The invention relates to a sensor for detecting substance concentration or activity or for determining the presence of substances based on electrochemical reactions. The electrochemical sensor comprises an electrode with surfaces inside the electrode, wherein electrochemical detection reactions occur. Said sensor guarantees high flow densities and is suitable for miniaturization. A substance-recognizing agent is advantageously placed in the electrode in contact with the inner surfaces. This enables not only short response times and long service life but also measurements with excellent linearity.

The invention relates to a sensor for determining material concentrations, activities or for material detection on the basis of electrochemical reactions.
A structure often used in electrochemical sensors consists of a flat support, on which is arranged a flat detection electrode. This electrode is in contact with the sample medium. Certain materials, in the case of platinum electrodes for example hydrogen peroxide, may be detected electrochemically as a result of electrochemical reactions on the electrode surface.
The disadvantage of sensor arrangements of this type is the comparatively small electrode surface and the often low current densities resulting therefrom. Particularly in the course of advancing miniaturization, the surface dimensions of flat electrodes required to achieve sufficiently high current densities are often an insurmountable limit to smaller sensor structural shapes.
The flat sensor electrode is often in contact with a material-recognizing substance in the form of a thin membrane. Materials which may be detected electrochemically at the electrode are formed in the membrane due to a specific detection reaction.
A thin membrane guarantees short diffusion paths from the site of the chemical detection reaction to the electrode and hence short response times. A further advantage of thin membranes is also the avoidance of substrate limitations. In the case of glucose sensors based on glucose oxidase by way of example, there is the danger of oxygen limitation and hence of undesirable non-linearities if the oxygen required for the detection reaction cannot diffuse into the membrane in sufficient quantity.
However, these preferences for thin material-recognizing membranes are partly compensated by adhesion problems due to the often difficult binding of the thin membrane to support and electrode as well as by encapsulation problems. A further disadvantage of thin membranes is the short service life of such sensors, since the comparatively few active membrane components due to the low membrane volume are deactivated or spent in a short time.
The disadvantages just mentioned can be partly avoided by using thicker material-recognizing membranes. However, for thicker membranes there is the problem that long response times for the sensor have to be taken into account due to the long diffusion paths from the site of the chemical reaction to the flat electrode arranged on the support. Furthermore, some of the reacted materials may diffuse from the material-recognizing membrane before detection at the electrode surface, as a result of which the sensitivity is reduced.
A problem with sensor cross-sensitivities often occurs independently of the membrane thickness. The required minimization of such cross-sensitivities is often associated with complex and therefore expensive modifications of conventional sensors.
The object of the invention is to overcome the disadvantages of the state of the art and to provide an electrochemical sensor which can be miniaturized to analyze liquid or gaseous samples, which has short response times and at the same time an increased linear measuring range as well as a long service life, particularly in combination with material-recognizing substances.
For an electrochemical sensor which has at least one electrode having inner hollow cavities into which the material to be determined and/or reacted reaction products may enter, and in which a material-recognizing substance is incorporated in these cavities at least in some regions, advantageously large active detection surfaces can be achieved in the electrode interior even for small external electrode dimensions. A sensor of this type permits realization of high current densities and is particularly suitable also for miniaturization.
Electrodes having inner hollow cavities and consequently having inner surfaces have, in contrast to the traditional flat electrodes, an essentially three-dimensional functionality. Electrodes of this type may have, for example a latticed, reticulated, filamentary or porous structure. It is important that pores, tubes or other hollow cavities having surfaces are present in the interior of the electrode, by means of which the medium to be analyzed and the material to be detected or reacted reaction products of the material to be detected may come into contact with the electrode surface.
The advantages of sensors based on thin-layer membranes and of those based on thick-layer membranes can be combined in a sensor having material-recognizing substance incorporated in the sensor electrode. Consistently short response times are achieved by incorporating the material-recognizing substance in the electrodes, in contrast to thick-layer membrane sensors, independently of the volume of the material-recognizing substances. This is due to the fact that the diffusion path between the site of the chemical reaction and the site of detection of the reaction on the electrode surface is minimal everywhere in the electrode interior. In addition to short response times, high sensitivities can be achieved for amperometric sensors. Since the volume of material-recognizing substance may be increased without considerable losses regarding the response times, a high number of active components are available. The operating period of the sensor is thus considerably extended.
For sensors having material-recognizing substance incorporated in the electrode, it may be advantageous to increase the hollow cavity volumes in favor of incorporating a larger quantity of material-recognizing substance for constant external electrode dimensions. Optimization of sensor service life and sensitivity adapted to the particular application is possible in this manner with consistently short response times.
The essentially three-dimensional sensor electrode is preferably in contact with an electric leakage arranaed on the support and is advantageously composed of several part electrodes (multi-layer structure). In individual or in all part electrodes a specific material-recognizing substance is introduced at least in some areas, for example by capillary forces. Hence the same or different material-recognizing substances may be embedded in different part electrodes. Embedding can often be carried out more simply in a multi-layer structure than for solid electrodes having inner surfaces. A layer electrode which permits simple, layer-like production of individual part electrodes is produced in this manner.
Individual part electrodes may be in electrical contact with one another on the surface so that only one single part matrix needs to be connected to an electric leakage. However, layers of an electrically insulating material may also be arranged between individual part electrodes preferably provided with separate leakages and may be permeable in each case to the material to be detected and to reaction-assisting or reaction-accompanying materials. The part electrodes may also be separated from one another by distancing layers (spacer) which have perforations in a central electrode region. The sandwich construction permits incorporation of different material-recognizing substances in different part electrodes and simultaneously detection of a plurality of materials in a sample solution.
The electrode or part electrodes may consist of a conductive parent substance, for example of metal, or of a conductively coated or metallised, non-conductive parent substance. Suitable conductive parent substances are, for example of metals, such as platinum, silver or gold or of a paste containing carbon and/or one of the afore-mentioned metals. These materials are also suitable as conductive coating for non-conductive parent substances.
Metallic parent substances having inner surface can be produced, for example by etching or by laser treatment. Non-conductive parent substances on the other hand often already have an inner surface from the start. Papers, such as filter paper, paperboards, glass fibers, plastic fibers, textiles, ceramics, mineral materials or materials of vegetable or animal origin, are suitable as non-conductive parent substances for electrodes or part electrodes. Application of metallisation may be effected, for example by sputtering, vaporization using pastes or adhesives or by chemical reaction.
The three-dimensional electrode preferably consists of an insulating parent substance which is surrounded as completely as possible by a very thin layer of a conductor. The production costs of the sensor can be considerably reduced by minimizing the metallisation thickness. Furthermore, it is possible to provide larger surface areas of the parent substance (for example paper webs) with metallisation simultaneously and uniformly. Smaller pieces of it are then used as an electrode or part electrode for the sensors. The production costs can thus be reduced and the signal reproducibility increased.
The material-recognizing substance incorporated in the sensor electrode preferably contains at least one active component, such as enzymes, microbes, bacteria or yeasts, which is preferably immobilized using at least one gel-like or elasticized polymer, such as polyvinyl alcohol, polyvinyl chloride, polyurethane, acrylate or silicone. The material-recognizing substance may be introduced into the electrode parent substance by utilizing capillary action, by vacuum infiltration or by pressure filling.
One or more three-dimensional support cavities receiving the at least one electrode are advantageously arranged on the sensor support or in the support or at least partly in the support of the electrochemical sensor. This at least one support cavity may advantageously be provided with at least one cover. The electrode may thus be encapsulated to provide protection in simple manner and therefore cost-effectively and fixed on the support. This method of encapsulation also avoids the problem of membrane adhesion which often occurs in sensors based on thin-layer membranes.
The support and/or at least one of the covers advantageously has an opening which permits entry of the substance to be detected into the support cavity. The sensor behavior can be optimized by suitable selection of the opening diameter. A small opening diameter, for example reduces the outward diffusion of the substance to be detected and the reacted substance.
Support and cover advantageously consist of a film material based on, for example polyethylene, polyester, polyvinyl chloride, polypropylene, polytetrafluoroethylene, cellulose acetate, silicone or a combination of these materials. The material should be permeable to reaction-assisting or reaction-accompanying materials, but impermeable to the material to be determined. The linear measuring range of the electrochemical sensor is extended in this manner, since depletion of the reaction-assisting or reaction-accompanying materials, that is a substrate limitation, is delayed. Particularly well suited material for support and cover are films, such as heat-sealing films, laminating films, self-adhesive films or sealable films which are joined to one another by melting or adhesion.
An electric leakage arranged on the support and contacting the electrode preferably consists of a metal, such as platinum, silver or gold or of a paste containing carbon and/or one of the afore-mentioned metals, and may be applied to the support by a screen printing process, a silk-screen printing process, a dispensing process, a spraying process, by vaporization or by sputtering.
In addition, a reference electrode or counter-electrode may be arranged on the support to have a reference which is not influenced by the sample matrix or the reaction products, and to facilitate current flow for voltametric measurements. A silver/silver chloride paste by way of example is a suitable material for this electrode.
Measuring electrode as well as reference electrode or counter-electrode may come into contact with the medium to be analyzed, for example via a flow channel arranged on the support. A sensor having integrated flow channel is particularly suited for automation of the detection process or for long-term monitoring. However, direct contact with the sample medium can also be conceived by immersion or trickling.
The structure of the electrochemical sensor of the invention permits minimizing of the influence of interfering materials and hence cross-sensitivities in simple manner. This is possible in two ways. Firstly, an interference protective layer may be arranged between sample to be analyzed and the electrode which prevents entry of interfering materials into the support cavity by size and/or charge exclusion. Layers of this type may consist, for example of polymer layers of silicone, polytetrafluoroethylene, polyacrylate, polyurethane, cellulose acetate, Naflon, polycarbonate or polyvinyl chloride. They may line the support cavity completely or even partly, for example in the region of the support or cover opening.
A further possibility for reducing the effect of interfering materials consists in arranging a further electrode, preferably in the region of the support or cover opening, between the detection electrode and the sample to be analyzed and connecting to a voltage source. Interfering materials may be oxidized or reduced by applying a voltage to this electrode, resulting in it being possible to reduce cross-sensitivities. The further electrode is advantageously situated in the immediate vicinity of the detection electrode having inner surfaces and is electrically separated from the latter by an insulating layer or a thin gap.
The further electrode may be designed like the detection electrode, but wherein material-recognizing substance is not incorporated in the hollow cavities. This guarantees that interfering materials are reduced or oxidized at the surface of the further electrode on their path through the further electrode to the detection electrode with considerable probability.
Further positive properties and preferences of the invention can be seen from the exemplary embodiments described below and the figures.

