An optical scanning device which forms a plurality of scanning lines in parallel in a main scanning direction on a photosensitive member by a plurality of laser beams detects the curvature values in the sub-scanning direction of the scanning lines, and corrects a curvature value in the sub-scanning direction corresponding to each of the scanning lines. When detecting the curvature value, the optical scanning device detects the curvature values in the sub-scanning direction of two scanning lines, and calculates the curvature value in the sub-scanning direction of a scanning line between the two scanning lines based on the detected curvature values in the sub-scanning direction of the two scanning lines. With this arrangement, the curvatures in the sub-scanning direction of scanning lines are corrected effectively with high accuracy for all laser beams in a multi-beam optical scanning device using a VCSEL or the like.

1. Field of the Invention
The present invention relates to an optical scanning device in an image forming apparatus, and a control method thereof and, more particularly, to an optical scanning device in an image forming apparatus such as a copying machine or printer, a control method thereof, and the image forming apparatus.
2. Description of the Related Art
Recently, copying machines and printers which form an image using laser scanning are requested to have higher speeds and higher resolutions. To meet this request, there are proposed a technique of rotating at a higher speed a polygon mirror which scans a laser, and a technique of increasing the number of emitting portions from which laser beams are emitted.
However, speeding up of the polygon mirror has limits considering heat and noise generated by windage, the strength of the mirror itself, the rotation capability of the motor, and the like.
From this, the mainstream for increasing the speed and resolution is shifting to the use of light of multi-beams emitted from a high-density light source such as a vertical-cavity surface-emitting laser (VCSEL). This is a technique of increasing the number of laser beam-emitting portions much more than the conventional one by using a high-density light source, and scanning with many laser beams in parallel.
To increase the speed, an image forming apparatus of a so-called tandem system is advantageous among recently popular color image forming apparatuses. In the tandem system, images of four colors, that is, yellow, magenta, cyan, and black are formed on independent photosensitive members, and finally overlaid on a transfer member. The image forming apparatus of the tandem system obtains a color image by overlaying images formed by separate scanning mechanisms. If the inclination or curvature of each scanning line occurs in the sub-scanning direction on the photosensitive member, this appears as color misregistration or color inconsistency and becomes a factor of making the image quality lost.
There has been conventionally known a method for correcting the curvature in the sub-scanning direction of a scanning line. For example, there is a method of canceling the curvature by mechanically bending the reversion mirror of an optical scanning device. Japanese Patent No. 3600228 discloses another method of correcting the curvature in the sub-scanning direction of a scanning line. According to this method, an image formable effective scanning area is divided into a plurality of regions in the main scanning direction. The write position in each divided region is offset in the sub-scanning direction, correcting the curvature in the sub-scanning direction of a scanning line.
However, the following problems arise in the conventional methods of correcting the curvature in the sub-scanning direction of a scanning line.
It is technically possible to increase the number of emitting portions to several ten in an optical scanning device using a VCSEL or the like in order to meet the recent demand for high speeds and high resolutions. If the number of laser beams reaches several ten, the laser beams distribute widely in the sub-scanning direction. Assuming that the number of scanning lines is 48 in a 2,400 dpi-resolution optical scanning device, the distance between scanning lines at both ends in the sub-scanning direction increases to about 0.4 mm.
A main factor of the curvature in the sub-scanning direction of a scanning line is aberration of an imaging lens. The aberration changes depending on the sub-scanning position of a laser beam passing through the imaging lens, so the value of generated curvature changes depending on the laser beam. In some cases, the difference in curvature value between laser beams spaced apart from as much as 0.4 mm increases to 5 to 10 μm. In an image forming apparatus, even 5-μm color misregistration lowers the image quality, so the difference in curvature value should be eliminated.
To the contrary, according to the conventional mechanical mirror bending and the method of correcting the curvature in the sub-scanning direction of a scanning line as disclosed in Japanese Patent No. 3600228, all laser beams are uniformly corrected, and the difference of curvature value in the sub-scanning direction between scanning lines cannot be eliminated.

Optical scanning device in image forming apparatus, and control method thereof


The present invention relates to a novel composite metal oxide catalyst, a method of making the catalyst, and a process for producing synthesis gas using the catalyst. The catalyst may be a nickel and cobalt based dual-active component composite metal oxide catalyst. The catalyst may be used to produce synthesis gas by the carbon dioxide reforming reaction of methane. The catalyst on an anhydrous basis after calcinations has the empirical formula:

Synthesis gas is a mixture of gases including varying amounts of carbon monoxide and hydrogen. Synthesis gas may be used, for example, as an intermediate in the production of synthetic natural gas, synthetic petroleum, ammonia and methanol. Synthesis gas may be produced by carbon dioxide reforming reactions of hydrocarbons, particularly light hydrocarbons such as methane.
Synthesis gas may be produced by carbon dioxide reforming of methane according to the following reaction:CH4+CO2=2CO+2H2 247 kJ·mol−1
This reaction is highly endothermic and generally requires temperatures in the range of 600 to 1100° to drive the reaction forward. Reforming catalysts such as Ni/Al2O3, Ni/MgO/Al2O3 and the like may be used to catalyze the reaction. Reforming catalysts used in the above reaction are generally Group VIII metals held on various supports.
Problems with known reforming catalysts include severe and rapid deactivation as a result of coking, or carbon deposition on the catalyst. Often, known catalysts are expensive to produce (e.g. some noble metal catalysts) and/or have low selectivity for target products such as hydrogen and carbon monoxide. Carbon dioxide reforming of methane to produce synthesis gas has therefore yet to be established on a commercial scale.
It is desirable to provide a stable, inexpensive reforming catalyst with high catalytic activity and high selectivity for products such as hydrogen and carbon monoxide.

Catalyst for production of synthesis gas

Abstract: M    a          m      +              N    b          n      +              Al    c          3      +              Mg    d          2      +              O          (                        am          2                +                  bn          2                +                              3            2                              c                +        d            )      Mm+ and Nn+ are two transition metals serving as dual-active components and selected from the group consisting of Ni, Co, Fe, Mn, Mo, Cu, Zn or mixtures thereof, a+b+c+d=1, and 0.001≦a≦0.8, 0.001≦b≦0.8, 0.1≦c≦0.99, 0.01≦d≦0.99.


A lubricating and drive system for a marine propulsion transmission that is comprised of an upper reversing transmission and a lower final drive transmission. A lubricant pump is driven off an input shaft to the reversing transmission for supplying lubricant for actuating its clutches and also for lubricating its gears. The pickup for the lubricant pump is disposed at a lower position in the final drive gear case so as to maintain a low lubricant level therein when the unit is operating so as to reduce drag.

