A pressure regulation servo-valve comprising a body having a utilization port, a feed port, and a return port, a spool mounted as a sliding fit in the body, the spool co-operating with the body to define a pilot chamber connected to the utilization port. The spool and the body together further define a priming chamber connected to the feed port via a second constriction and connected to the nozzle via a third constriction, and in which there exists a priming pressure acting on the spool in the first direction.

This type of servo-valve is used by way of example for controlling hydraulic brakes for a vehicle, in particular aircraft brakes.
Pressure regulation servo-valves are known that comprise a body presenting a utilization port, a feed port, and a return port, together with a spool movably mounted in the body so as to put the utilization port into communication either with the feed port or with the return port. The ends of the spool co-operate with the body to define at least one pilot chamber connected to a nozzle that is arranged to open out into a cavity that is connected to the return port. A flapper extending in the cavity and facing the nozzle is mounted to move in controlled manner. The pilot chamber is connected via a constriction to the feed port. Where applicable, the servo-valve may have two pilot chambers exerting opposing forces on the spool, with each of the pilot chambers being connected to a respective nozzle mounted facing each other and having the flapper extending between them.
The controlled movement of the flapper facing the nozzle(s) serves to modulate the pressures that exist in the pilot chambers, and thus to move the spool in order to modulate the utilization pressure.
A drawback of that type of servo-valve is that it presents a leakage flow rate that is considerable. Specifically, hydraulic fluid flows permanently through the nozzle and is redirected towards the return port. This leakage requires the hydraulic fluid tanks to be dimensioned accordingly so as to be capable of ensuring braking of the vehicle even in the event of a failure of hydraulic pressure generation.
A solution to this problem is proposed in Document FR 2 873 828, which consists in connecting the pilot chamber(s) to the utilization port. The utilization port is usually at pressures that are lower than the feed port. Connecting the pilot chamber(s) to the utilization port makes it possible to reduce the pressure that exists on average in the pilot chamber(s), thereby leading to a corresponding reduction in the leakage flow rate via the nozzle(s).
Nevertheless, there exist operating circumstances in which such a position can lead to difficulties in the response of the servo-valve. Specifically, when the brakes are not being used, the utilization pressure is substantially equal to the return pressure, and the pilot force, which is then produced essentially by the spring acting on the spool, can be insufficient to move the spool when the brakes are applied once more, e.g. at low temperature or if the movement of the spool is impeded by an impurity in the hydraulic fluid. Starting is then observed to be difficult, and can sometimes be followed with oscillations in the utilization pressure. The use of a pressure feedback loop for controlling the spool does not help the servo-valve when it is in such a situation.

Pressure regulation servo-valve with reduced leakage flow rate


In one example in accordance with the present disclosure, a method for determining fusing energy per page based on an applied voltage is described. According to the method, a resistance of a fusing system is acquired and an input voltage of a fusing system is estimated. A duty ratio of the fusing system is measured and a fusing energy per processed page is then determined based on the input voltage, the fusing system resistance, and the duty ratio of the fusing system. A media weight is then determined based on the fusing energy per processed page.

Some imaging devices, such as electro-photographic printers form printed marks, such as texts and images, on media by depositing a printing compound, such as toner or ink, onto the media. After application of the printing compound, a fusing system applies heat and pressure to the printing compound and the media.
Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements.

Determining media weight based on input voltage estimate

Hewlett-Packard Development Company, L.P.


The structural design, preparative methods and chemical composition of two structural formulations of bivalent vaccines against morphine-heroin addiction (morphine-6-hemisuccinyl-EDC-TFCS-tetanus toxoid and 3-O-carboxymethylmorphine-EDC-TFCS-tetanus toxoid), are disclosed. These vaccines are suitable for human use in which they are capable of triggering the synthesis of polyclonal antibodies against morphine opiate and its structural analogue, heroin, through the repeated in vivo administration of these formulations, in active vaccination protocols, in pre-clinical studies in rodents. The active vaccination paradigm through which these immunogens trigger a humoral immune response consolidated with a long-term immunological memory, characterized by the presence of high titers of specific antibodies against these two drugs of abuse, is also disclosed. Furthermore, the present invention reveals the efficacy of these conjugate formulations for triggering a sustained immunoprotection against morphine and heroin addiction using an intravenous self-administration paradigm of these two opiate substances in the rodent. Finally, a discussion is also made on the potential future use of these immunoconjugates in active vaccination protocols for treating both morphine and heroin addiction in the humans.

