An isolated polypeptide having carbonic anhydrase activity, the sequence of which corresponds to modified human carbonic anhydrase II is described. The isolated polypeptide comprises the mutations A23C, S99C, L202C, C205S and V241C and the polypeptide has increased physical stability compared to wild type carbonic anhydrase II. Further, the polypeptide comprises disulfide bridges between C23 and C202 and/or between C99 and C241.

Carbonic anhydrases (CA, EC 184.108.40.206) is a group of enzymes that catalyzes the reversible reaction of carbon dioxide and water into bicarbonate and proton according to:CO2+H2O⇄HCO3−+H+Carbonic anhydrases are widely distributed throughout nature and are categorized in five distinct classes, the α-, β-, γ-, δ-, and ξ-class[1]. The α-class carbonic anhydrases can be found in vertebrates, bacteria, algae and green plants whereas β-class carbonic anhydrases are found in bacteria, algae and chloroplasts. One of each δ and ξ-class carbonic anhydrases have been isolated from eukaryotic marine diatoms. The only γ-class carbonic anhydrase (Cam) isolated so far has been isolated from the thermophilic Archaeon Methanosarcina thermophila[2]. However, since the five classes have evolved through convergent evolution they differ significantly from each other with regard to amino acid sequence, structure and activity. The α-class carbonic anhydrases belongs to a superfamily of homologous proteins i.e. their genes have evolved from a common ancestral gene. Among the most effective carbonic anhydrases are the α-carbonic anhydrases from vertebrates with a turn over number (kcat) of up to 1.4·106 s−1, which is 107 times faster than the spontaneous reaction. Furthermore, the catalytic efficiency (kcat/Km) for e.g. human carbonic anhydrase II is 1.5·108 M−1 s−1, which is close to a diffusion controlled reaction. Since the natural function of the enzyme is e.g. to facilitate the removal of CO2 from the blood (human carbonic anhydrase II) it has been suggested that carbonic anhydrases can be used as biological catalysts in bioreactors designed for capturing CO2 from various gas streams. At this time there is a consensus view that the concentration of carbon dioxide in the atmosphere is the major contributor to increasing global warming, which has also been concluded by the Intergovernmental Panel on Climate Change (IPCC)[3]. Thus, several chemical methods have been suggested and tested for carbon capture and sequestration (CCS). However, most of these operate at extreme pressure or temperature and use harmful chemical compounds and still consume high amounts of energy at low efficiency. If, instead, an enzyme based bioreactor utilizing carbonic anhydrase as a catalyst could be used, this could solve the energy and environmental problem with chemical reactors. Several such bioreactors and processes have been suggested in e.g. WO2006/089423, U.S. Pat. No. 6,524, 842, WO2004/007058, WO 2004/028667, U.S. 2004/0029257, U.S. Pat. No. 7,132, 090, WO 2005/114417, U.S. Pat. No. 6,143,556, WO 2004/104160, US 2005/214936 and U.S. Pat. No. 7,892,814. The aforementioned processes generally operate by bringing carbonic anhydrase, either free in solution or immobilized, in contact with CO2 dissolved in the solution. However, since the operational conditions such as temperature, pH and chemical composition of the solution etc can vary widely depending on application, neither of these processes is of any value if the necessary carbonic anhydrase catalyst is not stable enough to function at the operational conditions or have long enough life time to be economically viable.
Unfortunately, since there are no organisms living under the conditions that can prevail in a CO2-capturing bioreactor, nature has not provided us with a carbonic anhydrase with the desired stability or efficiency. Mammalian, plant and prokaryotic carbonic anhydrases have through natural evolution been selected to be stable at the physiological condition of the respective organism. Thus, α- and β class carbonic anhydrases are generally only stable at physiological conditions, i.e. approximately 37° C. or lower. The only heat-stable carbonic anhydrase has been found in Methanosarcina thermophila, which has an optimal growth at 55° C. and produces a γ-carbonic anhydrase (Cam) with a heat denaturation temperature (melting point, Tm) of about 70° C. However, this enzyme has a catalytic turn over that is approximately a 10-fold slower than that of e.g. human carbonic anhydrase II (kcat of approx. 1.2·105 s−1 as compared to 1.4·106 s−1). Furthermore, the catalytic efficiency is approximately 20-fold lower (7.5·106 M−1·s−1) as compared to the 1.5·108 M−1·s−1 for human carbonic anhydrase II[4, 5]. Other features of γ-carbonic anhydrase from Methanosarcina thermophila that makes it less interesting as a catalyst for a bioreactor is that it is a homotrimeric protein, i.e. an enzyme built up from three identical polypeptide chains. Each of the polypeptides contains 213 amino acids and has a molecular weight of approx. 23 kD, i.e. a total of 639 amino acids and a molecular weight of 69.15 kD. This can be compared to HCA II which is a monomeric protein of 259 amino acids and a molecular weight of 29.3 kD[6]. Thus, an advantage of HCA II, as compared to Cam, is that it will not be inactivated by dissociation of polypeptides. Another problem associated with the use of γ-carbonic anhydrase from Methanosarcina thermophila is that to obtain the most active form of the enzyme (Fe2+-Cam) it needs to be produced anaerobically and to be protected from air during purification and use. If these prerequisites are not met, the naturally occurring Fe2+ in the active site is oxidized to Fe3+ and subsequently exchanged by Zn2+, which lowers the activity an additional 3-fold[6,7].
The conversion rate and efficiency is of course of great importance for the technical and economical feasibility of using carbonic anhydrases in any CO2-capturing process. Thus, if it would be possible to use human carbonic anhydrase II, a bioreactor would require 10-20 times less enzyme (alternatively be 10-20 times smaller with the same amount of enzyme) than a corresponding reactor using e.g. γ-carbonic anhydrase from Methanosarcina thermophila.
Enzymes are macromolecular protein biomolecules that are able to function as highly effective, high-performing biological catalysts and are fundamental for all biological life. They are substances that accelerate the chemical reactions of life without being consumed themselves in the reaction. Isolated enzymes are important in many industrial processes for treating biological substrates. Thus, enzymes for industrial and environmental applications have a large and increasing economical and ecological value.
One bottleneck in the application of enzymes in industrial processes is that in order to be active, enzymes and other proteins must keep a highly ordered and folded structure. However, the highly ordered structure of proteins is only maintained if the proteins are stable at the prevailing conditions, i.e. pH, ionic strength, temperature, etc., within certain limits that are specific for each type of protein. In terms of natural selection of proteins during evolution, this notion stresses the fact that a protein molecule only makes structural sense when it exists under conditions similar to those for which it was selected, in its so called native state. Protein stability can fundamentally be divided in chemical stability and physical stability. Chemical stability relates to changes in activity of the enzyme in response to various chemical alterations, e.g. deamidination of aspargine to aspartate and oxidation of methionine. Changes in activity can be due to changes of the amino acids involved in the enzymatic process or due to that the chemically modified enzyme looses its structure and hence activity. Physical stability relates to the intrinsic ability of the protein to find and maintain its structure (and hence activity). Physical stability can be measured in several ways, e.g. as the thermodynamic stability, the thermal stability and the kinetic stability which are all a function of the sum of interactions within the protein and between the protein and its surroundings.
Therefore, in the quest to design more stable proteins, it is important to understand the differences and benefits, as well as the underlying mechanisms, of each type of stability to be able to attain proteins with the desired increased stability.
Thermodynamic stability is a measure of the difference in free energy (ΔG) between the inactive unfolded (U) states and the folded state (F) in which the enzyme is active. Thermodynamic stability can be determined at equilibrium conditions if the protein is free to unfold and re-fold. This two-state model can be written as:F⇄UThus, in this case the stability is simply the difference in free energy between the U and the F states (ΔG=GUnfolded−GFolded) and the stability is defined as ΔGFU, whereΔGFU=−RT ln K.K represents the equilibrium constant between the unfolded and the folded state (K=[U]/[F]) and, therefore, the more thermodynamically stable the protein is the larger the difference in free energy (ΔG) is. This can also be graphically represented by plotting the difference in free energy between the unfolded and native state. (See FIG. 1).
Thus, simplified, the thermodynamic stability can be increased by either destabilizing the unfolded state (higher free energy of U) or stabilizing the native state (lower free energy of F) so as to maximize the difference in free energy (ΔGFU) between the two states. The change in free energy needs to be lower than zero (ΔG<O) for the folding reaction to be efficient, that is, favoring the native state of the protein. Since the difference in free energy is determined by its enthalpy (ΔH, interactions) and entropy (ΔS, disorder) according to ΔG=ΔH−TΔS a favorable ΔG can be accomplished by strengthening the interactions of the folded state, leading to lowered enthalpy (e.g. hydrogen bonds, ion bonds, better packing of the protein interior etc.). The same, i.e. a larger difference in free energy between the unfolded and folded state, can be accomplished by destabilizing the unfolded state. Furthermore, for the unfolded state, which can be assumed to be a random coil, the same can be accomplished by restraining the freedom of the unfolded state leading to lowered entropy of the unfolded states and thereby a higher level of free energy for the unfolded state.
The melting point (Tm) of a protein, i.e. the midpoint temperature of unfolding, is a measure of a proteins thermal stability. In industrial processes it is often desirable to use enzymes with a high melting point since it is in many cases beneficial if the reaction can take place at an elevated temperature (higher rates of reaction, lower viscosity, less microbial growth, less fouling etc). For this reason, what is often focused on for proteins that have a potential use in industrial, enzyme based, processes is that the protein has a high thermal stability (i.e. a high melting point).
It is, however, important to recognize that at standard temperature (25° C.) the ΔGFU values for a thermolabile protein are not necessarily lower than for a thermostable protein, i.e. a high thermal stability is not the same as a high thermodynamic stability at all temperatures[8]. Thus, it is not possible to deduce the melting point of a protein by simply determine its thermodynamic stability at ambient temperature or vice versa. The melting temperature (Tm) is the temperature at which U and F are at equilibrium and are equally populated and is determined by the ΔGFU(T) function, and will occur when the denaturing pressure (temperature) is so high that ΔGFU=0. When ΔGFU is plotted as a function of temperature, the ΔGFU(T) function displays a skewed parabola that intersects the x-axis twice (i.e. both heat- and cold denaturation occurs) (see FIG. 2).
