A stable ethanolic solution of budesonide is disclosed, which solution is suitable for use in nebulizers, together with a process for making such stable solution.

The present invention relates to pharmaceutical preparations in the form of stable ethanolic solutions of active substances for producing propellant-free aerosols.
In the last 20 years, the use of metering aerosols has become an established component of the treatment of obstructive lung diseases, particularly asthma. Usually, fluorochlorohydrocarbons have been used as propellant gases. Since the ozone-damaging potential of these propellant gases was recognised, more and more efforts have been made to develop alternatives. One alternative is the development of nebulisers in which aqueous solutions of pharmacologically-active substances are sprayed under high pressure so as to produce a mist of inhalable particles. The advantage of these nebulisers is that there is no need to use any propellant gases whatsoever.
Some nebulisers are described, for example, in PCT Patent Application WO091/14468, the contents of which are referred to hereinafter. In the nebulisers described therein, solutions of defined volumes containing active substances are sprayed, using high pressures through small nozzles so as to produce inhalable aerosols with a preferred particle size of between 1 and 10, preferably between 2 and 5 micrometers.
Hitherto, it has been assumed that, with conventional metering aerosols containing propellant gas, the optimum level of lung-bound particles is obtained in the aerosol. It has now been found, surprisingly, that by using ethanolic active substance solutions in combination with, for example, the above-mentioned nebulisers it is possible to generate a significantly better spectrum of inhalable particles than is usually the case with metering aerosols which contain propellant gas.
Suitable solvents for the pharmaceutical preparation within the scope of the present inventions are solutions containing at least 70% (v/v) of ethanol; solutions containing at least 85% (v/v) are preferred whilst solutions having an ethanol content of more than 95% (v/v) are particularly preferred. The concentration is given in percent by volume (v/v), the remainder being water. Most particularly preferred is ethanol which already contains small amounts of water, e.g. 96% ethanol, so that it is no longer hygroscopic and evaporates azeotropically.
Apart from water, the solvent may include other cosolvents and the pharmaceutical preparation may also contain flavourings and other pharmacological excipients. Examples of cosolvents are those which contain hydroxyl groups or other polar groups, e.g. alcohols, especially isopropyl alcohol, glycols, particularly propylene glycol, polyethylene glycol, polypropylene glycol, glycol ether, glycerol, polyoxyethylene alcohols and esters of polyoxyethylene fatty acids. Cosolvents are suitable for increasing the solubility of the excipients and possibly the active substances.
The proportion of dissolved pharmaceutical substance in the finished pharmaceutical preparation is between 0.001 and 5%, preferably between 0.05 and 3%, most particularly 0.01 to 2%, where the figures refer to the percentage by weight. The maximum concentration of pharmaceutical substance depends on the solubility in the solvent and on the dosage required to achieve the desired therapeutic effect.
As pharmaceutically active agent in the new preparations, it is possible to use any substances which are suitable for administration by inhalation and which are soluble in the solvent specified. These may include, in particular, betamimetics, anticholinergics, antiallergics, PAF-antagonists and particularly steroids and combinations of active substances thereof.
The following are mentioned specifically by way of example:
Tiotropium bromide, 3-[(hydroxydi-2-thienylacetyl)oxy]-8,8-dimethyl-8-azoniabicyclo[3,2,1]oct-6-en-bromide
As betamimetics:
1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2- butylamino]ethanol,
erythro-5xe2x80x2-hydroxy-8xe2x80x2-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one,
1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butyl-amino)ethanol,
1-(4-ethoxycarbonylamino-3-cyano-5-fluorophenyl)-2-(tert.-butylamino)ethanol.
As anticholinergics:
Ipratropium bromide
Oxitropium bromide
Trospium chloride
N-xcex2-fluorethylnortropine benzilate methobromide
As steroids:
Budesonide
Beclomethasone (or the 17,21-dipropionate)
Dexamethasone-21-isonicotinate
Flunisolide
As antiallergics:
Disodium cromoglycate
Nedocromil
Epinastin
As PAF-antagonists:
WEB 2086 (4-(2-chlorophenyl)-9-methyl-2-[3-(4-morpholinyl)-3-propanon-1-yl]-6H-thieno-[3,2-f][1,2,4]-triazolo[4,3-a][1,4]diazepine)
WEB 2170 (6-(2-chlorophenyl)-8,9-dihydro-1-methyl-8-[(4-morpholinyl)carbonyl]-4H,7H-cyclopenta[4,5]thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine)
The pharmaceutical preparations according to the invention may contain other excipients such as soya lecithin or surface-active substances.
Surprisingly, it has also been found that the addition of an organic or inorganic acid, preferably in conjunction with a complex forming agent, leads to an improvement in the stability (shelf life) of steroid-containing preparations. This has been found particularly useful for pharmaceutical preparations which contain as active substance Flunisolide or the hydrate or hemihydrate thereof or Budenoside, and which contain ethanol as solvent.
Examples of inorganic acids include, for example: hydrochloric acid, sulphuric acid or phosphoric acid; examples of organic acids include ascorbic acid, malic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid, propionic acid, etc.
The amount of acid in the finished pharmaceutical preparation is in every case selected so that the pH of the solution is between 2.0 and 7.0, especially between 3.0 and 4.0.
In a preferred embodiment, the pharmaceutical preparation also contains a complex forming agent. Examples of complex forming agents include EDTA, citric acid, nitrilo triacetic acid and the salts thereof. The quantity of complex forming agent is between 0.1 and 3 mg/100 ml, preferably between 0.2 and 2 mg/100 ml, particularly between 0.9 and 1.1 mg/100 ml, based on the finished pharmaceutical preparation.
The preferred complex forming agent is EDTA (ethylene diamine tetraacetic acid or a salt thereof, such as the disodium salt). A preferred pharmaceutical preparation according to the present invention contains 1.667% Flunisolide in the ethanol (96% v/v) as solvent, which contains 0.01% (v/v) EDTA as complex forming agent and is adjusted by the addition of acid to a pH of between 3.0 and 4.0.
Examples of steroids which may be used as an active substance in the pharmaceutical preparation according to the invention are:
9xcex1-chloro-6xcex1-fluoro-11xcex2,17xcex1-dihydroxy-16xcex1-methyl-3-oxo-1,4-androstadiene-17xcex2-carboxylic acid methylester-17-propionate.
Table 1 shows a comparison of a deposition study which was carried out on the one hand with a standard commercial metering aerosol Inhacort(copyright) (Flunisolide, dichloromathane, trichlorofluoromethane, cryofluoran, sorbitane triolate)=MDI, and on the other hand with the pharmaceutical preparation according to the invention containing Flunisolide in 96% (v/v) ethanol, which was carried out with a nebuliser as in the above-mentioned PCT Application WO 91/14468 (BINEB(copyright); technical data: volume of drug preparation administered 15 xcexcl, pressure approx. 300 bar, 2 jets squeezed out of two nozzle openings measuring 5xc3x978 xcexcm).
The Table clearly shows the advantage of the pharmaceutical preparation according to the invention which was administered with the nebuliser described.

Stable pharmaceutical budesonide preparation for producing propellant-free aerosols


An apparatus includes a semiconductor device that includes a three-dimensional (3D) memory. The 3D memory includes multiple memory cells arranged in multiple physical levels above a substrate. The 3D memory includes circuitry associated with operation of the multiple memory cells and includes a serializer/deserializer interface.

The capability to store data in memory devices continually improves with advances in technology. For example, flash memory enables non-volatile storage of data at a semiconductor device that may include one or more memory cores. A memory die that includes one or more NAND flash memory cores conventionally includes periphery circuitry, such as one or more charge pumps, state machines, and row decoders for each memory core, as illustrative examples. The periphery circuitry enables the memory die to be responsive to control signals from a memory controller to store and retrieve data. However, the periphery circuitry occupies space on the memory die that may otherwise be used for flash data storage elements.


A system and method for correcting for phase errors, in a phase locked loop, resulting from spread spectrum clocking involving a reference clock signal having a frequency modulation. A correction generation circuit generates an offset signal, that when injected after the charge pump of the phase locked loop, causes the voltage controlled oscillator to produce a signal with substantially the same frequency modulation, thereby reducing the phase error. The correction generation circuit may include a timing estimation circuit for estimating the times at which transitions (between positive-sloping and negative-sloping portions of the triangle wave) occur, and an amplitude estimation circuit for estimating the amplitude of the offset signal that results in a reduction in the phase error.

In high-speed electrical links, spread spectrum clocking (SSC) may be employed to reduce electromagnetic interference. Spread spectrum clocking may, for example, modulate the clock frequency with a triangular waveform, e.g., apply a triangle wave frequency modulation to the clock signal. The frequency ramp corresponding to a half cycle of the triangle wave may result in a phase error that is approximately constant if a second order phase-locked loop (PLL) is employed to track the clock signal. This phase error may reduce timing margins in the system.
Dual loop semi-digital phase-locked loops, which may be employed to reduce this phase error, may have various drawbacks. Such a phase locked loop may employ additional phase interpolators, digital to analog converters, and adaptation loops to estimate the frequency ramp rate and transition points of the triangle wave. Using dual loop semi-digital phase-locked loops may also be quite costly in terms of power; especially in double data rate or quad data rate systems which employ multiple phases of clock.
Thus, there is a need for an improved system and method for locking to a frequency modulated reference clock signal.

Spread spectrum clocking phase error cancellation for analog CDR/PLL


A retaining system for joints without utilising welds, screws or any other additional element or accessory, consisting in the making of a closing or locking mechanism, by means of a tab-slot configuration, using only the structure proper of the sections which are the object of the jointing, according to a first section (A) on which the cutting or machining that gives rise to the tabs and an embedment gap is made and a second section (B) that houses the slots and has to fit in the said embedment gap of section (A). Finally, the system is supplemented with the addition of tools that make it possible to release the system, thus making the joint demountable.

