The present invention relates to a process for purifying Factor IX from an impure protein fraction containing Factor IX. The purification process comprises the steps of adding a solvent and a detergent to an impure protein fraction and incubating the solvent/detergent protein solution to inactivate any viral contaminants. Factor IX is purified from the solvent/detergent protein solution by chromatography on a sulfated polysaccharide resin without first removing the solvent and detergent prior to the purification on the sulfated polysaccharide resin. The Factor IX, purified by the process has a specific activity of at least 85 units/mg.

The initiation of blood clotting is by two different, yet similar, molecular mechanisms called the intrinsic and extrinsic coagulation pathways, or cascades. The intrinsic pathway involves factors that are normally found in the blood. The extrinsic pathway involves tissue factors in addition to blood components. In each of the reaction steps of the two cascades, a proteinase converts an inactive zymogen into its enzymically active form. In the last step of the cascade, which is the same in both the intrinsic and extrinsic pathways, inactive prothrombin is converted to thrombin, which in turn catalyzes the conversion of soluble fibrinogen into insoluble fibrin.
Factor IX participates in the cascade of events that lead to blood coagulation. Specifically, Factor IX, when activated by the action of Factors XI.sub.a or VII.sub.1, activates Factor X to X.sub.a. Factor X.sub.a in turn activates Factor II (prothrombin) to Factor II.sub.a (thrombin). The activated Factor II then activates fibrinogen to form the fibrin polymers of the blood clot. A deficiency in the activity of any of the factors involved in blood clotting leads to an inability of the blood to clot properly or to longer-than-normal clotting times. For example, Factor IX is absent or deficient in patients who have a condition identified as "Hemophilia B." Thus, the blood of Hemophilia B patients does not clot properly. Factor IX is administered to Hemophilia B patients to provide sufficient Factor IX, to return the clotting ability of their blood to as close to normal as possible.
Commercially available Factor IX concentrates frequently include other blood factors in addition to Factor IX. For example, some such preparations comprise the prothrombin complex which includes Factors II, V, and X in addition to Factor IX.
The occurrence of thrombotic complications, such as deep vein thrombosis, disseminated intravascular coagulation, and pulmonary embolism have been reported in patients treated with prothrombin complex concentrates or in Factor IX preparations that are contaminated with Factor II and/or Factor X. These complications are frequently seen in premature infants, in patients with poor liver function, and in surgery patients. Such complications have also been observed in Hemophilia A patients receiving prothrombin complex concentrate as a Factor VIII inhibitor bypassing agent.
The thrombogenic component of prothrombin complex concentrates has been attributed most often to either activated factors, coagulant active phospholipid, or zymogen overload. Zymogen overload may be the basis of disseminated intravascular coagulation in surgical situations where patients receive large and repetitive doses of prothrombin complex concentrates. In such cases, a buildup of zymogens in the circulation, particularly of Factors II and X, is likely to occur due to their relatively long half-life in relation to Factor IX.
The thrombotic complications associated with the use of prothrombin complex make it desirable to provide a Factor IX concentrate, essentially free of other proteins, for use in treating Hemophilia B patients
Various methods for enhancing the purity of Factor IX concentrates have been reported. For example, processes for producing concentrates of Factor IX, essentially free of prothrombin, and of Factor X by use of affinity chromatography on a sulfated dextran resin have been disclosed (D. Menache et al., "Coagulation Factor IX Concentrate: Method of Preparation and Assessment of Potential In Vivo Thrombogenicity in Animal Models", Blood, 64. 1220-1227 [1984]). Factor IX has been purified by affinity chromatography on a heparin-sepharose resin (L-O. Andersson et al., "Purification and Characterization of Human Factor IX", Thrombosis Research, 7, 451-459 [1975]). Factors IX and X have been separated by using a process which includes heparin-agarose chromatographic techniques (S. P. Bajaj et al., "A Simplified Procedure For Purification of Human Prothrombin Factor IX and Factor X", Preoarative Biochemistry, 11, 397-412 [1981]). Procedures are a)so known in the art for separating Factor IX by affinity chromatography on a dextran sulfate-sepharose gel.
While Factor IX can be separated on sepharose (agarose gels) in the laboratory, the use of agarose gels for large-scale separations has been found to be unsatisfactory. When the agarose gels are packed into commercial-size columns, they compress to an undesirable extent and thereby inhibit flow of liquids through the column. This problem has been overcome by the use of dextran sulfate silica resin, as described in U.S. Pat. No. 4,725,673 to Herring, incorporated herein by this reference. While this purification method is desirable in that the silica gel results in higher flow rates and, therefore, faster purification procedures, it uses a heat treatment to inactivate any viral contaminants that may be present in the human blood-derived protein preparations The heat treatment results in denaturation of a portion of the Factor IX which can lead to low specific-activity Factor IX preparations.
In addition to the above methods, purification of Factor IX has been performed using immunoaffinity and ion-exchange chromatography (S.S. Ahmad et al., "Rapid Purification of Factor IX, Factor X and Prothrombin by Immunoaffinity and Ion Exchange Chromatography", Thromb. Res., 55, 121-133 [1989]), which has resulted in specific-activities as high as 269 units/mg, for Factor IX. While immunoaffinity methods lead to high specific-activity preparations, the necessity to prepare monoclonal antibodies against the proteins to be purified adds a significant cost to the purification procedure.
It is therefore desirable to provide, at a relatively low cost, a process for the purification of Factor IX which yields a high specific-activity Factor IX preparation that is safe for use in humans.


A turbine blade with single tip rail located on the suction side of the tip, and a plurality of curved diffusion holes to discharge cooling air onto the pressure side wall and the tip floor or tip corner of the blade to provide cooling and to limit leakage of the hot gas flow through the tip gap. The curved diffusion holes are curved in an upward direction toward the tip, and each includes a metering hole with an inlet axis normal to the cooling supply cavity surface. A suction side tip rail is flush with the backside wall and slants outward toward the front edge on the inner side. A first curved diffusion hole opens onto the pressure side wall just below the tip corner, a second curved diffusion hole opens adjacent to the tip corner, and a third curved diffusion holes opens onto the tip floor adjacent to the tip corner and at a midpoint between the tip corner and the tip rail. The second diffusion hole provides a layer of film cooling air to the forward side of the tip corner where the first layer of film cooling air does not come into contact so that the entire tip floor is covered by layers of film cooling air.