FIG. 2 illustrates how the thermostability of a hypothetic protein thus can be increased by other means than increasing the thermodynamic stability (ΔGUF) of the protein at standard temperatures.
Thus, thermal stability is related, but not equivalent, to thermodynamic stability. That is, at ambient temperatures a protein can have a relatively low thermodynamic stability and still prove to have a relatively high melting point.
Kinetic stability is a measure of at what rate a protein unfolds (kU). This is especially important for proteins or conditions that denature proteins irreversibly to unfolded states. A protein can denature irreversibly if the protein in the unfolded state rapidly undergoes some permanent change such as proteolytic degradation or aggregation (which often is the case with thermally denatured proteins).
In these cases it is not the difference in free energy between the folded and unfolded state that is important. That will only affect the equilibrium and this is not a true equilibrium process. Instead, for kinetic stability, the important thing is the difference in free energy between the folded state (F) and the transition state (ts#) on the unfolding pathway which determines the activation energy for unfolding (EA, unfolding). Hence, EA, unfolding determines the rate constant of unfolding (kU) and thereby at what rate an irreversible inactivation of the unfolded state can take place (See FIG. 3).
Thus, this is in no way related to the thermodynamic stability (ΔGFU) or the thermal stability (Tm) and other means are necessary to increase the kinetic stability as compared to ΔGFU and Tm. In order to change the free energy of the transition state the folding/unfolding mechanism of the protein needs to be affected. Simplified, when an ensemble of proteins fold they will mainly follow the fastest route that produces folding intermediates and transition states of lowest possible energy levels. However, if this route is no longer accessible, they will be forced to fold via an alternative route that has folding intermediates and transition states of higher energy. This will in effect lead to a route that places the transition state at a higher level of free energy. In this case, since the folded state has the same energy level as before (still needs to be in its highly ordered native fold to be active) the height of EA, unfolding will have increased and thus provide a barrier to unfolding leading to a slower unfolding rate constant (kU).
Thus, for a protein to be valuable for any application it needs to have a large negative ΔGFU at the temperature of operation so that the protein operates well below its melting point (Tm). Equally important is that it needs a high kinetic stability so that the protein is maintained in the natively folded state and the protein does not sample the unfolded state which will render it irreversibly inactive. Hence, a high kinetic stability will lead to slow unfolding and a long lifetime of the protein. This is true for all conditions and will for example increase shelf life of the protein at ambient temperatures, but the activation energy for unfolding (EA, unfolding) will also provide a barrier for unfolding also if the protein operates close to or even above its unfolding point (thermal or other) and thus keeping the unfolding rate constant (kU) low and the lifetime high also at conditions that induce unfolding.
There are numerous ways of stabilizing proteins[9], either by stabilizing the folded state or by destabilizing the unfolded state by different means. However, most methods to stabilize the folded state rely on strengthening local interactions that are only formed once the protein is folded and few will substantially affect the folding route and hence the kinetic stability. Furthermore, because of the often hundreds of amino acids to vary and the thousands of interactions within the protein and between the protein and the surroundings, it is very difficult to simply examine the structure and pinpoint what to change in order to increase the stability. This is also the reason why combinatory methods like directed evolution has been developed. Since these methods produce thousands of variants of the protein "by chance", which are subsequently tested for activity at different conditions, it circumvents the need for detailed knowledge of the protein structure, or understanding of protein stability. However, for those well acquainted with the art of protein stability and stabilization it is possible to design more stable proteins by knowledge-based protein engineering. One attractive way to stabilize a specific protein by knowledge-based protein engineering is to graft structural motifs that is known to be stabilizing from one protein homolog to the protein homolog that is to be stabilized, of which there are numerous examples in the literature [10,11]. Two proteins are considered to be homologous if they have identical amino acid residues in a significant number of sequential positions along the polypeptide chain. However, as is text book knowledge in protein chemistry, the three dimensional structure is much more conserved than sequence and it is often found that proteins with very low sequence identity still have similar function and similar three-dimensional structures[12]. Thus, members of such families are also considered to be homologous even though polypeptide sequence identities are not statistically significant, only structurally or functionally significant. Furthermore, homologous proteins always contain a core region (structurally conserved regions) where the general folds of the peptide chains are very similar. That is, the scaffold of even distantly related homologous proteins with low sequence identity have similar structure. It is these relationships that make it possible to transfer stabilizing amino acid combinations or motifs between structurally homologous proteins if there is three dimensional structural data available. Structural data can originate from X-ray crystallography, nuclear magnetic resonance spectroscopy or model building. If two such structures of homologous proteins are superimposed, one with stabilizing interactions of interest (the template) and the other to be stabilized (the target), the three dimensionally structurally equivalent position of stabilizing amino acids to be changed can be identified in the target structure.
One way of reducing the freedom (i.e. entropy) of the unfolded state and thus place the unfolded state on a higher energy level is to introduce covalent links between parts of the protein. This can be done by changing the original amino acids to cysteins which are able to form covalent disulfide bridges (S—S) if the thiol groups of the two amino acid side chains are correctly placed in space. To design such bridges is however not trivial since the geometry of an unstrained —CH2—S—S—CH2— bridge in proteins is limited to rather narrow conformational constraints, and deviations from the geometrical constraints will introduce strains into the folded structure. However, because of the geometrical constraints, identification of disulfide bridges are particularly amenable for homology modeling to identify amino acid positions to alter to cysteines in order to introduce disulfide bridges in homologous proteins, of which there are numerous examples of in the literature[13,14]
Although this method has a limited rate of success since the replacement of the wild type amino acid and the introduction of a disulfide bridge will often lead to loss of favorable interactions or strain in the folded state, it will lead to a larger thermodynamic stability (ΔGFU) if the folded state is unaffected (See FIG. 4).
Further, if the introduced disulfide bridge brings together parts of the protein that normally are in close contact during early stages of the folding event, it will not affect the folding pathway and will thus only increase the thermodynamic stability and possibly the rate of folding (under the prerequisite that the energy level of the folded state is unaffected). If however the introduced disulfide bridge brings parts of the protein together, that during normal folding does not interact early in the folding event, this will lead to that the protein likely needs to fold via an alternative route that has a transition state of higher free energy. Under the prerequisite that the energy level of the folded state is unaffected, this will lead to that the activation energy for unfolding (EA, unfolding) will become higher and thus the unfolding rate will be slower and the lifetime of the protein will be increased. If this can be accomplished, an ideal protein, with both a high thermodynamic stability (and possibly increased melting temperature) and a high kinetic stability, is constructed (See FIG. 5).
Besides being potentially able to increase both the thermodynamic and the kinetic stability of proteins, the stabilization is of entropic origin by restricting the freedom of the unfolded state by incorporation of a covalent bond (disulfide bridge). Thus, enthalpic stabilizing interactions by introducing disulfide bridges will not display a strong temperature dependence, which can otherwise weaken or strengthen e.g. hydrogen bonds, salt bridges, ionic bonds or hydrophobic effects. In addition, this also means that the stabilization will be less influenced also by other characteristics of the surrounding media, such as polarity and ionic strength etc, and the relative increase in stability will be maintained also in media other than buffered aqueous solutions.
From the above it can be presumed that to increase the physical stability of a protein even more, one simply adds more disulfide bridges. However, this is not uncomplicated for several reasons. Firstly, the introduction of even a single stabilizing disulfide bond is challenging, since often what is gained in energy difference by decreased entropy of the unfolded state is often also lost in enthalpic energy in the folded state, because of lost non-covalent interactions, or strain introduced into the structure so that the ΔGFU of the engineered protein is the same or even less than that of the wild type protein (i.e. thermodynamically destabilized). Thus, introducing two or more disulfide bridges might increase or decrease the stability of the protein. Secondly, with two disulfide bridges present, the folding pathway of the protein could be blocked, so that the protein is no longer able to fold into its native active form. Thirdly, when more than two cysteines are introduced in a protein there is a high risk that the cysteines make disulfide bonds with the wrong partner during synthesis or folding. This will always lead to an inactive protein as it will not be able to find its folded active conformation. This is also especially important during production of heterologous (e.g. mammalian) proteins with multiple disulfide bonds in recombinant systems (e.g. bacteria) as the formation of correct or native disulfide bonds in such systems is very inefficient, often leading to low yield of production of functional enzymes.