This invention relates to a transmission lubrication system and more particularly to a transmission lubrication system particularly adapted for use with marine outboard drives.
In one form of marine outboard drive, the lower unit contains a bevel gear transmission which drives one or more propellers in selected directions. With this type of transmission there is frequently provided at the upper end of the unit a further transmission which may include the actual clutches and/or the reversing transmission for effecting the selected forward and reverse drives. Frequently, this type of arrangement employs a hydraulic pump that is driven off of the rear of the input shaft for this upper transmission and which draws lubricant from the lower unit transmission for actuating the clutches and/or lubricating components of the upper transmission.
Such a general environment may be best understood by reference to FIG. 1 of the drawings, which is a partially schematic cross-sectional view through an inboard/outboard drive that may be constructed either in accordance with the prior art or which may embody the present invention.
Referring specifically to this figure, an inboard/outboard drive which may be utilized with watercraft is identified generally by the reference numeral 11. This inboard/outboard drive includes an internal combustion engine 12 that is mounted forwardly of the transom of the associated propelled watercraft and within its hull. The engine 12 has an output shaft 13 that extends rearwardly through the transom and which is connected to a universal joint 14. The universal joint 14 transmits propulsion power to an input shaft 15 of a reversing transmission, indicated generally by the reference numeral 16, and which forms a portion of an outboard drive unit 17.
Although the invention is described in conjunction with an inboard/outboard drive, certain facets of the invention may be employed with outboard motors per se, as long as they incorporate a hydraulic pump disposed at the upper end of the outboard drive and a transmission at the lower end from which lubricant is drawn by the pump.
Continuing to describe this construction shown in FIG. 1, the input shaft 15 has journaled upon it a pair of bevel gears 18 and 19, which may be considered to be the forward drive and reverse drive gears, respectively. These gears 18 and 19 are constructed so as to be journaled on the input shaft 15 so that the input shaft 15 may rotate relative to the gears 18 and 19.
A hydraulically operated clutching mechanism, indicated generally by the reference numeral 21 and which may be of any known type utilized in this art, is provided in the reversing transmission 16. This hydraulically actuated clutching mechanism 21, which is actuated in a manner which will be described, selectively couples one of the gears 18 or 19 to the input shaft 15 so as to rotate with it.
The bevel gears 18 and 19 are enmeshed with opposite sides of a driven bevel gear 22. This driven bevel gear 22 is affixed for rotation with the upper end of a drive shaft 23 that is journaled within a drive shaft housing of the outboard drive 17. Because the gears 18 and 19 are enmeshed with diametrically opposite sides of the driven bevel gear 22, the direction of rotation of the driven bevel gear 22 and drive shaft 23 will depend upon which of the gears 18 or 19 is coupled for rotation with the input shaft 15.
As has been previously noted, the gear 18 is a forward drive gear, and when coupled to the shaft 15, the drive shaft 23 will be driven in a forward propulsion mode. In a like manner, when the reverse bevel gear 19 is coupled for rotation with the input shaft 15, the drive shaft 23 will be driven in a reverse drive mode.
In the illustrated embodiment, the propulsion unit 11 includes a pair of counter-rotating propellers comprised of a forward propeller 24 and a rearward propeller 25. The forward propeller 24 is coupled to a tubular shaft 26 that extends forwardly and is connected to a first bevel gear 27 of a final drive assembly, indicated generally by the reference numeral 28.
The rearward propeller 25 is coupled to an inner drive shaft 29 about which the tubular drive shaft 26 rotates. This drive shaft 29 is affixed to a second bevel gear 31. As a result of this arrangement, the propellers 24 and 25 will both be driven simultaneously when the drive shaft 23 is driven, but will rotate in opposite directions. The propellers 24 and 25 are of an opposite hand so that they will both provide a driving force when driven in either the forward or reverse directions.
As has been noted, the clutch actuating mechanism 21 is hydraulically operated. The hydraulic fluid for its operation is contained within the lower final drive 28 and is drawn upwardly to a hydraulic pump 32 which is driven off of the input shaft 15. A selector gear is provided for actuating either the clutch associated with the forward drive gear 18 or the clutch associated with the reverse drive gear 19, depending upon the operator's selection. The fluid in the clutch which is not energized is dumped back to the lower unit final drive 28.
The reversing transmission 16 and specifically the gears 18, 19 and 22 are also lubricated by means including the pump 32. Thus some of the pump output is delivered to these gears.
The disadvantages of the prior art type of construction may be best understood by reference to FIG. 2, which is a large schematic view, in part similar to FIG. 1, but shows in more detail how the fluid is circulated.
The same reference numerals are applied to FIG. 2 as are utilized in FIG. 1 to identify the various components. In this figure, however, only a single propeller drive illustrated because this is the more conventional type of arrangement, and the final drive for driving the propeller shaft 31 is identified by the reference numeral 51. The transmission is still indicated by the reference numeral 28. It will be seen that a supply conduit 52 extends through the outboard drive unit 17 from an area at the upper end of the transmission casing 28 and connects to the fluid pump 23. This supply conduit has an inlet opening 53 disposed at the upper end of the case.
In addition to supplying lubricant for actuating the clutches 21 and as has been noted, the pump 32 also supplies lubricant that lubricates the gears within the reversing transmission 16. These gears are, therefore, contained within their own housing. A return conduit 54 extends from this housing back to the final drive housing 28 and discharges into the gear case containing the final drive transmission 28.
As indicated in FIG. 2, any air present in the prior art type of construction will tend to be drawn through the inlet opening 53 and delivered to the pump 32 through the conduit 52. To minimize the amount of air so drawn, it is the practice to totally submerge the lower unit, final drive transmission 28 in lubricant. In other words, the lubricant fills the total lower unit. This has a distinct advantage in that it means that the gears therein are totally immersed in lubricant, even though this much lubricant is not required for their lubrication. Therefore, there will be a large drag on the gears.
In addition, there is always the danger that as the lubricant level falls, no lubricant will be supplied to the reversing transmission 16 or available for actuation of the clutches 21.
It is, therefore, a principal object of this invention to provide an outboard drive transmission of this general type, but wherein these disadvantages are avoided.
It is a further object of this invention to provide an improved transmission lubrication system for a marine outboard drive wherein adequate lubrication is provided, but wherein drag on the gears lubricated can be reduced by avoiding submerging them completely in lubricant at least when the unit is being driven.
It is a further object of this invention to provide an improved hydraulic clutch actuating mechanism associated with a transmission wherein the clutch can be supplied with sufficient fluid for actuation, but wherein the transmission drag losses are substantially reduced.


A device for securing tubing or wiring to an article of clothing can be formed from plastic by injection molding. The device includes a primary body portion formed with a shaped opening therein. The shaped opening has an enlarged circular part and an integral linear part. The device also includes a closure button formed with a narrow neck attached to a support member, which in turn is connected to the primary body portion by a tether. The button is sized to fit through the circular opening so that the neck can slide into the linear part and trap an article of clothing between the closure member and the primary body portion. The primary body portion is also formed with a pair of clips that are appropriately sized to receive tubing, such as IV tubing, that can be supported on the patient's clothing and facilitate mobility for the patient.

Patients in hospitals are often connected to an intravenous system to deliver medicines and saline solution to the patient. Often the tubing interconnecting the supply of medicine and/or saline solution and the patient is sufficiently long in order to providing some maneuverability for the patient that the tubing hangs well below the patient's arms when standing. This low hanging tubing presents a safety hazard in that the loop of tubing hanging at the lowest point is subjected to engaging protruding obstacles and can then pull on the patient's catheter or other connection with the patient. While the use of catheter tubing may be the most common situation in which tubing is hanging from a patient, other similar situations can be found on patients with medicinal pumps, patients with urinary catheters, and patients with feeding tubes, as a few examples.
Another remotely similar situation occurs with respect to electronic equipment. In the medical field, a patient can have electronic medical equipment with lead wires, such as EKG monitors and the like, or simply head phone wires, or ear bud wires, such as are connected to iPods to allow the wearer to hear audio programs as well as music stored in the electronic device. Often these electronic wires dangle from the wearer's ears to the location of the electronic device is attached to the wearer where electronic device is supported with a sufficient length to allow the wearer to have significant flexibility in locating the support place for the electronic device. As with the catheter tubing, the electronic wiring can be engaged by protruding obstacles that pull the hearing implements or medical monitors, etc., away from the wearer and/or the electronic device, thus interrupting the transmission of the desired electronic signal or simply the listening enjoyment of the wearer.
A solution to this problem of dangling catheter tubing, wires, etc., particularly when the patient is ambulatory, is often solved by the use of a safety pin that captures the tubing/wiring and is then pinned to the clothing worn by the patient, which is often a thin cotton, or similar material, hospital gown. While this use of a safety pin presents a perfunctory solution to the problem of the dangling catheter tubing, the safety pin cannot be used when the patient is being subjected to tests such as a an X-ray or an MRI, as the metal safety pin has to be removed to perform the tests due to the nature of the machine not being receptive to metal.
It would be desirable to provide a retention device that could engage medical tubing or electronic wiring to permit the tubing or wiring to be supported on an article of clothing of the wearer, which would prevent the loop of tubing from hanging too low or away from the wearer for engagement with a protruding obstacle. If allowed with respect to a machine on which testing is being done on the patient, the retention device may not have to be removed, thus retaining control of the tubing even while certain tests are being conducted.

Device for securing loose tubing or wires to clothing


An automated sphygmomanometer which automatically determines when a blood pressure determination needs to be made. During a "guard mode" determination, a cuff on an appendage of the patient is frequently inflated to a check pressure, which is preferably below the patient's mean arterial pressure ("MAP"), and the signature (shape, amplitude, pulse period, etc.) of the measured oscillometric signal is compared to a stored signature of a portion of an oscillometric signal at a corresponding portion of the oscillometric envelope determined during a previous blood pressure determination. If these signals differ by some predetermined amount, it is determined that the patient's blood pressure has changed significantly and that a new blood pressure determination needs to be conducted immediately. These guard mode determinations are made in addition to the normal blood pressure determinations made at predetermined intervals typically selected by the user. In addition, the shape of the oscillometric signal is quantified during guard mode so that it is possible to discriminate oscillations on the diastolic side of a patient's oscillometric envelope from oscillations on the systolic side of the patient's oscillometric envelope, thereby preventing a large shift in the oscillometric envelope from going undetected.

The sphygmomanometric class of automated blood pressure monitors employs an inflatable cuff to exert controlled counter-pressure on the vasculature of a patient. One large class of such monitors, exemplified by that described in U.S. Pat. Nos. 4,349,034 and 4,360,029, both to Maynard Ramsey, III and commonly assigned herewith, employs the oscillometric methodology. In accordance with the Ramsey patents, an inflatable cuff is suitably located on the limb of a patient and is pumped up to a predetermined pressure above the systolic pressure. Then, the cuff pressure is reduced in predetermined decrements, and at each level, pressure fluctuations are monitored. The resultant signals typically consist of a DC voltage with a small superimposed variational component caused by arterial blood pressure pulsations (referred to herein as "oscillation complexes" or just simply "oscillations"). After suitable filtering to reject the DC component and to provide amplification, peak pulse amplitudes (PPA) above a given base-line are measured and stored. As the decrementing continues, the peak amplitudes will normally increase from a lower level to a relative maximum, and thereafter will decrease. These amplitudes thus form an oscillometric blood pressure envelope for the patient. The lowest cuff pressure at which the oscillations have a maximum value has been found to be representative of the mean arterial pressure ("MAP"). Systolic and diastolic pressures can be derived either as predetermined fractions of MAP, or by more sophisticated methods of direct processing of the oscillation complexes.
The step deflation technique as set forth in the Ramsey patents is the commercial standard of operation. A large percentage of clinically acceptable automated blood pressure monitors utilize the step deflation rationale. When in use, the blood pressure cuff is placed on the patient and the operator sets a time interval, typically from 1 to 90 minutes, at which blood pressure measurements are to be made. The noninvasive blood pressure ("NIBP") monitor automatically starts a blood pressure determination at the end of the set time interval. Typically, the user selects a short interval if the patient is unstable since blood pressure may change to dangerous levels in a short time and selects a longer interval as the patient becomes more stable. The reason a short interval is not used in all cases is that the probability of trauma to the limb from the cuff inflation increases as the determination frequency increases.
Unfortunately, setting the interval for blood pressure measurement is not an exact science. If it is wrongly assumed that the patient's blood pressure is stable and a long interval is set, critical minutes may pass before dangerous changes in pressure are detected. Conversely, if it is wrongly assumed that the patient's blood pressure is volatile, the patient's limb is subjected to many unnecessary cuff inflations and the possible trauma resulting from such cuff inflations.
It is, accordingly, a primary object of the present invention to automatically determine when a blood pressure determination should be made without completely inflating the cuff and possibly causing trauma to the patient.
It is a further object of the present invention to automatically determine whether the patient's blood pressure has changed significantly since the last determination so that a new blood pressure determination may be instigated immediately.
It is also an object of the present invention to provide a technique for monitoring the status of the patient's blood pressure between determinations so that a change in status between blood pressure determinations will not go undetected.
If is a further object of the present invention to provide a technique for monitoring the status of the patient's blood pressure so that full blood pressure determinations need not be taken as frequently, thereby minimizing the possibility of trauma to the patient.

