot of the support, and step b) is performed s−1 times.
The oligomer may be for example an oligonucleotide or an oligopeptide. When the oligomer is an oligonucleotide or analogue, then n is generally 4. When the oligomer is an oligopeptide, then n is generally about 20 when only natural amino acids are used. But the principles of the invention are equally applicable to other oligomers formed from other polymerisable monomers. The value of s is not critical, and may typically be from 2-100 e.g. 3-20 or more.
The fraction of each lot that is tagged in each step is generally less than 50%. Preferably from 0.25% to 25% of each lot of the support is tagged in each step with a different label. Preferably the support has cleavable linkers, wherein each cleavable linker has at least one group for chemical reaction e.g. chemical synthesis and another group for labelling. Preferably each resulting labelled compound comprises a single label and at least one chemical moiety.
The method involves the use of a set of up to and including n×s different labels. Although the nature of the labels is not critical, it is a preferred feature of the invention that each different label be distinguishable by the analytical procedure used to detect the labels. Groups used as labels should be much more stable to acidic (or other chemical) treatment involved in oligomer synthesis compared to the protecting groups commonly used (e.g. DMT groups to provide 5′ or 3′-protection in nucleotide synthons). Preferred labels are those in which a charged group, preferably a positively charged group is generated by cleavage e.g. photocleavage of a neutral molecule for analysis by mass spectrometry. Examples of such preferred labels are discussed below.
In a preferred embodiment, a split and mix strategy requires a solid support carrying cleavable linkers with three arms—one to attach to the solid support through a cleavable bond; one to initiate synthesis of a chemical product e.g. oligomer; and a third for attachment of the tags. The sites for coupling of synthon and tag monomers will optionally be protected by removable groups. The process can be illustrated by the synthesis of oligomers on a particulate solid support.
At each stage in the synthetic route, the particles of the support are first combined and mixed, and then divided into n lots, where n is the number of different monomers—4 in the case of natural nucleotides—and each monomer is coupled to its site on one lot of the support. A unique tag representing the monomer just added and its position in the sequence is then coupled to a fraction of the support, corresponding approximately to the number of monomers in the final oligomer (i.e. 1/ s for an oligomer with s monomer units). Alternatively, a tag may be coupled to a fraction of the support before or simultaneous with, rather than after the monomer which it represents. Partial coupling may be achieved in a number of different ways. For example, (i) a protecting group on the site may be partially removed; (ii) the coupling may be taken to a fraction of completion; (iii) a fraction of the support may be removed and coupling taken to completion before the fraction is returned to the pool. As the coupling steps proceed, the oligomer is extended one unit at a time, and the tags are added one at a time. The end result is a mixture of molecules on each particle; each molecule will carry the same sequence of monomers in the oligomer, but a fraction, 1/s for s-mers, will carry the tag added at any of the s coupling steps.
An example of this embodiment is shown in FIG. 1 of the accompanying drawings. At A, is illustrated a solid support in the form of a bead derivatised with cleavable linkers each having two arms. At B, one of the two arms of each linker has been reacted with a trityl group carrying a succinimidyl substituent. At C, the other branch of each linker has been reacted with a nucleotide residue shown as G; and one portion of the NHS groups has been substituted by a label R1. At D, oligonucleotide synthesis has continued by formation of dimer chains GT; and a second portion of the NHS groups has been substituted by a second label R2. At E, oligonucleotide synthesis has continued by formation of chains GTT; and a third portion of the NHS groups has been substituted by a label R3. At F, ammonolysis of the beads has given rise to a pool of oligonucleotides of the same sequence, in which each one is attached to a different tag. At G, photolysis has detached three derivatised trityl groups for analysis by mass spectrometry. The split and mix approach ensures that all the oligonucleotides attached to any bead have the same s-mer sequence; and that the bead also carries a total of s different labels, each of which indicates the position and identity of one monomer residue of the oligomer.
An alternative way of partial coupling is to cap the extension of a fraction of the chemical compounds e.g. oligomers with a stable tag group at each extension step. For example, in the case of oligonucleotide synthesis, the coupling agents could include a small proportion of a phosphoramidite protected by one of the stable trityl groups described below as mass tags. Elongation will produce a major proportion with the desired base and a small fraction with a corresponding tag marking the nature and position of the base.
An example of this embodiment is illustrated in FIG. 2 of the accompanying drawings. Oligonucleotide synthesis is performed on derivatised beads A, the first, second and third stages of this synthesis being shown as B, C and D. Each of four phosphoramidite reagents contains a small fraction depending on the length of the oligomer, preferably less than 1/s, of a capping phosphoramidite bearing a very acid-stable NHS-substituted trityl group. After each stage of synthesis, all incorporated NHS groups are reacted with an amine thereby attaching a label. For synthesis of longer oligonucleotides o-methyl phosphoramidite could be used to withstand repetitive amination reactions. The three different labels used in B, C and D are shown in FIG. 2 as R1, R2 and R3. At the end of synthesis, the oligonucleotides are deprotected by treatment with ammonia, but remain attached to the beads. Thus each bead carries a plurality of s-mer oligomers of identical sequence, together with a total of s different substituted trityl labels each of which indicates the identity and position of a monomer unit of the oligomer. The beads are used in an assay procedure. Thereafter photolysis of a bead generates charged substituted trityl moieties E for detection by mass spectroscopy. Alternatively the labelled oligonucleotides can be released into solution.
In another aspect, this invention provides a set of labelled compounds wherein a molecule of a compound of the set is tagged with a single label which identifies the nature and/or the position of a component of that molecule, and different molecules of the same compound are tagged with different labels. The set of labelled compounds may be releasably attached to a solid support e.g. beads; or may be mixed together in solution.
Also envisaged according to the invention is a library consisting of a plurality of the sets of the labelled compounds as herein defined, e.g. a library of ns labelled oligomers, where n is the number of different monomer units and s is the number of monomer units in each labelled oligomer.
In another aspect (e.g. as illustrated in FIG. 2) the invention provides a reagent comprising a solid support which carries on its surface molecules of an oligomer, with different oligomer molecules having the same sequence wherein the oligomer molecules include some shorter oligomer molecules and a shorter oligomer molecule carries a label which identifies the nature and position of a monomer unit of the oligomer molecule. A library consists of a plurality of the said reagents, in which the solid supports are preferably beads.
Preferred features of the labels used herein are:                They should be attached by linkages which are stable to the chemical procedures used in the preparative method and those used to detach the resulting chemical compound e.g. oligomer from a solid support. The trityl residues described below are stable throughout the procedures used to synthesise oligonucleotides.        They should have properties which allow up to n×s labels to be distinguished by the analytical procedure used to detect them, as each chemical moiety or reaction is tagged uniquely. In an example below, it is shown how all 262144 nonanucleotides can be coded uniquely using 36 different tag monomers. This number is readily achieved using the trityl derivatives described below. Alternatively, but less preferably, the same number of 9-mers could be coded for by 18 binary tags or even by a unique combination of 9 tags as described in WO 94/08051.        On cleavage, e.g. by photocleavage, chemical cleavage using acidic conditions, or enzymatic methods, from the parent molecule, they should generate stable species, either neutral molecules or preferably charged ions, for analysis by mass spectrometry. Mass spectrometry is a preferred method of analysis, allowing for the simultaneous detection of hundreds of labels. This property, of generating a preferably charged group by photocleavage of a neutral molecule, ensures that the ions are brought into the vapour phase without the need for added matrix. Therefore it is not necessary to search for "hot spots" as is the case when matrix is added. Not having matrix present also allows for further biochemical processes e.g. oligonucleotide ligation. In certain cleavage methods such as those involving acid, the addition of matrix may enhance the sensitivity of detection.
Bearing in mind these criteria, preferred labels according to the invention are groups of the formula R1R2R3C— where R1, R2 and R3 are the same or different and each is a monocyclic or fused ring aromatic group that is substituted or unsubstituted. These are groups of the trityl (triphenylmethyl) family. Other possible labels include troponium and those discussed in WO 97/27331. Trityl groups have the desirable property that they are readily cleaved by illumination with a laser in a mass spectrometer. Sensitivity of detection of trityl groups is high because of the stability of the positively charged carbonium ion. This sensitivity gives rise to a number of advantages, e.g. there are enough trityl groups in a molecular monolayer such as results if trityl labelled molecules are tethered covalently to a surface.