Human carbonic anhydrase II with increased physical stability


A proton type β zeolite is used as catalyst. Nitrogen oxides in the exhaust gas containing excessive oxygen is reduced/removed by making the exhaust gas contact with the catalyst under the existence of methanol and/or dimethyl ether as reducing agent. It is desirable that a SiO2/Al2O3 molar ratio of the proton type β zeolite is within 20-70. Thereby, the present catalyst has an excellent denitration performance and durability even against the exhaust gas containing sulfur oxides, and the denitration performance does not deteriorate even when the exhaust gas is at comparatively low temperature of 300-400° C.

Nitrogen oxides (NOx) such as nitrogen monoxide and nitrogen dioxide are contained in various types of exhaust gas from factories, electric power facilities, other industrial facilities and motor vehicles. This NOx not only affects especially on the respiratory system of human body but also causes acid rain seen as a problem in global environment conservation. Therefore, a technical development effective for removing nitrogen oxides in various types of exhaust gas is desired.
Among methods for removing such nitrogen oxides known so far, there are a ternary catalytic method being used in exhaust gas treatment of a motor vehicle (a gasoline-powered vehicle) and a selective catalytic reduction method using ammonia as reducing agent. But the ternary catalytic method cannot apply to the exhaust gas containing oxygen in excess of theoretical amount necessary to completely oxidize an unburned hydrocarbon or carbon monoxide remaining in the exhaust gas.
Meanwhile, among methods for reducing/removing NOx from the exhaust gas containing excess oxygen known so far, there is a selective catalytic reduction method using a catalyst comprising V2O5—TiO2 and using ammonia as reducing agent. In this way, however, it is not easy to care for because of using highly smelling and harmful ammonia, and facilities grow in size because it needs a special apparatus for limiting emissions of unreacted ammonia. Therefore, it is not adequate to apply to a small-sized exhaust gas source or mobile source, and undesirable in economical efficiency.
In recent years, it has been reported that using an unburned hydrocarbon as a reducing agent remaining in the lean-burned combustion exhaust gas containing excess oxygen (ex. diesel engine) can accelerate a reduction reaction of NOx in the exhaust gas. Since this report, various catalysts to accelerate the reduction reaction of NOx have been developed, and many reports have been made, for example, alumina and transition metal-impregnated almina are effective for a reduction/removal reaction of NOx which uses hydrocarbons as reducing agent.
As an example of a catalyst which reduces/removes nitrogen oxides in the combustion exhaust gas containing excess oxygen with using such hydrocarbons as reducing agent, besides alumina and transition metal-impregnated alumina, a reduction catalyst which comprises alumina or silica-alumina including 0.1-4 weight % Cu, Fe, Cr, Zn, Ni or V of 0.1-4 has been reported (Refer to JP KOKAI Hei 04-284848).
Furthermore, it has been reported that the reduction reaction of NOx proceeds even in a low-temperature range of 200-300° C. when alumina impregnated with Pt and the like. (Refer to JP KOKAI Hei 04-267946, JP KOKAI Hei 05-68855 and JP KOKAI Hei 05-103949). However, the catalyst using such precious metals has defect that it is difficult to get selectively proceed a reduction reaction into harmless N2 because a combustion reaction of hydrocarbon which is a reducing agent is promoted excessively or because N2O which is seen as one of causative agent of global warming is side-produced in large quantity.
Furthermore, it is reported that alumina and the like impregnated with silver, with using hydrocarbon as reducing agent in the exhaust gas containing excess oxygen, makes NOx reductive reaction proceed selectively (Refer to JP KOKAI Hei 04-281844). After this report, lots of similar methods for NOx reduction/removal using the catalyst containing silver have been developed and reported (Refer to JP KOKAI Hei 04-354536).
However, each method for purifying the exhaust gas using NOx removal catalyst has a problem that, in the exhaust gas containing sulfur oxides and excess oxygen, the NOx removal performance deteriorates remarkably and the practicable durability is insufficient. Furthermore, it has also a problem that NOx removal performance is low if the majority of the exhaust gas is at relatively low temperature of 300-400° C.
Furthermore, the method for the NOx reduction/removal under coexistence of organic compounds which uses a hydrogenated zeolite catalyst or zeolite catalysts impregnated with V, Cr, Mn, Fe, Co, Ni and the like has been reported and, as the zeolite, Y-type zeolite, L-type zeolite, offretite-erionite mixed crystal-type-zeolite, ferrierite-type zeolite and ZSM-5-type zeolite are shown (Refer to JP Patent No. 2139645). Furthermore, the method for the NOx reduction/removal in the presence of methanol which uses a proton-type zeolite has also been reported and, as the zeolite, Y-type zeolite, ZMS-5-type-zeolite and mordenite are shown (Refer to JP Patent No. 2506598).
However, each method for the NOx reduction/removal which uses above-mentioned specific zeolite catalysts can not obtain the practicably satisfying NOx removal performance, and at present, has not been put into practical use.
An object of this invention is, in consideration of such circumstances, to provide a catalyst for purifying exhaust gas, having an excellent NOx removal performance and durability even against the exhaust gas containing sulfur oxides, and having a high denitration performance and an excellent practicality even when the exhaust gas is at relatively low temperature of 300-400° C., and to provide a method of purifying exhaust gas using the catlyst.

Catalyst and method for clarifying exhaust gas


An apparatus for open-heart surgery includes a platform (20) to support the surgeon's hand (or an instrument) and a cam (30) for reciprocating the platform oscillation around a hinge (12). The cam is shaped so that the pattern of the platform oscillation follows the beating heart's motion. The platform motion triggers a momentary-contact switch on each cycle. The switch drives a pacer, which paces the heart to beat in synchrony. The platform rate is set slightly above the un-paced heart beat rate; this keeps the heart in close synchrony with the platform oscillation and stabilizes its motion. The platform and heart move together, relative motion is canceled, and the surgeon need not compensate. The platform is mounted (10) on an adjustable support and a laser beam is used to angularly align the platform to the heart oscillation. A capacitive sensor (21) detects the heart-to-platform distance, which is used to generate an audible tone proportional to the distance; the tone is used to adjust the platform oscillation amplitude and/or phase for minimum variation of the heart-platform distance.

