An objective of the invention is to provide anti-C5 antibodies and methods of using the same. The invention provides anti-C5 antibodies and methods of using the same. In some embodiments, an isolated anti-C5 antibody of the present invention binds to an epitope within the β chain of C5 with a higher affinity at neutral pH than at acidic pH. The invention also provides isolated nucleic acids encoding an anti-C5 antibody of the present invention. The invention also provides host cells comprising a nucleic acid of the present invention. The invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The invention further provides a method of producing an anti-C5 antibody comprising immunizing an animal against a polypeptide which comprises the MG1-MG2 domain of the β chain of C5. Anti-C5 antibodies of the present invention may be for use as a medicament. Anti-C5 antibodies of the present invention may be for use in treating a complement-mediated disease or condition which involves excessive or uncontrolled activation of C5. Anti-C5 antibodies of the present invention may be for use in enhancing the clearance of C5 from plasma.

The present invention relates to anti-C5 antibodies and methods of using the same. The complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus-infected cells and tumor cells. There are about 25-30 complement proteins, which are found as a complex collection of plasma proteins and membrane cofactors. Complement components achieve their immune defensive functions by interacting in a series of intricate enzymatic cleavages and membrane binding events. The resulting complement cascades lead to the production of products with opsonic, immunoregulatory, and lytic functions.
Currently, it is widely accepted that the complement system can be activated through three distinct pathways: the classical pathway, the lectin pathway, and the alternative pathway. These pathways share many components, and while they differ in their initial steps, they converge and share the same terminal complement components (C5 through C9) responsible for the activation and destruction of target cells.
The classical pathway is normally activated by the formation of antigen-antibody complexes. Independently, the first step in activation of the lectin pathway is the binding of specific lectins such as mannan-binding lectin (MBL), H-ficolin, M-ficolin, L-ficolin and C-type lectin CL-11. In contrast, the alternative pathway spontaneously undergoes a low level of turnover activation, which can be readily amplified on foreign or other abnormal surfaces (bacteria, yeast, virally infected cells, or damaged tissue). These pathways converge at a point where complement component C3 is cleaved by an active protease to yield C3a and C3b.
C3a is an anaphylatoxin. C3b binds to bacterial and other cells, as well as to certain viruses and immune complexes, and tags them for removal from the circulation (the role known as opsonin). C3b also forms a complex with other components to form C5 convertase, which cleaves C5 into C5a and C5b.
C5 is a 190 kDa protein found in normal serum at approximately 80 μg/ml (0.4 μM). C5 is glycosylated with about 1.5-3% of its mass attributed to carbohydrate. Mature C5 is a heterodimer of 115 kDa α chain that is disulfide linked to 75 kDa β chain. C5 is synthesized as a single chain precursor protein (pro-C5 precursor) of 1676 amino acids (see, e.g., U.S. Pat. Nos. 6,355,245 and 7,432,356). The pro-C5 precursor is cleaved to yield the β chain as an amino terminal fragment and the α chain as a carboxyl terminal fragment. The alpha chain and the beta chain polypeptide fragments are connected to each other via a disulfide bond and constitute the mature C5 protein.
Mature C5 is cleaved into the C5a and C5b fragments during activation of the complement pathways. C5a is cleaved from the α chain of C5 by C5 convertase as an amino terminal fragment comprising the first 74 amino acids of the α chain. The remaining portion of mature C5 is fragment C5b, which contains the rest of the α chain disulfide bonded to the β chain. Approximately 20% of the 11 kDa mass of C5a is attributed to carbohydrate.
C5a is another anaphylatoxin. C5b combines with C6, C7, C8 and C9 to form the membrane attack complex (MAC, C5b-9, terminal complement complex (TCC)) at the surface of the target cell. When sufficient numbers of MACs are inserted into target cell membranes, MAC pores are formed to mediate rapid osmotic lysis of the target cells.
As mentioned above, C3a and C5a are anaphylatoxins. They can trigger mast cell degranulation, which releases histamine and other mediators of inflammation, resulting in smooth muscle contraction, increased vascular permeability, leukocyte activation, and other inflammatory phenomena including cellular proliferation resulting in hypercellularity. C5a also functions as a chemotactic peptide that serves to attract granulocytes such as neutrophils, eosinophils, basophils and monocytes to the site of complement activation.
The activity of C5a is regulated by the plasma enzyme carboxypeptidase N that removes the carboxy-terminal arginine from C5a forming C5a-des-Arg derivative. C5a-des-Arg exhibits only 1% of the anaphylactic activity and polymorphonuclear chemotactic activity of unmodified C5a.
While a properly functioning complement system provides a robust defense against infecting microbes, inappropriate regulation or activation of complement has been implicated in the pathogenesis of a variety of disorders including, e.g., rheumatoid arthritis (RA); lupus nephritis; ischemia-reperfusion injury; paroxysmal nocturnal hemoglobinuria (PNH); atypical hemolytic uremic syndrome (aHUS); dense deposit disease (DDD); macular degeneration (e.g., age-related macular degeneration (AMD)); hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; thrombotic thrombocytopenic purpura (TTP); spontaneous fetal loss; Pauci-immune vasculitis; epidermolysis bullosa; recurrent fetal loss; multiple sclerosis (MS); traumatic brain injury; and injury resulting from myocardial infarction, cardiopulmonary bypass and hemodialysis (see, e.g., Holers et al., Immunol. Rev. 223:300-316 (2008)). Therefore, inhibition of excessive or uncontrolled activations of the complement cascade can provide clinical benefits to patients with such disorders.
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon blood disorder, wherein red blood cells are compromised and are thus destroyed more rapidly than normal red blood cells. PNH results from the clonal expansion of hematopoietic stem cells with somatic mutations in the PIG-A (phosphatidylinositol glycan class A) gene which is located on the X chromosome. Mutations in PIG-A lead to an early block in the synthesis of glycosylphosphatidylinositol (GPI), a molecule which is required for the anchor of many proteins to cell surfaces. Consequently, PNH blood cells are deficient in GPI-anchored proteins, which include complement-regulatory proteins CD55 and CD59. Under normal circumstances, these complement-regulatory proteins block the formation of MAC on cell surfaces, thereby preventing erythrocyte lysis. The absence of the GPI-anchored proteins causes complement-mediated hemolysis in PNH.
PNH is characterized by hemolytic anemia (a decreased number of red blood cells), hemoglobinuria (the presence of hemoglobin in urine, particularly evident after sleeping), and hemoglobinemia (the presence of hemoglobin in the bloodstream). PNH-afflicted individuals are known to have paroxysms, which are defined here as incidences of dark-colored urine. Hemolytic anemia is due to intravascular destruction of red blood cells by complement components. Other known symptoms include dysphasia, fatigue, erectile dysfunction, thrombosis and recurrent abdominal pain.
Eculizumab is a humanized monoclonal antibody directed against the complement protein C5, and the first therapy approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) (see, e.g., Dmytrijuk et al., The Oncologist 13(9):993-1000 (2008)). Eculizumab inhibits the cleavage of C5 into C5a and C5b by C5 convertase, which prevents the generation of the terminal complement complex C5b-9. Both C5a and C5b-9 cause the terminal complement-mediated events that are characteristic of PNH and aHUS (see also, WO 2005/074607, WO 2007/106585, WO 2008/069889, and WO 2010/054403).
Several reports have described anti-C5 antibodies. For example, WO 95/29697 described an anti-C5 antibody which binds to the α chain of C5 but does not bind to C5a, and blocks the activation of C5, while WO 2002/30985 described an anti-C5 monoclonal antibody which inhibits C5a formation. On the other hand, WO 2004/007553 described an anti-C5 antibody which recognizes the proteolytic site for C5 convertase on the α chain of C5, and inhibits the conversion of C5 to C5a and C5b. WO 2010/015608 described an anti-C5 antibody which has an affinity constant of at least 1×107 M−1.
Antibodies (IgGs) bind to neonatal Fc receptor (FcRn), and have long plasma retention times. The binding of IgGs to FcRn is typically observed under acidic conditions (e.g., pH 6.0), and it is rarely observed under neutral conditions (e.g., pH 7.4). Typically, IgGs are nonspecifically incorporated into cells via endocytosis, and return to the cell surfaces by binding to endosomal FcRn under the acidic conditions in the endosomes. Then, IgGs dissociate from FcRn under the neutral conditions in plasma. IgGs that have failed to bind to FcRn are degraded in lysosomes. When the FcRn binding ability of an IgG under acidic conditions is eliminated by introducing mutations into its Fc region, the IgG is not recycled from the endosomes into the plasma, leading to marked impairment of the plasma retention of the IgG. To improve the plasma retention of IgGs, a method that enhances their FcRn binding under acidic conditions has been reported. When the FcRn binding of an IgG under acidic conditions is improved by introducing an amino acid substitution into its Fc region, the IgG is more efficiently recycled from the endosomes to the plasma, and thereby shows improved plasma retention. Meanwhile, it has also been reported that an IgG with enhanced FcRn binding under neutral conditions does not dissociate from FcRn under the neutral conditions in plasma even when it returns to the cell surface via its binding to FcRn under the acidic conditions in the endosomes, and consequently its plasma retention remains unaltered, or rather, is worsened (see, e.g., Yeung et al., J Immunol. 182(12): 7663-7671 (2009); Datta-Mannan et al., J Biol. Chem. 282(3):1709-1717 (2007); Dall'Acqua et al., J. Immunol. 169(9):5171-5180 (2002)).
Recently, antibodies that bind to antigens in a pH-dependent manner have been reported (see, e.g., WO 2009/125825 and WO 2011/122011). These antibodies strongly bind to antigens under the plasma neutral conditions and dissociate from the antigens under the endosomal acidic conditions. After dissociating from the antigens, the antibodies become capable once again of binding to antigens when recycled to the plasma via FcRn. Thus, a single antibody molecule can repeatedly bind to multiple antigen molecules. In general, the plasma retention of an antigen is much shorter than that of an antibody that has the above-mentioned FcRn-mediated recycling mechanism. Therefore, when an antigen is bound to an antibody, the antigen normally shows prolonged plasma retention, resulting in an increase of the plasma concentration of the antigen. On the other hand, it has been reported that the above-described antibodies, which bind to antigens in a pH-dependent manner, eliminate antigens from plasma more rapidly than typical antibodies because they dissociate from the antigens within the endosomes during the FcRn-mediated recycling process. WO 2011/111007 also described computer modeling analysis showing that an antibody with pH-dependent binding directed against C5 could extend antigen knockdown.