The use of structural tubular sections has increased in the past few years thanks to the numerous advantages they have compared to traditional open sections, particularly in truss-like structures. Thus, the structural advantages of this type of section are especially evident when they are going to be subjected to compression or torsion.
Additionally, one of the reasons why the use of tubular sections is gaining traction is aesthetics since they provide neater and sleeker structures, which can have sections with the same outer appearance but very different mechanical properties.
However, despite how ubiquitous its use has become, this type of section has a big drawback when it comes to using it: their joints are harder to make. Thus, these joints are usually made by welding or using additional accessories, both solutions being very costly and hardly efficient. Unlike the state of the prior art, the present invention provides a solution that substantially simplifies the jointing of sections and significantly improves the efficiency and the costs of manufacture and assembly of any frame, framework or structure.
The inventions that make up the state of the art are listed below by title and publication number respectively:                Tubular part, embeddable electrical box, and kits formed y both        WO 2015166131 A1        Jointing system for plastic pipes for creating structures        WO 2000056990 A1        Rapid-action retaining for pipes        WO 2014072539 A1        Ready-to-assemble modular frames and windows and doors made using said system        WO 2014102558 A1        Set of construction parts which form a double-row and double-linkage system for building walls        WO 2007065961 A1        Node for reticulated structures        WO 2006097545 A1        Modular construction system        WO 2013041748 A1        Three-dimensional structural system        WO 2003018923 A1
However, the 'Retaining system for joints' proposed by means of the present invention provides the following advantages with respect to the state of the art:                1. It avoids welded or screwed joints, which entail a higher cost and complexity and a longer execution time.        2. It avoids using any additional element or accessory to make the joint and exclusively utilises the sections to be joined together.        3. It allows a solid, strong and irreversible joint to be made, unlike current joint systems by embedment, which require, once a part has been slid over the other one, fixing said joint by means of welds or other mechanical means since, otherwise, this joint could come undone in the same way that it was made.        4. Unlike welded joints, it allows disassembly thanks to including a tool consisting in a plain folded sheet of metal, which is easy to manufacture and is very economical, with which the joint can be undone without damaging or wearing down the sections.        5. It depends neither on the type of section used, be they open or closed—quadrangular, rectangular or even circular—nor on the type of material—metal, plastic, etc.        6. The tabs and slots on the sections themselves can be made by using any cutting or machining technology that is available on the market: laser, plasma, stock removal, 3D printing, etc.        7. Jointing is done in a simple, entirely manual manner without having to use tools or to first bend any of the elements that are involved in said joint, the locked position being clearly identifiable acoustically and visually, which simplifies the assembly process.


For fixation of an oblique fracture in a long bone, a fixation plate is placed along the bone across the fracture and tabs extending outwardly from the plate engage the bone at upper and lower surfaces respectively of the proximal and distal fragments of the bone. By applying compressive force to the bone by the tabs, the fragments are subjected to compression force across the fracture and to a torque which opposes bone shortening.

Achieving stable fixation of two bone segments having an oblique contact surface can be difficult. For example, external rotation injuries of the ankle may often result in a short oblique fracture of the lateral malleolus. Because of the oblique orientation of the fracture line, simple apposition of the bone surfaces is nearly always unstable, since axial loading forces on the bone cause sliding of the two bone surfaces along the oblique fracture line and contribute to potential problems of shortening, non-union, and loss of reduction. For fractures involving the lateral malleolus of the ankle, even as little as 1 millimeter of shortening can lead to debilitating arthritis and ankle instability.
In the case of an oblique fracture of the lateral malleolus, the opposing bone ends of segments or fragments have the tendency to slide in opposite directions and shorten since axial loading of the bone produces shear stresses contributed by the obliquity of the fracture surface. This will be explained with reference to FIG. 1. If a reference point C is considered at the exact center of the fracture, axial forces F on the bone segments 1,2 produce sliding of the segments along the oblique fracture in opposite directions. The displacement of the two bone segments 1,2 in opposite directions causes the axial forces F on either side of the fracture to displace off center, resulting in the production of a force couple or torque T that aggravates the instability. This torque across the fracture site leads to additional displacement of the bone segments 1,2 and shortening of the bone.
A conventional arrangement of treating oblique fractures of the lateral malleolus of the ankle is illustrated in FIG. 2 which comprises inserting two interfragmentary screws or pins 5 across the fracture site. The interfragmentary screws 5 produce simple side to side compression of the oblique fracture surfaces. Because the fracture is oblique and the screws 5 only have a single point of fixation 6 on each side of the fracture surface of fracture 3, the screws 5 rely only on frictional forces across the fracture site to prevent sliding of the oblique surfaces and resultant shortening. Often such interfragmentary screws 5 cannot be placed perpendicular to the plane of the fracture, which results in a contribution of a force component that adds shear to the fracture site. This is similar to the way a wedge will tend to slip out of a vise as the vise is tightened.
Furthermore, since interfragmentary fixation relies on a single point of contact of the screw within each bone fragment 1,2, there is poor resistance to angular displacements and loss of reduction with axial loading of the bone as shown in FIG. 3.
Even if the screws 5 can be placed perpendicular to the fracture, this manner of fixation is not optimal since the bone is often osteoporotic with the result that the threads of the screws strip and lose purchase as compression is applied.
In addition, placing relatively large diameter holes in a small bone fragment can result in further fracture propagation through the screw hole. These factors limit the amount of compression that can be achieved by simple interfragmentary bone screw 5.
Fixation with interfragmentary screws is based entirely on the use of one or two screws. The holding power of the screws is based entirely on the purchase of the screw threads in the thin cortex of the bone fragments 1,2, which is often tenuous. In addition, this type of fixation is extremely weak in resisting external rotational torque T on the ankle, which can also lead to failure of fixation and a poor clinical result.
Another traditional means for fixation of oblique fractures is shown in FIG. 4 in which a bone plate 7 is utilized. Such a bone plate is used to statically hold the fragments 1, 2 in position without any compression (so called neutralization plates) or to hold the bone and create compression along the long axis of the bone (so called compression plates). Neutralization plates do not produce compression at the fracture site but instead depend entirely on the purchase of bone screw 8 on either side of the fracture and the strength of the plate. Fixation is along a single axis and in one plane and is relatively weak in resisting torsional loads. In addition, this type of fixation requires bulky plates and a multitude of screws with larger surgical incisions. Neutralization plates do not provide any load across the fracture site, and may result in longer healing times as well.
Compression plates which produce compression along the axis of the bone are effective for stable fixation of simple fractures that are transverse (not oblique) to the long axis of the bone. However, using a compression plate in the context of a long oblique fracture produces shear forces at the fracture site as previously described, resulting in sliding of the bone fragments with shortening and loss of reduction. In addition, since the plate is situated predominantly within a single plane, like neutralization plates, they provide only a single plane of fixation with limited ability to control rotational forces.
Recently, a plate for distal radius fractures has been used in which there is a small tab extending from a distal edge of the plate to act as a gutter to catch an edge of the bone. However, this tab is designed as a positional reference for the plate to the edge of the bone and is positioned at the extreme distal edge of the plate. Because it does not extend deeply, rotation of the plate would not produce any translational force to the bone, but rather would cause the bone to slip out from under the tab. In addition, the extreme distal nature of the position of this tab would cause the distal fragment to rotate off the corner of the plate.
Another technique for fixation of long bone fractures is the use of intramedullary pinning or rodding. Intramedullary fixation is not effective for short oblique fractures as it provides no rotational control and allows shortening of the bone.


Methods, systems, and computer programs are presented for obtaining histogram data from a database utilizing an interface with histogram-related options. One method includes an operation for providing, by a server, an application programming interface (API), to access the database, which includes a histogram request, to obtain histogram data from the database, with histogram options. The server receives, from a client device, a first histogram request including histogram options. Additionally, the method includes an operation for identifying bins for the histogram based on the one or more histogram options. For each bin, the server accesses the database to obtain data for each bin. The server returns, to the client device, the histogram data for the histogram as a table containing bin values for all the bins, where the client device is configured to present the histogram to a user based on the histogram data.

Histograms provide an easy way to represent data visually, especially when dealing with large amounts of data (e.g., weather data or statistical data at a national level). Unfortunately, getting data for a histogram is usually an expensive activity. For example, a program executing in a client device must send several requests to the database in order to obtain the desired data. These requests may include obtaining the maximum and minimum values of the data, determining the bins for the histogram, and sending a request for each bin to the data value for the bin.
When the database has a large amount of data, these access operations may be expensive (e.g., utilize a large amount of computer resources). Also, if the user wishes to compare data from a previous histogram (e.g., from the previous year), the user has to make sure that the data (e.g., the bins) are aligned properly in order to be able to visually compare the old and the new histograms.


An automatic laundry machine is fashioned as a device having a washing machine and dryer in a single unit, a plurality of washing soap and fabric softener reservoirs, a means for calibrating the weight of a load of wash and automatically dispensing a corresponding amount of washing soap and fabric softener and a mechanical conveyor capable of moving washed clothing from the washing machine component to the drying component. Each component is capable of independent operation.

All of us know of the hassles and burdens associated with doing laundry. One must constantly monitor the washing machine and dryer, transferring clothes from one (1) to the other in order complete the process. In doing so, the user is somewhat trapped in the sense that the process cannot be left unattended and is forced to stay nearby while the washer or dryer is in operation. It is another common problem in that a load of wash cannot be started because it will sit wet in the washer for hours after the washing cycle is complete, whereupon wrinkles and odors may result. Thus, the time to wash and dry clothes has to be long enough, but the person must also be available in between cycles to move clothes as well. All of these restraints just add to the drudgery of laundry. Accordingly, there is a need for a washer/dryer that eliminates the need for constant human intervention to transfer wet items from the washer to the dryer. The development of the combination washer/dryer with automated interface fulfills this need.