Institut fur Chemo-und Biosensorik Munster E.V.


A novel soybean cultivar, designated 940021, is disclosed. The invention relates to the seeds of soybean cultivar 940021, to the plants of soybean 940021 and to methods for producing a soybean plant produced by crossing the cultivar 940021 with itself or another soybean variety. The invention further relates to hybrid soybean seeds and plants produced by crossing the cultivar 940021 with another soybean cultivar.

The present invention relates to a new and distinctive soybean cultivar, designated 940021. There are numerous steps in the development of any novel, desirable plant germplasm. Plant breeding begins with the analysis and definition of problems and weaknesses of the current germplasm, the establishment of program goals, and the definition of specific breeding objectives. The next step is selection of germplasm that possess the traits to meet the program goals. The goal is to combine in a single variety an improved combination of desirable traits from the parental germplasm. These important traits may include higher seed yield, resistance to diseases and insects, better stems and roots, tolerance to drought and heat, and better agronomic quality.
Choice of breeding or selection methods depends on the mode of plant reproduction, the heritability of the trait(s) being improved, and the type of cultivar used commercially (e.g., F1 hybrid cultivar, pureline cultivar, etc.). For highly heritable traits, a choice of superior individual plants evaluated at a single location will be effective, whereas for traits with low heritability, selection should be based on mean values obtained from replicated evaluations of families of related plants. Popular selection methods commonly include pedigree selection, modified pedigree selection, mass selection, and recurrent selection.
The complexity of inheritance influences choice of the breeding method. Backcross breeding is used to transfer one or a few favorable genes for a highly heritable trait into a desirable cultivar. This approach has been used extensively for breeding disease-resistant cultivars. Various recurrent selection techniques are used to improve quantitatively inherited traits controlled by numerous genes. The use of recurrent selection in self-pollinating crops depends on the ease of pollination, the frequency of successful hybrids from each pollination, and the number of hybrid offspring from each successful cross.
Each breeding program should include a periodic, objective evaluation of the efficiency of the breeding procedure. Evaluation criteria vary depending on the goal and objectives, but should include gain from selection per year based on comparisons to an appropriate standard, overall value of the advanced breeding lines, and number of successful cultivars produced per unit of input (e.g., per year, per dollar expended, etc.).
Promising advanced breeding lines are thoroughly tested and compared to appropriate standards in environments representative of the commercial target area(s) for three or more years. The best lines are candidates for new commercial cultivars; those still deficient in a few traits may be used as parents to produce new populations for further selection.
These processes, which lead to the final step of marketing and distribution, usually take from eight to 12 years from the time the first cross is made. Therefore, development of new cultivars is a time-consuming process that requires precise forward planning, efficient use of resources, and a minimum of changes in direction.
A most difficult task is the identification of individuals that are genetically superior, because for most traits the true genotypic value is masked by other confounding plant traits or environmental factors. One method of identifying a superior plant is to observe its performance relative to other experimental plants and to a widely grown standard cultivar. If a single observation is inconclusive, replicated observations provide a better estimate of its genetic worth.
The goal of plant breeding is to develop new, unique and superior soybean cultivars and hybrids. The breeder initially selects and crosses two or more parental lines, followed by repeated selfing and selection, producing many new genetic combinations. The breeder can theoretically generate billions of different genetic combinations via crossing, selfing and mutations. The breeder has no direct control at the cellular level. Therefore, two breeders will never develop the same line, or even very similar lines, having the same soybean traits.
Each year, the plant breeder selects the germplasm to advance to the next generation. This germplasm is grown under unique and different geographical, climatic and soil conditions, and further selections are then made, during and at the end of the growing season. The cultivars which are developed are unpredictable. This unpredictability is because the breeder""s selection occurs in unique environments, with no control at the DNA level (using conventional breeding procedures), and with millions of different possible genetic combinations being generated. A breeder of ordinary skill in the art cannot predict the final resulting lines he develops, except possibly in a very gross and general fashion. The same breeder cannot produce the same cultivar twice by using the exact same original parents and the same selection techniques. This unpredictability results in the expenditure of large amounts of research monies to develop superior new soybean cultivars.
The development of new soybean cultivars requires the development and selection of soybean varieties, the crossing of these varieties and selection of superior hybrid crosses. The hybrid seed is produced by manual crosses between selected male-fertile parents or by using male sterility systems. These hybrids are selected for certain single gene traits such as pod color, flower color, pubescence color or herbicide resistance which indicate that the seed is truly a hybrid. Additional data on parental lines, as well as the phenotype of the hybrid, influence the breeder""s decision whether to continue with the specific hybrid cross.
Pedigree breeding and recurrent selection breeding methods are used to develop cultivars from breeding populations. Breeding programs combine desirable traits from two or more cultivars or various broad-based sources into breeding pools from which cultivars are developed by selfing and selection of desired phenotypes. The new cultivars are evaluated to determine which have commercial potential.
Pedigree breeding is used commonly for the improvement of self-pollinating crops. Two parents which possess favorable, complementary traits are crossed to produce an F1. An F2 population is produced by selfing one or several F1""s. Selection of the best individuals may begin in the F2 population; then, beginning in the F3, the best individuals in the best families are selected. Replicated testing of families can begin in the F4 generation to improve the effectiveness of selection for traits with low heritability. At an advanced stage of inbreeding (i.e., F6 and F7), the best lines or mixtures of phenotypically similar lines are tested for potential release as new cultivars.
Mass and recurrent selections can be used to improve populations of either self- or cross-pollinating crops. A genetically variable population of heterozygous individuals is either identified or created by intercrossing several different parents. The best plants are selected based on individual superiority, outstanding progeny, or excellent combining ability. The selected plants are intercrossed to produce a new population in which further cycles of selection are continued.
Backcross breeding has been used to transfer genes for a simply inherited, highly heritable trait into a desirable homozygous cultivar or inbred line which is the recurrent parent. The source of the trait to be transferred is called the donor parent. The resulting plant is expected to have the attributes of the recurrent parent (e.g., cultivar) and the desirable trait transferred from the donor parent. After the initial cross, individuals possessing the phenotype of the donor parent are selected and repeatedly crossed (backcrossed) to the recurrent parent. The resulting plant is expected to have the attributes of the recurrent parent (e.g., cultivar) and the desirable trait transferred from the donor parent.
The single-seed descent procedure in the strict sense refers to planting a segregating population, harvesting a sample of one seed per plant, and using the one-seed sample to plant the next generation. When the population has been advanced from the F2 to the desired level of inbreeding, the plants from which lines are derived will each trace to different F2 individuals. The number of plants in a population declines each generation due to failure of some seeds to germinate or some plants to produce at least one seed. As a result, not all of the F2 plants originally sampled in the population will be represented by a progeny when generation advance is completed.
In a multiple-seed procedure, soybean breeders commonly harvest one or more pods from each plant in a population and thresh them together to form a bulk. Part of the bulk is used to plant the next generation and part is put in reserve. The procedure has been referred to as modified single-seed descent or the pod-bulk technique.
The multiple-seed procedure has been used to save labor at harvest. It is considerably faster to thresh pods with a machine than to remove one seed from each by hand for the single-seed procedure. The multiple-seed procedure also makes it possible to plant the same number of seeds of a population each generation of inbreeding. Enough seeds are harvested to make up for those plants that did not germinate or produce seed.