Preferably at least one of R1, R2 and R3 carries a substituent selected from C1-C20 alkoxy or hydrocarbyl either unsubstituted or substituted by carboxylic acid, sulphonic acid, nitro, cyano, hydroxyl, thiol, primary, secondary or tertiary amino, primary or secondary amido, anhydride, carbonyl halide or active ester. Hydrogen atoms in these substituents may be partly or wholly replaced by deuterium or halogen e.g. fluorine; this improves the range available for analysis by mass spectrometry.
Preferably each of R1, R2 and R3 is aryl, more preferably phenyl. While substituents may be present at any point in the aromatic (e.g. phenyl) ring, para-substituents are convenient and are preferred. The substituents may be present to confer desired physical or chemical properties on the trityl (or other) group. For example, electron withdrawing groups at ortho or para positions increase the stability of trityl groups to acid hydrolysis. Substituents may be present to alter the formula weight of the trityl (or other) group, so as to enable easy detection and discrimination by mass spectrometry. Non-radioactive isotopic substituents are suitable for this purpose, e.g. small alkyl groups containing 1, 2 or 3 deuterium atoms. Preferred substituents are amine or amide groups. There is a considerable number of amines having different molecular weights that are commercially available and that can be used to provide substituted trityl groups having distinctive formula weights, see for example Table 1 below.
The masses of the majority of commercially available amines lie in the range of 50-250 Da. For some applications it would be desirable to have up to a few hundred mass-tags. The resolution of the tags in TOF-mass spectrometry was found to be satisfactory with at least 4 Da difference between the masses of tags. Therefore, the above range of amines can only yield about 50 different tags. To increase this amount using the same pool of amines, it is possible to incorporate two or four or even more amide substituents per trityl group, and this is illustrated in the experimental section below.
The principle of the system is illustrated in FIG. 3 of the accompanying drawings. At A, an oligonucleotide has been synthesised on a CPG support. At B, a 5′-hydroxyl group of the oligonucleotide has been replaced by an NHS-substituted trityl group. At C, an amide group NHR has been introduced, in which R is chosen to have a characteristic formula weight. At D, the labelled oligonucleotide has been released into solution for use in an assay procedure. At E, the NHR-substituted trityl group has been volatilised by photolysis and has been detected by mass spectrometry.
The above mass spectrometry labels are useful in a variety of other biochemical methods and manipulations. Thus according to another aspect, the invention provides a nucleic acid determination method, which method comprises providing a labelled oligonucleotide or nucleic acid, and removing the label by cleavage to give a charged species which is subjected to mass spectrometry. Preferably nucleic acid analysis, e.g. sequencing or sequence difference analysis, is performed by the use of a labelled primer and/or labelled chain extending nucleotides and/or labelled chain terminating nucleotide analogues, wherein the label is as described above.
In another aspect, the invention provides an assay method in which a labelled probe is partitioned into two fractions of which one is determined, the probe comprising a ligand joined to a label by a link which is cleavable to give a charged species for analysis by mass spectrometry. The invention also includes a library of probes, each comprising a ligand joined to a label by a link which is cleavable to give a charged species for analysis by mass spectrometry, wherein each different probe has a different label. Preferably the labels are as described above.
Certain of the labels are envisaged as new compounds per se according to the invention. These are compounds of the formula R1R2R3CY; where Y is a leaving group e.g. halide or tosylate for displacement by a nucleophile e.g. a thiol, alcohol or amine group; and R1, R2 and R3 are as defined above, with the proviso that R1, R2 and R3 together carry at least two amide groups and/or at least two reactive groups for coupling e.g. N-hydroxysuccinimide ester groups.
In addition, the inventors have manufactured a disposable glass insert for use as a target surface for laser desorption ionisation mass spectrometry. The glass target may be used for analysis of samples spotted and dried directly on to the glass surface. The glass target may also be chemically activated and used as a solid support for immobilised nucleic acids or other compounds using methods already developed. Complementary nucleic acids, mass-tagged oligonucleotides or other compounds isolated and localised on the glass target may then be subjected to direct analysis by laser desorption ionisation mass spectrometry. One advantage of using a solid support is that it may be introduced directly into a mass spectrometer for subsequent detection and avoids unnecessary liquid handling of the sample. Organic polymeric surfaces such as polypropylene are possible alternatives to glass.
Any surface chemistry developed for attachment of compounds to glass may be used to immobilise these compounds directly on to a target for laser desorption ionisation mass spectrometry or matrix-assisted laser desorption ionisation mass spectrometry. For example 3-mercaptopropyl silane derivatisation (Rogers, et al 1999) or amine derivatisation (Beattie, et al 1995; Chen, et al 1999) for the attachment of nucleic acids. The glass inserts are significantly cheaper than conventional inserts and are truly disposable. Mass spectrometry performance is unaffected. (See Example 4 below).
The invention also provides an insert for use as a target for laser desorption ionisation mass spectrometry, which insert has a target surface of glass carrying an immobilised compound for analysis.
The invention also provides a kit comprising a mass spectrometer and a supply of inserts, for use as targets for laser desorption mass spectrometry, having target surfaces of glass.
In a preferred embodiment of the invention, a system for analysing nucleic acids comprises:                a solid support carrying an array of nucleic acids to act as targets for analysis or as probes to capture a target;        oligonucleotide reagents tagged with moieties suitable for analysis by mass spectrometry;        reagents and apparatus for biochemical procedures to allow specific interaction between the tagged oligonucleotides and the target;        a means to introduce the samples into a mass spectrometer;        a mass spectrometer.
In a more preferred embodiment of the invention, a system for analysing nucleic acids on a solid support comprises:                a solid support carrying an array of nucleic acids to act as targets for analysis or as probes to capture a target;        oligonucleotide reagents, tagged with moieties suitable for analysis by mass spectrometry;        reagents and apparatus for biochemical procedures to allow specific interaction between the tagged oligonucleotides and the target carried out on the solid support surface;        a means to introduce the solid support into a mass spectrometer;        a mass spectrometer.
In a further preferred embodiment of the invention, an automated system for analysing nucleic acids comprises:                oligonucleotide reagents, tagged with moieties suitable for analysis by mass spectrometry;        a mass spectrometer;
a computer to carry out the analysis;                software to interpret a mass spectrum.
Computer programs are provided for oligonucleotide sequence determination by mass spectrometry.
Each base and base position in an oligonucleotide is associated with a unique mass tag.
For oligonucleotides of length s, 4s tags are needed to distinguish between all 4s possible oligonucleotides.
Careful choice of tags ensures that all tags have sufficiently different masses to avoid ambiguity in tag assignment when analysing a mass spectrum.
The chemical formula for each tag is known, so each tag's monoisotopic mass can be calculated.
The isotopic abundances of the elements in the tag are also known, so a complete distribution of masses and abundances of all isotopic variants of each tag can be calculated.
For the tags used so far, the major heavy isotopes of a tag are those due to the presence of 13C, and a typical isotopic abundance distribution is that for C27H30O2N, with relative abundances of 73:22:3 for isotopic masses 400.228, 401.231 and 402.234 respectively. These abundance distributions characterise the tags presence in a mass spectrum, and help to distinguish tags from other features in the spectrum.
The use of elements such as chlorine or bromine in mass tags further aids tag detection and identification, since these elements have markedly different isotopic abundances from that of carbon:                for 35Cl:37Cl the abundance ratio is 76:24 and for 79Br:81Br it is 51:49.
Mass tags containing these elements will therefore have their own characteristic isotopic distributions. In general, the aim is to design tags with characteristic sets of masses which facilitate identification amongst a background of chemical 'noise'.
Mass standards are included in each spectrum to allow the spectrum's mass axis to be calibrated. Use of mass standards both within and on either side of the tag mass range ensures accurate mass measurement throughout this range. Ions representing a complete set of possible masses are often seen in mass spectra and these represent the ideal calibration set.
A program has been written to calculate the isotopic abundance distribution and corresponding isotopic masses of any mass tag, using the known masses and isotopic abundances of the elements in each tag. This information is calculated for all mass tags available for use in tagging oligonucleotides.
A second program uses this information to determine the presence of mass tags and hence the sequence in the mass spectrum generated by an oligonucleotide, and works as follows. For each base position in the oligonucleotide, the four regions of the mass spectrum corresponding to the masses of the four possible tags (including their isotopic variants) are examined and compared with the expected tag spectrum. The comparison is done either by identification of spectral peak positions and amplitudes and their differences from those of the potential tag, or by measuring the sum of squares of residuals between the experimental spectrum and that expected from the potential tag. In either case, the four potential tags are ranked by the chosen measure and the best tag is used to assign a base to that base position.
A more powerful approach is to examine each possible oligonucleotide in turn, obtaining a goodness of fit over all s tag regions by the method described above, and then ranking the oligonucleotide sequences by this measure.

