The invention relates to a method for determining the degree of polarization (P) of a nuclear spin polarized gas, in particular 3He, 129Xe, in which the nuclear spin polarized gas is placed in a container, comprising determining the magnetic field Bd of the pola gas by measuring the magnetic dipole field emerging therefrom and then determining from Bd the degree of polarization of the gas.

The invention relates to a method and apparatus for determining the degree of polarisation of nuclear spin polarised gases, in particular 3He or 129Xe.
Nuclear spin polarised gases, such as the helium isotope with mass number 3 (3He) or the isotope of xenon with mass number 129 (129Xe) and gases containing the fluorine, carbon or phosphorus isotopes 19F, 13C or 31P, are required for a wide variety of basic physics research experiments.
In the medical field, such isotopes have particularly been discussed for use in nuclear spin tomography (magnetic resonance imaging), for example of the lung. (See for example WO95/27438, WO97/37239, Bachert et al., Mag. Res. Med. 36: 192-196 (1996) and Ebert et al., The Lancet 347: 1297-1299 (1996)). In addition, Noxc3xal et al., J. Phys. III France 6: 1127-1132 (1996) discloses a 4He magnetometer used to detect the static magnetic field produced by optically pumped 3He nuclei submitted to RF discharge. Similarly, Cohen-Tannoudji et al., Phys. Rev. Letts. 22: 758-760 (1969) discloses the use of a sensitive low-field magnetometer to detect the static magnetic field produced by optically pumped 3He nuclei in a vapor. To be useful in nuclear spin tomography, the nuclear spin polarised gases require a degree of polarisation P of spin I of the atomic nucleus, or the nuclear magnetic dipole moment xcexcI connected therewith, which is about 4-5 orders of magnitude larger than PBoltzman the degree of polarisation of the gas in its relaxed state in normal thermal equilibrium in the magnetic field BT of the mr imaging apparatus. PBoltzmann is related to the Boltzmann constant, the magnetic dipole energy xe2x88x92xcexcIBT and thermal energy kT by:
xe2x80x83PBoltzmann=tan h(xcexcIBT/kT)xe2x80x83xe2x80x83(1)
(where k=Boltzmann constant, and T=absolute temperature in Kelvin).
Where PBoltzmann  less than  less than 1, then it approximates to xcexcI BT/kT.
Since routinely BT=1.5T and T=300K for the hydrogen isotope 1H used in tissue tomography, it has a PBoltzmann of only 5xc3x9710xe2x88x926, but in gas tomography a P greater than 1xc3x9710xe2x88x922 (i.e. 1%) is required. The requirement for such an extremely high P is mainly due to the low concentration of gas atoms in comparison to that of hydrogen in tissue. Gases with such degrees of polarisation (normally referred to as xe2x80x9chyperpolarised gasesxe2x80x9d) can be prepared using various known methods, advantageously by optical pumping or by polarization transfer.
In addition, large amounts of hyperpolarised gas, for example of the size of an intake of breath (0.5 to 1 litre) must be prepared for use.
Particularly high degrees of polarisationxe2x80x94for example  greater than 30%xe2x80x94in simultaneously high production amounts, for example 0.5 liters/h, may be achieved by compression of an optically pumped gas. This method is described in the following publications:
Eckert et al., Nuclear Instruments and Methods in Physics Research A 320: 53-65 (1992);
Becker et al., J. Neutron Research 5: 1-10 (1996);
Surkau et al., Nuclear Instruments and Methods in Physics Research A 384: 444-450 (1997); and
Heil et al., Physics Letters A 201: 337-343 (1995).
The extremely costly production of hyperpolarised gases, for example using the methods described above, generally involves production at a site remote from the place of use. As a result, they must be transported from the place of production to the user. Since a wide variety of relaxation processes (e.g. wall relaxation, relaxation in inhomogeneous, external, stray magnetic fields, etc.) causes the gas to depolarise to a greater or lesser extent, it is necessary to determine the degree of polarisation before using the hyperpolarised gas, for example in medical imaging.
One problem is that this must be determined as precisely as possible despite stray fields or applied fields. Further, the determination should be performable by relatively inexperienced personnel, ie. personnel who are not experts in the physics of hyperpolarized gases.
The present invention solves the above problem by providing a method for determining the degree of polarisation of nuclear spin polarised gases by exploiting the fact that nuclear spin polarisation of gases produces magnetic fields Bd in the nanoTesla to microTesla (nT to xcexcT) range.
Thus viewed from one aspect the invention provides a method of determining the degree of polarisation (P) of a nuclear spin polarised gas in a container, said method comprising determining the magnetic field Bd of the polarised gas using a magnetic field sensor and then determining therefrom the degree of polarisation of the gas.
In the method of the invention, the shape and size of the container into which the polarised gas is placed is important. Thus, the magnetic field Bd, which is dependent on the degree of polarisation of the gases, may be determined using a magnetic field sensor, e.g. a magnetometer, rather than a nuclear magnetic resonance polarimeter as has been used in the past, and the absolute degree of polarisation can be determined from Bd by taking into consideration the geometric shape of the container in which the gas is placed, the type of gas and its density, and the arrangement of the sensor relative thereto.
If, as is preferred, the container in which the gas is received is spherical in shape, then the magnetic field has a field gradient like that formed by a point dipole.
Thus for a spherical container, the magnetic field Bd of the polarised gas on the equitorial outer surface of the container deriving from the orientated nuclear magnetic dipole moment of the nuclear spin gas is:                               B          d                =                              -            P                    ·          n          ·                                                    R                3                                                          μ                0                                                    3                                            r                3                                              ·                      μ            N                                              (        2        )
where P represents the degree of polarisation to be determined and n the particle density of the gas. The factor R3/3r3 is termed the geometry factor, and depends on the shape of the container and thus on the volume in which the nuclear spin polarised gas is dispersed. R represents the radius of the sphere and r the distance of the sensor from the centre point of the container sphere perpendicular to the dipole axis. xcexc0=1.257xc3x9710xe2x88x926 Vs/Am, i.e. the permeability of vacuum, and xcexcN=1.075xc3x9710xe2x88x9226 Am2, the nuclear dipole moment of the gas (in this case 3He)
Similar equations to equation (2) may be generated for containers which are non-spherical.
The geometric factor also takes the position of the magnetic field measuring apparatus relative to the direction of the magnetic field of the gas into consideration. If the field emerges from the poles of the container, the sensor is positioned in the equatorial plane of the spherical gas container.
Different geometric factors must be used for different container geometries, as in each case there is a different calculable field gradient of magnetic field Bd. If the geometric factor, the distance from the measuring sensor and the particle density of the-nuclear spin polarised gas in the container are known, then equation (2) can be used to determine the absolute degree of polarisation P from the Bd determined using the measuring apparatus.
As an example, assuming a degree of polarisation P=50% and a particle density n=1020/cm3, then the field at the edge of the sphere (r=R) has a value Bd=0.22 xcexcT. This value is of the order of 1 thousandth of the homogeneous magnetic field caused by the polarisation, similar to, for example, transport fields of 0.3 mT, for example, or external stray fields.
In a preferred implementation of the invention, it is proposed that the sensor comprises a very sensitive magnetic field sensor. In this respect, SQUIDs or more preferably sensors operating on the Forster principle can be considered. Fxc3x6rster sensors operate on the principle of saturable-core magnetometers. The measuring element of saturable-core magnetometers essentially consist of one or more narrow cores of highly permeable materials (xcexc-metal or ferrite) with almost linear B(H) behaviour.
In a variation of a saturable-core magnetometer, a double core sensor comprises two mutually parallel cores each provided with a primary and a secondary winding. The former are opposed, the latter are connected in series. The primary winding is supplied with a constant current by means of a low frequency transmitter (xcexd=50 to 1000 Hz). The current intensity is sufficient to magnetise the highly permeable cores to saturation. A voltage is induced in the secondary windings by the changing magnetic field of the primary coils.
With no external magnetic field, the primary fields in the two cores are equal and opposite. Similarly, in the two secondary coils during the time in which the magnetic flux density B changes, equal and opposite voltages are induced, which add up to zero. In the presence of an external field component H0 parallel to the longitudinal axis of the cores, this symmetry shifts by the value of H0. The operating point on the B(H) curve is shifted, and the induced impulses no longer add up to zero, since with a change of H in one core, saturation is achieved faster than in the other. The result is that the voltage pulses of the derivative with time of the flux density dB/dt appear in the two cores at different times. The sum dB1/dt+dB2/dt goes from zero to different signals, the breadth and distance apart in time of which are dependent on the amplitude of the external magnetic field H0 and serve to determine the size of H0.
An example of a commercial sensor which operates using the principle described above is the MAG-03 MS-sensor from Bartington Instruments Ltd.
With such magnetic field sensors, an accuracy of about 5 nT can be achieved in the measurement range B less than 1 mT. Thus it is possible to determine the magnetic field Bd with such sensors.
In order to be able to determine the polarisation- dependent magnetic field Bd of polarised gas in the presence of an applied field B0 (e.g. the ambient field or a substantially uniform generated magnetic field within a transporter device), the polarisation-dependent magnetic field is advantageously determined by displacing the measuring apparatus and container (gas storage cell) relative to each other. This is advantageously achieved in that in a first position as close as possible to the wall of the container containing the nuclear spin polarised gas, a magnetic field sensor is used to record the field value, constituted by the field of the applied field B0 and the field of the nuclear spin polarised gases in the container (Bd at the equatorial plane of the container). After recording this signal the container is moved relative to the sensor to a position distanced from the sensor, preferably in the direction of the axial-applied field, by at least five times the radius of the container. The field component caused by the nuclear spin polarised gas then falls to less than 1% of its original value. This means than in this position only the value of the applied field B0 is measured. The difference between these two signals can be used to determine the value of Bd and thus the degree of polarisation P can be determined using equation (2) given above. It is clearly possible to increase the accuracy of the results obtained for the degree of polarisation using this method by making a series of measurements. In a further embodiment, the magnetic field sensor is displaced from the container. If the applied field B0 changes on displacing the sensor, this must be taken into consideration when calculating the degree of polarization. Moreover if measurement is not made in the equatorial plane of the container, this too must be taken into consideration. Thus if the field is measured in the polar direction of the container, the difference is Bdxe2x80x2=2xc3x97Bd.
