A flat display includes a front glass plate, substrate, cathode, gate electrode, a phosphor screen and metal-backed film, and matrix-like spacer. The front glass plate is at least partly transparent. The substrate is arranged to oppose the front glass plate through a vacuum space. The cathode is formed on the substrate and has an electron-emitting source made of nano tube fibers. The gate electrode has an electron-passing hole in a direction perpendicular to the substrate and is arranged in the vacuum space away from the cathode to oppose the substrate. The phosphor screen and metal-backed film are sequentially stacked on a surface of the front glass plate which opposes the substrate. The matrix-like spacer is stacked between the gate electrode and front glass plate and has a plurality of openings each corresponding to the electron-passing hole.

The present invention relates to a flat display in which electrons emitted from an electron-emitting source are collided against phosphors to emit light.
In general, as a display device such as a FED (Field Emission Display) or a flat vacuum fluorescent display in which electrons emitted from an electron-emitting source serving as a cathode are collided against a light-emitting portion formed of phosphors on a counterelectrode to emit light, a flat panel display is available. In recent years, as a flat panel display of this type, various types that use nano tube fibers, e.g., carbon nano tubes or carbon nano fibers, as the electron-emitting source have been proposed.
A conventional flat display described in Japanese Patent Laid-Open No. 2002-343281 (reference 1) has a substrate 101 made of glass or the like and a front glass plate 103 which is at least partly transparent, as shown in FIG. 5. The substrate 101 and front glass plate 103 are arranged to oppose each other through a spacer glass frame (not shown) at a predetermined gap, and are adhered to the spacer glass frame with low-melting frit glass to form part of an envelope. The interior of the envelope is held at a vacuum degree on the order of 10−5 Pa. A gate electrode structure 120 is disposed in the envelope to be substantially parallel to the substrate 101 and front glass plate 103.
A plurality of substrate ribs 102 are formed on one surface of the substrate 101 to be parallel to each other at predetermined intervals. Band-like cathodes 110, to the surface of which nano tube fibers, e.g., carbon nano tubes or carbon nano fibers, are fixed as an electron-emitting source and which are made of a metal member such as a 426 alloy, are arranged in regions sandwiched by the substrate ribs 102 on the substrate 101, such that the cathodes 110 are leveled with the substrate ribs 102.
A plurality of thin plate-like front ribs 104 are formed at predetermined intervals on that surface of the front glass plate 103 which opposes the substrate 101, in a direction perpendicular to the substrate ribs 102 and cathodes 110. The end faces of the front ribs 104 which oppose the substrate 101 have thin, elongated rectangular shapes. A predetermined number of sets each including red-, green-, and blue-emitting phosphor screens 105R, 105G, and 105B in this order are arranged in those regions on the front glass plate 103 which are sandwiched by the front ribs 104. Metal-backed films 106 to serve as anodes are formed on those surfaces of the phosphor screens 105R, 105G, and 105B which oppose the glass substrate 101.
The front ribs 104 are formed by repeated printing, e.g., screen printing, on the front glass plate 103 until the front ribs 104 reach a predetermined height. Regarding the front ribs 104, a direction perpendicular to the main surface of the front glass plate 103 (the moving direction of electrons extracted from the cathodes 110 (to be described later)) will be referred to as "the direction of height". The direction of the plate thickness of the front ribs 104 (the longitudinal direction of the substrate ribs 102) will be referred to as "the widthwise direction", and a direction perpendicular to "the widthwise direction" and "the direction of height" (the longitudinal direction of gate electrodes 123 (to be described later)) will be referred to as "the lengthwise direction" hereinafter.
The gate electrode structure 120 disposed in the envelope is sandwiched between the end faces of the substrate ribs 102 on the substrate 101 and the end faces of the front ribs 104 of the front glass plate 103. The gate electrode structure 120 includes a glass plate 121 parallel to the substrate 101, a field control electrode 122 formed on the front glass plate 103 side surface of the glass plate 121, the band-like gate electrodes 123 formed on the substrate 101 side surface of the glass plate 121 to respectively correspond to the phosphor screens 105B, 105G, and 105R, and an insulating layer 124 formed on the substrate 101 side surface of the glass plate 121 to cover the gate electrodes 123. A plurality of electron-passing holes 125, through which the field control electrode 122, glass plate 121, gate electrodes 123, and insulating layer 124 communicate with each other in "the direction of height", are formed in those regions of the gate electrode structure 120 where the gate electrodes 123 and cathodes 110 intersect.
The field control electrode 122 which is in contact with the front ribs 104 electrically shields the gate electrodes 123 and cathodes 110. A potential difference between the cathodes 110 and the metal-backed films 106 which serve as anode electrodes generates no electrical field in the region where the field control electrode 122 is formed. Thus, any damage due to electrical discharge to the electron-emitting source, particularly to the surface of the electron-emitting source, is prevented.
In the flat display with the above structure, a predetermined potential difference is supplied between the gate electrode structure 120 and cathodes 110 such that the gate electrode structure 120 side has a positive potential. Thus, electrons extracted from those regions of the cathodes 110 which intersect the gate electrodes 123 are emitted from the electron-passing holes 125. At this time, if a positive potential (acceleration potential) is applied to the metal-backed films 106, the electrons emitted from the electron-passing holes 125 are accelerated toward the metal-backed films 106, and collide against the phosphor screens 105B, 105G, and 105R through the metal-backed films 106 to emit light.
In the conventional flat display, the front ribs 104 formed on the front glass plate 103 cooperate with the substrate ribs 102 (and cathodes 110) formed on the substrate 101 to sandwich the gate electrode structure 120. The front ribs 104 also have the function of supporting the front glass plate 103, so the front glass plate 103 will not be broken by the pressure difference between the interior of the envelope and the outside, and the function of defining the distance between the metal-backed films 106 serving as the anodes and the field control electrode 122.
The front ribs 104 having the above functions are formed by repeating screen printing, as described above, so that, for example, they each have a width of 50 μm and that the distance between the gate electrodes 123 of the gate electrode structure 120 and the metal-backed films 106 is 2.0 mm to 4.0 mm.
To further improve the resolution of the conventional flat display as described above, the regions where the phosphor screens 105B, 105G, and 105R are arranged must be finer. For this purpose, it is indispensable to decrease the widths of the front ribs 104. As described above, however, of the shape of the end face of each front rib 104, the size in the widthwise direction is smaller than the size in the lengthwise direction. With the conventional method of repeating screen printing, to form narrower front ribs 104 at narrower pitches is limited. If the front ribs 104 are to be formed with narrower pitches, they cannot reach the predetermined height.
If the narrow-pitch front ribs 104 having a height smaller than in the conventional case are applied to a flat display, the gap between the anodes and field control electrode 122 becomes shorter than in the conventional case. When a high voltage of, e.g., about 10 keV is applied to the anodes, the field control electrode 122 cannot electrically shield the gate electrodes 123 sufficiently. Abnormal electrical discharge occurs between the anodes and gate electrodes 123 to damage the electron-emitting source.


A method of adaptively operating a medical triage system includes triaging a plurality of persons using a set of triage questions to select particular dispositions from a plurality of triage disposition. Triage-related data is acquired as a result of the triaging of the plurality of persons. The triage-related data is analyzed and the set of triage questions or the dispositions are modified based on the analysis of the triage-related data.

