An apparatus configured to obtain a physical property of an object by time-domain spectroscopy includes: a detection unit; a delay unit configured to adjust a time difference between generation and detection; a shaping unit configured to collect the electromagnetic wave pulses; a waveform obtaining unit configured to construct a time waveform of the electromagnetic wave pulses; and a collecting position adjusting unit configured to adjust a collecting position. When the collecting position is moved, an amount of adjustment when the collecting position matches first and second reflection portions, respectively, of the object, and a difference by the delay unit required for detecting first and second pulses of the time waveform are obtained, and from an amount of change of the amount of adjustment and the difference, a thickness and a refractive index of a region between the first and second reflection portions of the object are calculated.

Terahertz waves typically are electromagnetic waves having components of any frequency bands within a range of 0.03 THz to 30 THz. Such frequency bands include many characteristic absorption bands derived from structures or states of various substances including biomolecules. Using such characteristics, inspection techniques of non-destructive analysis or identification of substances have been developed. Also, application of terahertz waves to safe imaging techniques replacing X-rays or high speed communication techniques is expected. Further, it is noted that reflection terahertz waves from a refractive index interface in an object to be measured are applied to a tomography apparatus configured to visualize an inside of the object to be measured. Such an apparatus is expected to visualize an inner structure at a depth of several hundreds of μm to several tens of mm using a characteristic of transmission of terahertz waves. In many cases, terahertz waves in the form of subpicosecond pulses are used for such use. Usually, it is difficult to obtain such pulses in an actual time. Thus, a THz-TDS apparatus (terahertz time-domain spectroscopy apparatus) performs sampling measurement using ultrashort pulsed lights (also herein referred to as excitation lights) having a femtosecond pulse width. Sampling of the terahertz waves is achieved by adjusting an optical path length difference between excitation lights reaching a generation unit configured to generate the terahertz waves and a detection unit configured to detect the terahertz waves. For example, the optical path length difference is adjusted according to an amount of fold of the excitation lights by inserting a stage (also herein referred to as a delay optical unit) having a folded optical system into propagation paths of the excitation lights. In many cases, a photoconductive element having an antenna electrode pattern with a minute gap provided on a semiconductor thin film is used as the generation unit or the detection unit.
In an example of the present invention, physical properties of an object to be measured are obtained using the principle of a THz-TDS apparatus. The physical properties of the object to be measured mainly include a refractive index and a shape (thickness) of the object to be measured. These physical properties are often calculated using terahertz wave pulses, from a time difference between reflection pulses from a refractive index interface of the object to be measured (see PTL 1). An interval between the reflection pulses corresponds to an optical length of propagation of terahertz waves. The optical length of the terahertz waves is expressed in the form of n(ave)×t by multiplying a thickness t of the object to be measured by an average refractive index n(ave). The average refractive index refers to a typical refractive index of the object to be measured. For example, the average refractive index refers to an average value of refractive index dispersion in a frequency band used. Otherwise, the average refractive index refers a refractive index at frequency (wavelength) having highest intensity in a frequency spectrum of the object to be measured. It is difficult to calculate the thickness t and the average refractive index n(ave) of the object to be measured from a measurement result of the terahertz waves because there is only one measurement result for two unknowns. To solve this problem, PTL 1 calculates a refractive index of an object to be measured by another unit. As such, to separate the thickness t and the average refractive index n(ave) from the measurement result, either of them needs to be obtained using another measurement unit. For this purpose, properties of the object to be measured are desirably specified to some degree before measurement. However, such an act may limit an application range as a measurement apparatus.
Meanwhile, for an OCT apparatus (Optical Coherence Tomography apparatus), some techniques for separating such information have been developed as described below. A confocal optical system is constructed, and a thickness t and an average refractive index n(ave) are simultaneously calculated from, an amount of movement of a focus in a collecting position of the confocal optical system in a depth direction of an object to be measured, and an amount of change of an optical path length difference of an interference system required for obtaining a maximum interference signal for each focus. Specifically, the thickness t and the average refractive index n(ave) of the object to be measured are calculated from a ratio of the amount of change of the optical path length difference to the amount of movement of the focus (see PTL 2).

Measurement apparatus and method, tomography apparatus and method


The color video-endoscope (100) comprises in particular:. a single light source (10); PA1 a bundle of optical fibers (40) for transmitting the light to a field of observation; PA1 a periodic filtering device (50) including three filters (53, 54, 55) illuminating the field of observation with three respective primary colors (R, G, B), and a fourth filter zone (56) which is transparent and through which the light also passes; PA1 a photosensitive sensor (60) for picking up an image of objects situated in the field of observation; PA1 an analog-to-digital converter (91) for digitizing the periodic information from the sensor (60) representative of color images (RGB) and of a black-and-white image (B/W), with the digital information being stored in four respective memories (81 to 84); and PA1 a color toning device (85a, 85b) selectively combining the black-and-white image information (B/W) with the color information for the purpose of reconstituting a color image of very good quality.

The present invention relates to a method of sensing and processing images for a color video-endoscope, and to a video-endoscope implementing the method.
Patent FR-2 438 999 describes an endoscope for processing color information and for forming a read signal, in particular a signal compatible with a television set (a priori any television set of standardized format), i.e. for making color images of a field of observation (namely of objects situated in said field).
That French patent uses a lighting system based on the teaching of the U.S. Pat. No. 4,074,306 in which information about the image observed in the field scanned by the observation head of the endoscope is split into three primary colors, in particular Red, Green, and Blue (RGB). The original color image is then recreated by combining partial images in each of these three primary colors RGB. The three RGB images are formed by mechanically filtering the light used to illuminate the cavity being explored (by means of the observation head of the endoscope) by using a single light source associated with a rotary disk for providing RGB filtering of the light it provides. In a variant, the three RGB images may also be formed by splitting an image reflected from the field of observation by means of a series of dichroic mirrors.
French patent FR-2 438 999 thus differs from American U.S. Pat. No. 4,074,306 essentially in that the three separated light images, each containing data corresponding to an individual one of the primary colors RGB, are created by successively controlling a series of lamps that have short response times.
In addition, that French patent makes use of an individual light source for each of the primary colors (RGB) used in the video system adopted, which light is transmitted to the field of observation being explored by the head of the endoscope via a bundle of optical fibers. Furthermore, each of the primary color (RGB) images is formed in succession on a semiconductor image-forming device, and the output signals therefrom are coupled electrically to a memory for storing each of the read color signals individually, the color signals stored in the above memory being periodically applied to an image processing circuit for making the corresponding information available in a for-mat that is compatible with the format of a color receiver.
Nevertheless, the image of the observed field as reconstituted by analog means in this way does not have the brightness and contrast that is desirable in this kind of application, where it is essential to show up clearly the details of the field of observation that contain important optical information.
An object of the present invention is to eliminate the drawbacks of the prior art in such a manner as to obtain color images of the observed field having brightness and contrast that are better than those obtained in the prior art, with this having the additional advantage of an increase of at least 30% in the observation distance (between the read head of the video-endoscope and the field of observation).

Color filter wheel for endoscopes and processing of generated color

Fort Fibres Optiques Recherche et Technologie


A compound of formula I, including optical isomers thereof, ##STR1## wherein X represents --SO.sub.2 NH-- or --NHSO.sub.2 --,. p, q and r independently represent 2 or 3, PA1 Y represents thienyl optionally substituted by alkyl or halogen, or phenylthio- or phenyl optionally substituted by alkyl or halogen, and each R independently represents H or alkyl, and pharmaceutically acceptable salts, esters and amides thereof