These two methods have the advantage that commercially available magnetic field sensors can be used even by inexperienced personnel to determine the magnetic field of the nuclear spin polarised gases to an accuracy of 10%, advantageously 2%. With regard to geometric uncertainties, polarisation determination to 50%, advantageously to  less than 10%, is quite possible.
In a second embodiment of the method of the invention Bd, and hence P, may be determined by using a high frequency magnetic pulse to reverse the polarisation and by measuring the resulting magnetic field change xcex94B without moving the sensor and the container (the gas storage cell) relative to each other.
In this method, the polarisation-dependent magnetic field is advantageously determined by applying a high frequency magnetic pulse over the applied field, so that the sign of P is reversed by nuclear magnetic resonance. To this end, suitable coils or a solenoid are used to emit a high frequency magnetic field pulse of varying amplitude and frequency
B(t)=B1(t).cos(xcfx89(t).t)xe2x80x83xe2x80x83(3)
perpendicular to the applied field B0.
This magnetic field change based on the sign reversal of P preferably occurs on the principle of xe2x80x9cfast adiabatic passagexe2x80x9d, fully described in A. Abragam, xe2x80x9cThe Principles of Nuclear Magnetismxe2x80x9d, Oxford University Press, London, England, 1973 (see especially pages 34-36 and 65-66). In this method, the frequency xcfx89(t) of the high frequency magnetic field pulse during the pulse period is pushed beyond the resonance frequency of the nuclear dipole moment:                               ω          0                =                                            2                                            πμ                N                                                    h                                            xe2x80x83                                                          I                N                                              ·                      B            0                                              (        4        )
where h is Planck""s constant, and IN is the nuclear spin quantum number. If the pulse period is short and the high frequency field strength Bd (t) is chosen correctly, the polarisation is completely reversed with no reduction in magnitude. This means that the reading of the magnetic field sensor changes by an amount
xcex94B=2Bdxe2x80x83xe2x80x83(5)
In comparison with the method described above, in which the sensor and container are displaced with respect to each other, the method in which the field Bd is determined using a magnetic field pulse has the advantage that a measuring signal xcex94B=2Bd which is twice as large is obtained.
A complete reversal is obtained using the principle of xe2x80x9cfast adiabatic passagexe2x80x9d (see Abragam (supra)) if the following conditions are satisfied as regards emitting a high frequency pulse from a magnetic field pulse transmitter:
1. The applied high frequency magnetic field strength B1 must be large in comparison with the magnetic field variation xcex94B0 which the applied field B0 exhibits because of inhomogeneities in the container dimensions.
2. The frequency shift xcex94xcfx89 between the start and end of the high frequency pulse must be large compared with the broadening of the nuclear resonance lines caused by the field variation xcex94B0.
3. The pulse duration xcex94t must be short compared with the characteristic transverse relaxation time T2of the gas.
4. The product B1. xcex94t must be large compared with hIN/(2ΠxcexcN).
This polarisation reversal method is particularly suitable as a complete polarisation reversal can also be achieved in an extensive gas volume, although the applied field B0 for maintaining the polarisation can vary slightly spatially by xcex94B0. The method is thus robust and guarantees reproducible results, even when the nuclear spin polarised gas container is changed or, for example, external stray fields are superimposed, as may be the case in different locations. The method can advantageously be used in transportable magnetic fields to determine the polarisation of a gas on site even by inexperienced personnel.
A further method of producing a polarisation reversal is to apply a magnetic pulse using the principle of the 180xc2x0 nuclear resonance pulse or xe2x80x9cΠpulsexe2x80x9d, as fully described in A. Abragam (supra) pages 32-34.
In this method, suitable coils or a solenoid are used to produce a high frequency magnetic field pulse of varying amplitude and frequency (equation (3)) perpendicular to the applied field.
For a complete reversal of the nuclear spin polarisation of the gas using the n pulse principle, a magnetic field pulse with frequency xcfx890 (equation (4)) must be applied by a magnetic field pulse transmitter using the following conditions:
1. The applied high frequency magnetic field strength B1 must be large in comparison with the magnetic field variation xcex94B0 which the applied field B0 exhibits because of inhomogeneities in the container dimensions.
2. The pulse duration xcex94t must be short compared with the characteristic transverse relaxation time T2 of the gas.
3. The relationship                               j          ·          π                =                                                            2                                                  πμ                  N                                                            h                                                  xe2x80x83                                                                  I                  N                                                      ·                          B              1                        ·            Δ                                          xe2x80x83                              t                                    (        6        )
must be satisfied, where h is Planck""s constant and IN is the nuclear spin quantum number, xcexcN is the nuclear dipole moment of the isotope under consideration, and j=1,3,5,7, etc, however j=1 is normally selected.
In contrast to the xe2x80x9cfast adiabatic passagexe2x80x9d method, in the n pulse method the relationship (6) must hold exactly. This is rendered more difficult if variations xcex94B0 occur in the applied field B0 over the gas volume.
For larger gas volumes, as considered in the present invention, significant field variations xcex94B0 occur over the gas volume so the more robust xe2x80x9cfast adiabatic passagexe2x80x9d method with the particular advantage of complete reversal of the nuclear spin polarisation of the gas is preferred. This does not, however, constitute a limitation of the inventive concept of measuring a polarisation reversal with a magnetic measuring apparatus using nuclear resonance methods.
Viewed from a further aspect, the present invention also provides apparatus for determining the magnetic field (Bd) of a nuclear spin polarised gas (and preferably also for determining the degree of polarisation P thereof), said apparatus comprising a magnetic field sensor arranged to determine the magnetic field at at least two positions relative to a container containing a nuclear spin polarised gas, optionally magnetic field applying means arranged to apply a magnetic field to said container, and optionally computing means for determining the degree of polarisation of the polarised gas from the magnetic fields determined by the sensor.
In this apparatus, the sensor may operate to determine the magnetic fields at the various relative positions or it may simply determine the field difference between the positions.
In the apparatus, the sensor may be movable relative to the container or alternatively it may comprise separate sensors located at different positions relative to the container. The different positions will generally include positions relative closer to and further away from the container. The relative motion of sensor and container may be achieved by moving sensor and/or container to preset receiving sites or along a guide, e.g. using a drive means (for example a motor-driven or hand operated drive means)
In this apparatus, the means for applying a magnetic field are preferably means, e.g. a permanent or electromagnet, for applying a substantially uniform field Bo.
Viewed from an alternative aspect the invention also provides apparatus for determining the magnetic field (Bd) of a nuclear spin polarised gas (and preferably also for determining the degree of polarisation (P) of the gas), said apparatus comprising a magnetic field sensor and means for applying a time variant magnetic field to a container containing a nuclear spin polarised gas, optionally also means for applying a substantially uniform magnetic field to said container, and optionally computing means for determining the degree of polarisation of the polarised gas from the magnetic field variation determined by the sensor.
In this second form of apparatus according to the invention, there may if desired be two or more sensors and the sensor and container may be movable relative to each other.
In both forms of the apparatus of the invention the container is preferably spherical and the sensors are preferably highly sensitive, e.g. SQUIDs or Forster principle magnetometers.
The first apparatus of the invention thus conveniently comprises apparatus for determining the degree of polarisation (P) of nuclear spin polarised gases in which the nuclear spin polarised gas is placed in a container, the apparatus comprising: at least one highly sensitive magnetic field sensor, wherein the sensor and the container are arranged so as to be displaceable relative to each other, so that the magnetic field can be determined in at least two locations, e.g. one close to and one distanced from the container, and thus the magnetic field Bd can be determined.
The second apparatus of the invention also conveniently comprises apparatus for determining the degree of polarisation (P) of nuclear spin polarised gases in which the nuclear spin polarised gas is placed in a container, the apparatus comprising: at least one highly sensitive magnetic field sensor, and a high frequency magnetic field pulse transmitter arranged to emit a high frequency magnetic field pulse of variable amplitude and frequency.
The apparatus of the invention is desirably incorporated into apparatus for transporting hyperpolarised gases in which the container is placed within an area of highly uniform applied magnetic field in a chamber within the transporter apparatus.
In a special embodiment, the high frequency magnetic field pulse transmitter comprises coils or solenoids. In one particular embodiment, the magnetic field pulse transmitter is constructed so that a magnetic field pulse is emitted by which the polarisation is completely reversed with no reduction in magnitude.
The use of the apparatus and method of the invention are particularly advantageous with respect to the prior art for the following reasons:
Commercially available apparatus components (e.g. sensors) with high precision and with reproducible results with a relative error of only 0.5% or less can be used. These commercially available apparatus components are calibrated so expensive calibration can be avoided.
The prior art methods for determining the nuclear spin polarisation which induce small nuclear resonance excitations are based on recording the dynamic nuclear spin resonance signal thus produced, recorded with a receiver apparatus. A very costly calibration is necessary for absolute polarisation determination, in which very small resonance signals are measured, which are very sensitive to disturbances from external influences such as container geometry or the construction of the receiver apparatus. In order to produce good results, each receiver apparatus must be separately calibrated, and that calibration is only valid for one container geometry. Using a magnetic field sensor as in the invention means that the very expensive calibration of the receiver apparatus and standardisation of the container geometry is no longer required. The influence of container geometry can be readily calculated. The static magnetic field of the nuclear spin polarised gas is measured. Then a series of measurements of the static magnetic field before and after polarisation reversal can be made to substantially increase the accuracy of the method. The measuring method can thus advantageously be embodied in a measuring apparatus. The measuring apparatus itself is highly reproducible and reliable. In particular, the measuring method is also suitable for use by inexperienced personnel because of its robustness.