Libraries of oligomers labeled with different tags


A curable epoxy system useful in the production of composites capable of being used in various industries, including, for example, the aerospace industry. In particular, the present disclosure relates to a curable epoxy system comprising (i) an epoxy component selected from bisphenol C diglycidyl ether, one or more derivatives of bisphenol C diglycidyl ether, and combinations thereof, and (ii) 9,9-bis(4-amino-3-chlorophenyl)fluorene.

Curable epoxy compounds can be mixed with a variety of components to form curable epoxy systems that, when cured, form composites that can be used in myriad of industries, such as green energy, sports equipment, electronics, construction, automotive, and aerospace. Such curable epoxy systems can also be used to form coatings or reinforced foams that are useful in a number of applications.
Whether using a curable epoxy system to form a coating or a composite, it is necessary to heat the curable epoxy system in order for it to cure. However, curing is typically an exothermic reaction, which produces additional heat that needs to be controlled in order to prevent overheating the curable epoxy system. Overheating the curable epoxy system can damage the system as well as the coated substrate or composite produced therefrom. As such, there is a need in the art to better control the heat present when reacting (i.e., curing) curable epoxy systems. One means for doing so is by reducing the cure enthalpy of the curable epoxy systems, which reduces the amount of heat generated during curing. Reducing the cure enthalpy has the added benefit of leading to reduced curing cycles, which allows for improved manufacturing efficiencies and, ultimately, reduced manufacturing costs.
It would therefore be advantageous to provide a curable epoxy system having a lower cure enthalpy, but which still has the requisite physical properties for use in industrial applications, including, for example, in the aerospace industry.

HUNTSMAN ADVANCED MATERIALS AMERICAS LLC


An anchor structure for sensors of faucets is located in a sensing faucet. The sensor has a detection side and at least one notch on another side opposite to the detection side at an elevation same as an annular groove formed on an inner wall of a faucet body. An elastic clipping ring is provided to latch in the annular groove and the notch of the sensor to form a bucking effect to anchor the sensor at a selected location in the faucet. The elastic clipping ring is hollow and annular to provide a passage for watering piping and electric wiring. The structure is simpler and can be installed and removed rapidly.

1. Field of the Invention
The present invention relates to an anchor structure and particularly to an anchor structure for sensors of faucets to facilitate fast installation and removing of the sensors.
2. Description of the Prior Art
Conventional sensing faucets generally have a faucet body to couple with a sensor and a water supply device. The sensor can detect the presence and leaving of users to output a control signal to the water supply device to activate or disable a solenoid valve housed in the water supply device to supply water or stop water supply in an automatic manner.
Because the sensing faucet has to include the sensor and the solenoid valve in the water supply device, and the sensor and solenoid valve have to be connected electrically through conductive wires, the internal structure is more complicated than the conventional plain faucet. Moreover, the conventional sensor has a detection side or has to be wedged in an exposed port formed on the faucet body to detect user's presence with a greater sensitivity. But coupling by embedding is not secured. Other anchoring means have to be used to form a secure coupling without loosening off easily. The commonly used anchoring means at present include bonding the sensor to the faucet body through adhesive, fastening a screw through the faucet body to press the back side of the sensor, forming a tray seat on the bottom of the faucet to integrate the sensor and the piping of the water supply device, and forming a trough seat by casting on the inner wall of the faucet body to hold the sensor. Whatever the approach being adopted for anchoring the sensor, it is necessary to take into account installation and fastening issues such as bypassing the piping routes of water and electricity in the faucet. Due to the complicated structure inside the sensing faucet, fabrication difficulty and cost increase. The complex anchoring method also makes repairs and maintenance of the sensing faucet more difficult and time-consuming, such as removing of the adhesive or disassembling of too many elements.


A method comprises determining an importance value for each series data set among a plurality of series data sets and visually representing each of the series data sets in accordance with the importance values.

Data, particularly large amounts of data, is easy to show on a display, but often difficult to interpret. For example, sales data from an international corporation may comprise sales of many products sold in many regions across the globe. Displaying the data in a way that facilitates human interpretation of the data can be different.

Visually representing series data sets in accordance with importance values

Hewlett-Packard Development Company, L.P.


An FMA unit, for carrying out an arithmetic operation in a model computation unit of a control unit, is configured to process input of two factors and one summand in the form of floating point values, and provide a computation result of such processing as an output variable in the form of a floating point value. The FMA unit is designed to carry out a multiplication and a subsequent addition, the bit resolutions of the inputs for the factors being lower than the bit resolution of the input for the summand and the bit resolution of the output variable.

