A balloon catheter (10) has a shaft (12) having an elastically expandable balloon (11) on the distal end side and space provided inside and allowing a fluid to flow into and flow out the balloon (11), a heat generating member (22) provided in the internal space of the balloon (11), and optical fibers (20A, 20B) which are extended up to the internal space of the balloon (11) along the shaft (12) and emit light beams input into the proximal end to the heat generating member (22) from the distal end.

Heretofore, medical treatment of expanding a narrowed blood vessel by a catheter has been performed. For example, in order to expand a stenosis portion of the artery with a balloon catheter in a balloon dilation, a guide wire is inserted into a guiding catheter, so that the distal end is caused to reach the vicinity of the stenosis portion. The balloon catheter is inserted into the guiding catheter in such a manner as to be guided by the guide wire, so that a balloon portion is caused to reach the stenosis portion of the artery. Then, the balloon portion is inflated to expand the stenosis portion of the artery (refer to Patent Literatures 1 to 3).
The balloon dilation has a problem that the frequency of occurrence of restenosis after the operation is high. Although there are various opinions on the mechanism that the restenosis occurs, two phenomena mainly contribute to the occurrence of restenosis. First, the pressurization by the balloon causes mechanical damages (separation, cracking) in a vascular wall to thereby cause chronical migration and hyperproliferation of vascular cells, so that the cavity of the blood vessel is blocked. Secondly, a blood vessel itself is narrowed due to constrictive remodeling of the blood vessel. To address the problem, a technique of simultaneously performing pressurization and heating of a stenosis portion by a balloon catheter, i.e., a heating type balloon dilation, has been devised (refer to Patent Literatures 4 and 5). The heating type balloon dilation is a technique including heating a vascular wall during balloon pressurization to thereby thermally denature (soften) collagen fibers in the vascular wall to perform expansion treatment without causing separation of the vascular wall at a low expansion pressure. The technique can suppress mechanical damages of a blood vessel which is a problem of the balloon dilation.
In the above-described heating type balloon dilation, by heating a heat generating member provided in a balloon, the heat is transmitted to the vascular wall through a fluid (for example, physiological saline, water) for expanding the balloon. However, when the heating amount of the heat generating member is insufficient, the blood vessel is continuously heated over a long period of time in order to increase the temperature of the blood vessel to a target temperature. As a result, a problem that proteins forming the blood vessel are thermally denatured may arise. Moreover, this problem becomes more remarkable with an increase in the capacity of the internal space of the balloon.
Moreover, in the heating type balloon dilation, heat is transmitted to the vascular wall through a fluid (for example, physiological saline, water) for expanding a balloon from a heat generating member heated by irradiation with a light beam, for example. However, when a light source is disposed inside the heat generating member having a cylindrical shape and formed with a metal wire, a light beam emitted from the light source may leak out of a gap generated between the metal wires to the outside of the balloon catheter. This may cause a reduction in the heating efficiency of the heat generating member.


A bipolar transistor comprises a base region and an an extrinsic base region being located generally adjacent to the base region. The extrinsic base region has implanted therein a dopant and a dopant diffusion-retarding substance. The dopant diffusion-retarding substance serves to reduce the diffusion of the dopant into the base region. Preferably, the dopant and diffusion-retarding substances are implanted such that there is a buffer zone in the extrinsic base region immediately adjacent to the base region into which the dopant may diffuse after implantation. The dopant may for example be boron, and the dopant diffusion-retarding substance may for example be a group IV element such as carbon or germanium.

The invention generally relates to the formation of semiconductor devices, and more particularly, to the formation of a bipolar transistor in which migration of dopants is reduced.
As semiconductor devices have become smaller, the possibility of performance degradation from inter-diffusion between adjacent structures in the semiconductor devices has increased. Accordingly, it would be desirable to design structures that reduce such inter-diffusion, and develop associated manufacturing methods for such structures.
According to one aspect of the invention provided is a method of reducing lateral diffusion of a dopant in a transistor, comprising the steps of:
forming a first region of semiconductor in or on a semiconductor substrate;
forming a second region of semiconductor in or on the semiconductor substrate, the second region being located generally adjacent to the first region in a direction parallel to a general plane of the semiconductor substrate;
implanting or depositing a dopant diffusion-retarding substance in the first region; and
implanting or depositing the dopant in the first region.
According to one aspect of the invention, the step of implanting or depositing the dopant in the first region comprises the step of:
implanting or depositing the dopant in the first region such that there is a buffer zone, into which the dopant may diffuse, between a region in which the dopant is initially implanted and the second region.
The method may further comprise the step of:
determining a diffusion distance for the buffer zone based on an expected reduced diffusion as a result of the presence in the first region of the dopant diffusion-retarding substance.
According to another aspect of the invention, the first region forms a polysilicon layer and the second region forms a base, and the method further comprises the steps of:
forming a third region of semiconductor material for use as an emitter;
forming a layer of photoresist on the third region of semiconductor material;
patterning the layer of photoresist; and
removing part of the third region as defined by the patterned layer of photoresist to define an emitter, wherein the step of implanting or depositing the dopant comprises:
implanting or depositing the dopant using the patterned layer of photoresist as a mask.
In one embodiment, the patterned layer of photoresist extends partially over the first region to define a buffer zone into which the dopant may diffuse after implantation or deposition.
The dopant diffusion-retarding substance may be a group IV element, for example carbon or germanium.
According to another aspect of the invention, provided is a bipolar transistor comprising:
a first polysilicon region formed in or on a semiconductor substrate,
a second base region formed in or on the semiconductor substrate, the second polysilicon region being located generally adjacent to the first base region in a direction parallel to a general plane of the semiconductor substrate, the;
the first polysilicon region including therein a dopant and a dopant diffusion-retarding substance.
In one embodiment of the transistor, there is a buffer zone into which the dopant may diffuse, the buffer zone being between a region in which the dopant is initially implanted and the second base region.
In such a case, preferably a diffusion distance for the buffer zone is based on an expected reduced diffusion as a result of the presence in the first polysilicon region of the dopant diffusion-retarding substance.
The transistor may further comprise:
a third emitter region formed of semiconductor material, wherein the buffer zone is defined by an overlap between the third emitter region and the first polysilicon region.
The dopant diffusion-retarding substance may be a group IV element, for example carbon or germanium.
According to a further aspect of the invention provided is a bipolar transistor comprising:
a base region,
an extrinsic base region being located generally adjacent to the base region,
the extrinsic base region having implanted therein a dopant and a dopant diffusion-retarding substance, the dopant and dopant diffusion-retarding substance being implanted such that there is a buffer zone in the extrinsic base region immediately adjacent to the base region into which the dopant may diffuse after implantation.
Preferably, the buffer region is defined by an overhang of an emitter region over the base region.

Bipolar transistor and methods of forming bipolar transistors


A method of producing a pharmaceutical preparation comprising fibronectin and fibrinogen is disclosed. The method involves admixing into a starting solution of fibrinogen and fibronectin, in a single step, a precipitating composition comprising a polyalkylene glycol and at least one of glycine and xcex2-alanine which forms a precipitate. Next, the precipitate is collected and a pharmaceutical preparation is prepared from the precipitate. The pharmaceutical preparation has a fibronectin:fibrinogen ratio from about 0.02 to about 0.2.

