A biomimetic reagent system is provided containing an oxygen donor and a catalyst based on porphyrin, which are applied to a carrier. A device that contains the system is also provided for determining components of gas or vapor samples, especially aromatics, such as benzene. A process for hydroxylating aromatics, such as benzene, using the biomimetic reagent system is also provided.

The present invention pertains to a biomimetic reagent system, which is applied to a carrier and contains an oxygen donor and a catalyst based on porphyrin, to a device containing this reagent system, to its use for determining components of gas or vapor samples, especially aromatics, such as benzene, as well as to a process for hydroxylating aromatics, such as benzene, by using the biomimetic reagent system.
Various embodiments of testing elements with reagent systems, by means of which especially gases or vapors can be tested for components contained in them in a simple manner, rapidly and at low cost, have been known.
A measuring apparatus operating with a reagent-containing indicator strip is described in DE 34 07 686 C1. The gas to be tested is drawn actively through this indicator strip. The reagents on the indicator strip react specifically with the components to be determined in the sample. This leads to a change in color, which is detected photometrically.
Another embodiment is a plaque. A flat disk, e.g., a paper disk, which is impregnated with a reagent, reacts with the components of the gas sample to be determined, e.g., air, based on diffusion, while the color of the disk changes. The intensity of the change in color within a certain period of time is an indicator of the concentration of the constituents of the air.
The testing elements are also often designed as so-called detector tubes. The reagents in these are applied, in general, as very thin layers to fine-grained carrier materials, which are in turn fixed in a glass tube. The gas sample (analyte) is then actively drawn through the glass tube by means of a pump. The components to be determined now react with the reagents, while the color changes. The length of the color layer formed relative to a defined sample volume is an indicator of the concentration of the component to be determined. A plurality of layers of different chemical reactivity, which are arranged one behind the other, may be used within the same tube. For example, the analyte can be converted in a preceding layer into a chemically different analyte, for the detection of which there will be a suitable color reaction in another layer.
The automatic optoelectronic evaluation of the corresponding change in color of miniaturized detector tubes is usually performed as described in DE 39 02 402 C1.
A great variety of chemical reagent systems, which must meet a great variety of requirements, are used precisely in detector tubes. Besides the redox reagent systems, which are used very frequently, the changes in the pH value or even condensation reactions also play an important role in the systems used. Since the reactions of the reagent systems usually must take place as completely as possible at room temperature and within a very short time, the reagent matrices are, in general, chemically highly corrosive; for example, redox reactions take place with the use of fuming sulfuric acid. The gases released during an active operation, e.g., sulfur trioxide in this case, may cause damage, especially in automated measuring systems. Such corrosive reagent systems consequently have limited suitability for use in automated measuring systems. Furthermore, an accurate and complicated coordination of the properties of the reagent system and the carrier material used must be usually performed.
Moreover, the use of biochemical reagent systems in detector tubes has been known. Even though these highly complex systems are characterized by a high selectivity, their limited shelf life is disadvantageous.
Testing elements in the form of so-called biomimetic sensors have been known from the state of the art as well. Biomimetic sensors simulate the function of organs of sense: Chemical signals are recoded into physical signals or also vice versa by influencing the interaction between the carrier and bioactive materials. The response of the biomimetic sensor to such signals simulates the response of an organ of sense. The physicochemical signals are then converted by means of so-called transducers into measurable electric signals and optionally suitably amplified by an electronic component.
A biomimetic sensor system for determining the concentration of CO and other pollutants in air has been known from U.S. Pat. No. 5,063,164. The sensor reacts to the presence of CO with a sensitivity similar to that of the human organs of sense, i.e., it simulates the response of the human body to the presence of CO, etc. The sensor disclosed in U.S. Pat. No. 5,063,164 has a good service life. However, it consists of a very complex reagent system, which comprises five groups of inorganic/organic reagents, and some of the inorganic reagents are enclosed in larger organic molecules and these are in turn introduced into the pores of suitable carriers. The biomimetic sensor known from U.S. Pat. No. 5,063,164 also has the drawback that organic materials are made accessible for detection only by preceding reaction steps, such as oxidation by corrosive oxidizing agents into CO or by reactions induced by increasing the temperature.
Thus, the object of the present invention is to provide a biomimetic reagent system, which is suitable for the determination of components of gas or vapor samples, especially for determining organic materials of high toxicity, such as benzene. The biomimetic reagent system should be characterized by mild reaction conditions, i.e., it shall be able to be used at room temperature and without additional chemically corrosive auxiliary reagents and have a service life sufficient for practical purposes. Another object of the present invention was to provide a gas sensor that contains the biomimetic reagent system.
According to the invention, a biomimetic reagent system is provided that includes an oxygen donor and a catalyst based on porphyrin which are applied to a carrier.
The present invention also pertains to the use of the reagent system according to the present invention for determining components, especially aromatics, such as benzene, in gas and vapor samples.
The present invention also pertains to a process for hydroxylating aromatics by using the reagent system according to the present invention.
The present invention also pertains to a device containing the reagent system according to the present invention.
As was described above, biomimetic reagent systems are chemical models for one or more biochemical reactions. In the present invention, they are metal complexes, which are able to imitate, as a biomimetic system, monooxygenase reactions that are catalyzed by cytochrome P-450. Monooxygenases are enzymes that are able to activate oxygen by taking up two electrons and two protons and to hydrolyze or epoxidize substrates as a result. These reactions, which take place in the human body, are indispensable for the human body for the detoxification of drugs and foreign substances and after metabolism in the liver, they usually lead to water-soluble compounds, which are excreted renally.
These reactions are oxygenation reactions, in which the oxygen must be reduced enzymatically by NADPH. However, these reductions are difficult to carry out in the model with oxygen as the oxidizing agent.
It was surprisingly found according to the present invention that by using a carrier-bound biomimetic system, which contains certain oxygen donors combined with catalysts based on porphyrin, it is possible to react aromatics, especially benzene, into 1,4-benzoquinone derivatives under mild conditions, and these derivatives can then be easily made visible in color by condensation with 2,4-dinitrophenylhydrazine into the hydrazone.
This is surprising especially because molecules of low reactivity, such as benzene, which is highly resistant especially to oxidation, do not normally react chemically under such mild conditions, especially at a solid-gas interface.
The oxygen donor in the reagent system according to the present invention is selected from the group comprising iodosobenzene, magnesium monoperoxyphthalate, cumene hydroperoxide, hydrogen peroxide, hypochlorite, especially sodium hypochlorite, amine N-oxide, inorganic persulfate and mixtures thereof The oxygen donor contains, in particular, iodosobenzene, and the oxygen donor is preferably iodosobenzene. The said compounds per se and their preparation have been known from the state of the art.
The catalyst component of the reagent system according to the present invention contains, in general, a metalloporphyrin derivative, especially a substituted metalloporphyrin. The catalyst contains, e.g., a metal salene (salene is an abbreviation for N,Nxe2x80x2-bis(salicylidene)-ethylenediimino) (N,Nxe2x80x2-bis(salicylidene)-ethylenediimino-cobalt (II)), a tetraphenylporphyrin skeleton with iron or manganese, especially iron(III) tetraphenylporphyrin or manganese(III) tetraphenylporphyrin, preferably 5,10,15,20-tetrakis(pentafluoro)phenylporphyrin-Fe(III)Cl (FeTFPPCl), 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin-Fe(III)Cl (FeTDCPP) and/or octabromo-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin-Fe(III)Cl (FeOBTDCPP). FeTFPPCl is a synthetic metalloporphyrin with halogen substituents on the phenyl rings of the porphyrin skeleton. Its preparation, like that of the other porphyrin derivatives mentioned, is known to the person skilled in the art.
The suitable carrier materials of the reagent system according to the present invention are solids, such as silica gel, quartz glass or glass grains, silica gel being preferably used.
The particle size of the carrier materials is, in general, not critical. Fine-grained carrier material with a particle diameter small than 1 mm, especially smaller than 0.5 mm, and preferably smaller than 0.5 mm and larger than 0.2 mm is used, in general.
The components described so far are used, in general, at an oxygen donor: catalyst: carrier ratio of 10xe2x88x922 to 10xe2x88x923 moles: 10xe2x88x925 to 10xe2x88x926 moles: 0.5 to 1.0 g and especially at 5xc3x9710xe2x88x923 moles: 5xc3x9710xe2x88x926: 0.7 to 0.8 g.
A biomimetic reagent system that is composed of iodosobenzene and 5,10,15,20-tetrakis(pentafluoro)phenylporphyrin-Fe(III)Cl on fine-grained silica gel is particularly preferred.
A suitable reagent system for detecting, e.g., benzene is thus composed, e.g., of 80 g of silica gel carrier, 0.5 g of FeTFPPCl and 10 g of iodosobenzene.
The reagent system according to the present invention is prepared, in general, by intimately mixing the components with one another. For better adsorption on the carrier, the reagent system is usually first moistened with a solvent, such as dichloromethane, and is then mixed with the carrier material, e.g., silica gel. The solvent is then allowed to evaporate.
Using such a reagent system according to the present invention, it is possible to react, e.g., benzene into 1,4-benzoquinone under mild conditions, i.e., at room temperature and without additional auxiliary reagents. The stability and consequently the catalytic activity are obviously influenced especially advantageously by steric and electronic effects of the substituents of the porphyrins according to the present invention, especially FeTFPPCl. The sterically shielded complexes are highly resistant to oxidation and therefore stable for a long time.
Without being bound to a certain theory, it is assumed that the cause of this is a special reaction mechanism, which is determined by the reagent system according to the present invention. For example, a metal-oxo complex formed from an oxygen donor and metalloporphyrin attacks the aromatic compound such that a substituted 1,4-cyclohexadienyl radical is formed, which is converted by a second attack of the metal-oxo complex into a cyclohexadiene derivative. A hydroquinone is formed from this by splitting off the metalloporphyrin. The hydroquinone can then be reacted very rapidly into quinone under the reaction conditions and into the hydrazone by condensation with 2,4-dinitrophenylhydrazine.
The above reactions take place, in general, at temperatures of 10xc2x0 C. to 40xc2x0 C. and under pressures of 700 to 1,300 hPa.
Thus, the reagent system according to the present invention offers a process for hydroxylating aromatics, especially benzene.
As was described above, the reagent system according to the present invention reacts biomimetically to the presence of aromatics, such as benzene. The benzoquinone formed in the above-described reaction can then be made visible, e.g., by complex formation with hydroquinone (bluish green color). The coupling reaction with 2,4-dinitrophenylhydrazine, which leads to a red color with concentrated sulfuric acid (hydrazone formation), is another suitable detection reaction.
Thus, the reagent system according to the present invention can be used to detect or determine aromatics, e.g., benzene, as a component of gas or vapor samples. Very small amounts in the lower ppm range can be quantitatively detected. Consequently, the sensitivity of the reagent system according to the present invention to the presence of benzene is similar to that of the human body. In addition, it has a very good service life of more than 1 year for practical application.
Thus, the biomimetic reagent system according to the present invention may also be used in devices that are suitable for determining components of gas or vapor samples, e.g., as a gas-measuring system.
For example, the biomimetic reagent system according to the present invention may be arranged in a detector tube, which is then used for quantitative gas analysis in conjunction with pumps to be operated manually or automatically.
For use for measurement, the tips of the detector tubes, which were previously sealed in a gas-tight manner, are broken off, the detector tube is introduced into a corresponding gas-detecting pump and the specified volume of gas or vapor is drawn through the reaction layer by means of the pump. Most detector tubes are so-called scaled tubes, in which the color of the indication layer changes over a length that depends on the analyte concentration. Furthermore, detector tubes with a color comparison layer have been known, by means of which a color comparison is performed after the reaction. Contrary to this, so-called collection tubes contain coconut shell carbon, various types of silica gel or molecular sieves. Because of their exclusive collection behavior without a color change, these tubes can also be described as detector tubes without direct display, which are subsequently evaluated by an analytical determination method (e.g., HPLC: High Pressure Liquid Chromatography, GC: Gas Chromatography, GC-MS: GC-Mass Spectrometry) (Drxc3xa4ger-Rxc3x6hrchen Handbuch [Drxc3xa4ger Tube Manual], 1994).
One embodiment of the present invention may be such that the analyte, e.g., benzene, is chemically reacted, e.g., oxidized into benzoquinone in the case of benzene, in a reagent layer, and then transported by means of an extracting agent into a next layer, in which a detection reagent (e.g., 2,4-dinitrophenylhydrazine) is present. The intensity of the color formed in this second layer is now an indicator of the concentration of the analyte. It is also conceivable to bind the indicator of the second layer covalently to the carrier by strong adsorption forces and to thus form a scaled tube with a liquid transporting agent (extracting agent).
A measuring system based on the detection reagent 2,4-dinitrophenylhydrazine is particularly advantageous.
Finally, there are also embodiments in which volatile oxidation products are produced (e.g., oxidation of methane into formaldehyde, methanol, formic acid or CO). These products do not need to be transported into the second layer with an extracting agent, but they reach that layer with the gas flow and can then be displayed in a scaled tube.
Thus, the present invention also provides a device that contains the biomimetic reagent system, and is suitable for the determination of components of gas or vapor samples.
The present invention will be explained on the basis of exemplary embodiments below.
The various features of novelty which characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and specific objects attained by its uses, reference is made to the accompanying drawing and descriptive matter in which a preferred embodiment of the invention is illustrated.