Originally, medical triage was a process deployed during wartime or disasters by which a nurse or other medical professional personally performed an initial assessment of patients to group them into one of three categories: those too ill to benefit from immediate medical care, those well enough to survive without immediate care, and those who could benefit from immediate care. In situations in which immediate medical care was a scarce resource, triage methodology helped ensure that such care would be allocated rationally, for maximum aggregate benefit.
In a broader sense, medical triage is a process for sorting people with medical complaints into groups based on the likelihood of them benefiting from particular levels of medical treatment. For example, most hospital emergency rooms utilize some kind of triage methodology to determine the priority in which patients receive care. The methodology can also include a decision-making strategy for deciding whether a nurse is able to dispense an adequate level of care or a physician is required for a higher level of care. Much of this is done in person, using medical assessments such as blood pressure, pulse, skin color, and general observations of the patient to supplement what the patient describes about his or her condition. The staff then applies hospital triage rules based on that information to determine treatment priority and a level of care, typically aiding those with the most serious conditions first.
Such medical triage systems exist to ensure that an appropriate level of care is dispensed to all individuals, by evaluating the significance of their self-reported or observed symptoms and matching them with a particular level of care. Accurate triaging means that the patient's medical concerns receive a suitable level of medical attention—neither substantially more nor substantially less than what he or she needs.
Triage systems can also ensure that the dispensation of care is more economically efficient. In this age of ballooning medical costs, a medical triage system can mean that whoever ultimately pays for the medical services (e.g., government, companies or individuals) does not pay for an unnecessary level of treatment. For example, if someone with a minor injury is accurately triaged, an appropriate level of care can be determined, while expensive services, such as ambulance transport and emergency department care, can be avoided, if unnecessary.
Some triage systems are focused on controlling and limiting utilization of medical services (i.e., gate keeping). These triage systems are operated by or paid for by insurance companies and/or third party administrators responsible for general health care costs. The system guides callers to medical generalists, rather than to more costly specialists, except when a specialist is necessary. These systems will also direct referrals to in-network (i.e., discounted) medical providers, steering callers away from out-of-network (i.e., non-discounted) providers.
The spread of telecommunications means that some types of medical triage can be employed by persons who are not on-site with the patient. Advances in triage methods have enabled persons without extensive medical training to conduct some types of triage, so long as they are trained in the triage methods. A common form of triage that is conducted telephonically and by non-medical professionals with specialized training is that used by 911 Emergency Medical System (EMS) dispatching services. However, these services generally operate under the assumption that some emergency medical response will be sent to all callers. The dispatcher typically determines the level of response (e.g., whether basic or advanced life support is dispatched, which ambulance or other responder is closest to the caller, and which caller 105 gets priority when there are multiple simultaneous calls). EMS dispatchers also provide pre-arrival instructions, guiding callers in simple life saving techniques to help stabilize patients until emergency personnel arrive.
Medical providers, including clinic and hospital departments, may also utilize a triage service for screening purposes. For example, many expectant mothers and parents call obstetricians' and pediatricians' offices with a variety of medical complaints, concerns and questions. A triage service can play a role in determining which patients need to see a physician and which do not. Many clinics use their own staff for this triage service, but other clinics out-source to call centers. Similarly, many doctors' offices, clinics and hospital departments use call centers to answer their telephones on weekends and after business hours. In addition to handling scheduling and message services, these call centers often use a level of triage to determine which calls warrant paging an on-call doctor.
Most triage calls begin with a nurse recording the medical condition or injury as stated by the caller, along with the caller's demographic information. This is followed by questioning by the nurse and a short health history. The nurse will assess the symptoms, provide information on seeking care and improving symptoms, and refer the caller to a physician, if necessary. Documentation of the call can be the final part of the triage process.
Many of the existing services described above provide a triage service in which nurses apply a variation of the free-form triage, answering callers' medical questions using the nurse's own expertise or general guidelines. While sample protocols, risk factors and other information can be provided, these systems do not establish a broadly applicable and consistent decision-making process. Nurses are left to formulate their own questions and direct their own investigations. Even with general guidelines such a system can be rife with inconsistencies and other limitations. Each nurse can have his or her own particular predilections and can steer the inquiry in a direction not warranted by a fuller understanding of a particular patient's condition or optimal practices obtained by methodical study of prior triage cases. The nurse can miss critical points as a result of sloppiness or lack of knowledge and can, as a result, direct more treatment or less treatment than is appropriate. It can be impossible to ensure consistency and quality control with this kind of system.


The present invention provides an ophthalmic aqueous pharmaceutical preparation, which is excellent in anti-inflammatory effect, which is less stimulative and which has high safety and excellent storage stability. The ophthalmic aqueous pharmaceutical preparation comprises meloxicam and trometamol.

It has been known that meloxicam shows a cyclooxygenase-2-selective anti-inflammatory effect. A non-steroidal anti-inflammatory drug containing meloxicam as an effective component has presently been put on the market as a therapeutic agent for inflammatory diseases and rheumatism, in the form of drugs for internal use and parenteral injections.
It has been reported that if meloxicam is used in the ophthalmic application, it shows a strong anti-inflammatory effect and it also shows a low probability of damaging corneal epithelial cells or the conjunctival cells as compared with the conventional cyclooxygenase-1- and cyclooxygenase-2-nonselective non-steroidal anti-inflammatory agents (International Patent Application Serial No. PCT/JP99/02522).
Moreover, an ophthalmic pharmaceutical preparation containing meloxicam as an effective component is a non-steroidal anti-inflammatory agent and therefore, it would be expected that the pharmaceutical preparation could be used in the treatment of wide variety of diseases such as conjunctivitis, blepharitis, corneitis, scleritis, episcleritis, anterior (ophthalmic) uveitis and post-operative inflammation.
There have been known an ointment, a gel and an eye drop as dosage forms of the ophthalmic pharmaceutical preparation and the eye drop may further be divided into a suspension type pharmaceutical preparation and an aqueous solution type pharmaceutical preparation. The eye drop may easily be administered and therefore, it has widely been used, but the suspension type pharmaceutical preparation suffers from various problems such as uncomfortable feeling with foreign substances (or suspensoids) upon the administration thereof, the scattering of dose and the adhesion of the suspended matter or suspensoids to the container of the suspension. Contrary to this, the aqueous solution type pharmaceutical preparation never suffers from such problems associated with the suspension type one and it is advantageous in that the drug concentration is substantially constant or uniform and that the drug component may easily diffuse upon the administration thereof.
To use a certain drug in the form of an aqueous solution type pharmaceutical preparation (hereunder simply referred to as "aqueous solution"), the drug should be dissolved in water. Therefore, in case where meloxicam is used in the form of an aqueous solution, it is likewise necessary to dissolve A meloxicam in water. However, meloxicam has quite poor solubility in water. More specifically, meloxicam is slightly soluble in an alkaline aqueous solution, but it has a very low solubility in water at an almost neutral pH value.
It has in general been recognized that the pH value of the eye drop preferably ranges from 5 to 9 since it may give a stimulus to the eye (Monthly Ophthalmic Diagnostic Practice, "42. How to Use Eye Drops", published on Jan. 1, 1999). However, meloxicam could not be dissolved in water at an approximately physiological pH value to a concentration sufficient for ensuring the efficacy thereof.
To use a certain drug in the form of an aqueous solution, not only the drug should be dissolved in water to a concentration sufficient for ensuring the efficacy thereof, but also one should pay close attention to reduce the stimulus to a patient to the lowest possible level since the eye is quite susceptible for stimuli. In addition, the resulting aqueous solution should be excellent in safety and storage stability.
In case where an aqueous solution is prepared using meloxicam as an effective component, the foregoing requirements should likewise be satisfied, but there has not yet been known any conventional report, which can provide any useful suggestion for solving the foregoing problem.
As a method for dissolving meloxicam in water, there has been known a means for forming a salt of meloxicam with meglumine (N-methyl-D-glucamine salt) (Japanese Un-Examined Patent Publication (hereunder referred to as "J.P. KOKAI") No. Sho 54-92976). However, the meglumine salt of meloxicam suffers from such problems that it has considerably low solubility in water and that if the amount thereof dissolved in water is increased, the pH value of the resulting solution abruptly increases to such an extent that the pH value is beyond the preferred range of from 5 to 9. In fact, the inventors of this invention have tried to prepare an aqueous solution of meloxicam using meglumine, but it has been proved that only a small amount of meloxicam is dissolved in water and the pH value of the resulting aqueous solution is higher than the neutral range or higher than 9.0 and this requires the control of the pH value of the aqueous solution prior to practical use.
In the commercially available injection containing meloxicam, the meloxicam is dissolved using poloxamer as a surfactant and meglumine. This pharmaceutical preparation is excellent in the ability of solubilizing meloxicam as compared with the pharmaceutical preparation in which meloxicam is dissolved simply using meglumine (J.P. KOKAI No. Sho 54-92976), but the former is not preferred from the viewpoint of safety since it comprises a large amount of a surfactant, which may have a probability of causing hemolysis and of damaging cells.
International Publication No. W099/09988 discloses an ophthalmic aqueous gel in which meloxicam is dissolved using β-cyclodextrin. The tissue-transfer ability of the drug, which is dissolved in water through the formation of a clathlate compound with β-cyclodextrin is dependent on the strength of the bond of the drug with the β-cyclodextrin and accordingly, it has been pointed out that the bioavailability of the drug included in the eye drop, which makes use of β-cyclodextrin as a solubilizing agent, is low as compared with the commonly used eye drop. In addition, the gel suffers from a problem such that it is limited in the applications, as compared with the eye drop.
As has been discussed above in detail, it is very difficult to prepare an aqueous pharmaceutical preparation or a solution comprising meloxicam as an effective component, which is less stimulative to a patient and has high safety and excellent storage stability. For this reason, there has not yet been put on the market any ophthalmic aqueous pharmaceutical preparation containing meloxicam as an effective component.

