A system and method for supporting multi-tenancy in a federated data management system are provided herein. The method includes receiving a query from a client at a data management server, wherein the query includes a tenant property condition corresponding to the client. The method also includes identifying an external data store including data specified by the query and determining whether the external data store is multi-tenant enabled. The method further includes removing the tenant property condition and executing the query to retrieve the specified data if the external data store is not multi-tenant enabled.

Many organizations use diverse data stores to produce, store, and search the organization's data. The diversity of such data stores may result from many factors, including lack of coordination among an organization's operating units, different rates of adopting new technologies, mergers and acquisitions, or geographic separation of the organization's operating units. In many cases, combining the information from these various data stores allows an organization to more effectively exploit the data contained therein. For example, if two organizations merge to form a new organization, the new organization may inherit the data stores of the original organization. However, the data of the original organization may be stored in different types of data stores and/or in different formats than the data of the new organization. Therefore, it may be desirable to integrate the data stored within the diverse data stores such that the data can be easily retrieved from the data stores. This may be accomplished via any of a number of different techniques for retrieving data located on external data stores, including data warehousing and database federation techniques. Data warehousing and database federation techniques may be used to retrieve data from external data stores by providing users with a high-level query language that can be used to combine, contrast, analyze, and otherwise manipulate data.
Data warehousing techniques include loading data from one or more external data stores into a data warehouse. However, moving data from external data stores to a data warehouse, as well as transforming the data into a format that is supported by the data warehouse, may be very costly. Therefore, it may be desirable to use database federation techniques or, more specifically, configuration management database (CMDB) federation techniques, instead of data warehousing techniques. CMDB federation techniques may be used to extend the scope of existing topology query language (TQL) capabilities to encompass data that is stored and maintained in one or more external data stores. CMDB federation techniques may provide for the retrieval of such data from the external data stores to a CMDB on-the-fly without having to copy large amounts of data to the CMDB. This may reduce the burden on the CMDB in terms of capacity and performance, and may allow for the integration of a large amount of data located on any number of external data stores.

Supporting multi-tenancy in a federated data management system


Systems and methods of detecting fatigue and drowsy conditions of vehicle drivers without initially using any disruptive visual and sound alarms, and instead immediately interacting with the driver as to their condition and providing information on rest stops through onboard GPS (global positioning satellite) systems, as well as alerting acquaintances and friends of the driver through telephones such as a cellular phone. The systems and methods can interact with the driver through touch type screens, and/or audible feedback to alert the driver of their condition and to temporarily take the driver off the roads.

A driver's ability to stay awake when drowsy or fatigued is sometimes an impossible task and often dangerous. Once drowsiness and fatigue occurs, a driver can experience impaired reaction time, poor vision and bad judgment. The drowsy and fatigued driver can experience problems with information processing and short term memory. By encountering this level of fatigue or drowsiness, the performance of the driver is reduced and they can experience a lack of motivation. Managing risk is an important factor when driving. The driver generally needs to schedule regular stops every 150 miles or 2 hours. Once fatigued the driver should take a 20 minute nap or consume caffeine the equivalent of 2 cups of coffee. Regardless of the education and warnings about drowsy driving, the deaths continue to rise.
Various ways of managing these risks are through alert systems in the vehicle. Alerts provide warning triggers which are developing the patterns and indicating the on-set of sleep. There are a number of methods and technologies which can determine the on-set of sleep. These vary from visual monitoring of the driver's face, to physiological changes to detecting changes in driving performance. These known systems use various types of biometric analysis from analyzing visual conditions of the drivers head and face to sensing the position of the vehicle relative to the road.
See for example, U.S. Pat. Nos. 5,745,031 to Yamamoto; 7,302,327 to Kudo; 6,370,475 to Breed et al.; 6,426,702 to Young et al.; 6,559,770 to Zoerb; and 6,927,694 to Smith et al.
Once these systems detect a fatigue type condition in the driver's appearance and/or when the vehicle is detected moving off the roadway, alarms sound to alert the driver. The alarms have included sound and/or visual indicators. The warnings can sometime be so startling that the alarm can cause an accident.
The current systems can ding, sound a loud horn, vibrate the seat and even use tightening of the seat belt to let the driver know they are having sleep problems. This harsh alarm approach has not been very effective. The alarms have not caught up with the technology which has been developed for the detection of sleep. Once the reporting of fatigue/sleep is triggered, the approach of awakening or the fore warning given to the driver, has not met the same technology sophistication. The transitory nature of the alarm, its associated lack of interaction and the failure of the alarm to provide useful information regarding how to "manage the current situation", results in the systems being inefficient and under utilized, and often result in the causing of accidents and not avoiding them.
Each year tens of thousands of people are killed on the highways as the direct result of driving in a drowsy or attention compromised condition. Automobile manufacturers are very cognizant of the problem and are investing aggressively in technologies in order to combat the problem and avoid regulation and legal restrictions. To date the focus has been primarily on the detection of unsafe driving performance and to warn the driver. As previously described, these technologies span from camera's embedded in dashboard to watch for drooping eyes to cameras that detect lane departure swerving. These technologies can generally alert the driver of the situation, with the naïve belief that such a warning will be a wake-up call to the driver to either alter their behavior or get off the road. There is unfortunately a fundamental flaw is their logic. While an alarm may provide a temporary warning, it neither alters nor manages the situation. Once the driver has been warned, the same distractions are still available and the fatigue state remains and may return and elevate. While such an alert will temporarily increase the state of alertness and attention of the driver, there is nothing to sustain the state. Considering that the driver is unable to take any immediate action to alleviate the situation, an alarm without a situational management process will prove ineffective with regards to the majority of fatigue situations.
The current fatigue driving alarm systems that are being introduced in consumer automobile currently, suffer from a variety of problems. First is the driver perceived "false positive". Most drivers will not readily admit they are driving in an unsafe condition; rationalizing it was just an isolated momentary event. The sensitivity of the alarm system must be set to detect fatigue early enough for it to be effective from a safety perspective, but this is likely to cause frequent annoying alarming to the driver, even though the driver is in a dangerous situation. Drivers in such a circumstance are likely to turn-off or disable the system, leaving themselves completely unprotected and vulnerable. A safety system that is turned off is not a safety system.
The action of alarming the driver can increase the danger and potential of an accident. This results due to the physiological effects that an alarm has in an irresolvable constrained environment such as an automobile. An unexpected alarm during fatigue causes an immediate surge of adrenaline into the blood stream, reflecting the body's fight or flight response to such stimuli. Since the driver's actions are constrained by the situation, they can't or won't simply pull over and stop the car, they will continue to drive. Now the metabolic pendulum swings in the opposite direction and the body responds by rapidly over compensating from the hormonal stimulation leaving the driver to a potentially lower attention state than before. Unless the driver is able to take immediate action, which under the circumstance is unlikely, the driver will oscillate between the extremes of adrenaline stimulation from the alarm to metabolic crash, with the average performance trend declining rapidly.
Thus, the need exists for solutions to the above problems with the prior art.

Interactive fatigue management system and method


Bifidobacterium longum strains and cell wall fractions isolated from Bifidobacterium longum strains are useful in the prophylaxis or treatment of a respiratory viral infection in a subject. They are also useful in the prophylaxis of a secondary bacterial infection associated with a respiratory viral infection in a subject, especially a subject who is susceptible to respiratory infections.