A laser power grid for operation with data networks employs WDM and incorporates wavelength addressing. The laser power grid (100) includes a laser power supply station (110) comprising a plurality of continuous-work laser sources (112, 114, 115, 116, 118), a laser distribution grid (130) for distributing light propagations of different wavelengths throughout a data network and an optical switching network (142, 144, 145, 146, 148) coupled to the laser distribution grid for locally turning the laser power on when it is needed. The laser power grid replaces systems of tunable lasers. It is considerably faster and cheaper than systems of tunable lasers and produces less waste heat within the data network surroundings. The laser power grid incorporates parallel fast optical communication in complex multi-node communication and computer networks and enables the implementation of burst switching and packet switching by wavelength addressing.

The present invention relates to data networks, employing WDM multiplexing, and incorporating wavelength addressing, and in particular, to a laser power grid, for operation with these networks.
Communication traffic is steadily increasing, both in size and in complexity. Leading service providers for Internet Protocol (IP), for example, report a 300 percent growth per year in Internet traffic, while traditional voice traffic has grown at a about 13 percent. [Cisco documentation, of Sep. 28 05:50:55 PDT 2002, www.cisco.com/univercd/cc/td/doc/product/mels/cm1500/dwdm/dwdm_fns.htm]. In response to this explosive growth in bandwidth demand, long-haul service providers are moving away from Time division multiplexing (TDM) based systems, which were optimized for voice but now prove to be inefficient, to wavelength division multiplexing (WDM).
TDM was invented as a way of maximizing the amount of voice traffic over a medium by multiplexing, so that more than one telephone call could be put on a single link. In essence, TDM increases the capacity of a transmission link by slicing time into smaller intervals, so that the bits from multiple input sources can be carried on the link, thus, increasing the number of bits transmitted per second.
Using TDM, data may be transmitted at 10 Gbps and recent advances have resulted in speeds of 40 Gbps. Yet, the electronic circuitry that makes this possible is complex and costly. Furthermore, technical issues, such as chromatic dispersion and nonlinear effects that can affect waveform quality, may restrict the applicability of TDM at these rates.
An alternative to TDM, wavelength division multiplexing (WDM) now reigns as the leading technologies for transmitting high volume of data traffic over long distances. It is based on the inherent advantage of photons as data carriers, which is that photons of different wavelengths do not normally interact, thus enabling the transmission of many channels of data, in parallel, in a single fiber, with photons of a different wavelengths acting as channels. WDM uses single-mode fiber to carry multiple light waves of differing frequencies.
In a sense, multiplexing by WDM is analogous to radio broadcasting on different wavelengths. Each channel is transmitted at a different frequency, and one can select a frequency, as if by using a tuner.
Thus, in WDM, many wavelengths are combined onto a single fiber, so as to simultaneously multiplex signals of 2.5 to 40 Gbps each over a strand of fiber. In this manner, the effective capacity of existing fiber infrastructure can be increased by a factor of up to 100.
When using WDM, each of the wavelengths is launched into the fiber, at the transmitting end, and the signals are demultiplexed by an optical wavelength demultiplexer, at the receiving end. As with TDM, the resulting capacity is an aggregate of the input signals. But an important difference between TDM and WDM is that WDM carries each input signal independently of the others. In other words, each wavelength channel has its own dedicated bandwidth; all signals arrive independently, rather than being broken up and carried in time slots.
Dense wavelength division multiplexing (DWDM) is different form WDM mainly in degree. DWDM spaces the wavelengths more closely than WDM; in consequence, it has a greater overall capacity. DWDM systems with 100 channels per fiber each carrying 10 Gb/sec are commercially available, enabling data traffic at a rate of approximately 1 Terabit per second in a single fiber. The spacing limit is not precisely known yet, and has probably not been reached. The state of art of commercial systems is 50 GHz.
Similarly, coarse wavelength division multiplexing (CWDM) relates to spacing the wavelengths sparsely, thus reducing the cost of the systems.
The capability of two optical signals of different wavelengths to occupy the same fiber, at the same time, makes WDM point-to-point segments extraordinarily powerful. The challenge is how to harness this capability to supply the huge bandwidth that flows in high performance computing systems that are predominantly a complex mesh of parallel interconnections. In particular it is desirable to combine the inherent advantages of the packet/burst-switching paradigm with the vast data transfer capability of the optical fiber.
An added feature when using WDM is the possibility of using the channel wavelength as an address vehicle for delivering the transmissions to their destinations. This idea is termed wavelength addressing.
Wavelength addressing relates to assigning every processing element (PE), or node, in a data network a wavelength, as a receiving address. The processing element, or node, may be a chip, a board, a cabinet, or even a routing switch. A schematic illustration of a PE adapted for wavelength addressing is provided in FIG. 1A.
As seen in FIG. 1A, a PE 10 includes a processing unit 30, a transmitter 20 and a wavelength addressed receiver 90[λ0]. Processing unit 30 communicates to transmitter 20 an information defined by Ei; λi, wherein Ei relates to an electronic data to be transmitted, and λi is the address of the receiving PE, at a specific instant. It will be appreciated that the information defined by Ei; λi relates to a specific transmittal. A moment later, processing unit 30 may communicate to transmitter 20 an information defined by En; λn.
Transmitter 20 communicates the wavelength designation λi to a tunable laser 40 which produces a light propagation of wavelength λi. Additionally, transmitter 20 communicates the electronic data Ei to a modulator 60, which modulates the light propagation of wavelength λi so as to produce a data packet 50i;λi containing electronic information Ei and addressed to a PE whose receiving address is λi.
When information is received, wavelength addressed receiver 90[λ0] communicates the received data, for example, 59n;λ0 to processing unit 30.
FIG. 1B illustrates a data network 150 having a plurality of PEs of the type described in FIG. 1A, denoted, PE 12, PE 14, PE 15, PE 16, and PE 18, having processing units 32, 34, 35, 36, and 38, respectively, transmitters 22, 24, 25, 26, and 28, respectively, tunable lasers, 42, 44, 45, 46, and 48, respectively, modulators 62, 64, 65, 66, and 68, respectively, and wavelength addressed receivers 92[λ5], 94[λ6], 95[λ4], 96[λ8], and 98[λ2], respectively, the wavelength addressed receivers communicating their received data to processing units 32, 34, 35, 36, and 38, respectively.
Accordingly, a plurality of data packets, 52i; λ2, 54i; λ4, 55i; λ5, 56i; λ6, and 58i; λ8, each issuing from its respective PE, are coupled to an optical coupler 70 and transmitted, by WDM.
An optical-wavelength demultiplexer 80 decouples the data packets by wavelengths, and each is routed to its wavelength address.
It will be appreciated that by coupling the data packets to a single fiber, each PE needs to communicate only with optical coupler 70 and optical-wavelength demultiplexer 80, rather than with all the other PEs.
Additionally, the use of wavelength addressing reduces the electronic information that needs to be contained in the data packet.
The architecture of FIGS. 1A and 1B relies heavily on the performance and price of the tunable lasers; in fact, a major incentive for the development of tunable lasers is their application for wavelength multiplexing and addressing. Yet, tunable lasers are expensive, cumbersome, and slow, and their use limits scalability.
Rubin et al., (S. Rubin, E., Buimovich, G. Ingber and D. Sadot, "Implementation of an Ultra-Fast Widely-Tunable Burst-Mode 10 Gbps Transceiver," Electronic Letters vol. 38 No. 23 pp. 1462-1463, November 2002) describe a tunable 10 Gbps transceiver, for optical burst-switching applications. The burst-mode receiver has fast tuning of less then 50 nano-seconds between 80 channels over the entire C-band, together with fast locking, of less than 100 nanosecond.
Faster tunable lasers are under development; however, their projected performance and price may not justify their deployment in computer networks with multitude of nodes, in particular for board-to-board and chip-to-chip communication.
As a consequence, the range of applications implemented by tunable lasers is limited to networks in which the price of each node is high, and the length of the burst is comparatively long.
There is thus a widely recognized need for, and it would be highly advantageous to have WDM systems which implement wavelength addressing, devoid of the above limitations.

Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd.


A plurality of pairs of alignment marks are formed on a reticle along a scanning direction, and, when a first wafer is to be exposed, a base line amount of an alignment sensor is measured by using a first pair of alignment marks (steps 112, 113, 115), and, when a second wafer is to be exposed, the base line amount is measured by using a second pair of alignment marks and a magnification error of the reticle in the scanning direction is determined on the basis of positional displacement amounts of the alignment marks measured regarding the first wafer and positional displacement amounts of the alignment marks measured regarding the second wafer (step 115), whereby the magnification error of the reticle in the scanning direction is measured with high accuracy, without making a measuring device complicated and reducing through-put of the exposure process.