The invention provides a method or system where the UE sends the CQI to the base station (Node B) based on whether a HARQ retransmission is expected. For example, if a HARQ retransmission is expected, then the UE can reduce the CQI information to sending less (or no) bits in the uplink. In effect, the UE will automatically stop sending CQIs to the base station (Node B) for time-periods where it is known that HARQ retransmissions will be scheduled. The method or system may include one or more steps or elements for implementing this functionality in the UE.

1. Field of Invention
The present invention relates to a Universal Mobile Telecommunications System (UMTS) packet network; and more particularly to channel quality indicator (CQI) reporting schemes for Universal Terrestrial Radio Access Network (UTRAN) long term evolution (LTE) in the third generation partnership project (3GPP).
2. Description of Related Art
In the long term evolution (LTE) UTRAN, the architecture is modified so that there no longer will be a radio network controller (RNC). This UTRAN long term evolution is also using orthogonal frequency division multiple access (FDMA) in the downlink, as well as adaptive modulation and coding. The frequency band is divided into resource blocks (RB) in order to allow multiplexing of users in the frequency domain. The latter opens up the possibility for utilization of frequency domain link adaptation (FDLA), the frequency domain link packet scheduling (FDPS), etc. Moreover, the current working assumption for UTRAN long term evolution (LTE) is that the UE should send CQls in the uplink for different resource blocks (RBs) in order to facilitate the frequency domain link adaptation (FDLA) and the frequency domain link packet scheduling (FDPS) in the downlink. The exact definition of the CQIs and the reporting of those from the UE to the serving cell is currently under discussion in 3GPP. One of the design objectives in 3GPP is to agree on a good trade-off between minimizing the signalling overhead from sending the CQIs in the uplink versus the potential gain from using FDLA and FDPS in the downlink. In particular, there is a need for a method, system or technique for reducing the CQI signalling overhead for the special case where pending Hybrid Automatic Repeat-Request (HARQ) retransmissions are scheduled in the downlink.
In operation, the CQIs per RBs from the users are used by the base station (Node B) to determine (i) which users are going to be scheduled, (ii) which RBs to allocate to the scheduled users, and (iii) which modulation and coding scheme (MCS) to use for the scheduled users (i.e. for FDLA and FDPS). On the other hand, having "complete" CQI information frequently reported from all users and RBs might potentially cause excessive uplink signalling load. In view of this, there is a need for a way to reduce the CQI information significantly for users who are about to be scheduled HARQ retransmissions, since the base station has reduced degrees of freedom for transmitting such, as compared to new transmissions.


A device for the medical treatment of the eye with laser radiation uses auxiliary radiation for determining the eye position. With the aid of the auxiliary radiation, pictures are taken by means of a solid state image camera for determining eye movements and for causing the laser treatment radiation to follow accordingly. Infrared radiation sources, which are arranged in a triangle above the eye to be treated, are used for the auxiliary radiation.