The abuse of illegal substances with reinforcing addictive properties represents a major public health problem worldwide. For instance, in the United States of America, nearly 48 million people have been exposed to illegal drugs over a one-year period (Neurobiological Adaptations to Psychostimulants and opiates as basis of treatment development. In: New Medications for Drug Abuse, K. Severino, A. Olivito and T. Kosten, 2000). Thus, this health problem has serious and progressive deleterious effects on social, economic and medical areas in affected countries. Epidemiologically, the pyschostimulants such as cocaine and amphetamines, and to a lesser extent, opiate substances, like heroin and morphine, represent the most prevalent drugs causing the highest addictive morbidity worldwide. In developing countries like Mexico, the epidemiological data from the latest National Survey of Addictions (M. E. Medina-Mora and E. Rojas Guiot, Salud Mental, 26(2): 1-11, 2003) reported an alarming increase in the drug-intake of such substances in the central part of the country as well in cities located between Mexico and US border. At the clinical level, there are several co-morbid pathologies related to the addictive abuse of illegal substances, which fall into different categories. Firstly, the high death index related to the toxic effects induced by the overdose of such substances. Secondly, the induction of teratogenic effects in the newborn, which are frequently associated to the chronic abuse of illegal substances by addicted pregnant mothers. Finally, the high incidence of co-morbid diseases of acquiring viral infections such as the human immunodeficiency virus (HIV), frequently detected in heroin abusers, as well as the increased rates of crimes, violence and delinquency frequently associated to the drug-trade and drug-intake of such illegal substances. Thus, at the therapeutic level, there exist an urgent need to refocused and establish straightforward government strategies, health programs and novel medications to fight efficiently against drug abuse to illegal substances.
The neurobiology of drug addiction began more than three decades ago and most of investigations have dealt with drugs' pharmacokinetics and pharmacodymamics. At the pharmacokinetic level, illegal substances of abuse such as cocaine, morphine and heroin, exhibit potent drug-reinforcing properties and specific pharmacokinetic profiles, which ultimately lead to their high addictive drug effects in the brain. Morphine is an alcaloid with a phenantrenic chemical structure (see example 1) obtained from the milky extract (opium gum) of the Papaver somniferum, and represents the main compound extracted (≧10%) together with other structurally-related compounds such as codeine, tebaine, and papaverine (C. P. O'Brien, Drug Abuse, In: The Pharmacological Basis of Therapeutics. Pp. 621-642, 10th ed. J. G. Hardman and L. E. Limbird, eds. McGraw Hill, New York, 2001). Morphine possesses a hydroxyl group in the third position and an alcoholic hydroxyl group in the sixth position placed within the phenolic ring structure. Conversely, heroin, a semi-synthetic derivative of the morphine, has two acetyl groups condensed in the aforementioned positions within the opiate phenantrenic ring structure (C. P. O'Brien, Drug Abuse, In: The Pharmacological Basis of Therapeutics. pp. 621.642, 10th ed. J. G. Hardman and L. E. Limbird, eds. McGraw Hill, New York, 2001). Both morphine and heroin are absorbed from the gastrointestinal and respiratory tract, including oral mucosa, as well as from the subcutaneous, intramuscular, intravascular and intrathecal spaces. These two opiate compounds display a striking similar pharmacokinetic profile, based on their high blood-brain barrier permeation capability, mostly due to their high lipophilic properties (C. P. O'Brien, Drug Abuse, In: The Pharmacological Basis of Therapeutics. pp. 621-642, 10th ed. J. G. Hardman and L. E. Limbird, eds. McGraw Hill, New York, 2001). In fact, heroin is relatively more lipophilic than morphine and thus permeates faster the blood-brain barrier than morphine. The main catabolic route of morphine mainly occurs in the liver and depends on enzymatic-dependent conjugation with glucuronic acid at both the three and six hydroxyl groups placed at the phenantrenic ring structure, producing endogenous metabolites compounds, such as morphine 3-, morphine 6-, and to a lesser extent, morphine 3-6-glucuronide. These catabolic intermediate compounds, represent the structural secretory and/or excretory forms of morphine in the urine. Moreover, morphine-6-glucuronide has been shown to display a potent analgesic and psychotropic, drug-reinforcing effects in the brain. Thus, morphine metabolites generated from the liver into the bloodstream, rapidly permeate the blood-brain barrier and activate the mu opioid receptor subtype in the brain reward pathways mediating the reinforcing effects of drug of abuse (L. M. Kamendulis et al., J. Pharmacol. Exper. Ther. 279:713-717, 1996; C. W. Hutto Jr. y W. Crowder, Pharmacol. Biochem. Behav. 58(1):133-140, 1997; A. J. Halliday et al., Life Sci. 65(2)225-236, 1999 and D. E. Selley et al., Biochem. Pharmacol. 62:447-455, 2001). In fact, recent pharmacokinetic studies (see review and references therein in J. Halliday et al., Life Sci. 65(2)225-236, 1999) support the idea that the analgesic and/or addictive actions of morphine in CNS are not directly and predominantly mediated by morphine itself, but largely exerted by its glucuronated active metabolites such as the morphine-6-glucuronide. So far, several studies (L. M. Kamendulis et al., J. Pharmacol. Exper. Ther. 279:713-717, 1996 and A. J. Halliday et al., Life Sci. 65(2)225-236, 1999) have shown similar pharmacokinetic and pharmacodynamic mechanisms for heroin. Thus, once heroin is administered, a large fraction of the drug is rapidly catabolized in the plasma and/or liver into 6-monoacetyl-morphine, and subsequently catabolized into morphine and finally converted into morphine-6-glucuronide, before reaching their neuronal targets (e.g., mu opioid receptor) (R. E. Aderjan and G. Skopp, Ther. Drug Monit., 20(5): 561-9, 1998). These findings support the current concept that the pharmacological agonism of heroin and its endogenous metabolites (e.g., 6-monoacetyl-morphine and morphine) on the mu opioid receptor including the final biotransformation active metabolites (e.g., morphine-6-glucuronide) represents the pharmacodymamic mechanism by which these substances enhance their reinforcing addictive actions in the brain (a. J. Halliday et al., Life Sci. 65(2): 225-236, 1999, D. E. Selley et al., Biochem. Pharmacol. 62:447-455, 2001 and C. P. O'Brien, Drug Abuse, In: The Pharmacological Basis of Therapeutics. pp. 621-642, 10th ed. J. G. Hardman and L. E. Limbird, eds. McGraw Hill, New York, 2001).
Several pharmacodymic studies (see reviewed works in E. J. Nestler, Nat. Neuroci. 5:1076-1079, 2002 and P. N. Deslandes et al., J. Pharmacy and Pharmacol. 54:885-895, 2002) have shown that chronic abuse to both heroin and morphine leads to the development and establishment of specific long-term changes at the cellular and molecular level that ultimately produces the expression of biological neuroadaptations to opiate addiction. Moreover, these neuronal changes produce important electrophysiological, neurochemical and genomic changes, which are progressively established and consolidated upon a long-term period (e.g., years) in the brain during drug addiction. Therefore, the behavioral changes occurring during opiate addiction to these substance of abuse in the individual, follow a time-course of increased complexity and intensity with regard to the drug addiction symptomology. For instance, the repetitive administration of heroin by an addict, produces an increase stereotyped compulsive behaviors leading to uncontrolled drug-intake behaviors, associated with stereotyped rites of administration, initially accompanied by pharmacological tolerance and subsequently by physical signs and symptoms of drug withdrawal after acute suppression of the opiate drug (K. Severino et al., Ann. NY Acad. Sci 909: 51-87, 2000). Thus, heroin-intake behavior becomes the highest priority and necessity in the addicted individual, leading to the reinstatement of compulsive drug-intake and drug-seeking behaviors normally observed during drug withdrawal or abstinence. The neuroadaptative changes occurring during opiate addiction is primarily caused by the pharmacological actions displayed by the repetitive exposure of the drug over a clustered group of neurons localized in different areas of the brain (K. Severino et al., Ann. NY Acad. Sci 909: 51-87, 2000). These brain areas include the locus coeruleus, hippocampus, lateral hypothalamus, ventral-tegmental area, amygdaloid complex, nucleus accumbens and prefrontal cortex, which structurally comprised the neuroanatomical substrate and neural pathways where opiate substances and other illegal drugs of abuse (e.g., cocaine) mainly exert their drug-rewarding and drug-reinforcing activities (K. Severino et al., Ann. NY Acad. Sci 909: 51-87, 2000). In this context, the chronic administration of both morphine and heroin induces the development of a series of homeostatic cellular and molecular adaptative responses on neurons within the aforementioned brain structures impinged by the drug. Such adaptative responses involve several electrophysiological, biochemical and genomic alterations seen during drug addiction, which altogether, are produced to maintain and restore the pre-existing functional homeostasis of the implicated neural circuits and their operant neurons altered during drug abuse, prior to the compulsive drug-intake behavior (K. Severino et al., Ann. NY Acad. Sci 909: 51-87, 2000). Once these neuroadaptations have been established, the abrupt suspension of the drug-intake behavior enhances the development of new series of neurobiological changes and cellular adaptations in the neurons impinged by the drug, leading to the neuropathological basis that underlies the withdrawal syndrome during drug addiction. The withdrawal syndrome produced by both morphine and heroin in the addicted individual, as opposed to the withdrawal syndrome induced by cocaine and amphetamine, is characterized by highly intense physical and psychological alterations in the addicted individual (H. Ghodse, Drugs of abuse and dependence. In: Drugs and Addictive Behavior, a guide to treatment, Blackwell Science Ltd, ed., Oxford, UK, pp. 72-119, 1995; G. F. Koob, Ann. N. Y: Acad. Sci. Vol. 909:185 2000 and K. Severino et al., Ann. N.Y. Acad. Sci 909: 51-87, 2000). Clinically, the withdrawal syndrome is characterized by four different stages developed in a progressive or gradual time-course. During the first 1-7 hours, the addict under abstinence develops behavioral manifestations characterized by a compulsive craving and extreme anxiety for drug-intake. During a second stage (after 8-15 hours), physical alterations such as intense lacrimation, extreme sweating, rinorrhea and lethargy are added to the initial drug symptomology. Further on, after 16-24 hours upon continuing drug withdrawal, physical signs such as mydriasis, piloerection, muscular cramps and changes in body temperature (e.g., intense cold and heat perception) in addition to diffuse algias, anorexia and irritability may appear as well. Subsequently, upon persistent withdrawal (e.g., 2-6 days), other physical and behavioral signs may appear which include insomnia, fever, motor delay, abdominal pain, vomiting and diarrhea as well as increased abnormal breathing, including changes in pulse frequency and blood pressure. Thus, from the perspective of symptomology occurring in drug addiction, the duration and severity of morphine and heroin withdrawal depends on several pharmacokinetic and pharmacodynamic factors. Moreover, there has been reported that the severity of opiate withdrawal syndrome depends on several pharmacological and biological aspects, which include the daily amount of drug-intake (e.g., dose injected by the individual), the period of time of drug use and/or abuse, in addition to the physical and personality status of the individual affecting drug-intake response.
Thus, given the complexity of the natural history of the morphine/heroin addictive pathology, few currently available pharmacological treatments have been designed to modify the pharmacodynamic mechanisms by which these opiate substances produce their drug-reinforcing actions once they bind their specific receptor sites at their targeted neurons (D. M. Grilly, Opioids (narcotics) and their antagonists. In: Drugs and human behavior, 4th ed. pp. 238-262, Allyn and Bacon, eds. USA, 2002). In this context, the acute opiate detoxification treatment represents the initial and most currently used pharmacotherapeutic approach to treat clinically chronic addicts, which becomes a medical priority and emergency to relieve the individual's physical signs and symptoms of drug withdrawal, which are commonly associated with physiological, endocrinological and chemical disturbances induced by drug addiction. For example, mu opioid receptor partial agonists such as methadone and buprenorphine, in combination with benzodiazepines and/or sedative neuroleptics are commonly prescribed and administered for the acute desintoxication treatment to opiates. As opposed to the acute detoxification procedures used to treat opiate addiction, the substitution therapy using opiate substances such as methadone and/or buprenorphine as well as opioid receptor antagonists, such as naloxone and/or naltrexone, are not entirely recommended during opiate withdrawal, because they exacerbate the demand of drug-intake behavior of the parent opiate compounds that elicited or installed the former drug addictive state in the individual. Under normal circumstances, the treatment and maintenance of opiate withdrawal syndrome requires hospitalization and clinical care with the support of specialized medical personnel, which commonly results to be highly expensive.