Benzothiazolone derivatives are known. For example, international patent applications, publication numbers WO92/08708 and WO93/23385 disclose biologically active amines, among them biologically active aminoethyl benzothiazolone derivatives which are .beta..sub.2 -adrenoreceptor agonists and dopamine DA.sub.2 -receptor agonists, and which are indicated in the treatment of obstructive airways diseases.
WO 93/24473 discloses 7-(2-aminoethyl)-benzothiazolone compounds of formula ##STR2## wherein X and Y are independently --S(O).sub.n -- or --O--; n is 0,1 or 2; p, q and r are independently 2 or 3; Z is phenyl optionally substituted by halogen, OR.sup.1, NO.sub.2 or NR.sup.2 R.sup.3 ; or Z is a 5 or 6 membered N, O or S containing heterocycle; and R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen or alkyl C.sub.1-6. The compounds are .beta..sub.2 -adrenoreceptor agonists and dopamine DA.sub.2 -receptor agonists, and are indicated in the treatment of obstructive airways diseases.
We have now found a group of novel 7-(2-aminoethyl)-benzothiazolone derivatives which are useful as dopamine DA.sub.2 -receptor agonists and .beta..sub.2 -adrenoreceptor agonists.
Outline of the Invention
Accordingly, in one aspect of the present invention there are provided compounds of formula I including optical isomers thereof, ##STR3## wherein X represents --SO.sub.2 NH-- or --NHSO.sub.2 --,
p, q and r independently represent 2 or 3, PA1 Y represents thienyl optionally substituted by alkyl or halogen, or phenylthio- or phenyl optionally substituted by alkyl or halogen, and each R independently represents H or alkyl and pharmaceutically acceptable salts, esters and amides thereof.
The compounds are pharmacologically active. They show both dopamine DA.sub.2 -receptor agonism and .beta..sub.2 -adrenoreceptor agonism. They exhibit little or no .alpha..sub.1 -adrenoreceptor agonism. The compounds have an advantageous duration of action and DA.sub.2 /B.sub.2 ratio.
Preferably, q in formula I above is 2. r is preferably 2.
When Y is phenyl substituted by alkyl, the alkyl group is preferably a C.sub.1-6, for example a C.sub.1 or C.sub.2 group, most preferably methyl.
When Y is phenyl substituted by halogen, the halogen substituent is preferably a chloro- or fluoro-substituent.
Preferred compounds of the present invention are compounds of formula I wherein X is SO.sub.2 NH, p is 3 and q and r are each 2. Other preferred compounds are compounds of formula I wherein X is NHSO.sub.2, and p, q and r are all 2.
Suitable pharmaceutically acceptable salts of the compounds of formula I include acid addition salts derived from inorganic and organic acids. The compounds may also form salts with suitable bases. Examples of suitable salts include the hydrochloride, citrate, D,L-lactate, hemisulphate, hemitatrate, D-gluconate, methanesulphonate, p-toluenesulphonate, hemifurnarate, benzoate, xinafoate, hemisuccinate, 3-hydroxy-2-naphthoate, hemiembonate, hemimaleate, D-camphorsulphonate, 10-undecanoate, mandelate, naphthalene-1-sulphonate, naphthalene-2-sulphonate, 4-methoxybenzoate, 4-chlorobenzoate, 5-methylsalicylate, saccharinate, monomethyl suberate, hemisuberate and diphenyl acetate salts.
Suitable pharmaceutically acceptable esters of the compounds of formula I include phenylalkyl and alkyl esters.
Suitable amides include unsubstituted or mono- or di-substituted alkyl or phenyl amides.
The most preferred compounds of the invention are
3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-(2-phenylet hoxy)ethyl]propanesulphonamide; PA0 N-[2-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]ethyl]-2-(2- phenylethoxy)ethanesulphonamide; PA0 3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-[2-(5-methy l-2-thienyl)ethoxy]ethyl]propanesulphonamide; PA0 N-[2-[2-(4-Fluorophenyl)ethoxy]ethyl]-3-[2-(4-hydroxy-2-oxo-3H-1,3-benzothi azol-7-yl)ethylamino] propanesulphonamide; PA0 N-[2-[2-(4-Chlorophenyl)ethoxy]ethyl]-3-[2-(4-hydroxy-2-oxo-3H-1,3-benzothi azol-7-yl)ethylamino]propanesulphonamide; PA0 3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-[2-(4-methy lphenyl)ethoxy]ethyl]propanesulphonamide; PA0 (R,S)-3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-(2-ph enyl-1-propoxy)ethyl]propanesulphonamide; PA0 3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-[2-(2-methy lphenyl)ethoxy]ethyl]propanesulphonamide; and PA0 3-[2-(4-Hydroxy-2-oxo-3H-1,3-benzothiazol-7-yl)ethylamino]-N-[2-(2-phenylth ioethoxy)ethyl]propanesulphonamide;
preferably in salt form and more preferably as the hydrochloride.
The present invention also provides a method for the production of compounds of formula I, comprising selective reductive alkylation of a compound of formula II, ##STR4## with a compound of formula III, ##STR5## in which p, q, r, R, X and Y are as defined above, in the presence of a reducing agent.
The reducing agent may be, for example, hydrogen in the presence of a catalyst such as platinum, platinum oxide, palladium, palladium oxide, Raney nickel or rhodium, on a support e.g. charcoal, using an alcohol, e.g. ethanol, or an ester, e.g. ethyl acetate, or an ether, e.g. tetrahydrofuran, or water, as reaction solvent, or a mixture of solvents, at normal or elevated temperature and pressure. The preferred temperature is room temperature. The preferred pressure is 1-3atmospheres. Alternatively the reducing agent may be sodium borohydride or a metal hydride e.g. sodium cyanoborohydride. Suitable solvents for use with hydride reducing agents will depend on the particular hydride used and will be well known to the person skilled in the art. Suitable solvents will include alcohols, for example ethanol or methanol.
The process may give rise to intermediate imine compounds, which may be reduced under the described conditions, to give compounds of formula I.
The compound of formula II may be prepared by known methods, for example by the method described in J. Med. Chem., 1987, 30, 1116.
Aldehydes of formula III may be prepared in a number of ways known per se. For example, isothiazolidine dioxides (as in Example 1c, for instance) may be reduced with DIBAL in toluene; acetals (as in Example 2b, for instance) may be hydrolysed with 70% aqueous acetic acid; and esters (as in Example 3d, for instance) may be reduced with DIBAL in toluene. Specific syntheses of certain precursor compounds are described in the Examples and may be adapted to a variety of targets.
The aldehydes of formula III may also be prepared from the corresponding alcohols by partial oxidation using DMSO, DCC and anhydrous phosphoric acid; or using pyridinium chlorochromate or pyridinium dichromate.
The present invention also provides a further process for preparing compounds of formula I, comprising the selective reduction of a compound of formula IV, ##STR6## in which p, q, r, R, X and Y are as defined above.
Suitable reducing agents include electrophilic reducing agents, e.g., diborane and alane (aluminium hydride), or nucleophilic reducing agents, e.g., a complex metal hydride such as sodium bis(2-methoxyethoxy)aluminium hydride. The preferred reducing agent is diborane. The solvent should be inert to the reaction conditions. Aprotic solvents are preferred, e.g. tetrahydrofuran, diethyl ether, or 1,2-dimethoxyethane. The reaction may be carried out at a temperature of from about 0.degree. C., to about 100.degree. C., preferably at reflux temperature.
Compounds of formula IV may be prepared by coupling of the amine of formula II and an appropriate acid, of formula V ##STR7## or corresponding acid chloride by conventional means. For example, the coupling may be performed in the presence of dicyclohexylcarbodiimide using the method of Sheehan and Hess, J. Am. Chem. Soc., 1955, 77, 1067; or 1,1'-carbonyldiimidazole as described by Staab, Angew. Chem. Int. Ed. Engl., 1962, 1, 351; or bromotripyrrolidinophosphonium hexafluorophosphate in a solvent such as DMF, following the procedure of Example 1e. The acids required for the process may be obtained from the corresponding esters, by hydrolysis with lithium hydroxide in aqueous methanol, following the procedure of Example 1b. Examples 1a, 2d, 3d, 4f, 5d, 6d, 7d, 8d and 9d describe specific processes for forming is the esters, and these process may be adapted to give other esters, for forming further acids for coupling with formula II amines. The acid chlorides may be prepared from the acids for example by reaction with oxalyl chloride or thionyl chloride in toluene at a temperature from ambient to reflux.
The compounds of the present invention may be prepared by several other methods as well.
Alkylation of the compound of formula II, or a salt, ester or amide thereof, with an alkylating agent of formula VI ##STR8## in which p, q, r, R, X and Y are as defined above and L represents a good leaving group, for example a halide e.g. chloride, bromide or iodide, or an alkyl- or aryl-sulphonyloxy group, for example methanesulphonyloxy, is one such method.
The reaction may be carried out for example in the presence of a base, for example an inorganic base, e.g., sodium or potassium carbonate, or an organic base, e.g., triethylamine, N,N'-diisopropylethylamine or pyridine.
The reaction may be performed in a solvent, for example an ether, e.g. tetrahydrofuran or dioxan, a ketone, e.g. butanone or methyl isobutyl ketone, a substituted amide, e.g. dimethylformamide, or a chlorinated hydrocarbon, e.g. chloroform, at a temperature of between ambient temperature and the reflux temperature of the solvent. Preferably the reaction is carried out at ambient temperature.
The alkylating agent of formula VI may be prepared from the corresponding alcohol (i.e. the compound in which L represents OH) by methods known to the person skilled in the art. For example, the alcohol may be reacted with a halogenating agent to yield the compound of formula VI in which L represents a halogen atom. Suitable halogenating agents include, for example, triphenylphosphine-tetrahalogenomethane adduct (conveniently formed in situ, e.g. by the reaction of triphenylphosphine and carbontetrabromide). The reaction may take place in the presence of a solvent such as acetonitrile, or a chlorinated hydrocarbon, e.g. dichloromethane, for example at a temperature in the range of 0-30.degree. C.
Another method is the selective reduction of a compound of formula VII, ##STR9## in which p, q, r, R, X and Y are as defined above.
Suitable reducing agents include electrophilic reducing agents, e.g., diborane and alane (aluminium hydride), or nucleophilic, e.g., a complex metal hydride such as sodium bis(2-methoxyethoxy)aluminium hydride. The preferred reducing agent is diborane. The solvent should be inert to the reaction conditions. Aprotic solvents are preferred, e.g. tetrahydrofuran, diethyl ether, or 1,2-dimethoxyethane. The reaction may be carried out at a temperature of from about 0.degree. C., to about 100.degree. C., preferably at reflux temperature.
Compounds of formula VII may be prepared by coupling of an amine and an acid or acid chloride by conventional means. For example, the coupling may be performed in the presence of dicyclohexylcarbodiimide or 1,1'-carbonyldiimidazole or bromotripyrrolidinophosphonium hexafluorophosphate, as described above in relation to compounds of formula IV. The amines required for the coupling reaction may be prepared by reaction of compounds of formula VI, where L represents a good leaving group for example a halide such as chloride or bromide, with phthalimide in the presence of a base. The resulting imides may then be treated with hydrazine hydrate in ethanol to give compounds of formula VI with the leaving group replaced by an amino group.
In the above processes it may be necessary for any functional groups. e.g. hydroxy or amino groups, present in the starting materials to be protected. Suitable protecting groups and methods for their removal are, for example, those described in "Protective Groups in Organic Synthesis" by T. W. Greene and P. G. M. Wuts, John Wiley and Sons Inc., 1991.
Another process for preparing compounds of formula I comprises removal of a protecting group from a corresponding protected compound of formula I in which one or more of the functional groups is protected, and where desired or necessary converting the resulting compound of formula I to a pharmaceutically acceptable salt, ester or amide thereof or vice versa.
Pharmaceutically acceptable salts may be prepared for example by reacting the compound of formula I with an appropriate acid in the presence of a suitable solvent. Pharmaceutically acceptable esters of the compounds of formula I may be made by conventional techniques, e.g. esterification or transesterification.
Pharmaceutically acceptable amides of the compounds of formula I may be made by conventional techniques, e.g. reaction of a compound of formula I with an acid or acid chloride.
The intermediates of formula IV are novel, thus according to a further aspect of the invention there are provided compounds of formula IV, ##STR10## in which p, q, r, R, X and Y are as defined above.
The intermediates of formula VII as defined above are also novel and are thus also provided in accordance with the present invention.
Further, the aldehydes of formula III as defined above are novel and are provided by the present invention.
Still further the acids of formula V and corresponding acid chlorides are novel and are provided by the present invention.
The compounds of formula I and salts, esters and amides thereof are dopamine DA.sub.2 -receptor agonists. The binding affinities of the test compounds for the DA.sub.2 receptor binding sites in bovine pituitary membranes may be determined from the displacement of [.sup.3 H]-N-n -propylnorapomorphine and of [.sup.3 H]-spiperone in the absence or presence of nonhydrolysable GTP analogue respectively, D. R. Sibley, A. DeLean and I. Creese, Anterior Pituitary Dopamine Receptors, Demonstration of Interconvertible High and Low Affinity States of the D-2 Dopamine Receptor, J. Biol. Chem, 1982, 257(11), 6351-6361. The DA.sub.2 -receptor activity may also be demonstrated in a functional screen, the rabbit isolated ear artery, as described by Brown and O'Connor, Br. J. Pharmacol., 1981, 73, 189P. The compounds are also .beta..sub.2 -adrenoreceptor agonists. This activity may be demonstrated in the isolated trachea of the guinea pig, as described by I. G. Dougall, D. Harper, D. M. Jackson, and P. Leff, Br. J. Pharmacol., 1991, 104, 1057. .alpha..sub.1 -Receptor activity may be analysed using the rabbit isolated ear artery screen described in Pharmacological Example herein.
The compounds of formula I and salts, esters and amides thereof are thus indicated for use in the treatment of the range of airways diseases, including conditions such as asthma, including bronchial asthma, allergic asthma, intrinsic asthma (for example late asthma and airway hyper-responsiveness); and bronchitis and the like (see, for example, UK Patent No. 2022078 and Br. J. Pharmacol., 1987, 24, 4983).
The compounds of formula I and salts, esters and amides thereof are also indicated for use in the treatment of various other conditions, e.g. inflammatory and allergic skin disorders, cancer e.g. small cell lung cancer, congestive heart failure and glaucoma.
The term "treatment" as used herein includes prophylaxis as well as relief of the symptoms of disease.
Accordingly, in a further aspect of the present invention, there is provided the use of a compound of formula I, or a pharmaceutically acceptable salt, ester or amide thereof in therapy.
Further, there is provided the use of a compound of formula I, or a pharmaceutically acceptable salt, ester or amide thereof, in the manufacture of a medicament for the treatment of obstructive airways disease, in particular for the treatment of asthma or chronic bronchitis.
Still further, the present invention provides a method of treatment of airways disease, which method comprises administering a therapeutically effective quantity of a compound of formula I, or a pharmaceutically acceptable salt, ester or amide thereof, to a patient suffering from or susceptible to such a condition.
Typical daily unit doses may be for example 1 .mu.g-10 mg for topical administration, preferably 10-500 .mu.g, for example divided two or three times, or 10 .mu.g-100 mg for oral administration, preferably 100 .mu.g-10 mg, for example divided two or three times.
The compounds of formula I and salts, esters and amides thereof may be used on their own or in the form of appropriate pharmaceutical compositions.
Administration may be by inhalation as well as by other routes, for example by oral or intraveneous administration.
Nasal or pulmonary administration may be achieved via a suitable inhalation device.
For example metered dose inhaler devices may be used to administer the compound, dispersed in a suitable propellant and with or without additional excipients such as ethanol, surfactants, lubricants and stabilising agents.
Suitable propellants include hydrocarbon, chlorofluorocarbon and hydrofluoroalkane propellants, or mixtures of any such propellants. Especially preferred propellants are P134a and P227 each of which may be used alone or in combination with other propellants and/or surfactants and/or other excipients, for example in combination with each other.
Nebulised aqueous suspensions or, preferably, solutions may also be employed, with or without a suitable pH and/or tonicity adjustment, either as a unit-dose or multi-dose device.
Dry powder inhalers may be used to administer the compound, alone or in combination with a pharmaceutically acceptable carrier, in the latter case either as a finely divided powder or as an ordered mixture. The dry powder inhaler may be single dose or multi-dose and may utilise a dry powder or a powder-containing capsule.
Metered dose inhaler, nebuliser and dry powder inhaler devices are well known and a variety of such devices are available.
The invention is illustrated, but in no way limited, by the following Examples, in which temperatures are in degrees Celsius. Where necessary, the reactions were performed under an inert atmosphere of either nitrogen or argon. Where necessary, preparative HPLC separations were generally performed using a Novapak.RTM., Bondapak.RTM. or Hypersil.RTM. column packed with BDSC-18 reverse phase silica. Flash chromatography was carried out using Fisher Matrix 60 silica, 35-70 micron.