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The present invention relates to a device for the medical treatment of and/or operation on the eye with laser radiation making use of auxiliary radiation for determining the eye position.
Such a device can especially be used for the so-called PRK (photorefractive keratectomy), i.e. a method of correcting a defective vision of the human eye in the case of which especially the cornea is re-shaped. The device according to the present invention is particularly suitable for the so-called LASIK method where a small flap (lid) is first cut into the epithelium, Bowman""s membrane and stroma and opened up, the PRK being then carried out in the stroma.
In the laser treatment of the human eye, the use of various lasers is known; in connection with the present invention these lasers are in particular excimer lasers (having a wavelength of e.g. 193 nm) and also Er:YAG solid state lasers.
In the case of PRK (especially LASIK) material of the cornea is ablated. The ablation is a function of the energy density (energy per unit area) of the laser beam impinging on the cornea. Different techniques for forming and controlling the beam are known, e.g. the so-called slit scanning in the case of which the radiation is guided over the area to be treated by means of a moving slit, the so-called spot scanning in the case of which a radiation spot having very small dimensions is guided over the area to be ablated, and also the so-called full ablation in the case of which large-area application of the radiation is effected over the whole region to be ablated and the radiation density varies across the beam profile so as to achieve the desired ablation of the cornea. Suitable radiation-control algorithms for the respective methods of controlling the beam are known in the prior art so as to ablate the corneal surface such that the cornea will finally be given the desired radius of curvature.
Spot scanning, which has already been mentioned hereinbefore, uses a laser beam focussed to a comparatively small diameter (0.1-2 mm), said laser beam being directed onto various points of the cornea by means of a beam control unit and successively moved by means of a so-called scanner in such a way that the desired corneal ablation will finally be achieved. For the purpose of PRK, so-called galvanometric scanners can especially be used (cf. the article, G. F. Marshall in LASER FOCUS WORLD, Jun. 1994, p. 57). The present invention refers in particular to the so-called spot scanning executed in the LASIK method.
A special problem arising in connection with PRK and LASIK is the relative positioning of the laser beam and of the eye. A mechanical fixation of the eye is not satisfactory for medical reasons. Hence, the prior art knows a so-called optical fixation in the case of which a so-called fixation beam is used, which is normally coaxial with the material-ablating laser beam. The patient is requested to look precisely at the point defined by the fixation beam so that the eye will always maintain the same position during the whole surgical operation. The patient does, however, not succeed in doing so, at least not with sufficient reliability, so that movements of the eye occur which may seriously impair the whole ablation process.
The prior art knows so-called xe2x80x9ceye-trackersxe2x80x9d; these are means which detect movements of the eye so that the laser beam used for ablation can then be controlled (caused to follow) in accordance with the eye movements. With regard to the prior art, reference is made to the following documents:
Gobbi, Pier Giorgie et al.: Automatic Eye Tracker for Excimer Laser Photorefractive Keratectomy; Supplement to Journal of Refractive Surgery, Vol. 11, May/June 1995; in addition, Lin, J. T., Ophthalmic Surgery Method Using Non-Contact Scanning Laser, U.S. Pat. No. 5,520,679, May 28, 1996; and Manns, Fabrice, et al., Optical profilometry of poly(methyl-methacrylate) surfaces after reshaping with a scanning photorefractive keratectomy (SPRK) system, periodical APPLIED OPTICS, Vol. 35, No. 19, Jul. 1, 1996.
Furthermore, reference is made to German Utility Model 298 09 759.1. In this German Utility model white light, which is emitted by light-emitting diodes, is used for the auxiliary radiation which serves to determine the eye position for xe2x80x9ceye-trackingxe2x80x9d.
DE 197 02 335 C1 describes a laser system for treating the cornea with means for causing the laser treatment beam to follow when the eye moves relative to a reference axis. An image-recording means (CCD camera) is used for this purpose and auxiliary radiation is used for illuminating the eye for the image-recording process. In accordance with a movement of the eye relative to the reference axis, a control controls a beam control unit, e.g. a galvanometric scanner. A specific dependence with respect to the pulse repetition rate of the laser radiation is suggested for the image sequence rate at which the camera takes pictures. This prior art is here assumed to be known, and used. Summarizing, it can be stated that this prior art teaches that images of the eye are recorded by means of a camera and processed in rapid succession so as to determine movements of the eye. A change in the position of the eye (pupil position) can be determined from successive images (e.g. two successive images), and the ablation laser beam can then be caused to follow in accordance with the eye movement with the aid of suitable beam control means (e.g. the above-mentioned galvanometric scanner).
It follows that at least three different radiations are differentiated in connection with PRK (in particular LASIK). Firstly, the actual laser treatment beam which causes the ablation, secondly, the so-called auxiliary radiation, i.e. the radiation which serves to illuminate the eye so as to detect the eye position e.g. by means of the camera, and, thirdly, optionally, the so-called fixation beam which is stationary and which is intended to cause the patient to fixate always the same point with the eye (the latter is only a special option).
In the prior art, halogen light, which is introduced into the observation ray path by means of a bundle of fibres, is used for illuminating the eye. Also the use of a ring lamp or the coaxial coupling in of the illumination radiation via a surgical microscope is part of the prior art. Flexible swan necks for positioning the illumination light for illuminating the foreground of the eye, especially the comea, are known as well, so that the physician can selectively adjust the light for an optimum observation of the eye as a whole. The halogen lamps and xenon lamps used in the prior art are improvable with respect to the strain on the patient as well as with respect to the illumination quality for the physician carrying out the treatment.
When, especially during spot scanning for LASIK, pictures of the iris and of the pupil are taken by means of a camera system for determining the eye position and when the centre of gravity of the pupil is then calculated (on-line), a high contrast between pupil and iris is necessary for optimum recognition of the pupil. It turned out that the auxiliary radiation is very important with respect to its angles of incidence, wavelengths, etc. for achieving good results when the eye position is being determined.
It is therefore the object of the present invention to further develop a device for the medical treatment of the eye of the type mentioned at the beginning, in such a way that reliable results are achieved when the eye position is being determined, especially when the system is used for different eyes (patients) and under different conditions.
Solutions provided for this task in accordance with the present invention are described in the claims.
The present invention is based on the finding that particularly good measurement results with regard to the eye position will be achieved when at least two infrared radiation sources are used, the radiations of these infrared radiation sources extending at an angle of 30 to 70xc2x0, preferably between 40 and 60xc2x0, to the optical axis of the laser treatment radiation. Although the optical axis of the laser treatment radiation varies slightly during scanning, it can essentially be considered to be fixed in space; in particular, it can essentially be equated with the optical axis of the eye at rest.
According to a further variant of the invention, at least three radiation sources are provided for the auxiliary radiation, the radiations of these radiation sources extending at an angle of 30 to 70xc2x0, preferably between 40 and 60xc2x0, to the optical axis of the treatment radiation. Also in this case, the use of infrared radiation sources is specially preferred, these infrared radiation sources being preferably used in the form of light-emitting diodes (LEDs), in particular LEDs having a wavelength of approx. 810 nm.
The above-mentioned radiation sources themselves can each be composed of a large number of LEDs. A xe2x80x9cradiation sourcesxe2x80x9d in the sense of this application is then a system comprising a plurality of LEDs which are firmly connected to one another physically and the composite radiation of which is directed onto the eye from substantially the same direction.
A specially preferred embodiment is so conceived that the radiation sources define a triangle below which the eye to be treated can be positioned. The above-mentioned triangle can be positioned in a horizontal plane or in a plane which is slightly inclined relative to the horizontal. The terms xe2x80x9chorizontalxe2x80x9d and xe2x80x9cverticalxe2x80x9d are here used in the usual sense, i.e. it is assumed that the patient, who lies on his back, is horizontally oriented. Since electromagnetic radiation can, for the present purposes, be considered to be independent of gravitation and since also the patient can, in principle, be oriented in an arbitrary manner, the terms xe2x80x9chorizontalxe2x80x9d and xe2x80x9cverticalxe2x80x9d are here used only to give a general picture; it is assumed that the patient lies in the usual way and that his head is oriented such that the eyes face upwards.
When at least three radiation sources are used for the auxiliary illuminating radiation, a preferred embodiment of the invention is so conceived that the radiations of at least two radiation sources extend at an acute angle relative to one another towards the eye to be treated. This acute angle can e.g. be in the range of from 30 to 70xc2x0, preferably in the range of from 40 to 60xc2x0. A preferred embodiment of this variant of the invention is so conceived that, when projected onto a horizontal plane, the radiation of a third radiation source extends approximately in the direction of the angle bisector of said acute angle between the two other beams.

Device for medical treatment of the eye using laser illumination


A method for increasing the presence of glutathione in cells including treating or preventing impaired liver function by administering a composition which includes a precursor of gluthathione, and enhancer of glutathione biosynthesis, and a third component which is a lignan or the third component is a combination of an enhancer of gluthathione regeneration and an enhancer of glutathione-mediated conjugation. The precursor of gluthathione is cysteine or is a functional equivalent of cysteine which yields cysteine when administered to a mammal undergoing treatment.

