There is provided an apparatus for preventing and removing fog at an airport runway. The apparatus includes: a water tank 10 buried in a ground around a runway; a water tank temperature sensor 20 for sensing a water temperature in the water tank; a heater 30 provided inside the water tank, for heating water contained in the water tank; a cooling device 40 provided inside the water tank, for cooling water contained in the water tank; the sprinklers 50 installed at opposite sides along the runway and over the ground around the runway, and supplied with the water from the water tank to spray water towards the atmosphere over and around the runway; and a controller 60 controlling, on the basis of the water temperature of the water tank measured using the temperature sensor, operation of the sprinklers, the heater, and the cooling device, according to an externally inputted operational signal.

Generally, the occurrence of fog at the airport may frequently cause the cancellation of the aircraft flights. It causes delayed departure of passengers and air cargo transports, leading to inefficiency of the work. Further, it causes delayed arrival of aircraft, thus leading to vast economic loss, such as aircraft fuel consumption due to a circular flight over the airport. Also, the aircrafts may be exposed to danger due to poor visibility. Thus, the occurrence of fog at the airport causes the above and other various problems.
To solve the above mentioned problems, there have recently been proposed apparatuses or methods for preventing the frequent occurrence of fog at a runway and for removing the fog having occurred. The examples can be found in Korean patent application No. 10-2001-0041660, entitled "System for removing fog" and Korean utility model application No. 20-2001-0014033, entitled "Apparatus for preventing and removing fog at a runway using compressed air".
The former invention removes fog by evaporating nitrogen and oxygen liquids over a fog area to separate moisture contained in the fog, and simultaneously, by spraying dried and hot nitrogen and oxygen gases through nozzles towards the fog area to remove the above moisture. The latter invention has an air compression chamber around a runway, from which compressed air is sprayed through a vertical discharging pipe installed around the runway, which causes a turbulent flow used to remove the fog.

Apparatus for preventing and removing fog at runway using sprinklers


A gate apparatus is provided a convey path enabling an IC card (ID information storage medium) to be inserted and discharged from either of a front side and a rear side of the gate apparatus and, therefore, entering/exiting can be monitored by the single gate apparatus. A CPU determines the direction of discharge of the IC card on the basis of detection results of a card sensor and a door state detecting means. Thus, entering/exiting information can exactly be understood.

1. Field of the Invention
The present invention relates to a gate apparatus, installed at an entrance/exit of a specified area where secrecy is required, such as a factory or a research center, for monitoring and managing incoming/outgoing of a person or an object (e.g. vehicle) by using an ID information recording medium such as an ID card.
2. Description of the Related Art
A conventional gate apparatus is installed on the entrance side of a specified area, e.g. a research center, thereby managing incoming data of an owner of an ID card. When the owner of the ID card inserts the card into the gate apparatus, the lock is deactivated, and the card owner can open the door and enter the specified area. In this case, through a sequence of operations, three data items on the card owner, the deactivation of the lock and the opening of the door are obtained. Based on these data items, it is judged whether the card owner has entered the specified area.
However, in the conventional gate apparatus, information necessary for judging the incoming of the card owner is insufficient. Thus, it is only supposed that the card owner has entered the specified area, and it is not surely recognized that the card owner has entered. In addition, in order to monitor the incoming and outgoing of the card owner, it is necessary to provide separate gate apparatuses on the entrance side and exit side, causing problems with respect to the location and cost for installation of the gate apparatuses.

Gate apparatus using ID information recording medium


This invention is related to a metal hydride storage canister, comprising a storage canister body, a wafer baffle stacked on the body for containing metal hydride of a pre-determined amount, and a tubing having a porous surface for securing the wafer baffle in the body and for guiding hydrogen discharged from the metal hydride to an outlet of the body. This invention further discloses the manufacture of the storage canister.

Not Applicable
Not Applicable
1. Field of the Invention
This invention is related to a metal hydride storage canister, particularly a canister for use with a hydrogen fuel cell. The canister enhances thermal conductivity and provides space required by the expansion of the metal hydride. This invention further discloses the manufacture of the storage canister.
2. Description of the Related Art
With the rapid growth of human civilization the consumption of traditional energy sources, such as coal, oil and natural gas, increases rapidly. This results in serious pollution to the global environment and causes various environmental problems such as global warming and acid rain. It is now recognized that the existing natural energy resources are limited. Therefore, if the present rate of energy consumption continues, all existing natural energy sources will be exhausted in the near future. Accordingly, many developed countries are dedicated to the research and development of new and alternative energy sources. The fuel cell is one of the most important and reasonably priced energy sources. Compared with traditional internal combustion engines, the fuel cell has many advantages such as high-energy conversion efficiency, clean exhaust, low noise, and no consumption of traditional gasoline.
In brief, a fuel cell is an electrical power generation device powered by the electrochemical reaction of hydrogen and oxygen. Basically, the reaction is a reverse reaction of the electrolysis of water, which converts the chemical energy into electrical energy. The basic structure of a fuel cell, for example, a proton exchange membrane fuel cell, comprising a plurality of cell units. Each cell unit contains a proton exchange membrane (PEM) at the middle, with the two sides thereof provided with a layer of catalyst. Each of the two outsides of the catalyst is further provided with a gas diffusion layer (GDL). An anode plate and a cathode plate are further provided at the outermost sides adjacent to the GDL. After all of the above elements are combined together, a cell unit is formed.
For the practical application of a fuel cell, a plurality of the above cell units are stacked and serially connected to form a cell stack for providing sufficient power, The cell stack is positioned between two end plates provided at the longitudinal, opposing ends of the cell stack. A plurality of tie rods pass through a peripheral region of each end plate for positioning the cell stack between the two end plates.
While performing the aforesaid reverse reaction of the electrolysis of water, in order to convert the chemical energy into electrical energy, the cell stack must be maintained under a consistent pressure range. This ensures that the reverse reaction of the electrolysis of water is performed under the optimum pressure condition to enhance the conversion efficiency of the chemical energy into electrical energy.
One known measure of storing hydrogen is to use the so-called metal hydride. Metal hydride is able to discharge hydrogen at a pressure corresponding to the temperature that it experiences; the process of releasing hydrogen is an endothermic reaction. When the hydrogen stored within the metal hydride has been completely exhausted, pure hydrogen can be re-charged back to the metal hydride; the process of charging hydrogen is an exothermic reaction. The temperature that metal hydride experiences is positively proportional to the pressure of the hydrogen to be discharged from the metal hydride. Such a proportional relationship may vary among metal hydrides furnished by different suppliers.
Due to the highly combustive characteristic of hydrogen, an easy and convenient method for pre-storing hydrogen within a specific container, and for releasing hydrogen as required for performing the above reverse reaction, is needed. The commonly known storage container is mostly a metal container capable of sustaining a pre-determined pressure and temperature. The container is sealed after a pre-determined amount of metal hydride is loaded therein.
Since the volume of metal hydride increases 5 to 20% after being charged with hydrogen, excessive space must be reserved when loading the metal hydride into the container to provide the space required by expansion of the metal hydride. Expansion of the metal hydride will easily cause compaction of the metal hydride when it is placed within a mutual space in conventional containers. The exothermic reaction during the process of charging hydrogen may cause an increment in temperature thereby, reducing the rate of charging hydrogen, such that the process must rely on the container surface to release the thermal energy to reduce the temperature. On the contrary, the endothermic reaction during the process of discharging hydrogen also relies on the container surface to absorb heat to efficiently increase rate of heat transfer. The mechanism for enhancing the rate of heat transfer is essential because metal hydride has a relatively low thermal conductivity. Furthermore, an easy passageway is needed for guiding the hydrogen discharged from the metal hydride to an outlet of the container.
It should also be noted that aside from fuel cells, the metal hydride storage canister according to this invention could also be adapted in other applications, such as hydrogen driven pumps, and hydrogen driven air-conditioners.
It is a primary objective of this invention to overcome the defects of conventional containers:
to provide a storage canister capable of enhancing thermal conductivity
to reduce compactness among the metal hydride
to prevent cracks found in the metal hydride stack
to provide an easy passageway for guiding the hydrogen discharged from the metal hydride to an outlet of the canister
This will effectively enhance the operative efficiency of the fuel cell.
The major technical content of this invention mainly uses a wafer baffle made of a thermally conductive material placed in a storage canister for containing metal hydride, and a plurality of porous tubings for securing the wafer baffle in the storage canister as well as for guiding hydrogen discharged from the metal hydride to an outlet of the storage canister. This invention further discloses the manufacture of the storage canister.
The structures and characteristics of this invention can be realized by referring to the appended drawings and explanations of the preferred embodiments.

Metal hydride storage canister design and its manufacture

Asia Pacific Fuel Cell Technologies, Ltd.


A technique for controlling membrane denaturation reactions other than physical shear force was developed. For example, the present invention provides, a method for causing membrane disruption at a specific site by reacting a stimulus such as light with a compound that is activated by the stimulus, where the reaction occurs on a membrane such as a biomembrane. It also provides a membrane structure such as cells in which a specific site has been disrupted, which are obtained by the present method. Introduction of substances such as genes also became possible by using this membrane structure. Further provided is a membrane-destroying member for disrupting a membrane at a specific site. Thus, the present invention enabled, for example, easy membrane penetration using components constituting microelectrodes, micromanipulators, and microinjectors, which were conventionally hardly usable in penetrating cell membranes.