Intermediates for making benzothiazolone derivatives


Systems, methods, and techniques to efficiently and effectively verifying and calibrating a machine learning model. The method can include training a machine learning model by at least processing training data with the machine learning model. The method can further include manipulating a first data set of the training data and applying the manipulated first data set to the machine learning model to thereby determine a first matching rate. In addition, the method can include applying the manipulated first data set to a rule engine to thereby determine a second matching rate and determining a difference between the first matching rate and the second matching rate. The method can further include determining whether the difference is within a predefined threshold range and providing an error indication if the determined difference is outside of the predefined threshold range.

Machine learning algorithms and models can be popular for business applications, such as for automating repetitive tasks (e.g., matching deliveries with orders or payments with invoices). Such machine learning models can learn from historic or training data. Some issues can be associated with using some machine learning models. For example, a machine learning model can be dependent on a quality of the training data. For example, special cases that have not occurred in the past may not be correctly solved by the machine learning model. Additional issues can include overfitting or underfitting. For example, in the case of overfitting, the machine learning model may incorrectly match data entries, such as entries that have some similarities but are not a correct match. An example of underfitting may include when a small difference between two data entries results in a non-match when such entries should have been considered a match. Furthermore, over time machine learning algorithms can require re-trainings. However, it can be difficult for users to determine when and if machine learning models require retraining. Such issues can counteract the automation benefits of machine learning and reduce acceptance and trust by users.


A system and method are provided that allow analysis of alarm data to generate security reports. A security report system may include a monitoring tool and a data analyzer. The monitoring tool may include an alarm data acquiring module and an alarm database for storing the alarm data acquired by the alarm data acquiring module. The data analyzer may include a data parsing module for parsing the alarm data into a plurality of data segments each indicating an attribute of the alarm data, a data categorizing module for categorizing the plurality of data segments into a plurality of data groups in accordance with the attributes of the data segments, and a data processing module for processing the data segments of at least one of the data groups to generate a security report.

Security systems offer a degree of security for residential sites and for office, business, and/or industrial applications. Typically, a security device, such as a sensor or a camera, monitoring a protected area is provided as part of a security system. Such security system devices can detect the occurrence of various alerting events, such as a breach of the protected area, a fire condition, or other types of condition, and can generate alarm signals, notification and/or data indicative of the events. The signals or data are usually transmitted through wired or wireless connections to a security control panel configured for processing the alarm signals or data from the security device and for implementing other functionalities based on the processed results of the alarm signals or data, such as arming the system, disarming the system, providing system status and generating alerting messages indicative of the events, coordinating the operations of different functional modules of the system, and so on.
In addition, a central monitoring station is normally provided to communicate with the security control panel for receiving, routing and sending the messages generated by the control panel to the terminal devices of the users of the security system, notifying them of the occurrence of alerting events. The central monitoring station usually receives data from the security control panel and further processes the received data to generate alarm data. The alarm data can be in any suitable format.
FIG. 1 is a block diagram illustrating a known security system 10, which communicates with a user's terminal device 40 via an IP network 60. The security system 10 is generally configured to detect the occurrence of a predefined alert event and notify the user of the occurrence of the event through a message, such as an email or SMS.
The security system 10 includes at least one security device 20 configured to detect an event, such as a breach of protected premises, and transmit signals in response to the event. The system 10 further includes a security control panel 30 in communication with the security device 20 through the IP network 60, for processing the signals from the security device and controlling the operations of other functional modules of the system. A central monitoring station 50 is in communication with the security control panel 30 through the IP network 60. The central station 50 is capable of processing the received data to generate alarm data.
However, no extended applications of the alarm data generated by the central monitoring station have been envisioned and developed so far. Thus, it is desirable to provide extended application of the alarm data generated by the central monitoring station, for example, to produce extra revenues.