Oscillometric blood pressure monitor which automatically determines when to take blood pressure measurements


A liquid crystal display device includes a first substrate, a second substrate placed to face the first substrate, and a liquid crystal layer interposed between the first and second substrates. The liquid crystal layer further includes: a splay-aligned region in which a transformation from splay alignment to bend alignment or from bend alignment to splay alignment occurs according to a voltage applied; and a nucleation region serving as a nucleation site for initiating the transformation to occur in the splay-aligned region. A plurality of first splay-aligned regions include two first splay-aligned regions connected to each other via one of a plurality of second splay-aligned regions.

The present invention relates to a liquid crystal display device, and more particularly, to a liquid crystal display device using bend alignment of liquid crystal molecules for effecting display.
In recent years, active matrix liquid crystal display devices have dramatically improved in display performance such as contrast, brightness and viewing angle characteristic, to a level as high as that of cathode ray tubes (CRTs). The liquid crystal display mode currently used widely is a twisted nematic (TN) mode having a response time in the order of tens of milliseconds. With this level of response speed, which is low compared with that of CRTs, blurring occurs when a moving image with vigorous motion such as that in sports is displayed. The causes of this blurring of a moving image were studied in depth by Ishiguro, Kurita and others (Shuichi Ishiguro, Taiichiro Kurita, "Study on moving image quality of hold emission type display with 8X CRT", ITE Technical Report, IDY96-93, BCS96-23, BFO96-50).
According to the literature described above, the deterioration of the moving image quality of a liquid crystal display device is caused by delay of the response time of a liquid crystal material with respect to the frame rate and by adopting hold type display as the display scheme. The hold type display can be changed to impulse type display by letting a backlight blink or inserting screen erase intervals for the display with liquid crystal. As for the delay of the response time, mainly two measures as follows have been proposed.
One is a surface stabilized ferroelectric liquid crystal (SSFLC) mode using ferroelectric liquid crystal proposed by Clark and Lagerwall in 1980. This mode is however disadvantageous in that the way of gray scale display is complicated and that the alignment stability of smectic liquid crystal is inferior. Due to these and other disadvantages, commercialization of this mode, once started by Cannon Inc., is presently discontinued.
The other is a pi-cell approach using nematic liquid crystal invented by J. P. Bos and others in 1983. In this approach, a voltage is applied across a splay-aligned liquid crystal layer to transform the splay alignment to bend alignment, and a change in retardation with the intensity of the voltage application in the bend-aligned state is used for display. In this display mode, only liquid crystal molecules in the surface portion of the liquid crystal layer move with application of an external field, and a backflow generated in the process of relaxation of the alignment serves to accelerate the response. Due to these features, high-speed response of several milliseconds is reportedly possible.
In the pi-cell approach described above, splay alignment is energetically more stable than bend alignment in the non-voltage applied state. For this reason, some methods for transforming splay alignment to bend alignment have been proposed.
For example, U.S. Pat. No. 6,069,620, discloses a method in which an intense voltage is applied at the start of operation to allow liquid crystal molecules to overpass the energy barrier and thus be transformed to bend alignment. Japanese Laid-Open Patent Publication No. 11-7018 discloses a method in which a high pretilt region is formed on a surface of at least one of a pixel electrode and a counter electrode. Using the high pretilt region as a nucleation site, a liquid crystal layer is transformed to bend alignment, with expansion of disclination, during voltage application.
Japanese Laid-Open Patent Publication No. 9-96790 discloses the following. By adding a chiral dopant to a nematic liquid crystal material so that d/p>0.25 is satisfied (where d is the thickness of a liquid crystal cell and p is a pitch of a spontaneous helical structure of the liquid crystal material with the chiral dopant mixed therein), the liquid crystal layer exhibits 180-degree twisted alignment in the non-voltage applied state. When a voltage is applied to this twisted liquid crystal layer, the twisted alignment is smoothly transformed to bend alignment without generation of disclination.
The three methods described above have been mainly proposed in relation with the transformation of the liquid crystal layer from splay alignment to bend alignment. These conventional methods however find difficulty in attaining sufficiently swift transformation from splay alignment to bend alignment and also reliable transformation over the entire display plane.
The present inventors examined use of a 180-degree twisted region as a nucleation site. However, it was found difficult to form a 180-degree twisted region stably and reliably. In fact, part of the region failed to be 180-degree twisted, but splay-aligned.
An object of the present invention is providing a liquid crystal display device capable of attaining swift and reliable transformation from splay alignment to bend alignment or from bend alignment to splay alignment.


An A.G.C. circuit is disclosed having two modulators connected in series to modulate an input signal and an amplifier for amplifying the output of the second modulator and applying it to an output terminal. A detector detects the output of the amplifier and an integrator compares the detected level with a reference so as to produce a control signal dependent on the error. The control signal is applied to the first modulator through an impedance path having an impedance which decreases with increasing frequency, and is applied to the same modulator through an impedance path having an impedance which increases with increasing frequency. In this way, the first modulator performs modulation primarily dependent on the A.C. component of the control signal and a second modulator performs modulation primarily dependent on its D.C. components of the control signal. Therefore, changes in the gain of the amplifier, or in the level of the input signal, which tend to alter the upper limit of the loop bandwidth of the circuit, are substantially offset by the effect of the resultant change in the gain of the second modulator.

The invention relates to electrical circuit arrangements. One example of an electrical circuit arrangement to which the invention relates is an automatic gain control (AGC) circuit arrangement.
Various AGC circuit arrangements are known. However, a problem which can arise with known AGC circuit arrangements is that their bandwidth varies with gain and thus with the level of output signal for a given input. Where a wide loop bandwidth is required (e.g. to handle amplitude modulation up to 20 KHz or more), this variation of bandwidth can give rise to instability.
An object of the invention is an improved automatic gain control circuit arrangement.
A more specific object of the invention is an automatic gain control circuit arrangement having a bandwidth which is not unduly affected by the level of the input signal.


An arrangement for producing a molded concrete article which has a surface including zones at varying levels. The arrangement includes three groups of punches defining respective impression depths into the concrete article, and a molding device including three head plates, each of which is connected to a corresponding one of the groups of punches. An upper head plate is connected to a group of punches having a deepest impression depth. A lower head plate disposed below the upper head plate is connected to a group of punches having a shallowest impression depth. An intermediate head plate is connected to a group of punches which has an impression depth between the deepest impression depth and the shallowest impression depth, wherein the groups of punches are connected in a descending order of their impression depths to their corresponding head plates disposed successively below the upper head plate, and wherein any one group of punches connected to a head plate disposed above at least one other head plate passes through the at least one other head plate. Two guide rods suspend head plates below the upper head plate, each guide rod having a stop at a lower end thereof adapted to determine a lowest position of the corresponding one of the head plates. A load is applied to the head plates through the upper head plate.

An apparatus of the above type is known from European Patent Specification 0 118 872. This patent specification is concerned with the production of a molding which exhibits a lower-lying annular surface ruling along the border. The punch arrangement thus comprises two part-punches, one punch being guided on the other punch, and a stop, which limits the movement of one part-punch towards the bottom, being arranged on the other part-punch. In the case of a known two-part punch arrangement according to German Utility Model 87 14 786 too, one part-punch is guided on the other part-punch and has its movement clearance limited by stops.
The above type of punch arrangment is not, however, suitable for moldings with a multiplicity of adjacent impressions at different levels. Rather, the known designs are matched closely to the molding to be produced in each case, this resulting in non-commercially viable manufacturing and, in the event of a change in the molding to be produced, retiring re-designing again and again.

Apparatus for producing moldings from, in particular, concrete


This invention relates to radiation curable abrasion resistant coatings for solid substrates which are tintable. The compositions of the present invention contain a quaternary ammonium salt as a tintability enhancing compound. The cured coatings of this invention simultaneously resist abrasion and provide superior tintability.