The present invention relates to a projection exposure method for transferring a pattern of a mask onto a photosensitive substrate in a photolithography process for manufacturing semi-conductor elements, imaging elements (charge-coupled devices and the like), liquid crystal display elements or thin-film magnetic heads, which method is particularly applicable to a scanning exposure apparatus of step-and-scan type in which exposure is performed while scanning the mask and the photosensitive substrate are scanned in a synchronous manner.
As a related art, when a semi-conductor element is manufactured, a projection exposure apparatus for transferring a pattern of a reticle (as a mask) onto a wafer (or a glass plate or the like) on which photo-resist is coated through a projection optical system is used. Recently, in order to respond to a request that an area of a pattern to be transferred should become larger without making the projection optical system larger, there is proposed a projection exposure apparatus of step-and-scan type in which, after a wafer is stepped to a scan start position, by scanning a reticle and the wafer with respect to the projection optical system in a synchronous manner, a pattern image of the reticle is successively transferred onto shot areas on the wafer.
In the scanning exposure apparatus such as the projection exposure apparatus of step-and-scan type, since the pattern image of the reticle must be aligned with each shot area on the wafer with high accuracy during the exposure, there are provided a reticle alignment microscope for detecting positions of alignment marks on the reticle, and a wafer alignment sensor for detecting positions of alignment marks (wafer marks) on the wafer. When the reticle is exchanged for another one, the reticle is aligned with a wafer stage by using the reticle alignment microscope, and, when the wafer is exchanged for another one, the position of each shot area on the wafer is measured by using the wafer alignment sensor. Then, scanning exposure is performed in a condition that the pattern image of the reticle is overlapped with each shot area on the basis of the measured result.
In this case, for example, by detecting a position of a corresponding reference mark on the wafer by using the wafer alignment sensor while observing the corresponding alignment mark by using the reticle alignment microscope, a relative distance (i. e., base line amount) between a projection position (i. e., exposure center) of the reticle pattern image and a detection position (i. e., detection center) of the wafer alignment sensor is determined. A process for measuring the base line amount in this way is called as "base line check". By correcting the measured amount obtained by the wafer alignment sensor by the base line amount, the reticle pattern image can be overlapped with each shot area on the wafer with high accuracy.
In the above-mentioned scanning exposure apparatus, as mentioned above, the alignment between the reticle and each shot area on the wafer is performed by using the reticle alignment microscope and the wafer alignment sensor. However, for example, when one lot of wafers are successively exposed by using a single reticle, the reticle is thermally expanded gradually due to repeated illumination of exposure light illuminated onto the reticle, with the result that a length of the circuit pattern described on the reticle is gradually changed. Further, there is a danger of deviating the length of the circuit pattern from a design value due to the describing error. When it is assumed that the actual length of the circuit pattern described on the reticle is LR and the design length of the circuit pattern is LR.sub.0, a magnification error (%) of the reticle is represented as follows: EQU 100.times.(LR-LR.sub.0)/LR.sub.0
If such a magnification error of the reticle exceeds a limit of an allowable range, an error in overlap (hereinafter called "overlap error") between the reticle pattern image and each shot area (chip pattern) on the wafer will also exceed a limit of an allowable range, thereby worsening the yield of the semi-conductor elements finally obtained.
Regarding this, for example, by arranging a pair of reticle alignment microscopes along a non-scanning direction on the reticle, when the base line check is effected, the magnification error of the reticle in the non-scanning direction can be MEASURED by detecting a displacement amount of a distance between two alignment marks. If the magnification error in the non-scanning direction can be measured correctly in this way, the overlap error in the non-scanning direction can be reduced, for example, by adjusting projection magnification of the projection optical system accordingly.
Further, in the scanning exposure apparatus, if the magnification error of the reticle in a scanning direction can be measured correctly, the overlap error in the scanning direction can also be reduced, for example, by correcting a value of a ratio between a scanning speed of the reticle and a scanning speed of the wafer in accordance with the magnification error.
Thus, it could be considered that the magnification error of the reticle in the scanning direction is measured by arranging a pair of reticle alignment microscopes along the scanning direction on the reticle. However, since a projection area of the projection optical system used in the exposure apparatus of step-and-scan type is narrow (for example, slit) in the scanning direction, a distance between the pair of reticle alignment microscopes along the scanning direction must be so short corresponding to the narrow projection area, and it is therefore difficult to arrange them. Consequently, it is difficult to measure the magnification error in the scanning direction with high accuracy. Further, if additional reticle alignment microscope(s) for measuring the magnification error in the scanning direction is provided, in addition to the reticle alignment microscopes disposed along the non-scanning direction or in combination with the latter, the entire apparatus would be complicated and costly.
Further, since through-put (productivity) must be improved in the manufacturing process of the semi-conductor elements, it is desirable that the magnification error in the scanning direction is measured more efficiently.

Alignment in a projection exposure method


An image processing apparatus includes: an object setting section that sets an object image indicating an object which is placed in an image generated by an image capturing section; a detection section that detects the object included in a synthetic image in which the object image and the image generated by the image capturing section are synthesized; and an output section that outputs output information for setting a detection parameter used in a detection process performed by the detection section, that is, output information in which the synthetic image and a detection result of the detection process are associated.

The present application relates to an image processing apparatus. Specifically, the present application relates to an image processing apparatus and an image processing method capable of dealing with an image, and a program causing a computer to implement the method.
In the related art, image processing apparatuses such as an image capturing device, which captures an image of a subject such as a person and generates the image (image data), have come into widespread use. Further, there has been proposed a subject recognition technique of detecting an object such as a moving object or a person included in an image generated in such a manner.
For example, there has been proposed an image processing apparatus that detects a face of a person included in an image through image processing using a feature amount such as luminance or color (for example, refer to Japanese Unexamined Patent Application Publication No. 2008-131405).

Image processing apparatus including an object setting section, image processing method, and program using the same

Sony Semiconductor Solutions Corporation


In one aspect, an electronic device includes a switching circuit connected to a resistance circuit and ground, the resistance circuit connected to a port and the port configured to be connected in series to an external resistor and a supply voltage. A voltage at the port is a first voltage that is less than the supply voltage if the switching circuit is enabled to be a closed circuit and the voltage at the port is a second voltage that is equal to the supply voltage if the switching circuit is enabled to be an open circuit.

Traditionally electronic devices are manufactured in large quantities whenever possible in order to reduce costs. These identical electronic devices are integrated into electronic circuitry as opposed to having more costly individualized (e.g., specialized) parts integrated into the electronic circuitry. For example, a number of identical electronic devices may be integrated into electronic circuitry having a microcontroller. In order for the microcontroller to differentiate one identical electronic device from another identical electronic device in the electronic circuitry, each identical electronic device is separately addressed.

Determining an action by an electronic device based on voltage at a port of the electronic device


An optical control device is provided which can suppress crosstalk between electrodes without increasing the entire size of the device itself. The optical control device includes a substrate having an electro-optical effect, an optical waveguide formed in the substrate, and a modulation electrode modulating optical waves propagating in the optical waveguide. The modulation electrode includes at least two signal electrodes and ground electrodes arranged to interpose the signal electrodes therebetween. The optical control device further includes an electrical connection member that electrically connects the ground electrode disposed between the two signal electrodes to other ground electrodes and that is disposed to cross over part of the signal electrode.

Field of the Invention
The present invention relates to an optical control device, and more particularly, to an optical control device having two or more signal electrodes as a modulation electrode.
Description of Related Art
Optical control devices have been used in which optical waveguides and modulation electrodes are formed in a substrate such as lithium niobate or the like having an electro-optical effect and optical waves propagating in the optical waveguides are modulated by the modulation electrodes. Recently, in order to meet requirements such as an increase in communication speed or an increase in communication data rate in the fields of optical communications or the like, plural Mach-Zehnder type optical waveguides (MZ-type optical waveguides) are driven using plural modulation signals in a differential quadrature phase shift keying (DQPSK) format.
In an optical control device having plural optical waveguides and plural signal electrodes, different modulation signals are often input to the signal electrodes and the different modulation signals are applied to the optical waveguides. Accordingly, when an electric field other than from a predetermined modulation signal acts on a specific optical waveguide, optical characteristics of the optical control device such as an extinction ratio of signal light degrade. This phenomenon is referred to as crosstalk.
In order to suppress the crosstalk between electrodes, it is effective to increase the gap between the optical waveguides or the gap between the electrodes, but this method causes an increase in device size, which is not desirable. As described in Japanese Laid-open Patent Publication No. 2009-53444, a method of forming a groove between optical waveguides or between signal electrodes has been proposed. However, since a process of forming the groove is particularly added to the optical control device manufacturing process, the manufacturing time and cost increase. In optical control devices using a substrate with a thickness of 30 μm or less, there is a problem in that a groove cannot be formed or that the substrate is easily destroyed even when the groove can be formed.
With an increase in frequency bandwidth of a modulation signal, a local potential difference corresponding to an operating state is generated between ground electrodes interposing a signal electrode therebetween. Accordingly, a phenomenon occurs in which a variation in electric field generated between a signal electrode and ground electrodes interposing the signal electrode therebetween differs on both sides of the signal electrode. When such electric fields are applied to the optical waveguides, an intended operation of modulation cannot be expected and modulation characteristics of the optical control device degrade considerably.


A method, apparatus (100) and system (200) for altering the playback speed of recorded content (105) to match a target syllable rate is provided. A user may enter a desired, target playback syllable rate through a user interface (101), such as a keypad or touch screen. Alternatively, the target playback syllable rate may be determined from identification of the source of the recorded content (105). An actual playback syllable rate (106) associated with the recorded content (105) is then determined. The recorded content (105) is then altered, by time domain harmonic scaling in one embodiment, such that the altered playback speed (109) substantially matches the target playback syllable rate. In so doing, a listener is able to receive recorded content (105) at a faster or slower rate than it is produced. Elements that may compromise the intelligibility of the recorded content (105), including distortion (114), background noise (113), ambient noise (117) and audible intonations (115), may be measured such that the target playback syllable rate may be compensated.