Method for processing alarm data to generate security reports


A substrate treatment apparatus includes a processing chamber configured to be capable of storing a substrate; a substrate holder disposed in the processing chamber and configured to be capable of holding the substrate; a sublimation removing unit configured to remove, by sublimation, a sublimating material filled between structures formed on a surface of a substrate held by the substrate holder, and a sublimation status detecting unit configured to detect a progress or an end point of sublimation removal of the sublimating material.

After a liquid processing of a substrate such as substrate cleaning, the substrate needs to be dried by removing the liquid on the surface of the substrate. For example, an attempt to remove the liquid on the substrate by vaporization may cause fine structures formed on the substrate to collapse by liquid surface tension. A drying method utilizing a sublimating material is being proposed to prevent the collapse of such structures.
The method of drying the substrate using a sublimating material begins with supplying a liquid containing a sublimating material to the surface of the substrate. The supplied liquid substitutes the cleaning liquid remaining on the substrate surface which was used in the cleaning of the substrate surface. Then, the liquid containing the sublimating material is vaporized to cause the sublimating material to precipitate in the spaces between the structures. As a result, the spaces between the structures are filled with solids of the sublimating material. Then the precipitate of the sublimating material is removed by sublimation to dry the substrate surface. In the above described method, it is possible to prevent the collapse of the structures caused by liquid surface tension since the structures are supported by solids of sublimating materials filled between the spaces of the structures.
Conventionally, the process of removing the sublimating material by sublimation was controlled, for example, by time. Thus, the determination of whether or not the sublimating material has sublimated sufficiently from the substrate surface was made, for example, by the eyes of the operator or by using SEM (Scanning Electron Microscope). Thus, it was difficult to properly detect the progress or the end point, i.e. end period of the process for removing the sublimating material by sublimation and end the process by such proper detection.

Substrate treatment apparatus and substrate treatment method


A delay measurement technique using a tapped delay line edge capture circuit that captures tap position of edges within the delay line provides accuracy of measurement to one pico-second and below. A control circuit causes latches to capture an edge of a signal delayed through the delay line at taps of the delay line. The frequency of a clock from which the signal is derived is adjusted and tap outputs are captured by latches and averaged. A first frequency is found at which the average edge position is midway between two adjacent tap positions. A second signal, which may be the reference signal that clocks the latches, is propagated through the delay line and a second frequency is found for which the average edge position lies at the boundary between the two tap positions. The delay is determined from the difference between the periods of the first frequency and the second frequency.

1. Field of the Invention
The present invention is related to integrated circuits incorporating internal timing measurement circuits, and more specifically to techniques for measuring signal delays within an integrated circuit by frequency-stepping a clock signal.
2. Description of Related Art
Measurement of on-chip signal delay is performed routinely in microprocessors in order to determine whether timing windows are maintained and in some cases to measure temperature and power supply voltages indirectly. The limitations of such measurements are typically on the order of one delay stage (one inverter) delay in duration, which in present-day integrated circuits (ICs) is approximately 5 picoseconds (ps). In order to achieve measurement accuracies finer than this, off-chip measurements are generally necessary, but for measuring delays, the errors produced by the signal transit required to bring a signal-under-measurement off-chip typically negate any sort of accuracy improvement that can be had with any off-chip measurement. More accurate techniques s are available to measure delays within integrated circuits, but they typically require complex calibration and/or complex circuits.
Resonant clocking of digital integrated circuits provides low energy consumption and well-controlled clock characteristics, including reduction of jitter and predictable point-to-point delay. In some implementations, a reduced pulse width is employed in resonant clock drivers to further decrease energy consumption, since the clock drive only needs to be active long enough to restore the energy that is lost in the portions (sectors) of the resonant clock distribution network that is being driven by the individual clock drivers.
Mode changing in a resonant clock distribution network is needed for variable operating frequency, for example, in a processor integrated circuit with "turbo" operating modes or in which voltage-frequency scaling is employed to reduce energy consumption when processor activity is low. The mode changing may change operating frequency and/or may change the clock mode from resonant distribution to non-resonant. However, when changing the mode in a resonant clock distribution network, which generally change in the drive strength and/or pulse width of the clock driver circuits, the mode change may generate a short cycle or glitch that can cause improper operation of the integrated circuit in which the resonant clock distribution network is implemented. Changes in mode typically need to generate less than a 1% change in clock period/clock frequency in order to avoid timing margin violations that can result in functional errors. However, a 1% change at a clock frequency of 4 gHz is less than 2.5 ps, which would require at least 1 ps accuracy to measure with any certainty.
It would therefore be desirable to provide a measurement scheme that can be implemented within a microprocessor circuit to determine sub-ps delay values.

Measurement of signal delays in microprocessor integrated circuits with sub-picosecond accuracy using frequency stepping

INTERNATIONAL BUSINESS MACHINES CORPORATION


A headset in accordance with an embodiment of the present technology includes a headpiece, an earpiece, an arm extending therebetween, and a cord extending through the arm. The arm includes elongate first and second segments through which the arm is operably connected to the earpiece and the headpiece, respectively. The first and second segments have a telescoping arrangement such that the arm is movable between a lengthened state and a shortened state. The arm further includes a hinge operable to rotate the arm about an axis and thereby move the arm relative to the headpiece between a folded state and an unfolded state. Increased slack in the cord preferentially gathers within an interior region of the second segment when the arm moves from the lengthened state toward the shortened state and when the arm moves from the folded state toward the unfolded state.

Audio headsets are used for listening to music, playing video games, telephonic communication, noise cancelling, etc. The basic form of conventional audio headsets has remained fairly consistent for several decades. A typical dual-earpiece audio headset includes earpieces at respective ends of a headpiece shaped to bridge a user's head. Each of the earpieces includes a speaker that converts an audio signal into sound. The sound is generated in close proximity to a user's ear, so the sound can be fully audible to the user while still being inaudible or minimally audible to others around the user. This makes audio headsets ideal for use in public settings.
Unlike the basic form, the manner in which audio signals are conveyed from sources (e.g., music players) to earpieces varies among conventional headsets. One type of conventional headset includes an external cord that splits into two branches. One branch directly connects to a first earpiece and the other branch directly connects to an opposite second earpiece. Unfortunately, these branches are often prone to tangling. Furthermore, the branches often merge at a crook that is highly susceptible to damage. Another type of conventional headset includes a bridging cord that connects earpieces to one another through an associated headpiece. In this type of conventional headset, both of the earpieces can be operable even when only one of the earpieces is connected to a source. Conventionally, however, it has been difficult to effectively manage slack in the bridging cord that develops when the headset is adjusted for fit. In one example of a conventional approach to this problem, a bridging cord is exposed at joints in a headset so that the bridging cord can bulge or otherwise deform as needed in response to changes in slack. This approach is suboptimal. For example, exposed portions of the bridging cord may interfere with operation of the associated joints, snag during handling of the headset, interfere with the visual continuity of the headset form, and/or have other disadvantages. For these and/or other reasons, there is a need for innovation in this field.

Audio headset having internal cord management features and related technology


A new and distinct Hosta plant named ‘Independence’ characterized by very thick substance in the leaves, deep green coloring, upright habit in youth, lavender flowers held nicely above foliage, wide creamy-white margin, and the margin containing numerous small green flecks suitable for landscape, potted culture, or cut flower arrangements.

The new and distinct Hosta cultivar 'Independence', hereinafter also referred to as 'Independence' and "the plant" is a new and distinct plant. It was found by Jeff A. Westendorp in 1999 as an un-induced whole plant sport of the Hosta cultivar 'Revolution' (not patented) growing in a greenhouse in a nursery in Zeeland, Mich., USA. The plant has been successfully propagated by tissue culture and division methods at the same nursery to produce identical plants that maintain the unique characteristics of the original plant. The plant is stable and reproduces true to type in successive generations of asexual reproduction.
Hosta 'Independence' differs from its parent sport, 'Revolution', in that the color pattern is completely reversed in the leaf. 'Revolution' has the white center with green speckling within and a dark green margin. 'Independence' has a white margin with the green speckling within and a green center. The most similar known hosta cultivar is 'Lakeside Zinger' which has the same color pattern as 'Independence' but the margin is much wider on 'Independence'. The new plant is also about twice the size in total habit and leaf dimensions, and the thickness of the leaf of 'Independence' from top to bottom surface is much greater.


A portable organizer desk 10 comprising a sheet 12 of a substantially planar flexible material, a pair of elongate handle straps 34, 35 attached to the sheet on a first fold line 36 defining a first panel 72 and a second panel 97 in the sheet, a pair of loops 104, 105 attached to the sheet along a second fold line 39 defining a third panel 103, a pair of connecting straps 50, 51 attached to the sheet in the second panel, a plurality of pockets 56, 57, and 106 detachably connected to the sheet in the third panel, and a lapboard 52 detachably connected to the connecting straps, the lapboard having an activity surface 53 and an opposing padded surface 54, the pair of connecting straps permitting the lapboard to be selectively moved between a first position against the second panel of the sheet and a second position extending outwardly therefrom, and the lapboard detachably securing in the first position.