Likewise to the withdrawal syndrome, the complete morphine and/or heroin detoxification (suppression of drug-intake behavior) in addicted individuals is an important health issue to be pursued. Based on the wide range of abnormal functional changes established after a long-term period in the brain produced by chronic opiate abuse, it is easy to understand the difficulties to re-establish the homeostatic function of the brain, prior to drug-intake, by the current available detoxification therapies. Thus, despite these therapeutic limitations, an ideal detoxification treatment must be address to meet specific medical criteria described as follows. Firstly, it should be directed to block or blunt the physiological and psychological opiate dependence in order to re-establish the homeostatic balance of those neural systems chronically dysregulated by opiate substances. Secondly, the detoxification treatments should inhibit those pertinent physical and behavioral changes that appear to be exacerbated during drug withdrawal induced by therapeutic interventions, thereby resulting in a tolerable experience and safety treatments. Additionally, it should provide a complete suspension of the individual's drug-intake behavior, thus reorientating the addicted individuals to other alternate available non-pharmacological treatments (e.g., psychotherapy and counseling). Thereafter, once the complete opiate detoxification therapy is reached, the final medical goal to be approached is the prevention of subsequent relapses to opiate abuse. Thus, from a general medical viewpoint, the therapeutic challenges to blunt morphine/heroin addiction are enormous and, in most of cases, difficult to improve. The main obstacles faced by both pharmacological and non pharmacological-based treatments, are the lack of an adequate number of specialized clinics or hospitals, the high economical costs of therapy usually billed to the patient and, most importantly, the absence of either patient follow-up programs (i.e., years) or continuous clinical evaluation as well as the lack of application of long-term psychotherapy support to prevent drug-relapse. In addition, another major problem facing most of the current anti-addictive treatments against opiate abuse is the side-effect toxicity resulting from long-term dosification of single or combined pharmacological agents (K. Severino et al., Ann. NY Acad. Sci 909: 51-87, 2000). For example, methadone and buprenorphine, two long-lasting partial agonist of the mu opioid receptor, represent the most common substitution therapeutic drugs used today to blunt opiate withdrawal syndrome or to prolong opiate abstinence (M. J. Kreek, Ann. N.Y. Acad. Sci, 909: 186-216, 2000). In addition, α2 adrenergic receptor agonists such as clonidine, guanfacine and/or lofexidine represent another set of compounds used quite frequently in detoxification therapies to amielorate withdrawal signs and symptoms caused by the abrupt suppression of opiate drugs (M. J. Kreek, Ann. N.Y. Acad. Sci, 909:186-216, 2000). However, besides of their widely use in long-term detoxification therapies and/or treatment maintenance of abstinence, these drugs have been shown to induce several toxic side-effects. For example, methadone, buprenorphine and pentazocine have been reported to produce sleep disorders, anxiety and severe cognitive and emotional impairment. Additionally, α2 adrenergic receptor agonists have been reported to produce sedation, hypotension, extreme anxiety and asthenia upon long-term administration. In addition, patients receiving opiate-substitution with methadone, may not surprisingly, show the development of signs and symptoms of opiate-dependence due that this mu opioid receptor partial agonist produces same neurochemical, cellular and molecular neuroadaptative changes in the brain, as those reported for both morphine and heroin during opiate addiction (M. J. Kreek, Ann. N.Y. Acad. Sci, 909:186-216, 2000). Other available drugs currently used to prolong abstinence and to relapse prevention against morphine/heroin addiction in detoxified patients comprise the mu opioid receptor antagonists, naloxone and naltrexone. The toxic side effects often seen during the long-term administration of these compounds are mostly due to the blockade of the endogenous opioid transmission systems in the brain, leading to impairment of both cognitive and emotional brain functions, among many other physiological activities (M. J. Kreek, Ann. N.Y. acad. Sci, 909:186-216, 2000).
Thus far, one major conclusion drawn from the above described pharmacological therapies currently used to approach detoxification against opiate abuse including long-term maintenance treatments for drug-withdrawal and relapse-prevention against morphine/heroin addiction, is that none of these pharmacological treatments have shown an optimum efficacy. This conclusion is based on the fact that these drugs produce important toxic side-effects in patients receiving long-term maintenance of abstinence and/or relapse-prevention (T. Kosten and D. Biegel, Expert Rev. Vaccines, 1(3): 89-97, 2002). Thus, there is an urgent need to develop and validate novel anti-addictive therapeutic strategies, based on the synthesis, application and validation of highly effective new drug formulations, displaying minimum toxicity and no detected side-effects, when pretend to be use in the long-term therapies for acute detoxification and long-term maintenance of morphine/heroin abstinence.
For this reason, here are given and shown all the reports and documents concerning the state of the art of the development and application of techniques related to the present invention, which are detailed herein and are also included to be used only as reference material.
In this context, different groups have designed, applied and validated alternative therapeutic strategies in experimental animal models, which share a common pharmacokinetic mechanism. Thus, conversely to the classical anti-addictive pharmacology, this latter mechanism is based on altering the drug's pharmacokinetics by decreasing significantly or blunting the blood-brain barrier permeation of the "free" unbound drug in plasma, which ultimately represents the fraction of drug in plasma that permeates the brain causing the high reinforcing and rewarding effects in the addicted individual. All of these experimental approaches have been focused to decrease significantly or prevent the blood-brain barrier permeation of drugs of abuse, by enhancing the binding of the "free" unbound fraction of drug in plasma by specific antibodies, which recognize and bind with high specificity and avidity to these drugs in the blood. As immunoglobulins (antibodies) do not normally permeate the blood-brain barrier, the plasma fraction of "free-unbound drug", which is the available pool of drug that permeate the blood brain barrier, interact with immunoglobulins establishing drug-antibody complexes, which ultimately decreases significantly this fraction of free-unbound drug in plasma. This change in the drug's pharmacokinetics in plasma, leads to altered changes in drug's pharmacodynamics in the brain, thus blunting or abolishing the activity of addictive drugs on their specific targeted neurons. These latter pharmacodynamic changes ultimately lead to blunt both the development of the reinforcing activities and the rewarding pleasant effects induced by drugs of abuse in the brain. The main pharmacokinetic property shared by most drugs of abuse, is the high blood-brain permeation activity, which represents the basic and crucial mechanism, by which most of the potent drugs of abuse produced their highly intense reinforcing actions in the brain, leading to the continuous drug-intake and drug-seeking behaviors display by individuals upon exposure to these chemical compounds. In this context, the generation of specific serum antibodies against drugs of abuse represents an alternate therapeutic approach to blunt or prevent the blood-brain barrier permeation of drugs of abuse from reaching its neuronal targets. This antibody antagonism approach preventing drug's permeation into the brain has been shown to enhance an immunoprotective effect against drug-intake and drug-seeking behaviors, as demonstrated for cocaine, nicotine, PCP and amphetamines in rodents (see an account of reviewed works and references therein in T. Kosten and D. Biegel, Expert Rev. Vaccines, 1(3): 89-97, 2002 and K. Kantak, Drugs, 63(4): 342-252, 2003). With regard to cocaine, several research groups were able to develop and apply different experimental strategies based on the design, synthesis, application and validation of several immunogenic preparations of carrier proteins with covalently haptenized cocaine (Kantak et al., Psychopharmacology 148:251-262, 2000; Fox, B. S. et al., Nat. Medicine, 2:1129-1132, 1996; Sparenborg et al., Therapeutics 293(3): 952-961, 2000; Carrera et al. Nature, 378:727-730, 1995, Carrera, R. et al., Proc. Nat. Acad. Sci, USA, 97(11)6202-6206, 2000). Some high molecular weight proteins such as BSA and KLH have been used as carriers to covalently link cocaine using standard chemical covalent coupling procedures. In this way, following active immunization protocols in rodents, some of these immunogens have shown capabilities to generate low to moderate antibody titer responses against this drug of abuse in actively vaccinated animals. Moreover, other experimental approaches conferring immunoprotective effects against cocaine addiction have been explored by enhancing the generation of conventional and/or catalytic monoclonal antibodies administered during passive immunization protocols against this psychoactive drug in rodents (Metz et al., Proc. Natl. Acad. Sci. USA 95:10176-10180, 1998; Fox et al., Nat. Med. 2:1129-1132, 1996 and Landry et al., Science, 239:1899-1901, 1993). The immunoprotective effects against cocaine addiction using these immunological-based experimental strategies have been explored by detecting the abolishment of the drug-reinforcing behaviors in rodents in combined pharmacological and operant-behavioral paradigms. These experimental strategies share a common anti-addictive mechanism, which relies in the significant reduction and/or complete inhibition of the blood-brain permeation of the "free" unbound fraction of cocaine in plasma. Thus, in actively vaccinated hyperimmune animals, the fraction of "free" unbound of drug in plasma is significantly reduced, once specific serum antibodies in the blood bind to the psychoactive drug (Kantak et al., Psychopharmacology, 148:251-262, 2000; Carrera et al., Proc. Natl. Acad. Sci. USA, 97(11):6202-6206; Carrera et al., Nature, 378:727-730, 1995). Alternatively, monoclonal antibodies raised against cocaine, may bind the "free" unbound fraction of cocaine after being passively transferred into the blood (Metz et al., Proc. Natl. Acad. Sci. USA 95:10176-10180, 1998; Fox et al., Nat. Med. 2:1129-1132, 1996, Benowitz, Pharmacol. Toxicol. 72:3-12, 1993). In both cases, the common immunological neutralizing mechanism, which promotes altered changes in cocaine pharmacokinetics, leads to the significant decrement or complete inhibition of drug's entry into the brain, thereby decreasing or blunting the targeting of cocaine to the specific neuronal membrane dopamine reuptake transporter. This latter antibody-mediated mechanism inducing altered changes in cocaine's pharmacodynamic in the brain, would lead to changes in the synaptic level of amine neurotransmitters, abolishing the evoked-dependent increase in the central catecholaminergic tone, normally seen after cocaine's entry into the brain in addictive individuals. The final behavioral scenario that results from these altered changes in cocaine pharmacokinetics and neurochemical events is the lack of the intensified rewarding effects induced by this potent reinforcing drug in the brain of mammals. Thus, once cocaine has been neutralized to produce its reinforcing and rewarding effects in hyperimmune animals, the reinforcing properties of this drug will be lost upon a subsequent drug exposure, as demonstrated by the suppression of drug-seeking and drug-intake behaviors in such hyperimmune vaccinated animals (rodents) seen with use of some immunogenic conjugates of cocaine.
In summary, most of the aforementioned pre-clinical studies have shown the feasibility of using antibody-based antagonism approach for blunting drug-taking and drug-seeking behaviors in rodents. However, the type of the carriers proteins (e.g., BSA and KLH) used in the preparation of the immunogenic conjugates (vaccines) used in these studies preclude its potential use in vaccine formulations for use in human immunization protocols (Carrera et al., Proc. Natl. Acad. Sci. USA, 2001; Carrera et al., Proc. Natl. Acad. Sci. USA, 2000; Carrera et al., Nature, 378:727-730, 1995; Kantak et al., Psychopharmacology, 148:251-262, 2000; Ettinger et al., Pharmacol. Biochem. Behav. 58:215-220, 1997 and Fox, Drug and Alcohol Depend. 48:153-158, 1997). Furthermore, the synthesis of conventional and or catalytic mouse anti-cocaine monoclonal antibodies used as potential passive immunotherapy for addition in experimental animals (rodents), has the main limitation in conferring immunoprotection in a short-term period when passively administered. This is mostly due to the fast metabolic clearance of these murine immunoglobulins from serum of passively immunized animals other than mice (Goldsby et al., Vaccines, In: Kuby Immunology, 4th ed. Freeman and Co. New Cork, N.Y., pp. 449-466, 2000). Moreover, the potential use of the available murine anti-cocaine monoclonal antibodies as immunological therapeutic agents against cocaine addiction in humans, requires the use of DNA recombinant techniques, so as to "humanize" the Fc segment of murine immunoglobulins.
Finally, the potential application of this antibody-based antagonism against cocaine addiction in the human is a current issue under experimentation as a therapeutic approach. This immunopharmacological strategy was initially approached through the synthesis of an anti-cocaine vaccine formulation, structurally designed for human use, where cocaine was covalently conjugated to the recombinant β-subunit of the cholera toxin (used as carrier protein. At pre-clinical level, this conjugate showed moderate efficacies in triggering antibody responses in actively vaccinated rats that conferred immunoprotective effects to prevent relapse to cocaine taking-behavior in this animal (Kantak et al., Psychopharmacology, 148:251-262, 2000). Additionally, active vaccination with this immunogen in human volunteers, used to test the safety and immunogenicity of this vaccine formulation, unfortunately, showed little promissory therapeutic effects, in this single Clinical Phase I study (T. Kosten et al., Vaccine 2559:1-9, 2001), due to the fact that this vaccine formulation showed a poor immunogenic capacity, producing low antibody titer responses [e.g., low concentration range (μg) of specific immunoglobulin/ml of serum] in most of the vaccinated subjects. In addition to the aforementioned experimental limitations, new anti-cocaine vaccines developed by different groups of research, are currently being under study, using different carrier proteins, in order to generate an improved immunogenicity against this psychoactive drug in both pre-clinical and Clinical Phase I studies. Once the immunogenic properties of these vaccine formulations are validated in humans in Clinical Phase I studies, it may become available for a subsequent evaluation in Clinical Phase II studies assessing the immunoprotecting capabilities of these vaccine formulations against cocaine addiction. For instance, it could be used Clinical Phase II studies by assessing the enhanced long-lasting humoral-based immunoprotection against cocaine addiction, in former drug addicts, exhibiting a prolong and controlled abstinence but challenged to the pharmacological reacquisition of addictive cocaine-intake behavior.