Bifidobacteria are considered to be probiotics as they are living organisms which exert healthy effects beyond basic nutrition when ingested in sufficient numbers. A high level of ingested bifidobacteria must reach their site of action in order to exert a probiotic effect. A minimum 25 level of approximately 106-107 viable bifidobacteria per gram intestinal contents has been suggested (Bouhnik, Y., Lait 1993). There are reports in the literature which show that in vivo studies completed in adults and in infants indicate that some strains of bifidobacteria are capable of surviving passage through the gastrointestinal tract. Significant differences have been observed between the abilities of different bifidobacteria strains to tolerate acid and bile salts, 30 indicating that survival is an important criterion for the selection of potential probiotic strains.
Ingestion of bifidobacteria can improve gastrointestinal transit and may prevent or assist in the treatment of illnesses which may be caused by deficient or compromised microflora such as gastrointestinal tract (GIT) infections, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD)—Crohn's disease and ulcerative colitis, food allergies, antibiotic-induced diarrhoea, cardiovascular disease, and certain cancers (e.g. colorectal cancer).
Viral infections are a major cause of morbidity and mortality. Influenza virus, rhinovirus (common cold) and respiratory syncytial virus (RSV) are highly infectious viruses that usually are successfully cleared by an appropriate host immune response in healthy individuals. However much of the issue with these infections is not the initial virus but rather the secondary infections that often accompany it e.g. bacterial infections causing pneumonia, infection of sinus tissue etc. Susceptible individuals such as those suffering from COPD or Asthma or Obesity respond very poorly to viral infections and subsequent secondary infections are serious and can be life threatening to such individuals.
These virus-induced exacerbations of these conditions are associated with substantial healthcare costs and significant suffering. Development of new and effective therapies for these exacerbations would be beneficial as there is a major unmet clinical need. Administration of corticosteroids to patients affected by influenza virus, especially pandemic avian influenza virus, although relatively common, remains controversial. Routine steroid use is not be ideal for influenza virus infection as it does not reduce the viral burden and also inhibits the clearance of secondary bacterial infections afterwards (Yang et al, 2015).
In the early stages of infection, influenza, rhinovirus and RSV replication occurs in lung epithelial cells, leading to activation of viral sensors and the release of antiviral Type I and Type III interferons (IFN's) as well as chemokines and cytokines. These pro-inflammatory mediators help to clear the primary infection but Type I IFN's can also cause subsequent damage (immunopathology). IFN Type I responses, such as increases in IFN-α, and IFN-β molecules, have been shown to directly correlate with increased morbidity and mortality in models of influenza infection (Davidson et al, 2014). Over-production of antiviral Type I IFN's and the related IP-10 chemokine inhibit the appropriate immune response to clear secondary infections (Nakamura et al, 2011; Shahangian et al, 2009; Li et al, 2012) such as caused by bacterial agents such as Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae and even Staphylococcus aureus (Hewitt et al, 2016). These secondary infections cause excessive cell death within the lungs. In susceptible individuals, this leads to lung tissue injury and reduced lung function which causes serious complications and mortality in some cases e.g. in COPD patients. Importantly the pro-inflammatory activation occurs only to Type I IFN responses which cause the recruitment of neutrophils and not to Type III IFN responses (Galani et al, 2017).
However, Type III IFN's such as IFN lambda (IFN-k) can limit viral replication without inducing pro-inflammatory responses or immunopathology (Davidson et al, 2016; Galani et al, 2017).
Therefore, therapeutic agents that can limit the Type I IFN responses and accompanying pro-inflammatory and tissue damaging response to viral infection, while maintaining appropriate Type III responses and anti-viral defence, would be a significant advancement in the management of respiratory viral infections. This reduction of immunopathology is critical for host survival and resolution of disease.
Other innate sensors or immune mediators can also play an important role in early anti-viral defence Surfactant protein D (SP-D) can stop the influenza virus from entering epithelial cells which is part of the early phase of the infection. (Thiel et al, 1989; Sastry et al, 1993). Again, therapeutic agents that can induce this innate sensor which can bind to the virus and stop it from infecting the bronchial epithelial cells would be a significant advancement in the treatment of viruses such as influenza, rhinovirus and RSV. In addition, inhibition of tumor necrosis factor-alpha (TNF-α), an important inflammatory cytokine has a significant effect on the extent of lung immunopathology and inhibited inflammatory cellular infiltration and cytokine responses. TNF-α, has been shown to correlate with morbidity and mortality in macaques monkeys and humans infected with highly virulent influenza viruses. A decrease in influenza virus replication and an increased survival of influenza virus-infected mice was observed when the TNF-α was suppressed (Shi et al, 2013). Inhibition of this inflammatory cytokine with etanercept provides protection against lethal H1N1 influenza infection in mice (Shi et al, 2013).
Therapeutic agents which can induce Type III IFN-λ. and/or SP-D would have a role to play in early clearance of the primary viral infection while reducing the likelihood of secondary bacterial infections and would be a significant advancement in the management of ARDS, asthma, obesity and COPD.

This patent is subject to a terminal disclaimer.

Bifidobacterium longum able to beneficially modulate immune response to respiratory virus infection


Provided is a semiconductor device that has a low interface resistance between a contact plug and a bottom electrode of a real ferroelectric capacitor. A real capacitor oxidation suppression structure ST including a dummy ferroelectric capacitor 312 and a second plug 311 is formed. The dummy ferroelectric capacitor 312 includes a second bottom electrode 51, a second ferroelectric film 52, and a second top electrode 53, and is not used as a nonvolatile memory element. The second bottom electrode 51 is formed on an interlayer insulating film 50. The second ferroelectric film 52 is formed on the second bottom electrode 51. The second top electrode 53 is formed on the second ferroelectric film 52. The second plug 311 penetrates the interlayer insulating film 50 and electrically connects the second bottom electrode 51 to a semiconductor substrate 40.

A nonvolatile memory and a nonvolatile logic are known and used to store data by making use of hysteresis of ferroelectrics. A ferroelectric random access memory (FeRAM) is available as the nonvolatile memory. The ferroelectric random access memory includes a plurality of memory cells. As disclosed, for example, in Patent Document 1, the memory cells each include a field-effect transistor and a ferroelectric capacitor. Each of the memory cells in a ferroelectric random access memory is an example of a nonvolatile memory element including a ferroelectric capacitor.
As disclosed in Patent Document 2, the nonvolatile logic includes a plurality of nonvolatile logic cells (nonvolatile memory gates) and a control circuit for controlling the nonvolatile logic cells. The nonvolatile logic cells each include a volatile memory section and a nonvolatile memory section. The nonvolatile memory section retains data of the volatile memory section. The volatile memory section is formed, for example, of a flip-flop. The nonvolatile memory section includes, for example, a plurality of ferroelectric capacitors and a field-effect transistor provided for each of the ferroelectric capacitors. Each of the nonvolatile logic cells is an example of a nonvolatile memory element including a ferroelectric capacitor. When, for example, power supply is to be shut off, the control circuit backs up data from the volatile memory section to the nonvolatile memory section. Meanwhile, when the power supply is turned on, the control circuit restores the data from the nonvolatile memory section to the volatile memory section.


The transmission circuit includes a comparator that converts a phase-modulated signal from an orthogonal modulator into a pulse signal so as to use the pulse signal as the sampling clock of the a delta-sigma modulator, and an asynchronous clock transfer unit and an interpolating circuit, disposed between a circuit operating based on the baseband clock and the delta-sigma modulator. The asynchronous clock transfer unit converts the amplitude component signal synchronized with the baseband clock, into an amplitude component signal synchronized with an N-frequency divided clock obtained by dividing the frequency of the sampling clock by N. The interpolating circuit interpolates the output signal from the asynchronous clock transfer unit so that the amount of change of one sample in the N-frequency divided clock becomes equal to the amount of change of one sample in the sampling clock.