In their simpler form, portable desks have comprised flat roll-up trays such as that seen in U.S. Pat. No. 4,958,577 and lapboards with cupholders and small storage compartments such as those seen in U.S. Pat. Nos. 5,081,936 and 5,460,102. Portable desks have also comprised children's activity cases such as that seen in U.S. Pat. No. 5,467,853. These simple desks have provided minimal, if any, storage and organization capabilities.
In a more complex form, portable desks have comprised adult-oriented work station configurations such as those seen in U.S. Pat. Nos. 4,595,086 and 4,700,634. These complex desk configurations have required the manipulation of support legs and electric lamps.
In another form, folding trays have been made to attach to harnesses mounted to car seats as in U.S. Pat. No. 5,433,018. In still another form, feeding devices for young children have been made to anchor one end about the waist of a child and to attach another end to a car seat headrest as seen in U.S. Pat. No. 5,188,421.
Prior to now, portable desks for use in automobiles have not provided for organizing and storing toys, books, drinks and the like while simultaneously and independently providing an uninterrupted planar writing or playing surface for the child. Portable desks have also not been made for easy removal from a car seat and for readily being carried by a child or other person while also containing a child's tools and books. Portable desks have also failed to include movable storage compartments operable by a child or other person. Nor have these known portable desks provided an activity/teaching surface for facilitating interaction between drivers and passengers while travelling.
Accordingly, there remains a need in the art for a portable organizer desk that facilitates organization while being conveniently operable by both a driver and a passenger, and while providing easy access to a writing surface and an activity surface. It is to the provision of such that the present invention is directed.

Portable organizer desk for use while traveling


A customer relationship management system is disclosed for matching a given work item with an agent. The system includes a database to hold customer information, agent information, and system information, and a network contact center server operative to receive the given work item from the customer and route it to the agent based at least in part on the information in the database. The network contact center server is configured to control the conduction of an automated web dialogue with the customer via a separate web server and is further configured to control the conduction of an automated voice dialogue with the customer via an interactive voice response system. The automated web dialogue and the automated voice dialogue are thereby both conductable under the control of the network contact center server.

The invention disclosed herein relates generally to customer relationship management systems. More particularly, the present invention relates to multi-channel tracking, routing and managing of customer requests by one or more agents physically located at one or more locations to thereby create a virtual contact center.
The dramatic advent of business-to-business and business-to-consumer e-commerce operations has presented near endless opportunities in the Customer Relationship Management (CRM) market with an emphasis on customer satisfaction and retention. The availability of multi-channel customer interaction systems that combine telephone, the Internet, electronic mail, fax, and chat are quickly replacing traditional customer interaction methodologies, such as voice-only call centers. Furthermore, cost and efficiency considerations are driving the need for seamless interoperability of the front office CRM with other business functions such as back-office order management, order fulfillment, collection/analysis of customer behavior, and content management.
Conventional call center technology is primarily directed towards enhancing and personalizing customer contact for inbound and toll free public telephone network services. The traditional call center, however, is evolving into a "multimedia contact center" with a new set of drivers and operational challenges. These challenges include:                Multi-channel customer interaction, including voice, data, image, text chat, email and fax;        Personalization: enhanced caller segmentation and treatments based on customer profile, recent calling history, and current customer status, e.g., electronic shopping cart contents;        Productivity: voice response interaction, speech recognition, sophisticated web content management, integrated workflow, agent desktop integration; and        Geographic distribution: virtual contact centers that support global routing, distributed workforce, remote agents and PBX-free call centers.
Network service providers are well positioned to capitalize on the rapidly evolving drivers for a comprehensive contact center management solution. Service providers can address the technological challenges by leveraging their existing network assets, such as network elements, network services, administration and operations support systems, professional services, and intellectual property. Furthermore, a service provider hosted solution will have the advantage of achieving lower operating costs across multiple customers and will be a carrier-class solution with the ability to offer service level guarantees for performance, security and availability.
There is thus a need for a distributed and automated call center system that overcomes the challenges described above.

Customer relationship management system with network contact center server configured to control automated web and voice dialogues


A system and methods that provide a simple, but effective, technique for generating aliased and anti-aliased fonts while minimizing both processor and memory requirements are described. For each character of a font, a source pixel representation of the character is generated and stored in memory. Preferrably, the pixels of each anti-aliased character are divided among at least three non-overlapping regions which provide a color/intensity transition between the character and the background to produce an anti-aliased effect. Three of the regions are identified as the foreground region, middle region and background region. To generate a character of the font on a display the source pixel representation of the character described by the three regions is referenced from memory. If the character is to be aliased the middle and background regions are coded to the background color and the foreground region is coded to the foreground color of the character. If the character is to be anti-aliased, the foreground, middle and background regions are coded, respectively, to the color of the character, a value to provide an anti-aliased effect, and the background color. Thus, memory requirements are minimal since only one version of a font is stored. In addition, processor overhead is minimized as the time consuming calculations to generate anti-aliased characters are avoided.

Increasing the number of direct broadcast satellite receiver systems in homes has required system cost to be reduced despite increases in features. Reduction of system cost has meant that efficient system design practices must be pursued which, in turn, has meant that a feature that would normally consume large amounts of memory or require fast processors must now use memory and processing power more efficiently. Display of character fonts on a display screen is one feature that has required adoption of efficient memory and processor use.
Unfortunately, a display screen composed of discrete display points or pixels will generally not be able to display a diagonal line without producing a jagged line which has a "staircase" appearance. Since the jagged appearance is undesirable, a variety of anti-aliasing techniques are used to visibly minimize the aliased effects.
To minimize memory requirements, some display systems store only one version of a character font and generate the other version as needed ("on the fly"). It is well known that generation of an anti-aliased font from an aliased font, or vice versa, is a computationally intensive task that requires an expensive and powerful processor. Display systems without strict constraints on memory and processing power typically store both versions of a character font. However, where both adequate processing power and memory are not available, a system will be limited to just one version of a font. Thus, it is desirable to provide the flexibility of minimizing both memory and processor requirements for systems that provide for the display of both aliased and anti-aliased characters.

Displaying aliased and anti-aliased characters from a source font


An improved acetabular cup prosthesis has a cup body with a plurality of bores extending between an inner concave surface and an outer convex surface, wherein the bores can function as drill guides for providing alignment in the drilling of surgical openings after the acetabular cup body is placed in a patient. A plurality of pegs or spikes have proximate end portions that have connection members for forming connections with the bores, and distal end portions that can register into the drilled surgical openings.