1. Technical Field
This invention relates generally to a system and method of altering the playback speed of recorded content such as audio or video, and more specifically to a system and method where the playback speed of recorded content is altered so as to match a target syllable rate associated with user input or source of origin.
2. Background Art
With the advent of new technology, people have an increasing number of options for receiving news, entertainment and other information. For example, there was a time when the only way to "read" Tolstoy's War and Peace was to actually sit down and physically read the text on each page. At over 1400 pages in length, this was a daunting, time consuming task. At 20 pages a day, it would take nearly three months to complete the work. Additionally, while reading, the reader can do essentially nothing else—the hands must hold the book and turn the pages, while the eyes are fixed on the text. A person reading such a novel is simply unable to do another task simultaneously, like exercising, cooking or driving.
Advances in technology have given "books on tape". With a recorded book, rather than actually reading the words, a user may simply place a cassette tape or compact disc into a suitable player. The user then listens as an articulate reader reads the book aloud. With the advent of books on tape, an entirely new audience has been introduced to, among other works, classic novels as they can be "read" while driving, jogging, or doing other activities. Additionally, since the reader's pace is steady and never tires, a lengthy novel like War and Peace can generally be completed in a fraction of the time it would take to actually read every word. Still, even if the listener hears 40 pages a day, it will be more than five weeks before War and Peace is completed.
The problem with the recorded spoken word, when recorded in a format like cassette tapes or compact discs, is that the playback rate is the same as the generation rate. In the case of a novel, the listener hears the spoken words at the same rate that the reader produced them. People are generally capable, however, of comprehending the meaning of spoken words at a rate which is significantly higher than the rate at which it is produced. Testing has shown that comprehension at a playback speed that is 1.5 to 2 times; the original recording speed is often practical.
The problem with simply increasing the speed of a tape or similar recording format is that the intelligibility of the content can be compromised. A typical effect is that the pitch of the speaker's voice gets higher. While David Saville made a career using this technique to create his "Alvin and the Chipmunks", people often prefer to hear a speaker's voice with its normal pitch and tambre.
There is thus a need for an improved method and system for increasing the playback speed of a recording without reducing the intelligibility of the recorded content.
Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of embodiments of the present invention.

System and method for altering playback speed of recorded content


Technologies managing cross ring memory accesses by a device driver on a computing device includes configuring a memory page table associated with the device driver to disable cross ring memory accesses by the device driver, trapping attempted cross ring memory accesses by the device driver, and denying the attempted cross ring memory access if the device driver is determined to be malicious. If the device driver is determined not to be malicious, the memory page table is updated to allow the attempted cross ring memory access. The device driver may be analyzed to determine whether the device driver is malicious by comparing the device driver and the attempted cross ring memory access to security data, such as a device driver fingerprint and/or cross ring memory access heuristics, stored on the computing device.

Many computer architectures implement some form of hierarchical protection domains or "rings." Each protection ring has an associated privilege mode (i.e., from a high-privilege mode to a low-privilege mode). The operating system of a computing device, for example, is generally executed in the highest-privileged mode. In software vernacular, the protection ring with the highest privilege is often referred to as "Ring 0" or kernel-mode, with lower privilege rings being assigned increasing numbers (e.g. Ring 1, Ring 2, Ring 3, etc.). Although a particular computer architecture or operating system may utilize any number of protection rings, some computer architectures or operating systems utilize a reduced protection ring scheme having only a few protection rings (e.g. only Ring 0 and Ring 3). The use of protection domains or rings allow the corresponding computer system to provide protection of data and applications executed in each protection ring from those executed in other protection rings. For example, in some computer systems, cross ring accesses (e.g. a Ring 0-to-Ring 3 access) may be restricted or even prohibited.
Device drivers are software programs that control a particular device of a computing system. Device drivers act as an interface between an operating system of the computing system, or application executed by the operating system, and the corresponding hardware device. In many computing systems, device drivers are executed in a high-privileged protection ring such as Ring 0, along with the operating system. Software applications, on the other hand, are executed in a lower privileged ring, such as Ring 3. Many legitimate device drivers perform cross ring accesses (e.g. a Ring 0-to-Ring 3 access) during execution. Some operating systems facilitate the cross ring accesses by providing a specific application interface program (API), which must be used by the device drive to perform the cross ring access without causing a violation. However, many device drivers may not implement such APIs or otherwise be configured to perform the cross ring accesses in a secure manner. As such, to function properly, computer systems generally must allow all device drivers to run without any cross ring access protection or globally enforce cross ring access protection, which causes legacy device drivers to stop functioning properly. As such, the ability to provide cross ring access protection for memory accesses from a higher protection ring to a lower protection ring in a typical computer system using various device devices is limited.

Managing device driver cross ring accesses


An adjustable tourniquet includes a first component, a second component, a third component and a band. Two ends of the first component respectively have an axle for fixing the band and a buckling trough with an engaging element, wherein two ends of the axle respectively have a ratchet. The first and second components respectively have a rejecting element and a driving element to stop the ratchet. The axle is clamped by an axial cover, and two ends of the axle are respectively connected with a connecting axle for penetrating the second component. Furthermore, the ratchet includes an inner and an outer ratchet surfaces respectively for butting the rejecting element and the driving element, and the teeth of the inner and outer ratchet surfaces are respectively bent toward the same direction and the arrangement of the inner and outer ratchet surfaces are perpendicular to each other.

When accident happens, the most common situation might be the human body get hurt and some cuts or wounds are made with blood, so that stopping bleeding is the initial action of the first aid.
Usually, the slight trauma, like cut and wound, caused in daily life, is bleeding caused in the blood capillary or slight vein. The most common way to stop bleeding is to apply direct pressure on the bleed, and to band the wound then, so that the blood on the wound can have a spontaneous clot and callus. Moreover, when the trauma is more serious, such as injury of vein or slight artery, the bleeding volume becomes more and is more difficult to clot, so that in addition to direct pressure, lifting up the injured limb or applying point pressure for stopping bleeding have been used simultaneously. For the most severe situation, for example, the limb is broken to cause a large amount of blood loss, the most important thing is to keep alive, so that the emergent method is to use tourniquet to stop bleeding. But, as known, applying tourniquet might easily kill the tissue, so that it should be the last resort to use.
The principle of tourniquet is to constrict or compress the vicinity of the bleeding portion for stopping blood loss. Since it is usually used in the emergency, the essential conditions of a well-designed tourniquet should be easy to arrange with capabilities of providing sufficient strength, rapid fixing and easy to disengage. There are many types of the tourniquets. One of them is TWP No. M263082, entitled "Improved structure of tourniquet", including a release buckle with a tongue and an engaging portion which are connected by a band. When using this tourniquet, the band is applied circumferentially upon the bleeding portion, and the tongue and the engaging portion are engaged together for fixing the band. Then, through a circling structure in the tongue, the band can be tightened by pulling so as to stop bleeding. However, this application could not provide a strong pressure and might easily become loose owing to an external touch to contact the upright tourniquet. Another example is TWP No. M318404, entitled "Adjustable tourniquet", in which two ends of a band are respectively connected to a first housing and a third housing, which are buckled together to loop the band, and through a structure in the third housing, the band can be tightened by applying force. Further, it is characterized in that a second housing is included, wherein an axle of the second housing is passed through a hollow axial tube of the first housing, and the first and the second housings have a rejecting element, plural ratchets and a driving element, so that when the second housing moves by pivoting about the axial tube, through the orientation mechanism of the ratchets, the band can have a slight adjustment. However, when applying this structure, the user might easily touch the sliding portion so as to move the driving element, thereby loosing the tightening strength. Beside, the structure of hollow axial tube cooperating with the axle is complicated, and the overlapped rejecting element and the driving element form a thicker structure which increases the collision possibility, and thus, the loosing possibility would be present.


A modular software control system for an I/O subsystem. A central group of software modules are made to be hardware-independent, with interface modules translating from the host hardware configuration and the I/O subsystem hardware configuration. I/O commands are accomplished using a series of specialized threads, with each thread performing a particular function. An appropriate group of threads are assembled for each I/O command, the group being a "net".

The present invention relates to I/O controller software for I/O subsystems, and in particular for RAID subsystems.
Typically, memory subsystems, such as RAID (Redundant Array of Independent Disks) subsystems have been implemented using primarily hardware and firmware. This approach is driven by the need to provide high performance, high bandwidth storing and retrieving of data.
Some vendors attempted to create a "software RAID" solution with software which would run on general purpose computers and transform those computers into RAID servers. This approach suffered from lack of high performance and bandwidth for the storing of data.
An example of a RAID system is set forth in U.S. Pat. No. 5,140,592, the disclosure of which is incorporated herein by reference.

I/O controller software with each I/O command having a plurality of nets, each with a group of threads


A SIM for a mobile station used in a GSM mobile communications system the SIM operating system being adapted to perform data coding format conversion for data items stored in the SIM and transmitted to the mobile station. This ensures that the SIM is able to receive, and present, data items in the required standard format at the interface between the mobile station and the SIM, while allowing the data items to be stored in a compressed format in the SIM memory, thereby increasing the perceived storage capacity of the SIM.