The transmission device in a radio communications system includes a transmission circuit that amplifies a signal obtained from an orthogonal baseband signal and transmits the resultant signal. A transmission circuit with improved efficiency is needed in order to realize greater miniaturization and low power consumption.
Under such circumstances, in the recent years the transmission circuit using a delta-sigma modulator has attracted attention because high power efficiency switching amplifiers, for example those, represented by class-D amplifiers and class-E amplifiers are adopted as power amplifiers. Here in this description, the term 'delta-sigma modulator' indicates both the delta-sigma modulator and the sigma-delta modulator.
In general, when orthogonal baseband signals I(t) and Q(t) are subjected to orthogonal modulation with a carrier wave frequency fc from an oscillator by means of an orthogonal modulator, the orthogonally modulated signal e(t) can be represented by the following expression 1.[Math 1]e(t)=I(t)·cos(2πfct)−Q(t)·sin(2πfct)  (Ex. 1)
It is assumed herein that the amplitude (amplitude component) of the baseband signal can be represented by A(t) as in the following expression 2, the phase (angular component) of the baseband signal can be represented by θ(t) as in the following expression 3, the modulated signal e(t) of the above Ex. 1 can be replaced by the following expression 4.
                    [                  Math                                                              2                ]                                                                      A                                (            t            )                          =                                                            I                                                  (                  t                  )                                            2                        +                                          Q                                                  (                  t                  )                                            2                                                          (                  Ex          .                                                    2                )                                [                  Math                                                              3                ]                                                                      θ                                (            t            )                          =                              tan                          -              1                                                      {                                          Q                                                  (                  t                  )                                                            I                                                  (                  t                  )                                                      }                                              (                  Ex          .                                                    3                )                                [                  Math                                                              4                ]                                                                                e                                                  (                  t                  )                                            =                                                                            A                                                        (                    t                    )                                                  ·                                  {                                                                                cos                                                                          (                                                      θ                                                                                (                              t                              )                                                                                )                                                                    ·                                              cos                                                                          (                                                      2                                                        π                                                                                f                              c                                                                                t                                                    )                                                                                -                                                                  sin                                                                          (                                                      θ                                                                                (                              t                              )                                                                                )                                                                    ·                                              sin                                                                          (                                                      2                                                        π                                                                                f                              c                                                                                t                                                    )                                                                                }                                                                                =                                                                                A                                                              (                      t                      )                                                        ·                  cos                                                                  {                                                            2                                            π                                                                                f                        c                                                                  t                                        +                                          θ                                                                    (                        t                        )                                                                              }                                                                                (                  Ex          .                                                    4                )
The above Ex. 4 is equivalent to the result of multiplication between the phase modulated signal P(t) having an amplitude of 1, represented by the following expression 5 and the amplitude component signal A(t) of the above Ex. 2.[Math 5]P(t)=cos {2πfctθ(t)}  (Ex. 5)
Here, when the orthogonal baseband signals I(t) and Q(t) are converted by the following expressions 6 and 7, angular component signals I′(t) and Q′(t) that have an amplitude of 1 and that only show angular component information can be obtained.
                    [                  Math                                                              6                ]                                                                                I            ′                                          (            t            )                          =                  {                                    I                                            (                t                )                                                                                I                                                              (                      t                      )                                                        2                                +                                                      Q                                                              (                      t                      )                                                        2                                                              }                                    (                  Ex          .                                                    6                )                                [                  Math                                                              7                ]                                                                                Q            ′                                          (            t            )                          =                  {                                    Q                                            (                t                )                                                                                I                                                              (                      t                      )                                                        2                                +                                                      Q                                                              (                      t                      )                                                        2                                                              }                                    (                  Ex          .                                                    7                )
The phase modulation signal P(t) in Ex. 5 is equal to the signal which is obtained by performing orthogonal modulation on angular component signals I′(t) and Q′(t) with carrier wave frequency fc by means of an orthogonal modulator.
Accordingly, the modulated signal e(t) can be obtained in the following manner. First, orthogonal baseband signals I(t) and Q(t) are separated into amplitude component signal A(t) represented by the above Ex. 2 and angular component signals I′(t) and Q′(t) represented by the above Exs. 6 and 7. Subsequently, angular component signals I′(t) and Q′(t) are orthogonally modulated with the carrier wave frequency fc by means of an orthogonal modulator to obtain phase modulated signal P(t). Thereafter, phase modulated signal P(t) is multiplied by amplitude component signal A(t) to thereby obtain modulated signal e(t).
When, with the above configuration, amplitude component signal A(t) is subjected to delta-sigma modulation as described below, it is possible to realize a high-efficient transmission circuit using a switching amplifier.
FIG. 1 shows a configuration of a related art transmission circuit described in Patent Document 1.
As shown in FIG. 1, the transmission circuit described in Patent Document 1 includes phase modulator 1a, multiplier 2a, delta-sigma modulator 3a, band pass filter (BPF: Band Pass Filter) 4a, pre-processing circuit 6, switching amplifier 7, oscillators 8 and 9. Here, switching amplifier 7 is denoted as "PA (Power Amplifier)" in FIG. 1.
In Patent Document 2, as shown in FIG. 2 a transmission circuit equivalent to the transmission circuit shown in FIG. 1 from which switching circuit 7 is omitted is described. In FIG. 2, frequency modulator 1b, amplitude modulator 2b, delta-sigma modulator 3b, band pass filter 4b and data generator 5 are equivalent to phase modulator 1a, multiplier 2a, delta-sigma modulator 3a, band pass filter 4a and pre-processing circuit 6 shown in FIG. 1.
Therefore, the following description will be given on only the transmission circuit described in Patent Document 1 shown in FIG. 1.
Pre-processing circuit 6 separates orthogonal baseband signals I(t) and Q(t) into amplitude component signal A(t), angular component signal I′(t) and Q′(t) and outputs the resultant signals.
Phase modulator 1a corresponds to an orthogonal modulator and generates phase modulation signal P(t) from angular component signals I′(t) and Q′(t).
Delta-sigma modulator 3a subjects amplitude component signal A(t) to delta-sigma modulation to convert the signal into amplitude pulse modulated signal A′(t).
Multiplier 2a performs amplitude modulation on phase modulated signal P(t) with amplitude pulse modulated signal A′(t). As a result, multiplier 2a outputs a signal obtained by performing on-off modulation on phase-modulated signal P(t) of a fixed amplitude in accordance with information of "1" and "0" of amplitude pulse modulated signal A′(t). Accordingly, the amplitude of the output signal from multiplier 2a takes 0 or a constant value.
Switching amplifier 7 amplifies the output signal from multiplier 2a. The amplitude of the output signal from the multiplier 2a takes 0 or a constant value as stated above. Accordingly, even when the output signal from multiplier 2a is amplified by amplifier 7, the resultant signal will not involve any distortion accompanied by nonlinearity of the power amplifier and the signal can be amplified and transmitted at high power efficiency that switching amplifier 7 can inherently offer.
Here, amplitude pulse modulated signal A′(t) is a delta-sigma modulated signal that is obtained by subjecting amplitude component signal A(t) to delta-sigma modulation through delta-sigma modulator 3a. Therefore, as shown in the following expression 8, amplitude pulse modulated signal A′(t) is given as the sum of the amplitude component signal A(t) as the input signal to delta-sigma modulator 3a and the quantization noise N(t) accompanied by one-bit pulse modulation.[Math 8]A′(t)=A(t)+N(t)  (Ex. 8)
When amplitude pulse modulated signal A′(t) is used to perform amplitude modulation on phase modulated signal P(t) by means of multiplier 2a, the output signal from multiplier 2a also involves quantization noise.
It is assumed that Q(t) represents the quantization noise arising from quantization and Q(z) represents the Z-transform of Q(t). For example, when a first order delta-sigma modulator is employed as delta-sigma modulator 3a, residual noise N(z) in the output of the first order delta-sigma modulator can be represented by the following expression 9 based on the noise shaping characteristics in transmission characteristics of the first order delta-sigma modulator.[Math 9]N(z)=(1−Z−1)·Q(z)  (Ex. 9)
Here, in the above Ex. 9, Z−1 means one sample delay in the clock rate of delta-sigma modulator 3a.
Accordingly, the Z-transform of the above Ex. 8 is written as the following expression 10.[Math 10]A′(z)=A(z)+(1−Z−1)·Q(z)  (Ex. 10)
In other words, the above Ex. 9 is the expression representing the noise-shaping characteristics of delta-sigma modulator 3a for shifting the noise on the low-frequency side (the transmission signal band) of quantization noise Q(z) that is uniformly distributed over the frequency axis, to the high-frequency side (the outside of the transmission signal band).
Optimization of the noise-shaping characteristics of delta-sigma modulator 3a represented by the above Ex. 9 makes it possible to reduce and to eliminate quantization noise by band pass filter 4a downstream of switching amplifier 7.
Here, the noise-shaping characteristics of delta-sigma modulator 3a is determined depending on the order of delta-sigma modulation and the over sampling ratio (OSR: Over Sampling Ratio). However, if this noise-shaping characteristics have not been optimized, a problem occurs in which noise remaining in the lower frequency (in the transmission signal band) than the stopband of band pass filter 4a spoils the radio characteristics required for the transmission equipment.
Non-Patent Document 1 related to Patent document 1 describes the conditions required for a delta-sigma modulator to yield the characteristics of the desired signal-to-noise ratio for IEEE (Institute of Electrical and Electronic Engineers) 802.11b OFDM (Orthogonal Frequency Division Multiplexing) signals. Specifically, in the example of Non-Patent Document 1, even in the simulation level, a delta-sigma modulator is required to operate at a clock frequency set by an OSR of 32 (i.e., 640 MHz) or by an OSR of 64 (i.e., 1.28 GHz) for the sampling frequency 20 MHz in the original baseband signal.
In general, FPGAs (Field Programmable Gate Array) and ASICs (Application Specific Integrated Circuit) for processing the baseband signal have the advantage in which logic and filter circuits can be easily configured. However, the operation clock frequency (including not only the core but also input and output) of FPGAs and ASICs reach 200 MHz to 400 MHz at the highest even with use of recent miniaturization processes. Therefore, it is impossible with FPGAs and ASICs to realize the desired OSR. Accordingly, the above desired OSR needs to be realized with digital RF circuits that operate at a clock rate of some GHz like the example of Non-Patent Document 2.
Even if an upsampling process and a high-order filtering process that satisfy the aforementioned desired OSR can be realized in a digital RF circuit operating at a clock rate of some GHz, the following problems, still remain.
In the related art shown in FIG. 1, phase-modulated signal P(t) of carrier wave frequency fc, as the output signal from phase modulator 1a, is an analog continuous signal. Further, the carrier wave (frequency fc) from oscillator 9 and the sampling clock (frequency fs) for delta-sigma modulation from oscillator 8 are asynchronous. Even if a common reference generator is used for both signals, when there is duty difference resulting from the difference between the signals (sinusoidal signal and rectangular clock signal) or when the two signals take different paths, it is impossible to make the temporal relationship between the two signals constant. For these reasons, the two signals become asynchronous.
As described above, in multiplier 2a, phase modulated signal P(t) is on-off modulated by amplitude pulse modulated signal A′(t) as the output signal from delta-sigma modulator 3a. In this on-off modulating operation, when the carrier wave (frequency fc) in phase modulated signal P(t) and the sampling clock (frequency fs) for delta-sigma modulation are asynchronous, in order to alleviate its influence, it is necessary to adapt fc to be sufficiently higher than fs.
Also in Non-Patent Document 1 related to Patent Document 1, the condition in which fc should be sufficiently higher than fs (fs<<fc) is specified. However, actually, fs needs to be a frequency ranging from about 600 MHz to about 2 GHz, as stated above. In contrast, the radio frequency fc in UTRA (Universal Terrestrial Radio Access) and E-UTRA (Evolved Universal Terrestrial Radio Access) ranges from 700 MHz to 3.5 GHz. Accordingly, fc forms an asynchronous clock having a frequency approximately equal to or markedly close to fs. In this case, a the problem occurs in which the signal obtained by on-off modulation of phase modulated signal P(t) with amplitude pulse modulated signal A′(t) cannot form a desired pulse waveform, due to timing deviation of signal transitions.
Here, as a technique for synchronizing the carrier wave (frequency fc) in phase modulated signal P(t) with the sampling clock for delta-sigma modulation (frequency fs), phase modulator 1a can be formed of a digital circuit based on a synchronized clock system, instead of an analog circuit. In this case, I′(t) and Q′(t) are upsampled to 4× sampling rate of the carrier wave frequency fc while I′(t) is repeatedly multiplied by 1, 0, −1, 0 . . . and Q′(t) is repeated multiplied by 0, 1, 0, −1 . . . , to thereby realize digital orthogonal modulation. However, fc ranges from 700 MHz to 3.5 GHz as stated above. Accordingly, phase modulator 1a needs to be operated at four times the rate of fc, i.e., 2.8 GHz to 14 GHz. This entails a high level of difficulty and poses many problems.
Patent Document 3 proposes, as a technique for synchronizing the carrier wave in the phase modulation signal with the sampling clock for delta-sigma modulation, the technique illustrated in FIG. 11 of Patent Document 3. Specifically, in this technique, the phase modulated signal that has been orthogonally modulated with the carrier wave by an orthogonal modulator (IQ modulator) is transformed into a pulse phase signal by a pulse phase signal generator, and this pulse phase signal is used as the clock for the delta-sigma modulator. However, in this technique, the sampling clock for delta-sigma modulation has been synchronized with the carrier wave, but cannot have been synchronized with the actual data of the amplitude component signal of the baseband signal input to the delta-sigma modulator. Accordingly, the delta-sigma modulator will perform data transmission between asynchronous clocks. As a result, a problem occurs in which the delta-sigma modulator samples invalid data during the period in which the amplitude component signal, as the input signal, is transitioning.
Here, in the examples of FIGS. 3, 14 and 36 of Patent Document 3, since the amplitude component signal is not a digital baseband signal but is generated from the signal that has been orthogonally modulated by the carrier wave through the orthogonal modulator (IQ modulator), the above problem will not occur. However, since the input signal to the delta-sigma modulator is an analog signal, a 1 bit D/A converter that operates based on carrier wave frequency fc is needed in computing the difference between the output signal from, and input signal to, the delta-sigma modulator in the delta-sigma modulation process, which is difficult to achieve.