This invention relates to radiation curable abrasion resistant coatings for solid substrates which are tintable. The compositions of the present invention contain a quaternary ammonium salt as a tintability enhancing compound. The cured coatings of this invention simultaneously resist abrasion and provide superior tintability.
Plastic materials have been used as substitutes for glass in many applications because of their unique properties such as weight, ease of handling, and ease of formation of articles. Most plastics, however, are soft and scratch quite readily. In order to provide abrasion resistance to plastics, silicone coatings were developed. One premier coating that has found wide acceptance for coating plastics is a thermally cured abrasion resistant coating formed from a mixture of colloidal silica and trialkoxy-functional silanes in a alcohol and water medium. Such coating material is disclosed in U.S. Pat. No. 3,986,997, issued Oct. 19, 1976, and assigned to Dow Corning Corporation, Midland, Mich.
Another Dow Corning patent, U.S. Pat. No. 4,554,354, issued Nov. 19, 1985, rendered the coating composition of U.S. Pat. No. 3,986,997 tintable by replacing the methyl group on the trialkoxy-functional silane with a longer chain organic group. The tintability of such coatings was further improved through the addition of a tintability enhancing compound selected from the group consisting of polyhydroxyl-functional compounds and butylated urea formaldehyde compounds, as disclosed in U.S. Pat. No. 5,013,608, issued May 7, 1991, and assigned to Swedlow, Inc., Garden Grove, Calif. These coatings, however, have two major drawbacks. They must be thermally cured which involves a longer cure time than radiation curing and the high temperature cure environments may damage heat sensitive materials. In addition, adhesion of these thermally cured coatings to polycarbonate type resins is very poor, without the additional step of adding a primer. Thus, it would be desirable to develop a tintable abrasion resistant coating which would adhere to polycarbonate type substrates without the use of a primer and which would be radiation curable.
The incorporation of acrylate monomers into abrasion resistant coating compositions have solved some of the above mentioned problems. Acrylate monomers attack the surface of polycarbonate type resins allowing the coating composition to adhere to the substrate without a primer and allow such compositions to be radiation cured. Acrylate monomers, however, necessitated the replacement of the alkoxy-functional silanes used in the thermally cured compositions with silanes capable of reacting with acrylates such as acryloxy, glycidoxy or and/or vinyl functional silanes. Such compositions are described, for example, in U.S. Pat. Nos. 4,822,828, issued Apr. 18, 1989 and assigned to Hoechst Celanese, Corporation, Somerville, N.J., and U.S. Pat. No. 4,486,504, issued Dec. 4, 1984 and assigned to General Electric Company, Waterford, N.Y. While the cured coating films of these compositions are curable by radiation and adhere to polycarbonate without the need of a primer, they have a major drawback. They are not tintable.
Accordingly, the need exits for a single coating composition that, when radiation cured, can accomplish the objectives of high tintability combined with significant resistance to abrasion.

Tintable abrasion resistant coating compositions


Energetic electrons emitted by heated cathodes in a multi-beam color cathode ray tube (CRT) are directed to a low voltage beam forming region (BFR) of an electron gun, with the thus formed electron beams then directed through a high voltage main focus lens for focusing the beams on a display screen of the CRT. The BFR includes a G.sub.2 electron having three spaced inline apertures each disposed within an essentially electrostatic field-free region and through each of which a respective electron beam passes. Each G.sub.2 aperture intercepts an outer portion of an associated electron beam to provide an electron beam cross sectional shape which compensates for the asymmetric focusing effect of the main focus lens in correcting for beam spherical aberration to provide a rotationally symmetric electron beam spot on the display screen. The invention is also adapted for use in a monochrome, single electron beam CRT to provide a desired electron beam spot shape for optimum display pixel density and/or to eliminate display discontinuities and provide a smooth video image display.

In electron beam devices such as CRTs, the preferred electron beam cross section is not always rotationally symmetric so as to produce a circular spot on the display screen. For example, in recent years color CRT electron gun designers have adopted various asymmetric lenses in their designs to improve the overall performance of the raster display. In these asymmetric lenses, a rotationally symmetric electron beam can give rise to undesired aberration due to mismatched electron lens and electron beam shapes. The designer's goal is to provide an electron beam with a desired cross sectional shape which does not produce undesired electron beam aberration.
An example of electron beam aberration caused by mismatched electron lens and electron beam shapes can be explained with reference to the sectional view of a prior art QPF electron gun 10 shown in FIG. 1. Electron gun 10 is intended for use in a color CRT and thus includes three inline cathodes 12a, 12b and 12c. Electron gun 10 further includes a beam forming region (BFR) 58 comprised of a G.sub.1 control electrode, a G.sub.2 screen electrode, and the low voltage side of a G.sub.3 electrode. Electron gun 10 further includes a symmetric prefocus lens 60 comprised of the high voltage side of the G.sub.2 electrode, a G.sub.4 electrode and the low voltage side of a G.sub.5 electrode. The three electron beams are focused on a display screen of a CRT (which are not shown in FIG. 1 for simplicity) by means of a main focus lens comprised of the high voltage side of the G.sub.5 electrode and a G.sub.6 electrode. A sectional view of electron gun 10 shown in FIG. 1 taken along site line 2--2 therein illustrating the high voltage side of the G.sub.5 electrode is shown in FIG. 2. The G.sub.1 electrode is typically maintained at zero voltage, while the G.sub.2 and G.sub.4 electrodes are typically coupled to a common V.sub.G2 voltage source and the G.sub.3 and G.sub.5 electrodes are coupled to a common focus voltage V.sub.F source. The G.sub.6 electrode is typically coupled to an accelerating, or anode, voltage V.sub.A source. Each of the three electron beams is directed through a plurality of aligned apertures in the various electrodes of electron gun 10 as the electrons proceed from cathodes 12a, 12b and 12c toward the CRT's display screen.
More specifically with respect to the electron gun's main focus lens 64, the low voltage side of the G.sub.5 electrode includes spaced apertures 30a, 30b and 30c aligned with inner apertures 34a, 34b and 34c for passing respective electron beams. The high voltage side of the G.sub.5 electrode includes a peripheral wall 66 defining an elongated, recessed portion 32 which functions as a common lens for the three electron beams. The facing low voltage side of the G.sub.6 electrode includes an elongated, recessed portion 36 also forming a common lens for the three electron beams. The high voltage side of the G.sub.6 electrode includes three spaced apertures 38a, 38b and 38c for passing respective electron beams toward the CRT's display screen.
Referring to FIG. 3, there is shown a sectional view of the electron gun 10 shown in FIG. 1 illustrating only the G.sub.2, G.sub.5 and G.sub.6 electrodes of the electron gun for simplicity, it being understood that the remaining electrodes shown in FIG. 1 are also included in the electron gun shown partially in FIG. 3. In FIG. 3, line A--A' represents the red electron gun axis, line B--B' represents the green electron gun axis, and line C--C' represents the blue electron gun axis. As shown in FIG. 3, the three electron beams respectively transit apertures 16a, 16b and 16c in the G.sub.2 electrode prior to passing through the main focus lens comprised of the G.sub.5 and G.sub.6 electrodes. The main focus lens 64 applies an asymmetric electrostatic field to the three electron beams. This asymmetric electrostatic field arises from the inline alignment of the three electron beams and the shape of the common lens portions of the G.sub.5 and G.sub.6 electrodes formed from facing recessed portions 32 and 36. The facing common lens portions of the G.sub.5 and G.sub.6 electrodes form a combined optimum tube and yoke (COTY) lens.
The effect of this asymmetrical electrostatic field and resulting forces applied to the outer electron beams as they transit the common lens portion of the G.sub.5 electrode is shown in the upper portion of FIG. 3. It can be seen that electron beam rays crossover the axis of each of the electron guns prior to being incident upon a phosphor coating 42 deposited on an inner surface of the CRT's display screen 40. This electron ray crossover is effected primarily by the main focus lens 64 of the electron gun 10. The two outer electron beams form left and right beam spots 52 and 54, while the center electron beam forms a center beam spot 50 on phosphor coating 42. As shown in FIG. 3, the outer electron beam rays in the two outer electron beams undergo a greater focusing effect by the main focus lens 64 than the inner rays (those rays disposed closer to the axis B--B' of the center electron gun). Outer electron beam rays in each of these outer beams are deflected a distance r.sub.1 after crossover, while inner rays are deflected a distance r.sub.0 from the respective center axes A--A' and C--C' of the two outer electron guns, where r.sub.1 >r.sub.0. The increased inner deflection of the outer rays in the two outer electron beams arises from the asymmetric electrostatic field applied to the electron beams.
The result of the application of this asymmetrical electrostatic focusing field on the two outer electron beams is more clearly shown in FIG. 3a which is a sectional view taken along site line 3a--3a in FIG. 3. The axis of the center electron beam is shown as element 44, while the axes of the left and right outer electron beams are respectively shown as elements 46 and 48. From the figure, it can be seen that the over-focusing of the outer rays in the two outer electron beams prior to crossover gives rise to asymmetrical outer electron beam spots 52 and 54. Outer electron beam spot 52 includes an inward directed extension 52a caused by over-focusing of the outer rays as the electron beam transits the main focus lens of the electron gun. Similarly, the right electron beam spot 54 includes an inwardly directed extension 54a also caused by over-focusing of the outer rays as the electron beam transits the main focus lens. Inward extensions 52a and 54a, which are sometimes referred to as a beam spot tail or flare, appear as spherical aberration on the CRT's display screen and degrade video image quality. This electron beam spot tail also appears in the center beam spot when the center beam is deflected off-axis.
An obvious approach to correcting for this electron beam spherical aberration is to intercept the beam with a properly shaped aperture in an electrode of the gun. However, mechanically intercepting the electron beam by means of a physical obstruction in the beam path gives rise to other problems. For example, an electrostatic field in the region where the beam is intercepted and shaped will give rise to an additional asymmetric focusing effect imposed upon the beam which may cause some spherical aberration and operate to defeat the purpose of intercepting the beam. In addition, secondary electrons will be emitted by the beam intercepting grid. These secondary electrons are directed toward the display screen by the electrostatic field in the vicinity of the beam intercepting grid causing loss of contrast and/or loss of purity in a color CRT. A third problem also arises from the energetic electrons incident upon the beam intercepting grid about a beam shaping aperture. Because the electrons are intercepted in a high voltage region of the electron gun and have a high kinetic energy (an electron gun typically has a focus voltage of a few thousand volts), the intercepted high energy electrons release their kinetic energy at the aperture region causing a substantial increase in the temperature of the beam intercepting grid which in some cases may become vaporized before this energy can be dissipated.
The present invention addresses the aforementioned limitations of the prior art by compensating for the asymmetric electrostatic field of a main lens in an electron gun and correcting for the resulting electron beam spherical aberration in a color CRT to provide a small, circular beam spot on the CRT's display screen. The present invention corrects the spherical aberration in an electron beam arising from a main lens asymmetric electrostatic focus field by providing a compensated electron beam cross sectional shape as the beam enters the main lens to provide improved electron beam spot performance. The present invention also may be used to shape an electron beam in a monochrome CRT to provide optimum display pixel density and/or to eliminate display discontinuities and provide a smooth video display.