Method of detecting the presence of complement C5


A baffled muzzle brake and seal system for submerged gun operation includes a muzzle brake chamber mounted to the muzzle of a submerged gun barrel. A baffle assembly mounted within the chamber deflects the propellant gasses produced by operation of the gun and sabot fragments into an annular cher surrounding the baffle assembly while allowing passage of a projectile through the assembly. A valve seal in the muzzle end of the muzzle brake chamber cycles between a fully open condition, to allow passage of the projectile, and a fully closed position, to seal the muzzle brake chamber against the entry of water. At least one pressurized air input allows the muzzle brake chamber to be pressurized when the seal is not in the fully closed position, thereby preventing entry of water. A gas exhaust provides a means for removing propellant gasses from the chamber.

(1) Field of the Invention
The present invention relates to underwater guns and more specifically, to apparatus for preventing the entry of water into an underwater gun, for capturing a sabot, and for managing the propellant gases produced by firing the gun.
(2) Description of the Prior Art
Various underwater guns have been developed that utilize an explosive charge that must be kept dry and in the presence of air for proper detonation. Generally, such guns have utilized a single-use seal to prevent entry of water into either the gun or into a cartridge containing the explosive charge.
U.S. Pat. No. 3,585,934 discloses a disposable ammunition having a watertight barrel that is removably mounted into a carrier cylinder or block for firing. A head end cap assembly seals the breech end of the barrel and a closure cup seals the muzzle end of the barrel to provide a watertight enclosure. A propellant charge disposed in the barrel is ignited to propel a flechette from the barrel. The closure cup is destroyed as the flechette exits the barrel. Once the ammunition is fired, the barrel is removed and replaced with an unfired ammunition.
U.S. Pat. Nos. 4,651,454 and 4,742,775 each disclose a spear gun having a chamber in its breech for receiving an explosive power load. The power load has a closed end that is adapted to open when the propellant explodes. The closed end is sealed with a sealing compound to prevent the entry of water. Once the power load has been fired, the breech is opened and the spent power load is replaced with a new power load. A plurality of circumferential grooves in the breech end of the spear serve as pressure interrupters or dynamic seals to interfere with and inhibit the escape of the detonation gases within the barrel of the spear gun. Water is free to enter both the barrel and the breech of the spear gun.
It is also well known to provide projectiles in firearms with a sabot surrounding the projectile to enhance the projectile's muzzle velocity. Often this sabot is stripped away from the projectile during launch by the firearm thereby changing the projectile's flight characteristics.
The single use sealing systems of the prior art devices require replacement of the seal each time the underwater gun is fired. The seal is generally a part of a sealed unit such as the power load or ammunition discussed above. Therefore, replacement of the seal requires replacement of a larger structure. Consequently, such apparatus is limited in use to applications that allow access to this sealed unit. In addition, the time required to replace the sealed unit limits the speed at which multiple projectiles may be fired, and the prior art devices are either limited to single shot applications or require the use of multiple sealed units to permit rapid firing of multiple projectiles. Generally, the number of sealed units that can be supported is limited, thereby limiting the total number of projectiles that may be fired. Finally, prior art underwater guns do not control the propellant gasses once the projectile has been launched. The introduction of the propellant gasses into the surrounding water reduces the performance of the projectiles.

Baffled muzzle brake and seal system for submerged gun operation

The United States of America as represented by the Secretary of the Navy


A wheel suspension for a motor vehicle has a transverse control arm that can be attached to a vehicle body by way of bearings and a spring-elastic torsion bar assembly, and can be rotated about a longitudinal axis. The torsion bar assembly has a body spring that can be attached to the vehicle body with one end, and a transverse control arm spring that is attached to the transverse control arm with one end. The body spring and the transverse control arm spring are coupled with one another at their free ends. The transverse control arm spring and the body spring are coupled with one another by way of a setting element or a releasable connection, whereby the setting element or the releasable connection, respectively, allows rotation of the ends assigned to one another, for setting purposes.

1. Field of the Invention
The present invention relates to a wheel suspension for a motor vehicle, having a transverse control arm that can be attached to a vehicle body by way of bearings and a spring-elastic torsion bar assembly, and can be rotated about a longitudinal axis. The torsion bar assembly has a body spring that can be attached to the vehicle body with one end, and a transverse control arm spring that is attached to the transverse control arm with one end. The body spring and the transverse control arm spring are coupled with one another at their free ends. The wheel suspension is particularly provided as a single-wheel suspension, on at least one axle of a passenger car or a utility vehicle.
2. The Prior Art
A wheel suspension having the characteristics described initially is known from the reference DE 38 31 338 A1. Both the body spring and the transverse control arm spring are configured in tubular shape, as torsion bar springs, and are disposed coaxially, whereby the transverse control arm spring surrounds the body spring and whereby the torsion bar springs are rigidly connected at their free ends, by way of a coupling point.
At the opposite ends of the torsion bar springs, the body spring is connected with the vehicle body, and the transverse control arm spring is connected with the transverse control arm. A device that can be hydraulically activated is disposed between the coupling point and the transverse control arm, for adjusting the angle of rotation. This device makes it possible to actively adjust the spring force of the torsion bar assembly as a function of the driving situation. While the weight force that acts on the wheel suspension is essentially absorbed by the torsion bar assembly, the device for adjusting the angle of rotation makes it possible, proceeding from a normal position of the torsion rod assembly in the stressed state, to perform an active adjustment with comparatively small setting moments. In the force-free state of the device for adjusting the angle of rotation, the wheel height of a wheel attached to a vehicle with the wheel suspension is obtained, on the one hand, from the weight force that acts on the wheel suspension, and, on the other hand, from the spring-elastic properties of the torsion rod assembly.

ThyssenKrupp Presta München/Esslingen GmbH


Perfluorinated cycloalkanes, perfluorinated aromatic compounds and perfluorotrialkyl amines having a critical temperature greater than 150.degree. C. are solvents for certain carboxylic fluorinated polymers having an equivalent weight greater than 900 and dissolve the polymers more readily and completely at low temperatures than previously known solvents. A process for dissolution of the polymers and the solutions that are formed is disclosed. The solutions are useful for making polymer films and ion exchange membranes, particularly membranes for use in chloroalkali cells or fuel cells.

1. Field of the Invention
Novel perfluoro cycloalkane, perfluorinated aromatic compounds and perfluorotrialkyl amine solvents for dissolving fluorinated polymers having carboxyl groups and an equivalent weight greater than 900 are disclosed. The solvents have a critical temperature greater than 150.degree. C. Also disclosed are solutions of the polymers in the solvents, and a process for forming the polymer solution.
2. Technical Background
This invention concerns novel solvents for dissolving certain alkyl carboxylate forms of fluorinated polymers which are copolymers of tetrafluoroethylene ("TFE") and certain perfluorovinylether comonomers. The solvents readily dissolve such polymers more completely and at lower temperatures than previously disclosed solvents, an advantage in equipment utilization and other manufacturing concerns. Solutions of the polymers are particularly useful for preparing ion exchange membranes, including membranes for use in an electrolytic cell such as a chloralkali cell or a fuel cell.
The prior art generally discloses the solubility of certain fluorinated polymers but there is no mention of full solutions of carboxylic fluorinated polymers having high equivalent weights in this class of inventive solvents, particularly at low temperatures.
Some solvents are known in the prior art for this class of carboxylic fluorinated polymers; however, some of the solvents are very expensive or require high temperature to dissolve the polymer. The prior art teaches solvents for carboxylic fluorinated polymers with equivalent weights below about 900 and solvents for such polymers which require elevated temperatures or pressures. There is no teaching of a solvent for the ester form of carboxylic fluorinated polymers with an equivalent weight greater than 900 at low temperatures.
For example, U.S. Pat. Nos. 4,650,551; 4,778,723 and 4,784,900 disclose solutions near room temperature of highly swollen dispersions of resins which are copolymers of TFE and perfluorovinylether comonomers with acidic end groups having low equivalent weights less than 850. Heavily fluorinated alkanes, like 1,2-dibromotetrafluoroethane and 1,1,2-trichlorotrifluoroethane were used as "solvents". Examples of room temperature solutions were also given using polyhalogenated alkyl ethers with boiling points less than 190.degree. C.; the equivalent weight for these resins was exceedingly low at 690 or lower.
Fluorinated polymer resins commercially known as Nafion.RTM. (available from E. I. du Pont de Nemours and Company) with an equivalent weight greater than about 1000, must be dissolved at elevated temperatures and pressures due to the presence of crystallinity. U.S. Pat. Nos. 4,266,036; 4,272,560 and 4,298,697 discuss the use of high boiling perhalogenated alkyl ethers and perhalogenated alkanes as solvents at elevated temperatures. The examples describe the dissolution of 1050 to 1200 equivalent weight resins in oligomers of chlorotrifluoroethylene ("CTFE") at temperatures of about 225.degree. to 250.degree. C.; however, the polymers are more likely to decarboxylate at high temperatures. Chemical degradation of the polymer may occur in solutions of CTFE oligomer at 200.degree. C.
U.S. Pat. No. 4,535,112 describes dispersions or partial solutions of 1050 to 1200 equivalent weight polymers in a wide variety of heavily fluorinated liquids for purposes of repairing cation exchange membranes. These liquids include perfluorodecanoic acid, perfluorotributylamine, pentafluorophenol, pentafluorobenzoic acid, perfluoro-1-methyldecalin and decafluorobiphenyl. There is no mention of full solutions of carboxylic fluorinated polymers having high equivalent weights at low temperatures.
An article entitled "Solubility Characteristics of Perfluorinated Polymers with Sulfonyl Fluoride Functunality" by McCain and Covitch discusses the solubility of so-called sulfonyl fluorinated polymers, but does not mention alkyl carboxylate forms of fluorinated polymers.


The present invention is directed to an immersion lithography proximity sensor having a nozzle shroud with a flow curtain. The immersion lithography proximity sensor includes a shroud that affixes to the nozzle. A plenum is located inside the shroud that holds a shroud liquid, which is fed into the plenum through one or more intake holes. The shroud liquid is emitted out through a series of openings, such as holes or slots, along a bottom surface of the shroud in a direction away from the nozzle. The shroud liquid that is emitted forms a curtain around the nozzle to prevent cross currents from impacting the flow of liquid out of the nozzle.