Ophthalmic aqueous pharmaceutical preparation


An apparatus for displaying an EPG guide bar includes: an EPG data extraction part extracting EPG data from a signal through a channel; a first memory storing the EPG data; a second memory storing a broadcast program; a user interface display part producing a guide bar having a fixed indicator displaying a present time with the help of a graphic processor, sliding title areas of broadcast programs corresponding to the EPG data of the first memory in the guide bar on real-time correspondingly to the present time, and updating the title areas with a predetermined time interval centering around the fixed indicator so as to produce information indicating a record proceeding status on at least one of the title areas of the broadcast programs which are being recorded in the second memory; and an on-screen display part converting the information from the user interface display part into an on-screen display form so as to display the converted information on a display.

1. Field of the Invention
The present invention relates to an apparatus and method for displaying an EPG guide bar.
2. Background of the Related Art
Generally, the progression status of broadcasting a TV program is displayed as a time shifting bar or as a circular form such as a watch.
For instance, a horizontal bar is frequently used for a computer or a TV set. Such a bar can display a limited portion of a program on a screen, corresponding to one hour or half an hour.
FIG. 1 illustrates a diagram of a screen on which a time shifting bar is displayed according to a related art.
Referring to FIG. 1, such a bar generally has an indicator which depending on the progress of the program shifts from a left end where the program starts to a right end where the program ends. In other words, the indicator directs the progress extent of the current broadcasting program or the remaining extent of the program.
The bar displayed on the screen is tuned to the TV set to be used for indicating a record extent of the program on air. Generally, the TV set is equipped with a built-in memory enabling to record about one hour of broadcast program. Besides, the lengths of broadcast programs are different.
For instance, there may be a broadcast programs which lasts for half an hour, one hour, or the more.
In this case, the bar has an indicator indicating an record extent of the program as shown in FIG. 1. And, the indicator displays the progress of data recording in a memory having a capacity of one hour. In other words, the presently broadcasted program is continuously stored in the memory. When the broadcast program of one hour is completely stored in the memory having a capacity of one hour, the front parts of the contents stored in the memory are erased in order and, simultaneously, the contents of the program in progress are stored in the parts from which the previously-stored data are erased. In this case, the indicator moves slowly from the left end to the right end of the guide bar while the contents of the program in progress are stored in the memory. Namely, the indicator moves from left to right of the guide bar for an hour. After one hour, the indicator starts to move from right to left of the bar. Therefore, at least two broadcast programs may be stored in the memory entirely or in part. Instead, a single broadcast program may be stored in the memory entirely or in part.
However, in accordance with the above-explained related arts, the memory stores the contents of the programs broadcasted through one channel consecutively with an interval of one hour therein. And, the indicator of the bar indicates the data storage extent in the memory having a capacity of one hour. Hence, a viewer fails to check how far the presently broadcasted program is in progress as well as how much the memory is used for storing the data.
For instance, the viewer may leave the TV set temporarily for other purpose during watching a TV program. In this case, the viewer, who wishes to watch the missing part of the program, needs to know how far the program has run using the guide bar. If knowing how far the program that the viewer missed and how much the memory is used for recording the program, the viewer manipulates a key panel or a remote controller to keep up with the missing parts, i.e. time shifting to the starting point of the missing part stored in the memory. However, the guide bar and indicator of the guide bar fail to indicate the exact location of the missing part. This is because the indicator does not indicate the running extent of the presently broadcasted program but the storage extent of the memory.
Meanwhile, in the guide bar according to the related art shown in FIG. 1, the indicator moves within the guide bar having a fixed area. Such a technology, which is generally used for a scale or a speedometer of a car, fails to be applied to the case that the length of the program exeeds the maximum range of the scale.
For another instance, the TV broadcast programs have different lengths. It is substantially impossible to indicate the starting and ending points of the respective programs while carrying out recording/erasing such progras in/from the memory having the capacity of one hour. In other words, when a program of at least one hour is recorded, the guide bar having a length equivalent to the capacity of the one-hour memory is supposed to be located at the right end of the guide bar. Therefore, in order to indicate that the program has been recorded for at least an hour, another bar is necessary to show up on the screen.

Apparatus and method for displaying EPG guide bar


A system for deleting map data comprises an interface and a processor. The interface is configured to determine a location associated with a device. The processor is configured to determine one or more map bundles to delete based at least in part on the location and delete the one or more map bundles.

Modern vehicles (e.g., airplanes, boats, trains, cars, trucks, etc.) can include a vehicle event recorder in order to better understand the timeline of an anomalous event (e.g., an accident). A vehicle event recorder typically includes a set of sensors, e.g., video recorders, audio recorders, accelerometers, gyroscopes, vehicle state sensors, GPS (global positioning system), etc., that report data, which is used to determine the occurrence of an anomalous event. If an anomalous event is detected, then sensor data related to the event is stored for later review. A vehicle event recorder for cars and trucks (e.g., vehicles that operate on public roads) typically includes road map data comprising location-specific legal information (e.g., speed limit information, stop sign information, traffic light information, yield sign information, etc.). Location-specific legal information can be used to identify an anomalous event in the case of the vehicle acting against the law (e.g., traveling in excess of the speed limit, rolling through a stop sign, etc.). When a vehicle event recorder is installed in a vehicle, it will ideally have only an appropriate set of map data. However, building and shipping a set of different vehicle event recorders each with a different set of map data creates logistical complexity and increases cost of manufacturing.


An underwater coating composition for protecting a submerged steel structure from corrosion includes a base resin selected from the group consisting of an epoxidized polysulfide resin and a mixture of an epoxidized polysulfide resin and an epoxy resin, a moisture barrier pigment and an effective amount of a curing agent suitable for curing the composition while the composition is submerged in water and a method for protecting an underwater structure by coating the structure with the above described coating composition.

Many structures, e.g. dams, locks, bridge abutments, dock pilings etc., are immersed in either fresh or salt water Replacement of such structures is very difficult and at times impossible due to economic and engineering considerations, yet many of these structures are unprotected from corrosion. In order to prolong the service life of such structures it is desirable to protect said structures from further corrosion. This approach is complicated by the fact that it is not feasible to dewater many of the structures. Therefore, there is a need for a corrosion protective coating which can be applied to steel and other substrates while the substrates are submerged in water. While there are epoxy resin-based underwater coatings which are easy to apply and exhibit good adhesion t said substrate, said coatings exhibit several drawbacks, e.g. tackiness of the coating surface due to incomplete cure, brittleness of the cured coatings and consequent lack of impact resistance, solubility of various elements of the coatings, and leachability of various agents.
The present invention provides a coating composition with the strong adhesion and ease of application associated with the known epoxy based coating compositions but which avoids the drawbacks associated with the known epoxy coating compositions.

Underwater coating for submerged substrates


A new class of pseudo-trisaccharide aminoglycosides having an alkyl group at the 5″ position, exhibiting efficient stop codon mutation readthrough activity, low cytotoxicity and high selectivity towards eukaryotic translation systems are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders, as well as processes of preparing these aminoglycosides. The disclosed aminoglycosides can be represented by the general formula I:

The present invention, in some embodiments thereof, relates to a new class of aminoglycosides and more particularly, but not exclusively, to novel aminoglycosides with improved efficacy towards treatment of genetic disorders.
Many human genetic disorders result from nonsense mutations, where one of the three stop codons (UAA, UAG or UGA) replaces an amino acid-coding codon, leading to premature termination of the translation and eventually to truncated inactive proteins. Currently, hundreds of such nonsense mutations are known, and several were shown to account for certain cases of fatal diseases, including cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), ataxia-telangiectasia, Hurler syndrome, hemophilia A, hemophilia B, Tay-Sachs, and more. For many of those diseases there is presently no effective treatment, and although gene therapy seems like a potential possible solution for genetic disorders, there are still many critical difficulties to be solved before this technique could be used in humans.
Certain aminoglycosides have been shown to have therapeutic value in the treatment of several genetic diseases because of their ability to induce ribosomes to read-through stop codon mutations, generating full-length proteins from part of the mRNA molecules.
Typically, aminoglycosides are highly potent, broad-spectrum antibiotics commonly used for the treatment of life-threatening infections. It is accepted that the mechanism of action of aminoglycoside antibiotics, such as paromomycin, involves interaction with the prokaryotic ribosome, and more specifically involved binding to the decoding A-site of the 16S ribosomal RNA, which leads to protein translation inhibition and interference with the translational fidelity.