A hydraulic actuator system includes a power source, a controller in communication with the power source, a piezoelectric stack comprising a plurality of piezoelectric elements disposed within a sleeve to define a chamber at one end of the sleeve, pressure accumulators in fluid communication with the chamber, a flow control valve in communication with the accumulators, and a hydraulic piston in fluid communication with the flow control valve. The communication between the power source and the controller may be electrical or photo communication, and the power source is preferably remotely located relative to the other elements of the hydraulic actuator system. The method for controlling a remotely located hydraulic actuator includes communicating a signal to the hydraulic actuator, pressurizing a hydraulic fluid in the hydraulic actuator, and directing the hydraulic fluid to a cylinder in the hydraulic actuator to bias a piston either into or away from the cylinder.

1. Technical Field
This disclosure relates to actuating systems, and, more particularly, to an apparatus and method for actuating a remotely locatable hydraulic mechanism with pressurized fluid.
2. Related Art
Valve actuating systems of the related art are typically hydraulically controlled mechanisms (HCMs) requiring the running of hydraulic control lines from a hydraulic fluid source to a valve actuator. The hydraulic fluid source is generally a supply tank of sufficient volume to accommodate the amount of hydraulic fluid required for the HCM with some amount of fluid in reserve. The hydraulic fluid is typically supplied to the valve actuating system through an arrangement of two control lines, which, depending upon the location of the valve actuator relative to the hydraulic fluid source, may necessitate a configuration of equipment that may be complex and expensive, especially in oilfield applications where the valve to be actuated is located downhole in a wellbore.
The hydraulic fluid supply tank is typically sized to accommodate two or three times the amount of hydraulic fluid required for normal operation of the HCM and is generally located at a well head of the wellbore. Because the volume of the supply tank is a function of the amount of the hydraulic fluid required for use in the system, an HCM remotely positioned relative to the well head could require a surface-located supply tank of a very large volume. In particular, a valve located downhole in a wellbore may be positioned at a depth such that miles of control line are required to actuate the valve. As the length of the control line is increased, the volume of hydraulic fluid required to maintain hydraulic pressure within the system correspondingly increases.
The control lines themselves occupy space within either the casing or the tubing string such that their presence detracts from the usable volume of the downhole environment. Because the control lines are conduits for fluids, they are typically of considerable size relative to electrical wiring or fiber optic cable. Furthermore, two control lines are typically required for each HCM. In an effort to minimize the number of control lines in the wellbore, one control line is usually run to each HCM and a common control line is shared by all of the HCMs. Nevertheless, operation of an oil well with multiple HCMs provides a challenge to surface-located operators because of the multiple connections involved and the possibility that control lines may cross each other within the wellbore and provide a source for fluid communication problems between the hydraulic fluid supply tank and the downhole environment.

Remote closed system hydraulic actuator system


A feeding device includes: a hopper, adapted to support a medium; a feeder, operable to feed the medium in a first direction; a separator, operable to nip the medium with the feeder at a nip point; and a guide, having a guide surface which guides the medium in the first direction and is provided with a recessed portion at a downstream side of the nip point in the first direction.

The present invention relates to a feeding device which feeds a recording medium in a facsimile machine, a printer or the like, and to a recording apparatus equipped with the feeding device. Also, the invention relates to a liquid jet apparatus.
As used herein, the liquid jet apparatus implies not only a recording apparatus, such as a printer, a copier and a facsimile machine, which uses an inkjet recording head and carries out a recording on a recording medium by ejecting ink from the recording head, but also an apparatus which jets a liquid, in place of ink, which corresponds to the use of the ink, onto a jetting medium, which corresponds to the recording medium, from a liquid jet head, which corresponds to the inkjet recording head, thereby causing the liquid to adhere to the jetting medium.
The liquid jet head includes, in addition to the recording head, a color material jet head for use in manufacturing a color filter for a liquid crystal display or the like, an electrode material (electrically conductive paste) jet head for use in forming an electrode for an organic light emitting display, a surface emitting display (FED) or the like, a living organic material jet head for use in manufacturing biochips, a sample jet head as a precision pipette, and the like.
As an example of the recording apparatus or the liquid jet apparatus, there is an inkjet printer, and some inkjet printers are equipped with a feeding device (a so-called auto sheet feeder) on which a plurality of sheets of printing paper, acting as the recording medium or the jetting medium, is set in an inclined position. The feeding device includes a feeding roller which feeds the printing paper, a hopper which supports the printing paper in the inclined position, and a separating member which, being provided facing the feeding roller, separates one sheet of printing paper from another (prevents a multiple feeding).
At this point, as an example of the separating member, a separating roller such as is shown in JP-A-2005-112496 is used. The separating roller to which a prescribed rotational resistance (torque) applied is driven to rotate with respect to the feeding roller in a case in which a torque equal to or higher than the prescribed torque is applied to the separating roller, more specifically, in a case in which no printing paper or only one sheet of printing paper exists between the feeding roller and the separating roller. However, the separating roller is not driven to rotate with respect to the feeding roller in a case in which a torque equal to or lower than the prescribed torque is applied to the separating roller, more specifically, in a case in which two or more sheets of printing paper exist between the feeding roller and the separating roller. By this means, the leading edge of the next or subsequent sheet of printing paper, which is about to be multiply fed along with an uppermost sheet to be fed, stays at the separating roller, thereby preventing a multiple feeding of printing paper.
Although the related feeding device is configured in such a way that a multiple feeding of printing paper is prevented by such separating member as described heretofore, in a case of a strong adhesion between the sheets or a like case, the next or subsequent sheet of printing paper may advance downstream of a nip point between the feeding roller and the separating member, that is, may be multiply fed along with the uppermost sheet.


Disclosed are dopamine agonist and opioidergic compositions and methods for their use in the treatment of alcoholism. The invention discloses compounds and therapeutic kits useful in the treatment of alcoholics having the A1 allele of the dopamine receptor D2 gene. Also disclosed are methods of treating alcoholics having the A1/A1 or A1/A2 DRD2 genotype comprising administration of dopamine agonists such as aporphines, ergolines, related compounds, and their analogs, in combination with opioidergic compounds such as naloxone.