1. Field of the Invention
The present invention relates generally to a gas turbine engine, and more specifically to a turbine blade with tip cooling.
2. Description of the Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
In a gas turbine engine, especially an industrial gas turbine, engine, the turbine includes several stages of turbine blades that rotate within a shroud that forms a small gap between the rotating blade tip and the stationary shroud. The hot gas that flows through the turbine blades can also leak through this small gap as the hot gas flows leaks across the blade tip from the pressure side to the suction side. The blade tip region is difficult to properly cool which creates hot spots on section of the blade tip that eventually erode or corrode away. Engine performance and blade tip life can be increased by minimizing the gap so that less hot gas flow leakage occurs, and adequately cool the blade tip section. The blade tips are also subject to rub against the inner surface of the shroud that forms the blade outer air seal (BOAS). Blade tips include one or more tip rails to minimize the gap leakage and surface area of the tip crown that rubs.
High temperature turbine blade tip section heat load is a function of the blade tip leakage flow. A high leakage flow will induce a high heat load onto the blade tip section. Thus, blade tip section sealing and cooling have to be addressed as a single problem. A prior art turbine blade tip design is shown in FIGS. 1-3 and includes a squealer tip rail that extends around the perimeter of the airfoil flush with the airfoil wall to form an inner squealer pocket. The main purpose of incorporating the squealer tip in a blade design is to reduce the blade tip leakage and also to provide for improved rubbing capability for the blade. The narrow tip rail provides for a small surface area to rub up against the inner surface of the shroud that forms the tip gap. Thus, less friction and less heat are developed when the tip rubs.
Traditionally, blade tip cooling is accomplished by drilling holes into the upper extremes of the serpentine coolant passages formed within the body of the blade from both the pressure and suction surfaces near the blade tip edge and the top surface of the squealer cavity. In general, film cooling holes are built in along the airfoil pressure side and suction side tip sections and extend from the leading edge to the trailing edge to provide edge cooling for the blade squealer tip. Also, convective cooling holes also built in along the tip rail at the inner portion of the squealer pocket provide additional cooling for the squealer tip rail. Since the blade tip region is subject to severe secondary flow field, this requires a large number of film cooling holes that requires more cooling flow for cooling the blade tip periphery. FIG. 1 shows the prior art squealer tip cooling arrangement and the secondary hot gas flow migration around the blade tip section. FIG. 2 shows a profile view of the pressure side and FIG. 3 shows the suction side each with tip peripheral cooling holes for the prior art turbine blade of FIG. 1.
The blade squealer tip rail is subject to heating from three exposed side: 1) heat load from the airfoil hot gas side surface of the tip rail, 2) heat load from the top portion of the tip rail, and 3) heat load from the back side of the tip rail. Cooling of the squealer tip rail by means of discharge row of film cooling holes along the blade pressure side and suction peripheral and conduction through the base region of the squealer pocket becomes insufficient. This is primarily due to the combination of squealer pocket geometry and the interaction of hot gas secondary flow-mixing. The effectiveness induced by the pressure film cooling and tip section convective cooling holes become very limited. In addition, a TBC is normally used on an industrial gas turbine (IGT) airfoil for the reduction of blade metal temperature. However, applying the TBC around the blade tip rail without effective backside convective cooling may not reduce the blade tip rail metal temperature. FIG. 4 shows the state of the art turbine blade tip cooling design of the prior art.
One location on the blade tip that is difficult to adequately cool is the tip corner on the pressure or upstream side of the blade. Film cooling holes are used to discharge a layer of film cooling air onto the pressure side wall just below the tip corner as disclosed in U.S. Pat. No. 7,192,250 B2 issued to Boury et al. on Mar. 20, 2007 and entitled HOOLOW ROTOR BLADE FOR THE FUTURE OF A GAS TURBINE ENGINE, which shows a film cooling hole angled upward toward the tip, corner formed with a pressure side tip rail. The layer of film cooling air flows up and over the top or crown of the pressure side tip rail. The layer of cooling air does not touch the tip crown. Also, because of the presence of the pressure side tip rail, the cooling air flows over the forward side of the tip pocket formed between the pressure side tip rail and the suction side tip rail.
U.S. Pat. No. 7,029,235 B2 issued to Liang on Apr. 18, 2006 and entitled COOLING SYSTEM FOR A TIP OF A TURBINE BLADE discloses a blade with pressure side wall having a film cooling hole to discharge cooling air upward toward the blade tip, the blade tip having a flat crown with a tip cooling hole to discharge cooling air out from the tip crown in a direction straight up. The problem with this tip cooling design is that the cooling hole on the tip will push the layer of cooling air from the pressure side of the blade over the tip crown so that no cooling air reaches the tip surface to provide cooling. The only cooling occurring to the tip is convective cooling due to the cooling air passing through the hole formed within the tip itself.
U.S. Pat. No. 7,351,035 B2 issued to Deschamps et al. on Apr. 1, 2008 and entitled HOLLOW ROTOR BLADE FOR THE TURBINE OF A GAS TURBINE ENGINE, THE BLADE BEING FITTED WITH A "BATHTUB" discloses a blade tip with single tip rail on the suction side, a flat tip crown, and a front tip corner angled toward the oncoming hot gas flow. A cooling hole is formed in the tip corner and angled toward the oncoming hot gas flow and a tip floor or crown cooling hole to discharge cooling air up and into the area above the tip floor upstream from the tip rail. The problem with this design is that the pressure side wall of the tip corner is not cooled, and the cooling air discharge from the tip corner cooling hole is directed upward so as not to cool the tip surface immediately downstream from the cooling hole. Also, the tip floor cooling hole discharges cooling air straight up so that the layer of cooling air from the upstream hole is pushed up and away from the top surface of the tip to produce inadequate cooling thereof.
U.S. Pat. No. 6,602,502 B2 issued to Liang on Aug. 5, 2003 and entitled AIRFOIL TIP SQUEALER COOLING CONSTRUCTION discloses a blade with a tip floor that is not flat formed by two short tip rails on the pressure side and suction, side, and the pressure side wall adjacent to the tip corner includes one or two film cooling holes directed to discharge cooling air upward toward the tip corner. In this design, the layer of cooling air from the pressure side wall hole or holes flows up and over the pressure side tip rail without touching the tip surface immediately downstream from the pressure side tip rail. Inadequate cooling of the tip floor at this location occurs in this design.
U.S. Pat. No. 5,282,721 issued to Kildea on Feb. 1, 1994 and entitled PASSIVE CLEARANCE SYSTEM FOR TURBINE BLADES shows an earlier design in which the blade tip corner is pointed and slanted toward the oncoming hot gas flow, and one cooling hole located on the pressure side wall and just below the tip corner to discharge cooling air toward the oncoming hot gas flow. This design is intended to push away the hot gas flow from the gap. In a second embodiment, a second cooling hole discharges cooling, air from the tip crown surface at an angle toward, the oncoming hot gas flow to also block the hot gas from entering the gap. A film layer of cooling air is not developed onto the surface of the tip crown or floor at the pressure side corner.
This problem associated with turbine airfoil tip edge cooling can be minimized by incorporation of anew and effective blade tip cooling geometry design of the present invention into the prior art airfoil tip section cooling design.

Turbine blade with curved tip cooling holes


An objective of the present invention is to provide a transformant altered so as to produce a secondary metabolite in which a benzene ring of the secondary product is modified at the para-position with a functional group containing a nitrogen atom. A transformant according to the present invention is a transformant of an organism producing a secondary metabolite having a benzene ring skeleton without substitution at the para-position with a functional group containing a nitrogen atom, said transformant being transformed by introducing genes involved in a biosynthetic pathway from chorismic acid to p-aminophenylpyruvic acid, including a gene encoding an amino acid sequence (SEQ ID NO: 2) having 4-amino-4-deoxychorismic acid synthase activity, a gene encoding an amino acid sequence (SEQ ID NO: 4) having 4-amino-4-deoxychorismic acid mutase activity and a gene encoding an amino acid sequence (SEQ ID NO: 6) having 4-amino-4-deoxyprephenic acid dehydrogenase activity, so as to produce a secondary metabolite having a benzene ring skeleton substituted at the para-position with a functional group containing a nitrogen atom. Another objective of the present invention is to provide a novel gene involved in the biosynthetic pathway from chorismic acid to p-aminophenylpyruvic acid. A novel gene according to the present invention comprises genes encoding the amino acid sequences of SEQ ID NOs: 2, 4 and 6 or modified sequences thereof.

1. Field of the Invention
The present invention relates to transformants producing secondary metabolites modified by functional groups, more specifically, to transformants producing secondary metabolites in which a benzene ring is modified at the para-position with a functional group containing a nitrogen atom. Furthermore, the present invention relates to novel genes involved in a biosynthetic pathway from chorismic acid to p-aminophenylpyruvic acid.
2. Description of the Related Art
Since organisms produce a number of various kinds of secondary metabolites having biological activity, research for utilizing these metabolites for drugs for humans and animals, agricultural chemicals, and the like has been actively carried out. However, secondary metabolites from organisms can rarely be utilized for practical use as they are, and accordingly they are generally modified with various functional groups to optimize their biological activity. A modification with a functional group containing a nitrogen atom, such as a nitro group and amino group, is one of the most important modifications.
Chemical methods are available for modifying a certain substance with a nitro group. However, introduction of a nitro group into a benzene ring specifically at the para-position using a chemical method is extremely difficult, and its yield is very low. Furthermore, when a substance to be modified with a nitro group is as complex as a secondary metabolite from an organism, it is even more difficult to specifically modify a benzene ring at the para-position with a nitro group.
On the other hand, methods of introducing an amino group are generally classified into two groups, i.e., enzymatic methods and chemical methods. In enzymatic methods, an enzyme called aminotransferase (EC 2.6.1 group) is used. However, substances which can be a substrate for the aminotransferase are limited, and no enzyme has been known to directly transfer an amino group to a benzene ring. Therefore, only chemical methods have been available for modification of a benzene ring with an amino group.
However, in chemical procedure, it is necessary to first modify a benzene ring with a nitro group and then to reduce this nitro group into an amino group. Since the nitration reaction in the first step is very difficult, introduction of the amino group into the benzene ring by chemical methods is extremely difficult. Accordingly, development of a method of modifying a benzene ring specifically at the para-position with a nitro group or an amino group has been strongly needed.

Transformant producing secondary metabolite modified with functional group and novel biosynthesis genes


In a cooling roller which cools a molten resin strip discharged from a die, a temperature of a place where a resin comes into contact with the cooling roller, and that of a place where the resin is detached from the cooling roller are individually controlled. The cooling roller comprises: a non-rotatably disposed inner cylinder 11; a rotatable outer cylinder 3 disposed coaxially with the inner cylinder 11; an annular medium channel 13 formed by an outer peripheral surface of the inner cylinder 11 and an inner peripheral surface of the outer cylinder 3; a plurality of small medium channels 73, 75 divided from the medium channel 13 by a plurality of partition members 69, 71; a plurality of medium inflow ports 77, 79 disposed in a wall portion of the inner cylinder along an axis of the inner cylinder 11 so as to communicate with the respective small medium channels 73, 75; and a plurality of slit-like medium outflow ports 81, 83.

1. Field of the Invention
The present invention relates to a heating and cooling roller, more particularly to a heating and cooling roller which cools a molten resin strip discharged from a die of an extruder or which heats a solidified resin strip.
2. Description of the Related Art
Heretofore, a heating and cooling roller is known which includes: a non-rotatably disposed inner cylinder; a rotatable outer cylinder disposed coaxially with the inner cylinder; an annular medium channel defined by a gap between an outer peripheral surface of the inner cylinder and an inner peripheral surface of the outer cylinder; slit-like medium inflow and outflow ports which are disposed in the inner cylinder and which extend along the approximately whole length of an axis of the inner cylinder; medium supply and discharge paths which are disposed in the inner cylinder to communicate with the medium inflow port and the medium outflow port, respectively, and which supply a medium to the medium inflow port or guide the medium from the medium outflow port to the outside; and a partition member which is disposed between the medium inflow port and the medium outflow port of the inner cylinder to divide the annular medium channel in a peripheral direction and which extends in an axial direction of the inner cylinder (see, e.g., Patent Document 1).
When the heating and cooling roller is used, a temperature distribution of the roller in a width direction can be constantly homogenized, because the slit-like medium inflow and outflow ports are extended along the approximately whole length of the axis of the fixed inner cylinder. This can reduce a lateral temperature fluctuation of a matter to be heated or cooled.
Moreover, since the medium inflow port is disposed in a fixed position, the matter to be heated or cooled first comes into contact with the outer peripheral surface of the outer cylinder constantly maintained at a predetermined temperature, and the matter moves with the rotation of the outer cylinder. Therefore, any temperature unevenness is not generated in a flow direction of the matter to be heated or cooled. Therefore, a flow rate of the medium does not affect the temperature evenness, and the flow rate of the medium can be reduced to reduce the vibrations of the roller and simplify a piping line. In addition, it is possible to control the temperature of the matter to be heated or cooled at the end of contact by controlling not only the medium temperature but also the medium flow rate.
Furthermore, since the medium is supplied from the fixed inner cylinder, there is produced an effect that any rotary joint does not have to be disposed in a medium supply portion.
[Patent Document 1] Japanese Patent Application Laid-Open No. 6-87150
Additionally, in the conventional cooling roller which cools the molten resin strip discharged from the die of the extruder, if a temperature difference can be achieved between a contact start point (the point where the molten resin strip discharged from the die of the extruder comes into contact with the cooling roller) on this cooling roller and a detached point (the point where the strip is detached from the cooling roller) on the cooling roller (outer surface of the outer cylinder), moldability of the molten resin strip is improved.
That is, a higher temperature of the cooling roller is preferred at the place where the molten resin strip discharged from the die comes into contact with the cooling roller. This is because there is improved a close contact property of the molten resin strip with the cooling roller, and there is reduced a temperature difference between a front and a back of the molten resin strip (sheet) in contact with the cooling roller.
On the other hand, a low temperature of the cooling roller is preferred at the detaching place where the resin strip cooled by the cooling roller departs from the cooling roller. This is because crystallization of the resin strip can be inhibited, and peelability of the resin strip from the cooling roller is improved.
However, in the conventional cooling roller, there exists only one medium channel formed by the gap between the outer peripheral surface of the inner cylinder and the inner peripheral surface of the outer cylinder. Therefore, there is a problem that it is not possible to individually control the temperature at the place where the molten resin strip discharged from the die comes into contact with the cooling roller, and the temperature at the parting place where the resin strip discharged from the die of the extruder departs from the cooling roller.
In other words, a conflicting state is caused in which when the temperature of the contact start place is raised, the temperature of the detaching place also rises. On the other hand, when the temperature of the detaching place is raised, the temperature of the contact start place drops. The temperature difference is caused only by the heat received from the molten resin strip. That means that an only small temperature difference (e.g., about 2° C. to 3° C.) is achieved between the temperature at the contact start place and the temperature at the detaching place, and it is difficult to obtain the above-described effects (the close contact property and an improved peelability of strip).
It is to be noted that the above problems arise not only in a case where the molten resin strip discharged from the die of the extruder is cooled but also in the heating roller which heats the solidified resin strip.