1. Field Of The Invention
The present invention relates to acetabular prosthetic devices and more particularly to an improved acetabular prosthesis (and method of surgically implanting), wherein the prosthesis has a cup or shell that includes radially extending bores therethrough that can be used as drill guides by a surgeon after the acetabular cup or shell has been placed in the patient's acetabulum. Holes can be drilled surgically into the underlying bone tissue using the drill guide openings so that one or more pegs for improved anchoring can be placed into the bores and affixed rigidly to the acetabular cup using an interference or wedge fit. The prosthesis (including cup or shell and rigidly affixed pegs) is thus anchored into the underlying surgical openings. The cup has a shiny polished inner, concave surface that faces the liner so that relative motion between the liner and shell will generate minimal liner debris. The polished shell concave surface has a roughness of less that sixteen micro inches.
2. General Background
There are a number of commercially available acetabular prosthetic devices that include a cup shaped body, some of which have projections extending from the outer surface of the cup-shaped body. For example, U.S. Pat. No. 3,939,497 describes a socket for a hip joint prosthesis which is secured to a cavity in the bone tissue by a series of radially arranged pegs which can be projected outwardly from the wall of the socket into the surrounding tissue by a central screw which also has a self-tapping thread that enters the tissue.
U.S. Pat. No. 4,685,923 provides a hip joint socket made from a plastics material that can be installed without the use of bone cement or adhesive. The socket comprises a hemisphere of polyethylene. The socket may have four bores extending skewed to the equatorial plane to permit the surgeon to fix the socket in the acetabulum by means of screws or dowels temporarily or permanently. The primary anchoring is provided by two plugs or pins arranged on the outer surface of a socket. The pins may be substantially parallel to each other. The pins are inserted in bore holes drilled into the bone. The bore holes are drilled so that the pins are inserted under stress. A secondary anchor in the form of flaps are present near the actuarial plane of the socket. These flaps supplement the anchoring affect of the pins.
In U.S. Pat. No. 4,792,337 an acetabular cup is provided which has a metallic anchoring shell. The cup is for cement-less fixation in the acetabulum. The shell has several holes through which screws are driven into the bone. The screws have rounded heads and the holes are countersunk so that the orientation of the screws may be varied with respect to the cup and each other.
In U.S. Pat. No. 4,828,565 there is provided a cotyliodal component for a non-cemented hip prosthesis. The component has two parts, a titanium hemispherical shell and a cup of polymer which is engaged into it. The shell has two zones, the first zone is covered with porous titanium capable of being invaded by spongy bone and also has two projecting pieces. The other zone has a smooth metal surface. Two screws pass through the projecting pieces and are used to anchor the component in the acetabulum.
Another acetabular cup for cement-less fixation in the acetabulum is described in European Patent Application No. 13,863, published Jun. 8, 1980. The cup is anchored to the bone by a central pin and a number of other pins distributed over the surface of the cup. The pins have several sawtooth notches along their length. The bone may be pre-drilled to take the pins.
European Patent Application No. 169,978 published May 2, 1986, describes an acetabular cup which has an outer shell embedded into the patient's pelvis. The outer shell has a frustro-conical skirt and a spherical central cap. The shell has a number of small tufts with rounded ends projecting from its surface. The tufts are embedded in the bone tissue to provide improved anchorage.
In European Patent Application No. 211,169 published Feb. 25, 1987, an acetabular cup is described in which an external boss protrudes from the outer surface of the acetabulum body to fit into a pre-drilled hole in the acetabulum. The cup also has two anchoring lugs in the meridian plane. The lugs take screws to aid in anchoring the cup.
Other foreign patents and patent applications which describe acetabular cups include European Patent Application No. 212,087 published Apr. 3, 1987, wherein metallic pins project from the surface of the cup and contain holes in which tissue may grow. In European Patent No. 341,198 published Nov. 8, 1989, an acetabular cup has a metal outer shell and a plastic body for retaining the hip joint head. The shell is frustro-conical in cross-section with an opening at an apex and circular teeth around the outside. Three or more anchoring dowels parallel to the convexes protrude from the outer surface of the shells. The dowels are slotted and provide with circular teeth of a sawtooth cross-section over the portions which protrude. A central bolt may be fitted into the dowel to provide a rounded end.
The use of cement for fixation of acetabular process, and in some cases the use of spacers, is found in U.S. Pat. Nos. 4,563,778, and 4,566,138. This concept of the use of bone cement and spacers is also seen in United Kingdom Patent Nos. 1,170,295 and 2,080,118.
U.S. Pat. No. 4,923,473, issued to Peter Griss et al., entitled "Hemispherical Acetabulum", relates to a hemispherical acetabulum having a fixing pin which projects from the outside surface of the acetabulum.
In prior art acetabular cup prosthetic devices, the projections or spacers are often for the sole purpose of providing a space from the bone tissue that can be occupied by bone cement. Further, many acetabular cup prosthetic devices carry projections on their outer surface which are a part of the prosthesis as constructed and which cannot be added thereafter such as during surgery.
Still other prosthetic devices in the form of acetabular cups provide pegs which must be affixed to the tissue before the acetabular cup is placed in the position. Pegs which are preattached to the cup may require predrilling or other preparation which includes impaction for the purpose of forcing the projections into the bone. The bone bed may require advance preparation in some devices to accept the protrusions.

Acetabular prosthesis with anchoring pegs


A method of producing a magnesium compound by reacting the following components (i), (ii) and (iii):    (i) metal magnesium    (ii) an alcohol    (iii) a metal dihalide compound represented by the general formula (I) containing at least 0.001 mole of M relative to one mole of magnesium of the metal magnesium (i)MX2  (I)where X is a halogen atom and M is Mn, Fe, Co or Zn.

Hitherto, magnesium chloride and magnesium alkoxides have been widely used as a support material without being milled in the field of catalysts for olefin polymerization, specifically the homopolymerization or copolymerization of ethylene, propylene or the like. This may improve the catalyst activity and the morphology of polymer powder.
For example, for improving an obtained polymer in morphology including particle size, form, etc., there are known a method in which a magnesium compound is supported on an inorganic oxide such as silica (JP-A-S63-280707) and a method in which a magnesium compound once dissolved in a solvent such as an alcohol is precipitated again and the precipitate is used (JP-A-S56-000811). However, these methods include very complicated steps, since they require the procedures of supporting, dissolving and precipitating a magnesium compound. Further, these methods have a defect in that the catalyst is poor in performance stability.
The method of using as a support of catalysts a magnesium compound obtained by reacting metal magnesium, an alcohol such as ethanol and a certain amount of halogen (JP-A-H4-130107) has been developed. However, it has a problem in the point that the size and form of the polymer powder particle obtained depends on the conditions. For example, it does not permit omission of a pelletizing step and may not enable a copolymer of ethylene to be produced with sufficiently high efficiency.
In view of the above-mentioned problems, an object of the invention is to provide a magnesium compound, solid catalyst component and catalyst for olefin polymerization that exhibits high activity and can give an olefin polymer excellent in morphology of the polymer powder with a high stereoregularity.
Further, an object of the invention is to provide a method of producing an olefin polymer that can give an olefin polymer excellent in morphology of the polymer powder with a high stereoregularity.

Magnesium compound, solid catalyst component, olefin polymerization catalyst, and method for producing olefin polymer


An integrally formed locking clip has a unitary body and downwardly extending lateral side arms. The clip is made of resiliently flexible material which allows the side arms to extend over and around the top support member of a push broom head and attach to the broom head. The clip has an upper section consisting of a threaded opening which is configured to accept and threadably engage the threaded end connection of the handle of the push broom. When so engaged, the handle is securely mounted on and along the longitudinal axis of the broom head. The upper section of the clip may be formed of a closed circular threaded ring or a partially opened threaded cradle.

Push brooms have long been used as an effective cleaning tool. The standard push broom consists of a separable elongated handle and a brush or cleaning head. Usually the brush head is made up of bristles and a rigid bristle supporting base, often made of wood, plastic, light metal, or other hard material. The base routinely has two centrally located holes in its upper surface for receiving the handle. One hole is located on one side of the head and the second hole is located on the other side of the head. This allows the handle to be switched from one hole to the other, when the bristles become worn in one pushing direction. The holes are threaded to allow engagement with the end of the handle which has corresponding threads. The handle is easily screwed into the base in the cleaning use mode of the broom.
However, while this handle and cleaning head configuration provides a functional push broom, shipping, transport, and merchandising of these brooms presents a problem. Distribution of push brooms, when forwarded from the manufacturer to wholesalers, retailers, and vendors already connected in the cleaning use mode, i.e., with the handle secured to the threaded hole in the head, results in a cumbersome, awkward and difficult situation. Shipping brooms in this fashion also takes up valuable cargo and container space. Displaying assembled push brooms for retail merchandising and sale presents the same handling and spatial problems.
Push broom manufacturers have attempted to address these problems by shipping their brooms with the handles and heads separated and attached side by side. Handles and heads are attached with their respective longitudinal axii in parallel relationship. While this has, to a large extent, solved the handling and spatial problems, actually attaching the handles and heads so that they remain secured during transport and shipment and then during the merchandising and display process continues to be a problem. Handles and heads routinely become separated between the time of shipment from the manufacturer to the ultimate sale to the consumer. This causes inconvenience and inefficiency during transport, results in debris and waste from separated broom components and wrappers, leads to actual loss of components, and presents unattractive merchandising displays—all resulting in a general and substantial loss of sales.
In the past, manufacturers have attempted to attach push broom head and handles for transport and merchandising by means of string or twine, twist ties, and a variety of plastic and metal clips. One such spring clip type device is disclosed in U.S. Pat. No. 4,550,829. However, none of the prior broom handle to head attaching means which are designed exclusively and solely for attaching broom heads to handles for transport and merchandising purposes provides a system to guarantee an effective, practical, and economical system, which allows for the transport and merchandising of a push broom without handle to head separation.


A power MOSFET device formed in a face of a semiconductor layer of a first conductivity type is provided. A first, second and third source region of a second conductivity type are formed in the face of the semiconductor layer within a moat and adjacent to its edges. A source conductor is insulatively disposed adjacent the face of the semiconductor layer and contacts the first, second and third source regions at a plurality of locations. A first and second drain region of a second conductivity type is also formed in the face of the semiconductor layer disposed spaced from and between the first and second source regions and the second and third source regions, respectively. A drain conductor is insulatively disposed adjacent the face of the semiconductor layer and contacts the first and second drain regions at a plurality of locations. A first and second field plate are insulatively disposed adjacent the face of the semiconductor layer and substantially adjacent and surrounding the first and second drain regions respectively. A first, second, third and fourth prongs forming gates of the device are insulatively disposed adjacent the face of the semiconductor layer and between the first field plate and the first and second source regions and between the second field plate and the second and third source regions. A portion of each of the gate prongs is disposed substantially above a portion of the first and second field plates. Conductive contacts connect the first and second field plates and the first and second drain regions.