The present invention relates to a method for perforating a membrane by partially treating the membrane (cell membrane, etc.) with a membrane-denaturing agent, etc. It also relates to a membrane-disrupting material having a membrane-denaturing effect.
In gene therapy and artificial substance production systems using living organisms, means of introducing a nucleic acid, a protein, and such, into the interior of a cell are extremely important. On the other hand, techniques for extracting structures such as the nucleus of a cell, are also gaining wide attention. In other words, it can be said that injecting and extracting substances into/from cells, the basic unit constituting organisms, is a fundamental technique of bioengineering.
Conventional substance introduction techniques can be roughly categorized as follows:
a) Introduction techniques targeting non-specific cell groups
b) Introduction techniques targeting a specific cell
Examples of technique a) are, those using viral vectors (retroviral vectors, etc.), non-viral vectors (lipofectin, etc.), electroporation, calcium phosphate method, particle-gun method, etc. Technique b) could be exemplified by the microinjection method (xe2x80x9cFundamental techniques of gene therapyxe2x80x9d, Youdosha (1995)).
Generally, technique b) is used against large cells, such as egg cells. One reason for this is that the microinjection method uses shear force of a capillary glass tube to disrupt the cell membrane, and therefore, a technical limit probably arises due to the cell size. Also, this method requires skilled experience on the part of the handler, and therefore, automation is difficult. Furthermore, in many cases the pipette cannot be inserted due to the flexibility of the cell membrane of normal cells, except egg cells.
In technique a), a non-specific cell group is randomly treated, and it is hoped that the objective substance will be introduced to a part of the cell group. Therefore, very rarely does the objective substance get introduced into all cells. Also, it is generally difficult to separate only cells into which the objective substance has been introduced.
Moreover, a sophisticated micromanipulator is required to extract structures within the cell without causing them any damage, having drawbacks similar to the above microinjection method.
Thus, at a time when cell treatment has become a routine technique in medicine/engineering, the enhancement of reproducibility/precision of cell treatments is a vital issue. For example, when treating reproductive cells, considering that only an extremely small amount of egg cells can be obtained from each individual animal compared to somatic cells, an egg cell is a valuable genetic resource. Therefore, the fact that the success rate of their treatment largely depends on the technical experience of the technician is a grave problem from an engineering point-of-view.
Furthermore, all the above treatments were limited to single cells, migratory cells, or cells such as cancer cells that could be isolated/re-introduced from/into the body. Therefore, it was extremely difficult to modify treatments so that they could be used for cells that are inseparable from the body, such as nerve cells.
Other than the above examples, the possibility of technological developments that owe to cell modifications is on the increase. A few typical examples are,
1) To produce cloned animals, it is necessary to inject the nucleus as or chromosomal genes via the egg cell membrane, but the success rate of this procedure, is extremely low.
2) It a specific cell into which a magnetic structure has been incorporated can be made, it will be possible to magnetically control the location of the cell. The method of introducing magnetic bacteria-derived magnetosome-formation gene is generally used, and although there are successful examples, in most cases it is suitable to insert artificial magnetic structures when using cells, and such, for medical purposes.
3) When preparing micromachines such as micro surgical instruments, it is easily postulated that a cutting output sufficient for dissecting the cell membrane would not be obtained by mere physical means. Also, membrane disruption by mere chemical reactions would have problems regarding the regulation of the disruption.
4) In measuring action potential/electric stimulation of nerve cells, the measurement/stimulation were both done extracellularly by practical electrodes, except in fundamental research. This was the causative problem impeding the enhancement of precision, since it weakened the detection signal and increased stimulation input compared to the potential threshold value involved in original neuro activities. If it is possible to implant an electrode within nerve cells, not only would a measurement/stimulation equivalent to the original potential threshold value of nerves become possible, it will also enable information exchange between the electrode and nerve with a one-to-one precision.
5) In the field of energy conversion engineering, studies on placing micro photoelectric converting elements comprising photo potential onto artificial membranes are being conducted aiming at artificial photosynthesis. This approach aims to use the electromotive force given by photoelectric converting elements to generate transmembrane potential. If it becomes possible to place such micro photoelectric converting elements within cell membranes/mitochondrial membranes, it will enable the use of light to supply the energy needed for cellular metabolisms. Namely, it might be possible supplement various cells the ability to use photo energy just as the plants do.
A fundamental problem underlying these cell treatments is the lack of techniques that could control the disruption of the cell membrane. Various toxins have been examined for long for the purpose of just disrupting the cell. However, they could not respond to the demands of cytoengineering, which is to partially, and temporarily disrupt the cell membrane without causing cell death. Also there were limitations to the method utilizing physical shear force by using micro glass tubes, etc. The present invention attempts to resolve the issue of developing a technique by which a biomembrane could be perforated using a method other than physical shear force while regulating the disruption of the membrane, namely developing a membrane disruption regulating technique.
Though there are various membrane disruption techniques as mentioned above, those that could site-specifically disrupt a membrane were limited. Microinjectors and micromanipulators cause partial membrane disruption, however, they relied on physical shear force to disrupt and perforate the membrane. Namely, another issue that the present invention attempts to resolve is to develop a component for perforating a biomembrane while regulating the disruption using a method other than physical shear force.
What is needed for perforating a biomembrane while regulating the disruption of a biomembrane, is the regulation of the site and degree of disruption. Therefore, the inventors conducted zealous investigations on which methods would enable the denaturation and perforation of a membrane while regulating the membrane disruption activity.
Enzymatic disruption using lipases and proteases, and methods using xcex2-rays and laser-beams could be exemplified as methods that partially and temporarily disrupt a membrane. However, the inventors focused their attention on the phospholipid radical sequential peroxidation reaction.
Active oxygen such as singlet oxygen, and superoxide radicals peroxidize unsaturated phospholipids of the cell membrane by sequential reactions. As countermeasures, cells have radical scavengers such as xcex1-tocopherol (vitamin E), and L-ascorbic acid (a water soluble anti-oxidant; vitamin C), superoxide dismutase (SOD) and such oxidation defense mechanisms, to resist oxidation (xe2x80x9cFree Radicals in Biology and Medicinexe2x80x9d, Oxford university Press (1985)).
When such sequential oxidations exceed the oxidation defense capacity, phospholipid membrane disruption rapid progresses in an exponential manner, and the cell becomes unable to maintain metabolism as the membrane loses its permeation inhibiting capacity. If these sequential reactions progress further, the cell will ultimately perish.
Photosensitizers (PS) are molecules that trigger such lipid sequential peroxidation reactions by producing active oxygen using light. Rose Bengal, porphyrin, and such can be given as photosensitizers in general use.
By utilizing such photosensitizers as membrane-denaturing agents, when denaturing the membrane, it will be sufficient to conduct sequential peroxidation reactions partially on the minimum objective cell surface, for a short period of time. Furthermore, the membrane damaged by the sequential peroxidation reactions at the time of membrane perforation, is expected to be repaired after the perforation by the fluidity of the membrane itself, or by the aforementioned anti-oxidation systems.
The inventors coated terthiophene (5xe2x80x25xe2x80x3-bis(aminomethyl)-2, 2xe2x80x2:5xe2x80x2,2xe2x80x3-terthiophene dihydrochloride), a type of photosensitizer, on the surface membrane of the nerve cell line PC12. Photosensitizers are membrane-denaturing agents that could be controlled by light exposure. By measuring membrane resistance, the inventors revealed that membrane resistance, namely, the ion permeability of the membrane increases due to the action of the photosensitizer, which is activated by exposing the whole cell to laser beams. Furthermore, by controlling the amount of beams and amount of photosensitizer, the change in membrane resistance caused by laser beam exposure could be regulated in at least three ways:
1) No change in membrane resistance
2) The resistance decreases and then recovers
3) The resistance is lost
Noteworthy is the fact that the inventors found that the duration it takes for the membrane permeability to recover to the state prior to disruption, was around 30 sec at suitable conditions.
Also, a similar change in membrane resistance was observed when only the axon of the cell was exposed to laser beams.
To examine whether membrane denaturation by photosensitizers could be applied for introducing substances into cells, the inventors attempted the adaptation into microinjection treatment. At the time of microinjection treatment, an injection solution containing Lucifer Yellow CH (LY), a water-soluble fluorescent dye, was prepared, and the ability to inject LY into PC12 cells was used as the determining indicator of the success of the injection. The injection was also automated by using an electric manipulator to exclude, as much as possible, man-induced influences on the evaluation of the success rate.
Using such an injection treatment system, the inventors evaluated how the success rate of the injection varied according to the presence or absence of the photosensitizer, terthiophene (5xe2x80x25xe2x80x3-bis(aminomethyl)-2,2xe2x80x2:5xe2x80x2,2xe2x80x3-terthiophene dihydrochloride, 100 xcexcM) within the injection solution, and according to the presence or absence of a two-minute exposure treatment by a 100 W mercury lamp was done, was measured.
As a result, when light exposure was done using a photosensitizer-containing injection solution, the success rate of the injection turned out to be 80%. Other controls resulted in an approximately 0 to 10% success rate. Therefore, by utilizing membrane denaturation, a significant improvement in the success rate of the injection was accomplished.
Furthermore, the inventors compared the cell survival rate between photosensitizer-treatment and normal treatments taking the LY retention rate of cells following injection treatment as the indicator of cell survival. 90% of the photosensitizer-treated cells survived for three to six days, whereas normally treated cells had a survival rate of only 10%, the survival rate of photosensitizer-treated cells being significantly high.
These results show that compared to injection techniques using physical shear force, those using membrane denaturation are clearly superior as means that suppress damage to cells.
The above results showed that suitable membrane perforation is possible by combining a photosensitizer and light. Namely, conditions in which the cell membrane is repaired without the cell being perished can be easily discovered. Naturally, it goes without saying that by preparing a membrane-destroying member by coating a membrane-disrupting material such as a photosensitizer on a support, the membrane could be contacted with this membrane-destroying member easily.
For example, this membrane-destroying member could be contacted with cells by utilizing a floating membrane-destroying member, for example microbeads coated with a membrane-denaturing agent, and contacting this membrane-destroying member using laser tweezers. Under such contact conditions, it is also possible to start the membrane denaturation reaction and then introduce this membrane-destroying member into cells. The membrane-denaturing agent itself may be a membrane structure, such as a micelle.
Furthermore, the inventors converted the scanning probe of the atomic force microscope into an electrode, and coated the probe-tip with the photosensitizer 5xe2x80x25xe2x80x3-bis(aminomethyl)-2,2xe2x80x2:5xe2x80x2,2xe2x80x3-terthiophene dihydrochloride to create a novel component. When this photosensitizer-coated component is inserted into the cell membrane, resistance caused by the cell membrane could be observed between the electrode within and without the membrane. Since the physical shear force of the electrodes of the atomic force microscope is not intense enough to cause cell perforation, the newly prepared component showed that it could be used as a component that is equipped with both the electrode function of the atomic force microscope and the controllable membrane-disrupting function. Also, by coating or fixing photosensitizing compounds onto already existing numerous components, it is possible to give these components the controllable membrane-disrupting function in addition to their original functions.
Namely, the present invention features:
(1) a method of denaturing or perforating a specific site of a membrane. the method comprising contacting the whole or part of the membrane with a reagent containing a specific compound that induces a membrane-denaturing reaction by a specific stimulation, and giving said stimulation;
(2) the method of (1), wherein the membrane is a cell membrane, a cell wall, a biomembrane, or an artificial membrane;
(3) the method of (1) or (2), wherein the region stimulated is included in the region contacted with the reagent;
(4) the method of (1) or (2), wherein the region contacted with the reagent is included in the region stimulated;
(5) the method of (4), wherein the reagent is contacted using a support;
(6) a method of any one of (1) to (5), wherein the specific stimulation is light, and the compound is a photosensitizing compound;
(7) a membrane obtained by the method of any one of (1) to (6), wherein the specific site has been perforated or denatured, or a membrane structure containing said membrane;
(8) the membrane or membrane structure containing said membrane of (7), wherein the membrane is a cell membrane, a biomembrane, or an artificial membrane;
(9) the membrane structure of (7) or (8), which is a cell, a micelle, or a liposome;
(10) a method of injecting a compound into a structure, the method comprising mixing the structure of any one of (7) to (9) with a complex comprising a compound to be injected and a carrier;
(11) the method of (10), wherein the carrier is a liquid or solid;
(12) a method of (10) or (11), wherein the substance is a nucleic acid or protein;
(13) a membrane-destroying member for denaturing or perforating a specific site of a membrane, which comprises a support, and a membrane denaturation promoting portion comprising a membrane denaturation force other than physical shear force, which was formed on at least one site on the surface of the support;
(14) the membrane-destroying member of (13), wherein the support is rod-shaped, tube-shaped, needle-shaped, or spherical;
(15) the membrane-destroying member of (13) or (14), wherein the membrane denaturation promoting portion is coated or fixed with a compound that generates the membrane denaturation reaction at the membrane denaturation promoting portion;
(16) the membrane-destroying member of (15), which utilizes a sequential peroxidation reaction of the membrane components, in which the membrane denaturation reaction is started by a direct/indirect production reaction of reactive oxygen species;
(17) the membrane-destroying member of (15) or (16), wherein the membrane denaturation reaction is induced by a specific stimulation and reaction precursor, and includes the reaction which denatures or perforates the membrane;
(18) the membrane-destroying member of (17), wherein the specific stimulation is light, and the reaction precursor is a photosensitizing compound;
(19) the membrane-destroying member of any one of (13) to (18), wherein the support penetrates the membrane following membrane denaturation or disruption, and said penetrated membrane closely contacts with said support;
(20) the membrane-destroying member of any one of (13) to (19), wherein the membrane is a cell membrane, a biomembrane or an artificial membrane.
As to the combination of the compound and stimulation used for denaturing or perforating the membrane, any combination may be used, as long as it can perforate the membrane in a controllable manner, without completely destroying the membrane. As to the stimulations used, electromagnetic waves including light, particle rays including radiation, heat, cooling, electricity, magnetism, oscillations including ultrasonic waves, physical contact, chemical substances, as well as, living beings in general including cells, viruses, and such can be given as examples. These stimulations may be used alone or together with others.
As compounds that are used to denature and perforate the membrane, enzymes involved in membrane denaturation and disruption, antibody molecules, membrane bound proteins, glycoproteins, lipids, and such may be used. Photosensitizers such as porphyrin, rose bengal, methylene blue, acid red, alpha-terthienyl, etc., or their derivatives may also be used. Oxidants such as reactive oxygen species, reductants, explosive compounds such as nitro-glycerin/picric acid, magnetic particulates/magnetic fluids, metal particles/conductor particles/insulator particles/photoelectric converting elements/piezoelectric elements, and such may also be suitably used. These compounds may be used alone or together with others.
The membrane to be denatured or perforated, may be a membrane containing photoelectric converting elements and piezoelectric elements, or may be cell membrane or cell wall of animals/plants, biomembranes, or artificial membranes. As a biomembrane, a cellular coat including cell wall, cellular inner membrane including cell membrane, nucleus membrane, viral membrane, cytoplasmic micro tubule, microsome membrane, golgi apparatus membrane, lysosome membrane, endoplasmic reticulum membrane, tonoplast membrane, plastid membrane, peroxysome membrane, ribosome membrane, mitochondrial membrane, and such can be given. These may be combined to make a reconstituted membrane. Examples of artificial membranes are, protein membranes, lipid membranes, high molecular (collagen, etc.) membranes, metal membranes, conductor membranes, mitochondrial membranes, insulator membranes, electric conductive high molecular (such as polyacetylene, polythiophene) membranes, etc.
As membrane disruption methods the following are provided.
First is the method, wherein a compound is contacted with the cell membrane, and a part of the contact region is stimulated to denature or perforate only a range smaller than the region where the compound and the membrane contacted. For example, by exposing light through a micro slit against cells treated with a water-soluble photosensitizing compound solution, only the cell membrane portion that was exposed can be denatured, or perforated.
Second is the method, wherein a compound is contacted with a part of the cell membrane, and a region larger than the contact region that is stimulated to denature or perforate only the region where the compound and the membrane contacted. For example, by coating a part of a micro support obtained by processing silicon crystals, contacting the region coated with the photosensitizing compound with the cell surface under a microscope, and stimulating with light, will cause membrane disruption only to the region contacted with the support.
Examples of supports having membrane-destroying member as constitutive elements are, crystals, macro compounds such as C60, micro pipettes, glass micro electrodes, patch electrodes, metal micro electrodes, wires, whisker, living organisms including cells, magnetic particulates/magnetic fluids, metal particles/conductor particles/insulator particles/photoelectric converting elements/piezoelectric elements, micro structures such as micromachines, as well as objects in which these are conjugated.
Light is well used as the specific stimulation, corresponding compounds being photosensitizing compounds. Dyes can be generally used as photosensitizing compounds. Among dyes, porphyrin, rose bengal, methylene blue, acid red, alpha-terthienyl, etch, or their derivatives are well used.
By suitably using the above methods, a membrane in which a portion is denatured or perforated can be provided. Also, as a membrane structure containing a membrane that has been denatured or perforated, a membrane which could be fixed on crystal oscillators and electrode basel plates, and in which the resonance frequency/fluidity/adsorption and such physical features could be modified, or a membrane in which the permeability/permeable site of a substance could be regulated by contacting with a gas/liquid, and such membranes can be given. Also, it may be a membrane in which the cell membrane or cell wall of animals/plants, biomembranes, or artificial membranes has been membrane denatured/perforated. As a biomembrane, a cellular coat including cell wall, cellular inner membrane including cell membrane, nucleus membrane, viral membrane, cytoplasmic micro tubule, microsome membrane, golgi apparatus membrane, lysosome membrane, endoplasmic reticulum membrane, tonoplast membrane, peroxysome membrane, plastid membrane, ribosome membrane, mitochondrial membrane, and such can be given. These may be combined to make a reconstituted membrane. Examples of artificial membranes are, membranes containing a magnetic structure at a high density, protein membranes, lipid membranes, high molecular (such as collagen) membranes, metal membranes, conductor membranes, insulator membranes, electric conductive high molecular (polyacetylene, polythiophene, etc.)membranes, etc. As structures containing membranes subjected to denaturation and perforation, cells and micelles having a specific number of holes can be given. As cells, animal cells, plant cells, microbial cells, reproductive cells, somatic cells, and such can be given.
Compounds that are to be injected can be substances that permeate the membrane easily by normal diffusion, or substances that are to be passed through the membrane artificially in large amounts, specifically, nucleic acids, proteins, lipids, membrane structures, etc.
Carriers are gases, liquids, or solids that can be used to dissolve, or suspend the substance to be injected, examples being buffers in which nucleic acids are dissolved, etc.
The form of membrane-destroying member may be any used according to the objective, as long as it can carry out controllable disruption of the membrane. The membrane-destroying member contains a support and a membrane denaturation-accelerating site, and this membrane denaturation-accelerating site may be on the support surface according to the purpose, or may be a part of the surface. It may be kenzan (needlepoint flower holder)-shaped, spherical, needle-shaped, rod-shaped, tube-shaped, or may be provided in a combined shape of these. Examples of tube-shaped supports are, specifically, pipettes, tubes, injection needles, etc. Spherical supports could be beads that could be handled by the laser tweezer technique.
When coating or fixing a compound that generates a membrane denaturation reaction in a support constituting the membrane-destroying member, the methods that could be used are, solvent evaporation drying, spattering, vacuum deposition, plasma polymerization, chemisorption, physisorption, radical polymerization, ion polymerization, etc. The support and the compound may indeed be indirectly bound via a mediator.
When the membrane denaturation reaction utilizes a sequential peroxidation reaction of the membrane components that is started by a direct/indirect production reaction of reactive oxygen species, it is possible to initiate the production reaction by suitably supplying light energy, electrical energy, chemical energy, etc. Specifically, light is electromagnetic waves from the deep ultra-violet region to the deep infrared region with a wavelength of about 180 nm. Light due to laser oscillations may also be used. The above-described photosensitizing compounds may be used in this case as well.
When membrane denaturation or disruption is generated using membrane-denaturing component, there are cases where close contact of the penetrated membrane and the membrane-denaturing component or a support constituting the membrane-denaturing component is suitable. Namely, in the case of a membrane-denaturing component that is tube-shaped and is connected to a pump, and to which manipulations such as microinjection and micromanipulation could be done, it is suitable that the penetrated membrane and the membrane-denaturing component or a support constituting the membrane-denaturing component are in close contact at the time of substance transport into/out of the cell.
Membrane-denaturing component controllable by location controlling apparatus are also well used in cell treatments, etc. Examples of location controlling apparatus are, scanning probe microscopes of atomic force microscopes and such, laser tweezers, micromanipulators, etc. Specifically, as a support constituting the membrane-denaturing component, atomic force microscope""s scanning probe, or the proximal light scanning microscope""s scanning probe, and such could be used.
The present invention can be utilized as a technology in various fields by suitable simple-and-clear applications carried out by one skilled in the art. One example is indicated below.
First, as the membrane manipulation, membrane disruption/denaturation and other manipulations could be carried out on an objective membrane by ligating or using together with the membrane-denaturing or disrupting agent, a manipulator comprising the function of manipulating an object having a membrane such as a cells/viruses, and a binder having the ability to bind/contact the target membrane. The manipulator, binder, and the membrane denaturing or disrupting agent may be used alone, or one of these could serve as the other two. In this case, the target membrane is a liposome/cell membrane/intracellular organelle membrane/viral membrane, and such, and the binder is a polyclonal antibody/monoclonal antibody/metal beads/plastic beads/virus/cell/living organism, etc. Utilized environment may be within the atmosphere, within a liquid, within the body, etc. Examples of cell/virus manipulations are, denaturation/disruption/growth acceleration or suppression/transformation/cell death induction/division or fusion acceleration/agglutination or dissociation acceleration/substance uptake or excretion acceleration, etc.
The invention may also be applied as substance introduction/excretion techniques due to the temporary perforation of the cell membrane. For example, in the creation of clone animals, and gene therapy, the introduction of genes into cells is an important manipulation.
The invention may also be applied for cell fusion. It could be done by using the membrane denaturation reaction of the present invention, which utilizes chemical substances such as polyethylene glycol, and viruses such as Sendai virus, for the cell fusion treatment.