Method and apparatus for measuring the degree of polarization of polarized gas


A novel homogenous alcohol free, free flowing, clear and transparent pharmaceutical composition containing Cyclosporin is disclosed. The amount of Cyclosporin is easily measurable at a wide range of temperature of 15.degree. to 45.degree. C. The composition comprises a Cyclosporin in a hydrophillic carrier medium comprising propylene glycol, a transesterification product of a natural vegetable oil triglyceride and a polyalkylene polyol--such as Apricot Kernel Oil Polyethylene glycol 6 esters--such as Labrafil M1944 and polyethylene hydrogenated castor oils--such as Cremophor RH 40 and Glycerol Triacetate or Triacetin.

Cyclosporins comprise a class of structurally distinctive, cyclic, poly-N-methylated endecapeptides, commonly possessing pharmacological, in particular immunosuppressive, anti-inflammatory and/or anti-parasitic activity. The first of the Cyclosporins to be isolated was the naturally occurring fungal metabolite Ciclosporin or Cyclosporine, also known as Cyclosporin A and commercially available under several brands. Ciclosporin is the Cyclosporin of formula A. ##STR1## wherein--MeBmt--represents the N-Methyl-(4R)-4-but-2E-en-1-yl-4-methyl-(L) threonyl residue of formula B. ##STR2## in which --x--y-- is --CH.dbd.CH--(trans).
So far the primary area of clinical investigation for Ciclosporin has been as an immunosuppressive agent, in particular in relation to its application to recipients of organ transplants, e.g. heart, lung, combined heart-lung, liver, kidney, pancreatic, bone-marrow, skin and corneal transplants and, in particular, allogenic organ transplants. In this field Ciclosporin has achieved a remarkable success in its usage.
At the same time, applicability of Ciclosporin to various autoimmune diseases and to inflammatory conditions, in particular inflammatory conditions with an aetiology including an autoimmune component such as arthritis (for example rheumatoid arthritis, arthritis chronica progrediente and arthritis deformans) and rheumatic diseases, has been intensive and reports and results in vitro, in animal models and in clinical trials are wide-spread in the literature. Specific auto-immune diseases for which Ciclosporin therapy has been proposed or applied include, autoimmune hematological disorder (including e.g. hemolytic anaemia, aplastic anaemia, pure red cell anaemia and idiopathic thrombocytopaenia), systemic lupus erythematosus, poly-chondritis, sclerodoma, Wegener granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, psoriasis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (including e.g. ulcerative colitis and Crohn's disease) endocrine opthalmopathy, Graves disease, sarcoidosis, multiple sclerosis, primary biliary cirrhosis, juvenile diabetes (diabetes mellitus type I), uveitis (anterior and posterior), keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthirits and glomerulonephritis (with and without nephrotic syndrome, e.g. including idiopathic nephrotic syndrome or minimal change nephropathy).
Further areas of investigation have potential applicability as an anti-parasitic, in particular anti-protozoal agent, with possible uses suggested including treatment of malaria, coccidiomycosis and schistosomiasis and, yet more recently, use as an agent for reversing or abrogating anti-neoplastic agent resistance in tumours and the like.
A detailed write-up on the variety of naturally occurring and semi-synthetic Cyclosporins, their classification, nomendature etc. has already been published [c.f. Traber et al. 1, Helv. Chim Acta. 60, 1247-1255 (1977); Traber et al. 2, Helv. Chim. Acta. (65 no. 162, 1655-1667 (1982); Kobel et al., Europ. J. Applied Microbiology and Biotechnology 14, 273-240 (1982); and von Wart-burg et al., Progress in Allergy, 38, 28-45 (1986)]. U.S. Pat. Nos. 4,108,985, 4,210,581 and 4,220,641; European Patent Publication Nos. 0 034 567 and 0 056 782; International Patent Publication No. WO 86/02080; Wenger 1, Transp. Proc. 15, Suppl. 1;2230 (1983); Wenger 2, Angew. Chem. Int. Ed.,24, 77 (1985); and Wenger 3, Progress in Chemistry of Organic Natural Products 50, 123 (1986). Among all the Cyclosporins, Cyclosporin A (also known as Cyclosporine or Cyclosporin) has established its utility in the area of organ transplant and therapy of autoimmune diseases.
Although Cyclosporin is used most widely amongst all the immunosuppresants available so far, it suffers from a serious drawback of poor bio-availability.
The oral dosage forms existing lately in the market (i.e. those employing ethanol olive oil as carrier medium in conjunction with Labrafil as surfactant (U.S. Pat. No. 4,388,307) are unpleasant tasting galenic forms. The bio-availability levels using these dosage forms are low and exhibit wide inter-and intra-individual variations. Such dosage forms provide an average absolute bio-availability of ca 30%. Reported variation in bio-availability between subjects varies between a few percent for some patients to as much as 90% or more for others. Also a marked change in bio-availability for individuals with time is frequently observed.
Cyclosporin blood levels have to be maintained within a specified range to achieve the effective therapy. The required range varies according to the clinical status of the patient.
Because of poor and variable bioavailability daily dosages need to achieve the desired blood levels need to be varied considerably in the existing dosage forms of Cyclosporin and a concomitant monitoring of blood levels is essential. This adds an additional cost to be therapy.
In order to improve the bio-availibility several attempts have been made to improve formulations of Cyclosporin.
U.S. Pat. No. 4,388,307 has proposed a method of preparation of drinks solution containing Cyclosporin in a base of Labrafil, Miglyol, Ethanol, Corn/olive oil. However, such preparation suffered from the draw back that it can be presented only as a liquid for dilution in drinking water/fluid before use, otherwise it is very difficult to give an accurate dose. Bioavailability levels achieved using the systems is very low and exhibits wide variations between individuals, individual patient type and even for single individuals at different times during the course of therapy.
Han Gua Patent (Chinese Patent No. 94191895.5) explains the active compound of Cyclosporin, fatty acid sugar ester and diluent carrier having good bio-availability. However, this compound suffers from the drawback that diluent degrades due to hygroscopicity of sugar ester and the stability is not of desired standards, (See also Pharmaceutical Research, Volume 6, No. 11, 1989, P958, "Solid Surfactant Solution of active Ingredients in Sugar Ester" and International Journal of Pharmaceutics, Vol. 92, 1993, P197," Application of sucrose laurate a new pharmaceutical excipient, in Peroral formulation of Cyclosporin A").
Chinese Patent 9419189.5 having equivalent EP 0702562 describes a powder dosage form of Cycloproin possessing comparatively higher stability and to some extent bio-availability when compared to the earlier formulations. This art describes adsorption of Cyclosporin A with appropriate solvents on to a adsorbent along with a nonionic hydrophillic surfactant. The final product does not contain the solvent as this evaporates during the process of manufacturing. Thus this product does not suffer from the disadvantage arising out of solvent evaporation during shelf life and hence stability problems. The various pharmaceutical surfactants, polyhydric alcohols and solvents are well known to the art. The adsorbent used is Colloidal Silicon Dioxide. The blood level arising out of such product have been compared with the standard formulations as per U.S. Pat. No. 4,388,307 with significant improvement in bioavailability. However, if compared with the micro-emulsion based formulations these formulations do not show any advantage as the drug is adsorbed on solid surface and needs an additional process of dissolution prior to become bioavailable.
The effect of sucrose laurate on the gastrointestinal absorption of Cyclosporine is also described (Lerk-PC; Sucker-H, International Journal of Pharmaceutics; 1993; 92; (May 3); 197-202). The evaluation of the dosage form containing sucrose Laurate was found to enhance the in vitro absorption of Cyclosporine when normal epithelial tissue and Peyer's patch tissue of guinea pigs were used. Compared to the commercially available drinking solution, absorption was raised by a factor of 10. Excess amount of surfactant reduced drug absorption. Despite large excess of Sucrose laurate, the absorption of Cyclosporin was still superior to the drinking solution. Choleic acid was also found to increase absorption by a factor of 5-6. A comparison of the absorption between normal epithelial and Peyer's patch tissues indicated that the absorption by endocytosis does not contribute significantly to the overall absorption of Cyclosporin. It was concluded that preliminary formulation experiments showed that a solid oral dosage form of Cyclosporin could be made using sucrose laurate as an excipient.
Abdallah-HY; Mayersohn-M. Pharmaceutical Research; 1991;8(Apr);518-522 reported several formulations of Cyclosporin were prepared and examined in vitro and in dogs A tablet formulation was then selected for comparison with the commercial oil solution placed in a soft gelatin capsule in a randomized crossover study in dogs. Compared with an intravenous dose of the drug, absolute bioavailability was 46+11.1 and 45+9.9% for the capsules and tablets, respectively. Maximum concentration, time to reach maximum concentration and mean absorption time were not significantly different between the 2 formulations. It was concluded that the tablet formulation of Cyclosporin is equivalent in dogs to the commercial dosage form packed into soft gelatin capsules.
U.S. Pat. No. 5,051,402 describes that Cyclosporin may be rendered more soluble by the concomitant administration of .alpha.-Cyclodextrin, either separately, but essentially simultaneously or, preferably, in admixture.
U.S. Pat. No. 4,990,337 describes a formulation comprising a Cyclosporin in admixture with at least one mono or diglyceride of a C.sub.6 -C.sub.10 fatty acid sufficient to dissolve the Cyclosporin. The resulting solution can then easily be emulsified in water or an aqueous fluid.
Freeze dried liposome mixture containing Cyclosporin has been described in U.S. Pat. No. 4,963,362. This invention provides a freeze-dried potential liposome mixture having an amphipathic lipid and a Cyclosporin or derivative thereof for use in possible liposome delivery of Cyclosporin into cells. A method to produce the freeze-dried mixture is also desclosed. When reconstituted to yield liposomes in an aqueous medium, substantially all of the Cyclosporin present in the freeze-dried mixture is encapsulated in the liposomes.
Other galenic improvements in Cyclosporin emulsion formulations recorded in prior art are the use of tocopherol derivatives (EP 0724452), tocopheryl polyethyleme glycol carboxylic acid ester (EP 0712631), dimethylisosorbide (EP 0711550, EP 0650721), alkylene polyether or polyester (WO 9423733), emulsion compositions (EP 0694308), anhydromannitol oleylether, lactoglyceride, citroglycerides (EP 656212), phosphatidyl ethanolamine (EP 0651995), as surfactants and stabilizers etc.
Three Patent Applications namely European Patent App. No. 94110184.2, 95117171.9 and PCT/EP95/04187 describe the use of Dimethylisosorbide as a con-surfactant or a hydrophillic phase along with other ingredients to enhance the absorption of Cyclosporin.