The invention relates to processes for the production of unsaturated fatty acids, preferably of conjugated polyunsaturated fatty acids such as conjugated linoleic acid (CLA), by the recombinant expression of desaturases from insects of the order Lepidoptera. Expression preferably takes place in an organism selected from the group of the plant organisms, yeasts, fungi and algae. Also, according to the invention are recombinant expression cassettes for the recombinant expression of desaturases from insects of the order Lepidoptera, and the transgenic organisms transformed with these.

Fatty acids and triglycerides are used widely in the food industry, in animal nutrition, in cosmetics and in the pharmaceutical sector. Especially valuable and sought-after unsaturated fatty acids are what are known as conjugated unsaturated fatty acids. Conjugated polyunsaturated fatty acids are relatively rare in comparison with other polyunsaturated fatty acids. Examples of conjugated fatty acids are the conjugated linoleic acids (CLA; conjugated linoleic acid), α-parinaric acid (18:4 octadecatetraenoic acid), eleostearic acid (18:3 octadecatrienoic acid), the conjugated linolenic acids, dimorphecolic acid and calendulic acid (see scheme 1).

CLA is a collective term for positional and structural isomers of linoleic acid which are distinguished by a conjugated double bond system starting at carbon atom 8, 9, 10 or 11. Some examples are shown in scheme 2.
Geometric isomers exist for each of these positional isomers, that is to say cis-cis, trans-cis, cis-trans, trans-trans.

The CLA isomers (9Z,11E)-CLA and (10E,12Z)-CLA are known as the biologically active isomers. CLA is found predominantly in foodstuffs of animal origin. High CLA concentrations are found in particular in the meat and in dairy products of ruminants: approx. 3 to 4 mg of CLA/g fat in beef and lamb (Chin et al. (1992) J Food Comp Anal 5:185-197) and approx. 3 to 7 mg of CLA/g fat in dairy products (Dhiman et al. (1999) J Dairy Sci 82:2146-56), where (9Z,11E)-CLA at a concentration of approximately 80% is in each case the predominant isomer. Higher plants only contain traces of CLA, with the two biologically active CLA isomers not having been found in plants to date.
A range of positive effects have been found for CLA; thus, the administration of CLA reduces the body fat in humans and animals and increases the rate at which feed is converted into body weight in animals (Park et al. (1997) Lipids 32:853-858; Park et al. (1999) Lipids 34:235-241; WO 94/16690; WO 96/06605; WO 97/46230; WO 97/46118). The administration of CLA also has a positive effect on, for example, allergies (WO 97/32008) or cancer (Banni et al. (1999) Carcinogenesis 20: 1019-1024, Thompson et al. (1997) Cancer Res 57:5067-5072). An antiarteriosclerotic effect of CLA has also been confirmed (Wilson et al. (2000) Nutr Res 20:1795-1805). Studies were carried out with isomers and with isomer mixtures.
CLA can be synthesized by alkaline isomerization of linoleic acid. Vegetable oils with a high linoleic acid content are predominantly used on an industrial scale, for example sunflower oil, safflower oil. Heating to above 180° C. under alkaline conditions catalyzes two reactions:    (1) the fatty acid ester bonds of the triglyceride skeleton are hydrolyzed and the free fatty acids are liberated,    (2) unconjugated unsaturated fatty acids with two or more double bonds are conjugated.
Commercially available CLA oils contain a mixture of various CLA isomers and other saturated and unsaturated fatty acids. Owing to the presence of these biologically inactive and unnatural isomers, laborious purification of the biologically active isomers (9Z,11E) CLA and (10E,12Z) CLA is required, or it must be demonstrated that the isomer mixture does not represent a health hazard for humans and animals. It has hitherto not been possible to produce individual CLA isomers by alkaline isomerization in an economically relevant process. Fractional crystallization makes it possible to concentrate the isomers (9Z,11E)-CLA and (10E,12Z)-CLA, respectively. However, it is not possible in all of the abovementioned processes to prepare individual isomers in high quality. In the abovementioned processes, the reaction products are usually converted into methyl or ethyl esters so that the natural form of CLA, viz. the free fatty acids or the triacyl glyceride, are not available.
These disadvantages of chemical conversion can be overcome by carrying out the conversion of linoleic acid into CLA by biocatalysis. Various microorganisms of the rumen of ruminants are capable for example of converting linoleic acid into CLA during the biohydrogenation process. This is effected by the enzymatic activity of a CLA isomerase, inter alia. This enzymatic activity was described in Butyrivibrio fibrisolvens (Kepler and Tovee (1966) J Biol Chem 241:1350), Propionibacterium acnes (Deng et al., 1st International Conference on CLA, 2001, Alesund, Norway), Clostridium sporogenes and Lactobacillus reuteri (WO 99/32604; WO 01/00846). The CLA isomerases described to date utilize free fatty acids as substrate. The genes encoding CLA isomerase from Lactobacillus reuteri and Propionibacterium acnes were cloned, and the isomerase from Propionibacterium was expressed functionally in heterologous microorganisms. While the bioconversion of linoleic acid into CLA by microorganisms has qualitative advantages over alkaline isomerization, it is economically disadvantageous, owing to the fermentation costs, and only yields free fatty acids, but no triglycerides. However, free fatty acids have disadvantageous olfactory properties and are essentially unsuitable for use in the food- and feed sector. A subsequent conversion of the free fatty acids—for example glycerol or gylcerides with lipase catalysis—is possible, but complicated.
The methods which are based on bacterial CLA isomerases can always be applied to other organisms. So far, it has been shown that CLA isomerases convert free linoleic acid into CLA (Cepler and Tove (1967) J Biochem Chem 242:5686-5692). In higher organisms such as, for example, plants, linoleic acid predominantly exists in esterified form. Lipids such as triacyl glycerides constitute the storage form, while thioesters such as acyl-CoA constitute the active form of the fatty acid.
Fatty acids with trans double bonds are extremely rare. The seed oil of some plants contains fatty acids with double bonds in the trans position. Thus, an E5-fatty acid has been detected in the seed oil of various Thalictrum species (Rankoff et al. (1971) J Amer Oil Chem Soc 48:700-701). Moreover, E5-desaturase activity has been described in Aquilegia vulgaris (Longman et al. (2000) Biochem Soc Trans 28:641-643). However, no plants have been described which contain either trans-vaccenic acid (E11-octadecenoic acid) or E10-octadecenoic acid.
It is known that the desaturation of fatty acids in plants can take place mainly by two mechanisms:    (1) in plastids, fatty acid ACP esters are desaturated by a soluble desaturase, predominantly at position 9, and    (2) on the endoplasmic reticulum, membrane lipids, especially phosphatidyl cholins, are preferentially further desaturated at positions 6, 12 and 15 by membrane-bound desaturases.
In some plants, conjugated fatty acids are produced by the activity of a conjugase (Crombie et al. (1984) J Chem Soc Chem Commun 15:953-955; Crombie et al. (1985) J Chem Soc Perkin Trans 1:2425-2434; Fritsche et al. (1999) FEBS Letters 462: 249-253; Cahoon et al. (2001) J Biol Chem 276:2637-2643; Qiu et al. (2001) Plant Physiol 125:847-855). The biosynthesis of conjugated fatty acids such as calendulic acid, eleostearic acid or punicic acid proceeds via the desaturation of oleic acid to linoleic acid by a D12-desaturase and a further desaturation in conjunction with a rearrangement of the Z9- or Z12-double bond to the conjutrienic fatty acid by a specific conjutriene-forming desaturase (conjugase). Besides the production of calendulic acid, Qui et al. (2001) Plant Physiol 125:847-855) also describe the production of conjugated linoleic acid by the enzymatic activity of conjugase. However, the disadvantage of this secondary activity is that the enzymatic activity gives rise to the undesired 8,10-isomer of the conjugated linoleic acid.
Pheromone desaturases from lepidopterans display a wide range of substrate specificities and desaturation mechanisms (Roelofs and Wolf (1988) J Chem Ecol 14:2019-2031; Roelofs (1995) Proc Nat Acad Sci USA 92:44-49; Tillman et al. (1999) Insect Biochem 29:481-514). These enzyme activities cause the production of unusual unsaturated fatty acid CoA derivatives with a wide range of chain lengths and with double bonds at different positions and with different configurations. They act as starting material for the biosynthesis of pheromones. Liu et al. describe an E11-desaturase from the pheromone gland of a moth species ("light brown apple moth"), which is likely to play a role in pheromone biosynthesis (Liu W T et al. (2002) Proc Natl Acad Sci USA 99(2):620-624.
Knipple et al. (Genetics 2002 December; 162(4):1737-52) compare various integral membrane desaturases from moths and flies which have been isolated from the pheromone glands of these insects. A fragment of an acyl-CoA desaturase (PgosVASQ) from Pectinophora gossypiella is described. The corresponding sequence has been deposited under the GeneBank Acc. No.: AF482921. Neither the complete sequence nor the specific activity of the desaturase are described. It was named merely on the basis of homologies with other desaturases.