Control units are known from the related art which have a main arithmetic unit and a separate model computation unit for computing data-based function models. For example, the publication DE 10 2010 028 266 A1 shows a control unit having an additional logic circuit as the model computation unit which is designed for purely hardware-based computation of multiplications, additions, and exponential functions in one or more loop computations. This makes it possible to support Bayesian regression processes, which are needed in particular for the computation of Gaussian process models, in a hardware unit.
The model computation unit is designed overall to carry out mathematical processes for computing the data-based function model based on parameters and node or training data. The model computation unit is, in particular, designed for efficient hardware-based computation of exponential functions in two computational loops, so that it is possible to compute Gaussian process models at a higher computation rate than may take place in the software-operated main arithmetic unit. In order to accelerate the computation in the logic unit, multiplication and addition processes may be combined in a joint multiplier-accumulator (MAC) or FMA unit which makes a hardware implementation available for an addition and a multiplication operation in a particularly efficient manner.
For example, U.S. Pat. No. 7,080,111 describes such an FMA unit for an input-side and an output-side resolution of 32 bits, and U.S. Pat. No. 7,346,642 also shows such an FMA unit which, however, is more accurate.

FMA unit, in particular for utilization in a model computation unit for purely hardware-based computing of function models


An accelerometer sensor and method of controlling the sensor, the accelerometer sensor including at least one electrostatic pendular accelerometer having stationary first and second electrodes fastened to a housing and connected to an exciter circuit, and a third electrode carried by a pendulum connected to the housing, thereby being movable and being connected to a detector circuit. The exciter circuit has an output connected to a switch connected to the first and second electrodes, the switch having a first connection position and a second connection position for selectively connecting the first or second electrode to the exciter circuit. The detector circuit, the exciter circuit, the switch, and the detector circuit are connected to a control circuit arranged so the first and second electrodes are excited by pulse trains, thus keeping the pendulum in a setpoint position and determining an acceleration to which the pendulum is subjected.

The present invention relates to an electrostatic pendular accelerometer sensor and to a method of controlling such a sensor. By way of example, the sensor may be a sensor of the micro electromechanical system (MEMS) type.
An electrostatic pendular accelerometer comprises a housing having a seismic mass connected thereto via one or more hinges positioned in such a manner that the seismic mass forms a pendulum that is movable relative to the housing either in translation or in rotation. The movements of the seismic mass under the effect of acceleration are generally detected by means of three electrodes. Stationary first and second electrodes are secured to the housing and connected to an exciter circuit. The third electrode is movable and is carried by the pendulum, being connected to a detector circuit.
Each stationary electrode co-operates with the movable electrode to form a capacitor of capacitance that depends on the spacing between them. In the absence of any manufacturing defects and when the sensor is not being subjected to acceleration along its sensing axis, the pendulum remains in a neutral position in which the two capacitances are equal. In contrast, when the pendulum is subjected to an acceleration along its sensing axis, it moves, thereby decreasing the capacitance formed by the movable electrode and one of the stationary electrodes, and increasing the capacitance formed by the movable electrode and the other stationary electrode. This variation in capacitances also depends on the deformations of the housing and of the pendulum.
In open-loop operation, the acceleration applied along the sensing axis of the sensor is deduced from the difference that exists between the two capacitances. This mode of operation nevertheless presents several drawbacks:                the direction of the sensing axis varies depending on the position of the pendulum when the pendulum is movable in pivoting;        there is an offset due to asymmetries in fabrication of the capacitors (electrodes of different areas and/or different gaps between the electrodes);        measurement non-linearities exist because of the way the capacitances are non-linear as a function of the movement of the electrodes;        during movements of the pendulum, the gas surrounding the pendulum compresses and expands, thereby generating forces on the pendulum;        passband is narrow because of the resonant frequency of the pendulum.
In closed-loop operation, the position of the pendulum is servo-controlled to a neutral position or to a setpoint position, halfway between the stationary electrodes, by applying an electrostatic force to the pendulum. The electrostatic force must therefore compensate the acceleration that is applied along the sensing axis, thereby enabling the acceleration to be estimated. The electrostatic force is the result of voltages applied to the electrodes in order to keep the difference between the capacitances at zero.
The sensor has an exciter circuit for each stationary electrode that is arranged to power the electrodes so as to generate said electrostatic force.
The root means square (rms) nature of the electrostatic force relative to the applied voltages complicates the design of the control circuit serving to servo-control the pendulum and estimate acceleration. In order to work around this difficulty, it is known to apply on/off control to the pendulum using calibrated voltage pulses. The pulses are applied to one or other of the electrodes depending on whether the pendulum is to be pulled or pushed in order to be returned towards its setpoint position. The density of the pulses for pushing (or pulling) the pendulum, i.e. the number of pulses over a time interval, is then an affined function of the acceleration that is to be measured. Thus, zero acceleration is compensated by equal numbers, on average, of pulses in both directions.
Nevertheless, if the symmetry of the pulses applied to the two electrodes is imperfect (mainly because of a difference between the durations of the pulses applied respectively to the first and second stationary electrodes), the pulse density is modified by the servo-control in order to maintain the pendulum in the setpoint position, thereby biasing the estimate of the acceleration. By way of example, taking an accelerometer in which each of the voltages applied during the control stage exerts a mean force for a duration Ts=1 microsecond (μs), equivalent to an acceleration of the pendulum of 50 g, in order to maintain the bias of such an accelerometer to a value of less than 50 μg, it is necessary for the symmetry of the pulses to be controlled with an error less than the ratio 50 μg/50 g, i.e. less than 1×10−6. It is therefore necessary to control the duration of the pulses applied to each of the electrodes in such a manner that the asymmetry does not exceed 1×10−6×1 μs, 1 picosecond (μs), which is extremely difficult.
Asymmetries of implementation, which constitute the weak point of on/off control, are thus a major obstacle in obtaining better performance from such sensors.

Sensor with electrostatic pendular accelerometer and method of controlling such a sensor


A rear seat is foldable by moving downward a seat cushion and folding forward a seat back. A power source unit is disposed below a rear floor to the rear of the rear seat. When the rear seat is in an unfolded state, cooling air can be introduced from inside a vehicle compartment, through a space between a lower surface of the seat cushion and an upper surface of an underseat floor, into a cooling-air introduction port in the power source unit. When the rear seat is in a folded state, the cooling air is introduced from inside the vehicle compartment, through cooling-air introduction passages, into the cooling-air introduction port. Thus, the power source unit can be cooled irrespective of whether the rear seat is in the folded state, without reducing the foldability of the rear seat.