One of the most significant attempt to improve bio-availability of Cyclosporin from its dosage form is the described in U.S. Pat. No. 5,342,625. This art describes use of microemulsion pre-concentrate consisting of a three phse systems i.e. (1) a hydrophilic phase component (2) a lipophilic phase component and (3) a surfactant. Such composition has alcohol as an essential ingredient, such composition upon dilution with water provides an oil-in-water microemulsion with an average particle size of less than 1000 A.degree.. Such an enhanced surface area results in increased bio-availability of Cyclosporin when compared with conventional dosage forms. A comparison of bio-availability from micro-emulsion dosage form (Composition I from U.S. Pat. No. 5,342,625) with the conventional ethanol-oil based dosage form (composition from U.S. Pat. No. 5,342,625), earlier reported in U.S. Pat. No. 4,388,307) has been performed in healthy human volunteers and reported in U.S. Pat. No. 5,342,625. Bio-availability level of 149.0% (.+-.48%) is recorded for composition I as compared to composition X (for which bio-availability achieved is set as 100%). The mean AUC levels from composition I were 40% higher when compared to those from composition X but still had a high variation of 20%.
Alcohol is an essential part of composition as is evident from the products available in the market (Sandimun [U.S. Pat. No. 4,388,307] and Neoral [U.S. Pat. No. 5,342,625]) both of which contain Alcohol. Such compositions suffer from severe drawback of instability due to evaporation of a low boiling solvent like Alcohol. This is particularly true as the products are used in home environment, which cannot be precisely controlled with respect to temperature. Although very expensive cumbersome technology (such as cold formed Aluminium/Aluminium Blister packs) is adopted to protect these products, yet the problem of instability is not completely solved. The stability problems are evident from strict storage conditions and usage requirements as declared either on the labels or package inserts of commercial products Sandimun, and Neoral drink solutions and capsules. Some of the examples are:
1. There is a requirement of storage of product below 30.degree. C. at the same time refrigeration is prohibited. This means that a patient using this product in a tropical country need to have an air-conditioned home environment. This is not only a limiting factor in use of this product but sometimes in economically backward countries it may not be possible that every person using the product has an air-conditioned storage area. Sometimes factors like prolong electricity failure and mechanical and electrical defects in air-conditioning system can cause instability problems to these products rendering them unstable for use. PA1 2. There is also an a statement in Packing insert of Sandimun and Neoral drink solutions that "Sandimun Neoral solution should be used within 2 months of opening the bottle and be stored between 15.degree. and 30.degree. C., preferably not below 20.degree. C. for prolonged periods, as it contains oily components of natural origin which tend to solidify at low temperatures. A jelly-like formation may occur below 20.degree. C., which is however reversible at temperatures up to 30.degree. C. Minor flakes or a slight sediment may still be observed. These phenomena do not affect the efficacy and safety of the product, and the dosing by means of the pipette remains accurate" indicating instability problems.
U.S. Pat. No. 5,639,724 discloses pharmaceutical compositions comprising Cyclosporin, transesterification product of a natural vegetable oil with glycerol which is exemplified in the specification as MAISIN (transesterification product of corn oil and glycerol) which is an essential feature of the compositions. This composition necessitates that Cyclosporin be mixed with a transesterification product of a natural vegetable oil with glycerol. Such composition is not fit for drink solution because of formation of jelly like lumps, since the transesterification product is a jelly like substance at room temperature. Such composition also preferably uses alcohol. This compositions compares its bioavailability with that of older and inferior compositions based on U.S. Pat. No. 4,388,307 and does not compare bioavailability with a more recent a marketed compositions (NEORAL) as defined in U.S. Pat. No. 5,342,625.
The formulation of emulsion as well as microemulsion present their own technological problems relating to thermodynamic instability. Such problems may be partially solved by presenting the product in a microemulsion pre-concentrate form wherein the microemulsification occurs in vivo only. However, such systems may also present variability problems due to wide variations existing in GI tract of patients.
Any person skilled in the art attempting to make composition without use of alcohol and without careful and extensive experimentation and study of desired chemicals to be added to Cyclosporin will end with compositions which are highly viscous and which tend to solidify at normal room temperature conditions. Such compositions are undesirable not only due to physical unstability but also that they cannot be formulated as liquids whose dose can be measured exactly under normal conditions.
The major consideration here is the accurate measurement of dose in Cyclosporin which is an essential feature because of the narrow therapeutic condition of the drug i.e. below threshold the organ rejection occurs and above a particular level the drug causes severe toxic reactions.
None of the above mentioned inventions teaches the art of dissolving Cyclosporin A (which is a water insoluble hydrophobic drug) in a hydrophillic medium. This looks improbable and a person skilled in the art cannot conceive beyond an emulsion and/or a microemulsion
All the earlier approaches to enhance the bioavailability of Cyclosporin were towards making the drug in a emulsified form (U.S. Pat. No. 4,388,307) or substantially increasing the surface area by converting into microemulsion (U.S. Pat. No. 5,342,625).
MASINE is a fatty material which gets out not only when combined with Cyclosporin but even when combined with Labrafil along with Cyclosporin.
In the body of the specification of U.S. Pat. No. 5,639,724 Labrafil has been disclosed as a preferred ingredient to be added to the composition of Cyclosporin and MAISINE for drink solution. However, this patent does not address the problem of formation of flake like substances formed by the presence of MAISINE even though Labrafil has been added to the composition.
Our attempt has been to affect solution of Cyclosporin in a hydrophilic environment using micellar concept of a surfactant and a co-surfactant such that such compositions are substantially devoid of fatty materials and hence also devoid of the defects associated with such fatty materials. Our composition when diluted with water or aqueous medium retains the lipophilic Cyclosporin drug in a solubilized state. Hence making the drug bioavailable in therapeutic concentrations and with reproducibility.
It will be most appropriate to formulate Cyclosporin compositions in a way that the drug gets converted into a solubilized system on dilution in vivo. The composition of the invention when administered orally in the form of a drink solution or soft gelatin capsules get diluted with the gastrointestinal fluids to form micellar solutions such that the hydrophillic end of the surfactant and the cosurfactant are oriented towards hydrophillic environment of gastrointestinal fluid and the drug molecules are entrapped in the hydrophobic portions of the surfactant micelles. Such micellar solubilized systems, when in contact with the mucosa of the gastrointestinal tract, release the drug leading to absorption, thus providing an increased and less variable bioavailibility.
Such systems will definitely be more uniform and bio-available than microemulsions from where the drug has to partition out of Lipophillic phase for absorption.
Moreover, the inventors have done a detailed study of the type of products developed out of the technology based on microemulsion based systems.
The product existing in the commercial market are presented into two types of oral dosage forms.
One type is the oral solution concentrates to be diluted prior to intake as start up therapies. These dosage forms provide more flexibility in dosage adjustments to achieve the optimum therapeutic concentrations as desired by the physicians.
The second type of dosage forms are unit dosage forms for example Capsules generally soft gelatin capsules. These type of dosage forms are used as continuation therapies once the dosage adjustments have been done.
The inventors have, by careful experimentation and expenditure of mental faculties been able to invent a composition in which hydrophobic drug like Cyclosporin can be dissolved in a hydrophillic medium by careful selection of the hydrophilic medium, surfactants and manner of addition such that a hydrophobic drug can get dissolved in an array of surfactant molecules arranged in a manner that their hydrophilic portions are oriented outside i.e. towards the hydrophilic medium resulting in clear stable solutions based formulations. Such products when they come in contact with biological fluids result in total solubilization of Cyclosporin at molecular levels thereby increasing the surface area of Cyclosporin and such diluted solutions of Cyclosporin are highly bioavailable. Such compositions do not form emulsions on dilution.
In another embodiment of the invention there is disclosed an improved process for making soft gelatin capsules containing Cyclosporin as active ingredient in a "carrier medium" comprising propylene glycol, a transesterification product of a natural vegetable oil triglyceride and a polyalkylene polyol such as Apricot Kernel Oil Polyethylene glycol 6 esters such as Labrafil M 1944, poloxyyethylene hydrogenated castor oils such as Cremophor RH 40 and Glycerol Triacetate or Triacetin wherein the ingredients are present in the following range:
______________________________________ Cyclosporin 1-25% w/w Propylene Glycol 10-50% w/w A transesterification product of a natural 5-30% w/w vegetable oil triglycerodeand a polyalkylene polyol. Polyoxyethylene hydrogenated Castor oils 30-60% w/w Triacetin 0.1-30% w/w ______________________________________
Such dosage forms that is soft gelatin capsules pose unique technology problems when the solutions to be encapsulated are microemulsion preconcentrate. There is a tendency to loose weight due to the migration of materials with free hydroxy groups into the capsule-shell thus causing precipitation of drug due to loss of solvent.
In the present invention this problem has been solved by adding to the said composition of the invention substantially 10-25% excess of the "carrier medium" thereby compensating for the loss of weight due to migration. At the same time the amount of plasticizers in the capsule shell are reduced by the amount equivalent to the excess carrier medium added in the capsule.
The term "base" or "carrier medium" should be implied to mean everything added to the composition except the drug.
The composition is incorporated into the capsule shell by conventional procedures as described in standard texts. ("The theory and practice of Industrial Pharmacy" by Leon Lachman et al. Third edition, LEA AND FEBIGER, USA)
The Soft Gelatin Capsules have a very distinct advantage of ease of carrying and administration as compared with oral solutions. These dosage forms hence contribute to a very large segment of commercial market.
The present invention relates to formulation of Cyclosporin in compositions such that the drug is presented in solubilized systems of surfactant micelles appropriately stabilised in specific hydrophilic phase.