Several achievements in bacterial ribosome structure determination, along with crystal and NMR structures of bacterial A-site oligonucleotide models, have provided useful information for understanding the decoding mechanism in prokaryote cells and understanding how aminoglycosides exert their deleterious misreading of the genetic code. These studies and others have given rise to the hypothesis that the affinity of the A-site for a non-cognate mRNA-tRNA complex is increased upon aminoglycosides binding, preventing the ribosome from efficiently discriminating between non-cognate and cognate complexes.
The enhancement of termination suppression by aminoglycosides in eukaryotes is thought to occur in a similar mechanism to the aminoglycosides' activity in prokaryotes of interfering with translational fidelity during protein synthesis, namely the binding of certain aminoglycosides to the ribosomal A-site probably induce conformational changes that stabilize near-cognate mRNA-tRNA complexes, instead of inserting the release factor. Aminoglycosides have been shown to suppress various stop codons with notably different efficiencies (UGA>UAG>UAA), and the suppression effectiveness is further dependent upon the identity of the fourth nucleotide immediately downstream from the stop codon (C>U>A≧grams) as well as the local sequence context around the stop codon.
The desired characteristics of an effective read-through drug would be oral administration and little or no effect on bacteria. Antimicrobial activity of read-through drug is undesirable as any unnecessary use of antibiotics, particularly with respect to the gastrointestinal (GI) biota, due to the adverse effects caused by upsetting the GI biota equilibrium and the emergence of resistance. In this respect, in addition to the abovementioned limitations, the majority of clinical aminoglycosides are greatly selective against bacterial ribosomes, and do not exert a significant effect on cytoplasmic ribosomes of human cells.
In an effort to circumvent the abovementioned limitations, the biopharmaceutical industry is seeking new stop mutations suppression drugs by screening large chemical libraries for nonsense read-through activity. Using this approach, a non-aminoglycoside compound, 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid (PTC124), has been discovered. The facts that PTC124 is reported to have no antibacterial activity and no reported toxicity, suggest that its mechanism of action on the ribosome is different than that of the aminoglycosides.
The fact that aminoglycosides could suppress premature nonsense mutations in mammalian cells was first demonstrated by Burke and Mogg in 1985, who also noted the therapeutic potential of these drugs in the treatment of genetic disorders. The first genetic disease examined was cystic fibrosis (CF), the most prevalent autosomal recessive disorder in the Caucasian population, affecting 1 in 2,500 newborns. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, more than 1,000 different CF-causing mutations in the CFTR gene were identified, and 5-10% of the mutations are premature stop codons. In Ashkenazi Jews, the W1282X mutation and other nonsense mutations account for 64% of all CFTR mutant alleles.
The first experiments of aminoglycoside-mediated suppression of CFTR stop mutations demonstrated that premature stop mutations found in the CFTR gene could be suppressed by members of the gentamicin family and geniticin (G-418), as measured by the appearance of full-length, functional CFTR in bronchial epithelial cell lines.

Suppression experiments of intestinal tissues from CFTR−/− transgenic mice mutants carrying a human CFTR-G542X transgene showed that treatment with gentamicin, and to lesser extent tobramycin, have resulted in the appearance of human CFTR protein at the glands of treated mice. Most importantly, clinical studies using double-blind, placebo-controlled, crossover trails have shown that gentamicin can suppress stop mutations in affected patients, and that gentamicin treatment improved transmembrane conductance across the nasal mucosa in a group of 19 patients carrying CFTR stop mutations. Other genetic disorders for which the therapeutic potential of aminoglycosides was tested in in-vitro systems, cultured cell lines, or animal models include DMD, Hurler syndrome, nephrogenic diabetes insipidus, nephropathic cystinosis, retinitis pigmentosa, and ataxia-telangiectasia.
However, one of the major limitations in using aminoglycosides as pharmaceuticals is their high toxicity towards mammals, typically expressed in kidney (nephrotoxicity) and ear-associated (ototoxicity) illnesses. The origin of this toxicity is assumed to result from a combination of different factors and mechanisms such as interactions with phospholipids, inhibition of phospholipases and the formation of free radicals. Although considered selective to bacterial ribosomes, most aminoglycosides bind also to the eukaryotic A-site but with lower affinities than to the bacterial A-site. The inhibition of translation in mammalian cells is also one of the possible causes for the high toxicity of these agents. Another factor adding to their cytotoxicity is their binding to the mitochondrial ribosome at the 12S rRNA A-site, whose sequence is very close to the bacterial A-site.
Many studies have been attempted to understand and offer ways to alleviate the toxicity associated with aminoglycosides, including the use of antioxidants to reduce free radical levels, as well as the use of poly-L-aspartate and daptomycin, to reduce the ability of aminoglycosides to interact with phospholipids. The role of megalin (a multiligand endocytic receptor which is especially abundant in the kidney proximal tubules and the inner ear) in the uptake of aminoglycosides has recently been demonstrated. The administration of agonists that compete for aminoglycoside binding to megalin also resulted in a reduction in aminoglycoside uptake and toxicity. In addition, altering the administration schedule and/or the manner in which aminoglycosides are administered has been investigated as means to reduce toxicitys.
Despite extensive efforts to reduce aminoglycoside toxicity, few results have matured into standard clinical practices and procedures for the administration of aminoglycosides to suppress stop mutations, other than changes in the administration schedule. For example, the use of sub-toxic doses of gentamicin in the clinical trails probably caused the reduced read-through efficiency obtained in the in-vivo experiments compared to the in-vitro systems. The aminoglycoside Geneticin® (G-418 sulfate) showed the best termination suppression activity in in-vitro translation-transcription systems, however, its use as a therapeutic agent is not possible since it is lethal even at very low concentrations. For example, the LD50 of G-418 against human fibroblast cells is 0.04 mg/ml, compared to 2.5-5.0 mg/ml for gentamicin, neomycin and kanamycin.
The increased sensitivity of eukaryotic ribosomes to some aminoglycoside drugs, such as G-418 and gentamicin, is intriguing but up to date could not be rationally explained because of the lack of sufficient structural data on their interaction with eukaryotic ribosomes. Since G-418 is extremely toxic even at very low concentrations, presently gentamicin is the only aminoglycoside tested in various animal models and clinical trials. Although some studies have shown that due to their relatively lower toxicity in cultured cells, amikacin and paromomycin can represent alternatives to gentamicin for stop mutation suppression therapy, no clinical trials with these aminoglycosides have been reported yet.
To date, nearly all suppression experiments have been performed with clinical, commercially available aminoglycosides, however, only a limited number of aminoglycosides, including gentamicin, amikacin, and tobramycin, are in clinical use as antibiotics for internal administration in humans. Among these, tobramycin do not have stop mutations suppression activity, and gentamicin is the only aminoglycoside tested for stop mutations suppression activity in animal models and clinical trials. Recently, a set of neamine derivatives were shown to promote read-through of the SMN protein in fibroblasts derived from spinal muscular atrophy (SPA) patients; however, these compounds were originally designed as antibiotics and no conclusions were derived for further improvement of the read-through activity of these derivatives.
WO 2007/113841, by some of the present inventors, which is incorporated by reference as if fully set forth herein, teaches a class of paromomycin-derived aminoglycosides, which were designed specifically to exhibit high premature stop-codon mutations readthrough activity while exerting low cytotoxicity in mammalian cells and low antimicrobial activity, and can thus be used in the treatment of genetic diseases. This class of paromomycin-derived aminoglycosides was designed by introducing certain manipulations of a paromamine core, which lead to enhanced readthrough activity and reduced toxicity and antimicrobial activity. The manipulations were made on several positions of the paromamine core.

One such manipulation of the paromamine core which has been described in WO 2007/113841 is the determination of the beneficial role of a hydroxyl group at position 6′ of the aminoglycoside core (see, for example, NB30 and NB54 below).