In many surgical operations work must be done on a moving organ, such as a beating heart. This requires not only manipulations to perform the operation which would be required in any case (even if the organ were still), but also requires correction of the surgeon's hand motions to compensate for the organ motion so as to keep the surgeon's hands still relative to the work area.
One such operation which has recently been gaining in popularity is known as minimally invasive coronary artery bypass grafting. As described by Calafiore et al, "Minimally invasive Coronary Artery Bypass Grafting", Ann. Thorac. Surg., 62:1545-1548 (1996), minimally invasive coronary artery bypass (MICAB) is defined as an intervention that does not require median sternonomy or the use of cardiopulmonary bypass (CBP). The incision in the chest wall is small, and the aorta, in any portion, is not the direct source of inflow of blood supply to the bypass grafts. MICAB promises to become an important addition to the surgical treatment of coronary artery disease.
In this technique, the patient is anesthetized and intubated with a single endotracheal tube and hemodynamic monitoring. Short-acting anesthetic agents are used, as extubation of the patient in the operating room is routine. The chest is opened through a fourth or fifth intercostal space incision and the pericardium is opened longitudinally. The left anterior descending coronary artery (LAD) is identified and inspected. The LIMA is harvested through the same incision with or without the aid of a thoracoscope. One or more costal cartilages may be resected to achieve better visualization and dissection of the full length of the LIMA. The artery can be harvested as a pedicle or as a skeletonized vessel.
The patient is heparinized (1 mg/kg), and diluted papaverine is injected into the pedicle and intraluminally into the LIMA through a blunt-tipped cannula. Traction sutures are applied to the edges of the pericardium. After selection of a site for construction of the anastomosis and assessment of the length of the LIMA, distal and proximal control of the LAD is required. A snare of 4/0 PROLENE (Ethicon, Somerville, N.J.) or silicone suture can be applied proximally and distally to the site selected for the anastomosis. Alternatively, the vessel can be opened and a FLOW-RESTER placed intraluminally. The surgical blower (VISUFLOW, Research Medical, Midvale, Utah) is used for visualization. Electrocardiographic changes, arrhythmias, and ventricular fibrillation are rare events during occlusion of the LAD. Traction sutures can be applied to the visceral pericardium lateral to the LAD, thereby allowing for better stabilization of the artery. Alternatively, a suction device (Medtronic Inc, Minneapolis, Minn.) or a stabilizer (CTS Inc) can be used. Short-acting .beta.-blockers or calcium channel blockers are used to reduce heart rate when necessary.
The LAD to LIMA anastomosis is performed using a 7/0 or 8/0 running PROLENE suture, either as a single suture or as two strategically placed sutures at the toe and heel of the LIMA. Some surgeons prefer interrupted sutures. At completion of the anastomosis, heparin is reversed with protamine sulfate. Closure of the chest is as in any standard thoracotomy, leaving a pleural tube for drainage. An intrapleural catheter is placed for pain control. The patient is extubated in the operating room or shortly thereafter. Patency of the artery is confirmed by standard Doppler (velocity) echocardiography intraoperatively and by duplex scanning of the LIMA early and late postoperatively in every patient. This is usually done 2 to 3 hours postoperatively and 24 hours after operation. Diastolic flow predominates in a patent LIMA. Most centers report early discharge from hospital and significant cost savings associated with this procedure.
It has been reported that by mid-1996 at least 200 MICAB procedures had been performed in various universities and private hospitals in the United States and several hundred more in Europe and South America (Hartz, "Minimally Invasive Heart Surgery", Circulation, 94:2668-2670 (1996)). For other respects about such surgery, see also Calafiore et al, "Left Anterior Descending Coronary Artery Grafting Via a Left Anterior Small Thoracotomy Without Cardiopulmonary Bypass", Ann. Thorac. Surg., 61:1659-1665 (1996); Stanbridge et al, "Minimal-Access Surgery for Coronary Artery Revascularization", Lancet, 346:837 (1995); Acuff et al "Minimally Invasive Coronary Artery Bypass Grafting", Ann. Thorac. Surg., 61:135-137 (1996), and Subramanian et al "Minimally Invasive Coronary Artery Bypass Surgery: A MultiCenter Report of Preliminary Clinical Experience", Circulation, 92 (Suppl. 2):645 (1995).
While such operations have been successfully performed in many different centers, substantial risks are involved in performing surgery on a beating heart. In such operations the arteries are small, the stitches fine, and the sutures are liable to rip due to the heart motion. The risk to the patient is considerable. There have been cases in which the arterial walls were ripped, requiring the operation to be aborted and causing complications.
At first blush it might appear that the heart's motion, being regular, could be easily compensated for by the surgeon. However, the heart motion amplitude is about a half inch (1.3 cm), and this is quite large compared to the precision required of the surgeon's manipulations. The rhythm is erratic. The motion tends to sudden pulsations rather than a smoothly-varying motion such as a sinusoidal motion.
Thus, the acceleration of the heart surface changes rapidly. During the intervals of high acceleration the surgeon is substantially unable to do anything beyond keeping the instruments near their positions relative to the heart, so that no suture rips or unintended punctures occur. The operation is actually performed intermittently during the lulls of low acceleration.
Because of these difficulties, the heart is often artificially slowed down during operations, as discussed above, such as by means of short acting .beta.-blockers or calcium channel blockers. This improves the surgeon's situation in proportion to the change in rate, but for obvious reasons the degree of improvement is limited.
Moreover, the heart (like most organs) responds to stimulation. A suture needle prick often causes this muscular organ to twitch strongly, which is very difficult to compensate for. Twitching will not be lessened by slowing the heart down.
Calafiore et al, supra, report that stabilization of the heart during construction of the anastomosis is an important aspect of the procedure, and devices are being developed that will aid the surgeon during this critical part. However, physically immobilizing the heart is a less than desirable technique as it could damage the heart or impair circulation during this period.
Devices for surgery on a beating heart were reported in a front-page story in the Wall Street Journal of Apr. 22, 1997. The story said that CardioThoracic Systems, Inc. is marketing a device resembling a two-pronged fork which is pressed against the beating heart to stabilize the pressed region and allow the surgeon to operate. The cost is $1850 per operation. Another device sold by Medtronic is called the "Octopus"; it costs $10,000. Others are expected to be marketed soon by Baxter Inc. and U.S. Surgical Corp.
The CardioThoracic system can only be used in about 20% of all bypass operations, according the article. Triple and quadruple bypass and valve repairs require stopping the heart.
Pressing on the heart naturally will affect the blood flow through it, and the amount of pressure is limited. The problem of twitching is not overcome, and it appears that the heart surface cannot be immobilized completely.
The new devices "set off intense debate over safety and economics", according to the article. "Some surgeons are particularly skeptical that joining tiny blood vessels on the surface of the heart can be done as successfully while the heart is beating--the CardioThoracic way--as when it is stopped. . . . During a recent stopped-heart! operation, Dr. Colvin of New York University Medical Center! peered through magnifying goggles as he performed the delicate task of joining the replacement vessel to a coronary artery, using a tiny needle and barely visible sutures. `At this point, if you're doing it "beating-heart" you're cursing a mile a minute`, he remarked."
The article also reported on a stopped-heart kit which is being aggressively marketed in competition with the CardioThoracic device. Produced by Heartport Inc., is! it costs $5000 per kit. It has been used in about 500 cases. Like the CardioThoracic method, the Heartport method avoids opening the ribcage, instead using a smaller opening. Because opening the ribcage is a traumatic and painful operation, patients are more likely to chose an operation which requires only a smaller opening.
However, the Heartport method involves stopping the heart with a balloon in the aorta and drugs, and using a heart-lung machine to keep the patient alive during the operation.
The article noted that stopping the heart is stressful and dangerous, and is impossible if the patient is too sick. The cost of using the heart-lung machine is as much as $2,300 (the machines cost about $150,000) and about 6% of patients suffer complications, including stroke, depression, and severe infections. The ideal heart operation would need only a small incision, like the Heartport and CardioThoracic operations; avoid the expense and risk of a heart-lung machine, like the CardioThoracic operation; and stop the heart so the surgeon can safely operate on the delicate arteries, as in the Heartport operation. None of the available operations or devices achieve all these.
The prior art has not solved these problems of working on a moving organ, despite the great need for improvement.

Relative motion cancelling platform for surgery


Method and device for solid structure formation by localized microwaves for additive fabrication of solid bodies by use of localized microwave radiation applied to a source material, in the form of a powder, wire or other solid form, so as to generate a hotspot in a thermal-runaway process or through plasma breakdown, and melt a small portion of it (with at least one dimension smaller than the microwave wavelength) thereby consolidating small pieces of the molten source material in a stepwise manner to construct the entire body.

The concept of additive manufacturing has been developed in various directions, namely 3D-printing, 3D-prototyping, and rapid manufacturing. These technologies are widely used to produce a broad range of parts in various industries. Unlike conventional machining technologies, where material is removed from plain solid blocks to obtain the desired part, additive manufacturing technologies produce the solid body layer by layer by super-positioning cross sections of the raw material. Typically, custom-made products are manufactured directly from its 3D computer aided design (CAD) model, which is pre-processed —for part orientation, creation of horizontal cross sections, and definition of other relevant process parameters—and fed as an input file to the manufacturing machine control. Additive manufacturing is capable also of making parts that otherwise would be impossible to produce with conventional machining methods, or require expensive molds or dies. Currently, the technologies used for direct manufacturing of metallic parts from powders are selective laser sintering (or melting), stereo-lithography, direct-metal laser sintering and spark-plasma sintering. Such devices are generally too large and costly to be widely used.
US2004232583 describes an additive fabrication process for sequentially incrementing a workpiece to form a desired object, the process comprising:
a. providing a layer of pulverulent substrate;
b. selectively applying at least one microwave-absorbing susceptor to one or more regions of the substrate;
c. treating the layer at least once with microwave radiation, to melt the regions containing the susceptor.
d. cooling the layer.
GB2422344 describes an additive fabrication process for sequentially incrementing a workpiece to form a desired object, the process comprising the same steps a, b and c described in US2004232583, but using infrared radiation to meld the powder.
The cited prior art patents requires extending a layer of source material, and adding a susceptor to some regions of said source material layer. It has to be noted though that US2004232583 does not employ a localized microwave applicator, and that it requires adding susceptors (microwave absorbing additives) to the raw material, hence this method is not applicable for instance to pure metal powders. Regarding GB2422344, infrared is a different type of radiation than microwaves. It is generated and guided by completely different devices, and has different physical properties.
U.S. Pat. No. 6,243,616 B1 describes an additive fabrication device for sequentially incrementing a workpiece to form a desired object, the device comprising:                a feeder for providing source material onto a surface in a desired uniform thickness;        a microwave apparatus including a microwave generator able to create a microwave radiation in the frequency range of 430 to 6800 MHZ, and a microwave applicator able to provide said microwave, preferably focused onto a beam width of 0.1 to 3 mm, particularly preferably 0.3 to 1 mm;        a controlled displacement mechanism for generate relative displacement between said support structure and said microwave applicator so that a layer by layer structure is performed.
The referenced patent describes a microwave frequency range focused in a beam with a size which is essentially larger than the wavelength, so it can't induce a thermal-runaway process (note that U.S. Pat. No. 6,243,616 B1 does not present any implementation of the microwave applicator that can focus the microwave energy to a spot smaller than a wavelength, and it does not present any physical mechanism that may compensate for the natural diffraction of the microwave energy expected in the schemes presented there). Further this document deals also with a layer-by-layer deposition, whereas we propose, as discussed below, also localized feeding of the raw material either in a powder or a wire form, directly by and/or in combination with a microwave applicator. U.S. Pat. No. 6,243,616 B1 is relevant mainly for polymer materials, and to microwave absorbing materials (see column 4, lines 46-47, ". . . (materials) have a dipolar basic structure", hence it is not applicable for pure metal powders (which obviously have no dipolar structure). The irrelevance to pure metals is also indicated clearly in the description of the invention there (see column 4, Line 49, where the applicability is limited to "metal powders coated with these polymers", whereas the latter are needed as microwave absorbers. In the present invention, other mechanisms are employed, such as localized microwave inner plasma breakdown; hence the present invention is applicable also for metal powders, with no coatings or additives as the previous cited prior arts.
U.S. Pat. No. 6,214,279 describes an additive fabrication process, which deals with composite materials and multi-component fabrication, using an adhesive product to solidify the source material.
With regard to the previous art the proposed invention provide an additive fabrication method and corresponding device in which localized microwaves are employed to melt or sinter the source material to increment the object being fabricated wherein localized microwave radiation is applied through a near-field microwave applicator configured to apply the microwave radiation to transform the source material within an included volume receiving the localized microwave radiation, said included volume having at least one dimension smaller than a wavelength of the microwave radiation induces intentionally either a thermal-runaway instability and/or inner plasma breakdown in between the source material particles.
U.S. Pat. No. 6,114,676 discloses, but in the context of a microwave drill technology, localized application of microwaves" preferably achieved by use of a near-field applicator, to eliminate material from a solid concentrating the microwave radiation into a volume having at least one dimension smaller than the microwave wavelength, and most preferably smaller than half the microwave wavelength, thereby inducing a thermal-runaway process in which the local temperature increase is accelerated by the temperature-dependent parameters of the raw material, and a confined hotspot is formed rapidly. According to this method, small amounts of source material in front of the applicator are melted and removed. Therefore, it has to be noted that while the present invention employs a similar applicator to U.S. Pat. No. 6,114,676, the purpose is totally different, as the present invention deals with additive construction, mainly of powders, whereas U.S. Pat. No. 6,114,676 deals mostly with removing (e.g. drilling) of solid materials. The joining application in U.S. Pat. No. 6,114,676 refers to metal parts rather than powders.