This invention relates to a method of increasing the presence of glutathione in cells including treating or preventing of impaired liver function by administering to a mammal in the need thereof a dietetic or pharmaceutical composition and to a corresponding dietetic or pharmaceutical composition.
The liver is the major organ involved in metabolism of protein, carbohydrates, and fats, but is also the major organ for detoxification. Potential toxic compounds are converted into inactive metabolites by phase I-metabolising enzymes and excreted. Alternatively, metabolites are further conjugated by phase II-metabolising enzymes and excreted after all.
Many drugs and toxins can be detoxified by conjugation with glutathione. When the levels of these drugs or toxins, however, exceed the liver concentration of reduced glutathione; such components become acutely hepatotoxic. Striking is that in several kinds of liver disorders, glutathione levels are decreased, for example: in hepatitis infection, where the grade of activity of the liver disease is correlated with reduction of GSH in acute liver toxification, e.g. acetaminophen intoxication, and in alcoholics with liver failure.
Both hepatitis C and the exposure to liver toxins can lead to hepatocarcinoma, possibly via the same mechanism of incompetence of the liver to respond to toxins, either endo-toxins or exo-toxins.
Reduced glutathione (GSH) is the substrate of glutathione peroxidase (GPX) and as such contributes to the antioxidant defence mechanism as well.
Glutathione reductase enzymes reduce GSSG back to GSH, predominantly in the presence of NADPH, which is provided by e.g. the oxidative pentose phosphate pathway. The capacity of the glutathione system to cope with H2O2 in liver depends on the activity of GPX and giutathione reductase, the rate of NADPH supply, and the GSH content. Except for its effects on hydrogen peroxide, GSH can also react with e.g. OHo, HOCl, peroxynitrite, ROo, and RO2o in vitro. Upon reacting with free radicals, thiyl radicals (Gaf) are produced, which generate superoxide. Moreover, superoxide can also inactivate GPX in the absence of GSH. Hence, superoxide dismutase (SOD) or antioxidants can co-operate with GSH to remove free radicals in vivo.
Many xenobiotics supplied to living organisms are metabolised by conjugation with GSH. This process is catalysed by glutathione S-transferase enzymes (GST).
GSH is synthesised in two steps, catalysed by two different enzymes. During the first step, xcex3-glutamylcysteine synthetase (GCS) catalyses the formation of L-xcex3-glutamyl-L-cysteine from glutamate and cysteine. The second step incorporates glycine under influence of glutathione synthetase, yielding GSH.
One example of a drug that can deplete the concentration of reduced glutathione in the liver is the commonly used sedative acetaminophen (paracetamol). Acetaminophen has caused severe hepatic necrosis when ingested in large amounts, e.g. in suicide attempts or accidentally by children. Acetaminophen hepatotoxicity is mediated by a toxic reactive metabolite formed from the parent compound by the cytochrome P450 mixed-function oxidase system of the hepatocyte. The metabolite is then detoxified by conjugation with glutathione. If excessive amounts are formed, the glutathione reserves of the liver are depleted, and the quinonimine reacts with constituents of the liver cells, leading to necrosis. The hepatic injury may be potentiated by the use of alcohol or other drugs and also starvation and cachexia, conditions in which liver glutathione are lower, may potentiate the effect.
Milk thistle, or Silybum marianum (L.) Gaertn. (Compositae) is in Western countries well-known for its hepatoprotective effects. Its key components are flavanolignans, collectively known as silymarin. A composition for the protection, treatment and repair of liver tissue containing Milk thistle is for instance described in WO 99/43336.
Intraperitoneal administration of silymarin (200 mg/kg) in rats increased the total glutathione content and improved the reduced glutathione/oxidised glutathione ratio in the liver, intestine, and stomach, while levels of kidney, lung, and spleen were not affected (Valenzuela et al., Selectivity of silymarin on the increase of gutathione content in different tissues of the rat, Planta Medica 55, 420-2 (1989)). The main component of silymarin, silybin, exerted inhibitory effects on superoxide and hydrogen peroxide production in human neutrophils and increased the activity of both superoxide dismutase and glutathione peroxidase in human erythrocytes. Silymarin protects against acetaminophen-induced GSH depletion and cytotoxicity in hepatoblastoma Hep G2 cells in vitro. Silymarin and silybin protect in vivo against hepatic glutathione depletion induced by ethyl alcohol and paracetamol in rats. It was shown that silybin reduces the GSH depletion induced by acetaminophen, but does not affect GSH depletion by buthionine sulfoximide in isolated rat hepatocytes. This suggests that it enhances GSH oxidation or conjugation, without affecting glutamylcysteine synthetase or GSH synthesis (Garrido et al., Pharmacology an Toxicology 69, 9-12 (1991)).
Furthermore, silybin was found to be a potent, non-toxic, inhibitor of glutathione-S-transferase (Bartholomeus et al., Xenobiotica 24, 17-24, (1994)). This observation leads to the conclusion that, although silymarin might be effective as a hepatoprotective agent, secondary detoxification by conjugation to GSH, as is catalysed by GSH-transferase, is inhibited.
Silymarin treatment (Legalon, 420 mg, 6 months) in patients with chronic alcoholic liver disease in a double blind placebo controlled trial increased the serum level of free xe2x80x94SH groups and the activity of GSH peroxidase. Other clinical trials confirm the hepatoprotective effect of standardised Silybum extracts.
RO 102689 (Intr. Medicamente Biofarm) discloses the extraction of silymarin from armurariu fruit. Said extract shall be useful in the treatment of active chronic hepatitis, cirrhosis of the liver and for the protection of liver cells during administration of hepatoxic agents.
Picrorhiza kurrooa Royle (Scrophulariaceae) has been used in Ayurveda mainly for the treatment of liver disorders. Iridoid glucosides have been regarded as its active constituents; however, other compounds like acetophenones might also play a role.
Several iridoid glucosides have been isolated from P. kurrooa, most of them conjugates of catalpol with either benzoyl- or cinnamoyl-derived side chains.
Picroliv is a standardised fraction of Picrorhiza kurrooa containing the iridoid glycosides picroside I and kutkoside in a ratio of 1:1.5 to 1.2 (50-70%) and a mixture of cucurbitacin glycosides (4-5%) (U.S. Pat. No. 5,145,955). Picroside II has also been isolated from Picrorhiza kurrooa and 50 mg/kg p.o. in mice treated with CCl4 showed a hepatoprotective activity (DE-A 2203884).
Picroliv has been tested in a number of liver damage models in vitro and in vivo. These studies have demonstrated its antihepatotoxic, hepatoregenerative, choleretic, and hypolipidemic activities (reviewed by Dhawan, Medicinal Chemistry Research 5, 595-605, (1995)). Hepatoregenerative effects were associated with an increased recovery of the liver anti-oxidant system after partial hepatectomy or carbon tetrachloride-induced liver damage of Picroliv-treated rats. Furthermore, Picroliv significantly reversed paracetamol-induced biochemical changes in several liver cell markers after oral administration to rats (6 and 12 mg/kg) for 7 days. Injection of carbon tetrachloride in rats induced a drastic impairment of the hepatic mixed-function oxidase system, as indicated by several drug-metabolising enzymes such as glutathione-S-transferase and reduced glutathione. Administration of Picroliv (6 mg/kg) for 7 days significantly prevented liver damage (Rastogi et al., Drug Development Research 41, 44-47, (1997)). Picroliv, given to rats during the last 15 days (12 mg/kg/day p.o.) of a 45 days exposure to alcohol, prevented the decrease of superoxide dismutase, catalase, glutathione-S-transferase, and the level of reduced glutathione (Rastogi et al., 1196). Picroliv (6 mg/kg/day p.o.) recovered the depletion of reduced glutathione level and the inhibition of glutathione-S-transferase, glutathione reductase, and glutathione peroxidase activities in the livers of mice infected with Plasmodium berghei. (Furthermore, Picroliv recovered the decreased levels of cysteine, sulphydryl groups and glutathione synthesis by suppressing the enhanced activation of xcex3-glutamyl transpeptidase in mice infected with Plasmodium berghei. Pretreatment with the ethanol extract of Picrorhiza kurrooa (50 mg/kg/day, p.o.) prevented the decrease of glutathione peroxidase and glutathione transferase activity, and the decrease of reduced glutathione in rats with galactosamine-induced liver damage.
Apocynin, an acetophenone isolated from P. kurrooa, enhances intracellular GSH synthesis, mediated by the increased expression of xcex3-GCS mRNA and enzyme activity through activation of transcription factor AP-1 (Lapperre et al., Febs Letters 443, 235-9, (1999)).
Schisandra chinensis (Turcz.) Baill (Schisandraceae) is a winding herb found in the Far East. Its fruits have been used since long in traditional medicine in this part of the world, The main active ingredients are lignans, e.g. schisandrins (gomisins). These compounds were shown to be potent hepatoprotective agents (Hancke et al., Fitoterapia 70, 451-471, (1999)). They are able to enhance the GSH/GSSG ratio and the activity of GSH reductase, increasing the GSH status of liver cell mitochondria. Furthermore, they are able to enhance detoxification by enhancing cytochrome P450-mediated metabolism of hepatotoxins, followed by the induction of GSH-S-transferase-mediated conjugation.
Pretreatment with a lignan-enriched extract of Schisandra chinensis (1.6 g/kg p.o.) enhanced the hepatic glutathione status and protected against physical exercise-induced muscle damage in rats (Ko et al., Phytotherapy Research 10, 450-452, (1996)). Treatment of rats with extract from Schisandra chinensis (1.6 g/kg/day p.o.) increased the hepatic GSH level and activities of GSH reductase, G6PDH, and decreased the susceptibility of hepatic tissue homogenates to peroxide-induced GSH depletion; pretreating rats with these extracts (0.2-3.2 9/g/kg p.o.) dose-dependently protected against CCl4-induced GSH-depletion and oxidative hepatocellular damage. These data were confirmed by other experiments, showing that Schisandra chienesis extract (1.6 g/kg/day p.o.) increases hepatic GSH levels, GSH reductase and GSH-transferase activities and prevents liver damage in rats with aflatoxin- and cadmium-induced liver damage. Pretreatment of schisanhenol and schizandrin B (200 mg/kg) to mice with ethanol-induced liver peroxidation increased dismutase and catalase activity, while GSH-peroxidase activity was unaffected. Treatment of schisandrin B (3 mmol/kg/day p.o.) increased the mitochondrial GSH level and reciprocally decreased GSSG level, elevating the GSH/GSSG ratio, and increased mitochondrial GSH reductase activity. These effects were more pronounced in CCl4-intoxicated mice, providing protection against liver damage. BCNU, a specific inhibitor of GSH reductase, however, did not affect the protective activity, although it inhibited GSH reductase activity, suggesting that the enhancement of GSH reductase activity by Schisandrin B is not a primary factor of hepatoprotection.
The direct antioxidants are radical scavengers by their chemical composition or interfere with the formation of oxygen radicals. The antioxidants most commonly known for this function are vitamin C, vitamin E and flavonoids. Catechins from green tea and curcumin have similar effects and enhance the antioxidant activity.
Selenium is a component of glutathione peroxidase in erythrocytes and other tissues. Glutathione peroxidase reduces hydrogen peroxide to water. Selenium is thought to be well-absorbed both as inorganic selenium salts and organic selenium compounds. A 200 xcexcg/day supplement for 2 months in selenium-deficient patients with alcoholic cirrhosis significantly improved plasma selenium levels and glutathione peroxidase but had no effect on peroxidative parameters.
Zinc has a role in protection against oxygen radical damage, being an essential component of cytoplasmic superoxide dismutase. Zinc ions also bind to sulphydryl groups in proteins, protecting them against oxidation. Most (80-85%) plasma zinc is bound to albumin, 15% to alpha2-macroglobulin and  less than 2% to RBP. Plasma zinc levels are depressed by infections and other stressors, probably due to systemic redistribution mediated by metallothionein, and perhaps because plasma albumin levels are reduced in stress.
Copper is an essential part of many enzymes which are involved in protection against free radical damage, e.g. cytochrome oxidase, lysyl oxidase, Zn/Cu superoxide dismutase. About 30% of dietary copper is absorbed, and there is some evidence that this increases in deficiency. Dietary deficiency is extremely rare. Over 80% of plasma copper is bound to ceruloplasmin (a positive acute phase protein that increases in inflammatory conditions). Free copper ions (unlikely in normal conditions but may occur in the case of copper excess) are a major source of oxygen radicals.
Manganese is part of a number of metalloenzymes, including mitochondrial pyruvate carboxylase, superoxide dismutase and acetyl CoA carboxylase.