The present application claims priority to Austrian application number A 206/99, filed Feb. 12, 1999.
Not applicable
The invention relates to a method for producing protein compositions comprising fibronectin and fibrinogen and, optionally, further ingredients as well as to protein compositions obtainable according to this method.
Tissue adhesives based on fibrinogen (xe2x80x9cfibrin adhesivesxe2x80x9d) have been known for a long time. They serve for a seamless or suture-supporting connection of human or animal tissues or organ parts, for sealing wounds, haemostasis and assisting wound healing.
Their mode of action is based on an imitation of the final phase of blood coagulation.
By the action of thrombin, (soluble) fibrinogen at first is converted into fibrin monomers which aggregate spontaneously and form a sticky mass, a so-called fibrin clot. Simultaneously, factor XIII (F XIII) present is activated by thrombin in the presence of calcium ions to factor XIIIa. By the latter, the aggregated fibrin monomers and also fibronectin possibly present are cross-linked to a high polymer by new peptide bonds forming. By this cross-linking reaction, the strength of the clot formed is substantially increased. Generally, the clot adheres well to wound and tissue surfaces, which i.a. leads to the adhesive and haemostatic effect.
Therefore, fibrin adhesives frequently are used as two-component adhesives which comprise the fibrinogen component together with a thrombin solution which additionally contains calcium ions.
A particular advantage of a fibrin adhesive consists in that the latter does not remain at its site of application as a foreign body, but is completely resorbed just as in natural wound healing, and is replaced by newly formed tissue. Various cells, such as, e.g., macrophages and, subsequently, fibroblasts migrate into the clot, lyse and resorb the clot material and form new tissue.
Although the complicated procedures of wound healing so far by no means have become completely clear, it is considered to be certain that the presence of fibronectin in the clot is of crucial importance for the growing in of cells and thus for wound healing.
A fibrin clot of optimum composition threrefore should also comprise a content of fibronectin in addition to its main component, fibrinogen.
Although the mode of action of fibrin adhesives substantially corresponds to the natural processes of blood coagulation, for a sufficient efficacy (adhesive strength, haemostatic effect), a substantially higher concentration of the active components (in particular, of fibrinogen) is necessary than is present in blood, the fibrinogen concentration of human blood amounting to approximately 2.5-3 mg/ml.
It has been reported that by means of PEG precipitation a fibrinogen solution could be obtained with which a satisfactory adhesive strength could be attained already at fibrinogen concentrations of below 30 mg/ml in an artificial test system (WO 92/13495), yet with this, for many purposes of tissue adhesion a high density of the fibrin network (and the latter is substantially only attainable by high fibrinogen concentrations in the tissue adhesive) cannot be ensured,
To ensure an optimum efficacy, therefore, the fibrinogen content in a fibrin adhesive should be at least 70 mg/ml. The production of such concentrated ready-to-use fibrinogen or fibrin adhesive solutions, respectively, does, however, involve some difficulties:
Since the ready-to-use solutions are not storage-stable over longer periods of time, they have to be prepared upon demand either by reconstitution from lyophilized preparations or by thawing of liquid-deep frozen solutions.
Because of the relatively poor solubility of fibrinogen and the simultaneously required high fibrinogen concentration in an effective fibrin adhesive, in general this is still more cumbersome and time-consuming than desired by users thereof, despite diverse proposals for improvements. It is understandable that particularly in the field of emergency surgery, a particularly rapid and simple availability of a fibrin adhesive is required.
Moreover, concentrated fibrin adhesive solutions generally are highly viscous due to their high fibrinogen concentrations. A relatively low viscosity, however, is desirable not only for easier handling, but also for specific modes of application of a fibrin adhesive, e.g. when applying it by means of spray devices (such as, e.g., Duploject(copyright) with the associated spray set), or by means of a catheter.
Both requirements, i.e. rapid availability and low viscosity of the ready-to-use fibrin adhesive solutions, are even more difficult to meet if preparation thereof (dissolution or thawing, respectively) is to be effected without further auxiliary means, such as heating and/or stirring equipment, at room temperature, and if the fibrin adhesive preparations additionally contain high-molecular substances, in particular fibronectin. For also fibronectinxe2x80x94particularly in combination with fibrinogenxe2x80x94is relatively difficult to dissolve and generally leads to an even poorer solubility and an increased viscosity of fibrin adhesives.
Methods for producing fibrinogen-containing preparations which can be used as tissue adhesives comprise i.a. their production from cryoprecipitate, optionally with further washing and precipitation steps with ethanol, ammonium sulphate, polyethylene glycol, glycine or xcex2-alanine, and their production from plasma within the scope of the known plasma fractionation methods, respectively (cf., e.g., xe2x80x9cMethods of plasma protein fractionationxe2x80x9d, 1980, ed.: Curling, Academic Press, pp. 3-15, 33-36 and 57-74, or Blomb{overscore (a)}ck B. and M., xe2x80x9cPurification of human and bovine fibrinogenxe2x80x9d, Arkiv Kemi 10, 1959, p. 415 f.).
In the prior art, also various suggestions have been made to reduce the viscosity of highly concentrated fibrinogen solutions. Thus, e.g., the addition of solubilizers, such as substances containing urea or guanidine residue, e.g. arginine (cf. DE 3203775-A1), or the addition of unphysiologically high salt concentrations has been known. However, it has been shown that such tissue adhesives have cytotoxic and proliferation-inhibiting properties, respectively (Redl et al., Med. Welt 36, 1985, pp. 769-776)
According to EP 0 804 933, the addition of substances improving the solubility of fibrinogen has been suggested. Such substances are, e.g., vitamins, aromatic compounds, such as compounds derived from benzene or phenol, or those derived from heterocyclic compounds, such as piperidine, pyridine or pyrimidine.
Thus, it is an object of the present invention to overcome the drawbacks of known preparations, and to further improve the known preparations, respectively, and to provide protein compositions comprising a high fibrinogen content and an easily adjustable ratio of fibrinogen to fibronectin as well as, optionally, further ingredients, which are, e.g., suitable for an improved preparation of ready-to-use tissue adhesives, while particularly maintaining properties, such as a good cell compatibility, or the formation of a physiological fibrin structure after mixing with a thrombin solution. At the same time, also the viscosity properties of such protein compositions or pharmaceutical preparations are to be improved.
A further object of the present invention is to provide a simplified and more rapid method of producing such protein compositions. In particular, it shall also be possible to easily carry out the method on an industrial scale.
According to the invention, these objects are achieved by a method for producing protein compositions which comprise fibrinogen and fibronectin, which method is characterized in that a starting solution comprising fibrinogen and fibronectin is treated with a precipitating composition which comprises two different components that modify the solubility of fibrinogen and/or fibronectin, so that in a single-step precipitation a fibrinogen and fibronectin containing precipitate is formed, and the formed precipitate optionally is further treated by methods known per se. This method is characterized in that an efficient and protein-preserving preparation giving high yields can be produced with the precipitating composition by a single-step precipitation.
Following the single-step precipitation, the precipitate obtained may be further processed by methods known per se, preferably into a pharmaceutical preparation, in particular a tissue adhesive (fibrin adhesive).
By a solubility-modifying component, a substance is understood which has a precipitating effect or a solubility-improving effect on at least one of the proteins, fibrinogen or fibronectin, under the given other conditions, such as temperature, pH, ionic strength, etc.
Quite surprisingly, according to the invention it has been found that using two solubility-modifying components which are different (from each other) in cooperation allows for a recovery of fibrinogen and fibronectin in the precipitate in high yields, wherein the single-step precipitation of the invention quite amazingly has been found to be substantially less protein-damaging than the individual precipitation of the respective substances.
Moreover, it has also been shown that a composition precipitated according to the invention and comprising fibrinogen and fibronectin has enormously improved properties also with a view to its practical application, in particular as regards its viscosity and reconstitution, whereby an easier application of these preparations is made possible.
As the starting materials for preparing the starting solution, in principle all those can be used which so far have been used or are possible, respectively, in the prior art for preparing such protein compositions.
As the starting material, preferably, plasma, in particular human plasma, or a fibrinogen and fibronectin-comprising plasma fraction, preferably a fraction derived from cryoprecipitate, is used for preparing the starting solution or is used directly as starting solution, respectively.
Other fibrinogen and fibronectin-comprising starting materials or starting solutions, respectively, such as, e.g., cell culture supernatants, may, however, also be employed according to the invention.
The solubility-modifying components are chosen such that in a single-step precipitation a precipitate is formed which contains fibrinogen and fibronectin in a desired and pre-determined ratio of amounts.
According to the invention, the components contained in the precipitating composition are chosen such that, under the given conditions, they differ from each other in terms of their solubility-modifying, i.e. solubility-improving or precipitating, action on fibrinogen and fibronectin, respectively. One component may, for instance, have a precipitating effect substantially on merely one of the two proteins, i.e. on fibrinogen or on fibronectin.
It is, however, also possible that one of the components has a precipitating action on both proteins, whereas the other component has a precipitating action on merely one of the two proteins, or even increases the solubility of the other protein, respectively, i.e. does not act as a precipitating agent but as a solubilizer.
In particular, the solubility-modifying component is a substance selected from the group of alcohol, in particular alcohol having up to four carbon atoms, inorganic salt, organic salt, polyol, in particular polyalkylene glycol, polyether and amino acid. Also ethers, ketones and cyclic, heterocyclic or polycyclic organic compounds may be used. As the solubility-modifying components, particularly ethanol, polyethylene glycol, ammonium or alkali salts, respectively, such as ammonium sulfate or alkali sulfate, or the amino acids glycine and (xcex2-) alanine are preferably used.
Among the organic polymers, there are particularly the linear polymers, in particular those having an average molecular a weight approximately between 200 and 20,000, e.g. polyalkylene glycols. Polyethylene glycol has proven particularly suitable. These non-toxic, water-soluble synthetic polymers, in particular those having a molecular weight of from 400 to 10,000, preferably around 4,000, are preferably used in the precipitation because of their preserving effect on fibrinogen and fibronectin. In addition to the particularly gentle and preserving effect of the components to be used in the precipitating composition, also their safety as regards their use on humans is taken into consideration when selecting them.
As a pair of components usable according to the invention, for instance, polyethylene glycol (PEG), in particular PEG 4000 which has a precipitating action both on fibrinogen and on fibronectin, and, as the second component, glycine is usable, which in the presence of a further component, e.g. polyethylene glycol, surprisingly not only preferably precipitates fibrinogen as compared to fibronectin, but even acts as a solubilizer for fibronectin. Glycine in a concentration range of more than 0.6 M, in which so far glycine has only been known as a protein precipitating agent, has a particularly good, fibronectin-solubility increasing effect.
Of course, the present invention is not limited to combinations of PEG and glycine, since the average skilled artisan will easily be able to find also other components or component pairs, respectively, suitable according to the invention, by means of simple systematic tests.