Electron beam shaping aperture in low voltage, field-free region of electron gun


The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD18, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder.

Antibody-based therapies for cancer have the potential of higher specificity and lower side effect profile as compared to conventional drugs. The reason is a precise distinction between normal and neoplastic cells by antibodies and the fact, that their mode of action relies on less toxic immunological anti-tumor mechanisms, such as complement activation and recruitment of cytotoxic immune cells.
Targets for antibody-based therapies need to have particular qualities, which form the basis for proper discrimination between normal and neoplastic cells. Obviously, a target with either exclusive restriction to tumor cells and entirely undetectable on normal tissues is ideal for the development of efficient and safe antibody therapeutics. In another aspect, a high-level overexpression may be the basis for the therapeutic window and low side effects exemplified by the human epidermal growth factor receptor type 2 (HER-2), which as a result of gene amplification is a good target for the antibody trastuzumab (Herceptin).
Other targets for antibodies which are either already approved or in clinical development for tumor therapy have distinct qualities, which are not based on a numeric overexpression of target molecules on tumor cells. In the case of antibodies to the proteoglycan MUC-1, a peptide repeat epitope in the backbone of the target is underglycosylated in tumor cells and thus altered to its normal counterpart. In the case of antibodies to CD20 (rituximab), CD52 (Campath-1H) and CD22 (epratuzumab), antibody targets have comparable expression levels on tumor cells and normal lymphocytes. Here, the ablation of normal cells by the antibody is tolerable since target-negative stem cells restore the normal lymphocyte repertoire. Other examples of differential accessibility of antibody targets are carcinoembryonal antigen (CEA) and carboanhydrase IX (CA9). Both antigens are expressed on normal epithelia of colon and kidney, respectively. However, radioactively labeled imaging antibodies do distinguish well between tumor and normal tissue, and cytotoxic antibodies are well tolerated. This is most likely due to a restricted expression of CA9 and CEA on the luminal side of normal epithelial tissue where IgG antibodies do not have access. Also antigen epithelial cell adhesion molecule (Ep-CAM) belongs to this category. As a homotypic cell adhesion molecule for epithelial cells it is localized in the intercellular space. Intriguingly, whereas high-affinity anti-Ep-CAM antibodies are very toxic, intermediate-affinity antibodies are well tolerated. This suggests accessibility of the Ep-CAM target on normal cells but also indicates that kinetics of antibody binding may open a therapeutic window.
One possibility is that other epithelial cell-specific proteins involved in cell/cell adhesion may be also attractive for antibody approaches, since they may be barely accessible in well-structured epithelia to antibodies but become exposed on tumor cells. We therefore analyzed proteins involved in organizing epithelial tissue architecture for their suitability as targets for therapeutic antibodies. A protein, which particularly attracted our attention is claudin 18.
The claudin 18 (CLD18) molecule (Genbank accession number: splice variant 1 (CLD18A1): NP_057453, NM_016369, and splice variant 2 (CLD18A2): NM_001002026, NP_001002026) is an integral transmembrane protein with a molecular weight of approximately 27.9/27.72 kD. Claudins are integral membrane proteins located within the tight junctions of epithelia and endothelia. Tight junctions organize a network of interconnected strands of intramembranous particles between adjacent cells. In tight junctions, occludin and claudins are the most prominent transmembrane protein components. Due to their strong intercellular adhesion properties they create a primary barrier to prevent and control the paracellular transport of solutes and restrict the lateral diffusion of membrane lipids and proteins to maintain cellular polarity. Tight junction forming proteins are critically involved in organizing epithelial tissue architecture. We assumed that such proteins may be barely accessible to antibodies in well-structured epithelia but become exposed on tumor cells.
CLD18 is a tetraspanin and has as such 4 hydrophobic regions. We have generated data indicating that CLD18 displays several different conformations, which may be selectively addressed by antibodies. One conformation (CLD18-Conformation-1) implies, that all four hydrophobic regions serve as regular transmembrane domains (TM) and two extracellular loops (loop1 embraced by hydrophobic region 1 and hydrophobic region 2; loop2 embraced by hydrophobic regions 3 and 4) are formed, as described for the vast majority of claudin family members. A second conformation (CLD18-Conformation-2) implies that, as described for PMP22, another member of the tetraspanin family (Taylor et al., J. Neurosc. Res. 62:15-27, 2000), that the second and third hydrophobic domains do not fully cross the plasma membrane so that portion (loopD3) in between the first and fourth transmembrane domain is extracellular. A third conformation (CLD18-Conformation-3) implies, a large extracellular domain with two internal hydrophobic regions embraced by the first and fourth hydrophobic region, which serve as regular transmembrane domains. Due to the presence of classical N-glycosylation site in loopD3 the Claudin-18 topology variants CLD18 topology-2- and CLD18 topology-3 harbour an additional extracellular N-glycosylation site.
Another level of complexity is added to CLD18 molecule by the presence of two different splice variants, which are described in mouse and in human (Niimi, Mol. Cell. Biol. 21:7380-90, 2001). The splice variants CLD18A1 and CLD18A2 differ in the first 21 N-terminal amino acids, which comprise the first TM and loop1, whereas the primary protein sequence of the C-terminus is identical.
CLD18A1 is selectively expressed on normal lung and stomach epithelia, whereas CLD18A2 is expressed only on gastric cells (Niimi, Mol. Cell. Biol. 21:7380-90, 2001). Most importantly, CLD18A2 is restricted to the differentiated short-lived cells of stomach epithelium but is devoid from the gastric stem cell region. Using sensitive RT-PCR, we have shown that both variants are not detectable at all in any other normal human organ, but are robustly expressed in several cancer types including stomach, esophageal, pancreatic and lung tumors as well as human cancer cell lines. Expression is most prominent in the adenocarcinoma subtypes of these indications.
The molecular weight of the protein differs in some cancers and adjacent normal tissue. The higher molecular weight protein observed in healthy tissue can be transferred into the same molecular weight as observed in cancer by treating tissue lysates with the deglycosylating compound PNGase F. This suggests, that CLD18 is less N-glycosylated in cancer as compared to its normal tissue counterpart. This structural difference is likely to give rise to an altered epitope. A classical N-glycosylation motif is in position aa 116 within the loopD3 domain of the molecule.
The terms "CLD18" and "CLD18-variant" according to the invention shall encompass (i) CLD18-splice variants, (ii) CLD18-N-glycosylation variants, (iii) CLD18-conformation variants, (iv) CLD18-free and homotypically/heterotypically associated variants localized at intercellular tight junctions and (v) CLD18-cancer related and CLD18-non-cancer cell related variants.
The molecular and functional characteristics of CLD18 make this molecule a highly interesting target for antibody based cancer therapy. These are in particular (i) the absence of CLD18 from the vast majority of toxicity relevant normal tissues, (ii) the restriction of CLD18A2 variant expression to a dispensible cell population as differentiated gastric cells, which can be replenished by target-negative stem cells of the stomach, (iii) hints to potential differential glycosylation between normal and neoplastic cells, and (iv) the presence of different conformational topologies. Moreover, the role of CLD18 as tight junction protein may further contribute to a good therapeutic window. Because tumor cells express claudins but often do not form classical tight junctions by homotypic and heterotypic association of claudins as found in normal epithelial tissue, tumor cells may have a considerable pool of free claudin that is amenable to extracellular antibody binding and immunotherapy. It is possible that binding epitopes of claudins in healthy epithelium are shielded within tight junctions from the access by such antibodies.
The object of the invention is to provide antibodies useful for therapy of diseases wherein CLD18 is expressed, such as tumor diseases. The antibodies described herein have also utility in diagnosing such diseases.

This patent is subject to a terminal disclaimer.

Monoclonal antibodies against claudin-18 for treatment of cancer


Transgenic mice that produce high levels of humanized antibodies are described. Targeted gene replacement exchanges constant regions of the mouse immunoglobulin heavy and light chain genes with human genes, either through conventional gene targeting, or by use of the bacteriophage-derived Cre-loxP recombination system. The transgenic animals undergo antibody affinity maturation, and a class switch from the native immunoglobulin to the humanized form.