1. Field of the Invention
The present invention relates to an electrical device cooling structure in a vehicle, in which an electrical device disposed under a rear floor to the rear of a foldable rear seat is cooled by cooling air introduced from inside a vehicle compartment.
2. Description of the Related Art
Japanese Patent Application Laid-open No. 2004-1683 discloses an electrical device cooling structure, in which a battery pack for driving a motor for driving an automobile is mounted in a luggage space to the rear of a rear seat, and an intake duct for supplying cooling air to the battery back opens sideways of a seat back of a rear seat.
Japanese Patent Application Laid-open No. 2004-98722 discloses a so-called diving-down foldable seat, in which a seat cushion is moved downward and a seat back is declined forward to cause an upper surface of the thus-folded seat back to be continuous substantially flatly to a rear floor in the rear of a seat.
However, Japanese Patent Application Laid-open No. 2004-1683 has a problem that because the intake duct for supplying the cooling air to the battery pack opens sideways of the seat back of the rear seat, the opening situates near an occupant's ear and generates nose. In order to avoid this problem, it is conceivable that the cooling air is supplied from below the rear seat to the battery pack. However, in a vehicle provided with the diving-down foldable seat described in Japanese Patent Application Laid-open No. 2004-98722, it is difficult to secure a cooling-air passage when the seat is folded.

Electrical device cooling structure in vehicle


A circuit layout structure for a chip is provided. The chip has a bonding pad area, a nearby device area, and a substrate. The circuit layout structure essentially comprises a plurality of circuit layers, a plurality of dielectric layers and a plurality of vias. The circuit layers are sequentially stacked over the substrate. Each dielectric layer is sandwiched between a pair of adjacent circuit layers. The vias pass through the dielectric layers and electrically connect various circuit layers. The farthest circuit layer away from the substrate has pluralities of bonding pads within the bonding pad area. The bonding pads near the device area overstrides at least one non-signed circuit layer through the furthest circuit layer away from the substrate and electrically connects to a circuit layer nearer the substrate with vias. The circuit layout structure can avoid a direct conflict of signals between the power/ground circuits and the signal circuits.

1. Field of the Invention
The present invention relates to a circuit layout structure. More particularly, the present invention relates to a circuit layout structure with a power circuit and a ground circuit having a sufficient line width to maintain signal integrity during transmission.
2. Description of the Related Art
Due to the rapid development of the electronic industry in recent years, integrated circuit (IC) chips find applications in many areas. To meet the demands of as many customers as possible, semiconductor manufacturers have to increase the level of integration of their IC chips. Hence, the density of input/output terminals in each single chip has to increase correspondingly. In other words, for a conventional wire-bonded chip, either the size of the chip has to be reduced for the same number of signal input/output terminals or the number of signal input/output terminals has to be increased for a chip of a given size. In general, the density of input/output terminals con be increased by dispensing the bonding pads around the active surface of the chip in a multi-tier (three-tier or four-tier) organization.
FIG. 1 is a top view of a section of a conventional circuit layout structure on a chip. FIG. 2 is a cross-sectional view along line I–I′ of FIG. 1. As shown in FIGS. 1 and 2, the chip 50 has a bonding pad area A1 and a nearby device area A2. The chip 50 further comprises a substrate 60 and a circuit layout structure 100. The circuit layout structure 100 essentially comprises a plurality of circuit layers (M1, M2, . . . , M6), a plurality of dielectric layers 110, and a plurality of vias 120. The circuit layers M1, M2, . . . , M6 sequentially stacking over the substrate 60. The dielectric layers 110 sandwiching between adjacent circuit layers M1, M2, . . . , M6. The vias 120 passing through the dielectric layers 110 and electrically connect to various circuit layers (M1, M2, . . . , M6).
The sixth circuit layer M6 (the topmost layer or the layer farthest from the substrate 60) has a plurality of bonding pads 130˜133 within the bonding pad area A1. The bonding pads 130˜133 are organized into a plurality of rows including a first bonding pad row R1, a second bonding pad row R2, a third bonding pad row R3, and a fourth bonding pad row R4. In the conventional circuit layer structure 100, the bonding pads 130 and 131 of the first bonding pad row R1 and the second bonding pad row R2 are signal bonding pads. The bonding pads 132 in the third bonding pad row R3 are power bonding pads and the bonding pads 133 in the fourth bonding pad row R4 are ground bonding pads. Furthermore, the bonding pads 130 and 131 in the first bonding pad row R1 and the second bonding pad row R2 respectively are electrically connected to the second and third circuit layers M2 and M3 through a set of vias 120. Similarly, the bonding pads 132 and 133 in the third bonding pad row R3 and the fourth bonding pad row R4 respectively are electrically connected to the fourth and the fifth circuit layers M4 and M5 through another set of vias 120. Consequently, the power line L1 connecting the boding pads 132 of the third bonding pad row R3 and the ground line L2 connecting the bonding pads 133 of the fourth bonding pad row R4 alternate with the signal line L3 connecting the bonding pads 130 of the first bonding pad row R1 in area S1 and alternate with the signal line L4 connecting the bonding pads 131 of the second bonding pad row R2 in area S2.
FIG. 3 is a cross-sectional view along line II–II′ of FIG. 2. As shown in FIGS. 2 and 3, the power lines L1 and the ground line L2 alternate with the signal line L4 on the left side area S2. Meanwhile, the power line L1 and the ground line L2 alternate with another signal line L3 on the right side area S1. Thus, the line width of the power line L1, the ground line L2, the signal lines L3 and L4 is subjected to some limitations so that the circuit layout of the power line L1 and the ground line L2 is more complicated.
Because the power line and the ground line alternates with the signal line, a portion of the power line and ground line must be narrowed to make way for the passage of the signal line. Yet, the power line and the ground line must have a substantial cross-sectional area for the passage of current. Without increasing the size of a chip, the narrower section in areas where the signal lines alternate with the power line and the ground line in a conventional circuit layout structure is bound to compromise the signal transmission integrity of the chip.


Video information and sub-information pertaining to a partial image to be displayed on a small-screen monitor are input from a receiver, disk playback unit, or memory data reader. On the basis of the sub-information, a target region data extractor and target region setting unit extract and set a partial image. A partial enlargement processor enlarges the partial image and displays the enlarged image on the small-screen monitor.

With the advance of the liquid crystal display techniques, portable liquid crystal television receivers having screen sizes of 2 to 4 inches are commercialized, and the number of viewers who receive ordinary television broadcasting by using such small-screen liquid crystal television receivers is increasing. Also, ground-wave digital broadcasting is scheduled to be started in the near future, so portable apparatuses (e.g., Japanese Patent Application Laid-Open No. 2003-101898) capable of displaying broadcast digital images or digital images from the Internet are being developed.
On the other hand, various programs of ordinary television broadcasting are presumably produced by assuming receivers having screen sizes of about 14 to 30 inches.
Recently, HDTV (High Definition Television: high-quality television or high-resolution television) broadcasting is also started in addition to the ordinary broadcasting described above, in accordance with the introduction of the digital broadcasting techniques. With the start of the ground-wave digital broadcasting, the number of these HDTV programs will probably increase.
Programs of this HDTV are presumably produced by assuming screen sizes of about 30 to 50 inches or more as display conditions.
Additionally, the ability to display motion images of mobile apparatuses such as a cell phone, digital camera, camcorder, car navigation system, and notebook personal computer (PC) is rapidly advancing. Therefore, it is expected that motion images are generally played back on small screens of about 1.5 to 5 inches in the near future.
If, however, programs of the ordinary television broadcasting described above are viewed on portable liquid crystal television receivers of about 2 to 3 inches, the faces and expressions of cast are difficult to discriminate, and characters (e.g., signs in landscapes and headlines in papers) taken by cameras are difficult to read.
In particular, viewers will probably view programs of television broadcasting on cell phones and play back programs by using the DVD playback function of car navigation systems more often. Since the dependence on information acquisition from mobile apparatuses is thus increasing, it is necessary to alleviate the difficulties of viewing as described above.
Furthermore, with the progress of digital information, the resolution of motion images of, e.g., HDTV is more and more increasing as described above. This increases the difference between the expected display size when a program is produced and a small screen (as a part of diversification) which is the actual display size.
As a method of eliminating these inconveniences, an apparatus having a function of displaying an image by enlarging a part of the image during viewing is commercialized. However, a user must manually set the magnification and the (central) position of enlargement for each image. This can be done for still images by taking a certain time. For motion images, however, manually changing these two factors moment by moment is presumably a difficult operation which practically no general user is able to perform.