To carry out the method of the invention, the skilled artisan may, e.g. find suitable components or component pairs, respectively, according to the following test scheme. Under defined conditions, such as temperature, pH, ionic strength etc. and under stirring, aliquots of a starting solution prepared by common methods are admixed with precipitating compositions containing a first solubility-modifying component, e.g. an amino acid, and a second component different therefrom, e.g. PEG 4000, ethanol or ammonium sulfate. Precipitation series are carried out in which the concentration of one of the components always is kept constant, and the other one is varied. The precipitates formed are centrifuged off, and the total protein content as well as the relative contents of fibrinogen (Fbg), fibronectin (Fn) and albumin (Alb) are determined, e.g. by means of SDS PAGE of the non-reduced and reduced samples, staining with Coomassie Blue and densitometric evaluation.
Those components which lead to the desired fibrinogen and fibronectin-containing protein composition are then chosen for the precipitating composition according to the invention. Optimization of the respective component system will be effected by means of parameters easy to check, such as yield, relative content of fibrinogen and fibronectin, and viscosity, respectively, of the obtained preparation at a pre-determined fibrinogen-content (e.g. 70 or 100 mg of fibrinogen per ml).
In a preferred embodiment, the precipitating composition comprises polyalkylene glycol which is admixed to the starting solution, in particular to a final concentration of from 1 to 12% w/v, preferably from 4 to 8% w/v.
In a further preferred embodiment, the precipitating composition comprises one or more amino acids admixed to the starting solution, in particular to a final concentration of from 0.5 to 3 M, preferably 0.75 to 2 M, in particular 0.75 to 1.5 M.
In another preferred embodiment, an organic or inorganic salt, e.g. ammonium sulfate, is contained at a concentration of up to 20% w/v, preferably between 2 to 20% w/v, most preferred between 5 to 15% w/v.
The precipitating composition preferably is admixed in liquid form.
Also other ingredients of the starting material can be precipitated by means of the precipitating composition, such as in particular factor XIII. Also the ability of the solubility-modifying composition for co-precipitating such further substances may influence the final choice of the individual components in the precipitating composition.
According to a preferred embodiment it is attempted to keep the plasminogen in the precipitated protein composition or in the pharmaceutical preparation, respectively, rather low. Accordingly, preferably a precipitating composition is used in which plasminogen largely remains in the supernatant, which means that in the precipitate obtained, plasminogen is depleted relative to fibrinogen and/or fibronectin, as compared to the starting material.
According to a further preferred embodiment, further ingredients, in particular fibrinolysis inhibitors, factor XIII, antibiotics, growth factors, pain-alleviating substances, anti-inflammatory agents or mixtures thereof may be added to the protein composition. Such additions are possible before, during, and also after the precipitation step and preferably are effected after the precipitation step.
In the course of further processing, in particular in the final formulation, the protein composition according to the invention or the pharmaceutical preparation according to the invention preferably is deep-frozen or lyophilized, particularly if an improved storage stability is to be achieved. The ready-to-use pharmaceutical preparation according to the present invention preferably is provided in liquid form.
In particular, the method according to the invention has the advantage that well-defined protein compositions are obtainable directly in a simple manner, whereas hitherto used methods of protein fractionation, in particular of plasma fractionation, always have aimed at obtaining individual proteins as pure as possible and, optionally, at mixing them together again afterwards to give the desired mixture.
By the simplicity and brevity of the method according to the invention, also the danger of microbial contamination and the formation of pyrogens during production are minimized. Moreover, sensitive plasma proteins, such as, e.g., fibrinogen or fibronectin, are preserved and largely protected from denaturing, and this is probably why the preparations according to the invention have improved properties.
For surprisingly it has been shown that the protein compositions or pharmaceutical preparations, respectively, obtainable by the single-step combination precipitation of the invention, at similarly high fibrinogen concentrations have an approximately 25%, preferably even 30%, most preferred 40%, lower viscosity than comparable preparations, e.g. fibrin adhesives obtained by the classical production methods, in particular by precipitation with one agent only.
By comparable preparations, preparations are understood which have similar contents of fibrinogen, fibronectin and, optionally, further ingredients, and a comparable degree of purity, which exhibit a similarly good cell compatibility and which form clots of physiological fibrin structure after having been mixed with a thrombin solution.
In a particularly preferred embodiment, the protein composition and the ready-to-use pharmaceutical preparation, respectively, substantially do not contain any substances improving the solubility of the fibrinogen, and no such substances are admixed, respectively.
Surprisingly it has been shown that liquid compositions according to the invention have a markedly lower viscosity as compared to comparable known preparations, whereby particularly handling and use of fibrin adhesives is facilitated. Particularly at room temperature, the lyophilized compositions according to the invention can be reconstituted more easily and more rapidly than comparable preparations.
Particularly when carrying out the method of the invention on a large technical scale whichxe2x80x94and this is a further advantage of the present inventionxe2x80x94can be applied on a large scale very efficiently and in a cost-saving manner, it is preferred to admix the precipitating composition in liquid form. This may be a solution or a suspension.
It has also proven suitable that the precipitate obtained after the single-step precipitation is washed at least once with a washing buffer. In addition to a suitable buffer system, the washing buffer preferably contains tranexamic acid, lysine, xcex5-aminocaproic acid, detergents, or mixtures of these substances. Also fibrinolysis inhibitors or protease inhibitors, respectively, of plasmatic, animal or plant origin, or inhibitors produced by genetical engineering or synthetically, respectively, may be contained. Such substances may be admixed separately, or they may already be contained in the starting material.
A preferred protease inhibitor is, e.g., aprotinin, in particular aprotinin prepared by genetical engineering. A further preferred fibrinolysis inhibitor is tranexamic acid (trans-4-(aminomethyl)-cyclohexane carboxylic acid, t-AMCHA).
The protein precipitate obtained may be used as such, or it may be further processed to a further protein composition or to a pharmaceutical preparation, respectively, by methods known per se. Such methods for processing include, e.g., diverse purification steps, such as, e.g., treatment (washing) with a buffer solution in the cold, or formulation as a pharmaceutical preparation, respectively.
In particular, such final compositions or preparations, respectively, of the invention are suitable for tissue adhesion, haemostasis, and aiding or promoting wound healing.
Plasma which preferably is used as the starting material for the present invention, preferably is sufficiently pre-selected, e.g. according to the method of WO 96/35437, so that virus contamination can nearly be excluded. Preferably, only such a starting material is used which has been checked for an absence of pathogens, in particular viruses and/or prions.
In a further preferred embodiment, at least one step for inactivating or depleting possibly present pathogens is provided.
To inactivate pathogens, preferably a tenside and/or heat treatment (dry or vapor treatment) is carried out, e.g. a heat treatment in the solid state, in particular a vapor treatment according to EP-0 159 311, or EP-0 519 901, or EP-0 674 531.
Further treatments for pathogen inactivation also comprise treatment with chemical or chemical/physical methods, e.g. with chaotropic substances according to W094/13329, DE 4434538 or EP-0131740 (solvent), or photoinactivation.
Also the depletion by means of filtration, in particular ultrafiltration, preferably in the presence of virus-binding agents, such as, e.g. Aerosil, is a preferred method for depleting viruses within the scope of the present invention.
According to the invention, inactivation by means of a heat treatment, a solvent treatment, a detergent treatment, or a combination (simultaneous or sequential) of these treatments, as well as, optionally, a filtration, are particularly preferred.
Inactivation may be effected before or after the precipitation. Preferably, two independent inactivations are carried out, e.g., one treatment before the single-step precipitation, and a second treatment thereafter.
In a further preferred embodiment, the protein composition is characterized in that factor XIII is contained. Preferably, factor XIII is admixed, and the factor XIII content is, e.g., at least 80 units per g of fibrinogen, preferably at least 100 U/g of fibrinogen. In case also the fibrin-cross-linking reaction-inhibiting substances, such as, e.g., antibiotics, are present in the preparation, the factor XIII content preferably is increased to at least 500 U/g of fibrinogen. Preferably, factor XIII is admixed as a purified, separately virus-inactivated product (particularly preferably a factor XIII preparation produced according to EP 0 637 451).
In a further preferred embodiment; the protein composition is characterized by a low plasminogen content. The content of plasminogen preferably is 1.6 mg/g of fibrinogen at the most, more preferred less than 0.8 mg/g of fibrinogen, most preferred less than 0.3 mg/g of fibrinogen.
The protein composition according to the invention advantageously comprises fibronectin and fibrinogen at a ratio of from 0.02 to 0.5, preferably from 0.02 to 0.25, also preferred from 0.02 to 0.2, more preferred from 0.04 to 0.16, most preferred around 0.1 (0.05 to 0.15), i.e., in contrast to highly pure fibrinogen preparations (WO 94/20524), it still contains substantial portions of fibronectin.
The protein composition may further comprise active ingredients, such as antibiotics, growth factors, pain alleviating substances or combinations thereof.
In a preferred embodiment, the protein composition according to the invention is characterized in that
a) as a solution, it contains at least 70 mg of fibrinogen/ml or can be reconstituted or liquefied, respectively, to such a solution,
b) at 20xc2x0 C., it has a viscosity of 350 cSt at the most, preferably at an osmolarity of less than 500 mOsm, most preferred of less than 400 mOsm,
c) after mixing with a thrombin-CaCl2 solution, it forms a non-transparent clot of physiological fibrin structure, and
d) it does not contain an addition of a solubility-improving substance with a benzene, pyridine, piperidine, pyrimidine, morpholine, pyrrole, imidazole, pyrazole, furan, thiazole or purin-containing group.
In a further preferred embodiment, the protein composition according to the invention is characterized in that
a) as a solution it contains at least 70 mg of fibrinogen/ml, or can be reconstituted or liquefied, respectively, to such a solution,
b) at 20xc2x0 C., it has a viscosity of 150 cSt at the most, preferably at an osmolarity of less than 500 mOsm, most preferred of less than 400 mOsm,
c) after mixing with a thrombin-CaCl2 solution, it forms a non-transparent clot of physiological fibrin structure, and
d) it contains one or several solubilizing substances with a benzene, pyridine, piperidine, pyrimidine, morpholine, pyrrole, imidazole, pyrazole, furan, thiazole or purine-containing group at a concentration of a total of 150 mM at the most.
The inventive protein compositions or pharmaceutical preparations, respectively, are versatile in terms of use. In particular, the preparations according to the invention are used for tissue adhesion, haemostasis and/or wound healing.
In a further preferred embodiment, the inventive protein compositions or preparations, respectively, can also be used to produce a fibrin-based biomatrix. To this end, the solution of a protein composition or pharmaceutical preparation, respectively, of the invention is admixed with an enzyme suitable for converting fibrinogen into fibrin, preferably with thrombin, and the fibrin formed is used either in its fresh state or after lyophilisation and re-moistening, as the carrier material for growing cells, or as a so-called biomatrix (cf., e.g., WO 99/15209)
The biomatrix of the invention may be present in various forms, e.g. as a sponge, a film, as micro-beads or as flakes.
The fibrin-based biomatrix is particularly suitable for growing cells, in particular human cells. Keratinocytes, fibroblasts, chondrocytes are to be mentioned as an example of cells capable of being cultured or grown by means of this fibrin matrix. Such a biomatrix is also suitable for dressing wounds or as tissue substitute, respectively, particularly as a skin substitute.