The invention concerns a method for replacement of a homologous gene segment from mammals in the cell line of nonhuman mammals by homologous recombination. The invention also concerns a method for creation of a transgenic nonhuman mammal, as well as its use for expression of gene products and for testing of drugs and therapeutic models. In addition, a recombination vehicle for homologous recombination, a stably transfected cell clone and a transgenic, nonhuman mammal are disclosed.
The field of this invention is the production of humanized antibodies in a transgenic host.
Monoclonal antibodies find application in both diagnosis and treatment. Because of their capacity to bind to a specific epitope, they can be used to identify molecules carrying that epitope or may be aimed, by themselves or in conjunction with another moiety, to a specific place for diagnosis or therapy. Humanized antibodies posess significant advantages over rodent antibodies, however they have been difficult to produce in large quantities.
Various technologies have been developed to overcome problems related to the production of human monoclonal antibodies, one strategy is the generation of chimeric antibodies in which the rodent constant (C) regions of both heavy (H) and light (L) chains, with or without the framework of the variable region, are replaced by the equivalent domains or sequences of human immunoglobulin. Another strategy attempts to mimic the immune response in vitro, through bacteriophage expression of human variable region genes isolated from human B cell populations, followed by selection for rare, high affinity antibodies through antigen binding. A major drawback to these and similar approaches is the cumbersome work required to generate each specific mAb of appropriate biological function.
An ideal solution to these problems would be the generation of a mouse strain synthesizing human antibodies instead of mouse antibodies. This has been approached by introducing a mini-locus containing a few human V and C region gene segments in germline configuration into the mouse genome as a transgene. In such strains, antibodies carrying human H and L chains were indeed produced, but the levels of production were low and the repertoire of human V regions was severely limited. Thus, while the approach appears promising in principle, it is not yet at the stage to stand its final test. There is, therefore, substantial interest in finding alternative routes to the production of allogeneic antibodies for humans.
Relevant Literature
Homologous recombination between the DNA sequences present in a chromosome and new, added, cloned DNA sequences (hereafter referred to as gene targeting) permits insertion of a cloned gene into the genome of a living cell. Animals that are homozygous for the desired mutation can be obtained with this method using embryonal germ cells via chimeras (M. R. Capecchi, Science, 244, 1288 (1989)). The use of gene targeting to deactivate a gene (gene disruption) and for gene correction, i.e., incorporation of a gene segment previously not present, is described in R. D. Camerini-Otero, R. Kucherlapati, The New Biologist, 2(4), 334-341 (1990).
The insertion methods described in WO 90/11354 and WO 91/19796 in which a desired gene segment is introduced into the genome of a cell by homologous recombination are also included among the gene correction methods. In the latter method the still functional endogenous gene is removed in a second step and an endogenous gene segment thus replaced with a homologous gene segment. Moreover, WO 91/19796 discloses a virtually one-stage method, i.e., co-transfection, in which the resistance marker is not situated in the gene segment being introduced, but is introduced separately. In the examples cited in this document, however, only slightly varied homologous gene segments (maximum 2xc3x972 base variations) are introduced, raising the question as to the extent to which a selectable recombination event can still be established during a reduction in homology (given the limited recombination frequency of the two-stage method). Nor is it demonstrated in this document whether the executed mutation of the embryonal parent cells is transferred to the cell line. Moreover, K. Rajewsky (Science, 256, 483 (1992)) suggests the use of homologous recombination for gene substitution in order, for example, to identify the function of a newly discovered gene.
In this sense, the task of the present invention was to make available a direct successful method in one step for production of genetically engineered nonhuman mammals that contain homologous gene segments from other mammals via homologous recombination.
Homologous recombination between the DNA sequences present in a chromosome and exogenous DNA sequences permits insertion of a cloned gene into the genome of a living cell. The generation of transgenic animals using this methodology is described in Thomas and Capecchi (1987) Cell 51:503-512; Capecchi (1989) Science 244:1288 and Koller and Smithies (1989) P.N.A.S. 86:8932-8935. The use of gene targeting for gene correction is described in Camerini-Otero and Kucherlapati (1990) The New Biologist 2:334-341. Targeted deletion of gene segments using the bacteriophage-derived Cre-loxP recombination system is described in Sauer and Henderson (1988) P.N.A.S. 85:5166-5170 and Orban et al. (1992) P.N.A.S. 89:6861-6865. K. Rajewsky (1992) Science 256:483 suggests the use of homologous recombination for gene substitution in order to identify the function of a newly discovered gene. Yung et al. (1993) Science 259:984-987 describe the generation of transgenic animals using the Flp/frt recombinase system.
WO 90/11354 and WO 91/19796 further describe methods of homologous recombination. In the former, a functional endogenous gene is removed in a second step after homologous recombination, thereby replacing an endogenous gene with a homologous gene segment. WO 91/19796 discloses a method in which the resistance marker is not situated in the gene segment being introduced, but is introduced separately.
The genes encoding human and mouse immunoglobulins have been extensively characterized. Berman et al. (1988) EMBO J. 7:727-738 describe the human Ig VH locus. Sakano et al. (1981) Nature 290:562-565 describe a diversity segment of the immunoglobulin heavy chain genes. Blankenstein and Kruwinkel (1987) Eur. J. Immunol. 17:1351-1357 describe the mouse variable heavy chain region.
The generation of transgenic mice bearing human immunoglobulin genes is described in International Application WO 90/10077 and WO 90/04036. WO 90/04036 describes a transgenic mouse with an integrated human immunoglobulin xe2x80x9cminixe2x80x9d locus. WO 90/10077 describes a vector containing the immunoglobulin dominant control region for use in generating transgenic animals.
Animals, DNA compositions and methods are provided for the efficient production of high affinity humanized antibodies. Transgenic animals are produced through targeted gene replacement. The native immunoglobulin constant region is replaced with the corresponding human gene segment. Of particular interest is the use of non-mammalian recombinase systems in embryonic stem (ES) cells, which allows for a convenient replacement process. Humanized antibodies are made at a high level and efficiency. In a preferred embodiment, transgenic animals are obtained that undergo antibody affinity maturation and a class switch from the native immunoglobulin to the humanized form. A method was found by the applicant that permits targeted replacement of individual gene segments in the cell line of a mammal in one step with gene segments of other species.
The present invention thus concerns a method for replacement of a gene or gene segment in the cell line of a nonhuman mammal with a homologous gene or a homologous gene segment of another mammal, in which (i) an embryonal parent cell line is transfected with a selectably marked recombination vehicle; (ii) stably transfected cell clones are selected for the presence of the marker gene; (iii) they are subjected to targeted selection by PCR and/or Southern Blot; (iv) these are injected into the blastocysts of the nonhuman mammal; (v) the blastocysts are transferred to surrogate mothers, characterized by the fact that the endogenous gene or the endogenous gene segment is functionally replaced in one step by the homologous gene or the homologous gene segment in the recombination event by means of the selectably marked recombination vehicle.
It is preferred according to the present invention that the introduced gene or the introduced gene segment originate from humans and that the nonhuman mammal be a rodent, especially a mouse.
Genes or gene segments that code for proteins involved in the immune system, the nervous system, especially signal-mediating and adhesion molecules, virus receptors, the blood-forming system and support tissue, especially muscles, tendons and bones may also be replaced according to the subject methods. Those genes and gene segments that code for protein of the immune system are particularly preferred, especially antibody genes, T-cell receptor genes, cytokines, cytokine receptor genes, MHC genes, adhesion molecule genes and genes of signal-mediating molecules.
An antibody gene segment of the mouse is replaced by an antibody gene segment of man in a special variant of the present invention.
The selectably marked recombination vehicle according to the invention is a replacement vector and carries the gene or gene segment to be introduced, sequences that are homologous to the sequences that flank the endogenous DNA segment to be replaced and a marker gene, especially neomycin or hygromycin, neomycin being preferred. Moreover, the recombination vehicle can also contain viral recognition sequences (for example SV40), additional sequences to amplify gene expression, target sequences for pro- and eukaryotic recombination systems. The latter sequences, especially the Cre recognition sequence LoxP or the flip recognition sequence-Frt, can be used for targeted removal of marker genes, as well as any still remaining non-functional target gene segments. In this fashion it is possible to replace in the first step the endogenous gene segment with a homologous gene segment of another mammal and to remove the remaining residues in a second step by means of a selectively functioning recombinase (H. Gu et al., Cell, 73, 1155-1164 (1993)). The remaining residue is selectively removed in this method and only the desired recombination can occur, in contrast to the xe2x80x9chit and runxe2x80x9d method described in WO 91/19796.
The selectably marked recombination vehicle in a preferred variant of the present invention is the plasmid pTZ2-CkN (PAxe2x88x92)(DSM 7211).
Another object of the present invention is a recombination vehicle for homologous recombination that contains the gene to be replaced or the gene segment to be replaced and a selectable marker gene. The recombination vehicle can also contain the recognition, amplification and/or target sequences already mentioned.
Another object of the present invention is the stably transfected cell clone produced by the method according to the invention, as well as a method for creation of a transfected, nonhuman mammal. According to the latter method the stably transfected cell clones according to the invention are injected into mouse blastocysts, these blastocysts are transferred to the surrogate mother, the born chimeral animals are mated and their offspring selected for the presence of the mutation.
Transgenic nonhuman mammals that can be obtained in this fashion are also an object of the present invention.
Another object of the present invention is the use of the selectively mutated, transgenic nonhuman mammal for expression of gene products of another mammal instead of the product coded by the original gene segment and for testing of drugs and therapeutic models. The use of these gene products to produce humanized monoclonal antibodies and for virus production is particularly preferred in the sense of the present invention.
The method according to the invention permits replacement of genes or gene segments in the cell line of nonhuman mammals with a homologous gene or a homologous gene segment of another mammal in one step. Animals that are homozygous for the desired mutation are obtained via chimeras and can be used for expression of gene products of another animal instead of the endogenous gene or for testing of drugs and therapeutic models.