Process for the production of unsaturated fatty acids


This disclosure provides a LC panel and the UV curing method therein for the LC curing treatment. The LC panel includes: a first substrate with a plurality of protrusion electrodes formed thereon; a second substrate disposed on the first substrate; a LC layer interposed between the first and second substrates; and a deflecting structure disposed between the first and second substrates and configured for changing optical paths of UV light; wherein the UV light passes through the areas between the neighboring protrusion electrodes, and the deflecting structure is located in the optical paths of the UV light.

Blue phases are liquid crystal phases that appear in the between a chiral nematic phase and an isotropic liquid phase. Blue-phase LC has been applied to the LC display manufacturing due to its fast response and no need in rubbed alignment. However, such kind of LC operates in the blue phase mode and exhibits its advantages only over a quite limited temperature range. To solve the problem, some monomers can be added to the blue-phase LC, and the mixture is exposed to UV light for the curing treatment. This is the so-called polymer-stabilized blue phase (PSBP) LC, which may extend the temperature range of blue-phase mode.
Regarding the above-mentioned UV curing treatment, if a LC panel of the display has protrusion-typed electrodes, the UV exposure may be shielded and affected by the electrodes. The uneven exposure can lower the stability and uniformity of LC polymerization and diversify LC electro-optic characteristics, such as hysteresis and residual birefringence, in the blue-phase LC cell. This may at least causes the fact that the dark-state performance of the blue-phase LC display would be deteriorated. Consequently, it is in need to develop a new method for curing LC in the blue-phase LC display, which can provide a much uniform UV exposure, so as to improve the polymerization stability and electro-optic characteristics of the blue-phase LC.

Liquid-crystal panel and the UV curing method thereof


Certain bits of a packet, such as bits in the IP header of an IP packet, are used to designate the type of service or Quality of Service (QoS) level to be afforded to the packet as it passes through a data communications network. A user entitled to a certain QoS level logs into a service selection gateway SSG. The SSG queries an authentication, authorization and accounting (AAA) server in response to a log-in attempt by the user. Upon authorization, the AAA server returns an access accept signal in addition to an indication from the user's service profile (user profile) as to the QoS level to be afforded the user. While the user is logged in, all packets are routed through the SSG. The SSG sets the certain bits of the packet in accordance with the user's assigned QoS level so that as the packets are routed through the data communications network, they are consistently afforded the assigned Quality of Service level. In another aspect of the invention, on-demand QoS may be provided by the SSG and accounted for by communications with the AAA server.

1. Field of the Invention
The present invention relates to the field of data communications networks. More particularly, this invention relates to a method and apparatus for implementing a quality of service (QoS) policy in a data communications network so as to thereby prioritize network traffic into a plurality of service levels and provide preferential treatment of different classes of data traffic on the data communications network. A number of priority levels may be implemented in accordance with the invention.
2. The Background
This invention relates to switched packet data communications networks. There are a number of different packet types which are used in modern switched packet data communications networks.
FIG. 1A depicts a generic packet 8 using Layer 2 encapsulation. A number of different Layer 2 encapsulation protocols are recognized. Each includes a MAC (media access control) destination address 10 and a MAC source address 12. The data 14 may include Layer 3 encapsulated packet information. A CRC (cyclic redundancy check) 16 is also provided at the end of the Layer 2 encapsulation. The unlabeled block 18 may include an Ethernet type for Ethernet V 2.0 (ARPA) packets. The Ethernet type may include IPv4 (IP) (in the future, IPv6), IPX, AppleTalk, DEC Net, Vines IP/Vines Echo, XNS, ARP or RARP. Other known encapsulations include SAP, SAP1, SNAP and the like. The meaning of the bits in block 18 differs among the different encapsulation protocols. This information is sometimes referred to as the Layer 2 Flow Information.
FIG. 1B depicts a typical IP packet (Layer 3) structure. The IP packet format is presently one of the most common Layer 3 packet types. The fields of importance to this disclosure are the "ToS value" or type of service 26 which is a preferably 8-bit field also known as Differentiated Services ("DS"), "prot-typ" or IP protocol type 28 (typically either TCP (transmission control protocol) or UDP (user datagram protocol), the Source IP address 30 (usually the IP address of the originating station), the Destination IP address 32 (usually the IP address of the ultimate destination station), the Layer 4 source port number 34 (available for TCP and UDP packets only) and the Layer 4 destination port number 36 (available for TCP and UDP packets only). The Layer 4 flow information may be used to identify a particular packet flow as being the product of (source port) or directed to (destination port) a particular application. The ToS/Differentiated Services field is used by routers of the data communications network to provide priority/delay/dropping services.
As the use of data communications networks increases worldwide, congestion of those networks has become a problem. A given data communications network, a given node on a data communications network, or a given link connecting two nodes has a certain capacity to pass data packets and that capacity cannot be exceeded. When data traffic on the data communications network becomes heavy enough that one can anticipate congestion problems which might lead to packets being dropped, it is desirable to implement a "Quality of Service" or QoS policy so as to give priority to certain types of traffic and/or customers so as not to drop their packets, thus assuring that critical communications are able to pass through the data communications network and/or providing a guaranteed service level, albeit at the expense of less critical communications.
The QoS level mapped into the ToS/Differentiated Services precedence bits (or other bits of the packet) is used by devices such as routers, gateways and switches within a data communications network in a number of ways. For example, packet rate limiting may be imposed to cap a user's throughput of packets to a given contract level specified in a service agreement with the user. In this way limited system services may not be over-used by those paying the least for those services. In another example, packet rate limiting may be imposed under congested network conditions to drop or modify packets based, at least in part, upon the QoS level associated with the packet. Those with a "higher" QoS level will do better in getting their communications through in congested conditions than those with a "lower" QoS level.
One way in which the ToS bits of the IP header are presently used is to use edge routers 38 as shown in FIG. 2 to interface between users 40 and core routers 42, 44, 46. In accordance with this approach the edge routers are used to set the ToS precedence bits (the highest order three bits of the eight-bit ToS/Differentiated Services field) based upon the source IP address of the packet. While this can be effective in some environments, it is rather inflexible since it is based solely on pre-programmed IP addresses and creates administrative burdens in programming all of the edge routers. It is also ineffective in handling many types of roaming users and/or users with dynamically assigned IP addresses such as those obtained or leased from DHCP (dynamic host control protocol) servers.
Accordingly, a need exists for a QoS system which can provide for the QoS needs of roaming or DHCP users while simplifying the task of programming QoS levels associated with the user. Furthermore, it would be desirable to provide a QoS system that provides on-demand QoS rather than a fixed QoS for each user to better accommodate the shifting needs of users.

This patent is subject to a terminal disclaimer.

Use of precedence bits for quality of service


The present disclosure provides CDK9 inhibitors. Also provided are methods of treating a disease or a disorder comprising administering to a subject in need of treatment one of the CDK9 inhibitors disclosed herein. In some embodiments, the disease or disorder to be treated is cancer. In some embodiments, the disease or disorder is liver cancer.

Despite advances, treatment of cancer remains relatively difficult. Systemic treatments such as chemotherapies may be toxic and have negative side effects on patients. While CDK9 inhibitors have shown promise as small molecule cancer therapeutics, their potential utility has been limited by poor targeting to cancerous tissue and resulting peripheral exposure. Accordingly, there is a need for the development of CDK9 inhibitors as small molecule cancer therapeutics with improved targeting.

Certain chemical compositions and methods of use thereof


The present invention provides a system for transdermal delivery of water insoluble drugs and methods using the same. The system includes a pharmaceutical composition of a water insoluble drug and a carrier molecule that enhances the solubility of the drug in aqueous solution, a medical patch containing the same and an apparatus that generates hydrophilic micro-channels in an area of skin of a subject using the composition or patch. The system preferably avoids the use of penetration enhancers and is particularly useful for transdermal delivery of steroids.