Method for producing fibronectin and fibrinogen compositions using a polyalkylene glycol and glycine or xcex2-alanine


A vertically raised transistor (10) is formed having a substrate (12). A conductive plug region (22) is selectively or epitaxially formed to vertically elevate the transistor (10). A first doped region (16a) and a second doped region (16b) are each electrically coupled to the conductive plug region (22) via sidewall contacts. The doped regions (16a and 16b) are used to form current electrode regions (26) within the conductive plug region (22). A channel region separates the current electrodes (26). A gate dielectric layer (28) is formed to overlie the channel region. A conductive layer (30) is formed to overlie the gate dielectric layer (28). Conductive layer (30) forms a gate electrode for the transistor (10). The vertical raised transistor (10) and conductive plug region (22) provide improved device isolation and improved device operation.

Isolation of adjacent semiconductor devices is an important structural consideration when manufacturing integrated circuits. Isolation is critical for improving integrated circuit yield and performance. In most cases, in order to improve device isolation, integrated circuit surface area increases or integrated circuit process complexity increases.
For example, most integrated circuits are manufactured using metal oxide semiconductor (MOS) field effect transistor (FET) technology. The most commonly used MOSFET technology for integrated circuit (IC) fabrication is known as complementary MOS (CMOS). CMOS devices, or other known IC devices, are conventionally isolated by field oxide which is usually formed as a thermally grown oxide layer. As semiconductor film thicknesses and lithographic features shrink, the field oxide isolation structures do not scale downward accordingly. Therefore, field oxide isolation structures and similar technologies, such as local oxidation of silicon (LOCOS), polysilicon buffered LOCOS (PBL), and the like, may not provide sufficient circuit density or sufficient isolation for future IC designs.
Trench or dielectric plug isolation is sometimes used to improve isolation between adjacent devices. Trench isolation or dielectric plug isolation increases process complexity and introduces etch damage into an integrated circuit substrate. Interface states and etch damage increase undesirable leakage currents within the integrated circuit. In addition, process integration of trench isolation results in gate oxide reliability problems and device defectivity problems.
In order to achieve further isolation, a modified field oxide approach is used wherein epitaxial growth is utilized to grow substrate material vertically and/or laterally over a field oxide region. The grown epitaxial regions are then used to form lateral transistors which are conventional (i.e. identical to conventional top-contacted bipolar and top-contacted MOS transistors). Although the method of epitaxially growing adjacent and/or over oxides improved isolation, the transistor devices which are formed within the grown epitaxial region have surface areas which are large due to electrical contacts methodologies and lithographically defined features, such as gate electrodes, source and drains, and contacts.
Another form of isolation is achieved via the use of silicon on insulator (SOI) technology or a similar technology, such as silicon on sapphire (SOS). Many different SOI processes and devices exist but most SOI processes result in a device-quality substrate material, such as single-crystalline silicon, entirely overlying a dielectric layer wherein the device-quality substrate material is not connected to the substrate. In another form, an SOI structure may be formed which has a source region, a drain region, and a channel region formed overlying a dielectric layer wherein only the channel region is connected to the substrate by a conductive plug region.
SOI transistors provide improved isolation over field oxide approaches and most SOI transistors have several advantages over planar substrate-formed transistors. Some of these advantages are the absence of latch-up in SOI, higher soft-error immunity and reduced parasitic capacitance. SOI transistors with no substrate or body contact suffer from a known and understood "kink effect", suffer from a known and understood "snap-back" phenomenon (which is similar to the "kink effect"), and have an undesirable parasitic bipolar transistor. SOI transistors with a substrate contact tend to have no "kink effect" or "snap-back" problems and may allow for adjustable threshold voltages and noise margins due to substrate biasing and the known and understood body effect.
Therefore, SOI transistors with a substrate contact have advantages and disadvantages, and SOI transistors without a substrate contact also have advantages and disadvantages. Neither SOI transistor is optimal in all cases and applications. In most cases, the most desirable SOI transistor is a thin-film SOI device which operates in a fully-depleted mode of operation. A thin-film SOI transistor operating in a fully-depleted mode of operation reduces "kink effect", has low electric fields, has a high transconductance, has excellent short channel behavior, and has a quasi-real subthreshold slope. SOI processing tends to be complex or unreliable. For example, seperation by implantation of oxygen (SIMOX), which is used to form SOI devices, is a high temperature process and may produce substrate defects which degrade device performance.
Therefore, the need exists for an improved isolation structure and an improved method of isolation formation wherein the method is not complex. In addition, the structure should result in isolation which is superior to field oxide isolation, result in minimum device separation, and result in reduced device surface area. Furthermore, a flexible, dynamic, and easy to manufacture SOI device is desired for improved isolation and improved device performance.

Method for forming a compact transistor structure


A pump wherein a discharge port for discharging a working fluid in the vicinity of a mechanical seal to the outside of a casing is provided so as to be communicated to the portion of the outer circumferential surface of a rotary shaft between an impeller and the mechanical seal. The mechanical seal is fitted in the outer circumferential surface of the rotary shaft and adapted to seal the rotary shaft against the working fluid flowing from a fluid passage to the outer circumferential surface of the rotary shaft. The vane of the impeller is provided with a plurality of radially extending blades and recesses among the blades, the blades and the bottom portions of the recesses in the vane being joined together by curved surfaces.

1. Field of the Invention:
This invention relates to a pump adapted to generate lift in a working fluid by rotating an impeller in a fluid passage.
2. Description of the Prior Art:
A regenerative pump consists of a casing having therein an annular fluid passage communicated with a suction port and a discharge port of the casing, an impeller provided on the outer circumferential surface thereof with a vane fitted and adapted to be rotated in the fluid passage in the casing, a rotary shaft supported rotatably by the casing and having the impeller mounted unitarily thereon, and a mechanical seal fitted on the outer circumferential surface of the rotary shaft so as to prevent a working fluid, which flows in the fluid passage and contacts the outer circumferential surface of the rotary shaft, from leaking to the outside of the casing.
The vane of the impeller consists of a plurality of radially extending blades, and recesses provided among these blades.
When the rotary shaft is driven by a motor to rotate the impeller, the working fluid in the recesses in the vane of the impeller flows out from the outer circumferential portion of the vane into the fluid passage, and the working fluid in the fluid passage flows from a side portion of the vane into the recesses therein. The working fluid receives a pressure energy and velocity energy due to the centrifugal force generated by the rotating impeller, and the velocity energy is converted into pressure energy in the fluid passage. These operations are carried out repeatedly in the recesses in the vane of the impeller. Accordingly, the fluid pressure increases, and the working fluid is discharged from the discharge port.
The regenerative pump described above is constructed so that the impeller is rotated in a non-casing-contacting state, and the working fluid flows to the rotary shaft, on which the impeller is mounted, through the clearance between the impeller and the inner surface of the casing. Therefore, the leakage of the working fluid is prevented by the mechanical seal provided on the rotary shaft. This mechanical seal has a mechanical slide surface contacting the working fluid, and is necessarily subject to wear. The abrasion powder occurring as this mechanical slide surface is worn is mixed in the working fluid, and the abrasion powder-mixed working fluid is discharged through the fluid passage. Consequently, when the working fluid consisting, for example, of pure water which requires that no impurities mixed therein, such a conventional regenerative pump cannot be used.
In the conventional regenerative pump, further the vane of the impeller is formed so that the axis of a blade and the bottom portion of a recess in the vane extend at substantially right angles to cause an angular portion to occur between the blade and recess. Accordingly, the working fluid advancing from a side portion of the vane toward the outer circumferential portion thereof through the recesses does not flow smoothly at such angular portions. For example, when the working fluid consists of water, the microorganisms and impurities contained therein are deposited and accumulated on these angular portions. The same applies to a pump provided in its casing with a fluid passage having angular portions, i.e. a substantially square cross section.


A lightweight self-standing golf bag having a flexible liner disposed within an external frame assembly. The liner is easily removable from the frame assembly for cleaning or replacement. The frame assembly includes a number of legs having pointed ends to support the golf bag in the ground, and has a number of frame members permanently attached to the legs.