In the case of tobacco addiction, at least two immunogenic preparations (vaccines) to the reinforcing psychoactive substance, namely nicotine, have been designed for human application (see an account of reviewed works and selected references therein in T. Kosten and D. Biegel, Expert Rev. Vaccines, 1(3): 89-97, 2002; K. Kantak, Drugs, 63(4): 341-352,2003). Pre-clinical studies have demonstrated that these two vaccines were able to generate low to moderate serum titers of specific antibodies (i.e., 0.05-0.2 mg/ml of serum) against nicotine in actively vaccinated rodents. Moreover, active vaccination with these immunogenic preparations of nicotine, demonstrated to confer immunoprotection against the acquisition nicotine-intake behavior in intravenous drug-self-administration paradigms in rodents. The immunoprotective mechanism against nicotine addiction follows same pharmacokinetic mediated-mechanism described for cocaine addiction, that is, through the binding of the "free" unbound fraction of nicotine in plasma by specific serum antibodies, which prevents the blood-brain barrier permeation of this drug. Clinical Phase studies performed independently by Nabi Pharmaceuticals (Anti-nicotine vaccine NicVAX®) and Xenova Pharmaceutical Group in Belgium, reported successful results on the evaluation of the toxic and immunogenic properties of these two vaccine formulations. The reports on the evaluation of the immunoprotection capabilities of these two vaccine formulations against nicotine addiction in former drug addicted volunteers in Clinical Phase II studies are expected to be ready in the next two coming years.
In fact, the development of experimental strategies focused in the design and synthesis of immunogenic preparations and the subsequent validation of vaccination protocols for treating specific forms of drug addiction, were pioneered approached for opiates such as morphine and heroin, but not for cocaine and nicotine addiction. Retrospectively, at the beginning of the 70s, different research groups showed the feasibility of raising a humoral immune response against these two opiate substances using vaccination protocols in experimental animal models, such as the rat and the rabbit (S. Spector and C. W. Parker, Science, 168:1347-1348, 1970; S. Spector, J. Pharmacol. Exp. Ther. 178:253-258, 1971; E. L. Adler and C. Liu, J. Immunol, 106:1684-1685, 1971; H. Van Vunakis et al., J. Pharmacol. Exp. Ther. 180:514-521, 1972; B. H. Wainer et al., Science, 176-1143-1145, 1972; B. H. Wainer et al., Science, 178:647-648, 1972 and B. H. Wainer et al., J. Immunol. 110:667-673, 1973). These experimental approaches were focused in generating polyclonal antibodies against morphine, displaying distinct immunological cross-recognition against heroin and structurally related opiate analogues (e.g., codeine, meperidine, and hydromorphone). These antibodies were generated for using in specific-designed immunoassays (i.e., radioimmunoassay and ELISA immunoenzymatic assays) to detect and measure morphine and related opiate substances in biological fluids from humans. These studies showed, for the first time, the successful achievement on the design and validation of the covalent condensation of the exposed free 3- and 6-hydroxyl groups in the phenantrenic ring of the morphine molecule to carrier proteins such as BSA, using standard organic chemistry procedures (procedures that are still used when approaching chemical synthesis of such immunogenic conjugates). In addition, it is worth to mention that none of these chemical procedures were never reported and claimed in patent registries and they are mostly considered as classical chemical procedures in textbooks of organic chemistry, when describing the covalent linkage of the free 3- and 6-hydroxyl groups of the phenantrenic ring of morphine to carrier proteins. In such context, two structural intermediate products from morphine were successfully synthesized by different research groups and used for the development of vaccine formulations, namely, the 3-ortho-morphine-carboxymethyl-ether product (3-O-carboxymethylmorphine, see example 2) and the morphine-6-hemisuccinate (see example 3) (S. Spector and C. W. Parker, Science, 168:1347, 1970; S. J. Spector, J. Pharmacol. Exp. Ther. 178:253, 1971; H. Van Vunakis et al., J. Pharmacol. Exp. Ther. 180:514, 1972; and S. Gross et al., Immunochemistry, 11:453-456, 1974). With regard to the aforementioned intermediate derivatives of morphine used to develop vaccine formulations, two identical patent registries published on Sep. 13, 1991 (CH 678394 A5) and May 15, 1996 (EP 0 496 839 B1) by Erich Hugo Cerny, claim invention on the structural synthesis of novel anti-morphine vaccine formulations. However, it's worth to mention, that both of these patent registries reveal no real novelty or invention regarding the synthesis of the therapeutic vaccine formulations claimed. This argument is based on that both patent registries describe the same standard synthetic procedures previously reported to generate the intermediate 3-O-carboxy-methyl-morphine derivative used to covalently conjugate the KLH-carrier protein. In both instances, they used morphine-based and the sodium beta-chloroacetate and absolute alcohol as reagents in the reaction mixture. The other synthetic intermediate derivative used to activate the covalent linkage between morphine and carrier proteins, is the morphine succinyl ester linked to the free 6-hydroxyl group of the phenantrenic ring-structure of the morphine molecule, namely, morphine-6-hemisuccinate, (see example 3) (originally reported by B. H. Wainer et al., Science, 176:1143, 1972, A. Akbarzadeh et al., Biotechnol. Appl. Biochem, 30:139-145, 1999). In same context to the aforementioned synthetic procedures used to generate the 3-O-carboxymethylmorphine derivative for synthesizing vaccine formulations, an anti-morphine vaccine patent registry released from China (CN1196955), was unjustified granted from our own perspective, to Han Ying et al., on Oct. 28, 1998. These authors claim innovation and novelty regarding the synthetic procedures and the structural formulations of vaccine preparations to different opiate drugs, besides morphine, using same standard methods to synthetize morphine-6-hemisuccinate derivative, as previously reported (see in B. H. Wainer et al., Science, 176:1143, 1972, A. Akbarzadeh et al., Biotechnol. Appl. Biochem, 30:139-145, 1999). These authors used this intermediate derivative to haptenize morphine to BSA as carrier protein.
The structural design and synthesis of different immunogenic formulations, where morphine has been haptenized to carrier proteins such as KLH and BSA, represented the basis by which authors have invariably used chemical procedures to link covalently the intermediate derivatives of morphine 3-O-carboxymethylmorphine and morphine-6-hemisuccinate to these carrier proteins (as previously outlined in the experimental studies described above, including the aforementioned patent registries), using as cross-linker the homobifunctional chemical reagent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The EDC reacts with the available free carboxyl groups exposed in either the 3-O-carboxymethylmorphine or morphine-6-hemisuccinate derivatives, thus forming the corresponding two O-acylurea by-products, which are chemically reactive to generate covalent amide bonds with the epsilon (ε)-amino groups in the lateral chain of lysine residues of either BSA or KLH (see example 4).
The aforementioned studies demonstrating the feasibility to generate a humoral immune response against morphine and its structural cognate semi-synthetic opiate, heroin, led to a pioneer study reported nearly 30 years ago by Bonese (K. F. Bonese et al. Nature, 252:708-710, 1974). This study was in fact the pioneer report demonstrating that active vaccination with an immunogenic morphine conjugate in a single experimental animal, the non-human primate Macacus rhesus, was able to generate a protective humoral-mediated immune response that blunt the addictive self-administration behavior to heroin. The synthesis of this immunogenic conjugate was achieved by covalently haptenizing morphine to the BSA through a stable ester bond formed by the condensation of the succinic anhydride and the 6-hydroxyl group in the phenantrenic structure of the morphine molecule. The synthesized intermediate derivative, morphine-6-hemisuccinyl, was then covalently linked to the 1-ethyl-3-(3-Dimethylaminopropyl) carbodiimide (EDC) reagent, thus obtaining the complete immunogenic conjugate. The repeated subcutaneous injection of this immunogen into the primate triggered a humoral immunological response with specific morphine antibodies, which displayed cross-recognition for heroin. Additionally, the active vaccination approach with this conjugate demonstrated to be an effective procedure to blunt the re-acquisition of the intravenous self-administration behavior to heroin in this single primate, previously trained to self-administer different dose-units of this opiate. Although this pioneer report showed the first successful antibody-based antagonism procedure to blunt heroin-intake behavior in the primate, it was never patented and developed for clinical use. Similarly, no further experimental studies related to the design, synthesis and validation of further novel structural anti-morphine/heroin vaccine formulations using carrier proteins suitable for human vaccination were developed, basically due to the fact that BSA is not a licensed carrier protein for such experimental purposes. The main reason that these immunopharmacological studies were never approached in humans with suitable immunogens for morphine or heroin could be due, at least in part, to the simultaneous and continuous development of other neuropharmacological agents used to treat morphine-heroin addiction. For instance, synthetic drugs that display weak and partial agonist activities on the mu opioid receptor (i.e., methadone and buprenorphine) and other drugs which display antagonist activities on opioid receptors (i.e., naltrexone and naloxone). All these drugs are currently used for preventing relapse to opiate addiction.
Based on the aforementioned reports of experimental vaccines against morphine/heroin addiction, which never approached human vaccination, preliminary experimental studies conducted by our research group served as a basis, for the development of the present invention of the bivalent vaccine formulation against morphine-heroin addiction. These experiments describe the design, synthesis and evaluation of the immunogenicity induced by different synthesized structural models of a new generation of vaccines against anti-morphine/heroin (B. Anton and P. Leff., 31st Annual meeting of the Society for Neuroscience. San Diego, Calif. Nov. 10-16, 2001). Such structural formulations of vaccines were initially synthesized by linking covalently the morphine-6-hemisuccinate (M-6-H) intermediate derivative with several carrier proteins such as BSA, KLH and the recombinant cholera toxin-β-subunit protein. These coupling reactions used standard crosslinking procedures for linking the morphine-6-hemisuccinate (M-6-H) intermediate derivative to the 1-ethyl-3-(3-Dimethylaminopropyl)-carbodiimide (EDC) reagent. These preliminary experimental data gathered from such studies made possible the identification of candidate carrier proteins for covalent haptenization of morphine. It is worth to mention that this work was only presented in a slide session at the aforementioned International Neuroscience Meeting.
Furthermore, it did not show any information concerning experimental data related to the design of the structural molecular models of immunogens, methodologies describing the synthesis, purification, application and dosification procedures of these new vaccines. Moreover, no references or descriptions of the validation of the anti-addictive effects against morphine-heroin were also made, which are disclosed in the present invention of the therapeutic bivalent morphine-heroin vaccine formulation against the addiction to these opiate substances.
In addition to the pioneer study reported by Bonese and co-workers, who demonstrated the efficacy of the active vaccination with BSA-morphine to blunt the addictive self-taking behavior of heroin in a single primate, other research groups explored the immunoprotective effects of the passive immunization against morphine, using behavioral paradigms of intravenous self-administration of heroin in rodents (P. R. Pentel et al., Pharmacol. Biochem. and Behavior, 9:347-352, 1991). From a potential therapeutic viewpoint, a passive immunoprotection procedure against morphine and heroin addiction has practical limitations to prolong and maintain abstinence to opiate drugs in humans on a long-term basis, as opposed to the active immunization procedures. These limitations are based on some practical observations derived from experimental results of passive immunoprotection paradigms (R. A. Goldsby, Vaccines. In: Kuby Immunology, 4th ed. Freeman and Co, New Cork, N.Y., pp. 449-466, 2001). These data have demonstrated the relatively short biological half-life of murine monoclonal antibodies (3-23 days, depending on the immunoglobulin class and isotype) after being administered in vivo into different experimental animals. Thus, immunoprotection conferred via passive administration of murine monoclonal antibodies into non-murine hosts is usually short-lived. Moreover, as both monoclonal and polyclonal antibodies used in passive immunization therapies are commonly produced from different animal species (e.g., mouse, rabbit, etc.), such immunoglobulins are usually recognized as foreign antigenic molecules when injected into human subjects. In this context, passive immunization of patients with such immunoglobulins would trigger a rapid humoral immunological response against these molecules, which ultimately result in a blunted antibody-mediated neutralizing responses and reduced half-life of these types of immunoglobulins in plasma. Thus, once primed such antigenic responses against heterologous antibodies in passively immunized subjects, the subsequent administration of these types of immunoglobulins would lead to the development of abnormal immunological responses of hypersensibility upon repeated passive administration of such molecules.