1. Field of the Invention
The present invention relates to lithography, and more particularly, to immersion lithography proximity gauges.
2. Background of Invention
Many automated manufacturing processes require the sensing of the distance between a manufacturing tool and the product or material surface being worked. In some situations, such as semiconductor lithography, the distance must be measured with accuracy approaching a nanometer.
The challenges associated with creating a proximity sensor of such accuracy are significant, particularly in the context of photolithography systems. In the photolithography context, in addition to being non-intrusive and having the ability to precisely detect very small distances, the proximity sensor can not introduce contaminants or come in contact with the work surface, typically a semiconductor wafer. Occurrence of either situation may significantly degrade or ruin the semiconductor quality.
Different types of proximity sensors are available to measure very small distances. Examples of proximity sensors include capacitance and optical gauges. These proximity sensors have serious shortcomings when used in photolithography systems because physical properties of materials deposited on wafers may impact the precision of these devices. For example, capacitance gauges, being dependent on the concentration of electric charges, can yield spurious proximity readings in locations where one type of material (e.g., metal) is concentrated. Another class of problems occurs when exotic wafers made of non-conductive and/or photosensitive materials, such as Gallium Arsenide (GaAs) and Indium Phosphide (InP), are used. In these cases, capacitance and optical gauges may provide spurious results.
Commonly owned U.S. patent application, Ser. No. 10/322,768, entitled High Resolution Gas Gauge Proximity Sensor, filed Dec. 19, 2002 by Gajdeczko et al., ("'768 patent application") describes a high precision gas gauge proximity sensor that overcomes some of the precision limitations of earlier air gauge proximity sensors. The 768 patent application, which is incorporated herein in its entirety, describes a gas gauge proximity sensor that provides a high degree of accuracy. Similarly, commonly owned U.S. patent application, Ser. No. 10/683,271, entitled Liquid Flow Proximity Sensor for Use in Immersion Lithography, filed Oct. 14, 2003, by Violette, Kevin, ("'271 patent application") describes a high precision immersion lithography proximity sensor that provides a high degree of precision in an immersion lithography application. The '768 patent application issued as U.S. Pat. No. 7,010,958 on Mar. 14, 2006. The '271 patent application issued as U.S. Pat. No. 7,021,119 on Apr. 4, 2006.
Co-pending, commonly owned U.S. patent application, Ser. No. 10/322,768, entitled High Resolution Gas Gauge Proximity Sensor, filed Dec. 19, 2002 by Gajdeczko et al., ("'768 patent application") describes a high precision gas gauge proximity sensor that overcomes some of the precision limitations of earlier air gauge proximity sensors. The 768 patent application, which is incorporated herein in its entirety, describes a gas gauge proximity sensor that provides a high degree of accuracy. Similarly, co-pending, commonly owned U.S. patent application, Ser. No. 10/683,271, entitled Liquid Flow Proximity Sensor for Use in Immersion Lithography, filed Oct. 14, 2003, by Violette, Kevin, ("'271 patent application") describe a high precision immersion lithography proximity sensor that provides a high degree of precision in an immersion lithography application.
While the sensors disclosed in the '768 and '271 patent applications provide a high degree of precision, the precision can be impacted by cross flows of gas or liquid that intersect the stream of gas or liquid that is being emitted from a measurement channel of the proximity sensor. Specifically, purging gases, for example, can exhibit local cross winds with velocities of the order of a few meters per second. Cross-winds or cross-flows will cause gauge instability and drift, introducing non-calibratable errors within proximity sensors.
What is needed is an apparatus to neutralize these cross-flows, and in the case of immersion lithography, cross currents, to improve the accuracy of proximity sensors.

This patent is subject to a terminal disclaimer.

Immersion lithography proximity sensor having a nozzle shroud with flow curtain


A peak flow meter is described with a body having a sample channel and at least one bypass channel. One of at least two flow range scales may be selected using a flow range selector to adjust the sensitivity of the peak flow meter. A flow range selection indicator provides visual reference as to which flow range scale has been selected. A peak flow calculator used in cooperation with zone indicators on the peak flow meter permits a user to customize the peak flow meter for that user's predicted personal best exhalation range.

Peak flow meters are used for measuring the peak air flow of a patient's exhalation. Peak flow meters permit physicians to track changes in the patient's respiratory condition and diagnose potential or existing breathing problems. Patients may also use peak flow meters outside of a doctor's office to monitor their own condition on a regular basis.
A challenge for manufacturers of peak flow meters is to provide a reliable and accurate device that consumers can afford. Accuracy, particularly in lower flow ranges, can be a problem in full range peak flow meters, such as those that provide measurements over the range of approximately 20-800 liters per minute (L/min). Also, current peak flow meter performance guidelines related to the accuracy of how peak flow meters respond to certain defined impulse waveforms (representative of the initial impulse of airflow into a peak flow meter expected from a patient) may be difficult for existing peak flow meters to achieve.
Accordingly, there is a need for a peak flow meter that provides detailed, accurate information and is simple to set up and use.


Use of a cannabidiol for the manufacture of a medicament identified for the treatment or prevention of diabetes and/or insulitis.

The present invention relates to the use of a cannabidiol for treating or preventing diabetes and related disorders.
Diabetes is a disease characterized by failure of insulin feedback and secretion in the beta cells of the pancreatic islets of Langerhans and is one of the most common endocrine diseases across all age groups and populations. The most obvious metabolic effect in diabetes is chronic, erratic elevation of the blood glucose level which is associated with progressive damage to blood vessels. This may lead to heart attack, stroke, blindness, peripheral nerve dysfunction, and kidney failure. Presently there are 18.2 million people in the United States alone who have diabetes. In addition to the clinical morbidity and mortality, the economic cost of diabetes is huge, exceeding $90 billion per year in the United States alone, and the prevalence of diabetes is expected to increase more than two-fold by the year 2010.
There are two major forms of diabetes mellitus: insulin-dependent (Type I) diabetes mellitus which accounts for 5 to 10% of all cases, and non-insulin-dependent (Type II) diabetes mellitus which comprises roughly 90 to 95% of cases.
Type I diabetes mellitus is an autoimmune disease characterized by progressive destruction of pancreatic beta-cells and most often occurring in children and young adults. The disease is associated with high rate of severe irreversible complications which occur despite the availability of insulin replacement, usually through injections administered 1-4 times daily.
Most therapeutic strategies for treatment or prevention of type I diabetes mellitus are directed to suppression of the autoimmune response in order to prevent beta-cell destruction. Accordingly, various immunosuppressive agents have been considered for preventing destruction of pancreatic beta-cells have been attempted, such as glucocorticoids, cyclophosphamide, cyclosporin A, rapamycin, FK506 and prodigiosin. However, the use of such immunosuppressive agents may cause severe side effects such as drug-related toxicity to liver or kidney and to increase incidence of infectious complications, particularly in patients with diabetes mellitus that are already susceptible to infections as part of their disease.
Type II diabetes results from a loss of insulin production combined with body's inability to properly use insulin, and is oftentimes associated with aging. In Type II diabetes, patients typically begin therapy by following a regimen of an optimal diet, weight reduction and exercise. Drug therapy is initiated when these measures no longer provide adequate metabolic control. Initial drug therapy includes sulfonylureas (for example, tolbutamide, chlorpropamide and glibenclamide), biguanides (for example, metformin and buformin) and α.-glucosidase inhibitors (for example, acarbose and voglibose). However, over 50% of all diabetics treated by presently available drugs demonstrate poor glycemic control within six years, and require insulin replacement therapy as the last resort.
Although many of the symptoms of diabetes mellitus may be controlled by insulin therapy, the long-term complications of both type I and type II diabetes mellitus are severe and may reduce life expectancy by as much as one third. Over time, elevated blood glucose levels damage blood vessels, the heart, eyes, kidneys, nerves, autonomic nervous system, skin, connective tissue, and white blood cell function.
Moreover, insulin therapy may result in insulin allergy, insulin resistance, atrophy of the subcutaneous fat at the site of insulin injection (i.e., lipoatrophy), enlargement of subcutaneous fat deposit (i.e., lipohypertrophy) due to lipogenic action of high local concentration of insulin, and insulin edema.
There is thus a widely recognized need for, and it would be highly advantageous to have new, safe and effective therapies for diabetes mellitus. Accordingly, the present invention provides a novel method and an article of manufacture for treating or preventing diabetes mellitus and related disorders.

Treating or preventing diabetes with cannabidiol

Yissum Research Development Company of the Hebrew University of Jerusalem

Hadsit Hadasit Medical Research Services and Development Ltd.


Organic white-light-emitting blend materials were prepared by light-doping method and electroluminescent devices fabricated using the same, including a transparent substance, translucent electrode, white-light-emitting layer and metal electrode in order, can efficiently control Förster energy transfer in organic light-emitting materials by performing light doping, thus to fabricate a white electroluminescent device using the blend materials which can emit white-light with high efficiency. The white-light-emitting blend materials can be obtained by the light-doping method, in which the energy transfer occurs only between a host which is a donor and each dopant which is an acceptor, while the energy transfers between dopants are efficiently blocked.