This invention relates in general to article carriers, and in particular to a lightweight carrier for articles such as golf clubs or the like.
Although golfers have available a wide selection of conventional golf bags for carrying their clubs, along with other articles such as golf balls and items of apparel, the conventional golf bags generally are relatively heavy and cumbersome. The weight and sheer physical bulk of the conventional golf bag, particularly when loaded with a full complement of clubs and accessories, is simply too great for the average golfer to carry personally while playing a round of golf. Moreover, the problems of personally carrying one's own golf bag are compounded by the fact that such bags are not self-supporting, particularly on the uneven terrain which characterizes most golf courses. Consequently, the golfer carrying his own bag must pick up and reshoulder the heavy bag after each shot, further adding to the burden of carrying the conventional golf bag and further reducing the golfer's enjoyment of the game.
While the golfer can overcome the foregoing problems by expedients such as hiring a caddy to carry the bag, or renting a motorized golf cart to carry bag and golfer about the course, such expedients are becoming increasingly more expensive and simply may not suit either the budget or the style of many casual or weekend golfers. The conventional hand-towed golf bag cart merely adds to the total weight which must be moved about the golf course.
Although golf bags have been proposed in an attempt to overcome many of the foregoing problems associated with conventional golf bags, such prior-art designs have generally been less than satisfactory for a number of reasons. Some such bags amount to little more than scaled-down versions of conventional full-size golf bags, sometimes with spiked feet added to engage the ground, and are still heavier than desirable for self-carrying by the average golfer. Moreover, the fabric or other material constituting the outermost surface of the typical prior-art lightweight golf bag is likely to become stained or soiled from use, and is difficult or impossible to remove from the bag for cleaning or replacement.


The present disclosure relates to an organic light-emitting diode (OLED) device and a display device. The OLED device may include a substrate, thin film transistors (TFTs), an anode, a cathode, and an organic light-emitting layer between the anode and the cathode and configured to emit light. The organic light-emitting layer may be provided with a light-blocking layer which is configured to block ultraviolet (UV) light and arranged at a light-exiting side of the organic light-emitting layer. The display device may include the OLED device.

An organic light-emitting diode (OLED) device has the advantages, such as low-consumption, high-luminance, fast-response, wide visual angle and light-weight and so forth, which has been widely used in mobile communication terminals, personal digital assistances (PDAs), tablet computer and so forth. By compared with a liquid crystal display (LCD), a manufacturing process for the OLED devices is relatively simple and the cost is reduced too. And most important elements within an OLED display device are the OLED devices.
An organic light-emitting layer or thin film transistors (TFTs) within the OLED device may result in performance mutation or performance deterioration after being subject to ultraviolet (UV) light illumination. Specifically, with respect to oxide TFTs within the OLED device, after being subject to UV light illumination, valence band electrons and forbidden band gap enable electrons that are captured collectively to easily absorb energy, then to transit to the conduction band, thereby forming multiple electron-hole pairs. Thereafter a threshold voltage (Vth) may experience drift and sub-threshold swing (SS) may be increased, which causes an ON/OFF ratio to become smaller, thereby the whole OLED device may deteriorate and the displayed pictures may worsen significantly.

Organic light-emitting diode (OLED) device and display device


Implantable hearing aid for stimulation of the inner ear with a hydromechanical coupling element having an input side connected to an electromechanical converter for transmission to the inner ear of the mechanical vibrations generated by the converter.

The invention relates to an implantable hearing aid for stimulation of the inner ear.
In a known hearing aid for stimulation of the inner ear (German Offenlegungsschrift 28 25 233), the subassemblies forming the hearing aid, including a tritium battery, are hermetically encapsulated and are placed in the external auditory canal or are implanted in the mastoid, and the hearing aid is connected by an electric line directly to the auditory nerve on the output side. In a modified embodiment of the known aid, acoustic vibrations generated by the hearing aid implanted in the mastoid are transmitted by the mastoid-bone process into the middle ear by exploiting the fact that this bone exhibits hollow spaces that are connected to the middle ear by the vestibular window.
In another known hearing aid (European Application 242 038 A2), a microphone, an amplifier, a battery, a volume control and an excitation coil, for a magnet that is fastened to one of the auditory ossicles, are placed in a housing that is to be inserted into the external auditory canal. Further, a hearing aid is known (British Patent 1 440 724) in which a microphone, an amplifier and a battery are arranged in a housing that is inserted in a plug-like manner into a base and is implanted in the temporal bone behind the external ear. The output signal of the amplifier goes to an excitation coil, implanted in the middle ear, of a magnet fastened to the stirrup bone.
Further, a hearing aid is known (U.S. Pat. No. 4,532,930) in which, by an implantable electrode arrangement, a direct electrical stimulation of the inner ear occurs with the aid of signals that are made available by a suitable signal processing electronic device. Here the signal processing electronic device is placed in a relatively large-volume housing that is carried along externally in a separate pocket. The signal processing electronic device is connected by a connecting cable to a transmitting antenna that is placed in the area of the ear in question.
In the known hearing aids, the achievable sound quality often leaves something to be desired. Adaptation problems can occur, and the stimulation by a magnet fastened to an auditory ossicle makes necessary an intervention in the chain of auditory ossicles that poses risks.


A method and apparatus are disclosed for reducing the cross-coupled movement in a member of a CNC machine caused by movement in another member of the machine through the structural dynamics of the machine. The method includes receiving the discrete position commands for a member oriented in one axis of movement for the machine, transforming the discrete position commands to attenuate frequency components that contribute to the movement coupled through the structural dynamics of the machine, and generating velocity commands from the transformed discrete position commands to control the servos that drive the members. The discrete position command transform is preferably a second order filter that implements the transfer functions of a digital notch filter and digital low pass filter. The second order filter that transforms the discrete position commands is implemented in a digital computer by state variable difference equations.

Computer-numerically-controlled (CNC) machines for machining large parts with precision are well known. These machines typically include a platform to support a workpiece, a tool to machine the workpiece, and a computer for controlling the tool all mounted together such as in a frame or other structure The computer is programmed to generate position commands for tool control from a user-defined program to direct the incremental movement of the tool to machine a part from the workpiece.
To maneuver the tool for machining the part from the workpiece, the tool is mounted to movable members. Each member is oriented to move along an axis that is distinct from the axes of the other members. The computer includes several processors, one of which controls the tool maneuvers by generating discrete or digital position commands for each member from the user-defined program. A servo processor having a servo stage for each respective axis receives the discrete position commands. Each servo stage uses the position commands for its respective axis to generate velocity commands which are transmitted to a servomechanism, commonly called a servo, connected to each member by a mechanical joint such as a slide, a pivot or the like. The servomechanism drives the mechanical joint, and correspondingly, the member along its axis in accordance with the velocity command received from the servo processor to control the movement of the tool for machining the part. A CNC machine like the one described above is disclosed in U.S. Pat. No. 5,005,135 which is assigned to the assignee of the present patent application and the entire disclosure of which is hereby expressly incorporated by reference.
Because the workpiece from which the part is produced is frequently massive, the members are also heavy to provide rigidity for the tool as it cuts or bores the workpiece. These heavy members require the input of a substantial force, usually supplied by a motor within the servo, to initiate and halt their movement. Sometimes this force moves one of the members at a rate or frequency that induces movement in another member through the structural dynamics of the machine. This induced movement is called a cross-coupled response of the member through the structural dynamics of the machine. This cross-coupled response is superimposed on the driving of the member by its respective servo, and consequently, the tool. The superimposed movement may cause the tool to blemish the finish of the part which then requires hand finishing that adds substantial cost to the part.
One possible approach to this problem involves the use of a driving signal that corresponds to the drive from a servo connected to a first member to generate a correction signal for a servo that drives the member in which the cross-coupled response is induced. The correction signal may be used to counteract the cross-coupled response of the second member so the net movement change in the second member would be zero.
One problem with such an approach is that it requires a correction circuit that generates the correction signal from the driving signal derived from the servo driving the first member. Such a circuit may not only be very costly to design and implement, it may not even be feasible. Thus, it may be more desirable simply to put up with refinishing the blemished parts by hand.
Even if such a device could be implemented at a reasonable cost, coupling the correction signal generated by it to the servo driving the second member might require modification of the servo. For machines already operating in the field, such modifications may result in long down times caused by installation and testing of the correction circuit.
Another approach involves using a signal indicative of the position of the second member to generate an error signal that corresponds to a displacement distance. The displacement distance represents the error in position corresponding to the difference between the predicted position and the actual position of the member. This error signal might be used by the servo processor to generate modified discrete position commands that substantially cancel out the cross-coupled response transferred through the structural dynamics of the machine. To do this, however, the computer would have to be able to predict the response of the second member to its respective position command independent of cross-coupling errors so that the superimposed cross-coupling may be assessed and corrected. Without this predictive response capability, the computer would be unable to determine the error in the second member position. For machines already in operation, there might not be sufficient computing resources, such as processor time or memory, available to implement the predictive response capability.
Another problem in both of the aforementioned possible approaches is their potential adverse effect on the ability to coordinate tool movement between members for tool paths that require coordination between two members oriented in different axes. For example, to cut a hole, it may be necessary to move the cutting tool in small increments along two axes perpendicular to one another. In that way, the tool may be caused to move smoothly along a curved line to form a circle. If one of the approaches previously discussed were implemented then the processing of the correction signal or error signal may delay position movement in the first member. Such delay could disrupt the coordination between the first and second members causing errors in the path of the intended tool movement. Compensating for the delay in the correction circuit or the predictive response capability of the computer might require more modification to the servo or more computer resources than are available.