Pharmaceutical compositions containing cyclosporin


Systems, apparatuses and devices are used for front cable management of equipment modules mounted in equipment racks. One aspect is directed to an apparatus for front cable management generally including a cable management device for a rack-mounted equipment module supported in an equipment rack. The cable management device generally includes an articulated arm assembly movable between a retracted operational position and a service position extending forwardly out from the equipment rack. Another aspect is directed to a system for front cable management generally including an equipment rack and a rack-mount support for movably positioning a rack-mount equipment module on the equipment rack. The rack-mount support generally includes a front end configured to receive a cable management device for routing cables from a cable zone of the equipment rack to a front end of the rack-mount support.

It is well known to use equipment racks for mounting and supporting multiple equipment modules. For example, 19-inch racks are widely used in modern data centers, ISP facilities and corporate server rooms for mounting and supporting various equipment modules, including computing, telecommunication, audio, and/or video equipment.
Currently available cable management arms (CMAs) are mounted on the rear of equipment racks and connected to the rear of the equipment modules accessible from the "hot aisle". In particular, cables are managed by a conventional CMA as a chassis supporting an equipment module is pulled out from the equipment rack in a drawer-like manner for servicing the equipment module from the "cold aisle". As the chassis is pulled out, the space in the back side of the chassis is cleared for the CMA to follow with the chassis movement. Such conventional CMAs are designed for the currently used rack mount servers and storage enclosures that are all designed with I/O cables on rear of the chassis. An example of such a conventional CMA is described in U.S. Patent Application Publication No. 2011/0100933 A1 entitled "Reversible Cable Management Arm".
Recent efforts have been made to arrange I/O cables on the front of equipment racks for ready access from the "cold aisle". For example, the Open Compute Project (OCP) initiated by Facebook calls for an OCP rack that has the same outside dimensions as a conventional 19-inch rack (e.g., 600 mm width), but allows for wider equipment modules. The OCP rack design requires that the I/O cables be arranged on the front of the equipment rack. Unfortunately, conventional CMAs mounted on the front of the rack will block the chassis travel path as it and the equipment module supported thereon are pulled out for service. Also, power buttons, status displays and other items are generally located on the front of an equipment module for simple access by service personnel for service needs from the "cold aisle". Again, conventional CMAs mounted on the front of the rack may block access to the power buttons, status displays and other items, needlessly requiring the service personnel to manually manage the CMAs or cables supported thereon for various service needs.
This is not just the problem for the chassis used in OCP racks; it is well known issue for the most commonly designed blade servers from HP, Dell, and Cisco. Such blade servers have the I/O cable arranged on front and are thus not suited for front cable management using conventional CMAs. Instead, cables are left to dangle and hang on the front of the chassis, and service personnel generally has to disconnect the cables from the chassis (and equipment modules supported thereon) in order to pull the chassis out. Unfortunately, such disconnection will disconnect the data transfer and is not allowed for most applications.
Longer cables dangling on front of the chassis maybe used in order to avoid disconnecting data traffic. In this case, service personnel must manually manage the longer dangling cables while moving the chassis out. These dangled, unmanaged cables block the front of other chassis/modules mounted below the subject chassis, and thus eliminate or reduce the visibility of the status indicators and/or the airflow path of the lower chassis/modules. In some cases, the blockage of air vents could be fatal for the cooling systems of the lower chassis/modules.
In light of the foregoing, it would be beneficial to have systems and apparatuses which overcome the above and other disadvantages of currently available CMAs.

Front rack cable management system and apparatus


Spinal implant comprising a quick closure (4) for securing a connecting element (2) in a bone screw (1) where the quick closure (4) is rotatively attachable in the clockwise or counterclockwise direction and lockable such as to be able to take up torques applied to the bone screw (1) while preserving the bone anchorage from manipulative stress.

The present invention relates to a spinal implant set including a quick closure device according to the preamble of claim 1.
Such closure devices are typically used in the surgical treatment of the spine. As the patients are increasingly aged, they have more often porotic bones, thereby limiting the anchoring ability of screws. It is therefore particularly important that connecting elements can be fastened in screw heads with minimum stress, ideally in such a manner that the screw anchorage in the bone remains unaffected.
Various quick closures are known in the art, all of which suffer from one or several drawbacks, however, as shown below.
For their comparative assessment, quick closures of the prior art are classified as follows: Internally or externally slidingly attachable quick closures, internally or externally rotatively attachable quick closures, as well as internal and external bayonet-like quick closures. Also, a vertically snapping quick closure is referenced in the prior art.
Among the internally slidingly attachable quick closures, the following ones are e.g. known in the art: EP0672388 (Metz-Stavenhagen et al., 1995), slidingly insertable with an end stop in the insertion direction; U.S. Pat. No. 6,110,172 (Jackson, 1998), insertable from two directions with an end stop in both directions after raising the cap; U.S. Pat. No. 6,302,888 (Mellinger, 1999), insertable without end stops. EP0836436 (Wisnewski et al., 1995), not only slidingly but pivotably insertable without end stops.
Among the externally slidingly attachable quick closures, the following ones are e.g. known in the art: DE4107480 (Ulrich et al., 1991) and U.S. Pat. No. 6,139,549 (Keller, 1997), insertable at the bottom of the screw head near the bone thread without stops and with high space requirement.
Among the internally rotatively attachable quick closures, the following ones are e.g. known in the art: EP1119304 (Yuan, 1998), rotatively insertable in one direction with an end stop; U.S. Pat. No. 6,258,090 (Jackson, 2000), rotatively insertable in one direction without an end stop; U.S. Pat. No. 6,652,526 (Arafiles, 2001), rotatively insertable in two directions without an end stop; U.S. Pat. No. 6,786,903 (Lin, 2002), rotatively insertable in two directions with a positioning aid on the rod.
Among the externally rotatively attachable quick closures, the following ones are e.g. known in the art: U.S. Pat. No. 5,346,493 (Stahurski et al., 1993), rotatively insertable in both directions without an end stop; U.S. Pat. No. 6,251,112 (Jackson, 2000), rotatively insertable in one direction without an end stop; EP1190678 (Bono et al., 2001), rotatively insertable in one direction with an end stop.
Among the internal and external bayonet-like quick closures, the following ones are e.g. known in the art: DE9403231 (Aesculap, 1994), insertable at the bottom of the screw head from one side, with an end stop; U.S. Pat. No. 7,235,075 (Metz-Stavenhagen, 2003), insertable at the top of the screw head from one side, with an end stop.
A snapping quick closure is proposed by US 2005/0027292 (Bernard et al., 2005).
In this respect, a main disadvantage of slidingly insertable quick closures is that relatively high moments have to be applied to the typically long instruments used in spinal surgery by the surgeon with the risk of creating uncontrolled situations at the location of the screw. For rotatively insertable quick closures, the required torque along the instrument always remains the same. A rotational insertability from two sides is therefore important as due to the increasingly frequent application of dynamic stabilizing systems, plastic rods are being used more and more frequently. They are, however, larger than metal rods for reasons of stability and therefore require more space.
In situations of limited space at the pedicle entrance, a quick closure that is rotatively insertable from only one side may lead to collisions with transverse processes or facet joints, which is less probable in the case of a rotational insertability from two sides. With quick closures without end stops, screws cannot be tightened without being retained by an additional instrument for which the access to the screw is difficult. Consequently, an end stop in the tightening direction preserves the bone bed while fastening the clamping screw whereas an end stop against the tightening direction preserves the bone bed while releasing the clamping screw. An end stop in both directions optimally preserves the bone bed in both directions.
A major disadvantage of a metallic snapping mechanism are the required macroscopic elastic deformation achievable only through limited local strength and the rather complicated instruments required to unlock a snapped-in junction while demanding important removal forces with the risk of overloading the elastic elements. Also the tightening screw of Bernard et al. does not have a matching seat in the screw head and consequently cannot transfer the rod's load directly into the screw head, but must rather transfer them through the threads of the closure.
Also as a result of the increasing dimensions of plastic rods for dynamic stabilizing systems, the space left between the screw head and the pedicle entrance is mostly insufficient for a quick closure coupling. In such cases, only systems are applicable where the quick closure is arranged at the top of the screw head.