It is a primary object of the present invention to provide a method of increasing the presence of glutathione in cells including the prevention or treatment of impaired liver function by administering a certain combination of components to a mammal.
It is a further object of the present invention to provide improved compositions for increasing the presence of glutathione in cells including the prevention or treatment of impaired liver function.
It was surprisingly found that a combination of components is required for providing an optimal protection against liver damage. It was found that, for this purpose, a combination is required with components that enhance the glutathione status of the cells. In order to achieve this, components are administered which are precursors for the endogenous glutathione production. Together therewith components are administered which enhance the endogenous glutathione biosynthesis and which enhance the regeneration of oxidised glutathione and/or enhance the glutathione-mediated conjugation.
The present invention provides a method of increasing the presence of glutathione in cells including the prevention or treatment of impaired liver function and novel dietetic or pharmaceutical compositions for said purpose comprising in combination at least a) one precursor of glutathione which is selected from the group consisting of cysteine and functional equivalents containing said amino acid, b) one enhancer of the glutathione biosynthesis, and c) a third component which is either selected from lignans or which is a combination c1) of an enhancer of glutathione regeneration and c2) of an enhancer of the glutathione-mediated conjugation.
It was found that the ability to detoxify is crucial for liver health in general. If the capacity of detoxification is reduced, the liver itself becomes toxified by all the endo- and exo-toxins it would normally neutralise.
As already pointed out above many drugs and toxins can be detoxified by conjugation with glutathione. If the detoxifying capacity via GSH of the body (liver) is exceeded other detoxification pathways will be used to a greater extent. The overall clearance will however be slower whereby body parts can be damaged which are exposed too heavily. Said parts can be for instance the liver, the respiratory tract, the gastrointestinal tract, and the skin. This could lead to respiratory diseases like COPD, emphyseme, CARA, and cancer, and liver diseases like fatty liver, cirrhosis, hepatitis and liver cancer.
In addition many people are exposed to toxic compounds that require an adequate glutathione metabolism. This applies for instance to people who live in polluted areas (radiation, numerous halogenated, nitrated chemicals), who work with dangerous chemicals (organophosphorus insecticides or halogenated solvents) and who smoke cigarettes. Also during chronic inflammation of tissue, which may occur in the case of arthritis or inflammatory bowel disease, the glutathione levels in the inflamed tissues are often depleted. Also in this case a further stimulation of the endogenous glutathione production will be advantageous.
The method and the compositions of the present invention can treat and/or prevent the above mentioned diseases. According to the invention the glutathione presence or the glutathione status, respectively, in the cells is increased or improved, respectively. This applies in particular for the treatment and/or prevention of impaired liver function.
The present invention is applicable for mammals including human beings and animals, for instance birds. Several diseases here described can occur during intensive animal breeding due to the consumption of an unbalanced feed diet. Liver problems occur due to the excessive amount of fats of inferior quality or the consumption of waste products of the human food industry which for some reason have become contaminated or comprise too high levels of anti-nutritional factors. This happens predominantly in pig and poultry breeding.
According to the present invention a glutathione precursor a) is administered in a certain minimum amount. Said precursor a) is either cysteine or one or more functional analogue(s) containing said amino acid cysteine or a combination of both. Said functional analogues are for instance salts and common esters of cysteine, especially of the L-isomer, N-alkylated derivatives of cysteine, such as N-acetyl cysteine (NAC), cysteine-rich proteins and peptides, such as some proteins from whey or egg, and cystathionine, both in reduced or oxidised form Glutathione itself in reduced or oxidised form can also increase glutathione tissue levels. When methionine or S-adenosylmethionine (SAM) are used as cystein analogues the risk for elevated cystein levels is high in animals including men suffering from impaired liver function. In case said compounds are used as cystein analogues at least folic acid, vitamin B6 and/or zinc should be present in addition. Preferably all three compounds are present in amounts that exceed the recommended daily amounts.
The Glutathione precursor used according to the invention can be a single species or a mixture of different components or species, respectively. The minimum amount of the precursor a) administered per day is at least 100 mg cysteine, calculated as free amino acid. The minimum amount is preferably at least 200 mg per day. The maximum amount of cysteine should not exceed 2000 mg. The absolute amounts of the equivalents can be easily calculated by using the molar weight of the above mentioned amino acid.
The precursor of glutathione a) is administered together with an enhancer of the glutathione biosynthesis b) and together with a third component c) described below. In a simple embodiment of the invention the above mentioned components a) b) and c) are administered or contained in the composition of the invention.
The third component c) administered is either one or more lignans or a combination of an enhancer of glutathione regeneration c1) and of an enhancer of the glutathione mediated conjugation c2). In this context it should be noted that lignans can act as an enhancer of glutathione regeneration c1) as well as an enhancer of the glutathione mediated conjugation c2). Consequently, according to a first embodiment of the present invention, the third component c) can consist of one lignan alone or a mixture of different lignans. According to a second embodiment of the invention the third component c) can be a combination of one or more lignans either with one enhancer or more enhancers of the glutathione biosynthesis c1) which is or are different from a lignan, or with one enhancer or more enhancers of the gutathione-mediated conjugation c2) which is or are different from a lignan. According to a third embodiment of the invention the third component c) can be a combination of one enhancer or more enhancers of the glutathione biosynthesis c1) which is or are different from a lignan with one enhancer ore more enhancers of the gutathione-mediated conjugation c2) which is or are also different from a lignan. According to a fourth embodiment of the invention the third component c) can be a combination of i) one enhancer or more enhancers of the glutathione biosynthesis c1) which is or are different from a lignan, ii) one enhancer or more enhancers of the gutathione-mediated conjugation c2) which is or are also different from and of iii) one lignan or more lignans.
According to a preferred embodiment the enhancer of the glutathione biosynthesis b) contains apocynin or analogues.
Apocynin can be isolated from plants such as Iris species (Iridaceae) or from the rhizome of Apocynam cannabinum or other Apocynaceae.
More preferably the enhancer of the glutathione biosynthesis b) is a preparation obtained from Picrorhiza species; even more preferably the enhancer of the glutathione biosynthesis b) is selected from the group consisting of an extract of Picrorhiza kurrooa and an extract of Picrorhiza schrophulariiflora, whereby said extract contains most preferably 0.01 to 100 mg per day apocynin or analogues.
The enhancer of glutathione regeneration c1) is preferably selected from the group consisting of preparations rich in silymarin, such as extracts from Silybum marianum or armurariu fruit, and preparations rich in schisandrins, such as extracts from Schisandra species; and the enhancer of glutathione-mediated detoxification process c2) is preferably selected from the group consisting of preparations rich in iridoid glycosides, especially extracts from Picrorhiza species, and preparations rich in Schisandrins such as extracts from Schisandra species.
The preparation of Picrorhiza species is preferably an extract from Picrorhiza kurrooa or Picrorhiza scrophulariiflora (also known as Neopicrorhiza scrophulariiflora), which contains preferably 1-100 mg of total iridoid glycosides, in particular 1 to 100 mg picrosides, more preferably 1 to 50 mg picroside II, for example about 6 mg picroside II, and 0.01-100 mg apocynin.
According to the invention, analogues of apocynin may be used instead of or in addition to apocynin. Such analogues are in particular those in which the 4-hydroxy group is etherified, especially with a sugar moiety. The analogue in which the sugar moiety is xcex2-D-glucose is commonly known as androsin.
The preparation of Silybum marianum is preferably an extract containing 10-1000 mg silymarin, more preferably 175 mg of an extract containing 140 mg of silymarin.
The preparation of Schisandra species is preferably an extract from Schisandra chienesis or Schisandra sphenanthera containing 0.1-100 mg of lignans, in particular 0.1 to 100 mg schisandrins, more preferably 11 to 70 mg schisandrins, for example about 5 mg schisandrins.
The different components a), b), c), c1), and c2) are known and described above. Several traditionally used herbs, e.g. Milk thistle, Picrorhiza and Schisandra can be used, which are known to exhibit liver protective activities, and induce or enhance the endogenous glutathione production. This endogenous antioxidant plays a central role in the metabolisation and elimination of toxins. According to the present invention the GSH status in the liver is increased, and in addition, the enzyme xcex3-glutamylcysteine synthetase, responsible for GSH synthesis, is enhanced as well.
Therefore, the present invention includes precursors and cofactors important for glutathione synthesis, compounds that enhance glutathione regeneration, and compounds that induce the glutathione-mediated detoxification process.
Preferably, direct antioxidants like vitamin C, E, and flavonoids, and enzymatic antioxidants like selenium, zinc, copper, and manganese enhancing the antioxidant activity of the liver can be present in addition according to the present invention. This is preferred since several toxins are capable of exhibiting oxidative damage due to the formation of oxygen radicals.
Enzymatic antioxidants are in particular components that improve the activity of glutathione peroxidase or superoxide dismutase. Selenium can be used as selenium salt and preferably as selenium yeast that provides per daily dose 10-200 mcg selenium. Zinc can be present as an inorganic or organic zinc salt, such as ZnO providing preferably 0.1-30 mg zinc per daily dose. Copper can be present as a copper salt, providing preferably 0.1-8 mg copper per daily dose. Manganese can be present as a manganese salt, providing preferably 0.1-20 mg manganese per daily dose.
Furthermore, the composition can contain at least one compound that further enhances the glutathione status of the liver, as a cofactor in the biosynthesis of precursors of glutathione. Such a compound is selected from the group consisting of riboflavin, preferably 0.1-200 mg riboflavin, vitamin B6, preferably 0.1-200 mg vitamin B6, vitamin B12, preferably 0.1-3000 mcg vitamin B12, and folic acid or folate, preferably 10-1000 mcg folic acid. Preferred sources of vitamin B6 and vitamin B12 are pyridoxine and cyanocobalamine, respectively.
In addition, the composition can contain at least one component that enhances the antioxidant function by directly scavenging reactive oxygen species or by interfering with their formation. Such a component is selected from the group consisting of vitamin C, preferably 10-1000 mg vitamin C, vitamin E, preferably 1-800 mg xcex1-TE, flavonoids, preferably an extract of Matricaria recutita containing 1-100 mg apigenin, catechins, preferably an extract of Camellia sinensis containing 1-500 mg catechins, and curcuminoids, preferably an extract of Curcuma longa containing 1-1000 mg curcumin.
As already pointed out above the present invention applies also to animals and in particular to pig and poultry breeding. In this case the components used according to the present invention can be present in the extracts of plants which are preferably used in animal feed. Said components can also be included in a premix for blending with regular animal feed. The premix is preferably based on whey proteins as source of the glutathione precursor a).
The compositions of the invention can have a form that is normally used for the administration of a food or of a food supplement. They can be present for instance as powders, liquids, emulsions, bars, tablets, and capsules which can be packaged in cartons, cans, sachets, bottles, bags (tea bags) and can be prepared according to methods known in the art.
A composition according to the invention in the form of a tablet contains for instance 300 mg glutathione, 20 mg apocynin and 5 mg schisandrins.
The invention is further described by the following, non limiting examples.