Method and apparatus for reducing cross-coupled movement through the structural dynamics of a computer numerically controlled machine


A chair having a seat pivotally connected to a base frame, the seat's pivotal axis being horizontal and parallel to the front of the chair and located intermediate the front and back of the seat proximal its center of gravity. A hydraulic cylinder is attached; between the seat and base frame to dampen pivotal movement of the seat as a person is assisted into or out of the chair.

Persons suffering from physical maladies often experience great difficulty getting up from a chair well as lowering themselves into a chair. For example, arthritics, and persons having back and leg ailments, cannot easily flex their knees and initiate movements towards the standing or sitting position.
The problems to which this invention addresses itself have been most commonly solved with electric recliner chairs. Having motorized power available, it is an easy thing to add what is termed an "elevating seat". In addition to being expensive, chairs employing electric motor power generally also are designed in the cushioned easy-chair style, and to the knowledge of the inventor, are available only as an adjunct to the reclining feature. Not everyone who desires a occupant-assisting chair also wishes an easy chair and not disabilities.
Other chairs which have occupant-assisting features include those which employ hydraulic rams, extending arms which the occupant pulls or pushes in order to move the seat up or down with his body, and spring assisted chairs. Such devices are generally of benefit to one requiring such assistance. However, the hydraulic approach, like its electric powered counter part is expensive and subject to breakdown. Those with pull bars are suitable only for users having adequate strength in their arms and shoulders, and the spring assisted chairs are difficult to adjust for the different sizes and weights of users.


A portable toilet apparatus configured for use with a toilet liner is disclosed. The toilet apparatus comprises a toilet basin, and a toilet seat removably fitted to the toilet basin. The toilet seat further includes retention means for retaining the toilet liner at least partially within the toilet basin. A combination changing and toileting station is also disclosed. The combination changing and toileting station comprises a toilet assembly, and a changing table assembly removably attached to toilet assembly. The toilet assembly and changing table assembly are adjustable between a first position for use as a changing table, and a second position for use as a toileting station. A method of using a toilet liner with a portable toilet apparatus is also disclosed. The method comprises positioning the toilet liner within the toilet basin such that a first portion of the toilet liner is secured by the retention means, removing the first portion of the toilet liner from the retention means following use of the toilet apparatus, and disposing of the toilet liner. The toilet liner may comprise a diaper with an elastic edge or gusset.

This invention relates generally to the field of portable toilets, and more specifically to a changing and toileting station, and method of using wearable absorbent articles therein.
Child toilet training has changed considerably since disposable absorbent articles have become widely used. Parents do not begin potty training until much later, and when they do, older children are often more resistant to using a toilet. Therefore', the sooner an infant can be introduced to the use of a toilet, or toilet-like device, the likelihood increases that the child will not be as resistant to the potty training process. This situation is very similar to that observed with children that have been consistently placed in carseats starting with the first car ride home from the hospital. These children are less resistant to being placed in car seats when they are two years of age.
To speed up the child's introduction to the toilet and potty training, it may be possible to introduce these items with other staples of the child's development. For example, children are usually exposed to changing tables or stations from the time they come home from the hospital. These changing tables often remain with the child, even after they have been outgrown, as part of the child's room or nursery furniture. The constant exposure to these changing stations may offer an opportunity to provide a gradual introduction to potty training that builds on her comfort level.
In the use of portable toilets, for potty training or other uses, there are many challenges, such as, what to do with the bodily waste and where to clean the portable toilet, and how. There is a need for a safe, clean and efficient way of using portable toilets that is inexpensive and allows for easy cleaning and disposal of waste. Such a method of use may be found with the use of toilets liners, yet to be effective, such toilets must be adaptable for use with widely available liners that are not difficult to come by, specialized or costly to produce.
Accordingly, the invention provides an illustrative toilet apparatus, combination changing and toileting station, and methods of using the same, that overcome the disadvantages of known devices while offering features not present in known devices. Although certain deficiencies in the related art are described in this background discussion and elsewhere, it will be understood that these deficiencies were not necessarily heretofore recognized or known as deficiencies. Furthermore, it will be understood that, to the extent that one or more of the deficiencies described herein may be found in an embodiment of the claimed invention, the presence of such deficiencies does not detract from the novelty or non-obviousness of the invention or remove the embodiment from the scope of the claimed invention.


A microcomputer 18 obtains a variable RRT from a broadcast signal and stores, in a recording medium, the variable RRT in association with a physical channel; sets a viewing restriction flag for an item in the variable RRT based on an operation input from a user; applies viewing restriction to the broadcast signal when rating information indicates the level at which the viewing restriction flag has been set in the variable RRT; and, when a logical channel is not associated with the selected physical channel, tunes, as an alternative channel, a physical channel with which a logical channel has been associated in the channel map of the other tuner, and associates a variable RRT associated with the alternative channel, with the selected physical channel.

1. Field of the Invention
The present invention relates to a digital broadcasting receiving device, and particularly to a digital broadcasting receiving device having a viewing restriction function.
2. Description of Related Art
In United States and Canada, a regulation requires that television sets which receive television broadcast signals must have a V-chip allowing a viewer to restrict reception and display of improper video and sound of violence scenes and obscene images which are desired not to be watched by children. Specifically, with a conventional V-chip defined by CEA-766-A, each television set stores a rating region table (hereinafter, referred to as "fixed RRT") which includes predetermined TV rating and MPAA rating, and viewing restriction is applied based on the fixed RRT.
However, in order to change or expand the rating region table, the Federal Communications Commission has required since Mar. 15, 2006 that a digital television broadcasting receiving device having the size of 13 inch or more include a V-chip 2.0. With the V-chip 2.0, the digital television broadcasting receiving device can recognize a rating region table (hereinafter, referred to as "variable RRT") sent during broadcasting and apply program viewing restriction.
Also, with the V-chip 2.0, rating information of each program is sent together with the broadcast signal in the same way as with the conventional V-chip, and viewing restriction is applied based on a combination of the rating information and the fixed RRT or the variable RRT.
As a technique of using rating information in the conventional V-chip, JP 2003-198974 A discloses a technique in which the rating information of a channel being tuned is accumulated in association with program titles or the like to allow a user to refer to the rating information upon rating setting. Further, JP 2003-518881 A discloses a technique of obtaining, while one channel is being viewed, the rating information of another channel for the purpose of preventing a reduction in the speed of channel zapping caused by rating-information acquisition and decision processing. Further, JP 2003-110953 A discloses a technique of applying viewing restriction based on rating information for multiple days that is sent together with an EPG, to prevent a program to which viewing restriction should be applied from being displayed during a period of time required for rating-information acquisition and decision processing immediately after channel switching.
A device for receiving television broadcasting has a channel map that associates the number of each physical channel specified by a user through a key operation with the number of each logical channel assigned to the frequency band of a broadcast signal. In the channel map, if the number of a logical channel is not assigned to the number of a physical channel, video is not displayed even when the user selects that physical channel. However, when the user performs a key operation, the user expects some video to be displayed.


A filter includes: a coupled multi-mode acoustic wave filter connected between an input terminal and an output terminal; a first inductor connected between the coupled multi-mode acoustic wave filter and a ground terminal; an acoustic wave resonator, one end of which is connected between the input terminal or the output terminal and the coupled multi-mode acoustic wave filter; and a second inductor connected between another end of the acoustic wave resonator and the ground terminal.

Filters used in communication devices such as mobile phones are required to have low loss in a passband, and to exhibit a high degree of suppression outside the passband. In recent years, the use of the direct conversion method removes an intermediate filter (IF filter), and further requires the high degree of suppression. Exemplary acoustic wave filters used as a filter are a SAW (Surface Acoustic Wave) filter and an FBAR (Film Bulk Acoustic Resonator) filter. However, the filter behaves as a capacitor at frequencies far away from the passband. Thus, the degree of suppression degrades at frequencies outside the passband, especially in a high frequency band.
A coupled multi-mode acoustic wave filter, which is formed by acoustically connecting SAW resonators or piezoelectric thin film resonators, is used to increase the degree of suppression in a wide frequency band. There is disclosed a technique that connects a resonator in series or in parallel to a DMS (Double Mode SAW) filter in Japanese Patent Application Publication Nos. 6-260876, 2001-230657 and 10-93381 (Patent Documents 1, 2 and 3). Moreover, Patent Document 3 discloses a technique that reduces an inductance of a bonding wire to improve the degree of suppression in a high frequency band.
However, conventional techniques are mainly directed to improve the degree of suppression around the passband, and have difficulty in improving the degree of suppression in a wide band, especially in a high frequency band. In addition, the reduction of the inductance disclosed in Patent Document 3 does not improve the degree of suppression sufficiently.


Systems, methods, and apparatus provide integration of microscopic imaging and liquid chromatography-mass spectrometry on a microfluidic device. In one aspect, an apparatus includes a first wafer, a second wafer, and an emitter. The emitter is disposed between the first wafer and the second wafer. The first wafer defines a sample input hole. The first wafer and the second wafer define a first channel, the first channel including a first end and a second end. The first end of the first channel is proximate the sample input hole. The first channel is configured to contain separation media. The second end of the first channel is proximate the emitter.