Descriptions of other breeding methods that are commonly used for different traits and crops can be found in one of several reference books (e.g., Allard, 1960; Simmonds, 1979; Sneep et al., 1979; Fehr, 1987).
Proper testing should detect any major faults and establish the level of superiority or improvement over current cultivars. In addition to showing superior performance, there must be a demand for a new cultivar that is compatible with industry standards or which creates a new market. The introduction of a new cultivar will incur additional costs to the seed producer, the grower, processor and consumer; for special advertising and marketing, altered seed and commercial production practices, and new product utilization. The testing preceding release of a new cultivar should take into consideration research and development costs as well as technical superiority of the final cultivar. For seed-propagated cultivars, it must be feasible to produce seed easily and economically.
Soybean, Glycine max (L), is an important and valuable field crop. Thus, a continuing goal of plant breeders is to develop stable, high yielding soybean cultivars that are agronomically sound. The reasons for this goal are obviously to maximize the amount of grain produced on the land used and to supply food for both animals and humans. To accomplish this goal, the soybean breeder must select and develop soybean plants that have the traits that result in superior cultivars.
According to the invention, there is provided a novel soybean cultivar, designated 940021. This invention thus relates to the seeds of soybean cultivar 940021, to the plants of soybean 940021 and to methods for producing a soybean plant produced by crossing the soybean 940021 with itself or another soybean line, and the creation of variants by mutagenesis or transformation of soybean 940021.
Thus, any such methods using the soybean variety 940021 are part of this invention: selfing, backcrosses, hybrid production, crosses to populations, and the like. All plants produced using soybean variety 940021 as a parent are within the scope of this invention. Advantageously, the soybean variety could be used in crosses with other, different, soybean plants to produce first generation (F1) soybean hybrid seeds and plants with superior characteristics.
In another aspect, the present invention provides for single or multiple gene converted plants of 940021. The transferred gene(s) may preferably be a dominant or recessive allele. Preferably, the transferred gene(s) will confer such traits as herbicide resistance, insect resistance, resistance for bacterial, fungal, or viral disease, male fertility, male sterility, enhanced nutritional quality, and industrial usage. The gene may be a naturally occurring soybean gene or a transgene introduced through genetic engineering techniques.
In another aspect, the present invention provides regenerable cells for use in tissue culture of soybean plant 940021. The tissue culture will preferably be capable of regenerating plants having the physiological and morphological characteristics of the foregoing soybean plant, and of regenerating plants having substantially the same genotype as the foregoing soybean plant. Preferably, the regenerable cells in such tissue cultures will be embryos, protoplasts, meristematic cells, callus, pollen, leaves, anthers, roots, root tips, flowers, seeds, pods or stems. Still further, the present invention provides soybean plants regenerated from the tissue cultures of the invention.
In the description and tables which follow, a number of terms are used. In order to provide a clear and consistent understanding of the specification and claims, including the scope to be given such terms, the following definitions are provided:
Allele. Allele is any of one or more alternative forms of a gene, all of which alleles relate to one trait or characteristic. In a diploid cell or organism, the two alleles of a given gene occupy corresponding loci on a pair of homologous chromosomes.
Backcrossing. Backcrossing is a process in which a breeder repeatedly crosses hybrid progeny back to one of the parents, for example, a first generation hybrid F1 with one of the parental genotypes of the F1 hybrid.
Brown Stem Rot. This is a visual disease score from 1 to 9 comparing all genotypes in a given test. The score is based on leaf symptoms of yellowing and necrosis caused by brown stem rot. A score of 9 indicates no symptoms. Visual scores range to a score of 1 which indicates severe symptoms of leaf yellowing and necrosis.
Cotyledon. A cotyledon is a type of seed leaf. The cotyledon contains the food storage tissues of the seed.
Embryo. The embryo is the small plant contained within a mature seed.
Emergence. This score indicates the ability of the seed to emerge when planted 3xe2x80x3 deep in sand and with a controlled temperature of 25xc2x0 C. The number of plants that emerge each day are counted. Based on this data, each genotype is given a 1 to 9 score based on its rate of emergence and percent of emergence. A score of 9 indicates an excellent rate and percent of emergence, an intermediate score of 5 indicates average ratings and a 1 score indicates a very poor rate and percent of emergence.
Hilum. This refers to the scar left on the seed which marks the place where the seed was attached to the pod prior to the seed being harvested.
Hypocotyl. A hypocotyl is the portion of an embryo or seedling between the cotyledons and the root. Therefore, it can be considered a transition zone between shoot and root.
Iron-Deficiency Chlorosis. Plants are scored 1 to 9 based on visual observations. A score of 9 means no stunting of the plants or yellowing of the leaves and a score of 1 indicates the plants are dead or dying caused by iron-deficiency chlorosis, a score of 5 means plants have intermediate health with some leaf yellowing.
Lodging Resistance. Lodging is rated on a scale of 1 to 9. A score of 9 indicates erect plants. A score of 5 indicates plants are leaning at a 45xc2x0 angle in relation to the ground and a score of 1 indicates plants are laying on the ground.
Maturity Date. Plants are considered mature when 95% of the pods have reached their mature color. The number of days are either calculated from August 31 or from the planting date.
Maturity Group. This refers to an agreed-on industry division of groups of varieties, based on zones in which they are adapted primarily according to day length or latitude. They consist of very long day length varieties (Groups 000, 00, 0), and extend to very short day length varieties (Groups VII, VIII, IX, X).
Oil or Oil Percent. Soybean seeds contain a considerable amount of oil. Oil is measured by NIR spectrophotometry, and is reported on an as is percentage basis.
Oleic Acid Percent. Oleic acid is one of the five most abundant fatty acids in soybean seeds. It is measured by gas chromatography and is reported as a percent of the total oil content.
Palmitic Acid Percent. Palmitic acid is one of the five most abundant fatty acids in soybean seeds. It is measured by gas chromatography and is reported as a percent of the total oil content.
Phytophthora Tolerance. Tolerance to Phytophthora root rot is rated on a scale of 1 to 9, with a score of 9 being the best or highest tolerance ranging down to a score of 1 which indicates the plants have no tolerance to Phytophthora.
Phenotypic Score. The Phenotypic Score is a visual rating of general appearance of the variety. All visual traits are considered in the score including healthiness, standability, appearance and freedom of disease. Ratings are scored from 1 being poor to 9 being excellent.
Plant Height. Plant height is taken from the top of soil to top node of the plant and is measured in inches.
Pod. This refers to the fruit of a soybean plant. It consists of the hull or shell (pericarp) and the soybean seeds.
Protein Percent. Soybean seeds contain a considerable amount of protein. Protein is generally measured by NIR spectrophotometry, and is reported on an as is percentage basis.
Pubescence. This refers to a covering of very fine hairs closely arranged on the leaves, stems and pods of the soybean plant.
Quantitative Trait Loci (QTL). Quantitative trait loci (QTL) refer to genetic loci that control to some degree numerically representable traits that are usually continuously distributed.
Regeneration. Regeneration refers to the development of a plant from tissue culture.
Seed Protein Peroxidase Activity. Seed protein peroxidase activity is defined as a chemical taxonomic technique to separate cultivars based on the presence or absence of the peroxidase enzyme in the seed coat. There are two types of soybean cultivars, those having high peroxidase activity (dark red color) and those having low peroxidase activity (no color).
Seed Yield (Bushels/Acre). The yield in bushels/acre is the actual yield of the grain at harvest.
Seeds per Pound. Soybean seeds vary in seed size, therefore, the number of seeds required to make up one pound also varies. This affects the pounds of seed required to plant a given area, and can also impact end uses.
Shattering. The amount of pod dehiscence prior to harvest. Pod dehiscence involves seeds falling from the pods to the soil. This is a visual score from 1 to 9 comparing all genotypes within a given test. A score of 9 means pods have not opened and no seeds have fallen out. A score of 5 indicates approximately 50% of the pods have opened, with seeds falling to the ground and a score of 1 indicates 100% of the pods are opened.
Single Gene Converted (Conversion). Single gene converted (conversion) plant refers to plants which are developed by a plant breeding technique called backcrossing wherein essentially all of the desired morphological and physiological characteristics of a variety are recovered in addition to the single gene transferred into the variety via the backcrossing technique or via genetic engineering.