Method of increasing the presence of glutathione in cells


A microprocessor based exercise treadmill control system is disclosed which includes various features to enhance user operation. These features include programs operative to: permit a set of user controls to cause the treadmill to initially operate at predetermined speeds; permit the user to design custom workouts; permit the user to switch between workout programs while the treadmill is in operation; and perform an automatic cooldown program where the duration of the cooldown is a function of the duration of the workout or the user""s heart rate. The features also include a stop program responsive to a detector for automatically stopping the treadmill when a user is no longer on the treadmill and a frame tag module attached to the treadmill frame having a non-volatile memory for storing treadmill configuration, and operational and maintenance data. Another included feature is the ability to display the amount of time a user spends in a heart rate zone.

This invention generally relates to exercise equipment and in particular to exercise treadmills having control systems utilizing microprocessors.
Exercise treadmills are widely used for performing walking or running aerobic-type exercise while the user remains in a relatively stationary position. In addition exercise treadmills are used for diagnostic and therapeutic purposes. Generally, for all of these purposes, the person on the treadmill performs an exercise routine at a relatively steady and continuous level of physical activity. One example of such a treadmill is provided in U.S. Pat. No. 5,752, 897.
Although exercise treadmills that operate using a microprocessor based control system have reached a relatively high state of development, there are a number of significant improvements in the program software that can improve the user""s exercise experience.
It is therefore an object of the invention to provide an exercise treadmill having improved user programs.
A further object of the invention is to provide a treadmill having a control panel that includes a standard set of user controls with a second set of quick start user controls that permits the user to select certain predetermined treadmill operating parameters such as speed to initiate a workout or to change to one of the predetermined speeds during a workout.
Another object of the invention is to provide a treadmill having a control panel that includes user controls that permit the user to program custom user workouts which have certain operating parameters such as speed and inclination where the custom workouts have greater flexibility than the standard workouts normally programed in a treadmill.
An additional object of the invention is to permit the user to switch programs while the treadmill is operating by merely pressing a particular program button without having to stop the treadmill and start a new program.
A further object of the invention is to provide an automatic cooldown feature that automatically begins upon conclusion of the user""s workout where the duration of the cooldown is determined by the length of time of the user""s workout and where the treadmill includes a heart rate management system, the cooldown can be terminated by the user""s heart rate reaching 60% of maximal.
Another object of the invention is to increase the frequency of display information on the user display that is relevant to the manner in which the treadmill is being used and to decrease the frequency of the display information that is not relevant.
A still further object of the invention is to provide a user detect feature that can use a detector such as an IR receiver/transmitter to stop the operation of the treadmill in order to overcome the problem of users leaving treadmills before the end of their programs which can result in treadmills continuing to run for a period of time. This feature can be further enhanced by using treadmill operating criteria such as key pad or motor controller activity to determine if a user is on the treadmill.
Yet an additional object of the invention is to provide a frame tag module secured to the frame of the treadmill and that includes a nonvolatile electrically erasable programmable memory chip and a real time clock.
It is also an object of the invention to provide a treadmill with a quick start feature.
Another object of the invention is to provide a display of the amount of time a user spends in a specified heart rate zone.


A method and system for reducing the time it takes for a trader to place a trade when electronically trading on an exchange, thus increasing the likelihood that the trader will have orders filled at desirable prices and quantities. The “Mercury” display and trading method of the present invention ensure fast and accurate execution of trades by displaying market depth on a vertical or horizontal plane, which fluctuates logically up or down, left or right across the plane as the market prices fluctuates. This allows the trader to trade quickly and efficiently.

At least 60 exchanges throughout the world utilize electronic trading in varying degrees to trade stocks, bonds, futures, options and other products. These electronic exchanges are based on three components: mainframe computers (host), communications servers, and the exchange participants' computers (client). The host forms the electronic heart of the fully computerized electronic trading system. The system's operations cover order-matching, maintaining order books and positions, price information, and managing and updating the database for the online trading day as well as nightly batch runs. The host is also equipped with external interfaces that maintain uninterrupted online contact to quote vendors and other price information systems.
Traders can link to the host through three types of structures: high speed data lines, high speed communications servers and the Internet. High speed data lines establish direct connections between the client and the host. Another connection can be established by configuring high speed networks or communications servers at strategic access points worldwide in locations where traders physically are located. Data is transmitted in both directions between traders and exchanges via dedicated high speed communication lines. Most exchange participants install two lines between the exchange and the client site or between the communication server and the client site as a safety measure against potential failures. An exchange's internal computer system is also often installed with backups as a redundant measure to secure system availability. The third connection utilizes the Internet. Here, the exchange and the traders communicate back and forth through high speed data lines, which are connected to the Internet. This allows traders to be located anywhere they can establish a connection to the Internet.
Irrespective of the way in which a connection is established, the exchange participants' computers allow traders to participate in the market. They use software that creates specialized interactive trading screens on the traders' desktops. The trading screens enable traders to enter and execute orders, obtain market quotes, and monitor positions. The range and quality of features available to traders on their screens varies according to the specific software application being run. The installation of open interfaces in the development of an exchange's electronic strategy means users can choose, depending on their trading style and internal requirements, the means by which they will access the exchange.
The world's stock, bond, futures and options exchanges have volatile products with prices that move rapidly. To profit in these markets, traders must be able to react quickly. A skilled trader with the quickest software, the fastest communications, and the most sophisticated analytics can significantly improve his own or his firm's bottom line. The slightest speed advantage can generate significant returns in a fast moving market. In today's securities markets, a trader lacking a technologically advanced interface is at a severe competitive disadvantage.
Irrespective of what interface a trader uses to enter orders in the market, each market supplies and requires the same information to and from every trader. The bids and asks in the market make up the market data and everyone logged on to trade can receive this information if the exchange provides it. Similarly, every exchange requires that certain information be included in each order. For example, traders must supply information like the name of the commodity, quantity, restrictions, price and multiple other variables. Without all of this information, the market will not accept the order. This input and output of information is the same for every trader.
With these variables being constant, a competitive speed advantage must come from other aspects of the trading cycle. When analyzing the time it takes to place a trade order for a given commodity, various steps contribute in different amounts to the total time required. Approximately 8% of the total time it takes to enter an order elapses between the moment the host generates the price for the commodity and the moment the client receives the price. The time it takes for the client application to display the price to the trader amounts to approximately 4%. The time it takes for a trade order to be transmitted to the host amounts to approximately 8%. The remainder of the total time it takes to place an order, approximately 80%, is attributable to the time required for the trader to read the prices displayed and to enter a trade order. The present invention provides a significant advantage during the slowest portion of the trading cycle—while the trader manually enters his order. Traders recognize that the value of time savings in this portion may amount to millions of dollars annually.
In existing systems, multiple elements of an order must be entered prior to an order being sent to market, which is time consuming for the trader. Such elements include the commodity symbol, the desired price, the quantity and whether a buy or a sell order is desired. The more time a trader takes entering an order, the more likely the price on which he wanted to bid or offer will change or not be available in the market. The market is fluid as many traders are sending orders to the market simultaneously. It fact, successful markets strive to have such a high volume of trading that any trader who wishes to enter an order will find a match and have the order filled quickly, if not immediately. In such liquid markets, the prices of the commodities fluctuate rapidly. On a trading screen, this results in rapid changes in the price and quantity fields within the market grid. If a trader intends to enter an order at a particular price, but misses the price because the market prices moved before he could enter the order, he may lose hundreds, thousands, even millions of dollars. The faster a trader can trade, the less likely it will be that he will miss his price and the more likely he will make money.

Click based trading with intuitive grid display of market depth

Trading Technologies International, Inc.


The present invention is a two-component catalyst system comprising (a) an alkyl magnesium (MgR2) component and (b) a Lewis acid component. The catalyst system is used for catalyzing the oligomerization and polymerization of ethylene and/or xcex1-olefins to form homopolymers and copolymers. The products range from highly linear, high molecular weight, solid polymers to highly branched, lower molecular weight oils.