MOSFET transistors capable of handling high voltages have been used in power applications. Most power MOSFETs are of the DMOS (double diffused MOS) construction which inherently has a large drain-to-source parasitic capacitance. Power MOSFETs constructed by other processes may additionally have large gate-to-drain overlap capacitance. The large drain-to-source parasitic capacitance in effect increases the load capacitance, while the gate-to-drain overlap parasitic capacitance appears as an input capacitance augmented by the gain of the transistor. These parasitic capacitances adversely affect the transistor's performance when operating at high frequencies. Therefore, it is desirable to reduce the parasitic capacitances to improve the performance of a power MOSFET.
It is also beneficial to reduce or eliminate undesirable phenomena in a power transistor such as avalanche breakdown, hot electron stress, and punch-through to improve its performance. Conventional MOSFET transistors have the drain junction in direct contact with the p+ channel stop, therefore requiring a low doping concentration in the junction to maintain a high breakdown voltage. However, the lowered doping concentration also leads to an undesirable higher parasitic drain resistance. Some conventional MOSFET devices have the drain junction lying directly beneath the gate electrode, so that if the drain is biased at a large voltage, a drain induced tunneling current appears. This tunneling current may initiate an avalanche breakdown.
Hot electron stress is a phenomenon that may occur in a conventional MOSFET transistor under high current flow conditions. Hot holes generated in the pinch off region create traps in the oxide at the drain end of the channel. Electrons become caught in these traps and their accumulation induces stress in the gate oxide. The stress causes the transistor's performance to deteriorate, and in some instances, the stress is sufficient to cause destruction of the device.
Punch-through occurs with large drain biasing so that the drain depletion region grows to the point that the inverted channel vanishes. The result is a depletion region that extends from drain to source with carriers injected at the source driven to the drain by the high electrical field between the electrodes. Punch-through in effect adversely lowers the breakdown voltage of the device.
Accordingly, it is desirable to provide a MOSFET transistor which has reduced drain-to-source and gate-to-drain overlap capacitances that adversely affect the high frequency performance of the transistor. It is further desirable that the MOSFET transistor also has improved device parameters, such as breakdown voltage and threshold voltage, for improved high voltage and large current handling. Additionally, it is desirable to substantially reduce or eliminate the disadvantageous effects in the MOSFET transistor due to detrimental phenomena such as hot electron stress and punch-through.


Provided is an air-permeable sheet imparted with oil repellency, having a surface coated with an oil-repellent agent. The oil-repellent agent contains a linear fluorine-containing hydrocarbon group represented by —R1C5F10CH2C4F9 or —R2C6F13, where R1 and R2 are each independently an alkylene group having 1 to 12 carbon atoms or a phenylene group. The air-permeable sheet is a resin sheet having air permeability in a thickness direction of the resin sheet, the resin sheet is a non-porous sheet having two or more through holes formed to extend in the thickness direction, and the through holes are straight holes extending straight through the resin sheet. This air-permeable sheet is imparted with oil repellency without significantly reducing its air permeability.

Air-permeable sheets obtained by forming through holes in non-porous resin sheets (hereinafter also referred to as "non-porous sheets") in their thickness direction are widely used in various applications due to their particularly high air permeability. For example, Patent Literature 1 shows a suction sheet as an example of the applications of such non-porous sheets having through holes formed therein.
The air-permeable sheets described above are attached to various products (hereinafter also referred to as "workpieces"). An adhesive layer is provided on a part of the front or back surface of the air-permeable sheet, and the air-permeable sheet is placed on a workpiece such that the adhesive layer is in contact with the workpiece. Then, the interior of the workpiece is evacuated through a vent hole of the workpiece (formed on the opposite side of the workpiece from the air-permeable sheet placed thereon) so as to hold the air-permeable sheet by suction. This attachment technique has not only an advantage that it is easier to place the air-permeable sheet but also an advantage that the air-permeable sheet is less likely to be displaced from the position where it is placed. The adhesive layer is preferably made of a pressure-sensitive adhesive because it can be easily removed to replace the air-permeable sheet by a new one, but instead, a hot-melt adhesive, a thermosetting adhesive, a tackiness agent, or the like may be used.

Air-permeable sheet imparted with oil repellency


A two stage dispensing cap for a carbonated beverage container is described. The cap has a flip top which is hingedly connected to a collar wherein the collar is rotatable on the container. The cap, upon rotation of the collar, is first opened into a venting position wherein the flip top vents the pressurized contents of the container but remains locked partially closed. Continued rotation of the cap releases the locked flop top to allow the container to be fully opened. A set of cams on the container neck work in conjunction with annular beads to first allow partially opening of the flip top into the venting position and then allowing it to fully open.

The present invention relates to closures and particularly to a double latch flip seal closure which is utilized in conjunction with a carbonated beverage and container.
Flip top closures are fairly well known in the art. However, typical flip top closures incorporate a biased hinge and stationary base portion wherein the flip top portion of the closure is pushed forward by the biasing action of the hinge forcing the flip top up and away from the base portion of the closure. Further, most prior art flip top closures will not work appropriately with carbonated beverages as the contents are held under considerable pressure.
Other threaded closures are also fairly well known in the art for use with carbonated beverages. However, as is fairly well known, one of the drawbacks with use of standard threaded closures on carbonated beverages is a complete removal of the closure from the container thus allowing the closure to be dropped or misplaced after removal.
Of the known prior art, U.S. Pat. No. 4,941,580 discloses a flip top dispensing closure having a base ring which is rotatable. As is shown in some of the embodiments, rotation causes opening of a lid which is hingedly connected to the base ring. However, this closure lacks many fundamental aspects of a flip top closure necessary for use with carbonated beverages and does not adequately provide sufficient sealing integrity or a mechanism for two stage opening of the container. Further, when the flip top closure is placed in the open position, the opening structure prevents the flip top from being closed in that position thereby preventing immediate closing and possibly confusing the user.
The prior art therefore is lacking in a double latch flip top closure with sufficient sealing integrity which has a rotatable base allowing the flip top to be actuated by rotation of the base portion in a manner suitable for use in conjunction with carbonated beverage containers.
It is therefore been desired to provide a double latch flip top closure with sufficient sealing integrity which is available for use in conjunction with carbonated beverage containers. It is accordingly an object of the present invention to provide such a flip top closure which is a two-piece closure having a double staged opening process and which is suitable for use with carbonated beverages under high pressure. Typically, closures that are utilized on containers having carbonated beverages contained therein must provide adequate sealing for high pressure containment. Such objective is difficult to meet utilizing commonly known prior art flip top dispensers. The two-piece flip seal for carbonated beverages of the present invention meets this objective.
Another object of the present invention is to provide a double latch flip top closure which allows the user to vent the gas from within the container prior to fully opening the container. Additionally, an object of the present invention is to provide a double latch closure which allows the flip top to be closed when at the same location on the container rotationally that it has been opened, thus allowing the flip top to be fully opened and closed along the same circumferential point on the container neck.
An additional object of the present invention is to provide a double latch dispensing closure for utilization with pressurized containers wherein the flip top portion of the cap has a biased hinge which forces the flip top cap into the open or closed position.
An additional object of the present invention is to provide a two-stage dispensing cap for pressurized containers wherein the flip top has an annular plug seal or dome shaped sealing disc for tight sealing of the flip top with the container.
It is a further object of the present invention to provide a flip top closure which has adequate tamper-indicating means located thereon such that upon first use of the two-stage dispensing cap, visual means are provided indicating prior use.
A further object of the present invention is to provide a two-stage dispensing cap for utilization with pressurized containers wherein the dispensing cap remains permanently attached to the neck of the container, but is rotatable thereon.
It is an additional object in conjunction herewith to provide a two-stage dispensing closure which provides primary lugs for activation of the flip top upon initial rotation of the closure and which further provides for complete opening of the flip upon continued rotation of the collar for the closure.
A further object of the present invention is to provide a two stage dispensing cap for attachment to a container, comprising a collar rotatably affixed to said container, a flip top hingedly connected to said collar having a top wall and a depending side wall, said side wall having a lifting lug and a lid retaining lug co-aligned on the interior thereof, said lifting lug above said lid retaining lug, wherein said container further has an upper bead and a lower bead directly therebelow, a primary upper cam and a primary lower cam, said primary upper cam co-aligned with said primary lower cam, said primary upper cam extending upward from the upper surface of said upper bead, said primary lower cam extending downward from said lower bead, and further having a secondary cam, said secondary cam extending downward from said upper bead and located rotationally past said primary cams.
All of the above outlined objectives are to be understood as exemplary only and many more objectives of the invention may be gleaned from the disclosure herein. Therefore, no limiting interpretation of the objectives noted are to be understood without further reading of the entire specification and drawings included herewith.

Two stage dispensing cap for pressurized containers


The present invention concerns methods and compositions for identifying genes or genetic pathways modulated by miR-124, using miR-124 to modulate a gene or gene pathway, using this profile in assessing the condition of a patient and/or treating the patient with an appropriate miRNA.