A safety brake type rollator which is normally in detained state, but it starts to advance when releasing grips installed on both handle bars are gripped, is disclosed. The elaborate utilization of lever principle associated with power transmission between two ratchet wheels realizes innovative effect of the present invention.

1. Field of the Invention
The present invention relates to safety brake type rollator, and more particularly, to a rollator which is normally in detained state, but it starts to advance when releasing grips installed on both handle bars are gripped. The elaborate utilization of lever principle associated with power transmission between two follower blocks and ratchet wheels realizes innovative effect of the present invention.
2. Description of the Prior Art
A conventional rollator is used for helping a patient or disabled person""s activity and assuring his/her security. Accordingly, braking means is indispensable especially for users who are suffering from gout or having trouble in their feet. A rollator should be constructed perfectly firm, secure, and reliable to avoid any possible accident. A braking means like that which applied for a bicycle is generally installed on a conventional rollator for the user to apply a force to braking means to both brake grips at two sides of a handle bar.
Incidentally it is hard for such a handicapped person to stop the rollator timely when an emergency arises, on the contrary. He/she might tumble down and involuntarily push forward the rollator in stead of stopping it by holding the brake grips so that causing a deplorable result. Such is the case that is often encountered by a conventionally designed rollator.
In order to overcome the shortcomings inherent to the conventional technique described above, the present inventor has delved into this matter with a long time efforts and came to realization of the present invention.
It is an object of the present invention to provide a safety brake type rollator having a stable and reliable structure which is normally in detained state unless releasing grips are gripped so as to ensure security of the rollator.
It is another object of the present invention to provide a safety brake type rollator whose braking effect can be adjusted to meet requirements of all kinds of users.
The above object can be achieved by a safety brake type rollator mainly comprising two handle bars each with a releasing grip, two foot bars, an arm rest, and a braking mechanism. The braking mechanism is constituted by two pulling wires each of them conjoined to each releasing grip with its upper end being hinged to a transmission rod at its lower end, the transmission rod is tightened to a serrated follower block below, and the follower block is further teeth combined with a ratchet wheel which is installed coaxially with a rear castor. Being exerted by the resilient force of a coil spring situated on the follower block, the follower block engages its teeth with the ratchet wheel so that the rollator can not move. As the releasing grips are gripped so as to release the downward force of the follower block, the engagement between the follower block and the ratchet wheel is loosened so that the rollator can be free to move.