Method and devices for solid structure formation by localized microwaves


A patterned connection plane between two semiconductor chips which are connected using face-to-face technology is patterned into first pads, second pads, and conductor strips which are alternatively connected to one of these pads. The conductor strips are connected to a read-out circuit in one of the semiconductor chips via connections.

Increasing the storage density of ROM semiconductor chips is associated with considerable technical complexity. Since the dimensions of the memory cells can be reduced only with considerable effort, increasing the size of a ROM inevitably leads to an increased space requirement on the relevant semiconductor chip.
When fabricating semiconductor chip stacks using face-to-face technology, two semiconductor modules are directly connected to one another to form an overall system by electrically conductively connecting connection contact areas which are arranged on the top sides (which face one another) of the semiconductor modules to one another. In addition, the semiconductor chips are permanently connected to one another in a mechanically stable manner. To this end, a connection plane comprising a metallic solder is preferably arranged between the semiconductor chips, the connection plane ensuring that the two components are connected in a mechanically stable manner and, at the same time, ensuring that the connections are electrically connected. In this case, by far the largest area proportion of this connection plane is used only to mechanically connect the two components and is not used electrically.


A push fit connector system utilizes a locking sleeve which is inserted within an internal tapered section of a cylindrical housing. A pipe end inserted into the cylindrical housing is received within the locking sleeve. Withdrawal of the pipe from the cylindrical housing is prevented as the locking sleeve radially collapses as it is received within a smaller diameter of the internal tapered section.

The present invention relates to fluid flow systems and connectors utilized to couple adjacent components of a fluid flow system. More particularly, the present invention provides a secure connection between adjacent components with an easy and fast push-fit connection requiring no tools. In the present invention, a fluid conveying conduit is inserted into the connector of the invention and grasped upon insertion. Embodiments of the present invention provide this connection with a minimal number of components, thereby reducing the expense of the connector and related components.
Piping connection devices are necessary to join piping and pipe fittings together, as well as connecting piping utilized for supply and/or drainage to various components. Piping fittings may include straight lengths of pipe, elbows, tees, as well as pipe reducers, swages, valves, angle connectors, etc. Piping components may include faucets, headers, pumps, manifolds, tanks, and similar devices.
In the past, pipe connections have been made by welding, soldering, threaded, or glued connections. Welding, soldering and, in the case of plastic pipe, glued connections are time consuming, labor intensive, and non-reversible. Threaded connections are not appropriate for every application, and typically require the use of pipe unions.
In an effort to overcome the disadvantages of the other known devices and methods for connecting pipe, fittings and components, push-fit devices were introduced. While a step in the right direction, the known push-fit devices can be complex, utilizing multiple parts.


A protective cover for a pilot probe of an aircraft comprising a first tubular member formed of a rigid material, and a second tubular member formed of a rigid material, and a second tubular member formed of a flexible material including a first ply disposed on an inner side of the first tubular member, having an opening at a first end thereof for receiving the leading end of a pilot probe therein and a closed second end, and a second ply disposed on an outer side of the first tubular member, having a first end thereof secured about the first end of the inner ply and a second end secured to the second end of the first ply.

Typically, commercial and military aircraft are provided with probes mounted on the fuselages thereof for sensing wind pressure when in flight, used to compute the velocity and altitude of such aircraft in flight. Such probes are highly sensitive and proned to impairment upon being subjected to physical impact, extreme temperatures, certain reactive chemicals, various containments and the like, when the aircraft is out of service on the ground, simply parked, stored or undergoing repair and/or maintenance. In the prior art, there has been developed a number of protective covers for such probes, particularly pilot probes, which are designed to shield such probes from exposure to such harmful elements. Although such prior art covers have been useful in shielding such probes, more effective shielding and protection from such elements has been found to be desireable. In particular, it has been found to be desireable to more effectively shield such probes from physical impact which would impair their performance. Accordingly, it is the principal object of the present invention to provide a still more improved cover for a pilot probe which more effectively shields and protects such a probe from the aforementioned deleterious elements when an aircraft on which such probe or probes are mounted is on the ground, usually parked, stored or undergoing some form of repair or maintenance activity and subject to possible damage.

Protective cover for aircraft pitot probes


The present invention provides humanized antibody molecules (HAMs) having specificity for carcinoembryonic antigen (CEA) and having an antigen binding site wherein at least one of the complementarity determining regions (CDRs) of the variable domains is derived from the mouse monoclonal antibody A5B7 (A5B7 MAB) and the remaining immunoglobulin-derived parts of the HAM are derived from a human immunoglobulin. The HAMs may be chimeric humanized antibodies or CDR-grafted humanized antibodies and are preferably produced by recombinant DNA techniques. The HAMs are useful for in vivo diagnosis and therapy.

Natural immunoglobulins have been known for many years, as have the various fragments thereof, such as the Fab, (Fab').sub.2 and Fc fragments, which can be derived by enzymatic cleavage. Natural immunoglobulins comprise a generally Y-shaped molecule having an antigen-binding site towards the outer end of each upper arm. The remainder of the structure, and particularly the stem of the Y, mediates the effector functions associated with immunoglobulins.
Natural immunoglobulins have been used in assay, diagnosis and, to a more limited extent, therapy. However, such uses, especially in therapy, have been hindered by the polyclonal nature of natural immunoglobulins. A significant step towards the realisation of the potential of immunoglobulins as therapeutic agents was the discovery of procedures for the production of monoclonal antibodies of defined specificity (1). However, most MAbs are produced by hybridomas which are fusions of rodent spleen cells with rodent myeloma cells. The resultant MAbs are therefore essentially rodent proteins. There are very few reports of the production of human MAbs.
Since most available MAbs are of rodent origin, they are naturally antigenic in humans and thus can give rise to an undesirable immune response termed the HAMA (Human Anti-Mouse Antibody) response. Therefore, the use of rodent MAbs as therapeutic agents in humans is inherently limited by the fact that the human subject will mount an immunological response to the MAb and will either remove it entirely or at least reduce its effectiveness.
Therefore proposals have been made for making non-human MAbs less antigenic in humans. Such techniques can be generically termed "humanisation" techniques. These techniques generally involve the use of recombinant DNA technology to manipulate DNA sequences encoding the polypeptide chains of the antibody molecule.
Early methods for humanising MAbs related to production of chimeric antibodies in which an antigen binding site comprising the complete variable domains of one antibody are fused to constant domains derived from a second antibody. Methods for carrying out such chimerisation procedures are described in EP0120694 (Celltech Limited), EP0125023 (Genentech Inc.), EP-A-0171496 (Res. Dev. Corp. Japan), EP-A-0173494 (Stanford University), and EP-A-0194276 (Celltech Limited). The Celltech EP 0194276 application discloses a process for preparing an antibody molecule having the variable domains from a mouse MAb and the constant domains from a human immunoglobulin. It also describes the production of an antibody molecule comprising the variable domains of a mouse MAb, the CH1 and CL domains of a human immunoglobulin, and a non-immunoglobulin-derived protein in place of the Fc portion of the human immunoglobulin.
Subsequently a number of further patent applications have been published relating to chimeric antibodies, including tumour specific chimeric antibodies (e.g. WO 87/02671, Int. Gen. Eng. Inc.; EP 0256654, Centocor; EP 0266663, Int. Gen. Eng. Inc. & Oncogen; WO 89/00999, Int. Gen. Eng. Inc. and EP 0332424, Hybritech Inc.). The Genentech (EP0125023) and Hybritech (EP0332424) patent applications relate to anti-carcinoembryonic antigen (anti-CEA) chimeric antibodies.
Such humanised chimeric antibodies, however, still contain a significant proportion of non-human amino acid sequence, i.e. the complete variable domains. Thus such humanised antibodies may elicit some HAMA response, particularly if administered over a prolonged period Begent et al (ref. 2)!.
In an alternative approach, described in EP-A-02394000 (Winter), the complementarity determining regions (CDRs) of a mouse MAb have been grafted onto the framework regions of the variable domains of a human immunoglobulin by site directed mutagenesis using long oligonucleotides. Such CDR-grafted humanised antibodies are less likely to give rise to a HAMA response than humanised chimeric antibodies in view of the lower proportion of non-human amino acid sequence which they contain. There are 3 CDRs (CDR1, CDR2 and CDR3) in each of the heavy and light chain variable domains.
The earliest work on CDR-grafted humanised MAbs was carried out on MAbs recognising synthetic antigens, such as the NP or NIP antigens. However, recently examples in which a mouse MAb recognising lysozyme and a rat MAb recognising an antigen on human T cells respectively were humanised have been described by Verhoeyen et al (3) and Riechmann et al (4). The preparation of the CDR-grafted antibody to the antigen on human T cells is also described in WO 89/07452 (Medical Research Council). More recently Queen et al (5) have described the preparation of a humanised CDR-grafted antibody that binds to the interleukin 2 receptor.
It has been widely suggested that immunoglobulins, and in particular MAbs, could potentially be very useful in the diagnosis and treatment of cancer (6, 7). There has therefore been much activity in trying to produce immunoglobulins or MAbs directed against tumour-specific antigens. So far, over one hundred MAbs directed against a variety of human carcinomas have been used in various aspects of tumour diagnosis or treatment (8).
There have been a number of papers published concerning the production of chimeric monoclonal antibodies recognising cell surface antigens. For instance, Sahagan et al (9) disclose a genetically engineered murine/human chimeric antibody which retains specificity for a tumour-associated antigen. Also Nishimura et al (10) disclose a recombinant murine/human chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen.
We have now prepared humanised antibodies to carcinoembryonic antigen derived from the anti-CEA mouse MAb A5B7 (11).
Our copending International Patent Application PCT/GB 90/02017 relates to the CDR-grafting of antibodies in general and describes, among other things, that antibodies having specificity for cancer markers such as CEA, e.g. the A5B7 monoclonal antibody, have been successfully CDR-grafted according to the procedure described therein.