Video display method of video system and image processing apparatus


A drill bit for drilling a borehole in earthen formations. In an embodiment, the bit comprises a bit body having a bit axis and a bit face. In addition, the bit comprises a pin end extending from the bit body opposite the bit face. Further, the bit comprises a plurality of gage pads extending from the bit body, wherein each gage pad includes a radially outer gage-facing surface. The gage-facing surfaces of the plurality of gage pads define a gage pad circumference that is centered relative to a gage pad axis, the gage pad axis being substantially parallel to the bit axis and offset from the bit axis.

1. Field of the Invention
The invention relates generally to earth-boring bits used to drill a borehole for the ultimate recovery of oil, gas, or minerals. More particularly, the invention relates to drill bits designed to shift the orientation of its axis in a predetermined direction as it drills. Still more particularly, the invention relates to a drill bit having inclination reducing or "dropping" tendencies.
2. Background of the Invention
An earth-boring drill bit is typically mounted on the lower end of a drill string and is rotated by rotating the drill string at the surface or by actuation of downhole motors or turbines, or by both methods. With weight applied to the drill string, the rotating drill bit engages the earthen formation and proceeds to form a borehole along a predetermined path toward a target zone. The borehole thus created will have a diameter generally equal to the diameter or "gage" of the drill bit.
Many different types of drill bits and cutting structures for bits have been developed and found useful in drilling such boreholes. Two predominate types of rock bits are roller cone bits and fixed cutter (or rotary drag) bits. Many fixed cutter bit designs include a plurality of blades that project radially outward from the bit body and form flow channels there between. Typically, cutter elements are grouped and mounted on the several blades.
The cutter elements disposed on the several blades of a fixed cutter bit are typically formed of extremely hard materials and include a layer of polycrystalline diamond ("PD") material. In the typical fixed cutter bit, each cutter element or assembly comprises an elongate and generally cylindrical support member which is received and secured in a pocket formed in the surface of one of the several blades. A cutter element typically has a hard cutting layer of polycrystalline diamond or other superabrasive material such as cubic boron nitride, thermally stable diamond, polycrystalline cubic boron nitride, or ultrahard tungsten carbide (meaning a tungsten carbide material having a wear-resistance that is greater than the wear-resistance of the material forming the substrate) as well as mixtures or combinations of these materials. The cutting layer is exposed on one end of its support member, which is typically formed of tungsten carbide. For convenience, as used herein, reference to "PD bit" or "PD cutter element" refers to a fixed cutter bit or cutter element employing a hard cutting layer of polycrystalline diamond or other superabrasive material such as cubic boron nitride, thermally stable diamond, polycrystalline cubic boron nitride, or ultrahard tungsten carbide.
While the bit is rotated, drilling fluid is pumped through the drill string and directed out of the drill bit. The fixed cutter bit typically includes nozzles or fixed ports spaced about the bit face that serve to inject drilling fluid into the flow passageways between the several blades. The flowing fluid performs several important functions. The fluid removes formation cuttings from the bit's cutting structure. Otherwise, accumulation of formation materials on the cutting structure may inhibit or prevent the penetration of the cutting structure into the formation. In addition, the fluid removes cut formation materials from the bottom of the borehole. Failure to remove formation materials from the bottom of the borehole may result in subsequent passes by the cutting structure to re-cut the same materials, thus reducing cutting rate and potentially increasing wear on the cutting surfaces. The drilling fluid and cuttings removed from the bit face and from the bottom of the borehole are forced and carried to the surface through the annulus that exists between the drill string and the borehole sidewall. Still further, the drilling fluid removes frictional heat from the cutter elements in order to prolong cutter element life. Thus, the number and placement of drilling fluid nozzles, and the resulting flow of drilling fluid, may significantly impact the performance of the drill bit.
Depending on the location and orientation of the target formation or pay zone, directional drilling (e.g., horizontal drilling) with the drill bit may be desired. In general, directional drilling involves deviation of the borehole from vertical (i.e., drilling a borehole in a direction other than substantially vertical), and is typically accomplished by drilling, for at least some period of time, in a direction not parallel with the bit axis. Directional drilling capabilities have improved as advancements in measurement while drilling (MWD) technologies have enabled drillers to better track the position and orientation of the wellbore. In addition, more extensive and more accurate information about the location of the target formation as a result of improved logging techniques has enhanced directional drilling capabilities. As directional drilling capabilities have improved, so have the expectations for drilling performance. For example, a driller today may target a relatively narrow, horizontal oil-bearing stratum, and may wish to maintain the borehole completely within the stratum. In some complex scenarios, highly specialized "design drilling" techniques with highly tortuous well paths having multiple directional changes of two or more bends lying in different planes may be employed.
One common method to control the drilling direction of a bit is to steer the bit using a downhole motor with a bent sub and/or housing. As shown in FIG. 1, a simplified version of a downhole steering system according to the prior art comprises a rig 1, a drill string 2 having a downhole motor 6 with a bent sub 4, and a conventional drill bit 8. Motor 6 and bent sub 4 form part of the bottomhole assembly (BHA) and are attached to the lower end of the drill string 2 adjacent the conventional drill bit 8. When not rotating, the bent sub 4 causes the bit face to be canted with respect to the tool axis. The downhole motor 6 is capable of rotating conventional drill bit 8 without the need to rotate the entire drill string 2. For example, downhole motor 6 may be a turbine, an electric motor, or a progressive cavity motor that converts drilling fluid pressure pumped down drill string 2 into rotational energy at drill bit 8. When downhole motor 6 is used with bent sub 6 without rotating drill string 2, drill bit 8 drills a borehole that is deviated in the direction of the bend or curve in the bent sub 6. On the contrary, when the drill string is also rotated, the borehole normally maintains a linear path or direction, even when a downhole motor is used, since the bent sub or housing rotates along with the drill string, and thus, no longer orients the drill bit in a specific direction. Consequently, a combination of a bent sub or housing and a downhole motor to rotate the drill bit without rotating the still string generally provide a more effective means for deviating a borehole.
When a well is deviated from vertical by several degrees and has a substantial inclination, such as greater than 30 degrees, the factors typically influencing drilling and steering may have a reduced impact. For instance, operational parameters such as weight on bit (WOB) and RPM typically have a large influence on the bit's ROP, as well as its ability to achieve and maintain the required well bore trajectory. However, as the inclination of the well increases towards horizontal, it becomes more difficult to apply weight on bit effectively since the borehole bottom is no longer aligned with the force of gravity—increasing bends in the drill string tend to reduce the amount of downward force applied to the string at the surface that is translated to WOB acting at the bit face. In some cases, the application of sufficient downward forces at the surface to a bent drill string may lead to buckling or deformation of the drill string. Consequently, directional drilling with a combination of a downhole motor and a bent sub may decrease the effective WOB, and thus, may reduce the achievable ROP.
In addition, as previously described, directional drilling with a downhole motor coupled with a bent sub is preferably performed without rotating the drill string in a process commonly referred to as "sliding." However, in drilling operations where the drill string is not rotating, or is rotated very little, the rotational shear acting on the drilling fluid in the annulus between the drill string and borehole wall is decreased, as compared to a case where the entire drill string is rotating. Since drilling fluids tend to be thixotropic, the reduction or complete loss of the shearing action tends to adversely affect the ability of the drilling fluid to flush and carry away cuttings from the borehole. As a result, in deviated holes drilled with a downhole motor and bent sub alone, formation cuttings are more likely to settle out of the drilling fluid on the bottom or low side of the borehole. This may increase borehole drag, making weight-on-bit transmission to the bit even more difficult, and often resulting in tool phase control and prediction problems. These challenges encountered in sliding can result in an inefficient and time consuming operation.
Still further, drilling with the downhole motor and bent sub during a sliding operation deprives the driller of the use of a significant source of rotational energy and power, namely the surface equipment that is otherwise employed to rotate the drill string. In directional drilling cases employing a downhole motor powered by drilling fluid pressure (e.g., progressive cavity motor), the large pressure drop across the downhole motor consumes a significant portion of the energy of the drilling fluid, and may detrimentally reduce the hydraulic capabilities of the drilling fluid advanced to the bit face and borehole bottom. In other words, the large pressure drop across the motor results in a lower drilling fluid pressure at the bit face, potentially decreasing the ability of the drilling fluid to clean and cool the cutter elements on the bit face, and flush away cutting from the borehole bottom. To the contrary, when surface equipment is employed to rotate the drill string and the bit, rotational energy and power are directly translated to the bit, without the need to convert drilling fluid pressure to rotational energy. Consequently, the use of surface equipment to rotate a drill string and bit may result in increased ROP and improved bit hydraulics as compared to a bit rotated by a downhole motor alone.
In addition to deviating from vertical in directional drilling operations as shown in FIG. 1, it may also be desirable to have a drill bit capable of returning to a vertical drilling orientation in the event the drill bit inadvertently deviates from vertical. The ability of a bit to return to a vertical path after deviating from such a path is generally referred to as "dropping". In order to effect dropping, a drill bit must have the capability of drilling or penetrating the earth in a direction not parallel with the longitudinal axis of the bit.
As shown in the schematic view of FIG. 2, a drillstring assembly 50 including a drill string 53 and a bit 51 is shown drilling a borehole 55 that has deviated from vertical. Drillstring assembly 50 has a weight vector 52 that consists of an axial component 54 and a radial or normal component 56. Unlike the directional drilling operations described above in which deviations from vertical are desired, in some cases, deviations from vertical are unintentional or inadvertent. In such cases, it may be desirable to return drilling assembly 50 to a vertical orientation while drilling. To effect such a return to vertical, drill bit 51 must drill in a direction that is not parallel to axial vector 54. This may be accomplished by cutting and removing formation material from a sidewall 57 of borehole 55.
Accordingly, there remains a need in the art for an apparatus or system capable of altering the azimuth or inclination of a drill bit and well without relying solely on a downhole motor or rotary steerable device. Such an apparatus would be particularly well received if it was capable of altering the direction of the drill string and borehole trajectory in a controlled manner while maintaining the rotation of the entire drill string. In addition, it is desired that this change in direction be achieved with a drill bit having predetermined dropping tendencies, regardless of formation type, lithology, well trajectory, stratigraphy, or formation dip angles.