Another manipulation of the paromamine core which has been defined and demonstrated in WO 2007/113841 is the introduction of one or more monosaccharide moieties or an oligosaccharide moiety at position 3′, 5 and/or 6 of the aminoglycoside core. This manipulation is reflected as "Ring III" in the exemplary compounds NB30 and NB54 shown hereinabove.
An additional manipulation of the paromamine core which has been defined and demonstrated in WO 2007/113841 is the introduction of an (S)-4-amino-2-hydroxybutyryl (AHB) moiety at position 1 of the paromamine core. This manipulation is reflected in exemplary compound NB54 shown hereinabove. It has been demonstrated that such an introduction of an AHB moiety provides for enhanced readthrough activity and reduced toxicity.
An additional manipulation of the paromamine core which has been described in WO 2007/113841 is the substitution of hydrogen at position 6′ by an alkyl such as a methyl substituent. This manipulation has been exemplified in a derivative of compounds NB30 and NB54, referred to as NB74 and NB84 respectively.

Additional background art includes Nudelman, I., et al., Bioorg Med Chem Lett, 2006. 16(24): p. 6310-5; Hobbie, S. N., et al., Nucleic Acids Res, 2007. 35(18): p. 6086-93; Kondo, J., et al., Chembiochem, 2007. 8(14): p. 1700-9; Rebibo-Sabbah, A., et al., Hum Genet, 2007. 122(3-4): p. 373-81; Azimov, R., et al., Am J Physiol Renal Physiol, 2008. 295(3): p. F633-41; Hainrichson, M., et al., Org Biomol Chem, 2008. 6(2): p. 227-39; Hobbie, S. N., et al., Proc Natl Acad Sci USA, 2008. 105(52): p. 20888-93; Hobbie, S. N., et al., Proc Natl Acad Sci USA, 2008. 105(9): p. 3244-9; Nudelman, I., et al., Adv. Synth. Catal., 2008. 350: p. 1682-1688; Nudelman, I., et al., J Med Chem, 2009. 52(9): p. 2836-45; Venkataraman, N., et al., PLoS Biol, 2009. 7(4): p. e95; Brendel, C., et al., J Mol Med (Berl), 2010. 89(4): p. 389-98; Goldmann, T., et al., Invest Ophthalmol Vis Sci, 2010. 51(12): p. 6671-80; Malik, V., et al., Ther Adv Neurol Disord, 2010. 3(6): p. 379-89; Nudelman, I., et al., Bioorg Med Chem, 2010. 18(11): p. 3735-46; Warchol, M. E., Curr Opin Otolaryngol Head Neck Surg, 2010. 18(5): p. 454-8; Lopez-Novoa, J. M., et al., Kidney Int, 2011. 79(1): p. 33-45; Rowe, S. M., et al., J Mol Med (Berl), 2011. 89(11): p. 1149-61; and Vecsler, M., et al., PLoS One, 2011. 6(6): p. e20733.

This patent is subject to a terminal disclaimer.

Aminoglycosides and uses thereof in treating genetic disorders

Abstract: or a pharmaceutically acceptable salt thereof, wherein R1 is selected from the group consisting of alkyl, cycloalkyl and aryl; and all other variables and features are as described in the specification.

Technion Research & Development Foundation Limited


A diaphragm chuck for a machine tool has a first clamping diaphragm and a second clamping diaphragm which is offset relative to the first clamping diaphragm along an axial direction. The first clamping diaphragm has multiple first chuck jaws and the second clamping diaphragm has multiple second chuck jaws, and the first and the second clamping diaphragms are detachably connected to one another.

1. Field of the Invention
The present invention relates to a diaphragm chuck for a machine tool.
2. Description of the Related Art
Such diaphragm chucks are generally known. For example, a diaphragm chuck is known from the published German patent document DE 1 652 942 B which has two groups of chuck jaws which are situated at an axial distance from one another and which are each mounted on a diaphragm for chucking the workpiece, the diaphragm chuck also having an air pressure regulator for unchucking the workpiece. The diaphragm chuck is operated with compressed air in such a way that for unchucking the chuck jaws, compressed air is guided through a channel in the chuck housing, thus causing deformation of the clamping diaphragms. The chuck jaws of one group of chuck jaws are swiveled outwardly, partially parallel to an axial direction, while the chuck jaws of the other group of chuck jaws are swiveled inwardly, partially antiparallel to the axial direction. A workpiece may subsequently be inserted into the diaphragm chuck up to a stop, or removed from the diaphragm chuck. As a result of a targeted pressure reduction in the diaphragm chuck, the chuck jaws are swiveled back, so that a workpiece situated in the diaphragm chuck is securely clamped between the chuck jaws. It is disadvantageous that, due to the partially oppositely directed swiveling of the chuck jaws along the axial direction, the workpiece is slightly dislodged from the stop when the workpiece is gripped by the chuck jaws, so that the workpiece is acted on with play in the axial direction. The first and second groups of chuck jaws are also designed as one piece, so that a selective replacement of a single group of chuck jaws and/or individual, for example closing, chuck jaws is not possible.
Another diaphragm chuck is known from the published German patent application document DE 1 128 254 A, this diaphragm chuck having only a single clamping diaphragm. This has the disadvantage that the chucking power decreases as the axial distance between the chucking point and the diaphragm surface increases.


A first radio has duplex communication with a second radio and a third radio, without using a base station by using a multiple-access protocol system. The first radio is configured to switch back and forth between being a master radio and a slave radio in the multiple-access protocol system. In some embodiments, time-division multiplexing is used as the multiple-access protocol system for the first radio, the second radio, and the third radio to communicate. In some embodiments, the master radio provides timing synchronization and/or assigns transmission slots for radios in the multiple-access protocol system.

This disclosure relates in general to radio communication, and more specifically, without limitation, to time-division multiplexed communication. Two-way radios enable wireless communication between two or more people. To operate, many radios require either a push-to-talk (PTT) button or a voice operated switch (VOX). For example, walkie-talkies today require either a PTT button or VOX. One disadvantage of both PTT and VOX is that both PTT and VOX communications are half-duplex. In half-duplex communication, a radio can either transmit or receive at a given time, not both. In this application, the term PTT radio generally refers to radios using half-duplex communication where a user can either speak or listen at a given time, not both.
Full-duplex communication, commonly referred to as duplex communication, permits a radio to simultaneously transmit and receive at the same time, enabling a user of a duplex radio to both speak and listen at the same time. One way a radio can operate in a duplex mode, without needing a PTT button or VOX, is by using a base station. An example of wireless radios connected by a base station, and thus enabling full-duplex communication, is two users talking to each other using cell phones. Another example of wireless radios connected by a base station is a home telephone system with wireless telephones that can be placed in a conferencing mode.


The present invention discloses 1) a catalyst composition consisting of a crosslinked organic polymer compound and a palladium catalyst, wherein said catalyst is physically carried on said crosslinked organic polymer compound, 2) a manufacturing method of the above catalyst composition 1), characterized by homogenizing a straight chain organic polymer compound, having a crosslinkable functional group, and a palladium catalyst in a solvent dissolving said straight chain organic polymer compound, then depositing a composition thus formed and subjecting the crosslinkable functional group in said deposit to a crosslinking reaction, 3) a method for substitution reaction at an allyl position, characterized by reacting an allyl carbonate and a neucleophilic agent in the presence of the above catalyst composition 1), and 4) a method for oxidizing an alcohol, characterized by subjecting the above catalyst composition 1) to reaction with an alcohol.