CDR grafted anti-CEA antibodies and their production


A hydraulically adjustable walker including a frame that includes a plurality of telescoping legs and a leg adjustment assembly that includes at least one valve and at least one tube that delivers hydraulic fluid into the legs and allows a user to control the length of each leg. The legs of the walker are hydraulically adjustable, so that the front legs may be shortened and the back legs extended, or two side legs shortened and the two opposing side legs extended, so as to allow the walker to be securely placed on two different steps.

Field of the Invention
The invention relates to walkers and other similar devices that assist people in the act of walking and climbing stairs.
Discussion of Prior Art
The conventional walker is a well-known device that has a U-shaped frame formed by two pairs of legs that define the sides of the walker, each pair having a front leg and a rear leg that are connected at the top by a grip bar and a crossbar that connects the two front legs, thereby forming an opening or well for a person to stand in. The walker is typically about waist high, with the front slightly wider than the width of the user. The two sides are approximately 12 inches deep at the grip bar, i.e., the front and rear legs are approximately 12 inches apart at the top, but the distance between the legs gradually increases in the direction of the floor, for reasons of stability. A user uses the walker by standing in the well, gripping the grip bar, and pushing or moving the walker forward approximately the distance of a normal step, and then stepping into the well, to repeat the pushing motion, all the while holding on to the grip bars.
While the standard walker works well on flat and smooth surfaces, it is not as useful when climbing stairs, because the distance between the front and rear legs is significantly greater than the depth of a step on a standard staircase. The fact that the legs of the walker don't all fit on a single step makes it difficult for a user to pause for a rest when going up or down a staircase. When ascending a staircase, the user can lean into the walker for support, but descending a staircase with a walker is a treacherous adventure for the user, because the walker is always in danger of tumbling down the stairs, unless the user holds it in place. Manual adjustments to the lengths of the legs are sometimes possible, however, this requires a tedious process of turning the walker upside down and manually adjusting each leg. In effect, using a conventional walker on a staircase requires more strength, balance, and skill than the typical user is able to exert.
Some walkers deploy mechanical systems to raise or lower the front or rear legs, and this allows the walker to remain in a stable position while supported on two adjacent steps. However, these walkers only allow for the front legs or the rear legs to move in tandem and do not allow for individual leg movement or side-only leg movement. The known walkers also implement mechanical mechanisms that include relatively heavy equipment and are often cumbersome to operate.
What is needed, therefore, is a light weight walker with legs that are independently adjustable. What is further needed is such a walker that is easy to operate.


This invention provides apparatus for reliably and efficiently reading data from a magnetic storage medium under the condition that adjacent magnetization regions are partially erased. A simplified nonlinear description of a read signal resulting from such partially erased magnetization regions is used to derive a state machine model of the read signal. The state machine model implicitly defines a sequence detector for demodulating recorded data from received samples. For a PR4 signal, the state machine has ten states; for an EPR4 signal, the state machine has eighteen states; and for an EEPR4 signal, the state machine has twenty-six states. The PR4 machine is further simplified using squaring and state sharing to provide state machine models with six and four states.

In magnetic storage systems for computers, a digital data sequence serves to modulate current in a read/write head coil in order to write a corresponding sequence of magnetic flux transitions onto the surface of a magnetic medium in concentric, radially spaced tracks at a predetermined baud rate. To read this recorded data, the read/write head again passes over the magnetic medium and transduces the magnetic transitions into pulses of alternating polarity in a continuous time analog read signal. These pulses are decoded by read channel circuitry to reproduce the digital data sequence.
Decoding the pulses into the digital data sequence can be performed by a peak detector in a conventional analog read channel. In such conventional peak detectors, analog circuitry, responsive to threshold crossing or derivative information, detects peaks in the continuous time analog read signal generated by the read head. The continuous time analog read signal is segmented into bit cell periods and interpreted during these bit cell periods. The presence of a peak during the bit cell period is detected as a "1" bit, whereas the absence of a peak is detected as a "0" bit.
As magnetic flux transitions are packed closer together on the magnetic medium in an effort to increase data density, adjacent pulses begin to overlap with one another, resulting in a type of distortion, known as intersymbol interference (ISI), in the read signal. Intersymbol interference can cause a peak to shift out of its bit cell, or to decrease in magnitude. This can lead to detection errors.
The most common detection errors occur when the bit cells are not correctly aligned with the pulses in the continuous time analog read signal. Timing recovery, then, adjusts the bit cell periods so that peaks of the continuous time analog read signal occur in the center of the bit cells on average in order to minimize detection errors. Since timing information is derived only when peaks are detected, the input digital data sequence is normally run length limited (RLL) to place an upper limit on the number of consecutive "0" bits.
The ISI effect can be reduced by decreasing the data density or by employing a coding scheme that places a lower limit on the number of "0" bits that occur between "1" bits. Thus, a compromise must be reached between the requirement to reduce ISI (which calls for a large number of consecutive "0" bits), and the need for timing recovery (which calls for a small number of consecutive "0" bits). A (d,k) run-length limited (RLL) code constrains the minimum number of "0" bits between "1" bits to d, and the maximum number of consecutive "0" bits to k.
Discrete time sequence detectors in sampled amplitude read channels can compensate for limited amounts of intersymbol interference and are less susceptible to channel noise than analog peak detectors. As a result, discrete time sequence detectors increase the capacity and reliability of the magnetic storage system, and they are therefore preferred over simple analog peak detectors.
There are several well known discrete time sequence detection methods including discrete time pulse detection (DPD), partial response (PR) with Viterbi detection, maximum likelihood sequence detection (MLSD), decision-feedback equalization (DFE), enhanced decision-feedback equalization (EDFE), and fixed-delay tree-search with decision-feedback (FDTS/DF).
Sampled amplitude detection, such as partial response with Viterbi detection, allows for increased data density by compensating for intersymbol interference and the effect of channel noise. Unlike conventional peak detection systems that detect the presence or absence of a peak, sampled amplitude recording detects digital data by interpreting, at discrete time instances, the actual value of the pulse data.
To this end, the read channel comprises a sampling device for sampling the analog read signal, a timing recovery circuit for synchronizing the samples to the baud rate (code bit rate), a low-pass analog filter to process the read signal before it is sampled so as to reduce the effects of aliasing, a digital equalizing filter to equalize the sample values according to a desired partial response after the signal has been sampled, and a discrete time sequence detector, such as a Viterbi detector, to interpret the equalized sample values in context to determine a most likely sequence for the digital data sequence (i.e., using maximum likelihood sequence detection). In this manner, a sampled amplitude read channel can take into account the effect of ISI and channel noise during the detection process, thereby decreasing the probability of a detection error. This increases the effective signal to noise ratio and, for a given (d,k) constraint, allows for significantly higher data density as compared to conventional analog peak detection read channels.
The application of sampled amplitude techniques to digital communication channels is well documented. See, for example:
Y. Kabal and S. Pasupathy, "Partial Response Signaling," IEEE Trans. Commun. Tech., Vol. COM-23, pp. 921-934, Sep. 1975; PA0 E. A. Lee and D. G. Messerschmitt, "Digital Communication," Kluwer Academic Publishers, Boston, 1990; and PA0 G. D. Forney, Jr., "The Viterbi Algorithm," Proc. IEEE, Vol. 61, pp. 268-278, Mar. 1973. PA0 Cideciyan et al, "A PRML System for Digital Magnetic Recording," IEEE Journal on Selected Areas in Communications, Vol. 10, No. 1, pp. 38-56, Jan. 1992; PA0 Wood et al, "Viterbi Detection of Class IV Partial Response on a Magnetic Recording Channel," IEEE Trans. Commun., Vol. COM-34, No. 5, pp. 454-461, May 1986; PA0 Coker et al, "Implementation of PRML in a Rigid Disk Drive," IEEE Trans. on Magnetics, Vol. 27, No. 6, Nov. 1991; PA0 Carley et al, "Adaptive Continuous-Time Equalization Followed by FDTS/DF Sequence Detection," Digest of the Magnetic Recording Conference, Aug. 15-17, 1994, p. C3; PA0 Moon et al, "Constrained Complexity Equalizer Design for Fixed Delay Tree Search with Decision Feedback," IEEE Trans. on Magnetics, Vol. 30, No. 5, Sep. 1994; PA0 Abbott et al, "Timing Recovery for Adaptive Decision Feedback Equalization of the Magnetic Storage Channel," Globecom '90, IEEE Global Telecommunication Conference, 1990, San Diego, Calif., Nov. 1990, pp. 1794-1799; PA0 Abbott et al, "Performance of Digital Magnetic Recording with Equalization and Offtrack Interference," IEEE Trans. on Magnetics, Vol. 27, No. 1, Jan. 1991; PA0 Cioffi et al, "Adaptive Equalization in Magnetic-Disk Storage Channels," IEEE Communication Magazine, Feb. 1990; and PA0 R. Wood, "Enhanced Decision Feedback Equalization," Intermag '90.
Applying sampled amplitude techniques to magnetic storage systems is also well documented. See, for example:
Several forms of distortion in addition to intersymbol interference are present in the analog read signal. One such form of distortion that is particularly troublesome at high data densities is caused by partial erasure of magnetically-stored information. This occurs because each bit of information may, for example, be stored as an individual region in which most magnetic domains are oriented in the same direction. However, the transition from one orientation to another is not abrupt but takes place over a finite distance, and so, at high transition densities, adjacent regions of magnetization interact to reduce the strength of magnetization of individual regions. For example, if the magnetization in a particular region has a predominantly north-south orientation and both of its neighboring regions have similar orientations, then the strength of its magnetization will be substantially unaltered by its neighbors. However, if it has one neighbor with an opposite (i.e., south-north) orientation, the border with this neighbor will be ill-defined and the net magnetization of the region will be reduced. This reduction in magnetization is exacerbated if both of the region's neighbors have magnetic orientations opposite to its own.
The reduction of the strength of magnetization of regions with differently oriented neighbors, referred to as partial erasure, reduces the amplitude of corresponding pulses in the read signal. Thus decoders that do not account for partial erasure are not optimal.
One prior art solution to this problem is described in "Modified Maximum Likelihood Sequence Estimation in a Simple Partial Erasure Model," by I. Lee, T. Yamauchi, and J. M. Cioffi, IEEE International Conference on Communications, May 1-5, 1994, New Orleans. This paper describes how a sequence detector can be matched to a read signal that includes partial erasure. However, it also explains that conventional channel models for describing partial erasure may result in detectors with prohibitive complexity. The paper presents a simplified partial erasure model in which the amplitude of a pulse is reduced by a factor .gamma.<1 if the magnetic transition that caused it has one neighboring transition, and is reduced by a factor .gamma..sup.2 if the transition that caused it has two neighboring transitions. The authors derive a state machine model for a reduced complexity sequence detector matched to partial erasure in a PR4 d=0 read channel. The state machine has been reduced to eleven states. However, such an eleven state machine is still not the optimal implementation.
It is a general aspect of the present invention to implement a PR4 d=0 read channel comprising a sequence detector which operates according to a state machine matched to partial erasure and having less than eleven states.
It is a further aspect of the invention to implement a read channel comprising a sequence detector which operates according to a state machine matched to partial erasure and a coding scheme which increases a minimum distance error event of the sequence detector.
It is a further aspect of the present invention to provide an EPR4 d=1 read channel signal comprising a sequence detector that matched to partial erasure.
It is a further aspect of the present invention to provide an EEPR4 d=1 read channel signal comprising a sequence detector that matched to partial erasure.