The present invention relates to the oligomerization and polymerization of ethylene and xcex1-olefins using a two part catalyst system comprising an alkyl magnesium component and a Lewis acid. The products range from highly linear, high molecular weight, solid polymers to highly branched, lower molecular weight oils.
The polymerization of ethylene, propylene and other xcex1-olefins catalyzed by transition metal catalyst systems has been practiced commercially for many years. For example homo- and copolymers of ethylene with other materials such as olefins (acyclic and/or cyclic, optionally substituted), and other types of monomers, are being used as plastics for packaging materials, molded items, films, etc., and as elastomers for molded goods, belts of various types, in tires, adhesives, and for other uses. It is well known in the art that the structure of these various polymers, and hence their properties and uses, are highly dependent on the catalyst and specific conditions used during their synthesis. In addition to these factors, processes in which these types of polymers can be made at reduced cost are also important. Therefore, improved processes and catalyst systems for making such polymers are of great commercial interest.
Catalysts used in polyolefin preparation can be classified into a limited number of types. Ziegler-Natta type catalysts for polymerization of unsaturated hydrocarbons, such as xcex1-olefins, have long been the state of the art catalysts for such reactions. Typically, Ziegler-Natta type catalysts are composed of transition metal salts and aluminum alkyl compounds. While these catalysts are very effective and have a long-established record of use, they are not without drawbacks. For example, transition metals are expensive, potentially present some toxicity hazards, and to some extent are environmentally objectionable. Therefore, continuing efforts towards development of other suitable olefin polymerization catalysts have occurred. For example, metallocene catalysts have been developed for use in xcex1-olefin polymerizations. Even more recently, there have been attempts to use non-transition metal catalysts like Al compounds. For example, there are cationic Al compounds disclosed in U.S. Pat. No. 5,777,120 and neutral Al compounds disclosed by Sen et al. (Polym. Prepr. 34 (2) 818 (1998)). However, until the present invention, combinations of non-transition metal catalysts (e.g. Mg and Al) for these purposes were unknown.
The polymerization of ethylene and xcex1-olefins typically leads to the formation of highly linear polymers. One use for these polymers, when in a fluid form, is for synthetic lubricant compositions. However, polymerization of ethylene, the most widely available and least expensive of the olefins, by transition metal catalysts usually leads to the formation of solid polymers. Thus polyethylene is commonly used to make plastic containers such as milk jugs and for plastic films. As such, polyethylene is generally not suitable for use as soft materials or lubricants for most applications. Thus significant research continues to be performed to discover improved methods for synthesizing liquid polyolefins, especially polyethylene.
In general, synthetic lubricants are more desirable as they tend to provide lower friction and increased mechanical efficiency across the full spectrum of mechanical loads and do so over a wider range of operating conditions relative to traditional oil lubricants. The objective of industrial research on synthetic lubricants is, in general, to achieve a polymeric fluid that exhibits a useful viscosity over a wide range of temperature, i.e., has a good viscosity index (VI), while also exhibiting good lubricity, and a pour point equal to or better than mineral oil. One characteristic of the molecular structure of the polymeric fluids has been found to correlate very well with all of these desirable lubricant properties. This characteristic is the polymer""s branching index, BI. BI is the ratio of methyl protons to total non-aromatic, aliphatic group protons in the polymer product. The BI of a polymer is easily determined from proton NMR spectra by calculating the ratio of non-aromatic methyl hydrogens centered around 0.85 ppm, to the total non-aromatic aliphatic hydrogens in the range of 0.5 to 2.1 ppm. BI is related to the number of branches (n) per 1000 methylene (CH2) groups in the following way: BI=3n/2000.
Generally, as the BI increases, the pour point of the polymer fluid, i.e., the temperature at which the composition changes from a liquid to a solid, decreases. This is a desirable effect as a lower pour point extends the application range of the polymer fluid. BI, however, has a negative effect on the viscosity index of a polyethylene oil; it is well-known in the art that the viscosity index of polyethylene fluids decreases as the branching index increases. This is an undesirable effect because a lower viscosity index indicates a poor viscosity-temperature performance. Thus, the challenge in synthesizing polyethylene fluids is to achieve an amount of branching sufficient to maintain the polyethylene in a liquid state such that the polyethylene fluid has a good viscosity index.
Recently there have been a number of discoveries in the synthesis of branched polyethylene polymers. For example, DuPont and the University of North Carolina, have developed novel Ni(II) and Pd(II) based catalysts which catalyze the polymerization of ethylene to form polyethylene liquids. In this PCT Application (No. WO 96/23010) it has been disclosed that polymers having a moderate degree of branching can be synthesized by using palladium and nickel catalysts incorporating very bulky chelating xcex1-diimine bidentate ligands. The PCT application discloses, for example, polyolefins having about 80 to about 150 branches per 1000 methylene groups, wherein for every 100 branches that are methyl branches, there are about 30 to about 90 ethyl branches, about 4 to about 20 propyl branches, about 15 to about 50 butyl branches, about 3 to about 15 amyl branches, and about 30 to about 140 hexyl or longer branches. The olefin polymers described in the PCT application are said to be usefull as elastomers, molding resins, in adhesives, etc. Polymers containing monomer units derived other than from olefins are also disclosed in the PCT application; and polymers which contain olefin and olefinic ester monomer units, particularly copolymers of ethylene and methyl methacrylate and/or other acrylic esters, are said to be useful as viscosity modifiers for lubricating oils. The basis for the above PCT Application is believed to be an article by Johnson et al published in the Journal of the American Chemical Society (New Pd(II)and Ni(II)-Based Catalysts for Polymerization of Ethylene and xcex1-Olefins, J. Am. Chem. Soc. 1995, 117, 6414-6415). In these systems, however, the degree of branching is only 20 to 150 branches per 1,000 CH2 groups.
Other highly active Nickel(II) and Palladium(II)-based catalysts have been discovered by researchers at The Pennsylvania State University and have been employed for the preparation of highly branched polyethylene fluids having greater than 587 branches per 1000 CH2 groups. These polymers and their synthesis have been reported by J. S. Kim, J. H. Powlow, L. M. Wojcinski, S. Murtuza, S. Kacker, and A. Sen, xe2x80x9cNovel Nickel(II) and Palladium(II)-Based Catalyst Systems for the Synthesis of Hyperbranched Polymers from Ethenexe2x80x9d, J. Am. Chem. Soc. 120, 1932, 1998. Such highly branched polymers, however, have a VI that typically is too low to be used as, for example, a lube basestock. See also WO 98/33823 titled xe2x80x9cMetal Catalyzed Synthesis of Hyperbranched Ethylene and/or xcex1-olefin Polymersxe2x80x9d.
Another recent international patent application (PCT Application No. WO 97/02298) relates to the preparation of polyolefins by coordination polymerization of ethylene, styrene or norbornene using a catalyst comprising (a) a zerovalent tricoordinate or tetracoordinate nickel compound which has at least one labile ligand, (b) an acid of the formula HX, where X is a noncoordinating anion, and (c) at least one bulky ligand selected from a specified group thereof. At page 29, lines 25 et seq. of that PCT Application, it is suggested that the following materials (among others) should be absent during the polymerization process, or at least should not be present in an amount sufficient to affect the course of the polymerization: an organoaluminum compound; an aluminum halide; and any organometallic compound except for the nickel compounds. The polymers prepared in accordance with that PCT Application are moderately branched and are said to be useful as molding resins, films and elastomers.
A report from Switzerland [Adv. Poly. Sci. 1974,15,1] describes the use of a TiCl4/EtAlCl2 catalyst for the polymerization of ethylene in benzene to give branched polymers. The products obtained, however, were of relatively low branching and molecular weight. One detrimental side reaction associated with the use of benzene solvent is Friedel-Crafts alkylation of the solvent and thus, a large portion of the product is reported to contain aromatic rings.
Moderately branched ethylene polymers are also disclosed by de Souza et al in an article published in September 1997 ([xcex73-methallyl-nickel-dad] PF6 Complex: New Catalyst Precursor For Ethylene Polymerization, Macromol. Rapid Commun., 1997, 18, 795-800). In that article, it is disclosed that [xcex73-methallylnickel-dad] PF6 is active as an ethylene polymerization catalyst when used in the presence of usual organoaluminum compounds such as diethylaluminum chloride, at low Al/Ni ratios and under mild reaction conditions.
While the hydrocarbon polymers prepared in accordance with the above-discussed PCT applications and articles are characterized by a moderate degree of branching, there remains a need for hyperbranched, viscous, liquid hydrocarbon polymers and to a method for their preparation from simple and inexpensive olefins such as ethylene and propylene. Further, there is a continuing need in the art for polyolefin fluids having a molecular weight, a branching index, and a viscosity index such that they are suitable for use as synthetic lubricants. The present discovery of a novel method of manufacturing solid and liquid polyolefins using non-transition metal catalysts addresses these needs and others.
It is an object of this invention to provide a novel catalyst system useful for oligomerization, homopolymerization and copolymerization of ethylene and/or xcex1-olefins.
It is also an object of this invention to provide a novel method of making highly linear, high molecular weight, solid polyolefins with a molecular weight of from about 30,000 up to about 2,500,000.
It is an additional object of this invention to provide a novel method of making branched, viscous oils with a molecular weight in the range of from about 300 to about 30,000.
Yet another object is to prepare viscous, oily, branched hydrocarbon compositions that are useful as lubricants and lubricant components by homopolymerizing or copolymerizing xcex1-olefins in the presence of a non-transition metal containing catalyst.
Yet another object of the invention is to supply a catalyst system that produces little or no discoloration in the polymerization product thus eliminating or reducing an extra, costly clean-up step.
These and other objects and advantages are accomplished by the present invention, which comprises a novel catalyst system containing (a) an alkyl magnesium component and (b) a Lewis acid component. The invention also includes the use of the catalyst system for the oligomerization, homopolymerization and copolymerization of xcex1-olefins to form homopolymers and copolymers thereof. Preferrably, the reactions are performed in the presence of a solvent and/or reaction promoters.
The present invention comprises a catalyst system for the oligomerization or polymerization of ethylene and/or xcex1-olefins to prepare homopolymers or copolymers thereof. The catalyst system contains two components: (a) an alkyl magnesium compound having the formula MgR2 wherein R can be any aliphatic group and (b) a Lewis acid component such as FeCl3 or AlCl3. The reactions are preferably done in the presence of a halogenated or non-halogenated hydrocarbon solvent. The molar ratio of component a:b is in the range of 10:1 to 1:100, preferably about 2:1 to 1:10, and most preferably about 1:1 to 1:6.
In a preferred embodiment for making highly linear, high molecular weight solid polymers the Lewis acid is present at 1 molar equivalent or less. The molecular weight range for these linear solid polymers is generally in the range of about 30,000 up to about 2,500,000; preferably in the range of 50,000-1,500,000 and most preferably they are in the range of about 100,000-1,000,000.
In a preferred embodiment for making branched viscous oils, a Lewis acid is added to the reaction mixture in an amount greater than 1 molar equivalent relative to the alkyl magnesium component. Preferably it is added in an amount of about 2 to about 10 molar equivalent and most preferably in the range of 3-6 molar equivalent. The molecular weight of the viscous oils are generally in the range of from about 300 to about 30,000; preferably they are within the range of about 500 to about 10,000; and most preferably they are within the range of about 700 to about 3,000. This preferred embodiment may be used as a synthetic lubricant basestock. It should be appreciated by those skilled in the art that the term xe2x80x9cbasestockxe2x80x9d, as used herein, refers to a hydrocarbon oil without additives or, in the alternative, the primary component in a lubricant formulation.
In yet another preferred embodiment, the synthetic lubricant basestock may be combined with additional lubricating oil additives including, but not limited to, antioxidants, anti-wear additives, extreme pressure antioxidants, anti-wear additives, high pressure additives, friction modifiers, viscosity index improvers, pour point depressants, detergents, dispersants, corrosion inhibitors, metal deactivators, seal compatibility additives, demulsifiers, anti-foam additives, and mixtures thereof.
In a preferred aspect of the invention, linear solid polymers and branched viscous liquid polymers are prepared from ethylene as the sole monomer. In other aspects, ethylene may be replaced with or used in combination with other olefins such as propylene, butene, 1-pentene, 1-hexene, 1-dodecene and the like.
The polymerization preferably is carried out in the liquid phase using a halogenated or non-halogenated hydrocarbon solvent. In general any solvent known to those skilled in the art of olefin polymerization can be used. If a solvent is employed, it is preferred that the solvent is either a halogenated compound (preferably aromatic), an aliphatic hydrocarbon comprising from about 5 to about 20 carbons, or a mixture thereof. Examples of halogenated solvents are chlorobenzene, methylene chloride (CH2Cl2), tetrachloroethane (C2H2Cl4), dichlorobenzene (C6H4Cl2), trichlorobenzene, bromobenzene, dibromobenzene, tribromobenzene, and alkylated halobenzenes having C1-C10 alkyl groups, such as, for example, p-chlorotoluene, and the like. Especially preferred halogenated solvents are chlorobenzene and dichlorobenzene. Examples of aliphatic hydrocarbon solvents comprising from about 5 to about 20 carbons are toluene, xylenes, pentane, hexane, heptane, decane, and dodecane. These are non-limiting examples however and any halogenated or non-halogenated hydrocarbon solvent that effectively assists the polymerization is acceptable.
The catalyst system of the present invention comprises two components (a) an alkyl magnesium and (b) a Lewis acid. The alkyl magnesium component of the present invention is defined as MgR2 where R is any hydrocarbyl group attached to the magnesium. Suitable R groups include lower alkyls (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, etc.) and cyclic alkyls (e.g. cyclopentyl, cyclohexyl, etc.). Other suitable R groups are aryls and fluorinated alkyls and aryls. Mixtures of the above can also be used. Preferred alkyl magnesium compounds are diethylmagnesium [Mg(C2H5)2], dibutylmagnesium [Mg(C4H9)2] and dineopentylmagnesium [Mg(Np)2].
The second component of the catalyst system is a Lewis acid. The Lewis acid component of the present catalyst system may be any Lewis acid known to those skilled in the art. Some non-limiting examples of Lewis acids suitable for use in the present invention include the following: B(C6F5)3, B(C6H5)3, BF3, AlRnX3xe2x88x92n (R=alkyl, X=C6F5, F, Cl Br, n=0-2), PF5, and alkylaluminoxanes. Mixtures of the above can also be used. The preferred Lewis acids are B(C6F5)3, AlCl3, and AlBr3. Additionally, these Lewis acids can be used in combination. The total amount of the Lewis acid component used in the catalyst system is not particularly limited. However, to obtain liquid polymers, the Lewis acid component should be used in substantial molar excess relative to the alkyl magnesium component. Typically, the Lewis acid component should be used in an amount of from about 2 to about 50 moles per mole of alkyl magnesium component. Preferably, the Lewis acid should be used in an amount of from about 3 to about 10 moles per mole of alkyl magnesium component, and more preferably about 6 moles per mole of alkyl magnesium component.
Additionally, the catalyst system can contain other optional components known to those skilled in the art. One such group of compounds are promoters including acidic metal oxides (e.g., Al2O3, ZrO2) and organic molecules with oxygen and nitrogen functionalities (e. g., C6F5OH).
The polymerization in accordance with this invention may be carried out at temperatures ranging from about 0xc2x0 C. to about 200xc2x0 C. Typically, however, the polymerization will be carried out at a temperature of from about 20xc2x0 C. to about 80xc2x0 C. The pressure at which the polymerization is carried out is not critical, with pressures ranging from 15 psi to 1500 psi being suitable. Typically, we used pressures ranging from 300 to 900 psi.
In another embodiment of the present invention, preferably at least one component of the catalyst system is supported by an inert support. Such inert supports are well known to those skilled in the art such as, for example, silica, alumina, carbon, zirconia, magnesia, diatomatious earth, kieselgur, and mixtures thereof. Supporting the components of the catalyst system to such inert support is accomplished by techniques well known to those skilled in the art such as, for example, impregnation.
The following examples further illustrate additional objects, advantages, and novel features of the invention. It will become apparent to those skilled in the art, however, that such examples are not intended to limit the scope of the invention.
The following materials were used in the examples given below. Np2Mg (Np=neopentyl) was prepared as described in the J. Org. Chem. 27, 1868, 1962 using neopentyl bromide, magnesium, and dioxane. A highly pure Np2Mg was obtained by sublimation of crude product twice at 100xc2x0 C./60 mtorr. Diethylmagnesium was prepared from diethylmercury and magnesium as described in J. Organomet. Chem. 14, 1, 1968. Dibutylmagnesium, tris(pentafluorophenyl)boron (xe2x80x9cFABxe2x80x9d), pentafluorophenol, aluminum chloride and bis(cyclopentadienyl)magnesium were all used as received from Aldrich. Chlorobenzene (from Aldrich) was dried over LiAlH4 or K2CO3, and toluene (from Aldrich) was dried over Na benzophenone ketyl. Both solvents were stored under argon atmosphere with 4-xc3x85 molecular sieves. The reaction mixtures were prepared in a dry nitrogen-filled glove box. Polymerization reactions were performed in glass-lined 125 ml or stirred 300 ml autoclave manufactured by Parr Instrument Company.