Palladium is known as a useful catalyst since it induces various conversion reactions in organic synthesis. However, this metal has many problems in direct use as a catalyst because it is expensive and in addition, it loses partially its activity on contact with air and cannot be used repeatedly. Fixation of palladium on a polymer as a technology to solve these problems has been attempted and various reactions using palladium fixed on a polymer have been reported frequently so far. However, any of conventional palladium fixed on a polymer still has a common problem that catalyst recovery rate is low and activity decreases in repeated use, although stability of the catalyst itself is improved.
For example, the present inventors created a microcapsulated metal catalyst by fixing a palladium compound such as a palladium complex compound, an organic palladium compound, an inorganic salt and an organic salt, on a polystyrene-type compound, a polymer compound having an aromatic ring (for example, see the specification of Japanese application; JP-2001-59742). However, the above microcapsulated metal catalyst turned out to be difficult to use for a reaction employing a general organic solvent, because any of polymer compounds used as carriers is a non-crosslinked type and has defect of easily dissolving in an organic solvent to be used for a common organic reaction, such as methylene chloride, tetrahydrofuran, benzene and toluene. Because the polymer compound to be used as a carrier of the above microcapsulated metal catalyst was a non-crosslinked type, said metal-catalyst composition agglomerated easily, resulting in smaller surface area of said metal-catalyst composition, which caused a problem of very low catalyst efficiency due to smaller amount of actually functioning catalyst compared with an amount of the metal carried on a polymer carrier. Another problem was that raw materials or reaction products were caught into a carrier polymer constituting a catalyst composition in a reaction using these metal catalysts.
To solve these problems, the present inventors studied use of a crosslinked polymer carrier obtained by crosslinking with divinylbenzene or the like, as the above polystyrene-type polymer compound. However, it turned out to be impossible to fix a metal on polystyrene crosslinked by divinylbenzene, which is insoluble in a general organic solvent, because it was necessary to dissolve a polymer carrier in a solvent in order for the polymer to carry the metal physically.
On the other hand, a method for fixing a metal catalyst on a crosslinked polymer to which an ion-exchange group is introduced has been known as a method for fixing a metal catalyst on such a crosslinked polymer carrier (see Jp-A-59-27840, for example). However, a metal catalyst carried on a carrier obtained by such a method was sometimes difficult to use repeatedly due to leakage of the carried metal catalyst depending on properties of liquid to be used with.
In such situations, a more versatile new metal catalyst carried on a crosslinked polymer wherein the polymer carrier is insoluble in an organic solvent and the carried metal hardly leaks and can keep its activity in repeated use has been required.

Japan Science and Technology Corporation


A calibration device includes: a two-dimensional image conversion element having a plurality of pixels; and an optical system for forming an image-formation relationship between the two-dimensional image conversion element and a three-dimensional world coordinate space, the calibration device including a computer, the computer being configured to: acquire calibration data indicating a correspondence between two-dimensional pixel coordinates in the image conversion element and three-dimensional world coordinates in the world coordinate space; and calculate parameters of a camera model by fitting, to the acquired calibration data, the camera model representing two coordinate values of the two-dimensional pixel coordinates as functions of three coordinate values of the three-dimensional world coordinates, wherein the camera model represents the two coordinate values of the two-dimensional pixel coordinates by means of a linear sum of a plurality of two-dimensional vector functions having, as elements, the functions of the three coordinate values of the three-dimensional world coordinates.

There are known calibration devices for performing camera calibration of image-acquisition devices and projection devices (refer to, for example, Patent Literature 1). A camera model includes a plurality of unknown parameters (camera parameters), and by obtaining these camera parameters with a calibration device, real-world backprojection lines corresponding to two-dimensional coordinates in an image can be obtained mathematically. Alternatively, two-dimensional coordinates in an image corresponding to real-world three-dimensional coordinates can be obtained.
Here, the conventional camera calibration, disclosed in Patent Literature 1 and Non Patent Literature 1, will be described. Camera calibration is performed in the following procedure by using a mathematical camera model that expresses a process in which three-dimensional coordinates in the real world are image-captured by a camera and are converted into two-dimensional coordinates in an image. First, using Expression 1 below, three-dimensional coordinates in the real world (hereinbelow, referred to as world coordinates) (x, y, z) are projected on normalized image plane coordinates (up, vp).
                    {                                                                              u                  p                                =                                                                                r                        11                                                                  x                                        +                                                                  r                        12                                                                  y                                        +                                                                  r                        13                                                                  z                                        +                                          t                      x                                                                                r                        31                                                                  x                                        +                                                                  r                        32                                                                  y                                        +                                                                  r                        33                                                                  z                                        +                                          t                      z                                                                                v                  p                                =                                                                                r                        21                                                                  x                                        +                                                                  r                        22                                                                  y                                        +                                                                  r                        23                                                                  z                                        +                                          t                      y                                                                                r                        31                                                                  x                                        +                                                                  r                        32                                                                  y                                        +                                                                  r                        33                                                                  z                                        +                                          t                      z                                                                                {                  Expression                                                              1                }                                          R          =                      (                                                                                r                    11                                                                                r                    12                                                                                r                    13                                                                                r                    21                                                                                r                    22                                                                                r                    23                                                                                r                    31                                                                                r                    32                                                                                r                    33                                                                        )                          ,                  T          =                      (                                                                                t                    x                                                                                t                    y                                                                                t                    z                                                                        )                                              {                  Expression                                                              2                }
Note that the rotation matrix R and the translation vector T in Expression 2 express three-dimensional coordinate conversion of world coordinates into camera coordinates. These are values representing the position and orientation of the camera with respect to world coordinates and are called extrinsic parameters.
Note that Expression 1 is based on an assumption that all backprojection lines intersect at the optical center of the camera. Next, using Expression 3 below, (ud, vd) are obtained by adding distortion to normalized image plane coordinates (up, vp).
                    {                                                                                u                        d                                            =                                                                        u                          p                                                +                                                                              g                            1                                                                                (                                                                                u                                p                                2                                                            +                                                              v                                p                                2                                                                                )                                                                          +                                                                              g                            3                                                                                u                            p                            2                                                                          +                                                                                g                          4                                                                                u                          p                                                                                v                          p                                                                    +                                                                        k                          1                                                                                u                            p                                                                                (                                                                                u                                p                                2                                                            +                                                              v                                p                                2                                                                                )                                                                                v                        d                                            =                                                                        v                          p                                                +                                                                              g                            2                                                                                (                                                                                u                                p                                2                                                            +                                                              v                                p                                2                                                                                )                                                                          +                                                                              g                            3                                                                                u                            p                                                                                v                            p                                                                          +                                                                                g                          4                                                                                v                          p                          2                                                                    +                                                                        k                          1                                                                                v                            p                                                                                (                                                                                u                                p                                2                                                            +                                                              v                                p                                2                                                                                )                                                                                {                  Expression                                                              3                }
Note that (g1, g2, g3, g4, k1) are distortion parameters. Furthermore, using Expression 4 below, the normalized image plane coordinates (ud, vd) obtained by adding distortion are converted into pixel-unit pixel coordinates (u, v).
                    {                                                            u                =                                                                            α                      u                                                                                u                      d                                                        +                                      u                    0                                                                                v                =                                                                            α                      v                                                                                v                      d                                                        +                                      v                    0                                                                                {                  Expression                                                              4                }
In this way, in a standard camera model, conversion of world coordinates (x, y, z), obtained by image acquisition with the camera, into pixel coordinates (u, v) is expressed with Expressions 1 to 4. Because the parameters (αu, αv, u0, v0, g1, g2, g3, g4, k1) in Expression 3 and Expression 4 represent the properties of the camera itself, they are called intrinsic parameters.
The distortion parameters are variously defined according to usage. For example, although Expression 3 expresses a model in which distortion of up to a third order is taken into consideration, a model in which a term of a higher order, such as a fifth, a seventh, or a higher order, is added is also used. Among them, a representative distortion model is Brown's model disclosed in Non Patent Literature 2, shown in Expression 5 below.
                              (                                                                      u                  d                                                                                v                  d                                                              )                =                              (                                                                                u                    p                                                                                v                    p                                                                        )                    +                                    (                                                                    k                    1                                                                          r                    p                    2                                                  +                                                      k                    2                                                                          r                    p                    4                                                  +                                                      k                    3                                                                          r                    p                    6                                                  +                …                                                                                )                                                  (                                                                                u                      p                                                                                v                      p                                                                                )                                +                                    [                                                                                p                    1                                                                          (                                                                                r                              p                              2                                                        +                                                          2                                                                                u                                p                                2                                                                                2                                                                                u                              p                                                                                v                              p                                                                                )                                                  +                                                      p                    2                                                                          (                                                                                2                                                                                u                              p                                                                                v                              p                                                                                r                              p                              2                                                        +                                                          2                                                                                v                                p                                2                                                                                )                                                              ]                                                  (                              1                +                                                      p                    3                                                                          r                    p                    2                                                  +                …                                                                                )                                                          {                  Expression                                                              5                }
Here, rp2=up2+vp2.
In Brown's model, distortion is represented by parameters (k1, k2, k3, . . . ) for rotationally symmetrical radial distortion and parameters (p1, p2, p3, . . . ) for rotationally asymmetrical tangential distortion.
On the other hand, Patent Literature 2 discloses a camera model produced by directly modeling object-side backprojection lines corresponding to pixel coordinates. This model is characterized in that each coefficient of the distortion model is replaced with a linear expression of an object distance z. As one example thereof, Patent Literature 2 presents a camera model in Expression 6 below.
                              (                                                    x                                                                    y                                              )                =                                            (                                                                    k                                          A                                                                                0                                                                          z                                +                                  k                                      B                                                                                0                                                              )                                                  (                                                                    u                                                                                v                                                              )                                +                                    (                                                                    k                                          A                                                                                1                                                                          z                                +                                  k                                      B                                                                                1                                                              )                                                                  r                2                                                          (                                                                            u                                                                                v                                                                      )                                              +                                    (                                                                    p                                          A                                                                                1                                                                          z                                +                                  p                                      B                                                                                1                                                              )                                                  (                                                                                r                        2                                            +                                              2                                                                          u                          2                                                                                2                                            u                                                                                v                                                                                )                                +                                    (                                                                    p                                          A                                                                                2                                                                          z                                +                                  p                                      B                                                                                2                                                              )                                                  (                                                                                2                                                                                u                                                                                v                                                                                r                        2                                            +                                              2                                                                          v                          2                                                                                )                                +                      (                                                                                Δ                                                                                u                        A                                                                  z                                        +                                          Δ                                                                                u                        B                                                                                Δ                                                                                v                        A                                                                  z                                        +                                          Δ                                                                                v                        B                                                                                )                                              {                  Expression                                                              6                }
Here, changes from Brown's model in Expression 5 to Expression 6 are as follows. (1) A term including a coefficient k0, which represents lateral magnification of pixel coordinates to world coordinates, is added. (2) Third-order radial distortion k1 and second-order tangential distortion (p1, p2) alone are taken into consideration. (3) Lateral translation (Δu, Δv) of the pixel coordinates with respect to the world coordinates is added.
Furthermore, Patent Literature 2 disclose a camera calibration algorithm for optimizing the rotation matrix R and the translation vector T in Expression 2 so as to minimize the residual error of the camera model in Expression 6.
Typically, in camera calibration, an image of a calibration chart having a plurality of feature points whose world coordinates (x, y, z) are known is captured with a camera. Subsequently, through image processing, pixel coordinates (u, v) at which the feature points are image-captured are acquired. In this way, a plurality of measurement data representing a correspondence between the world coordinates (x, y, z) and the pixel coordinates (u, v) are obtained, thereby obtaining the camera parameters.