1. Field of the Invention
The present invention relates to organic materials for white-light-emitting and an organic electroluminescent device including a light-emitting layer made of the materials. The organic/polymer white-emitting devices are easy to form a film from a solution by spin casting and emit light under electric field. Thus, the device fabricated by using the materials can be applied to the back light of liquid crystal displays, lighting devices, or color flat panel displays.
2. Description of the Background Art
A white electroluminescent device using low molecular weight materials or polymer materials has been fabricated by mainly two methods. First, there is a method of manufacturing a multilayered device composed of a number of materials which emit lights of R, G and B colors, as carried out by Kido et al. [J. Kido, M. Kimura, K. Nagai, Science, 267, p 1332 (1995)], Xie et al. [Z. Y. Xie, Y. Liu, J. S. Huang, Y. Wang, C. N. Li, S. Y. Liu, J. C. Chen, Synth. Met. 106, p 71 (1999)], Ogura et al. [T. Ogura, T. Yamashita, M. Yoshida, K. Emoto, S. Nakajima, U.S. Pat. No. 5,283,132], and Deshpande et al. [R. S. Deshpande, V. Bulovic, S. R. Forrest, Appl. Phys. Lett. 75, p 888 (1999)]. In this method, it is difficult to form a multi-layered thin film and a white-emission can be obtained by trial and error to determine the thickness of each layer. In addition, disadvantageously the emission color may change depending on the applied voltage.
The other method is doping or blending organic luminescence colorant in luminescent host substances, as carried out by Granström et al. [M. Granström, O. Inganäs, Appl. Phys. Lett. 68, p 147. (1996)], Kido et al. [J. Kido, H. Shionoya, K. Nagai, Appl. Phys. Lett. 67, 2281 (1995)], Shi et al. [J. Shi, C. W. Tang, U.S. Pat. No. 5,683,823], and Chen et al. [S.-A. Chen, E.-C. Chang, K.-R. Chuang, U.S. Pat. No. 6,127,693]. Although the process in this method is simpler than the first method, a white-emission can be obtained by repeating trial and errors without a governing principle. Particularly, when blending or doping components have excellent miscibility between them, due to energy transfer from high-bandgap components to low-bandgap components, the spectrum of the host material may be largely varied depending on blending or doping level. Thus, it is difficult to predict the final emission spectrum. Particularly, when three or more components are blended to prepare a white-light-emitting material, it is more difficult to control energy transfer between the components. Successful white-light-emission depends on how energy transfer between the components to be blended is efficiently controlled.

Methods of determining a composition ratio of an organic white-light-emitting blend material

Korea Institute of Science and Technology


Provided is a method applicable to the production of silicon wafers having crystal orientation <100> or <110> and consisting in specifying wafer-supporting positions on the occasion of heat treatment in a vertical heat treatment furnace as well as a heat treatment jig for use in carrying out that method. It becomes possible to suppress the shear stress which contributes to the extension of the slip generated at each wafer-supporting element contact point as an initiation, suppress slip growth and thus markedly improve the yield of heat-treated silicon wafers. The heat-treated wafer obtained by using the supporting method and the heat treatment jig has few slip, in particular has no long and large slip, and is high in quality.

In the process for silicon wafer production, there are a number of steps in which silicon wafers directly contacted and supported on their back sides by a supporting member are subjected to heat treatment. For example, a heat treatment step using a vertical boat, an RTA (rapid thermal annealing) step, a single-feed type epitaxial growth step and an SOI heat treatment step are relevant, and in such many heat treatments, silicon wafers directly contacted and supported on their back sides by a supporting member are subjected to various processes.
For example, in the heat treatment of silicon wafers in a vertical batch-wise heat treatment furnace, use is made of a wafer supporter (hereinafter referred to as "supporting boat"), as shown in FIG. 1, which supports each wafer at three or four points in an outer peripheral portion on the back of the wafer. Thus, the supporting boat 1 comprises three or four columns 3, a top end plate 5 and a bottom end plate 6 that respectively are attached to the upper and lower ends of the columns 3, and a sideways opening 2. Each of the columns 3 has a row of wafer-supporting elements 4 and, after placing silicon wafers on such supporting elements 4 through the sideways opening 2, the whole boat is inserted into a vertical heat treatment furnace for each intended heat treatment.
However, when silicon wafers are placed on such supporting boat and subjected to heat treatment, a problem is encountered; namely, crystal defects called slip initiating from the damage incurred at the point of contact between the wafer and each supporting element surface may appear in each silicon wafer, and such slip grows and develops under the influence of the thermal stress caused during heat treatment, with the result that a wafer yield is decreased. In the case of wafers having a diameter of 300 mm or larger, such slip growth and extension may also be caused by the stress resulting from the wafer's own weight (gravity stress).
As a means for solving such problem, there is known a wafer supporting jig in which an area of contact between each wafer and each supporting element is widened so that the load incurred by the wafer's own weight may be dispersed and the gravity stress may be reduced as much as possible.
However, a groove (corresponding to a gap between surfaces of two neighboring wafer supporting elements 4 in the supporting boat shown in FIG. 1) in this supporting jig should have different machining accuracy or induce different contact surface conditions (flatness and surface roughness) and, for some grooves, the stress incurred by wafer's own weight may not be dispersed all over the contact surface but may be concentrated at a specific position, for example single point, and this contact point may act as an initiation point for slip generation.
For avoiding the state such that the contact point may act as an initiation point for slip generation in the wafer supporting jig, control is made so that each wafer may come into contact with the whole relevant surface of each supporting element at each groove; however, this is actually difficult. Thus, the supporting jig having an increased wafer-supporting contact area cannot be said to exhibit a satisfactory slip inhibiting effect.
On the other hand, it is known with regard to silicon crystals that the stress contributing to slip extension varies depending on the crystal orientation. Japanese Patent Application Publication (Kokai) No. Hei 09-139352 discloses an invention concerning a wafer boat for a vertical furnace by which stress generation by wafer's own weight can be reduced; in this document, the calculation of critical shear stresses upon application of a predetermined thermal stress to a silicon wafer are made for twelve crystal slip systems governing slip generation in silicon wafers.
According to those results, along the crystal orientations <110> and <100>, slip generation hardly occurs, and it is concluded that the slip generation can be suppressed by supporting the wafer having crystalline (001) face in a direction of the crystal orientation <100> or <110> on its back side.
However, even if this technology is utilized to suppress slip generation, it is difficult to suppress slip growth using the above-mentioned wafer supporting jig having an increased wafer-supporting contact area in the support since the crystal orientation varies according to directions on the wafer surface and the stress (shear stress) contributing to slip extension varies accordingly and the wafer-supporting element contact point which acts as an initiation point for the slip cannot be singled out.
This problem of slip generation is not limited to a vertical batch-wise heat treatment furnace but common to processes in which wafers locally supported on their back sides are subjected to heat treatment, for example in a single-feed type heat treatment furnace or epitaxial growth treatment furnace.

Silocon wafer supporting method, heat treatment jig and heat-treated wafer


This invention relates to a skin model system that can be used as an in vitro test system or which can be used for therapeutic purposes. The skin model system comprises a three-dimensional, cross-linked matrix of insoluble collagen containing fibroblast cells therein, and stratified layers of differentiated epidermal cells supported thereon.

For some time, there has been a move to develop an artificial skin that can be used (1) for wound healing and the repair of ulcerated, burned or lacerated skin, and (2) as a model to test substances for irritation, toxicity, inflammation and pharmacology so as to reduce the number of tests using live animals. This latter application for artificial skin is commonly referred to as an in vitro alternative to animal testing.
Berg and colleagues (U.S. Pat. Nos. 4,703,108 and 4,970,298, the disclosures of which are herein incorporated by reference) have developed a biocompatible, chemically crosslinked, three-dimensional collagen matrix as a substitute for the dermal layer of the skin where it promotes fibroblast ingrowth and proliferation when implanted into animals (Doillon, et al., "Fibroblast-collagen sponge interactions and the spatial deposition of newly synthesized collagen fibers in vitro and in vivo," J. Scanning Electron Microscopy, III:1313-1320 (1984). It has also been used to treat human Decubitus ulcers where it promotes healing (Silver, F. H., et al., "Collagenous materials enhance healing of chronic skin ulcers," Biomedical Materials and Devices Research Society, 110:371-376 (1989)). In vitro studies, this matrix has been used as a model for examining the role of various matrix components on fibroblast ingrowth (Doillion, et al., "Fibroblast growth on a porous collagen sponge containing hyaluronic acid and fibronectin," Biomaterials 8:195-200 (1987).
In this invention, this matrix is used as a support for human keratinocyte growth and differentiation. The matrix described herein, containing keratinocytes and fibroblasts, is referred to herein as a "skin model system" or "SMS." Dollion, et al., in "Behavior of fibroblasts and epidermal cells cultivated on analogues of extracellular matrix," Biomaterials, 9:91-96 (1988), report on efforts to use the Berg collagen matrix in attempts to manufacture artificial skin, but such attempts were not successful. Epidermal cells on the surface of the matrix were neither differentiated nor in stratified layers.
An alternative collagen-based system has been developed by Bell et al. (Bell, E., et al., "The reconstitution of living skin," Journal of Investigative Dermatology, 81:2s-10s (1983); Bell, E., et al., "Recipes for reconstituting skin," J. Biomechan. Eng., 113:113-119 (1991)) as a dermal replacement called "living skin equivalent" or "LSE". The LSE is manufactured by mixing living human fibroblasts with soluble rat tail collagen under conditions where the collagen forms a gel (See, U.S. Pat. Nos. 4,485,096, 4,604,346, 4,8356,102, and Bell, E., et al., "Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro," Proc. Natl. Acad. Sci. USA, 76:1274-1278 (1979)). During the five days of culture, the gel containing fibroblasts undergoes a contraction process where the collagen volume is reduced to a small disc approximately 10% to 20% of the original volume depending on the concentration of collagen, the cell number and the composition of the growth medium. This contracted collagen matrix is then used to support human keratinocyte growth. Although the Bell LSE is an advance over other previously known artificial skin systems, it does suffer from disadvantages. Since the manufacture or the collagen matrix requires living fibroblasts, it is expensive to manufacture and the matrix is not easily stored. The Bell collagen matrix is not cross-linked and contracts with the addition of the fibroblasts, so it is difficult to manufacture the matrix in a desired shape and size. It is difficult to make large sizes of LSE; the matrix contracts substantially and large numbers of living cells are required. The Bell collagen matrix utilizes soluble collagen, which is more difficult and expensive to extract than insoluble collagen. Still further, since the Bell collagen matrix requires living cells, the manipulations to which it can be exposed are limited, e.g., it cannot be exposed to toxic conditions which might manipulate or favorably alter the matrix structure but which would kill the cells. In view of cheese limitations, there remains a need for improved artificial skin systems.


In one embodiment, a magnetic resonance imaging apparatus includes: a scanner that includes a static magnetic field magnet configured to generate a static magnetic field, a gradient coil configured to generate a gradient magnetic field, and a WB (Whole Body) coil configured to apply an RF pulse to an object; and processing circuitry. The processing circuitry is configured to: set (i) a pulse sequence in which a sequence element is repeated, the sequence element including at least an inversion pulse and (ii) a data acquisition sequence executed after a delay time from the inversion pulse; and cause the scanner to execute the pulse sequence by using virtual gating.