I. Field of the Invention
The present invention relates to the fields of molecular biology and medicine. More specifically, the invention relates to methods and compositions for the treatment of diseases or conditions that are affected by microRNA (miRNA) miR-124 expression or lack thereof, and genes and cellular pathways directly and indirectly modulated by such.
II. Background
In 2001, several groups used a cloning method to isolate and identify a large group of "microRNAs" (miRNAs) from C. elegans, Drosophila, and humans (Lau et al., 2001; Lee and Ambros, 2001; Lagos-Quintana et al., 2003). Several hundreds of miRNAs have been identified in plants and animals—including humans—which do not appear to have endogenous siRNAs. Thus, while similar to siRNAs, miRNAs are distinct.
miRNAs thus far observed have been approximately 21-22 nucleotides in length, and they arise from longer precursors, which are transcribed from non-protein-encoding genes (Carrington and Ambros, 2003). The precursors form structures that fold back on themselves in self-complementary regions; they are then processed by the nuclease Dicer (in animals) or DCL1 (in plants) to generate the short double-stranded miRNA. One of the miRNA strands is incorporated into a complex of proteins and miRNA called the RNA-induced silencing complex (RISC). The miRNA guides the RISC complex to a target mRNA, which is then cleaved or translationally silenced, depending on the degree of sequence complementarity of the miRNA to its target mRNA. Currently, it is believed that perfect or nearly perfect complementarity leads to mRNA degradation, as is most commonly observed in plants. In contrast, imperfect base pairing, as is primarily found in animals, leads to translational silencing. However, recent data suggest additional complexity (Bagga et al., 2005; Lim et al., 2005), and mechanisms of gene silencing by miRNAs remain under intense study (Chendrimada et al., 2007; Kiriakidou et al., 2007).
Recent studies have shown that changes in the expression levels of numerous miRNAs are associated with various cancers (reviewed in (Calin and Croce, 2006; Esquela-Kerscher and Slack, 2006; Wiemer, 2007). miRNAs have also been implicated in regulating cell growth and cell and tissue differentiation—cellular processes that are associated with the development of cancer.
The inventors previously demonstrated that hsa-miR-124 is involved with the regulation of numerous cell activities that represent intervention points for cancer therapy and for therapy of other diseases and disorders (U.S. patent application Ser. No. 11/141,707 filed May 31, 2005 and Ser. No. 11/273,640 filed Nov. 14, 2005, each of which is incorporated herein by reference in its entirety). For example, cell proliferation, cell division, and cell survival are frequently altered in human cancers. Transfection of human lung carcinoma cells (A549) and human cervical cancer cells (HeLa) with synthetic hsa-miR-124 reduced viable cell numbers. In addition, the inventors showed that miR-124 significantly increased the capacity of two therapeutic compounds (TRAIL, an apoptosis pathway activator in cancer cells, and etoposide, a topoisomerase II inhibitor that activates the apoptosis pathway in cancer cells and normal cells) to induce cell death in A549 or HeLa cells. Overexpression of synthetic miR-124 in various cell lines decreased cell proliferation. In those studies, the inventors observed reduced proliferation of human breast cancer cells, (BT549), normal human breast epithelial cells (MCF12A), human cervical cancer cells (HeLa), human prostate carcinoma cells (22RV1), human basal cell carcinoma cells (TE 354.T), normal human skin cells (TE 353.Sk), and human lung carcinoma cells (A549, CRL-5826, HTB-57). Overexpression of miR-124 in HeLa cells significantly reduced the number of cells in the G2/M phase of the cell cycle when compared to cells transfected with a negative control miRNA. Also, others have recently observed that epigenetic silencing of miR-124a in cancers cells modulates activity the oncogene, CDK6 and the tumor suppressor gene, Rb (Lujambio et al., 2007).
Bioinformatics analyses suggest that any given miRNA may bind to and alter the expression of up to several hundred different genes. In addition, a single gene may be regulated by several miRNAs. Thus, each miRNA may regulate a complex interaction among genes, gene pathways, and gene networks. Mis-regulation or alteration of these regulatory pathways and networks involving miRNAs are likely to contribute to the development of disorders and diseases such as cancer. Although bioinformatics tools are helpful in predicting miRNA binding targets, all have limitations. Because of the imperfect complementarity with their target binding sites, it is difficult to accurately predict the mRNA targets of miRNAs with bioinformatics tools alone. Furthermore, the complicated interactive regulatory networks among miRNAs and target genes make it difficult to accurately predict which genes will actually be mis-regulated in response to a given miRNA.
Correcting gene expression errors by manipulating miRNA expression or by repairing miRNA mis-regulation represent promising methods to repair genetic disorders and cure diseases like cancer. A current, disabling limitation of this approach is that, as mentioned above, the details of the regulatory pathways and gene networks that are affected by any given miRNA, have been largely unknown. This represents a significant limitation for treatment of cancers in which a specific miRNA may play a role. A need exists to identify the genes, genetic pathways, and genetic networks that are regulated by or that may regulate expression of miRNAs.

MiR-124 regulated genes and pathways as targets for therapeutic intervention


An aircraft door is disclosed comprising a first (301), second (302) and third (303) door members pivotably joined and arranged to move from a closed position in which said members are located in a substantially linear arrangement in the aircraft skin to an open position in which said members are located in a relative folded arrangement with the second and third door members situated substantially above the lowest edge of the first door member.

Aircraft structures commonly comprise a number of doors such as passenger doors, cargo hold doors, maintenance door (or hatches) and landing gear doors. Such doors provide access to the internal parts of the aircraft when open and close so as to conform to the surrounding aircraft structure. An important aspect of many such doors is that during their opening procedure and in their open position they do not impinge, catch or otherwise undesirably contact other parts of the aircraft structure. Furthermore, when the aircraft in on the ground, the doors should not impinge on the ground or other ancillary structures such as loading ramps or gantries. For example, landing gear doors must provide clearance to the ground, the landing gear, and any symmetrically opposite landing gear door under all operating conditions of the aircraft.
A problem arises when a door is large and the distance available to clear other aircraft structures or other external structures is relatively small. For example, if the door is a landing gear door, the ground clearances may be small and the door may be liable to be damaged by contact with the ground. One solution is to provide a two-part door which folds up to provide the necessary clearance. Such doors, when provided for landing gear, commonly fold inwards towards the landing gear and can require additional devices to ensure that extension of the landing gear is achieved without interference between the landing gear and the door. Furthermore, the folding procedure and mechanism for a folding door can be complex.

Door for opening and closing a door aperture in an aircraft


An improved circuit and method for programmable cascading of impedance matching in a multi-chip configuration are disclosed. Handshaking is implemented in cascaded chips by defining a master-slave configuration, and impedance is evaluated in cascaded chips in a non-overlapping manner. The circuit includes a plurality of chips arranged in a cascading configuration. A cascade output pin of a chip is coupled to a cascade input pin of a cascaded chip to enable handshaking between the plurality of chips. The plurality of chips are coupled to a common precision resistor via a common impedance line to enable each chip to calibrate impedance of the chip. Each of the plurality of chips includes a control circuit. Each control circuit includes a state machine circuit. The control circuit is configured to control a non-overlapping clock cycle of each chip during which the impedance of the chip is evaluated.

1. Field of the Invention
The present invention relates to semiconductor memory devices. More particularly, the present invention relates to a method and circuit for cascading programmable impedance matching in a multi-chip memory system.
2. Background Information
A conventional Double Data Rate (DDR) static random access memory (SRAM) is a type of synchronous SRAM computer memory that can transfer up to two words of data in each access. A conventional Quad Data Rate (QDR) SRAM can transfer up to four words of data in each access. Conventional DDR and QDR SRAMs transfer data on both rising and falling edges of the clock signal, which doubles the maximum data transfer rate. These memory chips provide high performance architectures targeted at the next generation of, for example, switches and routers. Compared to existing memory solutions, QDR SRAMs are expected to greatly increase system memory bandwidth as well as serve as the main memory for lookup tables, linked lists, and controller buffer memory applications.
FIG. 1 illustrates a conventional system 100 for implementing impedance matching in memory devices. The conventional system 100 comprises a first QDR chip 102 coupled to second, third, and fourth QDR chips 104, 106, and 108, respectively, via a plurality of pull up program lines (e.g., PU_prog <0:n>). The first QDR chip 102 is configured to operate as a master chip which is coupled to a plurality of QDR chips 104, 106, and 108 that are configured to operate as slave chips. The impedance pin ZQ i2 of the first QDR chip 102 is coupled to a precision resistor Rq 110. No other QDR chips in the conventional system 100 are coupled to the precision resistor Rq 110. A pull up impedance calibration for the output driver is performed on the master QDR chip 102, and the impedance program lines are sent to the slave QDR chips 104, 106, and 108. Since, the ZQ pin i2 of the master QDR chip 102 is coupled to the precision resistor Rq 110, the impedance matching is performed by the master QDR chip 102 only, and the pull-up programming of the impedance is performed and transmitted to the plurality of slave QDR chips 104, 106, and 108 via the plurality of pull up program lines. A pull down programming of the impedance for the output driver is performed locally within every QDR chip. A disadvantage of the conventional system 100 is that there is an overhead of extra pins on each chip and multiple program lines on the board. Another disadvantage of the system 100 is that driver impedance mismatch between dies due to process, voltage, and temperature (PVT) variation is not compensated.
FIG. 2 illustrates a second conventional circuit 200 for implementing impedance matching in memory devices. The second conventional circuit 200 comprises a first QDR chip 202 coupled to second, third, and fourth QDR chips 204, 206, and 208, respectively, serially via signal lines, such as, for example, a clock signal zqclk 13, a load signal zqload i4 and a serial data signal zqdata i5. The first QDR chip 202 is configured to operate as the master chip and other QDR chips (204, 206, and 208) are configured to operate as slave chips. The pull up driver impedance calibration is performed on the master and is transmitted serially via the signal lines to the plurality of QDR chips 204, 206, and 208. The ZQ pin i2 of the master QDR chip 202 is coupled to the precision resistor Rq 210, and the impedance matching is performed by the first QDR chip 202 only. A pull up and pull down driver impedance calibration is also performed by the first QDR chip 202 only. A disadvantage of the circuit 200 is that there is an overhead of extra pins and multiple lines on the circuit board. Another disadvantage of system 200 is that driver impedance mismatch between dies due to PVT variation is not compensated.

Circuit and method for cascading programmable impedance matching in a multi-chip system