The present invention is directed to a method for the prophylactic treatment of cataract. The method involves the administration of a compound of Formula I

The present invention relates to a method for the prophylactic treatment of cataracts.
The lens of the eye is a transparent, bi-convex body, which functions as a refractive device to focus light onto the retina. A cataract is an opacity of the lens that adversely affects visual acuity. Cataracts are the leading cause of blindness in the world and incidence of cataract-induced blindness is expected to increase, especially in developing countries. Cataracts can appear at all ages, but are most commonly associated with aging adultsxe2x80x94approximately 90% of adults 70 years and older experience symptoms of cataracts. Cataract surgery accounts for the largest single item in Medicare expenditures. In the United States, approximately 1.2 million cataract surgeries are performed every year at a cost of over $3 billion (Taylor, Journal of the American College of Nutrition, 12(2): 138-146 (1993)).
The precise cause of cataract formation is unclear. Alteration in cell structure, formation of water pockets, and accumulation of high molecular weight proteins are but a few of the changes in lens architecture associated with cataract formation. Loss of transparency has been linked to formation of opaque fibers in the layers of the lens, as well as loss of transparency of previously clear fibers due to protein damage. Accumulation of extracellular materials and pigment also result in loss of transparency and scattering of light.
Various factors, besides age, have been associated with a predisposition to cataracts. Increased risk of cataract formation has been linked to exposure to ultraviolet light, infection, injury to the eye or the head region, exposure to radiation or toxic substances and prolonged use of corticosteroid drugs. These factors, alone or in concert, predispose one to cataracts by affecting the fibers and the biochemical reactions occurring naturally in the lens. Systemic disease, such as diabetes mellitus, also increases the risk of cataracts. In fact, it has been estimated that diabetics are three to four times more likely to develop cataracts than non-diabetics (Bunce et al., Annual Review of Nutrition 10: 223-254 (1990)). While the mechanism of action is unclear, it is believed that osmotic pressure increases with an increase in sugar molecules in the lens and leads to swelling of the lens and subsequently clouded vision.
Symptoms of cataracts include blurred and double vision, color confusion and reduced vision at night and in low light. As vision gradually deteriorates over time, affected individuals lose the ability to accomplish everyday tasks. Decreased vision results in difficulty in reading and watching television. Many have difficulty driving, especially at night. As such, many patients must alter their lifestyles and give up much of their independence. Cataract patients also have an increased risk of injury due to impaired vision.
Unless cataracts seriously interfere with vision and lifestyle, vision correction is accomplished by the prescribing of glasses or contact lenses. Ultimately, however, surgery is required to remove the cataract, once contact lenses and glasses are insufficient to maintain vision. Surgery is comprised of cataract extraction, wherein the affected lens is removed, and, in most cases, replaced with an artificial lens. Cataract surgery can be an outpatient procedure and accomplished with local anesthetic. Still, many complications can arise during and after surgery. Tearing of the capsule of the lens can cause the posterior capsule to rupture, thereby losing the lens to the vitreous cavity. Hemorrhage during surgery can stimulate inflammation and accelerate opacification of the capsule. Epithelial cells can invade the wound into the cornea, iris, and lens capsule, thereby causing uveitis and corneal decompensation. Retinal detachment is also a risk following cataract surgery. A rise in intraocular pressure is common after cataract surgery and causes glaucoma-like symptoms.
Given the prevalence of cataracts, the absence of any mode of prevention of cataracts, and the absence of any mode of treatment beyond surgery, there remains a need for an effective prophylactic treatment of cataracts. Accordingly, it is a principal object of the present invention to provide a method of prophylactically treating cataracts. This and other objects of the present invention will become apparent from the detailed description provided herein.
The present invention is directed to a method for the prophylactic treatment of cataract. The method involves the administration of a compound of the formula:
wherein V, W and X are selected from the group consisting of hydro, hydroxyl, alkoxy, halo, an ester, an ether, a carboxylic acid group, a pharmaceutically acceptable salt of a carboxylic acid group, and xe2x80x94SR, in which R is hydrogen or an alkyl group, Y is selected from the group consisting of oxygen, sulfur, C(OH), and Cxe2x95x90O, and Z is selected from the group consisting of hydro and C(O)OR1, wherein R1 is an alkyl. Preferably, the alkoxy is a C1-C6 alkoxy. Preferably, the halo is fluorine, chlorine or bromine. Preferably, the ester is a C1-C6 ester. Preferably, the ether is a C1-C6 ether. Preferred pharmaceutically acceptable salts of the carboxylic acid group include sodium and potassium salts. Preferably, the alkyl groups are C1-C6 alkyl groups. Desirably, the compound of Formula I is genistein.
The present invention is predicated on the discovery that compounds of Formula I are effective in the prevention of cataracts. Accordingly, the present invention provides a method for the prophylactic treatment of cataracts. By xe2x80x9cprophylacticxe2x80x9d is meant the protection, in whole or in part, against cataract formation. The present inventive method is particularly useful in the inhibition of age-related cataracts and diabetic cataracts. However, the present inventive method is also useful in the treatment of cataracts that have been or are being treated with surgery, cataracts that occur after surgical removal of an existing opacified lens, i.e., secondary cataracts, cataracts that occur after retinal detachment and surgery to repair the retinal detachment, cataracts associated with trauma to the eye or head, cataracts associated with tumors, cataracts associated with exposure to radiation, and cataracts associated with toxicity. The present inventive method is also useful in the prophylactic treatment of cataracts resulting from systemic disorders, for example, but not limited to, galactosemia, Farry""s disease, Lowe""s syndrome, Alport""s syndrome and dystrophia myotonica, as well as dermatologic disorders, such as atopy, ichthyosis, Rothmund-Thompson syndrome, Werner""s syndrome, incontinentia pigment and Cockayne""s syndrome. The present inventive method is also useful in the prevention of cataract formation due to central nervous system disorders, such as neurofibromatosis type II, Zellweger syndrome and Norrie""s disease, and local ocular disease, such as glaucoma, uveitis, retinitis pigmentosa, gyrate atrophy, degenerative myopia, ischemia and infection.
The method comprises the administration of a compound of Formula I in an amount sufficient to treat the lens for cataract prophylactically. Accordingly, a compound for use in the method of the present invention is a compound of the following formula:
wherein V, W and X are selected from the group consisting of hydro, hydroxyl, alkoxy, halo, an ester, an ether, a carboxylic acid group, a pharmaceutically acceptable salt of a carboxylic acid group, and xe2x80x94SR, in which R is hydrogen or an alkyl group, and Y is selected from the group consisting of oxygen, sulfur, C(OH), and Cxe2x95x90O, and Z is selected from the group consisting of hydro and C(O)OR1, wherein R1 is an alkyl. Preferably, the alkoxy is a C1-C6 alkoxy. Preferably, the halo is fluorine, chlorine or bromine. Preferably, the ester is a C1-C6 ester. Preferably, the ether is a C1-C6 ether. Preferred pharmaceutically acceptable salts of the carboxylic acid group include sodium and potassium salts. Preferably, the alkyl groups are C1-C6 alkyl groups. Preferably, the compound of Formula I is genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), a pharmaceutically acceptable analogue thereof, a pharmaceutically acceptable prodrug thereof, or a pharmaceutically acceptable salt of any of the foregoing.
The prodrug can be any pharmaceutically acceptable prodrug of genistein, a pharmaceutically acceptable, cataract-inhibiting analogue of genistein, or a pharmaceutically acceptable salt of either of the foregoing. One of ordinary skill in the art will appreciate, however, that the prodrug used must be one that can be converted to an active cataract-inhibiting compound in or around the lens of the eye. A preferred prodrug is a prodrug that increases the lipid solubility of genistein, an analogue of genistein, or a pharmaceutically acceptable salt of either of the foregoing. A preferred prodrug is one in which one or more of V, W and X are independently derivatized with an ester, such as pivalic acid.