1.1 FIELD OF THE INVENTION
The present invention relates generally to the field of molecular biology. More particularly, certain embodiments comprise dopamine agonist compositions and methods for their use in the treatment of alcoholism and related compulsive disorders. In preferred embodiments methods and compositions are disclosed for the treatment of patients having the A1 allele of the D.sub.2 dopamine receptor (DRD2) gene.
1.2 DESCRIPTION OF THE RELATED ART
1.2.1 TREATMENT OF ALCOHOLISM
A variety of effective drugs are now available in the treatment of many mental afflictions including schizophrenia, anxiety reactions and affective disorders. In contrast, with the recent exception of naltrexone, vide infra, no current accepted pharmacotherapy exists for decreasing alcohol consumption and relapse in alcoholics (for reviews see Noble, 1984; Liskow and Goodwin, 1987; Litten and Allen, 1991; Gorelick, 1992).
A variety of methods have been described in the literature in recent years relating to treatment of chronic alcoholism. Such methods have included stimulating electroacupuncture of zones in the ears (Soviet Pat. No. SU 1,757,671, 1992); intramuscular injection of meksidol (Soviet Pat. No. SU 1,777,878, 1992); oral compositions which contain vitamin, protein, fat and carbohydrate compounds (Soviet Pat. No. SU 1,717,069, 1992); visual stimulation using pulsed red light (Soviet Pat. No. SU 1,699,467, 1991); peroral administration of vitamin complexes and honey (Soviet Pat. No. SU 1,697,802, 1991); intravenous injection of cholecystokinin (Soviet Pat. No. SU 1,463,302, 1989); administration of phenylalkanoyl amines (European Pat. No. EP 424,528, 1992); administration of opiod antagonists (Intl. Pat. Appl. Publ. No. WO 960947, 1996); administration of spiroindane derivatives (U.S. Pat. No. 5,298,622, 1994); application of low frequency alternating currents to reflect reflexogenic zones (Russian Pat. No. RU 2,056,110, 1996); a variety of homeopathic compositions including sulfur and rattlesnake venom (Russian Pat. No. RU 2,039,561, 1995); -apomorphine-teturam administration (Soviet Pat. No. SU 1,806,743, 1993); and a variety of treatment methods involving acute negative reaction and somatic disturbance (Soviet Pat. No. SU 170,148; 1968). Each of the aforementioned patents is specifically incorporated herein by reference in its entirety.
Although significant literature exists on the use of various compounds for the treatment of alcoholics, results to date have been sporadic, unpredictable, and a majority of the tests have been limited to theoretical considerations.
European Patent EP 0346830 and corresponding U.S. Pat. No. 4,882,335 (each specifically incorporated herein by reference) report the possible use of naltrexone and naloxone for the treatment of alcoholism in humans, although the data presented was limited to decreased drinking of alcohol by rats following administration of naloxone or naltrexone.
Intl. Pat. Appl. Publ. No. WO 9609047A1 (specifically incorporated herein by reference) discloses a method for treating alcoholism in a mammal using a combination of opioid antagonists and serotonin reuptake inhibitors.
However, with the burgeoning advances in the neurosciences and molecular genetics, the time is propitious to apply this cumulative knowledge to the effective treatment of alcoholism.
1.2.2 ALCOHOL AND THE DOPAMINERGIC SYSTEM
Alcohol, like other substances of abuse, induces euphoria and pleasurable feelings in users. It has been hypothesized that these positive reinforcement effects are manifested through activation of the mesolimbic dopaniinergic reward pathways of the brain (for reviews see Wise and Rompre, 1989; Koob, 1992). In support of this hypothesis is a substantial body of physiological, neurochemical, pharmacological and behavioral evidence. Thus, alcohol, administered both in vivo and in vitro, dose-dependently increases the firing rate of dopaminergic neurons in the ventral tegmental area (VTA) of the brain, indicating that the drug activates the mesoaccumbens dopaminergic system (Gessa et al., 1985; Brodie et al., 1990). These observations are consistent with several studies showing that low doses of systematically and locally administered ethanol increases dopamine (DA) release in a calcium-dependent manner from the nucleus accumbens (NAC) in awake rats (Imperato and Di Chiara, 1986; Wozniak et al., 1991; Yoshimoto et al., 1991; Weiss et al., 1993). That the dopaminergic system is implicated in alcohol-related behaviors also comes from brain lesion studies. Following circumscribed ablation of dopaminergic neurons within either the NAC or tuberculum olfactorium (TO), preference for ethanol significantly increased in rats (Quarfordt et al., 1991). The authors of this report (Quarfordt et al., 1991) suggest that one of the functional roles for the dopaminergic neurons of the NAC and TO is to regulate the craving for a drug with addictive liability such as ethanol.
A role for the dopaminergic system in ethanol preference is also suggested by data from animal genetic models of alcoholism. DA concentrations in the NAC of alcohol preferring (P) rats were found to be significantly lower when compared to alcohol non-preferring (NP) rats (Murphy et al., 1987; Gongwer et al., 1989). More recently, two independent studies of alcohol-naive P and NP rats have shown that the maximum number of binding sites (B.sub.MAX) of the D.sub.2 dopamine receptor to be significantly reduced in the NAC and caudate nucleus of P compared to NP rats (Stefanini et al., 1992; McBride et al, 1993). It is suggested (Stefanini et al., 1992) that one possible interpretation of the reduced D.sub.2 numbers in the P rats is that it may reflect a parallel reduction in dopaminergic neurotransmission in limbic areas of the brain. To compensate for this deficit, the P rats consume more alcohol in order to release enough DA to produce an adequate level of reward.
Whereas ethanol consumption involves several brain neurotransmitters including norepinephrine (Ahlenius et al., 1973; Amit and Brown, 1982; Brown and Amit, 1977; Corcoran et al., 1983; Davis et al., 1979; Murphy et al., 1985), serotonin (McBride et al., 1988; Murphy et al., 1988) and GABA (Hwang et al., 1990; McBride et al., 1990), growing evidence, derived from the administration of neurotransmitter receptor agonists and antagonists, further supports an important role for the dopaminergic system in mediating the stimulating reinforcing effects of ethanol.
1.2.3 DOPAMINE AGONISTS AND DECREASED ALCOHOL INTAKE IN RATS
Decreases in alcohol intake of P and High-Alcohol-Dinking (HAD) rats were found after the administration of the D.sub.2 agonists bromocriptine (McBride et al., 1990) and quinpirole (Dyr et al., 1993). In another study (Weiss et al., 1990), the differential effects of naloxone (an opiate antagonist), bromocriptine and methysergide (a 5-HT antagonist) on ethanol consumption was compared in P and unselected Wistar rats. In P rats, naloxone treatment resulted in a dose-dependent suppression in responding for both ethanol and water, but did not alter ethanol preference. This suggests that the response decrements observed with naloxone was reflective of a more general depression in consummatory behavior. In contrast, bromocriptine produced a significant, dose-dependent shift in preference from ethanol toward water by inhibiting responding for ethanol while enhancing water consumption. In the Wistar rats, naloxone and bromocriptine treatments produced changes in ethanol preference patterns similar to but less than those observed with methysergide. Furthermore, a recent study (Rassnick et al., 1993) has determined the effects of a novel dopamine receptor agonist (SDZ-205, 152) in rats trained to orally self-administer ethanol. The results of this study showed that administration of this dopamine agonist selectively reduced ethanol-reinforced responding without affecting responses for water.
1.2.4 APOMORPRINE AND ALCOHOL DEPENDENCE IN HUMANS
Studies of humans provide additional support to connections between alcohol dependence and CNS dopaminergic function. Neuroendocrine evidence for reduced dopamine receptor sensitivity in alcoholics has been found. Using apomorphine (APO), a D.sub.2 agonist, the maximal growth hormone (GH) response was found to be significantly reduced in alcoholics who were 2 months (Balldin et al., 1992) and more than 6 years (Balldin et al., 1993) abstinent compared to controls. It was suggested that the reduced D.sub.2 receptor function in alcoholics was a trait marker for this disorder, although the possibility that this reduction is acquired after earlier periods of heavy alcohol consumption cannot be ruled out. Heinz et al., (1995) compared GH response to APO in relapsed (active) and in abstinent (recovering) alcoholics. Despite the fact that both groups had similar prior alcohol consumption history and no other clinical data differentiated these groups, the relapsed alcoholics had a more blunted GH response compared to abstinent alcoholics. Additionally, Weisbeck et al. (1995) determined GH response to APO in controls and in alcoholics who were either family history positive or negative for alcoholism. The blunted response in the positive but not the negative group was significantly different when compared to controls. These authors suggest that the reduced D.sub.2 receptor function in family history positive alcoholics may be a genetically influenced trait marker. Finally, very recent imaging studies including PET (Hietela et al., 1994) and SPECT (Tiihonen et al., 1995) analyses have shown a reduced central dopaminergic function in chronic non-violent alcoholics compared to controls.
1.2.5 EARLY STUDIES USING BROMOCRIPTINE
At least three early studies (Morgan et al., 1980; Morgan, 1981; Anokhina, 1984) have investigated the use of bromocriptine for the treatment of alcoholism in humans, but the data were not controlled. In another study of 60 alcoholics, randomly assigned to bromocriptine (2.5 mg tid) or placebo, the bromocriptine group compared to the placebo group showed a greater amelioration of withdrawal symptoms over the 10-day trial (Borg and Weinholdt, 1982). In the first double-blind bromocriptine/placebo study, 50 alcoholics, randomly assigned to bromocriptine (2.5 mg tid, months 1-3; 5 mg tid, months 4-6) or placebo were evaluated for 6 months (Borg, 1983). The overall effects on the number and duration of drinking episodes, psychological status and social functioning were significantly improved in the bromocriptine compared to the placebo group. Rater global evaluation of medication effect was assessed as moderate to very beneficial in 16 of 19 bromocriptine administered patients and in one of 23 placebo administered patients. The incidence of adverse reactions was low in both groups, and the higher dose of bromocriptine (15 mg/day) was no better than the lower dose (7.5 mg/day) in treatment outcome. In a second double-blind controlled study (Dongier et al., 1991), 84 alcoholics received either bromocriptine (2.5 mg tid) or placebo and were followed for two months. Drinking behavior showed a marked improvement in both the bromocriptine and placebo treated groups. Moreover, significant differences in favor of the medication were observed in psychiopathological measures, and trends in the same direction in most of the other iffcacy measures.