Spinal implant set including a quick closure


Systems, methods and computer program products are provided for preserving a session between an SNA application and a TN3270E server after loss of an IP network connection between the TN3270E server and a TN3270E client that is communicating with the SNA application via the SNA session.

Mainframe computer systems are widely used for a variety of data processing functions. For example, many corporate financial and accounting systems were developed for, and operate on, mainframe computing systems. Although the use of personal computers and personal computer networks has proliferated in recent years, mainframe computer systems, referred to as legacy systems, are expected to remain popular for many types of data processing for years to come.
A mainframe computer system typically includes multiple user terminals connected to a mainframe host computer. Various software applications may be resident on, or accessible to, the host computer. The user terminals, which are sometimes referred to as client terminals or "clients", communicate with the mainframe host computer via a host communications system. The International Business Machine Corporation's ("IBM") 3270 terminal system is one of the more widely-used systems for communicating with host computers.
Typically, a 3270 terminal does not have its own data processing capability. Instead, a 3270 terminal may display screens generated by applications running on a host, and may communicate information from a user back to a host for processing. A user interface of an IBM 3270 terminal system comprises a plurality of screens that are generated by host applications for display on the 3270 terminal. Over the past few years, many 3270 terminals have been replaced with personal computers (PCs) configured to communicate with the mainframe computer system via 3270 terminal emulation software.
In many applications, 3270 terminals, or other data processing devices (e.g., a PC) emulating a 3270 terminal, now access the host computer via the Internet. For example, in systems operating under the TN3270E protocols, the 3270 terminals may access application software on a host computer via a combination of a Transmission Control Protocol/Internet Protocol (TCP/IP) protocol connection between the TN3270E client terminal and a TN3270E server, and via a Systems Network Architecture (SNA) session between the TN3270E server and the SNA application software on the host mainframe computer. Such SNA application software or "SNA applications" refer to software applications designed for use by a plurality of terminals interconnected by an SNA network or a variant of an SNA network.
FIG. 1 depicts such a mainframe computing system environment in which several TN3270E client terminals 20 communicate with several SNA applications 30 via a TN3270E server 40. The SNA applications 30 may be resident on one or more mainframe computers or other data processing systems (not shown in FIG. 1), or, alternatively, may be physically located separate from the one or more main frame computers/data processing devices but accessible by such devices. As shown in FIG. 1, the TN3270E clients 20 are connected to the TN3270E server 40 via Internet protocol or "IP" connections 25. The TN3270E server 40 is connected to the SNA applications 30 via SNA sessions 35.
In the TN3270E environment of FIG. 1, the SNA sessions extend only between the TN3270E server 40 and the SNA applications 30. Thus, the TN3270E server 40 converts IP communications from one of the TN3270E clients 20 into SNA format and forwards them to one of the SNA applications 30. The TN3270E server 40 likewise converts SNA communications received from an SNA application 30 into IP format and forwards them to the TN3270E client over the IP network.
In many legacy systems, each 3270 terminal was assigned a unique logical unit or "LU" name. Typically, legacy systems originated as hard-wired systems, and the LU name served to identify the particular terminal/user that was accessing the mainframe host computer. Consequently, many SNA software applications that were developed to run on these legacy systems included software routines that made decisions based on the LU name of the device/user accessing the terminal. Consistent with the requirements of these SNA applications, under the TN3270E protocol, a data processing device that is acting as a TN3270E client may specify an LU name when connecting to a TN3270E server. Typically, the TN3270E server will have information, such as Logmode information, regarding one or more LU names which may attempt to connect to SNA applications through the TN3270E server. Upon receiving a connection request from a TN3270E client, the TN3270E server may provide the SNA application certain of the information regarding the TN3270E client before establishing the SNA session. Moreover, typically a TN3270E server will only allow one SNA session at a time involving a particular LU name.

Methods, systems and computer program products for resuming SNA application-client communications after loss of an IP network connection

International Business Machines Corporation


A method of operating a reservoir simulator can include performing a time step of a reservoir simulation using a spatial reservoir model that represents a subterranean environment that includes a reservoir to generate simulation results for a first time where the simulation results include a front defined by at least in part by a gradient at a position between portions of the spatial reservoir model; predicting a position of the front for a subsequent time step for a corresponding second time using a trained machine model; discretizing the spatial reservoir model locally at the predicted position of the front to generate a locally discretized version of the spatial reservoir model; and performing a time step of the reservoir simulation using the locally discretized version of the spatial reservoir model to generate simulation results for the second time.

A reservoir may be a subsurface body of rock that includes sufficient porosity and permeability to store and transmit fluids. As an example, sedimentary rock may possess more porosity than various types of igneous and metamorphic rocks. Sedimentary rock may form under temperature conditions at which hydrocarbons may be preserved. A reservoir may be a component of a so-called petroleum system. A geologic environment may be a sedimentary basin that may include one or more fluid reservoirs.


According to the present invention, a server computer discloses content data to client terminals used by predetermined members within a company or a division through groupware. The content data needs to be examined by the predetermined members. The server computer periodically collects feedback of the examination for the content data from the predetermined members, compares the collected examination feedback with a predetermined examination requirement, and when the collected examination feedback meets the predetermined examination requirement, transfers the content data to a Web server to disclose the content data to user terminals other than the client terminals used by the predetermined members.

1. Field of the Invention
The present invention generally relates to an information processing system, an information processing method, a software program for carrying out the information method, and an information storage medium comprising such software program.
More specifically, the present invention relates to an information processing system, an information processing method, a software program for carrying out the information method, and an information storage medium comprising such software program, which effectively shorten the time needed for examining the information to be disclosed through an electronic Bulletin Board System, etc., in particular, on the Web (World Wide Web) pages.
2. Description of the Related Art
It has become popular for various organizations such as business enterprises and research institutes, etc., with the recent increasing usage of the Internet, to utilize Web pages, etc. in order to disclose their activities, etc. to the public as a part of information disclosure. However, the wide usage of the Internet, at the same time, provides a possibility for the public to view the disclosed information, and thus it is necessary to pay attention to the contents of the information to be disclosed. In other words, it is necessary to obviate the problems such as an accidental leakage of company confidential information or a deterioration of the brand image of the company due to the typographical errors, the accidental omissions of letters and the like included in the disclosed information.
In order to solve such problems, the information to be disclosed needs examination in advance. As one of such techniques, for example, Japanese Laid-Open Patent Application Number 11-306100 discloses "Posted Messages Viewing Systems". The system prepares examination criterion data beforehand, and puts up in the viewing database only the posted message data that are considered allowable, as general-user viewable information, through the examination process using the examination criterion data. The examination process comprises a "primary level" for general examiners and a "secondary level" for experienced examiners, and the process is configured to proceed to the "secondary level" when the examination in the "primary level" is indecisive due to the lesser experience of the examiners, etc.
In such systems, however, the examination criterion data needs to be created previously and the examination quality is influenced by the validity of the data. That is to say, if the examination criterion data were biased, the examined posted messages would be inevitably biased as well. Therefore, a quality examination process may not be always provided. Further, the posted data are not disclosed until they have gone through the predetermined examination process, thus the disclosure may be delayed due the reasons such as absence of the examiners and the like.
Also, Japanese Laid-Open Patent Application Number 2000-49777 discloses "Electronic Bulletin Board Systems and Storage Medium used therein", in such a system, category information is added, by examiners, to each of the miscellaneous posted messages from the public, allowing an user-friendly way of surfing the Web pages by presenting them in categories based on the category information. The system includes functions such as automatically extracting broadcast-prohibited terms at the time of adding the category information to the posted messages. However, in such a system, the disclosure may also be delayed as a result of a possible delayed categorizing process due to the reasons such as absence of the particular examiners.
Additionally, Japanese Laid-Open Patent Application Number 11-253377 discloses "Public Information Transmitting Methods". Such method, when transmitting public information such as various news, etc. through an electronic bulletin board system, is configured to put up articles from reliable particular users without examination, but to examine previously, by particular examiners (users), articles from users besides the reliable particular users.
In such method, since the articles from the particular users are unexamined, broadcast-prohibited terms, for example, may not be checked and problems such as typographical errors and accidental omissions of letters may arise due to careless mistakes. In addition to that, since the articles from the users besides the particular users need to be examined by the particular examiners (users), the disclosure of such articles may also be delayed due to the reasons such as absence of such particular examiners and the like.
Also, it is possible to conceive such a system in which, when examining the information such as documents etc. to be disclosed to the public, requesting for a full approval from relevant members of a company, etc., for example, using groupware and the like in a company. In case of such a system, since full approval of the relevant members is required, when one of the members is missing due to the absence, etc., as mentioned above, the resolution is delayed, which could also lead to the delay in disclosure.
Therefore, according to the related art, there is a possibility that the disclosure of the information is delayed when, in particular, the examiners to check the information to be disclosed are absent, for example.