Compounds of Formula I are widely available commercially. For example, genistein is available from LC Laboratories (Woburn, Mass.). Those compounds that are not commercially available can be readily prepared using organic synthesis methods known in the art.
Whether or not a particular analogue, prodrug or pharmaceutically acceptable salt of a compound in accordance with the present invention can treat cataract formation prophylactically can be determined, for example, by its effect in the rat model used in Example 1.
The compound for use in the method of the present invention can be bound to a suitable matrix, such as a polymeric matrix, if desired, for use in the present inventive method. Any of a wide range of polymers can be used in the context of the present invention provided that, if the polymer-bound compound is to be used in vivo, the polymer is biologically acceptable (see, e.g., U.S. Pat. Nos. 5,384,333 and 5,164,188).
An advantage of genistein is that it is very safe and efficacious. For example, when genistein was orally administered to Zucker diabetic fatty rats, genistein was found to be nontoxic to the retina at dosages ranging from 75 mg/kg/day to 300 mg/kg/day over a period of six months as measured by electroretinography. In addition, oral administration of genistein was found to have no effect on food intake and body weight for male and female rats. Also, no effect of orally administered genistein was found with respect to the weight of the ovaries and the uterus in female rats.
The compound of Formula I, which is preferably genistein, a pharmaceutically acceptable analogue of genistein, a pharmaceutically acceptable prodrug of genistein, or a pharmaceutically acceptable salt of any of the foregoing, can be administered in accordance with the present inventive method by any suitable route. Suitable routes of administration include systemic, such as orally or by injection, topical, periocular (e.g., subTenon""s), subconjunctival, intraocular, subretinal, suprachoroidal, and retrobulbar. The manner in which the compound is administered for the prevention of cataract is dependent, in part, upon the cause of cataract formation.
For example, given that cataract is a risk associated with diabetes mellitus, the compound can be administered as soon as a subject is diagnosed with diabetes. For the prophylactic treatment of cataract that can result from diabetes, the compound is preferably administered systemically, e.g., orally or by injection, although intraocular administration is also acceptable. The compound is preferably administered intraocularly for the prophylactic treatment of secondary cataract formation following cataract surgery.
The prevention of cataract associated with trauma, such as to the eye or head, tumors, exposure to radiation, exposure to toxicity, systemic disorders (for example, but not limited to, galactosemia, Farry""s disease, Lowe""s syndrome, Alport""s syndrome and dystrophia myotonica), dermatologic disorders (such as atopy, ichthyosis, Rothmund-Thompson syndrome, Werner""s syndrome, incontinentia pigment and Cockayne""s syndrome), central nervous system disorders (such as neurofibromatosis type II, Zellweger syndrome and Norrie""s disease) and local ocular disease (e.g., glaucoma, uveitis, retinitis pigmentosa, gyrate atrophy, degenerative myopia, ischemia and infection) involves the administration of the compound by any suitable method, although intraocular administration is often preferred.
The compound of Formula I for use in the present inventive method is preferably administered as soon as possible after it has been determined that an animal, such as a mammal, specifically a human, is at risk for cataract. Treatment will depend, in part, upon the particular compound of Formula I used, the amount of the compound administered, the route of administration, and the cause and extent, if any, of cataract formation realized.
One skilled in the art will appreciate that suitable methods of administering a compound of Formula I, which is useful in the present inventive method, are available. Although more than one route can be used to administer a particular compound of the present inventive method, a particular route can provide a more immediate and more effective reaction than another route. Accordingly, the described routes of administration are merely exemplary and are in no way limiting.
The dose administered to an animal, particularly a human, in accordance with the present invention should be sufficient to effect the desired response in the animal over a reasonable time frame. One skilled in the art will recognize that dosage will depend upon a variety of factors, including the strength of the particular compound of Formula I employed, the age, species, condition or disease state, and body weight of the animal. The size of the dose also will be determined by the route, timing and frequency of administration as well as the existence, nature, and extent of any adverse side effects that might accompany the administration of a particular compound of Formula I and the desired physiological effect. It will be appreciated by one of ordinary skill in the art that various conditions or disease states, in particular, chronic conditions or disease states, may require prolonged treatment involving multiple administrations.
Suitable doses and dosage regimens can be determined by conventional range-finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. The present inventive method will typically involve the administration of from about 1 mg/kg/day to about 100 mg/kg/day, preferably from about 15 mg/kg/day to about 50 mg/kg/day, if administered systemically. Intraocular administration typically will involve the administration of from about 0.1 mg total to about 5 mg total, preferably from about 0.5 mg total to about 1 mg total. A preferred concentration for topical administration is 100 xcexcM.
Compositions for use in the present inventive method preferably comprise a pharmaceutically acceptable carrier and an amount of a compound of Formula I sufficient to inhibit cataract formation. The carrier can be any of those conventionally used and is limited only by chemico-physical considerations, such as solubility and lack of reactivity with the compound, and by the route of administration. It will be appreciated by one of ordinary skill in the art that, in addition to the following described pharmaceutical compositions, the compound of Formula I can be formulated as polymeric compositions, inclusion complexes, such as cyclodextrin inclusion complexes, liposomes, microspheres, microcapsules and the like (see, e.g., U.S. Pat. Nos. 4,997,652, 5,185,152 and 5,718,922).
The compound of Formula I can be formulated as a pharmaceutically acceptable acid addition salt. Examples of pharmaceutically acceptable acid addition salts for use in the pharmaceutical composition include those derived from mineral acids, such as hydrochloric, hydrobromic, phosphoric, metaphosphoric, nitric and sulfuric acids, and organic acids, such as tartaric, acetic, citric, malic, lactic, fumaric, benzoic, glycolic, gluconic, succinic, and arylsulphonic, for example p-toluenesulphonic, acids.
The pharmaceutically acceptable excipients described herein, for example, vehicles, adjuvants, carriers or diluents, are well-known to those who are skilled in the art and are readily available to the public. It is preferred that the pharmaceutically acceptable carrier be one which is chemically inert to the compound and one which has no detrimental side effects or toxicity under the conditions of use.
The choice of excipient will be determined in part by the compound of Formula I, as well as by the particular method used to administer the composition. Accordingly, there is a wide variety of suitable formulations of the pharmaceutical composition of the present invention. The following formulations are merely exemplary and are in no way limiting.
Injectable formulations are among those that are preferred in accordance with the present inventive method. The requirements for effective pharmaceutically carriers for injectable compositions are well-known to those of ordinary skill in the art (see Pharmaceutics and Pharmacy Practice, J.B. Lippincott Co., Philadelphia, Pa., Banker and Chalmers, eds., pages 238-250 (1982), and ASHP Handbook on Injectable Drugs, Toissel, 4th ed., pages 622-630 (1986)). It is preferred that such injectable compositions be administered intramuscularly, intravenously or intraperitoneally.
Topical formulations are well-known to those of skill in the art. Such formulations are suitable in the context of the present invention for application to the skin. The use of patches, corneal shields (see, e.g., U.S. Pat. No. 5,185,152), and ophthalmic solutions (see, e.g., U.S. Pat. No. 5,710,182) and ointments, e.g., eye drops, is also within the skill in the art.