Furthermore, it is possible to create a battery using the cell membrane potential caused by electrodes inserted into the cell. A major problem carried by micromachines and internal therapeutic instruments, is the securing of a power source for operation. By using membrane-disrupting material and electrodes, the potential that is within and without the cell membrane could be used as the power supply, and it will be possible to construct a system having suitable cells as batteries. The present invention could also be applied to create ultra microsurgery tools for cellular levels, such as cell scalpels. Though there are various dissecting instruments such as various types of scalpels, even if they are very small instruments, they cannot go beyond dissecting tissues. Dissecting instruments usable beyond the level of cells did not exist until now, but the membrane disruption technique of the present invention could be applied for dissecting cell membranes and intracellular membranes such as nucleus membrane.
The present invention could also be provided as a disruption technique that could be used site-specifically for micelles/liposomes containing medications for drug delivery systems (DDS) used in gene therapy. Namely, DDS research for using the system intensively around the target affected area, while suppressing side effects of the medications are being carried out, and by applying the present invention for disrupting microcapsules containing medications, an effective DDS could be accomplished.
The present invention could also be applied in manipulations of cellular organelles. Namely, the above-described micromanipulators and microinjectors could be used to easily manipulate cellular organelles such as lysosomes and the nucleus, to enable effective cell treatments. Specifically, egg cell manipulations and such (clone creation, etc.) in reproductive engineering could be given as an example.
The present invention could also be used for novel function expression and arrangement of functional molecules targeting flat/spherical membranes. In biomembranes, membrane proteins having various functions drift within the membrane while exerting their diverse functions, such as metabolism of chemical substances/transmission of electrons within the membrane surface and within and without the membrane, carrying out the functions alone or in suitable fissions-fusions. Such functional expressions by combinations of migratory functional units within the membrane surface and outside the membrane, are exactly what could be called micro chemical plants. Using such functional expressions of biomembranesxe2x80x94the scene of reactionxe2x80x94as a model, if biological functional molecules, and artificial objects such as piezoelectric elements, photoelectric converting elements, and memory elements would also become incorporatable as membrane devices by controlling the intake of various functional units into artificial membranes and biomembranes using the membrane disruption/denaturation technique, it will be possible to construct reaction systems with an extremely high degree of freedom.
Furthermore, cellular functions could be expanded by membrane manipulations and addition of devices. Namely, by using the membrane perforation technique of the present invention, novel functions could be given to already existing cells, by fusing a cell and an artificial functioning body. For example, a leukocyte could be magnetically guided to an affected area by creating a leukocyte in which a micro magnetosome particle deriving from magnetic bacteria has been inserted. This is a novel technique that could be called, not only a drug delivery system, but also a cell delivery system.
Also, by incorporating a photoelectric converting element into a membrane, it is possible to furnish cells with a function that is specific to plant cells, which is the ability to convert the energy of light into a chemical energy.
Furthermore, by applying a photoelectric converting element incorporated in the cell membrane for the input/output of nerve cell signals, it is possible to connect nerve cells directly with a photo information-processing computer.
Use of micromachines for therapeutic purposes is drawing great interest. Since such micromachines need to be small enough to enter even blood vessels, the energy source becomes restricted. Namely, energy supply via wires is difficult, and on the other hand, energy that could be mounted on the micromachine is highly trivial. Therefore, it is clear that an output provided by physical means by a built-in energy source would be overwhelmingly insufficient to cause influences such as cell disruption and cell denaturation when using micromachines. It could be said that membrane-disrupting agents and activation of these are indispensable in cell treatment. As an example, by using a photosensitizer that is activated by infrared light such as porphyrin as the membrane disruptor, the energy needed for membrane disruption could be supplied from outside the body by infrared lasers, etc.
By connecting an electrode to each nerve, the present invention could also be applied to create a nerve interface that exchanges information between nerves and electronic information instruments. Neural information is normally transmitted by the alterations in the cell membrane potential, namely, by action potential. To generate and measure this action potential, various analyses are being carried out regarding nerve-electronic instrument interfaces that input/output neural information, termed neural interfaces, however the distance between the electrodes and cells, and the degree of accumulation have become drawbacks. Although glass microelectrodes used for fundamental research purposes can be inserted into the cell membrane, or adsorped onto it to enable direct measurement/manipulation of cell membrane potential, high density accumulation was impossible since these electrodes are made by heat-processing glass tubes with diameters of only a few millimeters. On the other hand, metal microelectrodes that could be easily accumulated by semiconductor processing techniques, carry problems in cell membrane penetration ability, and stimulation/measurement have been done extracellularly, which is inefficient and also carries problems in site-specificity. By combining the membrane perforation technique of the present invention and metal electrode technique, it is possible to perforate the cell membrane, and set up micro metal electrodes within the cell. This will create an ideal neural interface where a cell and electrode could be connected one-to-one, or where several electrodes could be connected to a single cell.
The present invention could also be applied for the elucidation of cellular functions of the body such as for fundamental research of the brain. Namely, for brain function analysis, it is vital to analyze reciprocal information exchange between nerve cells. What is done at present is loading membrane potential sensitive dyes into nerves, and simultaneously measuring multi points of neural activity by optical measurement of the alteration of membrane potential as alterations in absorbance/fluorescence. However, in this case, it is impossible to optically carry out inputs into nerves, and to provide inputs/outputs to nerves, there is no alternative but to rely on electrical means, namely, electrodes. Analysis of the neural information processing mechanism by culturing nerve cells upon basal plate electrodes to form an artificial network, and research of applying nerve cells themselves as computing elements are also being carried out. Even in this case, signal inputting into nerves has become the stumbling block. Electrodes upon basal plates are extracellular electrodes, and in order to give nerve cells a stimulation to reach action potential generating threshold, the situation was such that an action potential could be finally generated as a total sum of stimulations received by each nerve following stimulation of nerve cell population upon the basel plate. The keys in assembling electrodes for exchanging information with each nerve are, downsizing electrodes into the cellular level, and means for connecting electrodes to each cell. This objective could be fulfilled by inserting intracellular electrodes obtained by combining micro metal electrodes downsized by semiconductor processing techniques, and the membrane perforation technique.
The present invention could also be utilized for functional electrical stimulation, and such, and for enhancing the accumulation/precision of stress-measuring therapeutic electrodes As a part of rehabilitation medicine, a method called functional electrical stimulation is being used, in which metal electrodes are inserted into nerve bundles and electrical stimulation is given to improve nerve/muscle functions. At present, the method has not gone beyond stopped at setting up electrodes in a few places within the nerve bundle, and is insufficient in the aspects of site specificity/precision of the nerve stimulation. By conjugating the membrane perforation technique and already existing electrode accumulation technique, one-to-one joining of a nerve and electrode will become possible, and thereby, stimulating only the nerve that needs functional improvement could be accomplished.
The present invention could also be applied as a technique for transmitting signals from nerves to various artificial organs. Organs embedded within the body are controlled, not by direct neural information of the body, but strictly by indirect control. One example is artificial urethral valve control. These valves that are made by shape-memory metals, open by heating and close at normal body temperature. This problem is, that the closing and opening is controlled by an external heating device switch and cannot be directly controlled by the will of the patient. If stabilization/enhancement of precision of neural information becomes possible by neural interfaces using membrane-penetrating electrodes, these valves could be controlled as if they were a part of the body of the user. It is true that artificial urethral valves are used only a few times throughout the day, and the handling, the opening/closing, is also easy, and therefore, not much inconveniences are caused by switch manipulations outside the body in daily life. However, to control artificial organs that carry out more complicated acts in place of visceral functions, it is indispensable to make the control signal source be from autonomous nerves.
The present invention could also be used for connecting/controlling prosthetic hand/legs equipped with sensory organs and joints that are controllable similarly to the human body. At present, there is a remarkable enhancement in performance of externally powered prosthetic hands/legs for functional assistance following dismembering. However, the controlling information source utilizes myoelectric power left in the wearer in most cases, and the power is overwhelmingly short compared to the information amount originally needed to control the limbs. Also, the transmitting of sensation through the prosthetic hand/legs to the wearer is limited to just physical contact information via the area connected to prosthetic limb. Therefore, even if the handling of the prosthetic hands/legs is learned by training, the reality is that the limbs are being used while enduring major inconveniences. One of the reasons impeding the enhancement of features of prosthetic limbs, is the fact that the information exchange pathways between the wearer and the prosthetic limb are poor. If stabile/highly precise measurement of each neural information becomes possible by neural interfaces using membrane penetrating electrodes, by joining the interface to the nerve that was connected to the wearer""s amputated limb, this nerve can be used as the controlling information source, and sensory signal input terminal. Namely, it will be possible to control a prosthetic limb equipped with a movement performance/sensory organ similar to the body.
The present invention could also be utilized for controlling an artificial sensory organ (visual/auditory) and connecting it to the body. Artificial inner ears for repairing auditory functions already exist. This substitutes the functions of the ear drum-inner ear through a microphone and signal converting circuit, and several tens of electrodes are set up in the cochlear organs, auditory nerves are stimulated electrically, and the auditory information is sent to the brain. The biggest reason why this instrument established itself as a therapeutic instrument is in the cochlear organs, in which auditory nerves are aligned according to frequency bands. Being a special case, information can be easily sent to the nerves from the electrodes in this instrument, but it is impossible to apply this electrode technique of the artificial inner ear to other organs. One of the technical targets is an electrode system sufficient to connect to the optic nerve, which contains one million neural axons per a 1 cm diameter, as the optic nerve is indispensable in repairing functions of the sense of sight, which among sensory organs is the most important information source of the body. Although such a highly dense, accumulative nerve electrode does not exist at present, the neural interface using membrane-penetrating electrodes will enable a highly dense accumulation able to respond to the optical nerve. Already, optical products using the charge-coupled device (CCD) has enabled one million picture elements at a low price, and using such photo information inputting instruments as functional artificial eyes, it will be possible to provide the human body with a sense of sight via the neural interface.
The present invention may also be used to expand brain functions. Although the brain, is energy-saving, has advantages such as parallel processing, and such, as an information processing device compared to semiconductor micro processors, it also carries weaknesses such as, the imprecision of information retention, difficulty of learning, etc. In order to overcome these weaknesses while taking use of the advantages of the brain, it is also possible to use together the brain and already existing semiconductor devices via the neural interface.