Sampled amplitude read channel with simplified sequence detector matched to partial erasure


This is a method of forming a conductor 26 on an interlevel dielectric layer 12 which is over an electronic microcircuit substrate 10, and the structure produced thereby. The method utilizes: forming an intralevel dielectric layer 14 over the interlevel dielectric layer 12; forming a conductor groove in the intralevel dielectric layer 14 exposing a portion of the interlevel dielectric layer 12; anisotropically depositing a selective deposition initiator 24 onto the intralevel dielectric layer 14 and onto the exposed portion of the interlevel dielectric layer 14; and selectively depositing conductor metal 26 to fill the groove to at least half-full. The selective deposition initiator 24 may selected from the group consisting of tungsten, titanium, paladium, platinum, copper, aluminum, and combinations thereof. In one embodiment, the selective deposition initiator 24 is paladium, and the selectively deposited conductor metal 26 is principally copper.

In the semiconductor industry the fabrication of microelectronic circuits typically uses single-crystal silicon and typically requires that several thin films of both insulating and conducting materials be formed and patterned sequentially on the silicon surface. The conventional wiring above a semiconductor substrate utilizes aluminum conductors with a small amount of copper, however, some microcircuits have been proposed using copper conductors. Copper wiring and electroless copper eposition are, of course, known for printed circuit boards.
Generally, the insulating films are a dense silicon dioxide dielectric, both horizontally between the conductors (intralevel dielectric) and vertically between layers of conductors (interlevel dielectric). Metal filled vias are used, e.g., to provide electrical connections between conductors in different levels. Such metal filling has generally been provided by physical vapor deposition (PVD), e.g. sputtering or vacuum deposition.

Process for conductors with selective deposition


A wound musical string includes a core wire and a wrapped wire covering about the core wire. End turns of the wrapped wire covering are coextensive portions of transition sections of the core wire. The transition sections have equilateral triangular, square or other cross sections such that the cross section exhibits equal principal moments of inertia. Consequently the inharmonicity of the string about two axes will be the same and the string will not produce false beats.

1. Field of the Invention
This invention generally relates to strings for producing musical tones and more particularly to the construction of improved wound musical strings and the method of making such strings.
2. Description of Related Art
When metal strings, typically steel strings, are placed in tension and struck or plucked, they vibrate and produce a musical tone. Some of these strings merely comprise a simple steel core wire, as used for treble notes in a piano. At lower frequencies, the string length increases. String lengths for the lowest notes become very long and cannot be incorporated in many pianos, such as spinet, upright and small grand pianos.
As known in the art, strings for the lower notes therefore incorporate a copper wrapping wire wound about a central portion of the core wire to load the wire and produce a tone with a string of significantly shorter length than would be required without the wrapping wire. Strings in the bass region may include one to three concentric windings. Each concentric winding has an intermediate section between two end turn sections.
U.S. Pat. No. 4,005,038 (1977) to Conklin, Jr. discloses an apparatus for wrapping strings for musical instruments that represents the conventional approach for producing such strings. The final wound string comprises a core wire of circular cross section. A single-, double- or triple-winding is coextensive with a central or intermediate length of the core wire. End turns of each winding wrap around a flattened area on the core wire produced by swaging or other similar technique. Winding the end turns around the swaged portion prevents the end turns from rotating on the core wire and loosening the entire wire wrap. Consequently in this form the core wire is circular except for the flattened transition areas that are coextensive with the end turns.
Many wound strings constructed in this conventional approach exhibit "false beats" when struck. It is generally recognized that one cause of false beats lies in the boundary conditions of orthogonal modes of vibration. More specifically such musical strings vibrate with components in various planes that shift around major axes displaced by 90.degree.. For example, in a horizontal string, the major axes are typically designated as the horizontal and vertical axes.
Tones emitted in the two orthogonal modes do not necessarily have identical speaking lengths. For example, in a piano it is quite possible for the pin that terminates the horizontal mode to be displaced from the corner of the bridge notching that terminates the vertical mode of vibration. Good bridge notching places the edge of the notch in line with the center line of the bridge pin to prevent false beats.
If the vibration components in both axes do not have identical frequencies, the difference represents a false beat. While the difference or false beat frequency may be minimal at the fundamental tone for the string, the frequency is multiplied by the partial number. Consequently at four octaves above the fundamental, the false beat frequency is sixteen times the beat frequency at the fundamental. Even if a string produces only a low slow frequency false beat in the low bass region, the overtones in the audible range beat much faster and thereby produce undesirable sounds. When objectionable false beats are detected, piano tuners generally replace the offending string in hopes that the problem will disappear because the effects from string to string tend to be random. The randomness comes from the possibility that the two ends can add or cancel depending on the orientation of the flats at each end.
Over the years a number of alternative string constructions have been proposed for a number of different purposes including the improvement of tonal quality. For example, U.S. Pat. No. 210,172 (1878) to Watson et al. and Great Britain Patent No. 300 (1885) to Hassel collectively disclose wound piano strings with core wires having triangular, oval, quadrangular, pentagonal or other polygonal cross sections. Both patents propose these cross sections to prevent loosening or longitudinal displacement of the wrapping wire on the core wire in a wound string.
U.S. Pat. No. 3,605,544 (1971) to Kondo discloses a string in which the end turns are wrapped in a contiguous fashion about a core wire. Intermediate turns, however, are spaced to eliminate undesirable resonances, buzzes or other noises, that is, to improve tonal quality.
U.S. Pat. No. 478,746 (1892) to Gill discloses another approach for improving tone quality. A string, whether wound or unwound, is formed with a triangular, rectangular or half-round cross section. In accordance with the Gill patent, however, any flat portion is located immediately above the corresponding note hammer so that the hammer strikes the flattened portion. This feature is stated to reduce hammer wear. In addition it is suggested that the string be twisted along its length to improve tone quality.
None of these references addresses the particular source of undesirable tone quality produced by false beats. Moreover none of the approaches suggested by these references seems to have been adopted in any wide-spread fashion. Pianos, particularly, continue to be manufactured with wound strings according to a method and construction as disclosed in the above-identified Conklin patent and other references. Moreover the cure for false beats when detected continues to be replacing the offending string.


A material handling vehicle for transporting loads includes a vehicle body and a control console connected to the vehicle body in a first position. The control console can be moved to a second position on the vehicle body by a user. The vehicle may include various devices for positioning the control console with respect to the body. For example, the devices may include separate post openings, a slot, a track, or a pivoting arm. In addition, the control console may include a stability support for the operator and various controls for operating the vehicle. The operator is able to maintain stability by holding the stability support with his or her hand. Furthermore, the operator does not need to remove his or her hand from the stability support in order to operate the various controls. The controls may be mounted on the stability support or may be located in relatively close proximity to the stability support.