In a third double-blind trial, alcoholics were given either bromocriptine (2.5 mg) tid, months 1-3; 5 mg tid, months 4-6) or placebo for six months (Powell et al., 1995). Alcoholics were divided, according to the authors, into three "not pure" subtypes: 1) "pure alcoholics," 2) alcoholics who had comorbid affective or anxiety disorders but not antisocial personality disorders (APD) and 3) alcoholics who had comorbid APD but were with or without Axis I disorders. Thirty-four alcoholics on bromocriptine and 31 alcoholics on placebo completed the trial. Analysis of data showed a significant decrease in anxiety (Beck Anxiety Inventory) and a trend in reduced craving and drinking days only in APD alcoholics receiving bromocriptine compared to APD alcoholics receiving placebo.
Thus while the early studies support a role for the use of bromocriptine in the treatment of certain aspects of alcoholism, relatively few patients were studied or remained in the trial, the reliability and validity of most of the measures used to assess outcome were not reported, and patient compliance to the bromocriptine schedule was not done.
1.2.6 OPIOIDERGIC AND DOPAMINERGIC SYSTEMS
There is growing evidence that the opioidergic and dopaminergic systems are anatomically and functionally interconnected. Nigrostriatal dopaminergic afferents have direct input into the opioidergic (enkephalinergic) neurons of the striatum (Kubota et al., 1986), and all detectable enkephalin neurons in the striatum contain the D.sub.2 dopamine receptor mRNA (Le Moine et a., 1990). Moreover, dopamine antagonists and lesions of the dopaminergic pathways in the brain affect preproenkephalin A activity (Morris et al., 1988; Normand et al., 1988).
Behavioral, pharmacological and neurochemical studies implicate the opioidergic and dopaminergic systems in the reinforcing effects of ethanol and other drugs of abuse (Koob and Bloom, 1988). Animal studies show that opiate receptor agonists increase preference for ethanol (Volpicelli et al., 1992; Wild and Reid, 1990), whereas antagonists of these receptors reduce ethanol consumption (Le et al., 1993; Myers et al., 1986). Further, studies on human alcoholics suggest the effectiveness of the opiate receptor antagonist naltrexone in reducing the positive reinforcing effects of alcohol consumption (O'Malley et al., 1992; Swift et al., 1985; Volpicelli et al., 1992). Moreover, ethanol-induced increase of brain doparnine levels in animals is blocked by both opiate receptor antagonists naloxone (Widdowson and Holman, 1992) and naltrexone (Benjamin et al., 1993). The gathering evidence suggests an essential role for the endogenous opioidergic system in mediating the effects of ethanol on brain dopamine pathways associated with reward.
1.2.7 NALTREXONE IN THE TREATMENT OF ALCOHOLISM
Lopez-Ibor-Alino (1990), in an uncontrolled naltrexone trial in an opiate treatment program, found that patients on regimens of naltrexone increased their alcohol use. In sharp contrast, however, other studies have shown the opposite effect. Volpicelli et al., (1992), in a double-blind, placebo-controlled trial, studied the effect of naltrexone in 70 male outpatient alcoholics. During the 12-week study, only 23% of naltrexone-treated subjects met the criteria of relapse, whereas 54.3% of the placebo-treated subjects relapsed. Moreover, subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. In an accompanying article, O'Malley et al. (1992), also in a double-blind, placebo-controlled trial, studied 97 alcoholics receiving supportive therapy or coping skills therapy over a 12-week period. They found that naltrexone proved superior to placebo in measures of drinking and alcohol-related problems, including abstention rates, number of drinking days, relapse and severity of alcohol-related problems. Moreover, those patients who initiated drinking and who had received naltrexone and coping skills therapy were the least likely to relapse. Bohn et al. (1994) conducted a single-blind study with two doses of naltrexone and found reduced drinking by alcoholics.
Mason et al. (1994), in a double-blind, placebo-controlled pilot trial, studied the effects of nalmefene (a new opiate antagonist and structurally similar to naltrexone) in 21 alcoholics. Nalmefene lowered the rate of relapse and decreased the number of drinks/drinking days when compared to the placebo group. A very recent study by Volpicelli et al. (1995) presented data on their previously studied alcoholics (Volpicelli et al, 1992) who deviated from abstinence. Of the 36 subjects who reported a slip from abstinence, 12 naltrexone- and 17 placebo-treated alcoholics were available for assessment. The week of their first reported slip averaged around week 3 for both groups with no significant difference between the two groups. However, the placebo subjects drank more alcohol during the first lapse than did the naltrexone-treated subjects (P<0.05). Moreover, retrospective self-reports showed that a significantly larger proportion of naltrexone than placebo subjects experienced less high than usual after drinking alcohol (P=0.006). However, the reported levels of uncoordination, alcohol craving, memory disturbance and loss of temper did not differ between the naltrexone and placebo groups. Moreover, there were no significant correlations between these subjective variables and whether the subjects drank until they met relapse criterion.
How naltrexone exerts its effects in humans remains yet to be determined. In a recent study, Swift et al. (1994) quantified the effects of naltrexone on alcohol intoxication in nonalcoholic humans. They found less positive reinforcement and more intense sedative effects when the subjects received naltrexone and ethanol as compared to subjects who received placebo and ethanol. The combination of naltrexone and ethanol also induced nausea and vomiting in some of the subjects. These findings are consistent with the idea that naltrexone alters the subjective effects of ethanol. In particular, naltrexone reduces the positive reinforcing effects of ethanol intoxication and increases the negative reinforcing effects. Swift et al. (1994) suggest that these changes may underlie the observed decrease in ethanol drinking reported in the above clinical trials.
The neurochemical mechanisms through which naltrexone exerts its effects in humans remain unclear. Whereas the above cited clinical studies suggest the involvement of the opioidergic system, there is a substantial body of evidence from animal studies which indicates a connection between the opioidergic and dopaminergic system in the brain. For example, a recent report by Benjamin et al. (1993) shows that naltrexone and other opioid antagonists block the ethanol-induced release of dopamine in animals. If then, as cited earlier, the positive reinforcing effects of ethanol (and other substances of abuse) are manifested through activation of the mesolimbic dopaminergic pathways of the brain, then naltrexone, by blocking ethanol-induced release of dopamine, may diminish the reinforcing effects of alcohol.
In 1990, the present inventor and colleagues reported (Blum et al., 1990) a molecular genetic association with alcoholism. Specifically, the A1 (minor) allele of the D.sub.2 dopamine receptor (DRD2) gene was found to be associated with severe alcoholics when compared to nonalcoholic controls. Subsequently, several studies, done in the U.S. and abroad, have further ascertained the role of this gene in alcoholism. Despite variations in the selection of subjects and other methodological issues, the combined evidence from these studies affirms the high prevalence of the A1 allele in alcoholics, especially when severe alcoholics are compared to nonalcoholic controls. Similarly, studies on cocaine addicts and polysubstance abusers have also found a high prevalence of the minor (A1 and B1) alleles of the DRD2 gene in these patients (Noble et al., 1993; Comings et al., 1991; Smith et al., 1992). Binding studies on the brains of deceased subjects showed that those carrying the A1 (minor) allele had reduced number of D.sub.2 receptors than those carrying the A2 (major) allele (Noble et al., 1991). Moreover, in recent neurophysiological Noble et al., 1994c) and neuropsychological (Berman and Noble, 1995) studies of alcohol- and other drug-naive children, evidence also suggests a reduced dopaminergic function in subjects carrying the A1 allele compared to those having only the A2 allele. Put together, the emerging data suggest that subjects who inherit the A1 allele have an inherent deficit of their brain dopaminergic system.
1.3 DEFICIENCIES IN THE PRIOR ART
Alcoholism, a heterogeneous disorder with hereditary and environmental determinants, is a major health and social problem with a high recidivism rate. With the exception of the aversive agent disulfiram, no accepted pharmacotherapy now exits for the treatment of this disorder. The advent of molecular genetic techniques makes possible the identification of genetic types of alcoholics. Such identification renders feasible specific pharmacogenetic approaches to the treatment of hereditary forms of alcoholism.
A need to effectively treat alcoholics has long been recognized. To this end, several workers have treated this group of patients with various drugs; some that cause an aversion to alcohol (e.g., Anabuse.RTM.) while more recent treatments have investigated drugs that act as dopamine agonists. While some success has been reported in treating alcoholics with bromocryptine, the results did not indicate that such treatment was generally suitable for all alcohol addiction. Apparently there has not yet been an effort to first identify those subsets of patients appropriate for treatment with dopamine agonists, nor have any efforts been made to tailor drugs to interact specifically with receptor molecules in alcoholic patients identified with a genetic predisposition to alcohol abuse. Additionally, as with many drug regimens, there is not only a lack of specificity for universal treatment of alcoholics, there is also the problem of drug side effects. This is particularly so in the reported attempts to treat alcoholism where the limited success with certain dopamine agonists can be associated with inappropriate effects and/or interactions with other drugs.