Drill bit with asymmetric gage pad configuration


In some examples, at least one connecting ring may connect a plurality of stator coils of the same phase. For instance, the at least one connecting ring may include at least one linear conductor formed in a ring-like shape. The linear conductor may include a plurality of terminal sections, each terminal section including an open groove extending perpendicular to a plane formed by the ring-like shape. The open grooves may be positioned around a circumference of the connecting ring for receiving respective wire ends of respective stator coils inserted into the open grooves for forming an electrical connection between the respective wire ends and the connecting ring at the respective terminal sections.

Power distribution for a rotary electric machine, such as an electric motor or generator, may include multiple phases. For example, in a three-phase stator, three conductors may each carry an alternating current of similar frequency and current amplitude relative to a common reference but with a phase difference of one third of a cycle between each of the three conductors. A fourth conductor, called the neutral conductor, may serve as the common reference for star-connection motors. Three-phase systems can produce a rotating magnetic field with a specified direction and speed. For example, the rotating magnetic field may be used to produce torque when coupled with a rotor filled with permanent magnet. However, manufacturing and assembling a power distributing apparatus for a rotary electric machine can be challenging. One example of an existing technique is set forth in U.S. Pat. No. 7,952,245, to Ueda et al., which is incorporated herein by reference.

Power distribution for rotary electric machine

HITACHI AUTOMOTIVE SYSTEMS AMERICAS, INC.


A method for reporting at least one detected active threat to the homeland security (HS). Each threat is either hidden inside at least one cargo container before transit, or is placed inside at least one cargo container while in transit. Each threat while interacting with its surrounding generates a unique threat signature. The method comprises; (A) substantially continuously probing each cargo container; (B) detecting at least one threat signature;—(C) processing each detected threat signature to determine a likelihood of at least one threat to become a threat to HS;—(D) identifying at least one said container that includes such threat to HS;—(E) reporting to at least one Homeland Security Monitoring Center (HSMC) that at least one container includes at least one such threat to HS; and receiving instructions from at least one Homeland Security Monitoring Center (HSMC) how to eliminate at least one such reported threat to HS while in transit; and—(F) using robotic means to eliminate at least one such detected threat to HS.

1. Field of the Invention
The present invention relates to the field of threat detection and identification, and more specifically, to the field of active detection, identification, communication of threats hidden inside cargo shipments and elimination of such threats while in transit.
2. Discussion of the Prior Art
The patent application entitled "ACTIVE THREAT DETECTION AND ELIMINATION WHILE IN TRANSIT", U.S. Ser. No. 11/025,447, is hereafter referred to as the patent application #1. The patent application #1 is incorporated herein in its entirety.
The patent application #1 was directed to a method of active detection of at least one threat to the homeland security (HS). Each such threat was assumed to be either hidden inside at least one cargo container before transit, or to be placed inside at least one cargo container while in transit. Each such threat while interacting with its surrounding was assumed to generate a unique threat signature.
However, the patent application #1 did not address the issue of reporting each such threat to HS to at least one Homeland Security Monitoring Center (HSMC).

This patent is subject to a terminal disclaimer.

Reporting and eliminating detected active threats while in transit


Methods for identifying MarR family inhibiting compounds are described. The methods include the use of computer aided rational based drug design programs and three dimensional structures of MarR family polypeptides.