Calibration device, calibration method, optical device, image-acquisition device, and projection device


Image forming apparatus includes a cleaning device for cleaning toner from a surface. Magnetic particulate cleaning material is moved through a cleaning zone by a rotating magnetic core. The particulate cleaning material moves on a surface which is extended generally in an upstream direction with respect to movement of the surface being cleaned. The extension increases the effectiveness of the cleaning without increasing pickup of the cleaning material by the surface.. An alternative cleaning device includes a magnetic shunt between a rotating core and a shell in which magnetic particulate cleaning material is driven by rotation of the core. The shunt interrupts the magnetic field of the core to increase the effectiveness of the cleaning without adversely affecting its softness.

This invention relates to a device for cleaning toner from a moving surface. Although not limited thereto, it is particularly usable in image forming apparatus in which a uniform layer of toner is applied to a surface, the toner is imagewise tacked to the surface and untacked toner is cleaned off the surface. It can also be used in conventional image forming apparatus.
U.S. patent application Ser. Nos. 07/632,698, now U.S. Pat. No. 5,138,388 (Kamp et al); 07/673,509 (DeBoer et al); 07/621,691, now abandoned (DeBoer et al); and PCT Application No. 91/08815, filed Nov. 26, 1991 disclose a process in which a uniform layer of toner is applied to a surface. The toner is imagewise tacked, preferably with a laser, to the surface and then the untacked toner is cleaned off the surface, leaving a toner image corresponding to the tacked toner. The tacked toner image can then be transferred to another surface, or it can be fixed to the surface to which it is tacked. This process can provide extremely high resolution and high density with fine toner particles and a precise laser. It does not require the use of light sensitive materials.
In this process, tacking can be accomplished by softening a heat softenable layer on the image surface, softening a toner particle where it touches the image surface, or both. Toner can be applied by a device comparable to that conventionally used to develop electrostatic images, for example, a magnetic brush development station. However, cleaning is somewhat more difficult, since the loose toner must be cleaned off without disturbing what may be quite lightly tacked imagewise toner. A preferable approach to this cleaning problem is to use a magnetic brush cleaner employing hard magnetic carrier particles and a rotating magnetic core which provides a relatively soft cleaning brush that will clean off the loose toner while leaving the lightly tacked toner image.
U.S. Pat. No. 4,797,704, granted to Hill et al Jan. 10, 1989, shows a magnetic brush development apparatus in which a rotating magnetic core drives developer, including a hard magnetized carrier around a noncylindrical shell. The shell is shaped to control the movement of the developer through an extended development or toning zone. The developer is moved in the same direction as an electrostatic image being developed, and the development zone is extended generally upstream with respect to that movement of the position at which the magnetic core is closest to the image. The shell curves rapidly away from the electrostatic image downstream of the core so that the magnetic field from the core can prevent pickup of the magnetized carrier by the electrostatic image. This extended zone has a tendency to increase the density of the image and thoroughness of the development. Some carrier pickup is tolerated to obtain thorough developing with this apparatus.
Other references which show extended development zones with rotating core development systems include U.S. Pat. No. 5,080,038, Rubin, Jan. 4, 1992; U.S. Pat. No. 4,235,549, Eisbein et al, Nov. 25, 1980; U.S. Pat. No. 4,287,850, Yamamoto et al, Sep. 8, 1981; Japanese Utility Model No. 51-164622, Laid-Open No. 53-81040, Jul. 5, 1978; and U.S. Pat. No. 4,804,994, Sasaki et al, Feb. 14, 1989.
U.S. Pat. No. 4,638,759, granted to Ville et al shows a rotating core magnetic brush development apparatus in which a magnetic shunt is positioned around a portion of the core to interrupt the magnetic field and alter the development characteristics of a two-component magnetic developer.

Cleaning device using magnetic particulate cleaning material


A method of increasing sterol accumulation in a plant by increasing the copy number of a gene encoding a polypeptide having HMG-CoA reductase activity is disclosed. The copy number is preferably increased by transforming plants with a recombinant DNA molecule comprising a vector operatively linked to an exogenous DNA segment that encodes a polypeptide having HMG-CoA reductase activity, and a promoter suitable for driving the expression of said polypeptide. Also disclosed are a method of increasing cycloartenol accumulation in a plant, a method of increasing the resistance of plants to pests and the transformed plants themselves.

Mevalonate (C.sub.6 H.sub.11 O.sub.4) is the metabolic precursor of a vast array of compounds vital for cell and organism viability. In plants, the major endproducts derived from mevalonate are the sterols and other isoprenoids. (see FIG. 1).
Exemplary plant isoprenoids include the terpenes (volatile C.sub.10 and C.sub.15 compounds giving rise to fragrances of many plants) the carotenoids (C.sub.40 compounds giving rise to the color of many plants) and polymers such as natural rubber.
Free sterols are constituents of virtually all eukaryotic membranes. The most abundant sterols of vascular plants are campesterol, 24-methylcholesterol, sitosterol and stigmasterol.
Mevalonate is formed from the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA). The reduction of HMG-CoA to mevalonate is catalyzed by the enzyme HMG-CoA reductase.
The HMG-CoA reductase enzymes of animals and yeasts are integral membrane glycoproteins of the endoplasmic reticulum. The intact enzyme comprises three regions: a catalytic region, containing the active site of the enzyme, a membrane binding region, anchoring the enzyme to the endoplasmic reticulum and a linker region, joining the catalytic and membrane binding regions of the enzymes. The membrane binding region occupies the NH.sub.2 -terminal portion of the intact protein, whereas the catalytic region occupies the COOH-terminal portion of the protein, with the linker region constituting the remaining portion. Basson, M. E. et al., Mol. Cell Biol., 8(9):3797-3808 (1988). At present, the sub-cellular localization of HMG-CoA reductase in plants is not known. Russell, D. W. et al., Current Topics in Plant Biochemistry, Vol. 4, ed. by D. D. Randall et al., Univ. of Missouri (1985).
The activity of HMG-CoA reductase in animals and yeasts is known to be subject to feedback inhibition by sterols. Such feedback inhibition requires the presence of the membrane binding region of the enzyme. See, e.g., Gil, G. et al., Cell, 41: 249-258(1985); Bard, M. and Downing, J. F. Journal of General Microbiology, 125:415-420(1981).
Given that mevalonate is the precursor for sterols and other isoprenoids, it might be expected that increases in the amount or activity of HMG-CoA reductase would lead to increases in the accumulation of both sterols and other isoprenoids. In yeasts and non-photosynthetic microorganisms, increases in HMG-CoA reductase activity are not associated with predictable increases in the production of sterols or other isoprenoids.
In mutant strains of the yeast Saccharomyces cerevisiae (S. cerevisiae) having abnormally high levels of HMG-CoA reductase activity, the production of two sterols, 4,14-dimethylzymosterol and 14-methylfecosterol, is markedly increased above normal. Downing, J. F. et al., Biochemical and Biophysical Research Communications, 94(3): 974-979(1980).
When HMG-CoA reductase activity was increased by illumination in non-photosynthetic microorganisms, isoprenoid (carotenoid), but not sterol (ergosterol), synthesis was enhanced. Tada, M. and Shiroishi, M. Plant and Cell Physiology, 23(4): 615-621(1982). There are no studies reporting the effects of such increases in HMG-CoA reductase activity in plants.