Information processing system, information procesing method, a software program for executing such method, and information storage medium comprising such software program


A method, carried out in an arrangement having a cable that provides programming information to a television monitor as well as telephony service, where call progress information of a telephone call is displayed on the monitor of the television monitor, and the method sends control information upstream, over the cable, in connection with desired information relative to the call progress.

This invention relates to telephone service over a cable network.
For many years, telecommunication service in the United States has been offered primarily through a network having wire pairs extending to customer homes. More recently, cellular telephony has taken off, and efforts are being made to similarly expand the telecommunication offerings through hybrid fiber-coax cable (HFC).
U.S. Pat. No. 6,236,653 describes an illustrative system, not unlike the one depicted in FIGS. 1 and 2, that provides telephone service through a cable network, as well as Internet service through the cable network. In FIG. 1, a fiber-coax cable 100 extends from head-end station 110 to a plurality of customers, such as customers 200 and 300, which tap into the cable. Cable 100 is representative of an entire network of cables that extend from head-end station 110. Station 110 obtains television signals from some source (for example, the antenna depicted with station 110), modulates those signals into preselected frequency bands, and forwards the signals downstream by means of HFC cable 100. Within a customer's premises, cable 100 signal is received in a set-top box, such as box 210, the set-top box demodulates the received signal in accordance with instructions provided to box 210 by a user, resulting in a specific channel (frequency band) being applied to television monitor 170 at the frequency band to which the tuner within television 170 is set. Thus the user receives a television signal from the specific channel. This is, basically, a one-way broadcast communication arrangement, from head-end 110 to all of the customers on cable 100.
Internet service is provided to PC 150 of customer 200 by interposing cable modem 220 between cable 100 and PC 150. To accommodate such a service, cable 100 and head-end 110 must be adapted to allow two-way communication between the PCs of the various customers that are connected to cable 100 and possess a cable modem, and head end 110 or, more specifically, a data point-of-presence (POP) 120 that is connected to head-end station 110. Relative to Internet service, POP 120 may be an Internet Service Provider (ISP) that is connected to the Internet. Information flows between POP 120 and cable modem 220 in IP packets that, while flowing through cable 100, are modulated onto a carrier.
Telephony service is provided also through cable modem 220, head-end station 110, and POP 120, by carrying the service also through IP packets that flow through cable 110. Thus, modem 220 is more than just a cable modem because it is adapted to handle telephone signals, and POP 120 is more than just an ISP because it is adapted to be connected to local switch 140 of the PSTN, through packet gateway 130, which converts between the analog signals of switch 140 and the IP packets signals of POP 120.
FIG. 2 depicts the structure of cable modem 220, essentially as illustrated in the aforementioned U.S. Pat. No. 6,236,653 patent. Viewed macroscopically, it includes Internet module 700 and a telephony module 600. In module 700, tuner 760 receives signals in the frequency band devoted to IP packet communication and applies its received signal to demodulator 735, which demodulates the received signal to recover a sequence of received TCP/IP or UDP/IP frames and applies them to framer 730. The latter provides a stream of packets to CPU 725, which is a stored-program controller with associated memory 705. CPU 725 provides timing, synchronization and error handling controls to framer 730. CPU 725 also provides IP packets to PC 150 via interface 745. In the upstream direction, packets from PC 150 are applied to framer 730 via interface 745 and CPU 725, and thence to transmitter 740, which provides error correction/detection coding such as Reed-Solomon coding and forms a modulated intermediate frequency (IF) carrier signal. The IF signal is applied to radio frequency (RF) modulator 750, which up-modulates its input signal to the proper frequency bands and forwards the modulated signal to cable 100. Thus, a path is provided for IP packets to flow back and forth between PC 150 and POP 120.
Telephony module 600 comprises a controller that is composed of digital signal processor (DSP) 620 and associated memory 625. The module further comprises analog-digital converter 610, and subscriber-line-interface-circuit (SLIC) 605. The controller performs all of the necessary control telephony functions, converter 610 provides the interface between the digital signals of DSP 620 and the analog signals of SLIC 605 and telephone 160, and SLIC 605 provides the tip/ring interface to telephone 160, such as the ability to sense off-hook, provide loop current, provide dial tone, detect dialing (pulse or DTMF), provide a ringing signal, etc. DSP 620 is coupled to CPU 725 to provide a two-way communication path of digitized telephony signals (IP packets) between telephone 160 and cable 100.
Perusing U.S. Pat. No. 6,236,653 may provide additional insights.
The above described arrangement provides telephony service for telephone 160, digital communication (Internet) service for PC 150 (which has computing capability as well as audio and video capability), and entertainment programming service for TV 170 (which also has audio and video capability)—but all of these services are independent, and do not commingle. We realized that an advance in the art can be attained by allowing these to commingle.
In a related art, U.S. Pat. No. 5,566,231 describes an arrangement for enhancing a customer premises message-recoding device. The enhanced recording device has the ability to store caller ID information arriving from the telephone network in association with the incoming call that is recorded, as well the ability to ascertain the call duration and other information. This information is stored in association with the stored message. Through a remote controller that connects to the enhanced recording device through an IR link, a user can retrieve the stored messages and the stored associated information. To display the retrieved information, the conventional cable-TV connection between the set-top box and the TV monitor is looped through the enhanced recorder, and the retrieved information is displayed on the TV monitor though a video interface connector that is connected to the TV monitor.
What the U.S. Pat. No. 5,566,231 patent suggests is the notion of storing caller ID and other data that is provided by the telecommunication network in association with an incoming call that is recorded, so that thereafter, the information is retrieved by a user and displayed by the user on a TV monitor. However, the patent does not teach how the incoming information is modified to a format suitable for a television monitor, or how the video interface connector interacts with the cable from the set-top box to inject its signal so that it may be displayed on the TV monitor. Moreover, the arrangement is not interactive, in the sense that the enhanced recording device stores information, but the user can only retrieve it. The user cannot control the call progress, or any other interaction with the telecommunication network, based on real time information obtained from the TV monitor.

This patent is subject to a terminal disclaimer.

Call progress information in cable telephony


A highway lane position detector including a photodetector for determining the existence of highway lines, wherein the detection circuitry maintains its detection ability over a wide range of ambient light conditions from bright sunlight to dim artificial light in ambient darkness, by providing a dynamic resistance element in series with the photodetector wherein the dynamic resistance element compensates for changes in the photodetector due to changes in ambient light conditions to maintain the photodetector in a detection condition (avoiding saturation) regardless of the ambient light condition. In the preferred embodiment of the detector, the dynamic resistance element is at least one reversed biased zener diode. In currently preferred circuitry of the invention, the detector detects the presence of intermittent lane dividing lines and provides an alarm when such lines are no longer detected.

1. Field
The invention is in the field of optical detection of lines on the surface of a highway from a moving motor vehicle.
2. State of the Art
Statistics from the National Highway Traffic Safety Administration show that vehicle lateral drift, i.e., drift from one lane to another or drift off the roadway, accounts for about 25% of fatalities on our nation""s highways. As a result, President Clinton has mandated motor vehicle safety devices be developed to help solve the problem and President Bush has continued the mandate.
It has been realized since at least 1973, U.S. Pat. No. 3,708,668, that it would be desirable to have a device for motor vehicles that would detect highway lines and sound or display an alarm to alert the driver of the vehicle when the vehicle approached or crossed such a line so the driver could correct and stay within his or her lane and avoid unintentional lateral drift. The search for a practical device to provide satisfactory highway line detection has continued and a number of devices have been suggested.
It was recognized as early as U.S. Pat. No. 3,708,668 that a significant problem with such a system is compensating for different ambient light levels. Thus, such a system has to be able to detect road lines in bright sunlight as well as in darkness at night. U.S. Pat. No. 3,708,668 provides a pair of sensors that balance each other when both detect a road surface, but result in a warning signal when one sensor detects a light reflecting line and the other does not. U.S. Pat. No. 4,143,264 provides a bridge circuit with an impedance element controlled by an integrated output of the bridge circuit to maintain a balance of the bridge for ambient light conditions and vary sensitivity of the detector with light conditions. Various infrared, laser, and CCD camera devices have also been suggested, U.S. Pat. Nos. 4,348,652, 5,979,581, 5,790,403, and 5,957,983. U.S. Pat. No. 5,982,278 shows various arrangements of detectors for detecting road lines and special line arrangements but does not teach any specific detection circuitry.
However, the need remains for a reliable line detector that can be built into a vehicle or provided as an aftermarket product to be easily mounted on a vehicle such as in or on side mirrors or mounted on one or more side windows of the vehicle.
As indicated, a major difficulty in the optical detection of highway lines is that the ambient light varies in intensity over many orders of magnitude from a sunny day to night. The detector must be able to accommodate these extremes, in particular during daytime, without current saturation. The inventor has discovered that the dynamic impedance characteristics of a reverse biased zener diode can be used to compress the voltage output signal of a phototransistor to accommodate extremes of light intensity. This approach is a simple and economical solution to the problem.
Dynamic impedance is, in general, defined as the incremental change in voltage across a device with respect to an incremental change in the current through the device.
The voltage at which the voltage across the reverse biased zener diode nearly ceases to increase with increases in current is referred to as the zener voltage. Zener diodes with various zener voltages are commercially available and should be chosen so that this voltage, or the series combination of these voltages, is below the saturation point of the photodetector in bright light, but so that the highest expected voltage across the zener diode in the series combination should always be less than the zener diode""s or series combination of zener diode""s zener voltage.