Site-specific cell perforation technique

Center for Advanced Science and Technology Incubation, Ltd.


Heterocyclic organic compounds are used as electron donors in conjunction with solid Ziegler-Natta type catalyst in processes in which polyolefins such as polypropylene are produced. The electron donors may be used in the preparation of solid catalyst system, thus serving as “internal electron donors”, or they may be employed during or prior to polymerization with the co-catalyst as “external electron donors”.

1. Field of the Invention
This invention relates to heterocyclic organic compounds that may be employed as an electron donor for polymerization catalyst systems, to polymerization catalyst systems employing the heterocyclic organic compounds as an electron donor, to methods of making such polymerization catalyst systems, and to polymerization processes to produce polyolefins, particularly polypropylene, which does not contain a phthalate derivative.
2. Description of the Related Art
Ziegler-Natta catalyst systems for polyolefin polymerization are well known in the art. Commonly, these systems are composed of a solid Ziegler-Natta catalyst component and a co-catalyst component, usually an organoaluminum compound. To increase the activity and sterospecificity of the catalyst system for the polymerization of α-olefins, electron donating compounds have been widely used (1) as an internal electron donor in the solid Ziegler-Natta catalyst component and/or (2) as an external electron donor to be used in conjunction with the solid Ziegler-Natta catalyst component and the co-catalyst component.
In the utilization of Ziegler-Natta type catalysts for polymerizations involving propylene or other olefins for which isotacticity is a possibility, it may be desirable to utilize an external electron donor, which may or may not be in addition to the use of an internal electron donor. Acceptable external electron donors include organic compounds containing O, Si, N, S, and/or P. Such compounds include organic acids, organic acid esters, organic acid anhydrides, ethers, ketones, alcohols, aldehydes, silanes, amides, amines, amine oxides, thiols, various phosphorus acid esters and amides, etc. Preferred external electron donors are organosilicon compounds containing Si—O—C and/or Si—N—C bonds, having silicon as the central atom. Such compounds are described in U.S. Pat. Nos. 4,472,524; 4,473,660; 4,560,671; 4,581,342; 4,657,882; 5,106,807; 5,407,883; 5,684,173; 6,228,961; 6,362,124; 6,552,136; 6,689,849; 7,009,015; 7,244,794; 7,619,049; and 7,790,819, which are incorporated by reference herein.
Common internal electron donor compounds, incorporated in the solid Ziegler-Natta catalyst component during preparation of such component, known in the prior art, include ethers, ketones, amines, alcohols, phenols, phosphines, and silanes. It is well known in the art that polymerization activity, as well as stereoregularity, molecular weight and molecular weight distribution of the resulting polymer, depend on the molecular structure of the internal electron donor employed. Therefore, in order to improve the polymerization process and the properties of the resulting polymer, there has been an effort and desire to develop various internal electron donors. Examples of such internal electron donor compounds and their use as a component of the catalyst system are described in U.S. Pat. Nos. 4,107,414; 4,186,107; 4,226,963; 4,347,160; 4,382,019; 4,435,550; 4,465,782; 4,522,930; 4,530,912; 4,532,313; 4,560,671; 4,657,882; 5,208,302; 5,902,765; 5,948,872; 6,121,483; 6,436,864; 6,770,586; 7,022,640; 7,049,377; 7,202,314; 7,208,435; 7,223,712; 7,351,778; 7,371,802; 7,491,781; 7,544,748; 7,674,741; 7,674,943; 7,888,437; 7,888,438; 7,964,678; 8,003,558; and 8,003,559, which are incorporated by reference herein.
Most of commercial propylene polymerization catalysts currently used employ alkyl phthalate esters as an internal electron donor. However, certain environmental issues have been recently raised concerning the continued use of phthalate derivatives in human contact applications. As a result, the employment of a phthalate-free propylene polymerization catalyst is now necessary for the production of phthalate-free polypropylene to remedy these issues.
U.S. Pat. No. 7,491,781 in particular teaches the use of an internal donor in a propylene polymerization catalyst component which does not contain a phthalate derivative. However the resulted propylene polymerization catalyst has poorer hydrogen response and lower isotacticity than the catalyst containing a phthalate derivative.
The polypropylene market also has an increasing demand in high melt flow rate (MFR) grade polypropylene to reduce cycle time and to achieve down-gauging while maintaining acceptable impact strength and stiffness. High MFR polypropylene is commonly achieved by adding peroxide to the polymer, but such obtained polypropylene usually has odor issues and the physical properties are sacrificed somehow. As such, production of reactor-grade high MFR polypropylene becomes necessary to avoid these issues.
There is a continuous need for developing catalyst systems that can be used to produce polyolefins, particularly polypropylene, which does not contain a phthalate derivative. Furthermore, the desirable catalyst systems should also offer capabilities to produce polypropylene with acceptable isotacticity and high MFR.

Heterocyclic organic compounds as electron donors for polyolefin catalysts


A thermalcycler includes a first thermalcycler body section having a first face and a second thermalcycler body section having a second face. A cavity is formed by the first face and the second face. A thermalcycling unit is positioned in the cavity. A heater trace unit is connected to a support section, to the first thermalcycler body section, to the second thermalcycler body section, and to the thermalcycling unit. The first thermalcycler body section and the second thermalcycler body section are positioned together against the support section to enclose the thermalcycling unit and the heater trace unit.