Transdermal drug delivery is an attractive concept as such means may offer a convenient and comfortable mode of delivery. The variable rates of absorption and metabolism encountered in oral administration are avoided, together with eliminating adverse effects such as gastro-intestinal irritation; it is a noninvasive method, and it may provide superior control of blood concentration of a particular drug over time.
However, skin is a complex structure that functions as a barrier to ingress of foreign substances into the body. Molecules moving from the environment into and through intact skin must first penetrate the stratum corneum, which presents the primary barrier to absorption of topical compositions or transdermally administered drugs, especially for oil-insoluble and ionized salt forms of drugs.
A number of different methods have been developed for transdermal drug delivery, enabling the administration of a variety of drugs. One approach includes formulations of drugs as to enable their delivery through the skin, including development of number of skin penetration enhancing agents, or "permeation enhancers", to increase skin permeability. The formulated drugs may be applied to the skin in the forms of patches, films, or matrices of various compositions. Another approach includes non-chemical modes for facilitating transdermal delivery, e.g. the use of iontophoresis, electroporation or sonophoresis.
Transdermal Delivery Apparatus
Electrotransport or iontophoretic drug delivery devices have been disclosed as being useful for the delivery of drugs for which it is anticipated that transdermal delivery would be advantageous. U.S. Pat. Nos. 6,169,920 and 6,317,629 to Alza for example disclose iontophoretic drug delivery apparatus, and U.S. Pat. No. 5,983,130 to Alza discloses an electrotransport agent delivery method and apparatus suitable for ionizable drugs.
Electroporation is also well known in the art as a method to increase pore size by application of an electric field. Electroporation is disclosed as a means for transiently decreasing the electrical resistance of the stratum corneum and increasing the transdermal flux of small molecules by applying an electric field to increase the size of existing pores (Chizmadzhev et al., Biophysics Journal, 1998, 74 (2), 843-856).
U.S. Pat. No. 5,019,034 to Weaver et al. describes apparatus for applying high voltage, short duration electrical pulses on the skin to produce electroporation.
WO 97/07734 to Eppstein et al. discloses thermal ablation of the stratum corneum using an electrically resistive element in contact with the stratum corneum, such that a high current through the element causes a general heating of tissue in its vicinity, most particularly the stratum corneum 10-50 micron thick outermost layer of the skin.
U.S. Pat. Nos. 5,885,211, 6,022,316, 6,142,939 and 6,173,202 to Eppstein et al., which are incorporated herein by reference, describe methods for forming micropores in the stratum corneum by heating tissue-bound water above the vapor point with a heat-conducting element, so as to enhance transdermal transport of an analyte or active substance. Further enhancement techniques include the use of sonic energy, pressure, and chemical enhancers.
U.S. Pat. No. 3,964,482 to Gerstel, U.S. Pat. No. 6,050,988 to Zuck, and U.S. Pat. No. 6,083,196 to Trautman et al. describe other apparatus and methods for facilitating transdermal movement of a substance.
U.S. Pat. No. 6,148,232 to Avrahami, which is incorporated herein in its entirety by reference, describes apparatus for applying electrodes at respective points on skin of a subject and applying electrical energy of radio frequency (RF) between two or more of the electrodes to cause ablation of the stratum corneum primarily in an area intermediate the respective points, forming micro-channels. Various techniques for limiting ablation to the stratum corneum are described, including spacing of the electrodes and monitoring the electrical resistance of skin between adjacent electrodes.
The apparatus of the type disclosed in U.S. Pat. No. 6,148,232 and continuations thereto (U.S. Pat. Nos. 5,983,135; 6,597,946; and 6,611,706, and International Patent Application Nos. WO01/85234; WO 02/085451; and WO 02/092163) is referred to hereinafter by the names ViaDerm or MicroDerm.
Transdermal Patches
There are two prevalent types of transdermal patch designs, namely the reservoir type where the drug is contained within a reservoir having a basal surface that is permeable to the drug, and a matrix type, where the drug is dispersed in a polymer layer affixed to the skin. Both types of device typically include a backing layer and a release liner layer that is removed prior to use. In an effort to increase skin permeability so that the drugs can be delivered in therapeutically effective amounts, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of adjuvants known as "increasers" or "permeation enhancers" to increase the rate of permeation of the active ingredient. Various materials have been suggested for this purpose, as described for example in U.S. Pat. No. 6,004,578 to Lee at al., and references therein, which are incorporated herein by reference.
However, such permeation enhancers often cause problems such as irritation, sensitization, or severe inconvenience, and therefore the number of drugs that can be safely and effectively administered through skin remains limited.
Delivery of Water-Insoluble Drugs
Many powerful drug substances are insoluble in water, limiting the effectiveness of their use as therapeutic agents. One approach to enhance the solubility of such drugs in water is to form a reversible complex between the water insoluble drug and a carrier molecule; the characteristics of the carrier molecule are such that the carrier molecule and the reversible complex are soluble in water. Among the carrier molecules are amorphous cyclodextrins described, for example, in U.S. Pat. Nos. 5,134,127; 5,376,645; 5,874,418; and 6,046,177. The use of cyclodextrin and its derivatives as solubilizing agents for water insoluble drugs for oral, intranasal, or parenteral administration is disclosed.
Steroid compounds affect a large number of important physiological functions in humans, and natural as well as synthetic steroids and their derivatives are in use for therapeutic purposes. Methods of steroid administration depend both on the steroid and on the specific disorder. Many of the beneficial steroids that are administered therapeutically to patients are insoluble in water.
The steroid testosterone is the main androgenic hormone formed in the testes. Testosterone therapy is indicated for the treatment of male hypogonadism, and is also suggested for treatment of wasting conditions associated with AIDS and cancer, for treatment of osteoporosis, and for combination hormone replacement therapy for women and male fertility control.
Transdermal delivery of androgens, alone or in combination with estrogenic agents has been disclosed, for example, in U.S. Pat. Nos. 4,867,982; 5,460,820; 5,622,944; and 6,214,374; and in International Patent Application Nos. WO 95/03764; WO 97/24148; WO 98/37871; and WO 00/76522. Many of the cited patents disclose the use of various patches for the transdermal delivery of testosterone. One limitation in the use of such patches is the requirement for scrotal application, which presents problems of inconvenience to the patients (U.S. Pat. Nos. 4,704,282; and 5,840,327). Although non-scrotal application was also suggested (for example, U.S. Pat. Nos. 5,152,997; and 6,132,760), efficient delivery through skin requires the use of permeation enhancers, which by themselves may cause severe problems of irritation and sensitization. In addition, the size of suggested patches is, for small patches, at the range of 30 cm2, while most frequently used patches are at a size range of 60 cm2. Another limitation in the use of such patches is the inability to adequately control androgen serum concentrations and hence androgen bioavailability. Transdermal delivery of androgen formulated into gels was also suggested (e.g. WO 0217927); the main limitation of administering androgen by way of a gel is the resulted undesired contamination of other subjects being in a close contact with the subject in need.
The use of amorphous cyclodextrins for pharmaceutical formulation of steroids to enable therapeutic administration has been disclosed, but nowhere in the background art is it taught or suggested that these formulations are suitable for transdermal use.
The aforementioned U.S. Pat. No. 5,874,418 demonstrates the utility of a specific cyclodextrin derivative having 7 sulfoalkyl ether substituents, (SBE)7-β-cyclodextrin, for the preparation of sustained release formulation of a pharmacologically active agent, with testosterone serving as an example.
U.S. Pat. No. 5,824,668 discloses compositions including at least one 5β steroid and an amorphous cyclodextrin formulated for parenteral administration. International Patent application WO 96/16659 discloses stabilized suspension of corticosteroids with cyclodextrins useful for therapeutic treatment of the eye, ear and nose.
Thus, there is a recognized need for, and it will be highly advantageous to have compositions and methods for an efficient transdermal delivery of water-insoluble drugs in general, and water insoluble steroids in particular, which scarcely cause irritation and are applied to small skin areas.

Transdermal delivery system for water insoluble drugs


A method and an apparatus for providing reference signal received power (RSRP) are disclosed herein. According to one embodiment, a signal is received in a modem. Signal elements at reference signal (RS) locations are extracted from the received signal. The signal elements are descrambled to remove a RS sequence. A linear average of the descrambled signal elements is performed to form virtual reference signal (VRS) elements. The RSRP is estimated from the VRS elements.

Existing approaches for estimating RSRP directly utilize reference signal (RS) elements of a received signal under the assumption that channels do not vary greatly. However, such approaches result in overestimation of the RSRP, since the noise power within the RS element contributes to the RSRP estimate. Additionally, such approaches result in an overestimation of the signal to noise ratio (SNR), and also poor mobility decisions.

Method and apparatus for providing enhanced reference signal received power estimation


What is disclosed is a device for extinguishing fires, and utilization of the device for stationary protection of specific objects, and for dust abatement during blasting operations, and a method for extinguishing forest or terrain fires with the extinguishing device. The extinguishing device comprises a container for receiving an extinguishing agent, and an explosive in or on this container, by means of detonation of which the extinguishing agent is atomized to form a mist and brought into the fire. In order to increase the flexibility and effectiveness in practical use, the container consists of a flexible hose which may be closed at both ends. The method of extinguishing forest or terrain fires with this device provides for the hose to be laid out in front of the fire front, filled with the extinguishing agent, and exploded by detonation of the explosive.

Atomization of an extinguishing agent into microfine particles by means of an explosive with the aim of extinguishing fires, is known. During detonation of a preferably high-explosive charge within or in the vicinity of a homogenous medium such as, for example, water, a pressure of several thousand bar is developed, so that the water is atomized into microfine particles and is thrown by the resultant pressure wave from the center of the explosive charge into the surrounding area. By a high-explosive charge is meant one which develops a detonation wave with a propagation speed of above 5000 meters per second. The mist of extinguishing agent, such agent used, and due to the small size of the individual droplets of extinguishing agent in relation to amount of such agent used, surface area, by means of which the extinguishing agent is applied to the fire in the neighborhood of the detonated container and extinguishes it by means of the known supercooling effect. In addition, the extinguishing effect during detonation of an extinguishing agent also results in a known way from the blowing-out effect of the detonation wave.
There are known from U.S. Pat. No. 1,119,779 and from EP 390 384 fire extinguishers provided for stationary use, and which utilized the effect described above of detonation of an extinguishing agent. These known devices for extinguishing fires have a cylindrical container for receiving an extinguishing agent, and a concentrically-disposed elongate internal container which extends in the longitudinal direction in the extinguishing agent container, and which is filled with an explosive charge.
From EP 488 536 there is known such a fire extinguisher, in which the explosive charge, in contrast to the fire extinguishers described above, is attached externally to the extinguishing agent container.
U.S. Pat. No. 3,980,139 and FR 1 473 621 respectively disclose a "fire-extinguishing bomb" comprising a cylindrical glass or plastics container for receiving an extinguishing agent, and also comprising a cylindrical, concentrically-disposed internal container, which in turn contains the explosive material. The difference between these fire-extinguishing bombs and the fire extinguishers described before consists purely in the ignition of the explosive, which is effected in the bombs either by a radio signal or by the effect of heat when the fire-extinguishing bomb is thrown into a fire.
All the fire-extinguishing devices described above have a common disadvantage, namely that, in practical use in extinguishing fires, they are insufficiently flexible and effective. Thus stationary fire extinguishers always have only a localized effect, so that fire-protection over a large area, or also in large-area firefighting, are impracticable for economic reasons, as too many of this type of fire-extinguisher would have to be used. With respect to mobile firefighting, for example in forest or other terrain fires, the "fire-extinguishing bombs" described have proved disadvantageous, as when the extinguishing bomb is launched they do not exert a directed extinguishing effect due to the detonation, and moreover, rather fan the flames when they are ignited in the center of the fire. Finally, launching these extinguishing devices over the seat of the fire is, to a great extent, complex and cost-intensive, not to mention unsatisfactory as regards hit accuracy.