Bromocriptine for the treatment of alcoholics diagnosed with the D.sub.2 dopamine receptor DRD2 A1 allele

The Regents of the University of California


The present invention relates to a method of disassembling large-caliber combat cartridges, particularly armor-piercing cartridges, including a combustible casing jacket that conically widens in the direction of the projectile, a casing bottom and a casing cover to which is fastened a sub-caliber projectile equipped with a propelling sabot.. To be able, on the one hand, to reduce expenditures for the disassembly of such combat cartridges and, on the other hand, to reuse a major portion of the original combat cartridges for the production of corresponding training cartridges, it is proposed to separate the casing jacket as well as the casing cover starting at their outer circumference, in regions having approximately the same, predetermined diameter D1. This diameter D1 here corresponds to the maximum diameter of the component of the new cartridge to be produced later from the disassembled components. The portion of the casing jacket and of the casing cover disposed between the regions is discarded and is replaced in the production of the new cartridge by a cylindrical casing jacket component having the diameter D1.

The present invention relates to a method of disassembling a large-caliber combat cartridge which is composed of a propelling charge casing and a sub-caliber projectile equipped with a propelling sabot. The propelling charge casing includes a combustible casing jacket, a casing bottom and a casing cover that is conically tapered toward the propelling sabot. The sub-caliber projectile is fastened to the casing cover and the casing jacket conically widens toward the casing cover so that it has its maximum diameter at the transition to the casing cover. The invention further relates to the use of the cartridge components obtained by the method according to the invention for the production of new cartridges, particularly for training purposes.
At present, many armies have the problem of having amounts of combat ammunition, particularly armor-piercing ammunition, stored in ammunition bunkers, which, however, will not be needed within the foreseeable future. Thought has therefore been given to how this ammunition can be economically converted to training ammunition. For this purpose, the combat cartridge must first be disassembled which generally requires opening the propelling charge casing at the connecting surface between the combustible casing jacket and the casing cover and removing the projectile together with the casing cover. The combat projectile is then replaced by a training projectile and a casing cover which are connected with the propelling charge casing. For this purpose, the new casing cover and the old casing jacket are connected with one another, for example, by means of glue.
Problems arise particularly in the disassembly and reuse of the disassembled components of older combat cartridges that can be fired from tank cannons. These cartridges are often equipped with a casing jacket that--for reasons of manufacturing technology--conically slightly widen toward the casing cover. It has been that, if such cartridges are stored for a longer period of time, the larger diameter and additionally created imbalance of the casing jacket at the casing cover may cause difficulties in loading. For that reason, cartridges have already been manufactured in the past that have cylindrical instead of conical casing jackets, with the diameter of the casing jacket being selected to be slightly less than the maximum diameter of corresponding cartridges that have a conical casing jacket.
In order to be able to utilize existing stocks of combat ammunition having conical casing jackets for the production of training cartridges, such cartridges have in the past been disassembled in such a way that the casing bottom as well as the projectile can be reused with a new guide mechanism. The casing jacket, however, was removed and replaced by a new cylindrical casing jacket.
The drawback of such a method is that many process steps are required for the disassembly of the old as well as the assembly of the new cartridge (removing the screws with which the casing cover is fastened to the projectile, unscrewing the casing cover, disassembling the safety ring and spring sheet at the bottom of the casing and corresponding assembly during the production of the new cartridge, disposal of the conical casing jacket and the casing cover, etc.).

Method of disassembling large-caliber combat cartridges and use of the cartridge components obtained by the method for the production of new cartridges


A system for implementing software objects using an object-prototype model. Objects are defined as collections of properties, each having a unique property name. A collection of property names defines a "shape." The use of shapes frees the representation of an object in memory from the order in which the properties of the object are declared. Methods are defined independently of objects and are applicable to a specified shape, rather than to objects that are derived from a class in which the method is defined. Methods can be applied to any object that has the specified shape or that has a superset of the properties defining the specified shape, regardless of the place of the object in any inheritance hierarchy. The definition of a shape can also include additional selection criteria, such as restrictions on the values of properties, so that the application of a method can be restricted to objects satisfying the specified criteria. The properties of objects can be divided into subgroups representing different aspects of the object and different subgroups of an object can be inherited from different parent objects, based upon either a has-a or an is-a hierarchy. The shape of an object is determine by all of its properties and is not confined by subgroup boundaries.