Targeted replacement of an immunoglobulin gene without endogenous and selectable residual sequences in mice

NAIAD, Bldg. 4, Room 111, N.I.H., 9000 Rockville Pike


A fuel cell comprising: a membrane electrolyte assembly having a polymer electrolyte membrane and a pair of catalyst electrodes, namely an air electrode and a fuel electrode sandwiching the polymer electrolyte membrane; a pair of separators, namely an air electrode separator and a fuel electrode separator sandwiching the membrane electrolyte assembly; two or more oxidizing gas channels running in a certain direction for the purpose of supplying an oxidizing gas to the air electrode; and two or more linear fuel gas channels arranged parallel to the certain direction for the purpose of supplying a fuel gas to the fuel electrode. Large gaps and small gaps are provided alternately between adjacent two oxidizing gas channels along the certain direction, and the fuel gas channels do not overlap portions of the oxidizing gas channels, that are parallel to the fuel gas channels.

A fuel cell is composed of a polymer electrolyte membrane which selectively transports protons, and a pair of catalyst electrodes (a fuel electrode and an air electrode) which sandwich the polymer electrolyte membrane. The fuel cell which has the above structure can continuously take out electric energy by supplying a fuel gas (hydrogen is contained) to the fuel electrode, and supplying an oxidizing gas (oxygen is contained) to the air electrode.
The polymer electrolyte membrane is composed of an electrolyte which contains a polymer ion-exchange membrane or the like, such as a sulfonic acid group-containing fluorine resin ion-exchange membrane or hydrocarbon resin ion-exchange membrane. In order for the polymer electrolyte membrane to have an ion transport function, it needs to contain a given quantity of water.
The catalyst electrode is composed of a catalyst layer that promotes a redox reaction therein and of a gas diffusion layer having air permeability and electric conductivity. The catalyst layer is positioned on the polymer electrolyte membrane side. The gas diffusion layer is composed of a carbon coat layer for improving adhesion to the catalyst layer and of a gas diffusion base layer through which a gas supplied from an external source is allowed to diffuse to the catalyst layer. The catalyst layer for the fuel electrode contains, for example, platinum or platinum-ruthenium alloy, and the catalyst layer for the air electrode contains, for example, platinum or platinum-cobalt alloy. An assembly of such a polymer electrolyte membrane and a pair of catalyst electrodes (each composed of a catalyst layer, a carbon coat layer, and a gas diffusion base layer) is called a membrane electrode assembly (hereinafter "MEA").
MEAs can be electrically connected in series by stacking them on top of each other. At this time, in order to keep a fuel gas and an oxidizing gas from being mixed and to electrically connect each MEA in series, a conductive separator is disposed between each of the MEAs.
Separators include a fuel electrode separator which contacts a fuel electrode, and an air electrode separator which contacts an air electrode. Usually, fuel gas channels for supplying a fuel gas to the MEA are formed in the fuel electrode separator, and oxidizing gas channels for supplying an oxidizing gas to the MEA are formed in the air electrode separator.
In a conventional fuel cell, linear gas channels run in parallel to one another (see, e.g., Patent Literature 1). FIG. 1 is an exploded perspective view of the fuel cell disclosed by Patent Literature 1. The fuel cell illustrated in FIG. 1 has membrane electrode assembly 1, air electrode separator 2, and fuel electrode separator 3. Air electrode separator 2 has linear oxidizing gas channels 8 that run in parallel to one another.
In a fuel cell configured as described above, the gap between oxidizing gas channels, i.e., rib width, is generally small. Since ribs do not contribute to supply of an oxidizing gas unlike oxidizing gas channels, reducing rib width makes it possible to supply more oxidizing gas to the MEA. Therefore, in the conventional fuel cell, in order to increase the amount of oxidizing gas to be supplied, rib width is tended to be made small.
Moreover, as described above, the polymer electrolyte membrane needs to contain a given quantity of water for exerting permeability to ions. Therefore, in the conventional fuel cell, in order to ensure sufficient water content, fuel gas and oxidizing gas are humidified in advance. However, a humidifier for humidifying the oxidizing gas does not contribute to power generation directly; rather, it requires a space for installation. Therefore, development of a fuel cell cogeneration system that does not need any humidifier can achieve reductions in size as well as overall system cost reduction. Development of such a fuel cell cogeneration system can also avoid energy loss from the humidifier, thus increasing overall system efficiency. For these reasons, development of a fuel cell has been desired in which power generation efficiency does not decrease even when a less humidified or non-humidified oxidizing gas is employed.
As a conventional technology aiming to prevent the flooding phenomenon, which occurs when the water generated in the reaction gas channel during power generation remains, two or more discrete reaction gas channels are provided in the separator (see, e.g., Patent Literatures 2, 3 and 4). In the fuel cells disclosed by Patent Literatures 2, 3 and 4, each discrete reaction gas channel is formed as a serpentine channel.
As a conventional technology aiming to ensure the hardness of ribs that define reaction gas channels, two or more reaction gas channels are provided in parallel to one another (see, e.g., Patent Literature 5). The reaction gas channels of the fuel cell disclosed by Patent Literature 5 are made serpentine. The separator for the fuel cell disclosed by Patent Literature 5 is a carbon separator.


A light-emitting device using a vacuum doughnut to serve as a current blocking layer is disclosed. The light-emitting device comprises: a substrate of a first conductivity type; a buffer layer formed on the substrate; a double heterostructure layer comprising a first cladding layer, an active layer and a second cladding layer, formed on the buffer layer; and a cap layer of a second conductivity type formed on the double heterostructure layer. A vacuum doughnut is formed between the active layer and an electrode formed on the cap layer to block a current flowing from the electrode formed on the cap layer so that the current flows through a region of the double heterostructure layer that is uncovered by the electrode. Furthermore, the vacuum doughnut can also be formed in the second cladding layer instead of forming in the cap layer.

1. Field of the Invention
This invention relates to a semiconductor light-emitting device, and particularly to a light-emitting device using a vacuum doughnut to serve as a current blocking layer.
2. Description of Prior Art
Generally speaking, light-emitting diodes that are characterized by a double heterojunction have low luminous efficiencies because of contact shadowing caused by current crowding at the p-n junction of the diode under the contact area. Referring to FIG. 1, a conventional light-emitting diode comprises a substrate 10, a buffer layer 12, a double heterostructure 14, a cap layer 16 and metal contacts 18a and 18b. As external contact is made to the structure through the metal contact 18b, light is emitted along the double heterostructure 14. However, the light emitted along the double heterostructure 14 under the contact 18b is absorbed or reflected by the contact, which in effect acts as a shadow to a portion of the light being emitted from the entire double heterostructure, thus reducing the total external light output. Therefore, in order to increase the output of the light being emitted along the entire double heterostructure of the diode, it is essential to minimize contact shadowing beneath the contact area.

Light-emitting device using vacuum doughnut to serve as a current blocking layer


A computerized system is of the type that responds to imminent loss of power by storing crucial data to a safe storage area. In the system, lockup caused by the system entering a tight loop awaiting power loss, is avoided by a combination of stored program and hardware. A test performed in the tight loop checks repeatedly to see whether the power-failure signal comes no longer to be present, and if that condition occurs the stored program causes the meter to return to normal function. As a consequence momentary power losses and other brief interruptions, whether due to user manipulation of the power switch or otherwise, are much less likely to result in undesired lockup of the system.