Method and device for extinguishing fires


Particles containing enzyme or optical brightener in a mixture with particles containing peroxy bleach, surfactant or builder stabilized during storage by coating the former and/or the latter particles with clay, e.g. bentonite.

Particulate detergents containing particles of an enzyme mixed with separate particles of a bleaching agent or a detergent builder are commonly used. It is known that the latter components may negatively affect the storage stability of the enzyme.
As a solution to this stability problem, the prior art suggests coating of the particles of the enzyme. It is known that the coating material needs to be carefully selected since it must on one hand protect the enzyme and on the other hand release the component rapidly when the detergent is dissolved.
As an example, WO 87/07292 (Novo) (which corresponds to U.S. Pat. No. 4,973,417) teaches that the use of an enteric coating on enzyme particles improves the stability in detergent with bleach; the enteric coating material dissolves at the pH of the detergent solution. However, we have found that this does not always give sufficient storage stability.
Thus, we have recognized that a need exists for a composition wherein the enzyme has improved stability during storage.


A communication terminal (10) is coupled to and operable in a power line network with at least one of plurality of intelligent circuit breakers (40) wherein each such circuit breaker (40) has a communication port. The terminal (10) includes a housing and connection means (12, 14) for connecting the terminal (10) to the power line network. The terminal (10) includes a processing circuit (76) and communication ports (24, 22, 20) for communicating over communication links with the circuit breakers (40) or other external devices according to a message protocol defined for the system.

In a typical AC power distribution system in a residential or small business building, an array of electromechanical circuit breakers protects various branch circuits of the electrical wiring. Such circuit breakers utilize a thermally operated switch which, upon reaching a predetermined temperature due to excessive current passing therethrough, will "trip" and open the circuit connected to the switch.
Improved circuit breakers are disclosed in U.S. Pat. No. 4,949,214, entitled "TRIP DELAY OVERRIDE FOR ELECTRICAL CIRCUIT BREAKERS" issued to George A. Spencer on Aug. 14, 1990, an assignee of the present U.S. Patent Application, and in pending U.S. Patent Application entitled "CIRCUIT BREAKERS WITH INTEGRATED CONTROL FEATURES", Ser. No. 08/695,076, filed by the inventors of the present application on Aug. 8, 1996 and assigned to the assignee of the present application, which patents are incorporated herein by reference. The improved circuit breakers disclosed therein include an array of trip profiles tailored to the current draw characteristics of the various kinds of devices which may be connected to the AC power line branch circuit protected by the circuit breaker. These trip profiles, which are dynamically changeable, determine the current versus time configuration of the particular circuit breaker. Such improved circuit breakers overcome the principal disadvantages of the conventional thermally operated circuit breakers, including, for example, slow response time, inability of responding to differing in-rush current characteristics, inability of opening a circuit upon the occurrence of arcing (a potentially serious fire hazard), inadequate response to electrical stalling of motors connected to a protected line, etc.
Although the circuit breakers with trip delay override and the electronically controlled circuit breakers with integrated control features referenced above and hereinbelow as digitally enhanced circuit breakers, offer superior trip performance under a variety of load fault conditions, several significant new features and capabilities, if provided in conjunction with such advanced circuit breakers, would overcome the following shortcomings. Neither of the aforementioned advanced circuit breakers has the cap ability of storing substantial quantities of system data, for example in a high capacity, non-volatile memory, when a total power failure occurs. Moreover, the performance of an individual digitally enhanced circuit breaker (DE breaker) is monitored only by the internally executed program within the individual DE breaker. Further, no provision is made in such DE breakers to analyze power line circuit conditions that are common to all DE breakers in the power distribution system in order to obtain an evaluation of the conditions of the system. There is additionally no affordable means available, even with the advanced circuit breakers mentioned hereinabove, for presently monitoring, controlling or reconfiguring circuit breaker elements within an electrical power distribution system in residential environments. Nor are there provisions for communicating control information and system data between individual circuit breakers in a power distribution network and a control or processing device coupled either directly or remotely to the network.

Communication terminal for electrical power line distribution system


A bootstrapping circuit capable of sampling input signals beyond a supply voltage is disclosed. In one embodiment, the bootstrapped circuit is implemented having a reduced area and/or power consumption requirement.

Generally, integrated power management applications may require the ability to sample and measure voltage from the surroundings. For example, integrated power management applications may employ a low power successive approximation register (SAR) analog-to-digital converter (ADC) to monitor on-chip and off-chip voltage quantities. Such ADCs often employ a bootstrapped circuit in a track and hold circuit having a plurality of capacitors. In fact, DC to DC converter applications may also employ such bootstrapped circuits. Unfortunately, the capacitors in the bootstrapped circuit require a certain amount of physical space and consume power. Accordingly, there exists a need in the art for a bootstrapped circuit having a reduced area and/or power consumption requirement.


A ferroelectric liquid crystal display having alignment films with different surface polarities. The alignment films induce an internal electric field through the liquid crystal. Because of the induced internal electric field, initial liquid crystal alignment, and subsequent liquid crystal alignments, can be performed without an externally applied electric field.

1. Field of the Invention
This invention relates to a liquid crystal display, and more particularly to a ferroelectric liquid crystal display having improved liquid crystal alignment films.
2. Description of the Related Art
A liquid crystal display (LCD) controls the light characteristics of a screen to display a desired image. Liquid crystals used in LCDs are in a neutral state between a liquid and a solid. That neutral state has both fluidity and elasticity.
While there are many types of liquid crystals, one type of great interest is the smectic C liquid crystal. During a thermodynamic phase transition, a smectic C liquid crystal rotates along an outer line of a virtual cone. Such a smectic C phase liquid crystal can undergo a spontaneous polarization. Such a liquid crystal is usually referred to as a "ferroelectric liquid crystal" (FLC). The FLC has been actively studied because of its fast response time. Furthermore, FLC LCDs can have wide viewing angles without the complications of special electrode structures or compensating films.
There are many different FLC modes, including a deformed helix FLC, a surface stabilized FLC, an anti-FLC, a V-mode FLC and a half V-mode FLC. Hereinafter, the V-mode FLC mode and the half V-mode FLC mode will be described in more detail.
FIG. 1 illustrates a liquid crystal cell having a V-mode FLC. As shown, that liquid crystal cell includes an upper substrate 1 having a common electrode 3 and an alignment film 5. That liquid crystal cell also includes a lower substrate 11 having a TFT array 9, which includes pixel electrodes, and an alignment film 7. A V-mode liquid crystal 13 is interposed between the upper and lower substrates 1 and 11. The alignment films 5 and 7 are aligned in a horizontal direction, usually by rubbing with a special cloth roller. The V-mode liquid crystal 13 forms multiple smectic layers that have molecular structures arranged with desired slopes with respect to a plane perpendicular to the smectic layers. In other words, the liquid crystal molecules have desired inclination angles with respect to the alignment directions of the alignment films. Furthermore, adjacent smectic layers have opposite polarities.
Light transmission through the V-mode FLC liquid crystal cell varies according to an applied voltage across that cell, reference FIG. 2. The liquid crystal 13 within the V-mode FLC liquid crystal cell responds to both positive and negative voltages. Since light transmissivity rapidly changes in accord with applied positive and negative voltages, the light transmissivity verses voltage curve has a V-shape as shown in FIG. 2. Thus, light transmissivity increases regardless of polarity.
FIG. 3 illustrates a liquid crystal cell having a half V-mode FLC. As shown, a half V-mode FLC liquid crystal 15 is interposed between an upper substrate 1 and a lower substrate 11. The half V-mode FLC liquid crystal 15 forms multiple smectic layers in which the liquid crystal molecules align at a desired inclination angle with respect to the alignment direction of the alignment films 5 and 7. However, as shown in FIG. 3, the liquid crystal molecules in adjacent smectic layers have the same polarity (unlike V-mode FLC liquid crystal molecules). Such a half V-mode FLC liquid crystal can be formed by applying a positive (or a negative) electric field to a hot liquid crystal while slowly lowering that liquid crystal's temperature into a smectic phase.
A half V-mode FLC mode liquid crystal 15 formed in this manner responds to only one polarity of applied voltage. Thus, as shown in FIG. 4, the light transmissivity verse voltage curve of a liquid crystal cell having the half V-mode FLC has a 'half V' shape. Still referring to FIG. 4, as shown, the light transmissivity verse voltage curve does react, slightly, to negative applied voltages, but dramatically to positive applied voltages.
The thermodynamic phase transition of a half V-mode FLC liquid crystal 15 is as follows:Isotropic→nematic (N*) phase→smectic C*(Sm C*) phase→crystalSuch a thermodynamic phase transition expresses the phase of the liquid crystal in accordance with temperature, which becomes less as phase changes move to the right.
An isotropic phase liquid crystal 15 interposed into a liquid crystal cell aligns in parallel with the rubbing direction of the alignment layers when the liquid crystal temperature is slowly lowered to the nematic phase. If a sufficiently strong electric field is applied across the liquid crystal cell while the liquid crystal temperature is slowly lowered more, the liquid crystal 15 is phase-changed into a smectic phase in which the direction of spontaneous polarization of the liquid crystal molecules arranges according to the electric field in the cell. Consequently, when the liquid crystal 15 within the liquid crystal cell is subject to parallel alignment treated alignment layers, the liquid crystal molecules arrange in a spontaneous polarization direction that is consistent with the electric field at the phase transition, and in one of two possible molecular arrangements. As a result, the liquid crystal 15 has a uniform alignment state.
FIG. 5 and FIG. 6 help illustrates this. First, as shown in FIG. 5, if a negative electric field E(−) is applied during alignment of the liquid crystal 15, then the spontaneous polarization direction of the liquid crystal 15 is along the electric field. In such an aligned liquid crystal cell, as shown in FIG. 6, the liquid crystal arrangement is changed by an applied positive electric field E(+), but not by an applied negative electric field E(−).
To utilize the response characteristics of the liquid crystal 15, perpendicular polarizers are arranged on the upper and lower portions of the liquid crystal cell. The transmission axis of one of the polarizers is along the direction of the initial liquid crystal alignment. Assuming a liquid crystal cell having the transmission curve of FIG. 4, an applied negative electric field E(−) does not change the liquid crystal arrangement and the perpendicular polarizer blocks light. A positive electric field E(+) rotates the liquid crystal alignment such that light transmission increases.
FIG. 7 shows an electric field applied across a half V-mode FLC liquid crystal cell. As shown, the half V-mode FLC liquid crystal cell includes an upper substrate 1 with a common electrode 3 and an alignment film 5, a lower substrate 11 with a TFT array 9 and an alignment film 7, and a liquid crystal 15 interposed between the upper and lower substrates 1 and 11. The alignment films 5 and 7 are beneficially comprised of the same material and are subject to the same alignment treatment. An internal electric field, E-intra, which is contrary to the externally applied electric field, E-ext, depends on the alignment film material and on the polarization of the liquid crystal 15. This internal electric field E-intra is an induced polarization field.
As described above, the half V-mode FLC liquid crystal cell uses both temperature and an electric field to obtain the initial liquid crystal alignment. However, liquid crystal cells made in this manner have a problem in that the initial liquid crystal alignment can be disturbed by external impacts, which almost inevitably occurs due to grinding of a shorting bar. Furthermore, simple heating of a conventional half V-mode FLC liquid crystal cell can disturb the liquid crystal alignment. To re-establish liquid crystal alignment, both temperature and electric field treatments are required, which is difficult to do without the shorting bar.
Therefore, a new ferroelectric liquid crystal display having a liquid crystal alignment that can be thermally re-established would be beneficial.