Process for the preparation and use of a bivalent vaccine against morphine-heroine addiction

Instituto Nacional de Psiquiatria Ramon de la Fuente Muniz


A rotary-anode X-ray tube includes a sleeve bearing having bearing faces which are rotatable relative to one another in a direction of rotation and at least one of which is provided with a pattern of grooves. The service life of such a sleeve bearing can be prolonged by providing the grooves with a recess at their rearmost end, viewed in the direction of rotation.

1. Field of the Invention
The invention relates to a rotary-anode X-ray tube, including a sleeve bearing having bearing faces which are rotatable relative to one another in a direction of rotation and at least one of which is provided with a pattern of grooves.
2. Description of the Related Art
An X-ray tube of this kind is known, for example from EP-A 378 274 which corresponds to U.S. Pat. No. 5,077,775, or from DE-OS 28 52 908. The sleeve bearings of these tubes can operate in a given direction of rotation only. Between the bearing faces which are rotatable relative to one another there is provided a liquid lubricant, for example a gallium alloy.
During steady operation of the sleeve beating in the relevant direction of rotation, such pressure conditions arise in the lubricant, inter alia under the influence of the groove pattern, that a hydrodynamic lubricant film is formed and the bearing surface cannot contact one another. At the beginning and at the end of the rotation, however, these conditions are not satisfied so that wear phenomena which limit the service life of the bearing may appear.
It is an object of the present invention to construct an X-ray tube of the kind set forth so that the service life of the sleeve bearing is prolonged. This object is achieved in accordance with the invention in that a recess is provided at the rearmost end of the grooves, viewed in the direction of rotation.
The invention is based on the recognition of the fact that particles become detached from the bearing surfaces during the start and landing processes; these particles will also be referred to hereinafter as abrasion particles. The abrasion particles collect at the areas of the grooves in which the highest pressure occurs in the lubricant during rotation of the bearing. This is the rearmost pan of the bearing, viewed in the direction of rotation. In the course of time such a large amount of abrasion particles could collect and be compressed in this part of the grooves that extensive wear can occur at that area, resulting in a breakdown of the bearing.
When the grooves are provided with a recess at that area, a substantially larger quantity of abrasion particles can collect at that area, so that the service life of the bearing is prolonged. The recess, extending over only a comparatively small pan of the overall length of the grooves, has an insignificant effect only on the bearing capacity of the bearing and can be taken into account right from the start of design. The recess should be provided only in the grooves, but not in the ridges between the grooves.
It is to be noted that from EP-A 204 359 there is already known a sleeve bearing comprising a groove pattern with a varying depth of the grooves. This bearing is a sleeve bearing for a horizontally positioned shaft which is journalled in a bearing sleeve. The groove depth therein varies continuously in the circumferential direction so that at the area where the bearing is exposed to the highest load, the depth of the grooves is smallest. As a result, the bearing has its highest bearing capacity at that area. However, the aim is not to prolong the service life of such a bearing nor is such a prolongation achieved by the described steps.
In an embodiment of the invention, one of the bearing faces is provided with a groove pattern in two adjoining areas, the grooves in one area extending towards the grooves in the other area at an angle which deviates from 180.degree. C. and which is preferably an acute angle, said grooves terminating at the boundary between the areas and a recess being provided in the grooves at their end near the boundary. In another embodiment of the invention, however, one of the bearing faces is provided with a pattern of grooves which extend in the direction perpendicular to the axis of rotation, which grooves start at the outer side and terminate at the inner side, viewed in the direction of rotation, the inner ends of the grooves opening into a ting-shaped or circular recess. In this case the rear part of the grooves, viewed in the direction of rotation, is situated at its inner end, so that the recess must be provided at that area.

Rotary-anode x-ray tube comprising a sleeve bearing


A cascade digital filer has a plurality of cascade-connecting pairs of integrators and differentiators to realize a transfer function obtained by cascade-connecting a plurality of moving average filters. Each of the integrators includes an adder which has a two's complement operating function which inverts its polarity on overflow. Each of the differentiators also includes an adder which has the same number of bits and the same function as does the adder of integrator. The adder in each of the integrators and differentiators prevents the output of the digital filter from diverging, thus resulting in normal filtered output.

In general, a FIR digital filter, as shown in FIG. 1, has a non-recursive configuration comprising k one-clock delay elements D1-Dk, k+1 multipliers M1-M(k+1) for multiplication of the respective tap coefficients b.sub.0 -b.sub.k+1, and an adder A1 for adding these products. The transfer function H(z) of this FIR filter is given by the following equation. ##EQU1##
In order to realize the configuration by means of hardware, a product-sum operation circuit as shown in FIG. 2 has been generally employed. In FIG. 2, the respective tap coefficients stored in a ROM (Read Only Memory) 1 and the input X are sequentially multiplied together by a multiplier 2 in accordance with the clock timing. The respective results are sequentially entered to an accumulative adder 5 comprising an adder 3 and an accumulator 4, which plays parts of the delay elements D1 to Dk and the adder A1 of FIG. 1. Thus, the transfer function as shown in equation (1) can be realized.
The filter output Y is output at each time when the accumulative adder 5 has operated (k+1) times. In other words, the output Y of the FIR filter is caused by 1/(k+1) decimation of the output of the accumulator 4. However, since this decimation frequency is two or more times as great as a frequency of the passband of this filter, there is no problem occurring in the resulting filter output.
The moving average filter is obtained by setting all the tap coefficients b.sub.0 -b.sub.k+1 of the FIR filter shown in FIG. 1 to 1. In consequence, from the equation (1), the transfer function of the moving average filter can be given by the following equation. ##EQU2## As seen from this equation (2), the moving average filter is a nonpolar or all-zero lowpass filter in which k zero points are assigned at equal intervals on a unit circle of the z-plane with a zero point and a pole canceling out at z=1. Such a moving average filter can be realized in the circuit of FIG. 2 by setting all the tap coefficients of the ROM 1 to 1 or by only the accumulative adder 5.
The FIR filter in which two or more moving average filters are cascade-connected has the tap coefficients each being a positive integer. In consequence, the function of the multiplier in the product-sum operation circuit can be realized by the adder so that the amount of hardware is reduced.
In particular, in the FIR filter where two moving average filters are cascade-connected, its tap coefficients can be represented by a monotone increasing or decreasing function. Assuming that the two moving average filters cascade-connected have (k+1) and (l+1) tap coefficients, respectively, its transfer function can be given by the following equation. ##EQU3## As shown by this equation, the tap coefficients sequentially increase one by one up to the (l+1)th tap, become a constant value (l+1) from the (l+1)th tap up to the (k+1)th tap, and sequentially decrement one by one from the (k+1)th tap to the last tap. Therefore, in the FIR filter which realizes such a transfer function by means of hardware, it becomes possible to produce the tap coefficients by using an up/down counter in place of the ROM 1 to thereby further reduce the hardware amount.
However, in the conventional arrangement as shown in FIG. 2, if three or more moving average filters are cascade-connected to form a FIR filter, the monotoneity of the tap coefficients described above disappears. As a result, a ROM for storing the tap coefficients becomes necessary, therefore it is difficult to drastically reduce the hardware amount.

Cascade digital filters for realizing a transfer function obtained by cascade-connecting moving average filters


This invention relates to a dispersant for an organic pigment comprising a compound represented by the below-described formula (1) or (2), and also to its use. According to the present invention, it is possible to provide a dispersant or the like, which can afford a coating formulation for a color filter. The coating formulation is prevented from an increase in viscosity and a reduction in storage stability even when the concentration of a pigment is high, and can fabricate the color filter with excellent transparency and color quality.