Given that the proteome reflects the physiological and pathological states of a patient, proteomics is a powerful tool for early diagnostics of diseases and monitoring of therapeutic responses. The majority of current protein assays in clinical settings are based on enzyme-linked immunosorbent assay (ELISA) immunoassays, which require high-quality antibodies and are hard to achieve with high multiplexing (e.g., greater than 10) due to the cross-reactivity of antibodies. Mass spectrometry (MS) measures the mass-to-charge ratio of charged species, and has become an enabling technology for proteomics. Aside from de novo identification of target proteins, MS has advantages over ELISA for detecting protein mutations, modification, truncations, and adductations, for example. Once combined with the liquid chromatography (LC), LC-MS enables separation, identification, characterization, and quantitation of complex mixtures of proteins and peptides. However, the penetration of MS into the in vitro diagnostics market, particularly for clinical proteomics, has remained low. Key challenges remain for an MS-based platform to achieve robustness, sensitivity, and throughput comparable to those of ELISA for analysis of small-volume biospecimens such as blood and urine.

Microfluidic devices for liquid chromatography-mass spectrometry and microscopic imaging

The Regents of the University of California


A bypassable latch circuit consumes less power in the bypass mode than it does in the latched mode. The circuit includes a flip-flop whose output is routed to an input of a multiplexer. The other input of the multiplexer is the input of the flip-flop as well. The multiplexer is used to select as the latch output either the registered or latched flip-flop output, or the flip-flop input. The flip-flop is modified by replacing the inverter at the flip-flop clock input with a logic gate that accepts as inputs both the clock input and a control input. The control input can cause the flip-flop to ignore the clock, preventing switching that consumes power by charging and discharging capacitive elements in the flip-flop.

This invention relates to a flip-flop for use in applications in which the flip-flop may be optionally bypassedxe2x80x94e.g., as an output latch for programmable logic circuitry whose output may be registered or unregistered. More particularly, this invention relates to such a flip-flop having a low-power mode for use when bypassed.
A flip-flop circuit is a well known and simple circuit for holding the value of an input for at least one clock cycle in a clocked system. For this reason, flip-flops frequently are used as output latches or registers in programmable logic devices. In such an application, the output of a programmable logic element typically is routed to the flip-flop, where it may be made available at the next clock edge, for one full clock cycle, for use by additional logic or as an output of the programmable logic device. It is also typical to provide a bypass route for the output of the programmable logic element, allowing it to be routed asynchronously to additional logic or to a device output.
A common configuration for an output bypass as just described is to route the programmable logic element output both to the input of the flip-flop and to an input of an output multiplexer. The output of the flip-flop also is routed to an input of the output multiplexer, and the multiplexer can be controlled to select either the direct, unregistered logic output or the registered output of the flip-flop. When this configuration is used, the flip-flop, which also is connected to the system clock, continues to switch at every clock cycle, even when the output multiplexer selects the unregistered bypass output. In addition, if the input data vary, that may also cause switching of components within the flip-flop. As a result, the flip-flop consumes power even though it is not being used.
In view of the foregoing it would be desirable to be able to provide a latch circuit that consumes less power in the bypass mode than it does in the latched mode.
It is an object of the present invention to provide a latch circuit that consumes less power in the bypass mode than it does in the latched mode. This and other objects of the invention are accomplished in accordance with the principles of one aspect of the invention by providing, for example as part of a programmable logic device, a latch circuit that includes a flip-flop that can effectively be turned off if it is bypassed.
In particular, there is provided, in accordance with the present invention, a latch circuit including a flip-flop having a data input, a data output, and a clock input, and a multiplexer including a first input connected to the data input of the flip-flop and a second input connected to the data output of the flip-flop. The latch circuit also has a latch output and a control input for selecting one of the first and second inputs as the latch output. The flip-flop circuit also has a low-power selection input connected to the control input of the multiplexer. When the control input selects the first input as the latch output, the low-power selection input causes the flip-flop to enter a low-power mode.


A system and method for dynamically expanding a snapshot repository based on predefined parameters is disclosed. The snapshot repository is monitored for determining if the amount of information stored in the snapshot repository has reached a predetermined volume increase threshold. If a determination is made that the volume increase threshold has been reached, the volume of the snapshot repository is automatically increased. The snapshot repository may also be monitored for determining if the amount of information stored in the snapshot repository has reached a predetermined maximum snapshot repository volume whereupon a warning may be provided.

The present invention generally relates to the field of snapshot repositories utilized in memory or storage systems such as RAID (Redundant Array of Independent Disks) storage systems and the like, and more particularly to a method for automatically dynamically expanding a snapshot repository volume.
Multiple drive storage systems such as RAID storage systems or the like commonly used by networked computing systems typically include a snapshot repository for storing a collection of information about the storage system. This collection of information, commonly referred to in the art as a xe2x80x9csnapshotxe2x80x9d, allows data stored by the storage system in the event of failure thereby allowing substantially instant backup of data in the storage system. Snapshots are periodically saved to the snapshot repository as data stored in the storage system is altered so that the repository information is kept current.
Presently, when a user, such as the system administrator of the storage system, or the like, defines a repository for a snapshot, that user must specify the exact size of the repository volume (e.g., as a set amount of memory such as 30 GB (gigabytes)). However, this requirement forces the user to anticipate the write mix of the I/O (input/output) pattern to the base volume. In other words, if the repository runs out of space because too many write operations were performed to the base volume, the snapshot becomes invalid or fails. Should this event occur, user intervention is required to increase the size of the repository, or, alternately, to make the snapshot valid via other means.
Consequently, it would be desirable to provide a means of automatically and dynamically expanding the size of the snapshot repository volume based on user defined parameters.
Accordingly, the present invention is directed to a system and method for dynamically expanding a snapshot repository volume. In this manner, automatic scaling of the repository volume may be provided so that the exact initial size of the repository volume need not be known. Further, the snapshot repository may be allowed to grow with the usage pattern of the system while keeping the repository sized to a relatively small and appropriate level.
In accordance with a first aspect of the invention, a method for dynamically expanding a snapshot repository is disclosed. The method includes the steps of monitoring the snapshot repository for determining if the amount of information stored in the snapshot repository has reached a predetermined volume increase threshold. If a determination is made that the volume increase threshold has been reached, the volume of the snapshot repository is automatically increased. In an exemplary embodiment, the method also includes the steps of monitoring the snapshot repository for determining if the amount of memory utilized by information stored in the snapshot repository has reached a predetermined maximum snapshot repository volume threshold and providing a warning if the maximum snapshot repository volume threshold is reached. In this manner, the method allows the size of the repository volume to be automatically increased each time a predetermined volume increase threshold is reached up to a predetermined maximum volume.
In accordance with a second aspect of the invention, a system for storing a snapshot of a memory is disclosed. The system includes a snapshot repository suitable for storing the snapshot and a controller for controlling the snapshot repository. The controller is capable of monitoring the snapshot repository for determining if the amount of memory utilized by information stored in the snapshot repository has reached a predetermined volume increase threshold and increasing the volume of the snapshot repository if the volume increase threshold is determined to have been reached. The controller may further monitor the snapshot repository for determining if the amount of memory utilized by information stored in the snapshot repository has reached a predetermined maximum snapshot repository volume threshold and provide a warning if the maximum snapshot repository volume threshold is (or is about to be) reached.
In exemplary embodiments of the present invention, the expansion behavior of the snapshot directory may be specified at the time it is created. This may be accomplished by allowing a user, for example, the system administrator, to define such parameters as the initial size of the snapshot repository volume, the maximum size of the snapshot repository volume, the amount of incremental increase of the snapshot repository volume, the volume increase threshold, the maximum snapshot repository volume threshold, and the like.
It is to be understood that both the forgoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention and together with the general description, serve to explain the principles of the invention.

System and method for automatic dynamic expansion of a snapshot repository


A process for filtering a liquid stream from a fixed bed reaction zone in order to remove catalyst fines contained in the stream. The effluent stream is passed to a filtering section which may contain at least two filtering vessels. Each filtering vessel includes at least two differently filtering sections, each section designed to collect differently sized particles. If a pressure drop occurs in one of the filtering vessels, it may be taken offline to remove the filtering sections and recover the metal in the particles collected on the filtering sections. The other filtering vessel can remain online to allow the filtering process to be continuous. Metal on the catalyst fines may be recovered.