An MRI apparatus is an imaging apparatus configured to excite nuclear spin of an object placed in a static magnetic field by a radio frequency (RF) pulse applied with the Larmor frequency, and reconstruct an image based on magnetic resonance (MR) signals emitted from the object due to the excitation.
Among the imaging methods using an MRI apparatus, there is known a non-contrast enhanced imaging for imaging blood flow or blood vessels without administering a contrast medium. Further, among the various non-contrast enhanced imaging methods, a Time-SLIP (time-spatial labeling inversion pulse) method is known as an imaging method in which an RF pulse (for example, an inversion pulse) is applied prior to data acquisition to control depiction of blood flow. The Time-SLIP method is an imaging method that can clearly depict or visualize the blood flow of a target blood vessel with high contrast, while suppressing the background of the imaging region. By using the Time-SLIP method, not only blood flowing through arteries or veins but also fluid such as cerebrospinal fluid (CSF) can be imaged.
Meanwhile, ECG (electrocardiogram) gating and respiratory gating are used to suppress body-motion artifacts caused by body motions due to heartbeat and/or respiration. The ECG gating is an imaging method in which data (i.e., MR signals) are acquired within a predetermined period of a desired cardiac time phase, in synchronization with an ECG signal, for example, an R-wave. On the other hand, the respiratory gating is an imaging method in which data are acquired within a predetermined period of a predetermined time phase during expiration in a cycle consisting of inspiration and expiration, in synchronization with the respiratory signal indicating the respiratory motion detected by a respiratory sensor, for example.
In a conventional MRI apparatus, the Time-SLIP method has been used in combination with the ECG gating and/or respiratory gating to suppress body motion artifacts. When the Time-SLIP method and gating imaging, such as ECG gating and respiratory gating, are used in combination, the total imaging time tend to be long.


A method for inhibiting the plugging of a conduit, the conduit containing a flowing mixture comprising an amount of hydrocarbons having from one to eight carbon atoms and an amount of water wherein the amounts of hydrocarbons and water could form hydrates at conduit temperatures and pressures, the method comprising the steps of:. adding to the mixture an amount of a hydrate formation inhibitor component of the formula ##STR1## wherein two of R.sub.1 -R.sub.4 are independently normal or branched alkyls having 4 or 5 carbon atoms, PA1 two of R.sub.1 -R.sub.4 are independently representing organic moieties having at least 8 carbon atoms, PA1 A represents a nitrogen or phosphorus atom, and PA1 Y represents an anion; PA1 the amount of the hydrate formation inhibitor component being effective to inhibit formation of hydrates in the mixture at conduit temperatures and pressures; and PA1 flowing the mixture containing the hydrate formation inhibitor component through the conduit.

Low-boiling hydrocarbons, such as methane, ethane, propane, butane and iso-butane, are present in natural gas and also in crude oil. Because water may also be present in varying amounts in natural gas and crude oil, the mixture, under conditions of elevated pressure and reduced temperature, tends to form gas hydrate crystals. Gas hydrates are clathrates (inclusion compounds) of gases in a lattice consisting of water molecules. The maximum temperature at which gas hydrates can be formed strongly depends on the pressure of the system. For example, ethane at a pressure of approximately 1 MPa can form hydrates only at temperatures below 4.degree. C. whereas at a pressure of 3 MPa stable hydrates can be present at temperatures as high as 14.degree. C. With respect to this strong dependence of the hydrate melting point on pressure, hydrates markedly differ from ice.
As described by M. von Stackelberg and H. R. Muller (Z. Electrochem., 58, 25 (1954)), methane and ethane hydrates form cubic lattices having a lattice constant of 1.2 nm (hydrate structure I). The lattice constant of the cubic propane and butane gas hydrates is 1.73 nm (hydrate structure II). However, the presence of even small amounts of propane in a mixture of low-boiling hydrocarbons will result in the formation of gas hydrates having structure II (J. H. van der Waals and J. C. Platteeuw, Adv. Chem. Phys. 2, 1 (1959)).
It has been known for a long time, that gas hydrate crystals, when allowed to form and grow inside a conduit such as a pipeline, tend to block or even damage the conduit. To prevent such blocking, the following measures are possible in principle: removal of free water; maintaining elevated temperatures and/or reduced pressures or the addition of melting point depressants (antifreezes). In practice, antifreezes are most frequently used. However, antifreezes, such as the lower alcohols and glycols, have to be added in substantial amounts to be effective, typically several tens of percent by weight of the water present. A disadvantage of such amounts is the cost of the antifreeze. A further disadvantage is that recovery is relatively expensive.
An attractive alternative to the anti-hydrate measures described above, particularly the antifreezes, is to use a crystal growth inhibitor.
Plants and poikilothermic animals such as insects and cold-water fish are known to protect themselves from freezing; both by antifreezes such as glycols and by special peptides and glycopeptides (termed antifreeze proteins and antifreeze glycoproteins) that interfere with ice crystal growth (A.L. de Vries, Comp. Biochem. Physiol, 73, 627 (1982)). Although we found such cold-water fish peptides and glycopeptides to be effective in interfering with the growth of gas-hydrate crystals, their production and use for this purpose are currently considered to be uneconomical.
In International Patent Application Publication WO 93/25798 the use of polymers and copolymers of N-vinyl-2-pyrrolidone for inhibiting the formation, growth and/or agglomeration of gas hydrate crystals is disclosed.
U.S. Pat. No. 5,460,728 discloses hydrate inhibition compounds that include ammonium alkyls having at least three alkyl groups of four or more carbon molecules. This patent includes examples of ammoniumalkyls, but does not include any examples of ammonium alkyls having two alkyl groups that have greater than ten carbon atoms. The ammonium alkyls disclosed in this patent are effective compared to the prior art hydrate inhibitors know at that time, but there remains a need for even more effective hydrate inhibitors. For example either greater depression of temperatures at which hydrates plug flowlines and/or effectiveness at lower concentrations would be desirable.
It is therefore an object of the present invention to provide a method to inhibit formation of hydrates in streams containing at least some light hydrocarbons and water. It is a further object to provide such a method wherein a high concentration of additive is not required.

Method for inhibiting the plugging of conduits by gas hydrates


A system and method for managing print services between multifunction peripherals and a print server includes a connector server. The connector server subscribes to event notifications from each multifunction peripheral through two or more network adapters. Events are relayed from the connector server to the print server, irrespective as to which network adapter receives them. The connector server also relays web content between the multifunction peripheral and the print server.

Document processing devices include printers, copiers, scanners and e-mail gateways. More recently, devices employing two or more of these functions are found in office environments. These devices are referred to as multifunction peripherals (MFPs) or multifunction devices (MFDs). As used herein, MFPs are understood to comprise printers, alone or in combination with other of the afore-noted functions. It is further understood that any suitable document processing device can be used.
Printing for larger enterprises may be managed with a print server, such as with managed print services offered by Pharos or PaperCut. In such systems, a user can send a document to a print server, and release their document for printing at any MFP by logging in. Login can be by a smart card, such as a near-field communication (NFC) device or a radio frequency identification device (RFID). Login can also be accomplished by entering login information on a MFP user interface, or by scanning a barcode or QR code on an MFP.

System and method for server connection using multiple network adapters


A method of treating prostate cancer by co-administering a tyrosine kinase inhibitor such as an indolocarbazole and a chemical castration agent is disclosed. A composition containing a tyrosine kinase inhibitor and a chemical castration agent is also disclosed.

The invention relates to oncology, endocrinology, andrology, and pharmacology.
Prostate cancer is the most frequently diagnosed cancer in men and is responsible for approximately 41,000 deaths in the United States annually (Parker, S. L., et al. (1996) CA Cancer J. Clin., 65:5-27). Early stage, organ-confined, prostate cancer is often managed with surgery or radiation therapy until the patient dies from unrelated causes.
Carcinomas such as breast cancer, colon cancer and adenocarcinoma are characterized by rapid cell division. Consequently, these cancers are amenable to treatment with chemotherapeutic agents that inhibit rapid cell division. In contrast, prostate cancer is not characterized by rapid cell division. Therefore, conventional chemotherapeutic agents generally display low efficacy against prostatic carcinomas.
Prostatic carcinomas are often sensitive to hormonal manipulation. Currently approved treatment of prostrate cancer includes surgical castration, chemical castration, or a combination of surgical and chemical castration. Removal of the testes, the primary testosterone producing organ, reduces the levels of circulating androgens, to less than 5% of normal levels. This reduction in androgen levels inhibits prostate tumor growth. Although the anti-tumor effects of surgical castration are direct, the anti-tumor effects can be temporary. Surgical castration often leads to clonal selection of androgen-independent prostate tumor cells. This results in re-growth of the prostate tumor in a form that proliferates without testosterone or DHT stimulation (Isaacs et al. (1981) Cancer Res. 41:5070-5075; Crawford et al. (1989) N. Eng. J. Med. 321:419-424).
Chemical castration (also called medical castration) is often substituted for surgical castration, as an initial treatment. Chemical castration can be achieved by administration of estrogens, e.g., diethylstilbestrol (DES); LHRH analogues, e.g., leuprolide acetate (LUPRON.RTM.) or goserelin acetate (ZOLADEX.RTM.); steroidal antiandrogens, e.g., cyproterone acetate (CPA); nonsteroidal antiandrogens, e.g., flutamide, nilutamide, or CASODEX.RTM.; or a combination of such agents.
Receptor-linked tyrosine kinases are transmembrane proteins that contain an extracellular ligand binding domain, a transmembrane sequence, and a cytoplasmic tyrosine kinase domain. Tyrosine kinases function in cellular signal transduction. Cell proliferation, differentiation, migration, metabolism and programmed death are examples of tyrosine kinase-mediated cellular responses.
Tyrosine kinases have been implicated in prostate epithelial cell transformation and tumor progression. Implicated tyrosine kinases include Fibroblast Growth Factor (FGF) receptors, Epidermal Growth Factor (EGF) receptors, and Platelet-Derived Growth Factor (PDGF) receptors. Also implicated are Nerve Growth Factor (NGF) receptors, Brain-Derived Neurotrophic Factor (BDNF) receptors, and Neurotrophin-3 (NT-3) receptors, and Neurotrophin-4 (NT-4) receptors.
U.S. Pat. Nos. 5,516,771, 5,654,427 and 5,650,407 discuss indolocarbazole-type tyrosine kinase inhibitors and prostate cancer. U.S. Pat. Nos. 5,475,110; 5,591,855; and 5,594,009; and WO 96/11933 discuss fused pyrrolocarbazole-type tyrosine kinase inhibitors and prostate cancer.