Formulations suitable for oral administration can consist of (a) liquid solutions, such as an effective amount of the compound dissolved in diluents, such as water, saline, or orange juice; (b) capsules, sachets, tablets, lozenges, and troches, each containing a predetermined amount of the active ingredient, as solids or granules; (c) powders; (d) suspensions in an appropriate liquid; and (e) suitable emulsions. Liquid formulations may include diluents, such as water and alcohols, for example, ethanol, benzyl alcohol, and the polyethylene alcohols, either with or without the addition of a pharmaceutically acceptable surfactant, suspending agent, or emulsifying agent. Capsule forms can be of the ordinary hard- or soft-shelled gelatin type containing, for example, surfactants, lubricants, and inert fillers, such as lactose, sucrose, calcium phosphate, and corn starch. Tablet forms can include one or more of lactose, sucrose, mannitol, corn starch, potato starch, alginic acid, microcrystalline cellulose, acacia, gelatin, guar gum, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, calcium stearate, zinc stearate, stearic acid, and other excipients, colorants, diluents, buffering agents, disintegrating agents, moistening agents, preservatives, flavoring agents, and pharmacologically compatible excipients. Lozenge forms can comprise the active ingredient in a flavor, usually sucrose and acacia or tragacanth, as well as pastilles comprising the active ingredient in an inert base, such as gelatin and glycerin, or sucrose and acacia, emulsions, gels, and the like containing, in addition to the active ingredient, such excipients as are known in the art.
Formulations suitable for parenteral administration include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain anti-oxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. The inhibitor can be administered in a physiologically acceptable diluent in a pharmaceutical carrier, such as a sterile liquid or mixture of liquids, including water, saline, aqueous dextrose and related sugar solutions, an alcohol, such as ethanol, isopropanol, or hexadecyl alcohol, glycols, such as propylene glycol or polyethylene glycol, dimethylsulfoxide, glycerol ketals, such as 2,2-dimethyl-1,3-dioxolane-4-methanol, ethers, such as poly(ethyleneglycol) 400, an oil, a fatty acid, a fatty acid ester or glyceride, or an acetylated fatty acid glyceride, with or without the addition of a pharmaceutically acceptable surfactant, such as a soap or a detergent, suspending agent, such as pectin, carbomers, methylcellulose, hydroxypropylmethylcellulose, or carboxymethylcellulose, or emulsifying agents and other pharmaceutical adjuvants. Oils, which can be used in parenteral formulations include petroleum, animal, vegetable, or synthetic oils. Specific examples of oils include peanut, soybean, sesame, cottonseed, corn, olive, petrolatum, and mineral.
Suitable fatty acids for use in parenteral formulations include oleic acid, stearic acid, and isostearic acid. Ethyl oleate and isopropyl myristate are examples of suitable fatty acid esters.
Suitable soaps for use in parenteral formulations include fatty alkali metals, ammonium, and triethanolamine salts, and suitable detergents include (a) cationic detergents such as, for example, dimethyl dialkyl ammonium halides, and alkyl pyridinium halides, (b) anionic detergents such as, for example, alkyl, aryl, and olefin sulfonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates, (c) nonionic detergents such as, for example, fatty amine oxides, fatty acid alkanolamides, and polyoxyethylenepolypropylene copolymers, (d) amphoteric detergents such as, for example, alkyl-p-aminopropionates, and 2-alkyl-imidazoline quaternary ammonium salts, and (e) mixtures thereof.
The parenteral formulations will typically contain from about 0.5 to about 25% by weight of the active ingredient in solution. Preservatives and buffers may be used. In order to minimize or eliminate irritation at the site of injection, such compositions may contain one or more nonionic surfactants having a hydrophile -lipophile balance (HLB) of from about 12 to about 17.
The quantity of surfactant in such formulations will typically range from about 5 to about 15% by weight. Suitable surfactants include polyethylene sorbitan fatty acid esters, such as sorbitan monooleate and the high molecular weight adducts of ethylene oxide with a hydrophobic base, formed by the condensation of propylene oxide with propylene glycol. The parenteral formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid excipient, for example, water, for injections, immediately prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described.
Such compositions can be formulated as intraocular formulations, sustained-release formulations or devices (see, e.g., U.S. Pat. No. 5,378,475). For example, gelantin, chondroitin sulfate, a polyphosphoester, such as bis-2-hydroxyethyl-terephthalate (BHET), or a polylactic-glycolic acid (in various proportions) can be used to formulate sustained-release formulations. Implants (see, e.g., U.S. Pat. Nos. 5,443,505, 4,853,224 and 4,997,652), devices (see, e.g., U.S. Pat. Nos. 5,554,187, 4,863,457, 5,098,443 and 5,725,493), e.g., a mechanical reservoir, an intraocular device or an extraocular device with an intraocular conduit (e.g., 100 xcexc-1 mm in diameter), or an implant or a device comprised of a polymeric composition as described above, can be used.
The present inventive method can involve the co-administration of other pharmaceutically active compounds useful in the treatment of cataracts. By xe2x80x9cco-administrationxe2x80x9d is meant administration before, concurrently with, e.g., in combination with a compound of Formula I in the same formulation or in separate formulations, or after administration of a compound of Formula I as described above. Preferably, a compound of Formula I can be co-administered with an aldose reductase inhibitor, an antioxidant, or both. Preferably, the aldose reductase inhibitor is selected from the group consisting of carboxylic acids, hydranthoids and related imides. The antioxidant is preferably selected from the group consisting of ascorbic acid, tocopherol, carotenoids, butylated hydroxyanisol, butylated hydroxytoluene, and riboflavin. More preferably, the aldose reductase inhibitor is ponalrestat, epalrestat, sorbinil, imirestat, AND-138, CT-112, zopolrestat, zenarestat, BAL-AR18, AD-5467, M-79175, tolrestat, SPR-210 or oxygen. The carotenoid is preferably zeaxanthin or lutein.
The present invention also provides for co-administration of compounds of Formula I with other pharmaceutically active compounds. For example, corticosteroids, e.g., prednisone, methylprednisolone, dexamethasone, or triamcinalone acetinide, or noncorticosteroid anti-inflammatory compounds, such as ibuprofen or flubiproben, can be co-administered. Similarly, vitamins and minerals, e.g., zinc, and micronutrients can be co-administered. In addition, inhibitors of the protein tyrosine kinase pathway, which include natural protein tyrosine kinase inhibitors like quercetin, lavendustin A, erbstatin and herbimycin A, and synthetic protein tyrosine kinase inhibitors like tyrphostins (e.g., AG490, AG17, AG213 (RG50864), AG18, AG82, AG494, AG825, AG879, AG1112, AG1296, AG 1478, AG126, RG13022, RG14620 and AG555), dihydroxy- and dimethoxybenzylidene malononitrile, analogs of lavendustin A (e.g., AG814 and AG957), quinazolines (e.g., AG1478), 4,5-dianilinophthalimides, and thiazolidinediones, can be co-administered with genistein or an analogue, prodrug or pharmaceutically acceptable salt thereof (see Levitzki et al., Science 267: 1782-1788 (1995); and Cunningham et al., Anti-Cancer Drug Design 7: 365-384 (1992)). In this regard, potentially useful derivatives of genistein include those set forth in Mazurek et al., U.S. Pat. No. 5,637,703. Selenoindoles (2-thioindoles) and related disulfide selenides, such as those described in Dobrusin et al., U.S. Pat. No. 5,464,961, are useful protein tyrosine kinase inhibitors. Neutralizing proteins to growth factors, such as a monoclonal antibody that is specific for a given growth factor, e.g., VEGF (for an example, see Aiello et al., PNAS USA 92: 10457-10461 (1995)), or phosphotyrosine (Dhar et al., Mol. Pharmacol. 37: 519-525 (1990)), can be co-administered. Other various compounds that can be co-administered include inhibitors of protein kinase C (see, e.g., U.S. Pat. Nos. 5,719,175 and 5,710,145), cytokine modulators, an endothelial cell-specific inhibitor of proliferation, e.g., thrombospondins, an endothelial cell-specific inhibitory growth factor, e.g., TNFxcex1, an anti-proliferative peptide, e.g., SPARC and prolferin-like peptides, a glutamate receptor antagonist, aminoguanidine, an angiotensin-converting enzyme inhibitor, e.g., angiotensin II, calcium channel blockers, "psgr"-tectorigenin, ST638, somatostatin analogues, e.g., SMS 201-995, monosialoganglioside GM1, ticlopidine, neurotrophic growth factors, methyl-2,5-dihydroxycinnamate, an angiogenesis inhibitor, e.g., recombinant EPO, a sulphonylurea oral hypoglycemic agent, e.g., gliclazide (non-insulin-dependent diabetes), ST638(Asahi et al., FEBS Letter 309: 10-14 (1992)), thalidomide, nicardipine hydrochloride, aspirin, piceatannol, staurosporine, adriamycin, epiderstatin, (+)-aeroplysinin-1, phenazocine, halomethyl ketones, anti-lipidemic agents, e.g., etofibrate, chlorpromazine, spinghosines and retinoic acid and analogues thereof (Burke et al., Drugs of the Future 17(2):119-131 (1992); and Tomlinson et al., Pharmac. Ther. 54: 151-194 (1992)).