Method and composition for increasing sterol accumulation in higher plants


An immunoglobulin G Fc region binding polypeptide is provided, consisting of an amino acid sequence selected from i) a variant of Protein A domain or Protein Z and ii) an amino acid sequence which has at least 95% identity thereto. Also provided are methods for producing the polypeptide, compositions comprising the polypeptide, polynucleotides encoding the polypeptide, multimers of the polypeptide, and methods of using the polypeptide.

In the industrial production of monoclonal antibodies and Fc fusion proteins, purification is frequently carried out using chromatography. Protein A from Staphylococcus aureus has long been used as affinity ligand in such applications, due to the native affinity of Protein A for the Fc portion of IgG. Protein A in its entirety, as well as the five individual Fc-binding domains thereof, have subsequently served as starting points for the rational design of engineered affinity ligands with improved properties.
For example, the B domain of Protein A served as a starting point for the creation of the engineered, IgG Fc-binding, single-domain protein Z (Nilsson B et al, Protein Eng 1(2):107-13, 1987). In order to improve the stability of this protein in alkaline conditions, such as those employed in cleaning-in-place procedures during industrial chromatographic processes, Linhult et al (Proteins 55(2):407-16, 2004) proposed a variant of protein Z comprising mutated asparagine residues. This variant was further developed by GE Healthcare, Uppsala, Sweden, into the commercial product MAbSelect™ SuRe. Additional Z variants with IgG Fc affinity are disclosed in WO2009/146755.
Mutated binding proteins based on protein Z, in which the native IgG Fc binding has been modified, are described in WO2009/080811.
Native Protein A, with its five individual IgG Fc-binding domains, has been shown to bind only 2 molecules of IgG, or 3 molecules of recombinant Fc-fragment, despite the fact that each of the five domains has the capacity to bind one IgG (Birger Jansson, PhD Thesis, Stockholm, Sweden, 1996, ISBN 91-7170-656-9).
Despite the comparable success of currently used IgG Fc affinity ligands, there is a continued need for improvement, especially with regard to the combined requirements of improving stoichiometry and at the same time maintaining, and ideally improving, stability towards acidic and alkaline conditions. The continued provision of agents with affinity for IgG Fc remains a matter of substantial interest.

Immunoglobulin G Fc region binding polypeptide


The present invention provides a method for purifying chlorinated hydrocarbon(s), comprising cooling a mixture containing hydrogen fluoride and at least one chlorinated hydrocarbon selected from the group consisting of 2-chloro-3,3,3-trifluoropropene, 2,3-dichloro-3,3-difluoropropene, 1,2,3-trichloro-1,1-difluoropropane, and 1,1,1,2,3-pentachloropropane to cause liquid-liquid separation of the mixture into an upper liquid phase having a high hydrogen fluoride concentration and a lower liquid phase having a high chlorinated hydrocarbon concentration, and a method for purifying a chlorinated hydrocarbon, comprising subjecting the lower liquid phase obtained by the liquid-liquid separation to a distillation operation. According to the present invention, a chlorinated hydrocarbon can be purified by separating and removing hydrogen fluoride from a chlorinated hydrocarbon-hydrogen fluoride mixture under simple and economically advantageous conditions.

Various methods are known as a method for producing fluorinated halogenated hydrocarbons, which are used as blowing agents, cleaning agents, refrigerants, etc. In most of these methods, halocarbons or halogenated hydrocarbons are used as a starting material, and are highly fluorinated by fluorination or a hydrogen fluoride (HF) addition reaction.
In this case, as a method for fluorinating halocarbons or halogenated hydrocarbons, a method in which halocarbons or halogenated hydrocarbons as a starting material are reacted with HF is known (Patent Literature 1). As a specific method, there is, for example, a method in which halocarbons or halogenated hydrocarbons as a starting material and hydrogen fluoride (HF) are supplied to a reactor packed with a catalyst, and subjected to fluorination treatment to obtain a highly fluorinated halogenated hydrocarbon.
With regard to a method for producing CF3CCl═CH2 (HCFO-1233xf), for example, among these methods, various methods have been reported. A method has been reported in which CCl3CHClCH2Cl (HCC-240 db) is used as a starting material, and hydrogen fluoride (HF) is supplied in an amount exceeding the stoichiometric amount and reacted with the starting material (Patent Literature 2).
In this method, an outflow obtained from a reactor is a mixture containing not only the desired product, i.e., HCFO-1233xf, but also an equimolar or excess amount of HF relative to HCFO-1233xf. Furthermore, this product also contains, in addition to unreacted starting material HCC-240 db, other hydrochlorofluorocarbons as intermediates. To purify and use chlorinated hydrocarbons such as hydrochlorofluorocarbons including HCFO-1233xf, and starting material HCC-240 db from such a mixture, it is necessary to remove HF contained in the product. As a method therefor, a method in which a mixture containing chlorinated hydrocarbons and HF is treated with water or an alkali aqueous solution to absorb HF can be used. However, this method requires a large amount of water or alkali solution, resulting in the discharge of a large amount of industrial wastewater. It is thus undesirable in terms of environmental protection and production costs.
In addition, as another method for removing HF, there is a method in which HF is reacted with H2SO4 to collect HF as hydrofluoric-sulfuric acid. This method can be applied to removal of HF from a mixture of one or more chlorinated hydrocarbons and HF. However, in this method, the produced hydrofluoric-sulfuric acid is highly corrosive, and thus the materials of devices to be used are limited to highly corrosion-resistant materials. This leads to an increase in production costs.
Furthermore, in the case of the above method for removing HF, advanced technology is required to reuse the removed HF for a reaction. This leads to an increase in production costs even when the collected HF is recycled.

Method for purifying chlorinated hydrocarbon


The present invention is a system and method for sensing the voltage at multiple sense points. The present invention acquires optimal feedback from a plurality of sources including those integrated on the same motherboard, for populated or unpopulated connectors and for adapter cards plugged into the connectors, for the purpose of controlling the voltage regulator output. The voltage regulator, connected to a logic system, provides voltage to those connectors needing the voltage.

Large scale integration of electronic circuits continues to require lower voltages as the circuit dimensions keep dropping. Circuits that generally were designed with 5V circuits on early personal computers now are fed with circuits less than 1.5V, and the trend of lowering the voltage needs continues. As the frequency of operation continues to rise and circuit density increases, power needs have risen from a few watts per device to more than 100 watts for many devices. As voltage drops and power needs increase, current must go up. Future memory currents of 100A or more will not be uncommon in servers.
When voltages were at 5V, the noise margin was typically 0.8V to ground or above 2V to power. Current voltage levels are now less than noise levels used to be, hence a requirement for better accuracy in delivery power.
Newer chip and adapter technology, including new memory technology, have more voltages, lower voltages, higher currents and more loads than previously but do not provide an improved power delivery mechanism to compensate. For example, current art senses the voltage on the power plane of the motherboard in the area of memory connectors for feedback control and does not accurately reflect the losses through the memory connectors or on the memory card or the ability to account for dynamic configuration changes.
There presently is a need for a system and method for sensing the voltage at multiple sense points.

System and method for multiple sense point voltage regulation

International Business Machines Corporation