Combination of tyrosine kinase inhibitor and chemical castration to treat prostate cancer


A novel global planarization process is disclosed which is fully compatible with semiconductor processing. The process disclosed is called metal melt-solidification planarization (MMSP). A layer of a low melting point/high boiling point metal such as tin or a suitable alloy is deposited on a nonplanar wafer surface via physical-vapor deposition or chemical-vapor deposition or evaporation or plating. The wafer is then heated to above the tin melting point, cooled back to resolidify tin, and etched back to form a globally planar surface.

Surface planarization is an important requirement for device reliability and depth-of-focus (DOF) requirements of advanced optical lithography tools. Depth-of-focus issues arise when attempting to focus a mask pattern on a surface area with uneven topography. The portion of the surface farther away from the imaging camera lens can be out of focus with respect to the portion of the surface closer to the imaging camera lens or vice versa. As the semiconductor technologies are scaled to sub-0.5 micron (.mu.m) dimensions, improved planarization techniques are required in order to achieve both local and global surface planarization. Local planarization involves planarization over a small portion or lateral scale of an area, while global planarization involves complete planarization over the entire chip area. To date, the following techniques have been proposed or employed for semiconductor device fabrication:
a) spin-on glass (SOG) and etch-back used for local planarization; PA1 b) spin-on resist and etch-back (REB) used for local planarization; PA1 c) in-situ planarized oxide deposition using electron cyclotron resonance, ECR, or plasma used for local planarization; PA1 d) chemical/mechanical polishing (CMP) used for global planarization; PA1 e) plasma deposited polymer films plus etch-back (e.g. that used in Lincoln Lab's work on disposable polymer films for local/global planarization); and PA1 f) phosphosilicate glass (PSG) or borophosposilicate glass (BPSG) reflow used for local planarization.
CMP is the main and until now, the only proven global planarization technique which is being seriously considered for sub-0.5 .mu.m technologies. However, successful implementations of CMP for semiconductor device manufacturing demands effective post-CMP cleaning process in order to remove the CMP-induced surface contaminants and damage. Much work remains to be done in order to make CMP a fully manufacturable and optimized process.


Compounds of Formula I and II, and their agriculturally-suitable salts, are disclosed which are useful for controlling undesired vegetation ##STR1## wherein X is a direct bond; O; S; NH; N(C.sub.1 -C.sub.3 alkyl); N(C.sub.1 -C.sub.3 haloalkyl); or N(allyl);. R.sup.1 is H; F; Cl; or Br; PA1 R.sup.2 is H; F; Cl; Br; CF.sub.3 ; nitro; or cyano; PA1 R.sup.4 is H; C.sub.1 -C.sub.3 alkyl; or halogen; PA1 R.sup.5 is H; C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; halogen; S(O).sub.2 (C.sub.1 -C.sub.6 alkyl); or C(.dbd.O)R.sup.8 ; or PA1 R.sup.4 and R.sup.5 are taken together along with the carbon to which they are attached to form a spiro-cyclopropane ring;. and R.sup.3, R.sup.8, and J are as defined in the disclosure.. Also disclosed are compositions containing the compounds of Formulae I and II and a method for controlling undesired vegetation which involves contacting the vegetation or its environment with an effective amount of a compound of Formula I or II.

This invention relates to certain cyclic sulfonamides, their agriculturally-suitable salts and compositions, and methods of their use as general or selective preemergent or postemergent herbicides.
New compounds effective for controlling the growth of undesired vegetation are in constant demand. In the most common situation, such compounds are sought to selectively control the growth of weeds in useful crops such as cotton, rice, corn, wheat, citrus and soybeans, to name a few. Unchecked weed growth in such crops (including plantation crops) can cause significant losses, reducing profit to the farmer and increasing costs to the consumer. In other situations, herbicides are desired which will control all plant growth. Examples of areas in which complete control of all vegetation is desired are areas around railroad tracks, storage tanks and industrial storage areas. There are many products commercially available for these purposes, but the search continues for products which are more effective, less costly and environmentally safe.
U.S. Pat. No. 4,818,275 discloses herbicidal acyclic sulfonamides of the formula ##STR2## wherein, inter alia X and Y are Br; Cl; or F;
R is alkyl; haloalkyl; or dialkylamino; and PA1 R.sup.1 is H; Na; lower alkyl; or SO.sub.2 R. PA1 JP 631988!-222167 discloses herbicidal cyclic amides and sulfonamides of the formula ##STR3## wherein X is H or halogen; PA1 Z is O or S; PA1 J is, inter alia, --CO-- or --SO.sub.2-- ; PA1 L.sub.1 is --CO-- or --CR.sub.4 (R.sub.5)--; PA1 R.sub.4 and R.sub.5 are each independently, inter alia, H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, or CO.sub.2 R.sub.a ; PA1 R.sub.1 is, inter alia, H, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 haloalkenyl, C.sub.3 -C.sub.8 cycloalkyl, --COR.sub.b, --CO.sub.2 R.sub.b, or --CH.sub.2 CO.sub.2 R.sub.b ; PA1 W is, inter alia, ##STR4## Q is N or CH; E is O or S; PA1 R.sub.12 is H, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 haloalkyl when Q is N; or PA1 R.sub.12 is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, or C.sub.4 alkylene which combines with Q to form a 6-membered ring when Q is CH; PA1 R.sub.13 is H, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 haloalkyl when Q is N; or PA1 R.sub.13 is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, or C.sub.4 alkylene which combines with Q to form a 6-membered ring when Q is CH; and PA1 m is 0 or 1. PA1 R.sup.1 is H; F; Cl; or Br; PA1 R.sup.2 is H; F; Cl; Br; CF.sub.3 ; nitro; or cyano; PA1 R.sup.3 is H; C.sub.1 -C.sub.8 alkyl; C.sub.3 -C.sub.8 cycloalkyl; C.sub.3 -C.sub.8 alkenyl; C.sub.3 -C.sub.8 alkynyl; C.sub.1 -C.sub.8 haloalkyl; C.sub.2 -C.sub.8 alkoxyalkyl; C.sub.3 -C.sub.8 alkoxyalkoxyalkyl; C.sub.3 -C.sub.8 haloalkynyl; C.sub.3 -C.sub.8 haloalkenyl; C.sub.1 -C.sub.8 alkylsulfonyl; C.sub.1 -C.sub.8 haloalkylsulfonyl; C.sub.3 -C.sub.8 alkoxycarbonylalkyl; S(O).sub.2 NH(C.sub.1 -C.sub.8 alkyl); C(O)R.sup.6 ; or benzyl optionally substituted on the phenyl ring with R.sup.7 ; PA1 R.sup.4 is H; C.sub.1 -C.sub.3 alkyl; or halogen; PA1 R.sup.5 is H; C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; halogen; S(O).sub.2 (C.sub.1 -C.sub.6 alkyl); or C(.dbd.O)R.sup.8 ; or PA1 R.sup.4 and R.sup.5 are taken together along with the carbon to which they are attached to form a spiro-cyclopropane ring; PA1 R.sup.6 is C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.1 -C.sub.6 alkoxy; NH(C.sub.1 -C.sub.6 alkyl); phenyl optionally substituted with R.sup.7 ; benzyl; or C.sub.2 -C.sub.8 dialkylamnino; PA1 R.sup.7 is C.sub.1 -C.sub.6 alkyl; 1-2 halogen; C.sub.1 -C.sub.6 alkoxy; or CF.sub.3 ; PA1 R.sup.8 is H; C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 alkoxy; or NH(C.sub.1 -C.sub.6 alkyl); PA1 J is ##STR6## wherein the dashed line in J-5, J-6 and J-12 indicates that the left-hand ring contains only single bonds or one bond in the ring is a carbon-carbon double bond; PA1 n and m are each independently 0; 1; 2; or 3; provided that m+n is 2 or 3; PA1 Z is CR.sup.9 R.sup.10 ; O; S; S(O); S(O).sub.2 ; N(C.sub.1 -C.sub.4 alkyl; or ##STR7## each R.sup.9 is independently H; C.sub.1 -C.sub.3 alkyl; halogen; hydroxy; C.sub.1 -C.sub.6 alkoxy; C.sub.1 -C.sub.6 haloalkyl; C.sub.1 -C.sub.6 haloalkoxy; C.sub.2 -C.sub.6 alkylcarbonyloxy; or C.sub.2 -C.sub.6 haloalkylcarbonyloxy; PA1 each R.sup.10 is independently H; C.sub.1 -C.sub.3 alkyl; hydroxy; or halogen; PA1 R.sup.11 and R.sup.12 are each independently H; halogen; C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 alkenyl; or C.sub.1 -C.sub.6 haloalkyl; PA1 R.sup.13 is H; C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 -C.sub.6 haloalkenyl; C.sub.3 -C.sub.6 alkynyl; C.sub.3 -C.sub.6 haloalkynyl; HC(.dbd.O); (C.sub.1 -C.sub.4 alkyl)C(.dbd.O); or NH.sub.2 ; PA1 R.sup.14 is C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 alkylthio; C.sub.1 -C.sub.6 haloalkyl; CF.sub.3 ; or N(CH.sub.3).sub.2 ; PA1 W is N or CR.sup.15 ; PA1 R.sup.15 is H; C.sub.1 -C.sub.6 alkyl; halogen; or phenyl optionally substituted with C.sub.1 -C.sub.6 alkyl, 1-2 halogen, C.sub.1 -C.sub.6 alkoxy, or CF.sub.3 ; PA1 each Q is independently O or S; PA1 Q.sup.1 is O or S; PA1 Z.sup.1 is CR.sup.16 R.sup.17 ; O; S; S(O); S(O).sub.2 ; N(C.sub.1 -C.sub.4 alkyl; or ##STR8## each R.sup.16 is independently H; halogen; hydroxy; C.sub.1 -C.sub.6 alkoxy; C.sub.1 -C.sub.6 haloalkyl; C.sub.1 -C.sub.6 haloalkoxy; C.sub.2 -C.sub.6 alkylcarbonyloxy; or C.sub.2 -C.sub.6 haloalkylcarbonyloxy; PA1 each R.sup.17 is independently H; hydroxy; or halogen; or PA1 when R.sup.16 and R.sup.17 are bonded to adjacent atoms they can be taken together with the carbons to which they are attached to form ##STR9## R.sup.18 is C.sub.1 -C.sub.6 alkyl; halogen; or C.sub.1 -C.sub.6 haloalkyl; PA1 R.sup.19 and R.sup.20 are each independently H; C.sub.1 -C.sub.6 alkyl; or C.sub.1 -C.sub.6 haloalkyl; PA1 R.sup.21 and R.sup.22 are each independently C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 -C.sub.6 haloalkenyl; C.sub.3 -C.sub.6 alkynyl; or C.sub.3 -C.sub.6 haloalkynyl; PA1 R.sup.23 is halogen or cyano; PA1 R.sup.24 is C.sub.1 -C.sub.6 alkylsulfonyl; C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 -C.sub.6 alkynyl; C.sub.1 -C.sub.6 alkoxy; C.sub.1 -C.sub.6 haloalkoxy; or halogen; PA1 R.sup.25 is C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.3 -C.sub.6 alkenyl; or C.sub.3 -C.sub.6 alkynyl; and PA1 R.sup.26 is C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 haloalkyl; or phenyl optionally substituted with C.sub.1 -C.sub.6 alkyl, 1-2 halogen, 1-2 nitro, C.sub.1 -C.sub.6 alkoxy, or CF.sub.3 ; PA1 provided that when X is O or S in Formula II, then J is other than J-6 or J-7. PA1 X is a direct bond or O; PA1 R.sup.1 is F or Cl; PA1 R.sup.2 is F; Cl; or Br; PA1 R.sup.3 is H; C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 cycloalkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 -C.sub.6 alkynyl; C.sub.1 -C.sub.6 haloalkyl; C.sub.2 -C.sub.6 alkoxyalkyl; C.sub.3 -C.sub.6 haloalkenyl; C.sub.1 -C.sub.6 alkylsufonyl; C.sub.3 -C.sub.6 alkoxycarbonylalkyl; C(O)R.sup.6 ; or benzyl optionally substituted on the phenyl ring with R.sup.7 ; PA1 R.sup.4 is H or halogen; PA1 R.sup.5 is H; PA1 J is J-1; J-2; J-3; J-4; J-5; J-6; J-8; J-12; J-15; or J-16; PA1 Z is CR.sup.9 R.sup.10 ; O; S; or N(C.sub.1 -C.sub.4 alkyl); PA1 each R.sup.9 is independently H; halogen; or C.sub.1 -C.sub.6 haloalkoxy; PA1 each R.sup.10 is independently H or halogen; PA1 each Q is O; PA1 Q.sup.1 is S; PA1 Z.sup.1 is CR.sup.16 R.sup.17 ; O; S; or N(C.sub.1 -C.sub.4 alkyl); PA1 each R.sup.16 is independently H; halogen; or haloalkoxy; PA1 each R.sup.17 is independently H or halogen; or PA1 when R.sup.16 and R.sup.17 are bonded to adjacent atoms they can be taken together with the carbons to which they are attached to form ##STR10## R.sup.18 is t-butyl or CH.sub.2 CH.sub.2 CH.sub.2 F; R.sup.23 is Cl or cyano; and PA1 R.sup.24 is C.sub.1 -C.sub.4 haloalkyl or C.sub.1 -C.sub.6 haloalkoxy. PA1 R.sup.2 is F or Cl; PA1 R.sup.3 is C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 cycloalkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 -C.sub.6 alkynyl; C.sub.3 -C.sub.6 alkoxycarbonylalkyl; or benzyl optionally substituted on the phenyl ring with R.sup.7 ; PA1 J is J-1; J-2; J-3; J-4; J-5; J-6; J-8; or J-12; PA1 Z is CR.sup.9 R.sup.10 or O; PA1 each R.sup.9 is independently H or halogen; PA1 R.sup.11 is C.sub.1 -C.sub.4 haloalkyl; PA1 R.sup.12 is C.sub.1 -C.sub.4 alkyl; PA1 R.sup.13 is CH.sub.3 ; PA1 R.sup.14 is CF.sub.3 ; PA1 W is CH; PA1 Z.sup.1 is CR.sup.16 R.sup.17 or O; PA1 each R.sup.16 is independently H or halogen; PA1 each R.sup.17 is independently H or halogen; or PA1 when R.sup.16 and R.sup.17 are bonded to adjacent atoms they can be taken together with the carbons to which they are attached to form ##STR11## Preferred 3. Compounds of Preferred 2 wherein: R.sup.2 is Cl; PA1 R.sup.3 is C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 alkenyl; or C.sub.3 -C.sub.6 alkynyl; PA1 J is J-1; J-2; J-3; J-4; J-6; or J-12; PA1 Z is CR.sup.9 R.sup.10 ; PA1 R.sup.9 is independently H or F; PA1 R.sup.10 is independently H or F; PA1 R.sup.11 is CF.sub.2 H; PA1 R.sup.12 is CH.sub.3 ; PA1 Z.sup.1 is CR.sup.16 R.sup.17 ; PA1 R.sup.16 is independently H or F; and PA1 R.sup.17 is independently H or F.
The cyclic sulfonamides of the present invention are not disclosed in either of these references.