Color filters employed in liquid crystal displays and the like are each primarily fabricated by applying a coating formulation, which is formed of a photoresist (photosensitive resin solution) and a pigment dispersed in the photoresist, onto a color filter substrate by the spin coating method, a coating method or the electrodeposition method, exposing the thus-formed color coating film to light through a photomask, and then developing the thus-exposed coating film to develop a pattern such that pixels are formed, that is, by a so-called pigment dispersion process (a process making use of a pigment as a colorant).
As a coloring pigment for a coating formulation to be used for the formation of blue pigments, a dioxazine violet pigment of a violet color (C.I. Pigment Violet 23) has been mixed and used for the purpose of color correction (color matching) in addition to ε-phthalocyanine (C.I. Pigment Blue 15:6) as a blue pigment. Especially with a view to improving the blue pixels of color filters for TV monitors, the demand for which is markedly growing in recent years, into pixels of more preferred color quality, there is an outstanding requirement to increase the mixing ratio of the dioxazine violet pigment to ε-phthalocyanine as a blue pigment.
Upon dispersing the above-described mixed pigment of the ε-phthalocyanine pigment and the dioxazine violet pigment in a dispersion medium such as a photoresist, however, the mixed pigment cannot be fully dispersed when it is simply dispersed in a conventional disperser. If blue pixels are formed from the resulting coating formulation, the pixels lack optical transparency and have insufficient light transmittance as blue pixels for color filters. The coating formulation comprised of the above-described mixed pigment is, therefore, dissatisfactory as a blue-pixel-forming coating formulation for color filters.
As resins generally employed in photoresists as dispersion media for pigments, on the hand, acrylic polymers of high acid value are primarily adopted so that color coating films after exposure can be developed by an aqueous alkaline solution. However, a coating formulation comprised of the mixed pigment and a photoresist, which contains such an acrylic resin of high acid value, involves problems in that the pigment tends to undergo aggregation and the viscosity of the coating formulation tends to become higher and also that with time, the coating solution thickens and the storage stability of the coating formulation deteriorates.
Upon formation of pixels of the respective colors of a color filter with coating formulations accompanied by such difficulties as described above, the coating formulations employed are each applied onto a substrate by the spin coating method and the resultant coating film is then exposed to light and developed to form a pattern. When the coating formulations so employed have high viscosity or show thixotropic viscosity due to aggregation of their pigments, the color coating films (before their exposure) formed from the respective coating formulations swell up at central parts. Fabrication of a large-size color-filter, therefore, leads to a problem in that unevenness and a difference occur in color hue and color density, respectively, between pixels on a central part of the substrate and those on a peripheral part of the substrate.
Although each coating formulation for a color filter generally has a pigment concentration in a high concentration range of from 5 to 20 wt %, it is therefore necessary that its dispersion state is free from aggregation of pigment particles, its viscosity is low (for example, 5 to 20 mPa·s or so) compared with general room-temperature drying coating formulations or baking coating formulations, and it is excellent in storage stability.
To meet the above-described requirements, methods have been proposed to date for cases where the pigment is ε-phthalocyanine (C.I. Pigment Blue 15:6), including the method that adds a substituted derivative of phthalocyanine blue or a substituted derivative of dioxazine violet as a dispersant to the pigment and the method that treats the pigment with the above-described derivative (see, for example, Patent Documents 1 to 6).    Patent Document 1: JP-A-56-167762    Patent Document 2: JP-B-1-34268    Patent Document 3: JP-A-4-246469    Patent Document 4: JP-A-6-240161    Patent Document 5: JP-A-6-240162    Patent Document 6: JP-A-7-188576

Dispersing agent for organic pigment and use thereof

Dainichiseika Color & Chemicals Mfg. Co., Ltd.


A method for the preparation of silver halide tabular emulsion grains, containing at least 75 % chloride, wherein at least 50 % of the total projected area of all the grains is provided by the tabular grains, and wherein the tabular grains exhibit an average aspect ratio of at least 5:1, an average thickness not greater than 0.5 micron and an average diameter of at least 0.6 micron. The method comprises. preparing a dispersion medium containing a gelatino-peptizer, and a compound ##STR1## wherein Z represents the atoms necessary to form a fused on aromatic carbocyclic or heterocyclic, unsubstituted or substituted ring, e.g., substituted with alkyl, alkenyl, aryl, alkoxy, hydroxy, mercapto, carboxy, amino or halogen, R is hydrogen or a substituent as defined for ring Z; n is 1 or 0, and Q represents carbon in which case n=1, or Q represents nitrogen, in which latter case n =0; in a concentration ranging from 10.sup.-4 to 10.sup.-2 molar. The pH of the medium is adjusted to between 5.0 and 9.0 and to a pCl between 1.0 and 2.0 by means of a chloride ions providing salt; PA1 performing a silver halide precipitation comprising at least one double jet step by introducing in the dispersion medium at least one solution containing chloride ions and at least one solution containing silver ions in such a way that pCl is maintained between 1.0 and 2.0, pH is maintained between 5.0 and 9.0 and the concentration of compound (Ia) or (Ib) is maintained between 10.sup.-4 molar and 10.sup.-2 molar; and PA1 removing excess of soluble salts by a wash technique performed at a pH value comprised between 4.0 and 9.0.

Tabular grains are known in the photographic art for quite some time. As early as 1961 Berry et al described the preparation and growth of tabular silver bromoiodide grains in Photographic Science and Engineering, Vol 5, No 6. A discussion of tabular grains appeared in Duffin, Photographic Emulsion Chemistry, Focal Press, 1966, p. 66-72. Early patent literature includes Bogg U.S. Pat. No. 4,063,951, Lewis U.S. Pat No. 4,067,739 and Maternaghan U.S. Pat. No. 4,150,994, U.S. Pat. No. 4,184,877 and U.S. Pat. No. 4,184,878. However the tabular grains described herein cannot be regarded as showing a high diameter to thickness ratio, commonly termed aspect ratio. In a number of U.S. applications filed in 1981 and issued in 1984 tabular grains with high aspect ratio and their advantages in photographic applications are described. So Wilgus U.S. Pat. No. 4,434,226 discloses tabular silver bromoiodide grains having a thickness less than 0.3 micron, a diameter of at least 0.6 micron and an average aspect ratio greater than 8:1 and accounting for at least 50 percent of the total projected area of all the emulsion grains. Kofron U.S. Pat. No. 4,439,520 discloses similar grains which are spectrally sensitized. Abbott U.S. Pat. No. 4,425,425 describes radiographic materials containing tabular grains with aspect ratio of at least 8:1 and Abbott U.S. Pat. No. 4,425,426 discloses similar grains with an aspect ratio between 5:1 and 8:1. Solberg U.S. Pat. No. 4,433,048 protects tabular silver bromoiodide grains with inhomogeneously distributed iodide. A survey on high aspect ratio silver halide emulsions appeared in Research Disclosure, Vol 225, Jan 1983, item 22534.
High aspect ratio tabular grains exhibit several pronounced photographic advantages. Thanks to their particular morphology greater amounts of spectral sensitizers can be adsorbed per mole silver halide compared to classical globular grains. As a consequence such spectrally sensitized tabular grains show an improved speed-granularity relationship and a wide separation between their blue speed and minus blue speed. Sharpness of photographic images can be improved using tabular grains thanks to their lower light scattering properties again compared to conventional globular emulsion grains. In color negative materials the conventional sequence of the light sensitive layers can be altered and the yellow filter layer can be omitted. In developed black-and-white images high covering power is obtained even at high hardening levels; alternatively reduced silver halide coverages can be achieved if wanted resulting again in improved sharpness. In double coated radiographic materials the presence of tabular grains reduces the so-called cross-over which is the dominant factor for sharpness in such materials.
The above cited references on tabular grains are mainly concerned with high sensitive silver bromide or silver iodobromide emulsions. However in a lot of photographic applications high sensitivity is of less importance. In these cases the use of chloride rich emulsions is advantageous e.g. thanks to their higher development and fixing rates. Typical examples include graphic arts materials, duplicating materials, radiographic hard-copy materials, diffusion transfer reversal materials and black-and-white or color print materials. So it would be interesting to try to combine the advantages of chloride rich emulsions with the advantages of tabular grain structure.
When using conventional precipitation conditions chloride rich emulsion grains show a cubic morphology with (100) crystal faces. It is known that to alter this crystallographic habit so-called "growth modifiers" or "crystal habit modifiers" are required. Klein and Moisar, in Berichte der Bunsengeselschaft 67 (4), p. 349-355, report inhibition of the growth rate of silver chloride by purine bases such as adenine. Claes et al., J. Photogr. Sci. Vol. 21 (1973), p. 39-50, showed that growth modifiers can be used to precipitate octahedral and rhombic dodecahedral silver chloride crystals and they attributed the crystal habit modification to variations in surface hydration caused by those additives; typical examples of these modifiers included adenine, thiourea, hypoxanthine, benzimidazole and benzothiazole derivatives. The mechanism of the growth modifying action of adenine was studied in detail by Szucs in J. Signal AM Vol. 6 (1978) No 5 p. 381-405.
In more recent patent applications tabular chloride rich emulsion grains are contemplated. So Wey U.S. Pat. No. 4,399,215 discloses tabular silver chloride with an aspect ratio of at least 8:1 and parallel (111) major crystal faces. Precipitation conditions include the use of ammonia. Rather thick tabular grains are obtained. Wey U.S. Pat. No. 4,414,306 discloses tabular silver chlorobromide grains with at least an annular region where the molar ratio of chloride to bromide ranges up to 2:3.
In U.S. Pat. No. 4,400,463 Maskasky describes the preparation of a new crystallographic form of tabular silver halide grains rich in chloride by performing the precipitation in the presence of a special peptizer having a thioether linkage and an aminoazaindene growth modifier. A preferred growth modifier is adenine. Control example Emulsion 2 describes the failure to produce tabular grains using adenine when the special peptizer is absent and only conventional gelatin is present. In this example the reaction vessel contained a rather high amount of chloride (0.5 molar) before the start of the precipitation and pH was adjusted to 3.0.
Maskasky U.S. Pat. No. 4,713,323 discloses the preparation of thin tabular grains (less than 0.35 micron) by a precipitation technique wherein at least a molar concentration of chloride ion is present in the reaction vessel at the start and oxidized gelatin is used containing less than 30 micromoles of methionine per gram. In a preferred embodiment, illustrated by examples, a growth modifier e.g. an aminoazaindene like adenine is used. Control Example 1D describes the failure to produce a tabular AgClBr (1.0% Br) emulsion in the presence of adenine but using conventional gelatin instead of oxidized gelatin. In this case the reaction vessel contained 0.5 molar chloride ions and pH was adjusted to 4.0.
Tufano U.S. Pat. No. 4,804,621 describes a process for preparing chloride rich tabular grains in the presence of aminoazapyridine growth modifiers represented by a general formula of which adenine and derivatives are excluded. A preferred compound is e.g. 4-aminopyrazolo[3,4, d]pyrimidine. Example Control 2 demonstrates the failure to prepare tabular grains using adenine as a growth modifier. In this example pCl was maintained at 0.7 and pH at 4.0.
It is an object of the present invention to provide a new method of preparing tabular silver halide grains rich in chloride.
It is a further object of the present invention to provide photographic materials which contain tabular grains prepared by this new method.
Other objects will become apparent from the description hereafter.