Petroleum refining and petrochemical processes include reaction zones that contain catalysts used to promote various chemical reactions. For example, hydrocracking, hydro-treating, naphtha reforming, naphtha isomerization are all process that use catalysts to promote the different chemical reactions associated therewith. These catalysts comprise, among other compounds, metals, typically noble or precious metals.
When the catalysts are spent, they may be processed to recover the noble metals. Since the metals are expensive, the loss of even a small amount of catalyst metal can be costly for a refiner. Therefore, refiners desire to maximize the recovery of the catalyst metals to minimize any losses.
The catalyst pellets are typically contained in one or more beds within the reaction zone. During the loading and the handling of these beds, catalyst fines are typically generated. Once the reactor is brought back on line, the catalyst fines migrate through the reaction zone and are carried out with the liquid flowing through the reactor. Not only does this result in a loss of catalyst fines, it can result in a loss of processing fluid, if the startup fluid is the fluid to be processed. Additional catalyst fines can be generated merely by the operation of the reaction zone. These catalyst fines can be carried along with the liquid effluent and lost into downstream equipment. Thus, any catalyst metal lost during operation as a result of catalyst fines generation will lower metals recovery and increase the capital loss for the refiner.
It is known to recover catalyst in various Fisher-Tropsch reactions in which the synthesis catalyst particles are in a slurry or processing fluid. For example, U.S. Pat. Pub. No. 2013/0144099 discloses the use of filters to capture the synthesis catalyst particles and separate same from the hydrocarbon oil. Another process for filtering an effluent stream from a Fisher-Tropsch reactor is disclosed in U.S. Pat. No. 8,344,199. The process disclosed in U.S. Pat. No. 8,344,199 uses two filter sections to avoid a pressure drop associated with filtering the effluent stream. However, in both of these references, various filters are separated, thus creating problems associated with changing the filters when they become saturated. Thus, it is believed that these processes fail to fully address minimizing downtime for a reactor. Furthermore, while presumably effective for their intended uses, these processes are not believed to be readily suited to recover catalyst fines from an effluent from a fixed bed reactor.
As mentioned above, catalyst fines are especially a problem during start-up periods for the fixed bed reactors after the beds have been re-loaded with new catalyst. Accordingly, during the start-up of the reactor, there will be an initial surge of catalyst fines in the liquid passing through the reactor. Typically, to avoid a pressure drop downstream created by the catalyst fines, the start-up liquid (or flush liquid) is used as a "once through" liquid. Once the liquid is substantially void of catalyst fines and any other impurities, the reaction process can be started.
One drawback with such a process is the loss of the reactor being online. Indeed, it can take between four to eight hours before the flush liquid is substantially free from catalyst fines. However, and more importantly, the flush liquid that is used is typically the processing stream. While the "once through" fluid can be recovered and used in other, less desirable processes, it would be more beneficial for a refiner to be able to recycle the flush liquid (which comprises the processing stream) back to the reactor.
Therefore, there is a need for an effective and efficient process to recover the catalyst fines from a liquid stream from a fixed bed reaction zone.
Additionally, there is a need for such a filtering process that can minimize, if not, eliminate any downtime for the reaction zone associated with the filtering process.

Process for removing catalyst fines from a liquid stream from a fixed bed reactor


20-HETE agonists and antagonists are disclosed along with therapeutic applications. In a preferable form of the invention, the 20-HETE agonists are selected from the group consisting of 21-hydroxyheneicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid, 20-hydroxyeicosa-5(Z),4(Z)-dienoic acid and 20-,21-dimethyl 20-HETE. Preferable 20-HETE antagonists include 5(S)-HETE, 15(S)-HETE, 19(S)-HETE, 19-hydroxynonadeca-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid and 20-hydroxyeicosa 6(Z),15(Z)-dienoic acid.

Recent studies have indicated that vascular smooth muscle cells in a variety of vascular beds express enzymes of the cytochrome P450 4A and related families (CYP 4A) that catalyze the formation of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a potent constrictor (EC50 less than 10-xe2x88x928 M) of renal, cerebral and skeletal muscle arterioles. It promotes Ca2+entry by depolarizing VSM cells secondary to blockade of Kca channels and by increasing the conductance of L-type Ca2+channels (Harder, D., J. Vasc. Research 34:237-243, 1997; Roman, R., News in Physiological Sciences, 1999, in press). In the kidney, 20-HETE is also produced by renal tubular cells where it participates in the regulation of sodium transport in the proximal tubule and thick ascending limb of the loop of Henle. In (Roman R., Supra, 1999) human and rabbit lung, 20-HETE is also produced by the airways where it serves as an potent endogenously produced bronchodilator (Zhu, D., Am. J. Resp. Cell Mol. Biol. 19:121-128, 1998; Jacobs, E. R., Am. J. Physiol. 1999, in press).
Despite the importance of 20-HETE in the regulation of vascular tone, kidney function, and airway resistance, little is known of its mechanism of action. Recent studies have indicated that the vasoconstrictor response to 20-HETE and its inhibitory actions on sodium transport is associated with activation of PKC and MAP kinase signal transduction cascades (Sun, C.-W., Hypertension 33:414-418, 1999). Activation of these pathways are usually triggered by receptor mediated events, however, at present time there is no evidence for a 20-HETE receptor. To date, there have been no published studies to determine whether 20-HETE binds to membrane or cytosolic proteins or to determine whether the vasoconstrictor response is specific to 20-HETE or can be mimicked by closely related analogs.
The present invention springs from a study designed to perform structure activity studies with a series of 20-HETE analogs to determine the structural determinants to the vasoconstrictor response in interlobular arteries microdissected from the kidney of rats.
In one embodiment, the invention is a method of reducing a patient""s vascular diameter or preventing 20-HETE from reducing vascular diameter, comprising the step of supplying to the patient an effective amount of a 20-HETE agonist or antagonist.
Preferably, the compound is of the following formula:
R1 is selected from the group consisting of carboxylic acid; phenol; amide; imide; sulfonamide; sulfonimide; active methylene; 1,3-dicarbonyl; alcohol; thiol; amine; tetrazole or other heteroaryl.
R2 is selected from the group consisting of carboxylic acid; phenol; amide; imide; sulfonamide; sulfonimide; active methylene; 1,3-dicarbonyl; alcohol; thiol; amine; tetrazole or other heteroaryl.
W is a carbon chain (C1 through C25) and may be linear, cyclic, or branched and may comprise heteroatoms, such as S, O, N or Se.
Y is a carbon chain (C1 through C25) and may be linear, cyclic, or branched and may comprise heteroatoms such as S, O, N or Se.
Sp less than 3 Center is selected from the group consisting of vinyl; aryl; heteroaryl; cyclopropyl; and acetylenic moieties.
X is an alkyl (linear, branched, cyclic or polycyclic) group with or without heteroatoms; or a vinyl; aryl; heteroaryl; cyclopropyl; or acetylenic group.
m=0, 1, 2, 3, 4 or 5 and n=0, 1, 2, 3, 4 or 5.
In a preferred embodiment of the method, the compound is an agonist and vascular diameter is reduced or bronchiole smooth muscle is dilated. In this embodiment, the compound is a 20-HETE agonist. Preferably, the agonist compound is selected from the group consisting of 21-hydroxyheneicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid; 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid; and dimethyl 20-HETE.
In another embodiment of the method, the compound is a 20-HETE antagonist and the vascular diameter is prevented from being reduced by endogenous 20-HETE. Preferably, the compound is selected from the group consisting of 5(S)-HETE; 15(S)-HETE; 19(S)-HETE; 19-hydroxynonadeca-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid (C19 analog); and 20-hydroxyeicosa 6(Z),15(Z)-dienoic acid (Ps rev 20-HETE).
In another embodiment, the present invention is a method of treating a patient comprising the steps of supplying an effective amount of a 20-HETE agonist or antagonist.
In another embodiment, the patient has a disease selected from the group consisting of diabetes, toxemia of pregnancy (preeclampsia), hepatorenal syndrome, cyclosporin-induced nephrotoxicity, cerebral vasospasm, stroke, and hypertension and the vasoconstrictor actions of the patient""s excess endogenously-produced 20-HETE is moderated when treated with a 20-HETE antagonist.
In another embodiment, the patient has septic shock or other inflammatory disease associated with induction of nitric oxide synthase and is treated with an amount of 20-HETE antagonist sufficient to reduce symptoms.
In another embodiment, patients are treated with a 20-HETE antagonist to prevent vascularization of granular or neoplastic tissues. This treatment reduces blood supply and prevents growth of tumors.
In another embodiment, the patient has a condition selected from the group of congestive heart failure, pulmonary edema, hepatorenal syndrome and hypertension and is treated with an amount of 20-HETE agonist sufficient to provide a diuretic effect, lower blood volume, and prevent edema.
In another embodiment, the patient has asthma and the 20-HETE agonist is delivered as an inhalational therapy to dilate constricted airways.
In another embodiment, the patient may have pulmonary hypertension and 20-HETE or a 20-HETE agonist is infused to dilate the pulmonary circulation.
In another embodiment, the patient may have cerebral vascular injury, vasospasm, migraine or cluster headaches, stroke or cocaine-induced vasospasm and is treated with a 20-HETE antagonist to increase blood flow and relieve symptoms.
The present invention is also a pharmaceutical preparation comprising a compound selected from the group of 20-HETE agonists and antagonists and a pharmaceutically acceptable carrier. The preparation is preferably selected from the group of the 19-hydroxynonadeca-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid, 20-hydroxyeicosa 6(Z),15(Z)-dienoic acid, 20 hydroxyeicosa-5(Z),14(Z)-dienoic acid, dimethyl 20-HETE 21-hydroxyheneicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acid, N-methylsulfonyl-20-hydroxyeicosa-5(Z),14(Z)-dienamide, or N-methylsulfonyl-20-hydroxyeicosa-6(Z),15(Z)-dienamide and a pharmaceutically acceptable carrier.
It is a feature of the present invention that 20-HETE agonists and antagonists are provided. A general formula is also provided describing 20-HETE agonists and antagonists.
It is another feature of the present invention that therapeutic uses of 20-HETE agonists and antagonists are described.
Other features, objects and advantages of the present invention will become apparent after examination of the specification, claims and drawings.