This invention relates to a smart card for a user station used in a mobile communications system, such as a subscriber identity module (SIM) as used in a GSM (Global System for Mobile communications) digital cellular radio system, to a mobile station including such a smart card, and to a method of transmitting data items to and from such a smart card.
In a known conventional GSM system, each mobile station, such as a mobile telephone handset, is provided with a SIM, herein also referred to as a smart card, which is inserted into the mobile station in order to allow the mobile station to receive service in a GSM network.
A typical SIM includes a microprocessor, memory elements including a permanent memory (e.g. ROM), a non-volatile rewritable memory (e.g. EEPROM) and a volatile rewritable memory (e.g. RAM), and contacts for forming the data transfer interface between the SIM and the mobile station.
The GSM standard also specifies a command set for use by a mobile station to access data records in the SIM and retrieve and write data from and to the SIM. Such data records may be permanent data records, such as a record of the international mobile subscriber identity (IMSI) whereby the mobile subscriber is recognised by a mobile communications network.
Other data records are modifiable, either at the initiative of the mobile station (such as the data record holding the current location area information (LAI) for the mobile station) or at the initiative of the mobile subscriber (such as an abbreviated dialling number (ADN) record which is used to allow the subscriber to automatically initiate calling of the stored dialling number by selection of the associated dialling number identifier when displayed by the mobile station).
Other modifiable data records include a short message data record, which stores data relating to one or more short messages in alphanumeric characters received by the mobile station, for future retrieval by the subscriber.
For more details of the records which may be stored in a SIM, reference should be made to GSM Technical Specification 11.11 (ETS 300 608).
The memory capacity of the SIM is necessarily limited, primarily due to cost considerations.
Accordingly, the data records referred to above are limited in size and number in accordance with the memory capacity of the SIM, which can be a drawback. For example, in the case of ADN records, it is conventional to allocate sufficient memory capacity dedicated to an ADN list such that up to 90 ADN records can be provided. Some subscribers however require a greater ADN storage capacity. This is evidenced by the fact that ADN storage capacity is used as a positive marketing point by suppliers who are able to provide SIM""s having relatively large ADN storage capacities. However, with a fixed amount of total memory capacity available, an increase in the memory capacity allocated to ADN records must be compensated for by a reduction in the memory capacity allocated to other data records.
Further information relating to known subscriber identity modules used in GSM may be found in Farrugia A J et Al.: xe2x80x9cSmard Card Technology Applied to the Future European Cellular Telephone on the digital D-Networkxe2x80x9d, selected papers from the Second International Smart Card 2000 Conference, Oct. 4-6 1989, Amsterdam, NL, 1991, pages 93-107.
GB-A-2251357 describes a radio telephone terminal which includes a terminal unit having a transmitter-receiver and an external device. The external device has a storage unit for storing subscriber information, a recaller unit for selectively recalling the stored information. Information may be recalled from the external device to the radio telephone unit, so that it is possible to originate a call from the terminal unit using a subscriber telephone number stored in the external device without the need for a dialling operation on the terminal unit. Thus, subscriber information stored in the terminal unit may be augmented by subscriber information stored in the external device.
U.S. Pat. No. 4,875,230 describes a cellular telephone which includes logic circuitry allowing keystroke sequences to be stored and recalled for activation using a short form recall command. It does not describe the use or a smart card.
The present invention in one aspect provides a smart card for a mobile station used in a mobile communications system, said smart card including:
a memory for storing data items communicated via an interface between said card and said mobile station; and
data item converting means,
said converting means being for receiving a data item transmitted via said interface in a standardised data coding format, for converting said data items to a compressed data coding format and for storing said data item in said memory in said compressed data coding format, and
said converting means being for receiving said data item from said memory in said compressed data coding format, for decompressing said data item to said standardised data coding format and for transmitting said data item via said interface in said standardised data coding format.
Thus, even if a standardised data coding format for a data item transmitted via the smart card/mobile station interface is not optimal for storage, by use of the present invention the data item can still be stored in the smart card in a compressed data coding format, without rendering the smart card incompatible with the chosen standard.
The data coding format conversion can be implemented invisibly to the mobile station. That is to say, the communication of data items via the interface between the smart card and the mobile station can be implemented in the data coding format required by the chosen standard, irrespective of the data coding format used for stored items.
Thus, the smart card can remain compatible with all mobile stations complying with the chosen standard.
In some cases, data items are required to conform to a standardised fixed length data coding format when communicated to or from the mobile station. The data item converting means then preferably converts data items from said fixed length data coding format to a variable length data coding format. More efficient data coding can thereby be achieved. For example, in the case of ADN records, the use of a variable length coding format for storage of ADN data items can increase the amount of ADN records available, compared to the conventional storage format, by over 50%. Thus, the number of ADN records available can be increased to over 100, without increasing the memory allocated to the ADN list.
The data items may comprise a variable Quantity of non-padding character data (i.e. data relating to useful information), and when in the standardised data coding format a variable quantity of padding data (i.e. data of which the contents are ignored). The data item converting means is preferably operable to reduce the amount of padding data when converting the data items to the different data coding format. Data items can then be stored in a more compact coding format in a given allocation of memory capacity.
In a further aspect, the invention provides a method of writing a data item to, and transmitting a data item from, a smart card for a mobile station used in a mobile communications system, said card including a memory for storing data items communicated via an interface between said card and said mobile station, wherein said method comprises:
receiving a data item transmitted via said interface in a standardised data coding format, converting said data items to a compressed data coding format and storing said data item in said memory in said compressed data coding format; and
receiving said data item from said memory in said compressed data coding format, decompressing said data item to said standardised data coding format and transmitting said data item via said interface in said standardised data coding format.

Mobile communications terminal smart card

Orange Personal Communications Services Limited


An MR measuring assembly (3) with an MR device (2) is provided, which has a main magnet (4) generating a stray magnetic field and a platform (1), having a side border (5), on which the MR device (2) is placed. The border (5) marks an iso-contour surface of the stray field at a specified magnetic field strength. The platform (1) therefore forms a natural barrier that prevents people or objects being exposed to magnetic field strengths that are too high. To this end provision is additionally made, in accordance with the invention, for a step (15) for the marking of an iso-contour surface of a stray magnetic field of an MR device (2) at a specified magnetic field to be used.

Every MR device has a main magnet which generates a magnetic field in order, thereby, to align the nuclear spins of MR-active atoms such as the nuclear spins of hydrogen atoms. Generally, the main magnet consists of a current-carrying magnetic coil. As a rule this is made from superconductive material and therefore, as a rule, is massively cooled.
During the generation of the magnetic field by the main magnet, an unwanted stray field is also generated which decreases with increasing distance from the main magnet. These stray fields constitute a hazard to humans and to magnetic objects, meaning that there is a need to control the impact of the stray magnetic fields.
Safety procedures here are frequently based on what is known as the 5 Gauss line, in other words on the isosurface of the stray field at a field strength of 5 Gauss.
The term "line" is vague, since in reality it refers to a three-dimensional surface in the space. Consequently the text below shall refer to an iso-contour surface or an isosurface of a particular field strength, e.g. to the 5 Gauss iso-contour surface.
The geometry of the iso-contour surface of a particular field strength differs from one MR device to another, and therefore represents an individual property of a specific MR device which on the one hand depends on the main magnet and on the other on possible shielding. MR devices constructed in the same manner, however, also generate magnetic fields of the same shape.
In order to reduce the hazards ensuing from the stray field, a known technique is to shield the magnetic field generated by the main magnetic field with respect to the outside. This may take place through passive shielding, by magnetic materials being arranged outside of the main magnet. For example, the shield may also be integrated in room paneling of the room in which the MR device is set up. As a rule, however, the shielding is performed actively by means of a current-carrying, superconductive coil, which largely counterbalances the stray magnetic field.
A residual stray field remains despite shielding, however. While this decreases faster with increasing distance owing to the screening, safety-relevant field strengths are still frequently exceeded in the vicinity of the MR device. In particular, the 5 Gauss iso-contour surface is frequently located outside of the housing of the MR device, meaning that despite shielding, hazards still remain.
A known technique from the prior art is to apply markings in the form of tapes or similar to the floor at a distance from the MR device regarded as safe. However these are often unspecific and in addition may be accidentally crossed.


A method of inhibiting bacterial growth by contacting a bacteria with at least one disaccharide compound of General Formula I,

Bacteria have a great ability to generate resistance to drugs through lateral gene transfer, mutation of enzymes, or by expressing enzymes which actively pump out the drug or break it down. Over the past 10 years resistance to existing drugs has become a significant problem in many countries. No new antibacterial drugs have been developed over the past 15 years. Vancomycin is currently the drug of last resort to combat the multidrug resistant Gram-positive bacteria In many places vancomycin-resistant Staphylococcus aureus and Enterococci (VRE) have been discovered. There is thus a desperate need for a new antibacterial drug to replace the drug of last resort.
There are a host of cytoplasmic targets for the development of new antibacterials, such as gyrase inhibitors, protein synthesis inhibitors, muramyl cascade inhibitors and many more. The major hurdle in designing such drugs is that in addition to enzyme based activity these drugs need to cross the bacterial cell wall to exert their antibacterial effect. On the other hand, enzymes involved in the stage III synthesis of the bacterial cell wall exist on the cell wall exterior, and therefore drugs inhibiting these enzymes can exert their bactericidal or bacteriostatic effect without having to cross the cell wall. Penicillin, cephalosporin and vancomycin are drugs that act on the transpeptidase enzymes which control the final steps in the peptidoglycan biosynthesis. Moenomycin is known to act on the transglycosylase enzymes, which are similarly involved in the polymerization of disaccharide precursors. Moenomycin displays very high potency at MIC level, and is used in animal feed as a growth promoter.
Moenomycin is a lipid-linked pentasaccharide. Through extensive SAR experiments it was realised that smaller fragments of moenomycin were capable of exerting antibacterial activity. Trisaccharide fragments of moenomycin still display antibacterial activity, but are not sufficiently stable to be useful drugs. On the basis of this, Sofia and coworkers discovered a new series of disaccharides, carrying aromatic substituents in well defined positions around the disaccharide, which displayed significant MIC activity [WO0064915 and WO9926596].
A further class of disaccharide molecules, based on a sub-structure of vancomycin was shown to have antibacterial activity against vancomycin resistant bacteria. This class of molecules was subsequently demonstrated to contain transglycosylase inhibitors, and were not transpeptidase inhibitors as is vancomycin itself [WO9853813].