Systems and methods are provided for efficient calculation of sets of distinct results in an information retrieval service. A query is received having at least one requested attribute and one or more conditions. For each row identifier in a database table that matches the one or more conditions, a tuple of value identifiers having an entry for each requested attribute is calculated. A unique number is generated and assigned to the tuple for each distinct combination of the value identifiers. Duplicate entries in the tuple listing are identified and removed, so that a result set provides only distinct results.

In today's commercial enterprises, knowledge management (KM) includes the collection and unification of information that exists in the enterprise, and making that information usefully accessible to users. For example, a major KM activity is searching in unstructured data such as text documents. Unstructured information is contained in unstructured or semi-structured documents, in formats like Microsoft Office for collaborative desktop applications, or a markup language such as HTML or XML used for web-based applications. These documents are stored as files, where the associated metadata is an example of structured data but in this case provides only secondary information.
Another major KM activity is extracting requested sets of records containing structured information from databases. Searches on structured data are usually performed either directly or indirectly on data in the fields of relational database tables. Search requests or queries from the users of a KM system who wish to access structured information may be formulated for the purposes of information retrieval in a syntax similar to Standard Query Language (SQL).
A conventional information retrieval service of the sort used in such a KM system breaks down query processing into several steps. These steps typically include planning and optimization, calculation, and projection. Consider an exemplary query formulated by a user of a KM system who wishes to retrieve certain information from the sales records that have been stored in the system by or on behalf of a book store, where these records are stored as structured information. In a relational data model illustrated in FIG. 1, this data can be stored in three relations: BOOKS, SALES, and CUSTOMERS. The information retrieval service may be configured to answer a question such as "Which customers purchased at least one book in 2004, and by which author(s)?" when this question is suitably formulated in an SQL-like syntax.
For any customer who purchased more than one book from the same author in 2004, there is more than one sales record in the data. For any customer who bought any book in 2004, the result set is expected to include one row per author. For any customer who bought several books from the same author, only one row in the result set is expected. In the calculation step, tuples of RowIDs of the result set that match the SELECT and JOIN condition(s) are listed. In the projection step, the listed RowIDs are materialized by translation into values of the requested attributes for return as results.
The step of making the final results distinct with respect to some requested attributes can occur after the projection step, but this is inefficient because there may be a large number of intermediate results to be materialized, most of which are then removed when a DISTINCT condition is applied. In the example, there may be many customers who bought more than one book from the same author in 2004, and the lines for all the second and further books need to be removed. Conventional information retrieval services typically generate duplicate rows for any given customer and author when processing the result set.

Efficient calculation of sets of distinct results in an information retrieval service


An angle-dependent reflectometer or transmissometer includes an optical imaging array in the incident and reflected or transmitted light path that breaks up an incident light beam into mutually spatially incoherent light bundles. The individual light bundles are then focused to a common spot by a high numerical aperture objective lens so as to provide a range of incidence angles on a sample surface. In a reflectometer, reflected light returns through the objective lens and imaging array and is imaged onto a detector array where different incidence and reflection angles are received by different groups of detection elements. In the angle-dependent transmissometer, the imaging array and high numerical aperture focusing objective lens are used for illuminating a spot on the sample, with a second high numerical aperture collection objective lens and detector array used for receiving transmitted light over a wide range of collection angles. The angle-dependent reflectance or transmittance measurement provided by the detector array can be analyzed to determine a desired characteristic parameter of the illuminated area of the sample surface. For example, a periodic text pattern on a wafer or mask surface can be illuminated to obtain a linewidth measurement. The break up of the light by the imaging array into light bundles allows the spot size to be controlled independently of the range of illumination angles so that areas much larger than the diffraction limit can be illuminated.

There are a variety of optical measuring and testing applications in which light is incident upon a surface and then selected parameters of the reflected or transmitted light, such as intensity or polarization, are measured. Thus, it may be desired to measure surface roughness, thin film layer thickness, etch depth of various surface structures, or linewidth. Various common techniques include spectrometry, interferometry, polarimetry, ellipsometry, scatterometry, reflectometry and transmissometry. For example, one way to measure the dimensions (width or thickness) and shape of lines formed on a generally flat, reflective semiconductor wafer surface is to provide a test pattern of such lines formed as a high frequency grating in designated areas on the wafer surface interspersed among the integrated circuit patterns, then to illuminate the test pattern with monochromatic light from a laser source, and to detect and measure the resulting reflectance at various angles. From an analysis of the measured angle-dependent reflectance data, for example by comparison with reference data obtained from either a theoretical model or previous measurements done on calibration standards, the desired line parameter or parameters can be determined.
One type of optical instrument for carrying out this measurement is described in U.S. Pat. Nos. 4,710,642 (McNeil) and 5,164,790 (McNeil et al.) and in a paper by S.S.H. Naqvi et al. in the Journal of the Optical Society of America A, vol. 11, no. 9, pages 2485-2493, September 1994. FIG. 1 illustrates the basic configuration from the Naqvi et al. paper. The measurement instrument is described as an angle-scanning scatterometer in which a spot 10 on a sample 12 is illuminated by a laser beam 14 incident at an angle .theta..sub.i relative to the surface normal of the sample. Normally, the laser wavelength and incidence angle are fixed for a given measurement. Scattered light 16 is detected by a photodiode 18 over a range of scattering angles .theta..sub.s at a constant radius from the point of incidence 10 on the sample surface, as indicated by the circular detector path 20 in FIG. 1. For this purpose, the photodiode 18 may be mounted on a rotary stage (not shown) with its rotation axis passing through the illumination spot 10. In this instrument, the specularly reflected beam 22, and usually the first order diffraction beams, are removed from the data. The photodiode output may be amplified, sampled by an analog-to-digital converter, and analyzed in a microprocessor or computer 24. This apparatus, which directs a laser beam directly on the sample surface offers the advantage of being able to control the illumination area. However, the measurement is serial in nature, and therefore slow. The above-referenced '642 McNeil patent describes a variation in which a detector array, positioned in an arc extending partially around the sample, is used instead of a movable photodiode. Here, the entire range of scattering angles is detected at one time. Additional detector arrays are provided to measure the radiation of the incident beam when the sample is not in place and also to monitor the specularly reflected light to ensure proper orientation of the sample.
Another type of instrument employing angle-dependent intensity measurements is disclosed by Gold et al. in U.S. Pat. No. 4,999,014. FIG. 2 illustrates this configuration. There the measurements are used to determine the thickness of a thin film layer 30 on the surface of a sample substrate 32. A laser 34 generates a beam 36 that is reflected downward by a beamsplitter 38 towards the sample 32. A lens 40 having a large (at least 0.5) numerical aperture ("N.A.") focuses the beam to a spot 42 on the thin film layer 30. The N.A. of the lens 40 creates a spread of incidence angles from substantially normal to the thin film surface for the central (chief) ray to at least 30.degree. from normal for the extreme ray. A preferred embodiment has an 0.95 N.A. lens, giving a spread of greater than 70.degree.. The incident beam is reflected upwardly by the sample back through the lens 40, through the beamsplitter 38 and onto a photodetector array 44. Each discrete detecting element of the photodetector 44 corresponds to an incidence (and reflectance) angle at the sample surface. In a preferred embodiment there are two orthogonal linear arrays of detectors corresponding to respective S and P polarization components of the light. The intensity information obtained by the detector array 44 is used by a processor 46 to calculate the thin film thickness (and index of refraction) of the layer 30 on the sample 32. The apparatus provides parallel measurement, wherein light at many angles of incidence (and reflection) are intercepted by different elements of the detector array and detected simultaneously. In addition to providing a large angular spread for the incident and reflected light, the large N.A. lens 40 also focuses the light down to a very small spot 42 on the sample surface 30, typically on the order of 1 .mu.m diameter or less, so that only a very small area is illuminated and highly localized variations in the sample parameters can be measured. While such a small spot is highly useful for the thin film thickness measurements for which the instrument was invented, it would be completely unsuitable when line width or other parameters are to be determined from a periodic surface structure, like a test pattern. For such a measurement, a much larger illumination area, on the order of 10 .mu.m diameter, is required, like that provided by the instrument in FIG. 1.
Serial measurement over a 50.degree. to 60.degree. range of reflection angles, one degree at a time, is relatively inefficient, typically taking about a minute to complete, including the time needed to physically move the detector to each measurement position. Parallel measurement by a fixed detector array would be much faster, taking as little as a millisecond to complete. Unfortunately, the diffraction properties of light create a conflict between a high N.A. objective lens used to obtain a large range of incidence and reflection (or transmission) angles over which simultaneous measurements are taken and the large illumination area needed for measurements of a periodic test pattern on a wafer surface. The spot size of a light beam at the focus is proportional to .lambda./N.A., where .lambda. is the wavelength of the light and N.A. is the numerical aperture of the optical system. The proportionality constant is usually between 0.6 to 1.2, depending on the definition of beam size and other factors, such as the degree of coherence of the beam. It can be seen from this relationship between normal aperture and the beam size at the focus that the larger illumination areas required for periodic test patterns necessitates optics with a much smaller numerical aperture, or even direct laser beam illumination as in the instrument shown in FIG. 1, thereby reducing the range of angles over which a measurement is taken. Likewise, if large numerical aperture optics are used to obtain a larger range of incidence and reflection (or transmission) angles for simultaneous measurement, then a small illumination spot results. Illuminating a relatively large area, e.g., on the order of 10 .mu.m diameter, is important in those measurement applications where the effects of light interaction with periodic surface structures are needed, and also where it is desired that the measurement be an average over the illumination area so as to be relatively insensitive to localized variations in the sample properties.
Accordingly, it is an object of the present invention to provide angle-dependent optical measurements simultaneously over a wide range of incidence and reflection (or transmission) angles for an illumination area that is many times larger than the diffraction limit of the objective lens.