1. Field of Endeavor
The present invention relates to thermocyclers and more particularly to a thermalcycler for various operations including polymerase chain reactions, testing for DNA hybridization, isothermal reactions, nucleic acid sequence-based amplification, rolling-circle amplification, incubation for immunoassays, and other uses.
2. State of Technology
U.S. Pat. No. 5,779,981 for a thermal cycler including a temperature gradient block provides the following state of technology information:
"Systems which require multiple or cyclic chemical reactions to produce a desired product often require careful temperature control to produce optimal results. Such reactions include nucleic acid amplification reactions such as the polymerase chain reaction (PCR) and the ligase chain reaction (LCR). For this reason, apparatus have been developed which permit the accurate control of the temperature of reaction vessels in which such amplification reactions are performed.
For example, there are a number of thermal 'cyclers' used for DNA amplification and sequencing in the prior art in which one or more temperature controlled elements or 'blocks' hold the reaction mixture, and the temperature of a block is varied over time.
The PCR technique typically involves the step of denaturing a polynucleotide, followed by the step of annealing at least a pair of primer oligonucleotides to the denatured polynucleotide, i.e., hybridizing the primer to the denatured polynucleotide template. After the annealing step, an enzyme with polymerase activity catalyzes synthesis of a new polynucleotide strand that incorporates the primer oligonucleotide and uses the original denatured polynucleotide as a synthesis template. This series of steps (denaturation, primer annealing, and primer extension) constitutes a PCR cycle. As cycles are repeated, the amount of newly synthesized polynucleotide increases geometrically because the newly synthesized polynucleotides from an earlier cycle can serve as templates for synthesis in subsequent cycles. Primer oligonucleotides are typically selected in pairs that can anneal to opposite strands of a given double-stranded polynucleotide sequence so that the region between the two annealing sites is amplified.
The temperature of the reaction mixture must be varied during a PCR cycle, and consequently varied many times during a multicycle PCR experiment. For example, denaturation of DNA typically takes place at around 90°-95° C., annealing a primer to the denatured DNA is typically performed at around 40°-60° C., and the step of extending the annealed primers with a polymerase is typically performed at around 70°-75° C. Each of these steps has an optimal temperature for obtaining the desired result. Many experiments are required to determine the optimal temperature for each step.
For example, while the temperature at which DNA denatures is generally between 90°-95° C., slight variations in the particular temperature necessary are observed depending on the length of the DNA and the percentage of each of the four deoxynucleotides present (guanine-cytosine pairs and adenine-thymine pairs). Insufficient heating during the denaturation step is a common reason for a PCR reaction to fail. However, overheating during the denaturation step can result in excessive denaturation of the polymerase.
Achieving the optimal temperature for the PCR annealing step is even more critical. An annealing temperature which is too low will result in non-specific DNA fragments being amplified. At too high of an annealing temperature, the primers will anneal less efficiently resulting in decreased yield of the desired product and possibly reduced purity. In the annealing step, the optimal temperature will depend on many factors including the length of the primer and the percentage of each of the four deoxynucleotides present (guanine-cytosine pairs and adenine-thymine pairs). For a typical 20-base oligonucleotide primer comprised of roughly 50% guanine-cytosine, a temperature of 55° C. is a good estimate for the lower end of the temperature range. However, as one increases the primer length in order to attain greater primer specificity, differing annealing temperatures may be required. Thus, the number of subtle influences on the optimal annealing temperature makes difficult the task of quickly identifying the optimum for a given system.
Achieving the optimal temperature for the extension reaction is also important for obtaining the desired PCR result. Temperature may affect both the rate and the accuracy of the extension reaction. If the rate of the polymerase reaction is too low, then the newly synthesized polynucleotide may not contain a site for primer annealing. Additionally, the denatured polynucleotide sequence for amplification may contain one or more regions of secondary structure that may form or disappear according to the temperature selected. Furthermore, several different enzymes with polymerase activity may be used for PCR. Each enzyme will have its own optimum temperature for activity, stability and accuracy.
Determination of the optimal denaturing, annealing, and extension temperatures for a particular PCR is complicated by the fact that the optimum will be different for each of the reactions. Thus, in order to determine the three optimal temperature ranges, multiple separate experiments must be run where two temperature variables are held constant while a third temperature variable is changed. As a result, determination of the optimal temperature for running a PCR system can be a time consuming task."

Lawrence Livermore National Security, LLC.


A compound represented by the following general formula (1) or a salt thereof, which has superior inhibitory activity against type 4 PLA2, and thus has prostaglandin and/or leucotriene production suppressing action [X represents a halogen atom, an alkyl group which may be substituted, or the like, Y represents hydrogen atom or an alkyl group which may be substituted, and Z represents hydrogen atom or an alkyl group which may be substituted].

In living bodies of mammals, various prostaglandins and various leukotrienes are produced by various stimulations such as inflammatory and physical stimulations. Both of prostaglandins and leukotrienes are metabolites of arachidonic acid, and they are physiologically active substances called lipid mediators. They trigger various kinds of physiological reactions of mammals by binding to their respective receptors expressed on cell surfaces or expressed intracellularly.
Arachidonic acid is produced from phospholipids such as phosphatidylcholine as substrates, which are components of cell membranes, with the aid of the enzymatic activity of phospholipase A2 (PLA2). In particular, type 4 PLA2 is activated by inflammatory stimulation, and plays an important role in the arachidonic acid production. Arachidonic acid produced by PLA2 is converted into prostaglandin (PG) H2 by an enzymatic activity of constitutive-type cyclooxygenase (COX) 1 or inducible-type COX-2 and further converted into PGE2, PGD2, PGF2α, PGI2, thromboxane (TX) A2 and the like by each synthetic enzyme. Further, arachidonic acid is also metabolized by 5-lipoxygenase (5-LO) to give leukotriene (LT) A4, and further converted into LTB4, LTC4, LTD4, LTE4 and the like by enzymatic activities of LTA4 hydrolase, LTC4 synthase, and glutathione-S-transferase [Goodman and Gilman's the Pharmacological Basis of Therapeutics, 11th edition (Hirokawa Shoten), 2007, p. 814; C. D. Funk, SCIENCE, 2001, vol. 294, p. 1871].
Each of the prostaglandins binds with a specific receptor to cause, for example, inflammatory reactions such as fervescence, increase of blood vessel permeability, vasodilation, swelling, and pain, bronchial smooth muscle contraction, platelet aggregation, tumor cell proliferation, bone resorption promotion, nerve cell degeneration and the like, and plays an important role in expression of symptoms or formation of pathological states in various diseases. Leukotrienes are physiological substances, each of which binds with a specific receptor to cause, for example, inflammatory reactions such as excessive accumulation of leucocytes and increase of blood vessel permeability, smooth muscle contraction, mucus secretion, tumor cell proliferation and the like, and also play an important role in expression of symptoms or formation of pathological states in various diseases.
Although inflammatory reactions, per se, are essential reactions in order that living bodies can survive when they face a pathogenic substance or affection, inflammatory reactions sometimes occur in excess levels in certain conditions or diseases, or they may sometimes continue without any reason for bringing evident benefits [Goodman and Gilman's the Pharmacological Basis of Therapeutics, 11th edition (Hirokawa Shoten), 2007, p. 837]. Conditions of living bodies exhibiting acute or chronic inflammatory reactions referred to in the present specification mean conditions where excess or non-profitable inflammatory reactions are generated acutely and transiently or chronically and continuously. Further, inflammatory reactions are a series of events caused by stimulations including physical hazards such as those caused by heat, infectious substance, ischemia, antigen-antibody reaction and the like, and they are accompanied by flare, swelling, algesia, and pain generation as well-known macroscopic clinical symptoms. As histological mechanisms of these symptoms, it is known that vasodilation, increase of blood vessel permeability, invasion of leucocytes and phagocytes, decomposition or fibrosis of tissues and the like are caused [Goodman and Gilman's the Pharmacological Basis of Therapeutics, 11th edition (Hirokawa Shoten), 2007, p. 837]. It is known that many of these histological reactions are triggered by prostaglandins and/or leukotrienes, and prostaglandins and/or leukotrienes have important roles in the inflammatory reactions.
For example, in a pathological tissue of rheumatoid arthritis, which is an autoimmune disease and is one of chronic inflammatory diseases, expression of COX-2 and production of PGE2 or TXA2 as well as expression of 5-LO and production of LTB4 are observed [Bonnet et al., Prostaglandins, 1995, vol. 50, p. 127]. In a mouse deficient in FLAP which is a protein required for activation of 5-LO, symptoms of collagen-induced arthritis, as a disease model of chronic rheumatoid arthritis, are reported to be milder compared with those in a wild-type mouse [Griffiths et al., J. Exp. Med, 1997, vol. 185, p. 1123]. Thus, prostaglandins and leukotrienes are demonstrated to be responsible for important roles in the formation of pathologies of chronic rheumatoid arthritis.
In a pathological tissue of bronchial asthma, which is one of chronic allergic diseases, overproduction of PGD2 and TXA2 as well as overproduction of LTC4 and LTD4 are observed [Wenzel et al., Am. Rev. Respir. Dis, 1990, vol. 142, p. 112], and airway hypersensitivity, which is a disease model of bronchial asthma, is reported to unlikely occur in a PGD2 receptor deficient mouse [Matsuoka et al., SCIENCE, 2000, vol. 287, p. 2013]. Accordingly, roles of prostaglandins and leukotrienes are demonstrated to be important in bronchial asthma.
In a cerebral tissue after ischemia and reperfusion, expression of COX-2 is increased to increase PGE2 and TXA2 concentrations, whereas activity of 5-LO is increased to increase production of LTC4 [Ohtsuki et al., Am. J. Physiol., 1995, vol. 268, p. 1249]. Thus, it is known that prostaglandins and leukotrienes are responsible for important roles in the formation of infarct, which is recognized as a disorder from ischemia and reperfusion. In a pathological tissue of Alzheimer's disease, which is one of diseases accompanied by neurodegeneration, it is demonstrated that COX activity and 5-LO activity are increased, and prostaglandins and leukotrienes cause formation of β-amyloid proteins which constitute one class of pathogenic substances of Alzheimer's disease to induce degeneration of nerve cells [Sugaya et al., Jpn. J. Pharmacol., 2000, vol. 82, p. 85]. Thus, it is considered that prostaglandins and leukotrienes are responsible for important roles in formation of neurodegenerative diseases such as Alzheimer's disease.
In a pathological tissue of colon cancer, for example, COX and 5-LO are expressed, and the production of prostaglandins and leukotrienes are increased [Dreyling et al., Biochim. Biophys. Acta, 1986, vol. 878, p. 184]. Further, leukotrienes are reported to cause proliferation of colon cancer cells [Qiao et al., Biochim. Biophys. Acta, 1995, vol. 1258, p. 215; Hong et al., Cancer Res., 1999, vol. 59, p. 2223]. Thus, it is considered that prostaglandins and leukotrienes also play important roles in tissues of colon cancer.
Involvements of prostaglandins and/or leukotrienes in diseases and pathological conditions are not limited to the diseases exemplified above. It has been demonstrated that prostaglandins and/or leukotrienes are involved in various conditions, diseases, and pathological states accompanied by acute or chronic inflammatory reactions, and that their roles are important. From the above facts, various kinds of inhibitors against prostaglandin production or against leukotriene production have been used as agents for prophylactic or therapeutic treatment of conditions, diseases, and pathological conditions with acute or chronic inflammatory reactions.
Drugs having suppressing actions on prostaglandin production include various kinds of non-steroidal anti-inflammatory drugs (NSAIDS), and they have been used as agents for therapeutic treatment of chronic rheumatoid arthritis and osteoarthritis, anti-inflammatory analgesics for external injury and the like, agents for prophylactic treatment of cerebral infarction or myocardial infarction, agents for prophylactic treatment of colorectal polyposis and the like. However, various kinds of NSAIDS inhibit only the production of prostaglandins, and as a result, they increase production of leukotrienes to cause side effects such as asthmatic attack and gastrointestinal injury, and in addition, exhibit side effects of nephropathy and the like. Further, differences in an effective dose and a dose inducing the side effects are small in these NSAIDS, and no satisfactory drug is available also from a viewpoint of a therapeutic effect. For example, it has been reported that inhibition of COX by the above drug leads to suppression of biosynthesis of PG required for maintaining homeostatic functions in the upper gastrointestinal tract such as stomach and duodenum, kidney, and the like, and as a result, for example, they induce side effects such as upper gastrointestinal injury and/or renal dysfunction [Goodman and Gilman's the Pharmacological Basis of Therapeutics, 11th edition (Hirokawa Shoten), 2007, Chapter 26].
5-LO inhibitors described in EP279263 are available as drugs having suppressing action on leukotriene production and are known as prophylactic agents for asthma. However, their doses are limited because of induction of side effects such as hepatotoxicity, which results in unsatisfactoriness from a viewpoint of a therapeutic effect. Steroids inhibit productions of both of prostaglandins and leukotrienes, and accordingly, they are used as prophylactic or therapeutic agents for treatment of conditions of living bodies, various diseases, or pathological states with various acute or chronic inflammatory reactions. However, their actions are not limited to the suppressing action on lipid mediator production, but they have severe side effects such as induction and exacerbation of infection due to immune suppressing effects, growth delay and dermatrophy due to suppressing action on normal cell proliferation, digestive ulcer and the like. Therefore, their use has been limited.
Under the circumstances as explained above, a compound which suppresses production of both of prostaglandins and leukotrienes and shows less side effects is considered to be effective as a therapeutic or prophylactic agent for the conditions, diseases or pathological states of living bodies in mammals as described above, and a method of using such compound and an existing medicament in combination is considered to be a further effective method for therapeutic treatment or prophylactic treatment. Therefore, it is desired to create a compound which suppresses production of both of prostaglandins and leukotrienes and to develop the compound as a medicament.
Although the compounds disclosed in Patent documents 1 to 3, for example, are known as compounds exhibiting the same affect as that of the compounds of the present invention, all of these compounds are structurally different from the compounds of the present invention.    Patent document 1: International Patent Publication WO99/19291    Patent document 2: International Patent Publication WO03/07686    Patent document 3: International Patent Publication WO05/016862