Provided are calcium salts of a 1,5-benzodiazepine derivative represented by the following formula (I):

The present invention relates to benzodiazepine derivatives having an important role in a medical field. More specifically, the invention relates to calcium salts of 1,5-benzodiazepine derivatives having a gastrin and/or CCK-B (cholecystokinin-B) receptor antagonism and at the same time having potent gastric acid secretion inhibitory action; preparation processes of the compounds; and drugs containing the compounds as an effective ingredient.
Cholecystokinin (CCK) is a gastrointestinal hormone which is produced by and released from duodenal and jejunal mucous membranes, and is known to have actions such as secretion of pancreatic juice, gallbladder constriction, and stimulation of insulin secretion. CCK is also known to be present in the cerebral cortex, hypothalamus, and hippocampus at a high concentration and exhibit actions such as inhibition of eating and hunger, augmentation of memory, and generation of anxiety. Gastrin is a gastrointestinal hormone which is produced by and released from G-cells distributed in the pylorus and is known to exhibit actions such as secretion of gastric acid and constriction of the pylorus and gallbladder. CCK and gastrin, having the same five amino acids in their C-terminals, express actions via receptors. CCK receptors are classified into CCK-A which are peripheral type receptors distributed in the pancreas, gallbladder, and intestines; and CCK-B which are central type receptors distributed in the brain. Since gastrin receptors and CCK-B receptors show similar properties in receptor-binding tests and have high homology, they are often called CCK-B/gastrin receptors. Compounds having antagonism to these receptors, for example, gastrin or CCK-B receptor, are presumed to be useful for prevention or treatment of gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis, pancreatitis, Zollinger-Ellison syndrome, vacuolating G-cell hyperplasia, basal-mucous-membrane hyperplasia, cholecystitis, attack of biliary colic, dysmotilities of alimentary canal, irritable bowel syndrome, certain types of tumors, eating disorders, anxiety, panic disorder, depression, schizophrenia, Parkinson""s disease, tardive dyskinesia, Gilles de la Tourette syndrome, drug dependence, and drug-withdrawal symptoms. Moreover, the compounds are expected to induce pain relief or to accelerate induction of pain relief by opioid medications (Folia Pharmacologica Japonica, Vol. 106, 171-180 (1995), Drugs of the Future, Vol. 18. 919-931 (1993), American Journal of Physiology, Vol. 269, G628-G646 (1995), American Journal of Physiology, Vol. 259, G184-G190 (1990), European Journal of Pharmacology, 261, 257-263 (1994), Trends in Pharmacological Science, Vol. 15, 65-66 (1994)).
As a gastrin receptor antagonist, proglumide is known as a remedy for gastric ulcer and gastritis. Proglumide""s affinity with gastrin or CCK-B receptors is however very low, and its curative effect is weak. It is reported that some benzodiazepine derivatives such as L-364,718 (devazepide, Japanese Patent Application Laid-Open (kokai) No. 63666/1986) and L-365,260 (Japanese Patent Application Laid-Open (kokai) No. 238069/1988) exhibit CCK-A receptor antagonism or CCK-B receptor antagonism. It is also disclosed that compounds having strong CCK-B receptor antagonism suppress pentagastrin-stimulated secretion of gastric acid (WO 94/438 and WO 95/18110). Administration in vivo of these compounds however does not always bring about satisfactory effects. In WO98/25911 and WO99/64403, the present inventors therefore disclosed 1,5-benzodiazepine derivatives having potent gastrin and/or CCK-B receptor antagonism and at the same time, having strong gastric acid secretion inhibitory action. There is however a demand for compounds which have potent gastrin and/or CCK-B receptor antagonism and gastric acid secretion inhibitory action, particularly strong in gastric acid secretion inhibitory action, and are suited for clinical use.
With the foregoing in view, the present inventors have carried out an extensive investigation. As a result, it has been found that compared with 1,5-benzodiazepine derivatives as specifically described in WO98/25911 and WO99/64403, calcium salts of 1,5-benzodiazepine derivatives having a specific structure, which salts fall within a range disclosed in WO98/25911 and WO99/64403 but are not specifically described therein, have markedly potent inhibitory activity against gastric acid secretion; and owing to low hygroscopicity and easy purification, are desirable as drugs from the viewpoint of quality maintenance so that they are useful as drugs, particularly preventives or remedies for various diseases of digestive tracts resulting from excessive secretion of gastric acid, leading to the completion of the invention.
In one aspect of the present invention, there are thus provided a calcium salt of a 1,5-benzodiazepine derivative represented by the following formula (I):
(wherein, R1 represents a lower alkyl group, R2 represents a phenyl or cyclohexyl group, and Y represents a single bond or a lower alkylene group); and a preparation process of the calcium salt.
In another aspect of the invention, there is also provided a gastric acid secretion inhibitor, which comprises, as an effective ingredient, a calcium salt of a 1,5-benzodiazepine derivative represented by the formula (I).
In a further aspect of the invention, there is also provided a drug comprising, as an effective ingredient, a calcium salt of a 1,5-benzodiazepine derivative represented by the formula (I), particularly, a preventive or remedy for gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis or Zollinger-Ellison syndrome.
In a still further aspect of the invention, there is also provided a pharmaceutical composition comprising a calcium salt of a 1,5-benzodiazepine derivative represented by the formula (I) and a pharmaceutically acceptable carrier, particularly, a pharmaceutical composition for preventing and/or treating gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis or Zollinger-Ellison syndrome.
In a still further aspect of the present invention, there is also provided the use of a calcium salt of a 1,5-benzodiazepine derivative represented by the formula (I) for the preparation of a preventive and/or remedy for gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis or Zollinger-Ellison syndrome.
In a still further aspect of the present invention, there is also provided a treating method of gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis or Zollinger-Ellison syndrome, which comprises administering a calcium salt of a 1,5-benzodiazepine derivative represented by the formula (I).
The term xe2x80x9clowerxe2x80x9d as used herein means a linear or branched carbon chain having 1 to 4 carbon atoms.
Accordingly, examples of the xe2x80x9clower alkyl groupxe2x80x9d include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, while those of the xe2x80x9clower alkylene groupxe2x80x9d include methylene, ethylene, propylene, butylene, methylmethylene, dimethylmethylene, 1-methylethylene, 1,1-dimethylethylene, 1-methylpropylene and 2-methylpropylene.
The term xe2x80x9chalogen atomxe2x80x9d as used herein means a fluorine, chlorine, bromine or iodine atom.
The term xe2x80x9cmetal atomxe2x80x9d as used herein means a metal atom which can be converted into a monovalent or divalent cation and examples include sodium, potassium and calcium atoms.
It is preferred that in the formula (I), R1 represents a branched C4 alkyl group, particularly, a tert-butyl group; R2 represents a cyclohexyl group and Y represents a single bond or dimethylmethylene.
The present invention not only embraces optically active isomers and diastereomers but also solvates such as hydrates and polymorphs.
Of the invention compounds (I), particularly preferred from the viewpoint of inhibitory action against gastric acid secretion and storage stability are calcium (R)-(xe2x88x92)-3-[3-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]benzoate (Compound of Example 1) and calcium (R)-(xe2x88x92)-2-[3-[3-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]phenyl]-2-methylpropionate (Compound of Example 4), with Compound of Example 1 being still more preferred.
The invention compounds (I) can be prepared by various synthesis processes in consideration of their essential skeleton or features of the constituent groups. The following are typical preparation processes of them. Preparation Process A:
(wherein, R1, R2 and Y have the same meanings as described above, Boc represents a tert-butoxycarbonyl group and X represents a halogen atom).
Step A1
Reaction of a 3-substituted aminobenzodiazepine derivative (V) with cyclohexanone leads to preparation of the corresponding 5-substituted derivative (VI). For the preparation of the 5-substituted derivative (VI) having a cyclohexyl group as R2, a catalyst such as platinum oxide or palladium carbon is added to a solution of the derivative (V) dissolved in acetic acid, followed by stirring under normal pressure or under pressure in a hydrogen atmosphere. Usually, this reaction can be carried out at room temperature, under warming or under heating. For the preparation of a 5-substituted derivative (VI) having a phenyl group as R2, on the other hand, a hydrogen acceptor such as cyclooctene or nitrobenzene is added to the derivative (V) in a solventless manner or in a solvent inert to the reaction such as xylene, and then a catalyst such as palladium carbon is added, followed by stirring. Usually, this reaction can be carried out under warming or heating.
Step A2
Reaction of the 5-substituted derivative (VI) with a halomethyl ketone compound (VII) leads to preparation of the corresponding 1,5-substituted derivative (VIII). This reaction is usually conducted by adding a base such as sodium hydride, potassium carbonate or potassium tert-butoxide to the 5-substituted derivative (VI), adding the compound (VII) to the resulting mixture and then adding, if necessary, a phase transfer catalyst such as tetrabutylammonium bromide. For the reaction, any solvent inert to the reaction is usable. Usually employed is an ether solvent such as tetrahydrofuran or dioxane, toluene, ethyl acetate, N,N-dimethylformamide or dimethylsulfoxide. Alternatively, the reaction can be effected in a two phase system such as water-toluene in the presence of a phase transfer catalyst such as tetrabutylammonium bromide. The reaction is usually conducted within a temperature range of xe2x88x9278 to 150xc2x0 C.
Step A3
The 1,5-substituted derivative (VIII) can be converted into an oxalate (III) of a 3-amino-1,5-benzodiazepine derivative after deprotection. The deprotection is effected by adding an acid such as hydrochloric acid or trifluoroacetic acid to the derivative (VIII). This reaction is usually conducted in the presence or absence of a solvent within a temperature range of from 0 to 100xc2x0 C. Examples of the solvent usable here include alcohols such as methanol and ethanol, halogen solvents such as chloroform and ether solvents such as dioxane and diethyl ether. The subsequent conversion into an oxalate is conducted in a manner known per se in the art by adding oxalic acid or hydrate thereof to the hydrolyzate obtained by the above-described reaction.
Step A4
Reaction of the oxalate (III) of a 3-amino-1,5-benzodiazepine derivative with Compound (IV) leads to preparation of the corresponding 1,5-benzodiazepine derivative (II). This reaction is usually conducted in the presence or absence of a base such as triethylamine within a range of 0xc2x0 C. to reflux temperature. For the reaction, any solvent inert to the reaction can be used and N,N-dimethylformamide or dimethylsulfoxide is usually employed.
Step A5
Aqueous ammonia is then added to the 1,5-benzodiazepine derivative (II), followed by treatment of the mixture by adding thereto a calcium chloride solution, whereby the invention compound (I) can be prepared. This reaction is usually conducted by adding aqueous ammonia under ice cooling, at room temperature, under warming or under heating; stirring the mixture; and then adding a calcium chloride solution. For this reaction, any solvent one inert to the reaction can be used and ethanol is usually employed.
Preparation Process B
(wherein, R1, R2 and Y have the same meanings as described above, R3 represents a hydrogen atom or a metal atom and X represents a halogen atom).
Step B1
Reaction of the oxalate (III) of a 3-amino-1,5-benzodiazepine derivative with Compound (IX) leads to preparation of the corresponding 3-phenoxycarbonylamino derivative (X). This reaction is usually conducted under ice cooling, at room temperature, under warming or under heating in the presence or absence of a base such as potassium carbonate or triethylamine. For the reaction, any solvent inert to the reaction is usable and ethyl acetate, tetrahydrofuran or N,N-dimethylformamide is usually employed.
Step B2
By adding an aniline derivative (XI) to the 3-phenoxycarbonylamino phenoxycarbonylamino derivative (X), the corresponding 1,5-benzodiazepine derivative (II) can be prepared. This reaction is usually carried out in the presence or absence of a base such as triethylamine or potassium carbonate within a range of 0xc2x0 C. to reflux temperature. For the reaction, any solvent inert to the reaction is usable and usually employed is dimethylsulfoxide or N,N-dimethylformamide.
The 1,5-benzodiazepine derivative (II) obtained in Step B2 can be introduced into the invention compound (I) in accordance with step A5 of Preparation Process A.
The invention compound (I) thus prepared is isolated and then purified by the ordinarily employed operation selected as needed from extraction, concentration, evaporation, crystallization, filtration, recrystallization, pulverization, and chromatography. The optically active invention compound (I) can be produced using a proper raw material compound, or by ordinarily employed racemic resolution method such as a method of introducing the compound into the corresponding diastereomer salt with a typical optically active acid such as dibenzoyl tartrate, followed by optical resolution; or a method of introducing the compound into the corresponding diastereomer compound, separating it and then subjecting the separated compound to Edman degradation.
The invention compound (I) can be administered orally or parenterally after incorporation therein a pharmaceutically acceptable carrier or adjuvant. For oral administration, the compound of the present invention may be formed into solid preparations such as tablets, powder, and capsules by using, in combination, proper additives, for example, excipients such as lactose, mannitol, corn starch, and crystalline cellulose; binders such as cellulose derivatives, gum arabic, and gelatin; disintegrators such as carboxymethyl cellulose calcium; lubricants such as talc and magnesium stearate. These solid preparations may be formed into enteric coating preparations by using a coating base such as hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate or methacrylate copolymer. Alternatively, they may be formed into liquid preparations such as solutions, suspensions, and emulsions.
For parenteral administration, the compound of the present invention may be formed into a liquid formulation for injection by using, in combination, water, ethanol, glycerin or ordinarily employed surfactant. It may also be formed into a suppository by using a suppository base.
The dose of the invention compound (I) varies depending on the dosage form, administration route, age, or symptoms. Orally, the dose is 1-1,000 mg, preferably 5-500 mg, per day for an adult and it is preferably administered once or 2 to 3 portions a day.
As described later, invention compounds (I) exhibit strong inhibitory action against secretion of gastric acid compared with the compounds as described in WO98/25911 and WO99/64403. In addition, they have low hygroscopicity and can be purified readily so that from the viewpoint of maintenance of its quality, they are excellent as a drug. Moreover, they exhibit potent antagonism against gastrin and/or CCK-B receptor, and therefore, they are useful for treatment, amelioration, or prevention of various diseases of digestive tracts resulting from excessive secretion of gastric acid, for example, gastric ulcer, duodenal ulcer, gastritis, reflux esophagitis, pancreatitis and Zollinger-Ellison syndrome. They are also useful for the treatment, amelioration or prevention of diseases related to gastrin and/or CCK-B receptor antagonism, such as vacuolating G-cell hyperplasia, basal-mucous-membrane hyperplasia, cholecystitis, attack of biliary colic, dysmotilities of alimentary canal, irritable bowel syndrome, certain types of tumors, eating disorders, anxiety, panic disorder, depression, schizophrenia, Parkinson""s disease, tardive dyskinesia, Gilles de la Tourette syndrome, drug dependence, and drug-withdrawal symptoms; and induction of pain relief or augmentation of induction of pain relief by an opioid medication.