In micromechanical pressure sensor device and a corresponding production method, the micromechanical pressure sensor device is provided with a first diaphragm; an adjacent first cavity; a first deformation detection device situated in and/or on the first diaphragm for detecting a deformation of the first diaphragm as a consequence of an applied external pressure change and as a consequence of an internal mechanical deformation of the pressure sensor device; a second diaphragm; an adjacent second cavity; and a second deformation detection device situated in and/or on the second diaphragm for detecting a deformation of the second diaphragm as a consequence of the internal mechanical deformation of the pressure sensor device, where the second diaphragm is developed in such a way that it is not deformable as a consequence of the external pressure change.

Although applicable to a wide variety of micromechanical pressure sensor devices, the present invention and the problems on which it is based are described on the basis of micromechanical pressure sensor devices on silicon bases such as those known from WO 2013/152 901 A1, for example.
FIG. 5, parts (a)-(c) show schematic illustrations of an exemplary micromechanical pressure sensor device in order to describe a problem on which the present invention is based, i.e., in a cross-section in FIG. 5, parts (a)-(b), and in a plan view in FIG. 5, part (c).
Reference sign F in FIG. 5 denotes a micromechanical function layer, e.g., a silicon layer. A diaphragm M having a cavity A disposed underneath is formed in micromechanical function layer F. Cavity A is sealed by a sealing layer V on the backside.
Reference signs P1-P4 denote a deformation detection device situated in or on diaphragm M, e.g., piezoresistive elements, for detecting a deformation of diaphragm M as a consequence of an applied external pressure change. FIG. 5, part (a) denotes the state in which external pressure P is equal to Pa, corresponding to the pressure inside cavity A. In this state, the deformation detection device having piezoresistive elements P1-P4 outputs a first measured value, e.g., via a bridge circuit. If external pressure P is raised to a higher pressure P=Pb, then diaphragm M deforms in the inward direction into cavity A, and the deformation detection device outputs a second, different measured value. This therefore makes it possible to detect the applied external pressure change.
As illustrated in FIG. 5, part (c), four piezoresistive elements P1-P4, for example, are provided on four oppositely situated edges of diaphragm M.
In the known pressure sensor device, however, mechanical deformations of diaphragm M are not exclusively attributable to the external pressure change but also to external influences that subject the micromechanical pressure sensor device to mechanical stress, e.g., deformations by mechanical tension as a result of a packaging process (not shown), by a development using a material mix that features different thermal coefficients of expansion or by the stressing of soldered joints of the developed and packaged sensor on an assembly circuit board (not shown).
Because the mechanical stress is either coupled into the pressure measurement signal in the pressure sensor device or mechanical stress relief structures lead to a reduction in the mechanical robustness, the known pressure sensors are flawed to some extent.

Micromechanical pressure sensor with two cavities and diaphragms and corresponding production method


In a mounting system for an assembly in a high-frequency desktop device, a chassis element ("element") provides ground. For best ground, features formed in the element near a first edge of the assembly force the two together with no fastener there. Fasteners or other provisions secure the assembly, near its second edge, to the element. The features capture the first edge at installation; the fasteners etc. secure the assembly, near its second edge so that the features pinch the first. In another form of the system (1) first raised shapes formed in the element support the assembly near its first edge; (2) features, also formed in the element next to the first shapes, engage and capture the first edge; (3) second raised shapes, formed in the element, support the assembly near its second edge; and (4) fasteners etc. secure the assembly, near its second edge. Preferably the features are so spaced above the first raised shapes as to slightly flex the assembly; no separate fastener holds the assembly to the element near the first raised shapes; the first or second shapes, or both, are metallic and engage grounding pads; and the element is formed metal, structurally integrated with other chassis and case pieces. In another form, the invention is an entire image-related device including the stated items. A method installs and removes the assembly with just one-side access: inserting its first edge between the retainers and first raised shapes, rotating it to operating position to engage it with the second raised shapes near a second edge and pinch the first edge between the retainers and first raised shapes, and securing it--or reversing the steps to remove it.