Optical system and method for angle-dependent reflection or transmission measurement


A stripper clip (100) for a die board (300) of a stripping machine, the stripper clip (100) comprising: a hub (110) to be fitted into a corresponding socket (320) of the die board (300); a bridge extending from the hub (110) to a distal end (122); and a cantilevered arm (130) extending from the distal end (122) of the bridge. The clip (100) is dimensioned to fit into a socket (320) of the die board (300) with the cantilevered arm (130) extending from an underside of the die board (300) into an aperture (310) of the die board (300) for receiving waste pieces from blanks. The clip (100) is formed of a resilient material so that the cantilevered arm (130) is deflected towards the hub (110) as a waste piece (410) passes through the die board (300) and so that the arm (130) reflexes as the waste piece (410) passes the cantilevered arm (130) to assist in disposing of the waste piece (410).

A variety of products are produced from card, paper or plastics blanks that are typically made from plain sheets which are cut and creased before being folded into shape.
Typically, an outline for a product blank can be defined using, for example, a computer controlled laser or equivalent cutting device which can define outlines in either a single sheet or a stack of sheets. The outline can be defined as a line of weakening in which a number of frangible links (nicks) maintain the blank in position within the original sheet. When required, the blank can then be punched or stripped from the original sheet (or vice versa) leaving a peripheral piece of waste.
It can also be desirable for a blank to include internal apertures requiring waste pieces to be removed from within the blank. Again, respective outlines for these apertures can be defined using a laser or equivalent cutting device which can define outlines in either a single sheet or a stack of sheets—this can be done at the same time as defining the external outline of the product. Removal of waste product from within a blank is usually performed by feeding the blank through a stripping machine and punching the waste piece(s) through a die from where they are collected.
One type of stripping machine, available for example, from Bobst of Switzerland, can be loaded with: a moveable punching board comprising punching members, such as pins or blades; a fixed die board, having a major surface juxtaposed a major surface of the punching board; and, where the punching board comprises pins, a moveable bottom stripper frame disposed adjacent a surface of the die board opposite the punching member.
Each of these 2 or 3 boards is especially designed for the blank which is to be processed by the stripping machine with pins/blades located and apertures defined in accordance with the shape, size and location of waste pieces to be removed from the blank.
The die board is provided with machined apertures corresponding to the shape of the waste pieces to be removed from the blank. During operation, the punching board reciprocates between a refracted state, where its punching members are spaced apart from the die board and enable one or more blanks to be located between the punching board and the die board with waste pieces lying in register with corresponding apertures, and an extended state, where the punching members have passed through corresponding apertures within the die board having broken the respective waste pieces from the blank and driven them though the aperture where they can be collected along with any other waste pieces from the blank and other blanks.
Blanks can be fed through a stripping machine either individually, in stacks or they can form part of a continuous web which is cut into individual blanks after being processed by the stripping machine.
Where the punching board punching members comprise pins and no bottom stripper frame is employed, a common problem is that waste pieces may not be cleanly or fully removed from a blank. Such waste pieces are either carried away with the blank and so may require that a product be rejected or need to be reworked—or worse, a waste piece may become stuck within a die board aperture, so preventing subsequent blanks from being properly positioned within the stripping machine and so causing the stripping machine to break down.
In order to facilitate cleaner and more precise removal of waste pieces from a product blank, the bottom stripper frame includes a plurality of stripping pins which correspond with and lie in register with respective punching pins of the punch. The bottom stripper frame also moves from a retracted state, where it is withdrawn below the die board, to an extended state where each punch pin and a corresponding bottom stripper pin catch a respective waste piece while fixed within the blank. The bottom stripper frame then retracts in tandem with the advancing punching board until the punching board reaches its fully extended state. The punching board then begins to move back towards its retracted state and so opens a gap between the punching pins and the corresponding bottom stripper pins. This allows waste pieces which have been stripped from a blank by the combined punching pin and stripper pin to fall away where they can be recovered. The punching board then fully retracts to its retracted state to allow the blank(s) now stripped of its waste piece(s) to be fed from the stripping machine and for a new blank or stack of blanks to be fed into the stripping machine.
While bottom stripper pins are effective—assembling, mounting and dismantling of the bottom stripping frame is expensive and time consuming.


In the present invention, a method for determining at least one pore-related parameter of a porous structure is provided. In a preferred embodiment, an enhanced evapoporometry (EP) technique is provided to determine pore size distribution of continuous pores of a porous structure. In this enhanced EP technique, a volatile liquid, such as isopropoyl alcohol or water, is supplied to one side of a porous structure in order to enable the volatile liquid to penetrate and saturate the porous structure through capillary force. Thereafter, an immiscible non-volatile liquid, such as glycerol, mineral oils, silicon oils or hydrophilic ionic liquid, is supplied to the one side of the porous structure. As the volatile liquid evaporates progressively from the filled pores, the emptied pores may be immediately filled by the non-volatile liquid drawn upwards by capillary action. This prevents formation of a t-layer formed from the adsorption of vapour emanating from the volatile liquid that is used to saturate the pores.

It may be necessary to characterize the pore size and pore-size distribution for a variety of applications involving porous materials. For example, it may be necessary to accurately characterize the pore size and pore-size distribution of semi-permeable membranes that are used for applications such as water desalination, industrial gas separations, renal dialysis, membrane-lung oxygenators, controlled release drug-delivery devices, and membrane sensors. In these applications, the pore size determines the ability of the membrane to retain larger particles, bacteria, macromolecules, molecular aggregates, and/or molecules, relative to the liquid/gas that permeates through the membrane.
It may also be necessary to characterize the pore size and pore-size distribution for porous electrodes used in batteries and fuel cells. In these applications, the pore size determines the available surface area for charge transfer. Another application relates to porous catalysts used in a variety of chemical processes. The pore size of the catalysts may determine the available surface area for the heterogeneous catalytic reaction.
Current state-of-the-art methods may not be capable of determining pore sizes over the full range of interest, which may range from the nanometer scale up to the micron scale. Techniques such as displacement porometry may require relatively expensive dedicated equipment that involves the application of high pressures which can deform the material being studied. Moreover, displacement porometry can characterize only relatively large pores typically greater than 0.01 microns. Gas adsorption/desorption based techniques require relatively expensive dedicated equipment that involves measuring the gas pressure very accurately. Moreover, gas adsorption/desorption relies on a phenomenon known as capillary condensation whereby pores fill by progressive adsorption. For this reason gas adsorption/desorption can accurately characterize only relatively small pores typically less than 0.01 microns. The equipment required for scanning electron microscopy is very expensive. Further, scanning electron microscopy can measure the pore size for a sample area of only a few hundred microns in width on a planar area. As such, scanning electron microscopy does not characterize the pore size throughout a porous sample of interest.
Other less commonly used pore-size characterization techniques such as thermoporometry and permporometry also require dedicated relatively expensive equipment and are difficult to implement reliably.

Method and arrangement for determining at least one pore-related parameter of a porous structure