Alkyl magnesium catalyzed synthesis of ethylene and xcex1-olefin polymers

ExxonMobile Research and Engineering Company

The Pennsylvania State Research Foundation


A method and system for transferring offline browsing content information of a wide area network from a host computer to a mobile device includes connecting the mobile device to the host computer and obtaining characteristic information of the mobile device pertaining to at least one of hardware and software capabilities of the mobile device. The content information is transferred from the host computer to the mobile device as a function of the characteristic information.

The present invention relates to personal mobile computing devices commonly known as mobile devices. More particularly, the present invention relates to a system and method for offline viewing of content from a wide area network, such as content from the Internet, with the mobile device.
Mobile devices are small electronic computing devices often referred to as personal digital assistants. Many such mobile devices are hand-held devices, or palm-size devices, which comfortably fit within the hand. One commercially available mobile device is sold under the trade name HandHeld PC (or H/PC) having software provided by Microsoft Corporation of Redmond, Washington.
Generally, the mobile device includes a processor, random access memory (RAM) , and an input device such as a keyboard and a display. The keyboard can be integrated with the display, such as where the keyboard is incorporated as a touch sensitive display. A communication interface is optionally provided and is commonly used to communicate with a desktop computer. A replaceable or rechargeable battery powers the mobile device. Optionally, the mobile device can receive power from an external power source that overrides or recharges the built-in battery.
Commonly, the mobile device is used in conjunction with a desktop computer. For example, the user of the mobile device may also have access to, and use, a desktop computer at work or at home, or both. The user typically runs the same types of applications on both the desktop computer and on the mobile device. Thus, it is quite advantageous for the mobile device to be designed to be coupled to the desktop computer to exchange information with, and share information with, the desktop computer.
Another technique for providing information to such mobile devices is through a wireless transmission link. Such information can include electronic mail or pager information including news, weather; sports, traffic and local event information.
In addition to the above-mentioned uses of the mobile device, there is also a desire to use the mobile device for xe2x80x9cofflinexe2x80x9d browsing of Internet content. U.S. patent application Ser. No. 09/107,666 filed Jun. 30, 1998, entitled xe2x80x9cSYSTEM FOR DELIVERING DATA CONTENT OVER A LOW BIT RATE TRANSMISSION CHANNELxe2x80x9d and U.S. patent application Ser. No. 09/107,941. filed Jun. 30, 1998, entitled xe2x80x9cCHANNEL DEFINITION ARCHITECTURE EXTENSIONxe2x80x9d describe a system and method wherein Web or Internet content is rendered on a mobile device using a channel definition format, (CDF) file, a set of script files and a set of data files. Briefly, navigation of the content on the mobile device is performed using the CDF file, which includes references to the script files and the data files. When a particular page of content is to be displayed, a script file is accessed and is used to operate upon the data file in order to render the desired information. This architecture allows wireless updates of data files, because, typically, only the data files will change with time. However, if desired, the CDF file and the script files can also be updated wirelessly. Likewise, each of these files can be updated through synchronization of the mobile device with the desktop computer.
Although the above-described system allows wireless updates for Internet content, the content provider must adapt to this architecture and make available to the mobile device user separate script files and data files. In many cases, this requires the content provider to maintain two different types of Internet sites, one for browsers that expect to receive HTML (hypertext markup language) pages for rendering information, and a second site using the above-described architecture.
Another technique for xe2x80x9cofflinexe2x80x9d browsing with a desktop computer involves traversing or xe2x80x9ccrawlingxe2x80x9d through a particular Internet site and storing the information locally. If the information is stored as pages, simple transfer of this information to the mobile device would not be efficient since the mobile device typically has limited memory resources and the information may contain portions that cannot be used or are unsuitable for the mobile device. Thus, memory may be wasted in storing irrelevant information.
There is an ongoing need to provide efficient offline browsing of content, particularly, when performed on a mobile device. The downloading of information for offline browsing should allow access to existing Internet sites without requiring the content provider to maintain separate Internet sites.
A method and system for transferring offline browsing content information of a wide area network from a host computer to a mobile device includes connecting the mobile device to the host computer and obtaining characteristic information of the mobile device pertaining to at least one of hardware and software capabilities of the mobile device. The content information is transferred from the host computer to the mobile device as a function of the characteristic information.

Offline viewing of internet content with a mobile device