To cope with the rising complexity of computer programs, many modern programming languages use discrete programming structures called "objects" that present well-defined interfaces to the outside programming environment and are, in principle, self-contained. Objects typically contain information and methods that operate on the contained information or external information.
The pieces of information associated with an object are referred to as "properties" of the object. Each property has a name and can be assigned a value. The type of datum that can be assigned to a property as its value may be, for example, a datum of a simple type, such as an integer or a floating point number, or a datum of a complex type, such as a data structure or another object. When an object is defined, a programmer typically declares the properties that the object contains and specifies the data type for each property. The data type of a property indicates the type of data that the property can represent. For example, a property of the type "integer" can have values 1, 2, 3, etc., whereas a property of the type "pointer to a method" contains a memory address of the beginning of a set of instructions. The properties of an object collectively define its structure.
Each property of an object has associated attributes, such as its name, type, accessibility (e.g., in C++: public, protected, or private), and position within the object. The values of these attributes are not typically accessible to the programmer, i.e., a programmer cannot typically query an object to determine its type or its availability. In C++, a programmer can query the size of a property and could indirectly determine its position within an object by subtracting a pointer to the property from a pointer to the object. The inability to determine attributes of an object further limits programmers from specifying how a program will function.
A method comprises one or more lines of computer code that perform an operation. A method is typically executed by departing from the sequential execution of program lines at the point of the method call, jumping to the lines of code constituting the method, and then returning to the sequential execution of the program below the method call. In object-oriented programming, methods are typically defined as part of a class definition and can be applied only to objects of the defining class, or objects of classes derived from the defining class. The methods that can be applied to an object are collectively called the "behavior" of the object.
One fundamental goal of object-oriented programming is to encapsulate properties and methods within an object so that a second programmer can use an object defined by a first programmer after learning only the interface of the object. The interface contains code needed to send data to an object and to receive output, such as calculation results, error codes, and object status, from the object. The second programmer should not need to understand the internal workings of the object. Programmers should, therefore, be able to write programs that access objects defined by other programmers and reuse previously defined objects as building blocks of new programs. For example, once a programmer defines an object that represents an automated teller machine, another programmer should be able to use the automated teller machine object in different programs that, for example, model the same automated teller machines in a different banking network. Encapsulation of objects also allows a programmer to modify the internal workings of a particular object to eliminate an error or improve efficiency without having to change other parts of the program that use the object. Encapsulation thus reduces complexity in large programming endeavors.
Another fundamental goal of object-oriented programming is extensibility, i.e., allowing previously created objects to be extended to include additional properties or functionality. This is accomplished by allowing one object to inherit properties and methods from another source, such as a parent object. For example, if a new type of automated teller machine having additional features becomes available, a programmer should be able to easily create, based upon an existing automated teller machine object, a new automated teller machine object that has additional properties and materials representing the additional features. By eliminating the duplication of programming efforts, inheritance allows existing object-oriented code to be expanded into new uses. Inheritance also facilitates building complex objects from relatively simple building blocks.
The class-instance programming model is one technique for implementing software objects. In the class-instance programming model, abstract objects, known as class objects, are defined, and then instances of the class can be declared. A class object defines the structure and methods of instances of the class, but properties in the abstract class itself do not have values. An instance of a class is an object having the structure defined by the class and capable of being assigned property values. All instances of a class, therefore, have a separate memory structure for storing the property values of that instance. Unlike properties, there is typically only one copy of each of the methods of a class. Method calls, therefore, typically include as an "invisible parameter" an indication of which instance of the class is calling or being passed to the class method.
To facilitate the creation of new classes in the class-instance programming model, a "child" class can be defined that is derived from and inherits the structure of its parent class. An instance of the child class would, therefore, have all the properties and methods defined in the parent class and any additional properties and methods defined specifically in the child class. For example, a class "Vehicle" may have derived from it a child class "Spacecraft," an instance of which is a particular spacecraft, e.g., the space shuttle Discovery. Because the child class (Spacecraft) is a specific type of the more general parent class (Vehicle), this type of inheritance is known as an "is-a" inheritance.
To take advantage of inheritance, object-oriented programming languages are often sold with libraries of predefined abstract classes that aid programmers in building new classes and that promote use of standardized objects to build application software. Class libraries theoretically greatly simplify creation of new software.
Many programming languages allow multiple inheritance, i.e., inheriting properties and methods from more than one parent object. For example, FIGS. 1A, 1B, and 1C show, respectively, an "Airplane" class 10, a "Boat" class 12, and a "Seaplane" class 14 that inherits from the Boat and Airplane classes. FIG. 1C shows that the memory structure 16 of an instance of the derived Seaplane class 14 is a concatenation of the memory structures 18 and 20 of Boat class 12 and Airplane class 10, respectively, the concatenation being performed in the order that the inheritance was declared. (The heavy lines of FIGS. 1A, 1B, and 1C enclose the actual memory structures and separate them from label information included in the drawings to facilitate understanding of the prior art and the invention. This convention is also followed in other figures in this specification.) Thus, properties having the same name in multiple parent classes are typically inherited in the children as separate properties. With duplicate method names, however, one method will override another and only one method will be inherited.
Unfortunately, multiple inheritance can cause encapsulation to break down in complex programming environments. One difficulty arises because inheritance lacks granularity, i.e., it is an all-or-nothing proposition. A derived class inherits the entire set of properties and methods of its parent class or classes; a child class cannot inherit only specified properties or methods from individual parents. The following example illustrates the point.
FIG. 2A shows an airplane 24, having an engine 22, a fuselage 26, landing gear 28, wings 30, a rudder 32 and a propeller 34. FIG. 2B shows a boat 36 having a hull 38, a mast 40, a sail 42, an anchor 44, a rudder 46 and riggings 48. In accordance with prior art multiple inheritance, Seaplane class 14 inherits all the properties and methods of Airplane class 10 and Boat class 12, even if some of the properties are redundant or inappropriate for a Seaplane.
FIGS. 2C and 2D illustrate the absurdity of all-or-nothing inheritance. All the components of Boat 36 and Airplane 24 are force-fit into a composite seaplane. FIG. 2C shows a Seaplane 50 that inherited first from Boat 36 and then from Airplane 24. FIG. 2D shows a Seaplane 52 that inherited first from Airplane 24 and then from Boat 36. In both cases, the Seaplane object has some inappropriate properties, such as a Sail 42, and duplicate properties, such as Rudders 32 and 46, Rudder 32 being an aircraft rudder and Rudder 46 being a boat rudder. When a programmer refers to the Rudder property of the Seaplane object, it is unclear which rudder will be referenced.
To avoid some of the absurd results from multiple inheritance and produce a useful derived class, it is sometimes necessary to modify one or more of the parent classes. For example, it may be necessary to change Boat class 12 by eliminating Sail 42 to produce a derived Seaplane class that accurately models a Seaplane. Changing Boat class 12, however, can have consequences in other parts of a program that use objects that inherit properties and methods from the original Boat class 12. For example, a programmer would be required to track down other objects and classes that inherit from the modified Boat class to ensure that other sections of the program are not unintentionally affected. Needing to understand and modify the internal definitions of parent classes is anathema to the concept of encapsulation, which dictates that objects be self-contained so that users of an object need not understand the internal workings of the object. Moreover, changes to a class object in a class library will often require not only recompilation of the library itself, but also recompilation of existing software that uses the changed class object. The problems demonstrated by the foregoing example arise in part because a programmer cannot specify which aspects of a derived class will be inherited from one parent class and which aspects will be inherited from another parent class. A small modification in a parent class may be inappropriate if inherited in all instances of child classes and a modification cannot be made to a single instance if class inheritance is used to provide the change.
If a particular property name or method name appears in more than one parent object, the method that will be inherited and the order of properties in the child class depends upon the order of inheritance and upon arbitration rules. For example, a programmer may wish to define a class E (FIG. 3) that inherits properties and methods from classes C and D, which are defined in two different class libraries, possibly from different software manufacturers. If some of the properties or methods in class A have the same names as properties or methods in class B, the methods and order of properties in classes C and D will depend on the order of inheritance from classes A and B. To function properly, class C may require that a method be inherited from class A, rather than from class B, or that the properties in class C be in a particular order. In the multiple inheritance example of FIG. 3, in which class E inherits from classes C and D, each of which inherits in a different order from classes A and B, it is very difficult to determine the resulting methods and property order in class E. In some cases, class E may be defective because a method inherited from class C may depend upon a property being inherited first from class B, whereas a method inherited from class D may depend upon the same property being inherited first from class A.
Applying arbitration rules to objects having multiple parent classes, each of which can also have multiple parents, can quickly become very complex. The arbitration rules require a detailed knowledge of the structure of the parent classes in the inheritance tree. Because complex classes in class libraries are often built upon simpler classes in the library, a programmer may need to understand the structure of many of the classes in the library before he or she is able to predict how an object he or she creates using class objects from the library will function.
For this reason, programmers that produce class libraries typically provide source code for their class libraries so that applications programmers can determine the inheritance order and redefine classes in the library if necessary. To require knowledge of the parent objects and of complex arbitration rules greatly increases the complexity of object-oriented programming and related source code, vitiates the purpose of encapsulation, and reduces the reusability and extensibility of code. This defeats the purpose of having extensible objects as a result of encapsulation and inheritance and requires extensive knowledge of preexisting class libraries by the programmer.
The complexity and inflexibility of inheritance in languages such as C++ derives in part from the close relationship between the memory structure in which an object is stored and its class definition. As shown in FIG. 1C, a child object is stored in memory as a concatenation of the objects from which it derives. This allows the child object to be "type cast," i.e., treated as though it were of the same object type as the parent object. Such a system, however, requires that all properties of an object be inherited to maintain the relationship in memory of the different components of a derived object. The rigid memory structure in which properties of objects are stored in the order in which they are declared and inherited also constrains the allocation of memory by a compiler, thereby causing inefficient use of available memory. The compiler is not free to reorder or eliminate duplicate properties when such reordering or elimination of duplication would produce more efficient memory usage.
The object programming model is another technique for implementing software objects. In the object programming model, objects are defined and can then be copied or used to derive other objects. This technique differs from the class-instance model in that there are no abstract classes. In some respects, the object model is more flexible because objects are independent entities and can be created and modified independently of any definition of abstract classes. Moreover, methods can be attached to individual objects, rather than to all members of a class. The object model is also consistent with the use of visual programming tools, such as Microsoft's Visual Basic.TM., to create graphical user interfaces. In using such tools, programmers can create, for example, menu objects on the screen, without having to first create an abstract menu class.
In the object model, objects can be created by copying them from other objects, but there are no links between the original object and the newly created object which receives the defined structure and assigned property values from the original object. Property values in the new object do not change when property of the original is changed. Visual Basic.TM., Asymetrix's Toolbook.TM., and Apple's Hypercard.TM. are examples of applications based upon an object model without is-a inheritance.
A variation on the object programming model, the object-prototype programming model, provides for inheritance. When the value of a property of a parent object changes, the corresponding property in the child object also changes. A child object in the object-prototype model inherits from a particular parent object, rather than from an abstract class as in class-instance model inheritance, thereby allowing an object to inherit actual property values, in addition to structure. As in the class-instance model, inheritance in the object-prototype model is typically based upon an is-a hierarchy, i.e., a derived object is a type of the parent object. Applications using the object-prototype models are not in widespread commercial use.
Another approach to object-oriented language architecture is the use of a containment, or "has-a," hierarchy as opposed to an is-a hierarchy. In a containment hierarchy, a child object is contained in a parent object, instead of being a type of the parent object. An object is contained within only a single container, although the parent container can itself be contained within another container.
Most implementations do not allow inheritance from the parent in a container hierarchy. In some applications, such as Hypercard.TM. and Toolbook.TM., when a method cannot be found associated with an object, the container of the object is checked to determine whether the container defines the method. Such a technique can be considered inheritance of methods from a parent container.
In summary, the class-instance programming model uses abstract classes that define a structure and methods. The structure and methods of one or more abstract classes can be inherited by a child abstract class. Inheritance in the class-instance model is based upon an is-a hierarchy, in which child classes are a type of the parent class and a child class inherits everything in its parent class or classes. Instances, which include property values, are created from the abstract classes, but instances cannot be derived from other instances. Therefore, structure and methods can be inherited, but property values cannot be. This restricts reusability and makes the programmer's task more complex. Expert knowledge of complex rules of arbitration and of the parent classes are often required to create specific child classes and to understand inherited behavior.
In the object programming model, objects can be copied from other objects, so structure, behavior, and data can be derived. Object systems allow copying of objects, but do not provide for inheritance. Object-prototypes systems provide for inheritance, with the inheritance hierarchies based upon is-a relationships in which each child is a type of the parent. In some applications, limited inheritance of methods is based upon has-a relationships, in which each child is contained in the parent. Has-a inheritance relationships are generally inconsistent with inheritance of property values.
Although the mission of object-oriented programming is to create modular applications using reusable and extensible objects, this promise remains largely unfulfilled in standard object-oriented programming. Classical object-oriented programming is hampered by the complexity of native object classes adopted by programming languages (such as C++), which complexity results in well-known problems in object definition and encapsulation and the related difficulty in dynamically changing objects and methods during application run-time.
Recognizing problems with multiple inheritance in the standard object-oriented language architecture, the prior art takes several approaches to programming unique objects, including binding objects at run-time, modifying and recompiling parent class libraries, and writing custom code to override the inherited properties or methods and assert the class membership of a branch object instead of letting the program architecture determine inheritance. The properties and behavior of an object, however, become dependent on its parent classes and its custom coding, thereby causing difficulty in determining how the object will behave. Complexity of the program architecture increases. The apparent solutions treat only the symptoms and produce further difficulties of their own, making it difficult to create code that is reusable and extensible by other developers.
As a result, current object-oriented programming systems require knowledge of complex rules for arbitrating inheritance and require that a programmer learn entire native class libraries to obtain consistent behavior from objects, determine inheritance, and debug code.

Method and system for implementing software objects