Phenylpropionic acid derivative and use thereof


A pumpless lubrication system for a power transfer assembly equipped with a hypoid gearset having a ring gear and a hollow pinion unit. Lubricant splashed from one of the ring gear and the pinion unit is collected in a collection reservoir and directed through a conduit unit into the hollow pinion unit. The lubricant is delivered to a torque transfer coupling for lubricating and cooling a multi-plate clutch pack.

This section provides background information related to the present disclosure which is not necessarily prior art.
In view of increased consumer demand for four-wheel drive (4WD) and all-wheel drive (AWD) motor vehicles, a large number of power transfer systems are currently utilized in vehicular applications for selectively and/or automatically transmitting rotary power (i.e., drive torque) from the powertrain to all four wheels. In most power transfer systems, a power transfer assembly is used to deliver drive torque from the powertrain to one or both of the primary and secondary drivelines. The power transfer assembly is typically equipped with a torque transfer coupling that can be selectively actuated to shift operation of the power transfer system from a two-wheel drive mode into a four-wheel drive mode. In the two-wheel drive mode, drive torque is only transmitted to the primary driveline while drive torque can be transmitted to both of the primary and secondary drivelines when the vehicle is operating in the four-wheel drive mode.
In most 4WD vehicles, the power transfer assembly is a transfer case arranged to normally transmit drive torque to the rear driveline and selectively/automatically transfer drive torque through the torque transfer coupling to the front driveline. In contrast, in most AWD vehicles, the power transfer assembly is a power take-off unit (PTU) arranged to normally permit drive torque to be transmitted to the front driveline and to selectively/automatically transfer drive torque through the torque transfer coupling to the rear driveline.
Many power transfer assemblies are equipped with an adaptively-controlled torque transfer coupling to provide an "on-demand" power transfer system operable for automatically biasing the torque distribution ratio between the primary and secondary drivelines, without any input or action on the part of the vehicle operator, when traction is lost at the primary wheels. Modernly, such adaptively-controlled torque transfer couplings are equipped with a multi-plate clutch assembly and a power-operated clutch actuator that is interactively associated with an electronic traction control system having a controller unit and a plurality of vehicle sensors. During normal operation, the clutch assembly is maintained in a released condition so as to transmit drive torque only to the primary wheels and establish the two-wheel drive mode. However, upon detection of conditions indicative of a low traction condition, the power-operated clutch actuator is actuated to frictionally engage the clutch assembly and deliver a portion of the total drive torque to the secondary wheels, thereby establishing the four-wheel drive mode.
In virtually all AWD power transfer systems of the type noted above, the secondary driveline is configured to include a propshaft, a drive axle assembly equipped with the torque transfer coupling, and one or more constant velocity universal joints. Typically, the opposite ends of the propshaft are drivingly interconnected via the constant velocity universal joints to a rotary output of the power take-off unit and to a rotary input of the torque transfer coupling associated with the drive axle assembly. In most instances, a rotary output associated with the torque transfer coupling is a hypoid gearset configured to transmit drive torque to a differential gear mechanism associated with the drive axle assembly. The torque transfer coupling also includes a multi-plate friction clutch assembly disposed between the rotary input and the rotary output. The differential gear mechanism may include a differential carrier rotatably supported in an axle housing by a pair of laterally-spaced differential bearings and which drives at least one pair of bevel pinions which, in turn, are commonly meshed with first and second output bevel gears. The first and second output bevel gears of the differential gear mechanism are drivingly connected to corresponding first and second axleshafts which, in turn, drive the secondary wheels. The hypoid gearset includes a pinion gear meshed with a ring gear. The pinion gear is typically formed integrally with, or fixed to, a solid pinion shaft that is also rotatably support in the axle housing. Due to the axial thrust loads transmitted through the hypoid gearset, it is common to utilize at least two laterally-spaced tapered pinion bearing to support the pinion shaft for rotation relative to the axle housing.
As is known, a lubrication system is required in association with the drive axle assembly to lubricate and cool the clutch pack of the multi-plate friction clutch assembly and the differential and pinion bearings. In many arrangements, a combination of splash lubrication (generated via rotation of the hypoid gearset) and pumped lubrication (generated via an oil pump) is used to provide adequate system lubrication. The pumped lubrication typically requires either a mechanically-actuated gear pump or an electrically-actuated oil pump to provide the required lubrication for the multi-plate clutch assembly. Obviously, use of mechanical and/or electrical fluid pumps increase the overall cost and packaging requirements of the drive axle assembly as well as possibly lowering its efficiency. Likewise, splash lubrication of the clutch assembly would require rotating components through an oil sump, also reducing efficiency and increasing system drag while requiring a larger volume of lubricant and causing difficulty in accurately directing lubricant flow to the clutch assembly due to centrifugal forces working against the lubricant.
While such conventional drive axle assemblies and pinion shaft support arrangements are adequate for their intended purpose, a need still exists to advance the technology and structure of such products to provide enhanced configurations that provide improved efficiency, reduced weight, packaging requirements, and enhanced lubrication.

Ultra-lightweight rear axle drive (ULRAD) assembly with clutch lubrication system


A remote plasma enhanced CVD apparatus and method for growing semiconductor layers on a substrate, wherein an intermediate feed gas, which does not itself contain constituent elements to be deposited, is first activated in an activation region to produce plural reactive species of the feed gas. These reactive species are then spatially filtered to remove selected of the reactive species, leaving only other, typically metastable, species which are then mixed with a carrier gas including constituent elements to be deposited on the substrate. During this mixing, the selected spatially filtered reactive species of the feed gas chemically interacts, i.e., partially dissociates and activates, in the gas phase, the carrier gas, with the process variables being selected so that there is no back-diffusion of gases or reactive species into the feed gas activation region. The dissociated and activated carrier gas along with the surviving reactive species of the feed gas then flows to the substrate. At the substrate, the surviving reactive species of the feed gas further dissociate the carrier gas and order the activated carrier gas species on the substrate whereby the desired epitaxial semiconductor layer is grown on the substrate.