Calcium salts of 1,5-benzodiazepine derivatives, process for producing the salts and drugs containing the same

Abstract: (wherein, R1 represents a lower alkyl group, R2 represents a phenyl or cyclohexyl group, and Y represents a single bond or a lower alkylene group); a process for preparing the salts; and drugs containing the same as the active ingredient.

Abstract: The compounds exhibit a potent inhibitory activity against the secretion of gastric acid and potent antagonism against gastrin and/or CCK-B receptor.


Magnetic resonance systems are provided which employ a shielded, asymmetric magnet to produce an offset dsv. The magnets include at least a first coil C1, which carries current in a first direction, and two coils C2 and C3, which are located at least in part within the internal envelope EC1 defined by the first coil and which carry current in an opposite direction to the first coil. The magnets are shielded by a shielding coil C4, which carries current in a direction opposite to that of the first coil, and/or a ferromagnetic structure (FS). The magnets can include additional coils, such as a fifth coil C5 at the magnet's distal end. The magnets can be used in, for example, orthopedic imaging.

The field of clinical magnetic resonance imaging (MRI) depends for its success on the generation of strong and pure magnetic fields. A major specification of the static field in MRI is that it has to be substantially homogeneous over a predetermined region, known in the art as the "diameter spherical imaging volume" or "dsv." Errors less than 20 parts per million peak-to-peak (or 10 parts per million rms) are typically required for the dsv. The uniformity of the field in the dsv is often analyzed by a spherical harmonic expansion.
The basic components of a typical magnetic resonance system for producing diagnostic images for human studies include a main magnet (i.e., a superconducting or non-superconducting magnet which produces the substantially homogeneous magnetic field (the B0 field) in the dsv), one or more shim magnets, a set of gradient coils, and one or more RF coils. Discussions of MRI, including magnet systems for use in conducting MRI studies, can be found in, for example, Mansfield et al., NMR in Imaging and Biomedicine, Academic Press, Orlando, Fla., 1982, and Haacke et al., Magnetic Resonance Imaging: Physical Principles and Sequence Design, John Wiley & Sons, Inc., New York, 1999. See also Crozier et al., U.S. Pat. No. 5,818,319, Crozier et al., U.S. Pat. No. 6,140,900, Crozier et al., U.S. Pat. No. 6,700,468, Dorri et al., U.S. Pat. No. 5,396,207, Dorri et al., U.S. Pat. No. 5,416,415, Knuttel et al., U.S. Pat. No. 5,646,532, and Laskaris et al., U.S. Pat. No. 5,801,609, the contents of which are incorporated herein by reference in their entireties.
In modern medical imaging, there is a distinct and long-felt need for smaller magnetic resonance systems. The typical aperture of a conventional MRI machine is a cylindrical space having a diameter of about 0.6-0.8 meters, i.e., just large enough to accept the subject's shoulders, and a length of about 2.0 meters or more. The dsv for such systems is located near the center of the aperture, which means that it is typically about a meter from the end of the aperture.
Not surprisingly, many people suffer from claustrophobia when placed in such a space. Also, the one-meter distance between the portion of the subject's body which is being imaged and the end of the magnet system means that physicians cannot easily assist or personally monitor a subject during an MRI procedure.
In addition to its effects on the subject, the size of the magnet is a primary factor in determining the cost of an MRI machine, as well as the costs involved in the siting of such a machine. In order to be safely used, MRI machines often need to be shielded so that the magnetic fields surrounding the machine at the location of the operator are below FDA-specified exposure levels. By means of shielding, the operator can be safely sited much closer to the magnet than in an unshielded system. Larger magnets require more shielding and larger shielded rooms for such safe usage, thus leading to higher costs.
Extremity MRI (also known as orthopedic MRI) is one of the growth areas of the MRI industry, with 20% of all MRI procedures in the United States in 2002 being performed on upper (e.g., arms, wrists, and elbows) and lower (e.g., legs, ankles, and knees) extremities. Extremity MRI systems are much smaller than whole-body or conventional MRI systems and are much easier to site, due both to their reduced size and reduced stray fields. They are therefore a low cost solution to the imaging of extremities.
While extremity MRI systems have a number of advantages to the subject and the operator, they represent a challenge in terms of the space available for the various coils making up the magnet and in terms of cooling those coils, whether they be superconducting or resistive coils. The close spacing between coils can also lead to high peak fields in some circumstances, as well as to substantial inter-coil and intra-coil stresses.
The present invention is directed to providing magnets which address these and other challenges of extremity MRI systems.

Shielded, asymmetric magnets for use in magnetic resonance imaging