(a) Conventional shell--Typically enclosures for modern desktop use in the office or home have been either:
nonstructural plastic skins over sheet-metal frames, as in usual manufacture of computers; or PA1 rigid shells enveloping the mechanism, as in usual manufacture of printers.
Both of these approaches produce structures that are expensive to make, due to relatively thick-walled parts that lead to subtle added costs for material, molding and storage. The first also produces structures that are heavy and so cost more to ship, and the second produces overall structures that are relatively large and so again cost more to store.
(b) Cantilevered mechanical modules--The second technique also has an even more severe disadvantage: the internal mechanisms in general are usually cantilevered within their shells. This construction invites mechanical deformation in event of shock loading, such as can occur during shipping--or even when the machine is moved within a home or office.
Dropping the machine a relatively short distance, or shoving the machine only moderately hard, creates relative acceleration between the chassis and the cantilevered mass. This relative acceleration can cause the mass to act on the cantilevering structure like a force operating through a lever--to exert much higher, damaging levels of force on the components in the region of attachment.
In other words, the deformation magnifies the shock load and so tends to aggravate damage. The relatively heaviness of the parts worsens this problem.
(c) Noncantilevered electronic assemblies--As to internal mounting of electronic boards and assemblies, in a sense the prior-art difficulties are opposite to those discussed above for mechanical modules (although part of the difference may be due to somewhat different usages of the word "cantilever"). Here the normal practice is to firmly screw down electronic modules at all corners, or along opposing edges--or both.
Such practice has three drawbacks. First, installation of screws to assemble electronics into a product is relatively time consuming. In a mass-production environment, each screw takes several seconds--translating into not only cost for labor but also significant aggregate added cost for workstations.
This consideration alone is sufficient motivation to seek mounting arrangements requiring fewer screws. It is a particularly important concern in view of rework requirements, because major electronic assemblies in image-related devices typically have a relatively high rejection rate.
Such assemblies usually carry a very large number of components, many or most of which are simply purchased at wholesale, off-the-shelf as finished products from independent manufacturers, and failure rates of all these components are multiplicative. Finished assemblies therefore constitute a major cause of product failure--even in the testing process that is associated with manufacture.
Accordingly it is common for a particular electronics module to require not only initial installation into a device but also subsequent removal from the device, and then reassembly of a replacement into the device, before the product leaves the factory. Of course this kind of occurrence multiplies the adverse effects of the screw mounting.
(d) Field service, and fastener time--As a second drawback, the same considerations continue into the after-market environment. The same kind of excess time consumption--in both disassembly and reassembly--are necessary when failure occurs in the field.
A very common way of dealing with functional failure, whether in a product purchaser's facility or in a service center, is to change out an electronics assembly that is responsible for the related function. Even in the field, failure of major electronics assemblies remains one of the highest sources of service events.
Of course such failures amount to an undesirable expense regardless of who pays for them, and the manufacturer wishes to cultivate a reputation for products that do not fail in the field--or at least that are not very expensive to fix if they do fail. Hence the manufacturer always has a strong motivation to avoid such failures.
Since it is the manufacturer, however, who most commonly also bears the expense directly, it is particularly natural for the manufacturer to seek manufacturing techniques that minimize the time consumption and therefore the cost of field service. Therefore it is doubly desirable to find manufacturing configurations that make electronic modules very fast and easy to put in and take out.
(e) Access--This third drawback is more peculiar to the aftermarket environment, in which a technician seldom enjoys the luxury of having the entire device initially disassembled on the workbench. Even in the production context, however, when final product testing indicates that an electronic board must be replaced, accessibility of the components for removal and replacement becomes very important.
As mentioned earlier, electronic printed-circuit assemblies are conventionally screwed down along opposite edges or at all corners. When an assembly is thus installed in a relatively crowded case, in common interior layouts other modules of the device obstruct access to at least some of the screws. Just such tight packing, however, is generally required for good economy, as well as space in the end-user's office.
In particular, if entry to the interior is provided only through a relatively narrow or shallow access port, ordinarily just some of the screws can be within easy reach for removal. Such configurations require extra time for removal of other modules, merely to reach mounting screws for replacement of the circuit board--and then to replace those other modules later.
A conceptually and functionally trivial task thus becomes an exceedingly onerous chore: the service technician faces the task of taking apart much of the apparatus, merely to change out a board. It is compounded by the risk of damage (especially hidden damage) to those other modules in the course of the removal and replacement.
Interestingly, this is so even with some devices whose cases come off completely for service--as for instance a typical personal computer. Replacing a motherboard, even when the technician can look straight down at almost all of it, may take twenty to forty minutes.
(f) Solutions to the mechanical problems--The previously mentioned patent document of Hong et al. introduces a radical approach to structure and enclosure design for desktop image-related devices. That document teaches integration of an external shell with an internal framework of several chassis that cooperate to distribute specifically anticipated shock loads in a predetermined way.
The resulting configurations make the most of both investment and weight, since the enclosure essentially functions as one of the structural elements--but without being in itself being heavy or rigid. The invention of the Hong et al. document also resolves several other knotty problems of the prior art, which are detailed in that document but may be summarized here:
vulnerability to shock that is transfered directly through an attachment of an exterior face to an internal chassis;
flexure or failure of shells not strong enough to withstand impact--so that impact passes directly through the shell to apparatus within; and
overly demanding requirements for time-consuming, costly alignment (and forcible distortion) to fit shells onto the chassis for installation of mounting screws.
(g) Broad metallic base--Since many image-related devices require high operating frequencies, e. g. for firing of multiple nozzles at high resolution, these devices are subject to stringent regulations on control of electromagnetic interference ("EMI"). Such constraints in turn call for very effective grounding, preferably at several different locations on an electronic assembly. A common approach to meeting these requirements is to screw the main circuit board to a broadly extended metallic chassis element, preferably at the bottom of the device.
To avoid the problems of access mentioned earlier, in a device with such a broad metallic pan or base, an enclosure is often made with bottom access--i. e. with the base itself removable (together with any shell below it) through the bottom of the product. The main circuit board is then taken out through the bottom, with the base.
This option is foreclosed, however, in an integrated structural/enclosure system such as that of Hong et al. previously discussed. Such a product does have a broad metallic base, but its function as an integral part of the structural system, cooperating in the interconnections of the various chassis and shell members, precludes its easy demounting and removal.
Hence it remains to be shown how an effective grounding strategy, as well as relatively quick and easy assembly and disassembly, can be provided for major printed-circuit assemblies while maintaining the benefits of an integrated enclosure-and-structural system. As will be understood, this problem interacts with the access problem discussed above:
If a solid, positive ground could be obtained without access to all the fasteners--at opposed sides--that hold the board in position and also ground it, then technicians would be able to install and remove printed-circuit assemblies much more quickly and easily. Both the grounding and the access would be greatly simplified and improved, particularly in an integrated enclosure-and-structural system.
An integrated system would then be comparable with, for instance, a conventional bottom-access system in ease and rapidity of service. In short, a fastenerless around for printed-circuit assemblies would significantly advance the field of image-related devices.
(h) Conclusion--Conventional approaches have continued to impede achievement of uniformly excellent electronic serviceability as well as mechanical integrity, in lightweight, economical cases and chassis for desktop printing machines. Thus important aspects of the technology used in the field of the invention remain amenable to useful refinement.

Image-related device with printed-circuit assembly cantilevered from sheet-metal base & with clip fastenings


An electrical connector includes an insulative housing (1), a plurality of contacts (2) arranged in the insulating housing, a pair of locking pieces (4) received in the insulative housing and a metal shell (3) receiving the insulative housing. The insulative housing has a base portion (11) and a tongue portion (12) extending from the base portion. The metal shell includes a main shell (31) and a sub shell (32) an ached to the main shell. The main shell has a front shroud portion (311) surrounding the tongue portion of the insulative housing and a rear portion (312) supporting the base portion. The front shroud portion forms at least one embossed portion (313) thereon. The sub shell is attached to the rear portion of the main shell and has a curve portion (321) abutting against a rear end of the front shroud portion to enclose the base portion of the insulative housing. The main shell and the sub shell each have curve arms (3102, 3202) abutting against the rear ends of the locking pieces.

1. Field of the Invention
The present invention generally relates to an electrical connector, and more particularly relates to an electrical connector with a metal shell having at least one embossed portion extending from the front shroud portion thereof.
2. Description of Related Arts
Electrical connection between a system and peripherals is established through a receptacle connector and a plug connector. Generally, the receptacle with recessed space is installed in the system and the plug with protruding front mating portion is extended from a peripheral, such as a cable end.
Chinese Patent CN No. 2886835 Y discloses an electrical connector, i.e. a plug connector. The plug connector typically comprises a separable metal shell, an insulative housing and a plurality of contacts. When the plug connector is connected with the receptacle, the retention force for securing the plug within the receptacle is ensured by the normal force between contacts of receptacle connector and contacts of plug connector. The receptacle and plug connector assembly are often jerked out by accidental force if the retention force is not robust enough.
Hence, an improved electrical connector is required to overcome the aforesaid disadvantages of the prior art.

Electrical connector with metal shell having convex hull extending from the surface of the front portion thereof


A hydrostatic continuously variable transmission comprises: a hydraulic pump; a power input shaft engaged with the hydraulic pump to transmit power from a power source to the hydraulic pump; a hydraulic motor in hydraulic communication with the hydraulic pump; a casing that houses the hydraulic pump and the hydraulic motor; a port block mounted to the casing, the port block having a block main body and a cover member connected to a power input side of the block main body, said cover member having an outer surface; a cooling hydraulic path provided in the port block in a region where the block main body and the cover member meet, the cooling hydraulic path being connected to a first hydraulic path in the port block, the cooling hydraulic path having a plurality of bends; a cooling fan provided on the power input shaft to provide air flow directly to the outer surface of the cover member.

The present invention relates to a hydrostatic continuously variable transmission which is used as an automotive transmission in various work vehicles, such as a tractor, a lawnmower, a combine harvester, a rice transplanter, and the like.
In hydrostatic continuously variable transmissions (HSTs), hydraulic fluid needs to be cooled since the hydraulic fluid is heated by friction. For example, as disclosed in JP No. 8-145168 A, charge fluid pumped from a charging pump is cooled through an oil cooler before being supplied into a charge fluid path.
Conventionally, the oil cooler is provided in a cooling air path in a radiator of an engine, and the oil cooler is connected to related devices via external pipes. A number of parts for connecting the pipes are required, and piping requires much labor.

Hydrostatic continuously variable transmission


An energy-absorbing bumper assembly includes an impact beam having a front vertical wall with a central inwardly projecting channel. A molded energy absorber formed as a multi-sectioned cellular unit includes mounting towers integrally formed with the unit. Resilient tabs on the mounting towers spring outwardly into complementary openings in the channel when the mounting towers are inserted into the channel, thereby removably attaching the energy absorber to the impact beam.

1. Field of the Invention
The present invention relates to vehicular energy-absorbing bumper assemblies, and in particular is concerned with an integrally formed attachment feature for an energy absorber.
2. Description of the Related Art
Many automotive bumper assemblies include an impact beam and an energy absorbing medium covered by a fascia. The energy absorbing medium can be formed as a multi-sectioned cellular unit molded from a suitable resilient material. An example of such an energy absorbing medium can be found in U.S. Pat. No. 4,275,912. The resilient cells of such media have been generally effective in absorbing low speed impact energy.
Prior to the present invention, an energy absorbing medium was secured to an impact beam with a variety of fasteners. This assembly technique adds to the bumper assembly cost by requiring additional labor and parts.

Integral fasteners for an energy absorber of a vehicular bumper assembly