A lithographic apparatus is provided with a charged object on a projection system of the lithographic apparatus, a substrate table of the lithographic apparatus, or both that is configured to have an electric charge to attract particles thereto.

A lithographic apparatus is a machine that applies a desired pattern onto a target portion of a substrate. Lithographic apparatus can be used, for example, in the manufacture of integrated circuits (ICs). In that circumstance, a patterning device, which is alternatively referred to as a mask or a reticle, may be used to generate a circuit pattern corresponding to an individual layer of the IC, and this pattern can be imaged onto a target portion (e.g. comprising part of, one or several dies) on a substrate (e.g. a silicon wafer) that has a layer of radiation-sensitive material (resist). In general, a single substrate will contain a network of adjacent target portions that are successively exposed. Known lithographic apparatus include so-called steppers, in which each target portion is irradiated by exposing an entire pattern onto the target portion at one time, and so-called scanners, in which each target portion is irradiated by scanning the pattern through the projection beam in a given direction (the "scanning"-direction) while synchronously scanning the substrate parallel or anti-parallel to this direction.
Sulfur dioxide, organic phosphates, amines, and oxygen are contaminants typically found in a lithographic apparatus that may decrease the yield of good dies by attaching to the substrates, to the projection system of the lithographic apparatus, or to other sensitive parts of the lithographic apparatus. While the internal and external ambient atmosphere of the lithographic apparatus is typically controlled to reduce the levels of such contaminants, there is however invariably some level of contamination of sensitive parts of the lithographic apparatus or contamination of materials supplied to the lithographic apparatus. For example, contaminants may be introduced into the ambient atmosphere via an incoming substrate, outgassing of materials, leakage of contaminated gas into the lithographic apparatus, maintenance of the lithographic apparatus by personnel, etc.

Lithographic apparatus and device manufacturing method


The present invention is directed towards a flexible flat cable of a vehicular clockspring whose conductors are directly attached to the contacts of a mounting header. The flat cable comprises a series of conductors “printed” in-between a pair of insulating layers. The conductors are directly connected to the contacts of a mounting header, which partially form the connection module of a clockspring. Other devices or cables within the vehicle can than quickly mate to the clockspring connection module, via a corresponding connector. This method of termination is in contrast to prior art clockspring cables which typically weld their cable conductors to rigid printed circuit boards or overmolded metallic insert grids.

A majority of automobiles today utilize airbag crash systems. An airbag is typically located on the steering wheel facing the driver and must be in continuous electrical connection with sensors in the car body. The sensors provide an electrical signal to the airbag crash assembly which instantly inflates the airbag in the event of a crash. Clocksprings are found in virtually every vehicle to electrically connect rotating devices in the steering column to stationary components in other parts of the vehicle.
There are generally two types of clocksprings designs, the coil and the "loop-back" design. In the coil design, long lengths of flat cable (typically 6 to 13 feet) are wrapped around a central hub of a clockspring, in a coil-type fashion. In a loop-back design, a roller and carrier mechanism loop a flat cable (typically 2 to 3 feet) back onto itself inside the clockspring.
In both types of clocksprings, the flat cable comprises a series of parallel conductors sandwiched between two insulating layers of plastic or similar material. The flat cable is terminated by welding the flat cable's conductors to a rigid circuit board or overmolded metallic insert grid.
FIGS. 1A-1C show a prior art flat cable 10 and flat cable termination structure. FIG. 1A shows a rigid circuit board 11 having ten (10) contacts 12 thereon. The contacts 12 are connected to metal conductors 14 traced onto the circuit board 10, which eventually form metal leads 16.
FIGS. 1B and IC show a top and perspective view, respectively, of the flat cable 10 welded to the metal leads 16. The flat cable 10 is generally formed by sandwiching a series of conductors 20 between two insulating layers of plastic or similar material. The insulating layers in FIGS. 1B and 1C are transparent so that the cable conductors 20 can be seen. The insulating layers have an adhesive bonding agent on their interior sides which bond to each other and the cable conductors 20. The ends of the flat cable 10 are stripped to expose the cable conductors 20 therein, which are then welded to the metal leads 16.
The flat cable and flat cable termination structure of the prior art suffers from the disadvantage that it requires the cable conductors 20 and the metal leads 16 to be spaced apart a certain pitch, resulting in larger clocksprings. Additionally, the cable conductors 20 are attached to the contacts 12 via the circuit board 11, adding a structural component between the flat cable 10 and the contacts 12.
In view of the foregoing, it would be advantageous to provide a flexible flat cable for a clockspring having conductors "printed" or "screened" onto a flat cable in order to increase the conductor density (i.e. the amount of conductors in a given space) of the cable. It would further be advantageous to provide a flat cable termination structure which eliminated the circuit board, and directly connected the conductors of the flat cable to the contacts of a connector, thereby eliminating the need for a circuit board or other intermediary connecting device.

Flexible flat cable termination structure for a clockspring


A fluid-filled vibration damping device having an elastic body connecting two mutually spaced-apart mounting members, a fluid chamber filled with a non-compressible fluid, and a movable member which partially defines the fluid chamber and which is oscillated to control a pressure of the fluid in the fluid chamber, for regulating damping characteristics of the device. The movable member partially defines a working air-chamber on one of opposite sides thereof which is remote form the fluid chamber, and is oscillated by a periodic change of an air pressure which is applied to the working air-chamber. A restoring member is disposed on at least one of opposite sides of the movable member for elastically supporting the movable member, so that an elastic force of the restoring member acts on the movable member to restore the movable member to an original position thereof during oscillation thereof.

1. Field of the Invention
The present invention relates to a fluid-filled vibration damping device which has a fluid chamber or chambers filled with a non-compressible fluid and which is capable of exhibiting a high damping effect with respect to input vibrations, by controlling the pressure of the fluid within the fluid chamber or chambers and thereby positively utilizing flows of the fluid and a change of the pressure of the fluid.
2. Discussion of the Related Art
As one type of a vibration damper interposed between two members of a vibration system so as to flexibly connect these two members or mount one of these members on the other member in a vibration damping manner, there is known a fluid-filled vibration damping device as disclosed in JP-A-6-294438 (laid-open publication of Japanese Patent Application). Such a fluid-filled vibration damping device includes: a first and a second mounting member which are spaced apart from each other; an elastic body elastically connecting the first and second mounting members; and a movable member which partially defines a primary fluid chamber filled with a non-compressible fluid the pressure of which changes as a result of an elastic deformation of the elastic body upon application of a vibrational load between the first and second mounting members. The movable member is oscillated at a frequency corresponding to a frequency of the input vibrations to be damped by the vibration damping device, whereby the pressure of the fluid in the primary fluid chamber is controlled so as to suitably regulate vibration damping characteristics of the vibration damping device.
As another type of the vibration damper, there is proposed a fluid-filled vibration damping device as disclosed in JP-U-61-191543 (laid-open publication of Japanese Utility Model Application). This type of fluid-filled vibration damping device includes: a first and a second mounting member which are spaced apart from each other; an elastic body elastically connecting the first and second mounting members and partially defining a primary fluid chamber filled with a non-compressible fluid the pressure of which changes upon application of a vibrational load between the first and second mounting members; a movable member which partially defines an auxiliary fluid chamber filled with the non-compressible fluid and which is oscillated to cause a periodic change of a pressure of the fluid in the auxiliary fluid chamber; and means for defining an orifice for fluid communication between the primary and auxiliary fluid chambers. In this type of vibration damping device, the pressure in the auxiliary fluid chamber by the oscillation of the movable member is controlled based on the pressure change which is induced in the primary fluid chamber as a result of elastic deformation of the elastic body upon application of the vibrational load. With the pressure in the auxiliary fluid chamber being controlled, vibration damping characteristics of the vibration damping device can be suitably regulated, based on the flows of the fluid through the orifice or the resonance of the fluid flowing through the orifice, or based on the fluid pressure change which is induced in the primary fluid chamber due to transmission of the pressure change from the auxiliary fluid chamber through the orifice.
In the above-described fluid-filled vibration damping devices, electromagnetic drive means is usually employed for oscillating the movable member. For assuring a high damping effect by controlling the pressure of the fluid in the fluid chamber, it is necessary to oscillate the movable member at an amplitude and a frequency corresponding to those of the input vibrations. To this end, the electromagnetic drive means has to have a sufficiently large drive force for oscillating the movable member, inevitably resulting in an increased size of the electromagnetic drive means including a coil and a permanent magnet, and accordingly an increased size of the entire vibration damping device. That is, the known vibration damping device tends to suffer from difficulty to exhibit a satisfactory damping performance with a required small size thereof.
Further, for assuring a sufficient degree of stability of the electromagnetic force generated by the electromagnetic drive means, the coil, permanent magnet and other components must be built in the damping device with high positional and dimensional accuracy, requiring a high level of skill for the manufacture, complicating the fabrication of the damping device, and accordingly reducing the efficiency of the manufacture of the damping device in a large scale.
Further, the known fluid-filled vibration damping device suffers from other problems such as a temperature rise due to heat generated by energization of the coil, and a relatively large amount of electric power consumption, where the oscillation of the movable member is required to be effected continuously for a long time or with a large drive force, depending upon the specific operating condition or required operating characteristics of the damping device.

Fluid-filled vibration damping device having pneumatically oscillated member partially defining fluid chamber