Method for the prophylactic treatment of cataracts

Abstract: wherein V, W and X are selected from the group consisting of hydro, hydroxyl, alkoxy, halo, an ester, an ether, a carboxylic acid group, a pharmaceutically acceptable salt of a carboxylic acid group, and xe2x80x94SR, in which R is hydrogen or an alkyl group, Y is selected from the group consisting of oxygen, sulfur, C(OH), and Cxe2x95x90O, and Z is selected from the group consisting of hydro and C(O)OR1, wherein R1 is an alkyl, or an analogue or prodrug thereof or a pharmaceutically acceptable salt of any of the foregoing to an animal, such as a mammal, in particular a human, in an amount sufficient to treat cataracts prophylactically. The compound of Formula I is preferably genistein.

Johns Hopkins University, School of Medicine


An apparatus, system, and method are disclosed for managing tray devices. A tray slot module creates a tray slot object of a tray slot class that extends a SMI-S CIM CIM_Slot class. The tray slot object describes a tray slot. A tray physical package module creates a tray physical package object of a tray physical package class that extends a SIM-S CIM CIM_PhysicalPackage class. The tray physical package object describes a tray device, references the tray slot object, and comprises a universal unique identifier. A tray object module creates a tray object of a tray class that extends SMI-S CIM CIM_LogicalDevice class. The tray object describes a tray, is referenced by a SMI-S CIM CIM_ComputerSystem object, references the tray physical package object, and comprises a device identifier. A management module manages the tray device using the tray slot object, tray physical package object, and tray object.

1. Field of the Invention
This invention relates to tray devices and more particularly relates to managing tray device.
2. Description of the Related Art
A data processing system may employ one or more device trays, referred to herein as trays. The trays may mount tray devices such as hard disk drives, processors, and the like. A tray may allow a tray device to communicate with the data processing system through a connector. The tray may also provide power, cooling, and the like for the tray device.
The tray may allow an administrator to easily add tray devices to or remove tray devices from the data processing system. For example, the administrator may remove a first hard disk drive from the tray and replace the first hard disk drive with a second hard disk drive.
Data processing systems are often heterogeneous environments, with hardware components and software from many suppliers working together. As a result, standards have been developed to coordinate interoperability between hardware and software components from different suppliers.
For example, the Storage Networking Industry Association's Storage Management Initiative (SMI) was created to develop and standardize interoperable storage management technologies for the storage, networking and end user communities. The Storage Networking Industry Association published a SMI specification (SMI-S) that includes a Common Information Model (CIM). The CIM defines software classes that can be used to create objects that facilitate communications between disparate hardware and software components.
Unfortunately, SMI-S CIM does not include classes for objects that manage trays. As a result, vendors often must employ ad hoc solutions to manage trays in data processing systems.

Apparatus, system, and method for managing tray devices

International Business Machines Corporation