Preparation of tabular emulsion grains rich in chloride


A recording transparency and method of preparing the same from water solution are disclosed. The transparency is receptive to a wide variety of inks and other indicia, exhibits rapid ink drying times, excellent dot size and shape retention, and excellent water resistance and stability. The transparency comprises a transparent substrate coated from an aqueous solution of a polymeric sorbent selected from synthetic transparent cellulosic polymers, especially one or a mixture of hydroxyethyl cellulose polymers, and a surfactant composition comprising nonionic detergent, anionic detergent and complexing agent.

1. Field of the Invention
This invention relates generally to recording or printing media and, more particularly, this invention relates to a recording transparency useful in connection with ink jet and other recording processes.
2. Description of Related Art
The use of recording transparencies in connection with, for example, overhead projection systems is well known. Typical recording transparencies comprise a flexible substantially transparent film, usually of a hydrophobic polymeric material such as polyester, with a surface coating which accepts various indicia, such as inks from ink jet printers or pens and the like.
It is desirable that the surface coating be substantially clear and capable of providing high density images which are permanent and smear resistant. It is also important that images imparted to the coating dry quickly. The latter characteristic is generally a function of the rate of ink sorption, while smear resistance is principally determined by the hydrolytic stability of the coating.
While some prior coatings used in recording transparencies have provided acceptable ink drying times and/or smear resistance for various specific types of inks, it is desirable for a recording transparency to accept any of a wide range of indicia, including indicia from ink jet printers, solvent based inks such as used in marker pens, and xerographic toners. Such transparencies would be highly versatile in a commercial setting, allowing users to utilize more than one type of printer, marker or copier to produce a given transparency. Heretofore, recording transparencies having the versatility to accept different types of inks and/or toners while providing fast drying times and smear resistance have not been known.
Also, because of the hydrophobic nature of the film surface, the coating of the film with the ink receptive layer is usually done from a solvent.


Computer-executable instructions that are directed to the performance of consequential actions and automatically elevate to execute at a higher privilege level to do so can perform such consequential actions only after user notification. Doing so can enable monitoring processes to avoid presenting duplicative user notification upon detection of such auto-elevation. In addition, prior to presenting user notification, input from the execution environment can be ignored and access to DLLs for performing consequential actions can be avoided. A static analyzer can identify non-conforming computer-executable instructions. A wrapper can be utilized to provide compliance by otherwise unknown or non-conforming computer-executable instructions.

Traditionally, computing devices performed tasks exclusively in response to input from users of the computing device. As computing devices, and application programs, became more powerful and complex, an increasing amount of tasks were performed by the computing devices in response, not to explicit user input, but rather to requests initiated by the execution of other computer executable instructions. Indeed, modern computing devices executing a typical operating system and suite of application programs perform a substantial number of tasks automatically and without explicit user input.
Unfortunately, not all of the tasks automatically performed by a computing device may be tasks that the user of such a computing device actually wanted performed. For example, malicious instructions, when executed, may cause the computing device to erase, change, or send elsewhere, some or all of a user's data, including data that may be very difficult for the user to reconstruct, operate without, or wish to have disseminated. To a user of such a computing device, such malicious instructions may be very obvious, but to the processes being executed on the computing device which were tasked to perform these instructions, there may be no meaningful way to distinguish between legitimate tasks and those requested by malicious instructions.
Forcing a computing device to "double-check" each instruction, or even each instruction capable of affecting the user's data, with a user prior to performing the instruction can cause the user to be bombarded with questions from the computing device, potentially as often as multiple times every second. Even if substantial filtering is applied, thereby reducing the number of times that the computing device double-checks its actions with a user prior to performing them, users can quickly grow tired of the repeated double-checks. A user's frustration can be further increased if such double-checks occur immediately upon the heels of an explicit instruction by the user requesting that the computing device perform the very action it is now double-checking. As a result, users can become immune to, or downright ignore, the information presented in such repeated double-checks, and can, as a result, simply proceed to approve every double-checked action. Of course, blanket approval, whether by the user or otherwise, negates the purpose of such double-checks in the first place.

Unobtrusive assurance of authentic user intent


A device for charging a measuring apparatus for thermal analysis with material specimens filled into containers includes a vertically displaceable gripping member and a rotatable specimen plate with a plurality of openings arranged in a circle. For transferring a specimen container to the measuring location in the measuring apparatus, the specimen container is moved underneath the gripping member by rotating the specimen plate, the gripping member is lowered and the specimen container is gripped by gripping fingers attached to the gripping member. The container is then raised from the specimen plate by raising the gripping member. Subsequently, the specimen plate is rotated until a recess in the specimen plate is located underneath the gripping member. The measuring location is also located directly underneath the gripping member. By lowering the gripping member through the recess in the specimen plate, the specimen container can now be placed on the measuring location and can be released for carrying out the measurement by spreading apart the gripping fingers.

1. Field of the Invention
The present invention relates to a device for charging a measuring apparatus for thermal analysis with material specimens or samples filled into containers. The device includes a revolving specimen plate or turntable with cutouts or recesses for receiving the specimen containers and means for gripping, lifting and transferring each container from the specimen plate to a measuring location in the measuring apparatus.
2. Description of the Related Art
Thermal analysis in the narrow sense includes methods of examining materials as a function of temperature, for example, differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermal gravimetry (TG).
In a broader sense, thermal analysis could also include methods of determining the dry substance or moisture contents of material specimens.
For carrying out measurements on large quantities of specimens of the same type, it is desirable and known in the art to mechanize the manipulation of the specimens partially or entirely by means of charging devices. For example, DE-A1-4023483 discloses an apparatus for dry substance determination in which the specimens are arranged on a turntable within a microwave oven. The weighing dish of the balance is also located within the microwave oven underneath the turntable. The specimens are positioned above openings in the turntable and can be placed individually on the weighing dish by lowering the turntable, so that the weighing dish extends through the opening in the turntable located above the weighing dish. The specimens are picked up again in the reverse sequence.
The known apparatus described above has the disadvantage that all specimens are located within the oven and, therefore, the oven must be opened for charging it with new specimens. In addition, the oven must be very large. A further disadvantage of the known apparatus is to be seen in the fact that the person operating the apparatus does not have an opportunity to observe the apparatus during operation to see whether the specimens are correctly placed on the weighing dish.
DE-A1-3814959 discloses a hygrometer with a specimen changer. The specimens are also placed on a turntable which is provided with openings arranged in a circle. The turntable and the weighing dish of the balance are arranged within the drying chamber and, therefore, are not accessible during measurements.

Device for charging a measuring apparatus for thermal analysis with material specimens filled into containers


The extendable drag plow provided by this invention has a laterally-fixed center section, and moveable outer sections positioned by a controllable actuator system. The moveable plow sections are equipped with followers engaging oppositely-extending pairs of guideways in the central plow section, with the actuators positioned between these pairs. A lifting actuator extends between pivotal connections to a bracket mounted on the vehicle and a terminal fixed with respect to the central plow section. Drag arms are also pivotally connected to a bracket mounted on the vehicle and are secured at their opposite end to the central plow section. A diagonal brace extending between the top portion of the central plow section and the drag arm is also used as a terminal for the actuator.

Snow plowing in residential and commercial areas has become a fine art, and is practiced by contractors on a seasonal or individual job basis. Plow assemblies are designed for attachment to standard vehicles-usually pick-up trucks. Lifting and positioning of the plow blade is usually done with hydraulic actuators operating on pressure generated by a pump driven by the vehicle engine. Occasionally, electric screw jacks are used.
A drag plow is often mounted on the back of the vehicle as a supplement to the action of the front-mounted principal plow. The vehicle is backed up to an obstruction with the plow raised. It is then lowered. A typical use of the drag plow is in pulling snow away from a wall or a garage door far enough for the operator to then swing the vehicle around and move the snow off to the side with the main plow. The load on this type of plow is thus relatively light. In the interest of saving time, these plows have been designed for lateral extension from a retracted central position to an extended position sweeping a path about twice as wide. The conditions under which these plows operate dictate that simplicity and ruggedness are a prime requirement.


High-frequency amplifier circuitry includes first amplifier circuitry, second amplifier circuitry, and noise figure improving circuitry. The first amplifier circuitry includes a first transistor and a grounded-gate third transistor. The first transistor has a source grounded via a first source inductor and a gate to which an input signal is applied. The third transistor is configured to output from a drain a signal obtained by amplifying a signal outputted from a drain of the first transistor. The second amplifier circuitry includes a same circuit constant as a circuit constant of the first amplifier circuitry and includes a second transistor and a grounded-gate fourth transistor. The noise figure improving circuitry connects the source of the first transistor and the source of the second transistor to each other.