Material handling vehicles are used to transport items from one location to another location. For example, items may be transported from one location in a factory to another location in a factory. In another example, material handling vehicles can be used in a warehouse to store or retrieve various items. In some material handling vehicles, the operator stands while operating the vehicle. In other material handling vehicles, the operator sits while operating the vehicle.
The operator has several controls which are used to control the operation of the vehicle. For example, the controls may control the speed and direction of the vehicle and also the operation of the lift portion. Some manufacturers of material handling vehicles locate the controls in the forward position. Other manufacturers locate the controls in the side position. Furthermore, other manufacturers position the controls so that they are at an angle between the forward position and the side position. The customer must decide at the time the vehicle is purchased the position of the controls. The customer is not able to change the position of the controls after the vehicle has been manufactured and delivered to the customer.
For example, if a customer had material handling vehicles with the controls in the forward position, the customer would not be able to change the position of the controls to the side position. The customer would need to determine the position of the controls at the time the vehicle was ordered from the manufacturer. In addition, if the first customer wished to sell its used vehicles with the controls in the forward position to a second customer, the number of perspective purchasers would be limited to customers who were only interested in vehicles with the controls in the forward position. Therefore, it would be advantageous if the customer could change the position of the controls.
Similarly, if a manufacturer only sells vehicles with the controls in the forward position, then the manufacturer would not be able to sell vehicles to customers who wished the controls to be in the side position or the angled position. Also, if a manufacturer offered one model of a vehicle with the controls in the forward position and another model with the controls in the side position, the manufacturer may need additional parts and/or assembly operations for each model. In addition, the manufacturer or distributor may need to have additional inventory in order to stock both models. Furthermore, as noted above, the customer would need to determine the model (i.e., the position of the controls) at the time the vehicle was ordered. Thus, it would be advantageous if the manufacturer and/or distributor could have one model with multiple positions for the controls.
As noted above, the operator must use his or her hands to operate the controls for the vehicle. These controls move with respect to the control console. Thus, if the operator is using both hands to operate the controls, the operator does not have a fixed surface to hold in order to maintain his or her stability in the vehicle. This situation is more important in the vehicles where the operator stands to operate the vehicle. Thus, it would be advantageous if the control console provided a fixed surface for the operator to hold to maintain stability and which also allowed the operator to manipulate the controls.

Control console for material handling vehicle


A remote control system with a pointing device which can control the computer itself also by the pointing device as well as by the key input device.. The remote controller comprising a key input device, a pointing device, a first controller which is provided for encoding a key code (KC) signal to a remote control signal, a second controller provided for encoding a pointer control (PC) signal to a remote control signal, an output device outputs the remote control (RC) signal, and said receiver comprising a receive device for receiving the RC signal, a third controller outputs a control signal for controlling a computer a fourth controller outputs a coordinate signal for moving a pointer on a computer display, a first decoder decodes the RC signal to the KC signal and outputs the KC signal to the third controller, and a second decoder decodes said RC signal to the PC signal and outputs the PC signal to the fourth controller and also the third controller.

Referring now to the accompanying drawings, an example of a wireless remote control system with a pointing device of prior art is described below, which, for example, is typically described in the Japanese Patent Application No. 5-7721 of 1993.
FIG. 1. describes a electric circuit of a wireless remote control system with a pointing device of a prior art. A remote controller 6 comprises a key input device 1, a pointing device 2, a first controller 3, a second controller 4, and optical output device 5. Usually, a computer key board may be the key input device 1 and mouse or track ball may be the pointing device 2. The key input device 1 is provided to input a character, text data and the like to a computer or to operate a computer itself. The operations of the computer itself are, for example, the picture adjustment of the computer display, changing the input source of the computer, an operate of a memory device and the like. As described below, the key input device 1 outputs a key code signal to the first controller 3. The pointing device 2 is provided to move a pointer on the computer display. The pointing device 2 outputs a pointer control signal to the second controller 4. The first controller 3 is provided for encoding the key code signal to a remote control signal by means of a carrier-wave-modulation. The second controller 4 encodes the pointer control signal to a remote control signal. The optical output device 5 outputs the remote control signal in a form of infrared rays to the receiver 10.
The receiver 10 comprises a receive device 7, a decoder 8 and a controller 9. The receive device 7 receives a remote control signal from optical output device 5 of the remote controller 6. A receptor unit is preferably used as the receive device 7. The decoder 8 decodes a remote control signal received by the receive device 7 to a key code signal or a pointer control signal and outputs them to the controller 9, The controller 9 outputs a control signal to a computer on the bases of said key code signal or coordinate signal.
FIG. 2. shows a structure of the remote control signal. The remote control signal comprises Reader Codes, Custom Codes, and Data Codes. The remote control signals are consisting of digital signals which transformed by the pulse modulation. The Leader Codes are identification codes for discriminating the remote control signal from noises. The Custom Codes are identification codes for specifying the equipment which is controlled with the remote controller. The order which inputted with the key input device 1 or the pointing device 2 is discriminated by the Data Codes. A user of the computer makes an order to control the computer with the key input device 1 and the pointing device 2. The operation in this constitution of prior art is explained as follows;
(1) When the receive device 7 receives the remote control signal of the key code signal inputted with the key input device 1, the decoder 8 decodes the remote control signal to the key code signal and controller 9 transforms the key code signal to the control signal in the form of the controlled computer to input characters or text data to the computer or to bring the computer itself in control by order of the key input device 1 .
(2) When the receive device 7 received the remote control signal of the pointer control signal inputted with the pointing device 2, the decoder 8 decodes the remote control signal to the pointer control signal and controller 9 transforms the pointer control signal to the coordinate signal in the form of the controlled computer to move a pointer on the computer display by order of the pointing device 2.
Thus, according to this constitution of a prior art, a computer input system with a key board and a pointing device can be wireless from a computer.
However, the remote control system with a pointing device of a prior art can not implement the order of controlling the computer it self with the pointing device 2 because the key code signal and pointer control signal which decoded by the decoder 8 are independently inputted to controller 9.

Remote control system with a pointing device

Matsushita Electric Industrial Co., Ltd.


The invention provides polymerizable dental, compounds, compositions, including the compounds and products for mixing the compositions and methods of using the compositions. Aryl acid compounds are provided in accordance with the invention. The compositions include at least one polymerizable aryl acid compound, an effective amount of a polymerization initiator, and at least 10 percent by weight of ceramic, metal and/or metal oxide filler particles having a particle size less than 500 microns. The dental products of the invention include a polymerizable composition in an enclosure having at least two chambers separated by a wall adapted to be ruptured prior to or during mixing of the composition. Compositions of the invention are preferred for use in these enclosures. Core build up material including a polymerizable acid containing compound is used to support dental crowns and adhere them to teeth in accordance with the invention.

The prior art does not provide a polymerizable dental composition, which includes one or more polymerizable aryl acid compounds within the scope of formula I; a polymerization initiator; at least 10 percent by weight of ceramic, metal and/or metal oxide filler particles having a particle size less than 500 microns, or products enclosing such compositions and methods of use thereof.
The prior art does not provide a dental product including an enclosure having at least two chambers separated by a wall adapted to be ruptured, and enclosing a polymerizable dental composition including a polymerizable compound and an effective amount of a polymerization initiator and at least 10 percent by weight of ceramic, metal and/or metal oxide filler particles having a particle size less than 500 microns.
It is an object of the invention to provide a polymerizable dental composition which includes one or more polymerizable aryl acid compounds within the scope of formula I, a polymerization initiator at least 10 percent by weight of ceramic, metal and/or metal oxide filler particles having a particle size less than 500 microns, products enclosing such composition and methods of use thereof.
It is an object of the invention to provide a dental product including an enclosure having at least two chambers separated by a wall adapted to be ruptured, and enclosing a polymerizable dental composition including a polymerizable compound and an effective amount of a polymerization initiator and at least 10 percent by weight of ceramic, metal and/or metal oxide filler particles having a particle size less than 500 microns.
"PENTA" as used herein refers to dipentaerythritol pentacrylate phosphoric acid ester which may be prepared according to Example 2 of U.S. Pat. No. 4,816,495.
"OEMA" as used herein refers to the reaction product of 1 mole 4,4' oxydiphthalic anhydride (chemical name: 5,5'-oxybis-1,3-isobenzo furandione) and 2 moles of HEMA.
"ODPA" as used herein refers to 4,4'-oxydiphthalic anhydride.
"HEMA" as used herein refers to 2-hydroxyethylmethacrylate.
"TEGDMA" as used herein refers to triethylene glycol dimethacrylate.
"BHT" as used herein refers to butylated hydroxytoluene.
"bisGMA" as used herein refers to bisphenol A-glycidylmethacrylate.
"CQ" as used herein refers to camphorquinone.
"EDAB" as used herein refers to ethyl 4-dimethylaminobenzoate.
"6-FDMA" as used herein refers to the reaction product of 1 mole of hexafluoroisopropylidene-2,2-bis(phthalic acid anhydride) (6-FDA) and 2 moles of 2-hydroxyethyl methacrylate.
"Monomer" as used herein means monomer or oligomer.
"Packable" as used herein refers to compositions which are packable as disclosed in Dougherty et al, U.S. Pat. No. 4,514,174, particularly at columns 6 and 7 and preferably refers to compositions having resistance values greater than about 175 g/mm and more preferably greater than 200 g/mm.sup.2.
"Set" as used herein means a polymerizable composition undergoes a change so that it becomes firm, stiff and nonpliable.
As used herein "The MAX Lite" means THE MAX.TM., a curing unit for light-polymerizable dental materials sold by Dentsply International Inc. through its L.D. Caulk Division.
Throughout this disclosure unless otherwise specified amounts of each component of a composition are in percent by weight.

Dental compounds, compositions, products and methods