This invention relates generally to handling loss of power in a computerized apparatus, and relates more particularly to the optimal handling of a condition of return of power following the initiation of the handling of loss of power.
It is commonplace to use a processor (typically a microprocessor) under stored program control to replace or augment functions previously performed by mechanical apparatus or by dedicated circuitry. The many internal states of the processor, stored in processor registers, are lost if the processor loses power. Similarly the contents of a volatile RAM chip are lost if power to the RAM chip is lost. In many consumer products using a processor there is no particular need to save the processor states or RAM contents, so that turning the product off cuts power to the processor and the RAM, and as a result the processor states and RAM contents are lost. This is the case, for example, with most personal computers depending on the application program being executed. If the user has entered data into the RAM of the computer, to avoid losing the data the user must typically explicitly invoke a routine for storing data to a nonvolatile memory (such as to a magnetic medium) before turning off the computer. In other systems some or all the RAM is made nonvolatile, typically by providing a backup battery that preserves the memory contents.
The integrity of the stored data is threatened not only by the possibility of loss of power to the memory device itself, but also by the possibility the CPU or data bus may during loss of power give rise to a condition that makes a spurious change to the stored data. For example, during the nonzero time interval during which power to the processor and address decoder drops from nominal levels (5 VDC) to zero, there is the possibility the CPU may execute an instruction that changes important data. This could occur if the processor were to perform a "write" transaction on the data bus to a harmless location, with the address decoder (because of less-than-nominal power) incorrectly decoding the address to some location containing crucial data. The result would be a spurious change in the value of the crucial data.
In many such systems the risks relating to possible loss of power are of little concern since important information will have been backed up elsewhere, or is capable of being reconstructed from other sources if necessary. Likewise the prospect of processor malfunction or data bus or address decoder malfunction that overwrites important information is not particularly daunting, again because it is usually quite straightforward and workable to let the user reconstruct important data, if suspected of being incorrect, from a backup or other sources.
One type of equipment typically having information stored in nonvolatile RAM is the electronic postage meter. In such postage meters the amount of postage available for printing is typically stored in what is called the "descending register". In postage meters it is important that the descending register is to be stored in such a way that there is minimal likelihood of the user printing postage which has not been paid for. For example, when the meter is turned off and later turned back on, the descending register is to have an unchanged value.
Before the development of electronic postage meters it was commonplace to use mechanical meters, that is, meters in which the descending register is a mechanical device. In a meter employing a mechanical register with value stored in gear positions, the requirement of the descending register remaining unchanged is satisfied by the simple fact of the gears maintaining position with or without external electric power. Such a meter maintains the register contents both in the face of a normal termination of power and in the face of an accidental or unintentional termination of power.
In recent years mechanisms having many moving parts have been replaced with simpler mechanisms in which many formerly mechanical functions are accomplished by a processor under stored program control. In such cases, pure mechanical registers are replaced with RAM memory. This has been the case with postage meters and their descending registers, as in the above-mentioned electronic postage meters.
As in other electronic equipment with nonvolatile memory, with electronic postage meters there is the nonzero probability of loss of the information in the nonvolatile memory due to processor, address decoder, or data bus malfunction. By definition the amount of postage available for printing is a particular stored value that is assumed to be correct. While the availability of a backup copy of data is satisfactory for, say, a word-processed document it is not very satisfactory for a postage meter descending register. In a postage meter it should not be within the discretion of the user to determine unilaterally, for example, that the descending register contents in the nonvolatile RAM are to be ignored and overwritten with supposedly correct backup data from some source that is within the control of the customer. Instead, if customers and the postal authorities are to be satisfied with the meter the stored value must have an exceedingly high level of confidence as to its correctness.
Similar imperatives present themselves in other electronic equipment where a stored value must be correct to a high degree of confidence and where it is of little or no utility to consider external backups and the like. These include gas pumps, automated teller machines, smart credit cards, and cash registers.
In an electronic system employing a processor and storing crucial data in RAM, it is necessary to ensure that the system maintain its crucial data unchanged after the power is turned off and back on, even in the midst of other operations. The system typically has a power supply which gives power to the processor and other circuitry for a time interval after external power is switched off. The power provided during this interval is sometimes called "reserve" power. The system design may have a power-failure warning signal, generated by the power supply circuitry, which provides what might be termed an "early warning" to the processor. The design of the stored program for the system typically provides that arrival of the power-failure warning signal invokes a routine for storing data to nonvolatile memory or updating information in the nonvolatile memory.
The routine of the stored program that is responsive to the power-failure warning signal, as just mentioned, has as one of its first tasks the updating of crucial data. The reserve power, typically provided by a large electrolytic capacitor together with other circuitry, is designed so that the interval during which reserve power is reliable exceeds by a comfortable margin the time required for completion of the data-updating routine. In the particular case of a postage meter, for example, the interval during which reserve power is reliable exceeds the time required to update the descending register as needed. The interval is also long enough to permit the processor to indicate by a particular message that power was lost in the midst of a postage printing operation, if such be the case. In the latter case, upon the restoration of power to the meter the processor encounters the message and updates the descending register accordingly.
A decision facing the designer of an electronic system containing crucial data is what to have the processor do after it has finished its required tasks responsive to the receipt of the power-failure warning. That is, the reserve power will presumably persist for some time after the data-updating activities have been completed pursuant to the stored program. When the reserve power runs out, the processor stops completely. But prior to that, it is desired that the processor not cause any harm to the crucial data such as the nonvolatile memory, so the stored program will typically put the processor into a tight loop, that is a loop which does nothing externally observable other than to keep the processor occupied. This loop, often called a "power-fail" loop, may be as simple as a few null instructions and a jump. One way that keeping the processor in such a loop minimizes risk to crucial data is that few transactions take place on the bus, and none of the transactions are write transactions.
Putting the processor into a tight loop prior to the eventual loss of reserve power can give rise to an anomalous result, from the user's point of view, if external power is returned during the time that the processor is using the reserve power. That anomalous result is lockup of the equipment. The processor remains in the tight loop, and does not respond to user keyboard inputs, even though there is no apparent power loss causing this result. One way this lockup might come about is a rapid switching of the equipment off and back on. Another way this might come about is a momentary loss of external AC power. The lockup can happen in either of two ways--(i) return of external power after the power-failure warning arrived and before the processor has entered the tight loop (i.e. during the routine that saves data to the nonvolatile memory), or (ii) return of external power after the processor has entered the tight loop and before loss of reserve power (i.e. during the execution of the tight loop). In equipment having such a design, the only way to free the meter from the lockup is to turn it off, leave it off long enough for the reserve power to be exhausted, and turn it back on. But the user may not know this, or may be unaware of the cause and so only perceive a malfunction. An example of such a loop may be seen in the postage meter of U.S. Pat. No. 4,675,841 at col. 14, line 59. In that system, "[t]he main program can only be re-entered through a complete power-up cycle".
In electronic systems having crucial data, then, it is desirable to minimize risk to the data during the period of loss of power, and yet to avoid the problem of system lockup if the loss of power is brief.


A new and distinct hybrid of Sedum plant substantially as shown and described characterized by glossy, green to olive green leaves with red serrated leaf margins, showy red stems, strongly upright stems, a medium, clumping habit, and excellent vigor.

The present invention relates to a new and distinct cultivar of Sedum (Hylotelephium) and given the cultivar name of 'TNSEDDM'. Sedum is in the family Crassulaceae. Sedum 'TNSEDDM' originated from a planned cross for compact multicrowned Sedum using Sedum 424-8, as the seed parent, and Sedum 420-8, as the pollen parent. Both parents are unnamed proprietary, unpatented Sedum telephium seedlings.
The Trademark designation for this variety is Double Martini.
Compared to Sedum telephium 424-8, the seed parent, the new cultivar has olive green leaves with red stems rather than green leaves with pink stems.
Compared to Sedum telephium 420-8, the pollen parent, the new cultivar has olive green leaves with red stems with multiple crowns rather than dark red leaves and few crowns.
Compared to Sedum 'Rosetta', U.S. Plant Pat. No. 26,190, the new cultivar has glossy green to olive green leaves with red leaf margins and red stems rather than blue green leaves and green stems.
This new and unique Sedum is distinguished by:                1. glossy, green to olive green leaves with red serrated leaf margins,        2. showy red stems,        3. strongly upright stems,        4. a medium, clumping habit, and        5. excellent vigor.
This new cultivar has been reproduced only by asexual propagation (division and tissue culture). Each of the progeny exhibits identical characteristics to the original plant. Asexual propagation by division and tissue culture using standard micropropagation techniques with terminal and lateral shoots, as done in Canby, Oreg., shows that the foregoing characteristics and distinctions come true to form and are established and transmitted through succeeding propagations. The present invention has not been evaluated under all possible environmental conditions. The phenotype may vary with variations in environment without a change in the genotype of the plant.


A sensing device includes a propulsion system that is typically substantially or completely within the sensing device. The propulsion system may include, for example, a rotatable propeller. The sensing device may be an in-vivo autonomous capsule with an imager, but may be another type of sensing device.

Devices and methods for performing in-vivo imaging of passages or cavities within a body are known in the art. Such devices may include, inter alia, various endoscopic imaging systems and devices for performing imaging in various internal body cavities. Devices are also known for collecting other in-vivo data, such as temperature or pressure.
Typical in-vivo sensing systems are passive and are passively moved within the gastrointestinal (GI) tract by gravitation and by the peristaltic action.
There is suggested in the art a remote controlled microscale device for use in in vivo medical diagnosis and/or treatment, which includes a transport capsule containing a propulsion system.
Among the disadvantages of the devices known in the art is that any parts such as propellers, or the like, which protrude out of the rounded form of the medical device during the passage of the device through the intestines or other body cavity may increase the probability of puncturing or wounding or otherwise damaging or irritating the intestinal wall, or the walls of the bodily cavity in which the device is disposed.
Therefore there is a need for a device such as an in-vivo device which includes an improved propulsion system, one less likely to cause damage to a lumen being traversed.


A memory arrangement that includes a static memory cell with two MOSFETs that are connected such that an input signal for setting the memory cell is applied to one MOSFET, and the output of the other MOSFET is connected to the input of the first MOSFET, so that one MOSFET is always conductive while the other is blocked. The two MOSFETs are connected with positive feedback. In each case, the gate electrode is connected to a voltage equal to half the battery voltage. The source electrode of the first (N channel) MOSFET forms the input of the memory cell. The drain electrode of the first MOSFET is connected to the source electrode of the second (P channel) MOSFET. The blocking resistance of the drain-substrate diode of the first MOSFET is greater than the blocking resistance of the source-substrate diode of the second MOSFET. Also, the output voltage of the first (N channel) MOSFET is greater than the sum of the gate voltage and the threshold voltage of the second (P channel) MOSFET.

Simple static memory cells, for example, may be flip-flops which are composed of two transistors coupled with feedback. Flip-flops have two defined operating states. In each state one of the transistors is conductive and the other is blocked. Flip-flops can be switched from the one stable operating state to the other through an input signal at one of the two transistors, i.e., the input transistor.
U.S. Pat. No. 4,158,239 (Re. 32,071) describes a memory cell which has high power and space requirements. For memory cells that have transistors, additional components, especially resistors, must be used in order to adapt the operating parameters of the transistors to each another. These additional components must also be connected with the transistors via connection lines. This results in a relatively high amount of circuit complexity. This becomes significant, in particular, for the integration of the memory cell on semiconductor chips. In such integrated memory cell arrangements, it is desirable to keep the space requirement for the individual memory cells, as well as for the connection of these individual memory cells, as small as possible, in order to integrate the largest possible number of memory cells on a semiconductor chip.

Memory arrangement with a read-out circuit for a static memory cell