1. Field of the Invention
This invention relates to a remote plasma enhanced chemical vapor deposition (RPECVD) apparatus and method for growing an epitaxial semiconductor layer.
2. Discussion of Background
Plasma enhanced processes have figured prominently in research efforts to lower process temperatures. In conventional plasma enhanced chemical vapor deposition (PECVD), the parent gas molecules are dissociated into precursor atoms and radicals which can deposit on substrates at lower temperatures than in thermal chemical vapor deposition. The deposition occurs at lower temperatures than purely pyrolytic processes because the plasma supplied energy to break chemical bonds in the parent molecules that would only be broken by thermal decomposition if the plasma were not present. Parent molecule dissociation is accomplished in the plasma through various processes involving collisions with electrons, ions, photons, and excited neutral species. Unfortunately, the precursor species are also subject to the same active environment which dissociated the parent molecules. This can lead to further dissociation or reaction of gas phase species to form more complicated radicals before the radicals can condense on the substrate In a low pressure, low power silane (SiH.sub.4) immersion plasma, Matsuda et al. Thin Solid Films 92,171 (1982), have shown using mass spectroscopy that there are a host of gas phase species. These species include H, H.sub.2, Si, SiH, SiH.sub.2, SiH.sub.3, SiH.sub.4, Si.sub.2, Si.sub.2 H, Si.sub.2 H.sub.2, Si.sub.2 H.sub.3, Si.sub.2 H.sub.4, and Si.sub.2 H.sub.5. The most dominant line in the mass spectroscopy is the SiH.sub.2 line, even though it is ony 12% taller than the SiH.sub.3 line and 125% taller than the Si.sub.2 H.sub.5 line. There is a wide spectrum of precursor species incident on the growing film. A further complication is that in conventional PECVD the substrate is immersed in the plasma region. This results in a large flux of charged species incident on the substrate during film deposition. The incident energies of these ions may be as high as 160 eV in some immersion systems (See Chapman, Glow Discharge Processes, John Willey & Sons, N.Y. 1980, Chap. 4). This can lead to ion implantation, energetic neutral embedment, sputtering, and associated damage This residual damage must be annealed out during growth if high quality epitaxial layers are to be produced. Thus, this damage imposes a minimum growth temperature, based on annealing conditions below which high quality material cannot be obtained. Thus, there are two major problems associated with conventional PECVD: adequate control over incident gas phase species, and ion damage as a result of the substrate being immersed in the plasma region.
RPECVD deposition of silicon nitride Si.sub.3 N.sub.4 and silicon SiO.sub.2 for gate insulators in (In, Ga) As FET devices has recently been disclosed by Richard et al. J. Vac. Sci. Technol. A3(3), May/June 1985 (pages 867-872). According to this reference, to deposit SiO.sub.2, for example, one reactant, O.sub.2, is excited in the plasma tube remote from the semiconductor substrate. The other reactant, SiH.sub.4, enters the reactor separately, near the substrate and is not excited to a plasma state. An important point is that one of the reactants, O.sub.2, bearing one of the component atoms of the SiO.sub.2, is introduced through the plasma tube. The process is thought to follow the following reaction model. Monosilane (SiH.sub.4) molecules interact with the metastable oxygen O.sub.x *(.sup.3 P.sub.j) flux resulting from the remote plasma. The lifetime of the metastable oxygen is quite long, allowing pathlengths of 1-2 meters in the RPECVD reactor using the SiO.sub.2 deposition parameters. (In contrast, the pathlength of a typical metastable excited noble gas specie, e.g. He*, used in the RPECVD epitaxial growth of semiconductor layers, according to the present invention, is 5-30 cm.) This interaction leads to disiloxane, (SiH.sub.3).sub.2 O, formation in the gas phase. On the heated substrate, disiloxane is further oxidized by excess metastable oxygen, O*. This oxidation removes H from the silyl groups, SiH.sub.3. Dehydrogenation is accompanied by oxygen bridging of silicon atoms originally bound in adjacent disiloxane molecules on the heated surface. An excess of the plasma excited species is used to drive the dehydrogenation of the silyl groups to completion, minimizing Si--H bonding. Silicon-poor films do not form; thus the process is stable. For this case, CVD can be thought of as a polymerization of disiloxane brought about by oxidation of the SiH bonds of the silyl groups.
Important features of the SiO.sub.2 process described by the above-noted Richard et al article are:
1) In the SiO.sub.2 process, O is activated by the plasma in the plasma generation region and becomes incorporated in the deposited layers.
2) The interaction between the reactive species existing the plasma generation region and the injected reactant results in the formation of the chemical groups.
3) The lifetimes and therefore the pathlengths of the reactive species exiting the plasma formation is quite long: for metastable oxygen the pathlength is 1-2 meters.
4) The dielectric material formed, SiO.sub.2, is an amorphous material and therefore has no long-range or crystalline order. For SiO.sub.2 deposition, metastable O* promotes the further oxidation of disiloxane adsorbed on the substrate surface, which reduces the surface of adatoms and enhances the formation of amorphous material.
Another prior art reference of interest is an article by Toyoshima et al, Appl. Phys. Lett. 46(6), 15 March 1985, pp 584-586, which describes a PECVD process to deposit hydrogenated amorphous silicon. However, the deposited a-Si:H films retain from 5-30 atomic percent hydrogen in the deposited layers, which is critical to the performance of a-Si:H, but disastrous if one is trying to grow epitaxial Si layers. No process used to deposit high quality a-Si:H films has proven successful in depositing epitaxial Si layers.

Remote plasma enhanced CVD method and apparatus for growing an epitaxial semconductor layer


An electrophotographic copying machine including consumptive parts or materials which are used or consumed upon every operation is disclosed. In the copying machine, a remainder number of copies to be obtained until consumption of either one of said parts or materials reaches a predetermined value is determined, and a planned total number of copies to be obtained is estimated under copying conditions. Then, it is judged whether or not the copying operation can be completed to obtain said planned total number of copies by comparing said planned total number of copies with said remainder number of copies, and when it is judged that the completion of the copying operation is impossible, a warning is made prior to the start of the copying operation. The copying machine also has a display for displaying the number of reproducible copies and displays a half of the remainder number of copies as the reproducible number of documents when in the both sides copying mode.

1. FIELD OF THE INVENTION
The present invention relates to an electrophotographic copying machine, and more particularly, to an electrophotographic copying machine, wherein copying operation is prohibited when consumption of either one of consumptive parts or materials which are used or consumed upon every copying operation reaches a predetermined value.
2. DESCRIPTION OF RELATED ART
A conventional electrophotographic copying machine comprises articles consumed upon every copying operation such as a cleaning web for removing waste toner adhering to a fixing roller, and a waste such as the waste toner is produced upon every copying operation. When the articles become empty or when a waste container for accommodating the waste becomes full of the waste, it is warned to the operator.
In this type of conventional copying machine, for example, there is provided a waste toner container for accommodating the waste toner produced upon every copying operation. When the weight of the waste toner container becomes larger than a predetermined value, a detecting switch is turned on, and it is displayed that the quantity of the waste toner reaches a predetermined value. Further, the copying operation is automatically suspended as soon as the quantity of the waste toner reaches a predetermined value even though it is during the copying operation.
In another conventional copying machine, there is provided a waste toner full counter for counting the number of copies obtained from an empty state of the waste toner container to a full state thereof. It is judged based on the counting value of the waste toner full counter whether or not the waste toner is to be discarded, and the copying operation is prohibited if it is judged that the waste toner is to be discarded.
In the above copying machine for detecting the timing when the waste toner should be discarded and thereby the copying operation should be prohibited, as soon as the waste toner container becomes full of the waste toner, the copying operation is suspended during the copying operation. Particularly, in the case of the copying operation for obtaining a lot of copies, the operator sets documents on a document tray of an automatic document feeder (referred to as an ADF hereinafter), and presses a start key in order to start the copying operation. Thereafter, the operator leaves the copying machine in order to do other works and returns thereto to take the copied papers and the documents around a timing when the copying operation may have been completed.
In this case, the following state may occur. Namely, after it is displayed that the waste toner container becomes full of the waste toner during the copying operation for obtaining a predetermined number of copies, for example, one thousand copies, the copying operation is suspended automatically. Thereafter, the number of copies obtained actually becomes less than the predetermined one although the copying machine has been stopped as if the copying operation has been completed. At that time, the operator opens the front door of the copying machine, draws out the waste toner container, and discards the waste toner from the waste toner container. Then, the operator sets the waste toner container at a predetermined position of the copying machine, and presses the start key so as to start the copying operation for remaining copies.
As described above, if the waste toner container becomes full of the waste toner during the copying operation, the working efficiency upon the copying operation decreases extremely.
Incidentally, there is another type of copying machine in which a display indicative of a full state of waste is preliminarily turned on at the time when the condition of the waste container becomes not completely but substantially full of the waste and only a predetermined number of copies are permitted with turning on of the display. This type of copying machine, however, has the same drawback as mentioned above if a number of copies to be produced is larger than the permitted number of copies.

Electrophotographic copying machine having a function of judging whether a copying operation can be performed responsive to a remainder amount of consumptive parts or materials