The Mar phenotype in E. coli is attributed largely to the action of MarA, the expression of which is regulated by MarR (Alekshun, M. N. supra (1997)). MarA is a transcription factor that autoactivates expression of the marRAB operon and regulates the expression of a global network of more than 60 chromosomal genes (Martin, R. G. et al. J. Bact. 178, 2216-2223 (1996); Barbosa, T. M. & Levy, S. B. J. Bact. 182, 3467-3474 (2000)). Mar mutants in isolates of clinical origin have now been identified (Maneewannakul, K. & Levy, S. B. Antimicrob. Agents Chemother. 40, 1695-1698 (1996); Oethinger, M. et al. Antimicrob. Agents Chemother. 42, 2089-2094 (1998); Linde, H. J. et al. Antimicrob. Agents Chemother. 44, 1865-1868 (2000); Ziha-Zarifi, I., et al. Antimicrob. Agents Chemother. 43, 287-291 (1999); Koutsolioutsou, A et al. Antimicrob. Agents Chemother. 45, 38-43 (2001)). Constitutive overexpression of MarA or a MarA homolog in many of these strains is a key contributor to the maintenance of the resistance phenotype, particularly with respect to the fluoroquinolones, and recent studies have documented the selection of Mar mutants, bearing mutations in MarR, MexR, or other homologous loci, in E. coli, Pseudomonas aeruginosa, and other organisms during antimicrobial chemotherapy (Oethinger, M supra; Linde, H. J. et al.; supra; Ziha-Zarifi, I. et al. supra; Kern, W. V., et al. Antimicrob. Agents Chemother. 44, 814-820 (2000)).
MarR is a regulator of multiple antibiotic resistance in Escherichia coli. It is the prototypic member of a family of regulatory proteins found in the Bacteria and the Archae that play important roles in the development of antibiotic resistance, a global health problem. In the absence of an appropriate stimulus, MarR negatively regulates expression of the marRAB operon (Cohen, S. P., et al. 1993. J. Bacteriol. 175: 1484-1492.; Martin, R. G. and Rosner, J. L. 1995. Proc. Natl. Acad. Sci. 92: 5456-5460; Seoane, A. S. and Levy, S. B. 1995. J. Bacteriol. 177: 3414-3419, 1995). DNA footprinting experiments suggest that MarR dimerizes at two locations, sites I and II, within the mar operator (marO) (Martin and Rosner, 1995, supra). Site I is positioned among the −35 and −10 hexamers and site II spans the putative MarR ribosome binding site (reviewed in Alekshun, M. N. and Levy, S. B. 1997. Antimicrob. Agents Chemother. 10: 2067-2075).
MarR is a member of a newly recognized family of regulatory proteins (Alekshun, M. N. and Levy, S. B. 1997. Antimicrob. Agents Chemother. 10: 2067-2075. Sulavik, M. C., et al. 1995. Mol. Med. 1: 436-446) and many functional homologues have been identified in a variety of important human pathogens and have been found to regulate a variety of different processes. For example, some MarR homologues have been found to control expression of multiple antibiotic resistance operons, some regulate tissue-specific adhesive properties, some control expression of a cryptic hemolysin, some regulate protease production, and some regulate sporulation. Proteins of the MarR family control an assortment of biological functions including resistance to multiple antibiotics, organic solvents, household disinfectants, and oxidative stress agents, collectively termed the multiple antibiotic resistance (Mar) phenotype (Alekshun, M. N. & Levy, S. B. Trends Microbiol. 7, 410-413 (1999)). These proteins also regulate the synthesis of pathogenic factors in microbes that infect humans and plants (Miller, P. F. & Sulavik, M. C. Mol. Microbiol. 21, 441-448 (1996)). Insight into the three dimensional structure of MarR family proteins would be of great value in designing drugs that interact with this family of proteins and modulate MarR function, for example, antibiotic resistance and virulence.

Methods for identifying and using MarR family polypeptide binding compounds


In order for the user to perform a transmission of packet data to a desired communication counterpart on a virtual network across a wireless circuit exchange type network system and a LAN without being bothered by address exchange between an address of a physical network and an address of a virtual network, an exchange (10a) performs an address exchange necessary for establishing a communication channel between the terminal equipments within the system using a conversion table, in a mobile wireless data communication system in which a wireless circuit type network system comprising a wireless mobile station (30a), a wireless connection equipment (20a) and the exchange (10a) is connected to a LAN (40a) through a TA (60a) and a router (50a).

The progress of a recent wireless technology is remarkable. Even if it is limited to a private usage, the technology for making the indoor telephone fully wireless became a reality with the use of a PBX private branch exchange) system, etc., based on the technique for personal communications which is a result of the development of cordless telephones. Moreover, a wireless LAN (local area network) is widely practiced also in the field of data communications. This LAN undertakes a role for making offices and the like wireless.
In the wireless PBX, mobility, as well as wireless of telephones, was pursued. That is, a movement in the wireless area under the control of a single PBX is made possible as a matter of course, and in addition, even a movement across between PBX is also made possible by the automatic position registration, without compelling the user a useless registration change (or, transmitting an incoming signal, etc.). This technology is often referred to as "loaming between PBX". In principle, it realizes a possibility of endless movement even within the private branch. Moreover, a PBX added-service based on the use of the PBX which mostly uses the voice is realized in an almost perfect shape with the realization of this mobility.
On the other hand, recently, needs to a telephoneless communication as represented by e-mail have been increasing. This telephoneless communication method includes a method for performing a communication through a telephone line (channel exchange) and a method for performing a communication from a terminal equipment accommodated within the LAN. Needless to say, the method using the LAN is chiefly employed in recent offices. In addition, the appearance of the Internet is spurring the popularization of this LAN further. Now, the technology of the Internet is briefly described.
The Internet is one embodied form of a virtual network which aims at performing worldwide communications across the various physical networks represented by LAN such as Ethernet, essentially satisfying the following items.
(a) The network principle of the Internet is to realize a virtual network and not to specify a form of realization of a physical network.
(b) The Internet address does not obligate the existence of a switching node which performs the switching intensively. On the other hand, it is necessary for the terminal equipment to be fixed to the physical network.
In order to perform a routing between the terminal equipments across the various physical networks, it is necessary that the terminal equipments are uniquely identified in the world. Concretely, it is necessary that a connection point with the physical network where the specific terminal equipment is accommodated is uniquely identified in the world. In the Internet, therefore, an address called "IP (Internet Protocol) address" is assigned to each terminal equipment based on a common system in the world, and the routing is performed based on this Internet Protocol address.
The wireless PBX chiefly comprising the channel exchange and the Internet based on the LAN were explained hereinbefore. The former is becoming main communication means in offices by adding mobility thereto, and the latter is becoming main communication means for data communications. It seams that importance of those communication means will rise more and more as a basic structure for supporting activities in offices in the future.
By the way, in the virtual network across the wireless PBX and the LAN, the data communication terminal equipment, which is under the control of the wireless PBX, occasionally transmits packet data. In such occasions, a communication channel in the wireless PBX system was established by signal outputted from the telephone (personal station) connected to the data communication terminal equipment, and a data communication was performed via the LAN. That is, the role to make the address on the virtual network and the address (in this case, telephone number) on the physical network correspond to each other was played by man as an addresser of the data. Therefore, the operation was troublesome.

Mobile wireless data communications system