For Low Noise Amplifier (LNA), a SiGe bipolar process has been generally used, and the one made by a Silicon On Insulator (SOI) CMOS process becomes more frequently used in recent years. This is because a high functional circuitry can be realized by incorporating a high-frequency switch FET in the LNA. Recently, Carrier Aggregation (CA) is introduced to speed up the radio communication. The mode of CA includes an intra-band CA in which case the output of the LNA needs to be branched into two, and a single output mode and a split output mode are needed as output modes for realizing the LNA corresponding to the intra-band CA. However, about 25 dB of isolation between outputs during the split output mode is required but is not easy to realize.

High-frequency amplifier circuitry and semiconductor device

Toshiba Electronic Devices & Storage Corporation


The present invention relates to a method for searching a menu in a mobile communication terminal, wherein a plurality of main menus and sub menus of each main menu are simultaneously searched on a single menu screen using various navigational keys.

1. Field of the Invention
The present invention relates to a mobile communication terminal, and more particularly, to a method for searching a menu in a mobile communication terminal.
2. Background of the Related Art
In recent years, along with the rapid progress in information communication technology, the information and communication environment is being dramatically changed. In particular, the number of mobile communication users is rapidly increasing. Accordingly, the demand for personal portable communication apparatuses, e.g., mobile communication terminals, is increasing at an explosive rate.
The mobile communication terminal provides a variety of text/character services. For example, a user can send/receive messages, store data, receive weather forecasts and securities market information. The terminal can also be used for telephone calls, and recently provides internet services using mobile communication.
FIG. 1 is a schematic diagram of an external structure of a related art mobile communication terminal. As illustrated in FIG. 1, the related art mobile communication terminal (hereinafter "terminal") includes a terminal main body 101, a liquid crystal display (LCD) 102, and a key input unit 103. In addition, the key input unit 103 can include various function keys, for example, a numeric key, call key, end/power key, search key, store key, delete key, and menu key.
FIG. 2 is a schematic diagram of an internal structure of a mobile communication terminal as illustrated in FIG. 1. Referring to FIG. 2, the key input unit 103 is used as a user data input device. It typically includes at least 22 key buttons. The mobile station modem (MSM) 104 has a microprocessor unit (MPU) for controlling all devices, and stores an event signal inputted through the key input unit 103 in a flash memory 105 or converts data read out from the flash memory 105 into a CD signal to output the same to a LCD 102.
The flash memory 105 stores initial data to be displayed on the LCD 102, and a cache memory 106 reads the stored data in the flash memory 105 and edits final data to be outputted to the LCD 102. The LCD 102 receives the data stored in the cache memory 106 through the MSM 104, and displays the same so that a user can recognize it.
A method for searching a menu in the thusly constructed related art mobile communication terminal will next be described.
When a user presses the menu key in the key input unit 103, the LCD 102 displays a main menu, such as "volume control," "telephone bell selection," "talk time," and the like, as illustrated in FIG. 3A. In this state, when the user selects, for example, the "telephone bell selection" menu, the LCD 102 displays sub-menus, such as "telephone bell type," "basic melody," "OTA melody," as illustrated in FIG. 3B. Subsequently, if the user selects the "telephone bell type" menu from the sub-menus, items such as the "telephone bell," "vibration," "vibration+telephone bell," and the like are sequentially searched, as illustrated in FIG. 3C.
A desired function can thus be selected.
Meanwhile, if the user knows the number corresponding to each menu item, he or she can search a desired menu item. However, there is typically a limit in the user's ability to memorize the numbers of menu items.
In addition, if the user realizes that the desired item is not included in the selected main menu while sequentially searching the main menus and the sub menus, the user must press the "end" key, and thereafter release the search step in the order of a lowest level sub menu, an upper level sub menu, and finally the main menu, and try to access the desired item again. Alternatively, the user can perform the search step from the beginning by pressing the "end" key to release the menu search, and then pressing the menu key again.
The related art mobile terminal, however, has various problems. For example, since the searching method has a hierarchical menu tree structure, it is necessary to pass through an upper menu in order to move from a first lower level menu to another lower level menu of another category. Accordingly, when accessing a single item contained in a specific menu using the related art menu searching method, the user must navigate hierarchically configured menus, one by one.
In addition, if a menu is selected in error, the user must again perform the search step in the reverse order, or must start searching from the beginning after releasing the corresponding menu selection, in order to locate a desired menu.
The above references are incorporated by reference herein where appropriate for appropriate teachings of additional or alternative details, features and/or technical background.

This patent is subject to a terminal disclaimer.

Method for searching menu in mobile communication terminal


A nozzle for the introduction of liquefied plastic material into a mold has a channel terminating at one end in an injection orifice and adjoining at its other end a reduced bore serving for the guidance of a valve pin slidable with all-around clearance in that channel, the pin having a rear extremity projecting from its guide bore. A passage for the admission of liquefied molding material under pressure enters the channel at its junction with the reduced guide bore, rearwardly of a set of skew fins of the pin serving for additional guidance thereof in the channel and for imparting relative rotary motion to the flow and the pin. The orifice is blocked at the end of an injection operation by a pusher acting upon the projecting rear extremity; it is unblocked, upon withdrawal of the pusher, by the pressure of the molding material in the channel upon a forwardly facing annular shoulder of the pin.

The usual shut-off devices of the type referred to include plungers or pins which may be displaceable either transversely to the flow path or longitudinally thereof; see, for example, U.S. Pat. Nos. 4,073,944 and 4,076,485. Conventional mechanisms used for this purpose have the drawback that the channel carrying the plastic flow to the nozzle orifice has discontinuities forming dead-air pockets in which the plastic mass tends to accumulate and degrade while being bypassed by the mainstream of that mass. Some of these mechanisms, moreover, are rather complicated and require an enlarged nozzle body calling for extra heating energy to keep the mass fluid.

Injection nozzle provided with shut-off means


For AlGaAs LEDs the confining layers adjoining the active layer possess the highest Al composition. From failure analysis of non-passivated, WHTOL-aged, AlGaAs LEDs, it was discovered that corrosion occurs the fastest at the exposed surfaces of the high Al-content confining layers. By placing a high-quality native oxide at the exposed surfaces of the high Al-content confining layers which protect from the formation of the `poor` oxide, it is possible for LEDs to retain essentially their same light output after 2,000 hours of WHTOL testing. Further, it is possible to improve carrier confinement, carrier injection, wave guiding, and other properties by increasing the Al-content of different layers.

The general background of the present invention is disclosed in U.S. Pat. No. 5,262,360 by Holonyak, Jr. and Dallesasse (Holonyak '360) entitled "AlGaAs Native Oxide" granted Nov. 16, 1993 and U.S. Pat. No. 5,517,039 by Holonyak, Jr. et al (Holonyak '039) entitled "Semiconductor Devices Fabricated with Passivated High Aluminum Content III-V Materials" granted May 14, 1996. Holonyak '039 is co-assigned with the present invention to the Hewlett-Packard Company.
High aluminum (Al) containing III-V semiconductor materials degrade in wet; high-temperature environments due to the formation of an undesirable Al-oxide, primarily thought to be Al[OH].sub.3. These oxides tend to be optically absorbing and limit the transmission of light from light emitting semiconductor devices. The poor Al-oxide can also attack the crystal structure of the device.
One method of preventing device degradation is to grow a high quality native oxide that effectively seals the device and prevents the formation of a poor, optically absorbing Al-oxide. Native oxides are formed at higher temperatures and include Al(O)OH and Al.sub.2 O.sub.3. A device is considered passivated if the native oxide prevents or significantly reduces the formation of the poor oxide (e.g., Al[OH].sub.3) when the device is operated in wet, high-temperature environments. Within this description, there can be different degrees of passivation for devices that have been subjected to wet, high-temperature operating life (WHTOL) testing based on the amount of device degradation after operating for a fixed time. For example, a light emitting diode (LED) may be considered fully-passivated if the emitted light output power (LOP) has degraded less than 20% after 2000 hours of WHTOL operation. An LED is considered partially-passivated if the LOP has degraded less than 50% after 2000 hours of WHTOL operation. Thus, the term "passivated" describes devices from partially to fully passivated. Herein, the conditions of a WHTOL test are under 20 mA loading (i.e., forward bias in an LED) in an atmosphere of 85% relative humidity and a temperature of 85.degree. C.
A method for forming high quality native oxides through the use of a water vapor environment at elevated temperatures is described in Holonyak '360 and is applicable herein. A wide range of temperatures is described between 375.degree. C. to 1000.degree. C. to grow native oxides in Al-bearing materials. In Holonyak '039 it was specified that the most critical areas of a semiconductor device to passivate were those in which the majority of the light generated by the light emitting diode (LED) are transmitted. This is based on the belief that corrosion was accelerated by photon interactions. Holonyak '039 also specifies the need to control the temperature and time of the oxide growth period so the thickness of the native oxide growth is within a particular thickness range. Specifically, the native oxide film must be thicker than 0.1 um to avoid pinholes or cracks in the film, but thinner than 7.0 um which can cause cracks in the film due to internal stress. The cracks can prevent complete passivation and result in light output loss during WHTOL tests. In Holonyak '039 it also stated that that the water vapor oxidation temperature range should be 375.degree. C. to 550.degree. C., preferably from 450.degree. C. to 550.degree. C., and the most preferable oxidation time is 0.25 hour to 2 hours.
In light emitting devices it is often desirable to incorporate wide band gap, high Al content layers for improved carrier confinement, carrier injection, wave guiding properties, etc. For example, it is known that the emission efficiencies of red-emitting aluminum gallium arsenide (AlGaAs) LEDs can be improved by increasing the Al-mole fraction, x, of the high-composition Al.sub.X Ga.sub.(1-x) As confining layers immediately adjoining the active layer. However, the destructive oxide degradation problems have limited the content of these Al.sub.x Ga.sub.(1-x) As layers to the range where the Al mole-fraction, x, is less than 0.75. The mole fraction, x, indicates the amount of Al in the layer and is defined as the fractional composition of Al to the Group III element in the layer.
The prior art has shown the performance of Al-bearing semiconductor devices can be greatly improved through the use of native oxide passivation. Although many issues have been addressed, there is still no viable method for using this technique in high volume manufacturing. To successfully implement this technology, it is critical to have processing techniques that can be used to passivate the device areas that have the greatest impact on the device performance and reliability.

Advanced semiconductor devices fabricated with passivated high aluminum content III-V materials