A lead connection suitable for use in connecting a flexible coiled lead to an implantable device. The implantable device is provided with a threaded projection having an outer diameter sized with respect to the inner diameter of the lead's conductor coil to provide a secure interconnection therewith when attached thereto. The threaded projection is disposed on top and around a feedthrough pin projecting out of the implanted device's hermetic canister. The threaded projection is screwed into the conductor coil establishing sound electrical contact between the projection and the conductor. A strain relief collar surrounds the post and lead, and a twist-and-pull type connecting ring surrounds the base of the strain relief collar. The connecting post is prevented from being unscrewed from the conductor coil, since an unscrewing motion tends to tighten the conductor coil around the threaded post. Since no connecting structure is required at the connecting end of the lead, the lead can be cut to any appropriate length at the time of implant, thereby eliminating problems with excess implanted lead. If disconnection is required, the lead may be simply cut off just beyond the threaded connecting post, or the post may be unscrewed by applying inward radial or circumferential pressure on the conductor coils. In an alternative embodiment, the threaded projection is replaced with a tapered triangular post with either smooth or toothed edges, which is inserted into the coiled conductor lead.

A multitude of devices are known for which an electrical and mechanical coupling between a conductive lead and an electronic component must be established. For example, implantable medical devices such as cardiac pacemakers, cardioverters, defibrillators, neural stimulators, and the like, must be electrically and mechanically connected to one end of an electrical lead. In the case of an implantable medical device, there are particularly stringent design criteria with regard to the mechanical and electrical properties of the lead connection (i.e., the connection between a conductive lead and the device itself). In particular, the lead connection for an implantable device should preferably be highly reliable, both from a mechanical and from an electrical point of view. Any physical structure used in an implantable device lead connection should be small, light-weight, and biologically inert. A lead connection should preferably be capable of withstanding repeated flexing of the lead with respect to the device itself; this consideration is one reason that implantable leads are frequently of a coiled conductor type. Also, the lead connection should be strong enough to resist disconnection due to the various forces that may be exerted on the lead connection when implanted in a human body. Furthermore, since the implantation of a medical device is a delicate surgical process, the lead connection should be relatively simple to effectuate in the surgical environment.
Implanted medical devices such as pacemakers are battery-powered electronic devices which are susceptible to breakage, failure, or battery depletion. Thus, these devices may occasionally need to be explanted and/or replaced. Often, though, a lead associated with a device need not be removed along with the device. The previously implanted lead may be functioning adequately and may have even become ingrown within human tissue, making lead removal undesirable. Consequently, a further preferable feature of a lead connection for an implantable pulse generator is that it should allow for disconnection without damage to either the lead or the generator, in order that it may be removed and/or replaced without removal or replacement of the lead.
One prevalent means in the prior art for establishing the electrical and mechanical connection between a lead and an implantable pulse generator has been to provide a connector with molded-in connector blocks containing set screws. A terminal pin provided at the terminal end of the lead is received in a terminal receptacle in the connector, and the lead is then secured in place by tightening the set screws, which may also provide the requisite electrical contact between the lead conductor and the pacemaker's hermetic feedthrough elements.
With conventional connector and set screw lead connecting arrangements, proper tightening of the set screws is of critical importance. Over-torquing of a set screw can cause stripping of the set-screw threads or damage to the lead terminal or lead conductor. On the other hand, under-torquing of the set screw can lead to post-implant problems, since the lead terminal may become disengaged from the connector receptacle. In some cases, therefore, a specially designed set-screw driver or other tool may be provided as a means to ensure proper tightening. For instance, the tool may be designed to "break away" or flex after a proper amount of torque has been applied to the set screw.
A further complication with set-screw-type lead connector arrangements is that after tightening, the set screw must be sealed from bodily fluids which could cause corrosion or short-circuiting of the connector top or feed through. This sealing is typically accomplished through the use of grommets, which may be damaged during tightening of the set screw.
Several other techniques in the prior art for establishing the electrical and mechanical connection of a lead and an implantable medical device are briefly described in U.S. Pat. No. 4,540,236 to Peers-Trevarton, which patent is hereby incorporated by reference.
Implantable medical devices are typically implanted subcutaneously and may be implanted in a patient for many years. Accordingly, both for cosmetic reasons and for avoiding discomfort and pocket erosion at the implant site, it has always been an objective in the design of implantable devices that the devices be as small and lightweight as possible. In recent years, improvements in various technological fields, particularly those in the field of electronics, have enabled fully-featured implantable devices to be made smaller and smaller. It is believed by the inventors, for example, that a single-chamber demand pacemaker weighing less than five grams, approximately 2.8 centimeters in diameter, and having a volume of approximately 2.5 cubic centimeters is technologically feasible and could soon be commercially available. A conventional connector, even in its smallest practical configuration, would be larger and possibly heavier than an implantable device of such dimensions. The practical limitations on the miniaturization of a connector arise from the fact that the connector's set screws must not be made so small as to become difficult to seat a tool and tighten, or to become insufficiently strong. There are similar limitations on the miniaturization of other types of lead connection structures.
For any type of lead connection which requires a lead terminal to be disposed at the connected end of the lead, the length of the lead is determined at the time of manufacture of the lead, and cannot be changed at the time of implant. Since every patient's anatomy is unique and the implant site of a pacemaker may vary from patient to patient, there is typically some excess length of lead when a fixed-length lead is implanted. Typically, the excess length of lead is gathered together or simply wrapped around the implanted device. This can result in problems such as discomfort to the patient, lead failure due to kinks or bends in the excess length of lead, or displacement of the lead due to forces exerted on the excess length of lead. Additionally, the excess lead wrap may adversely effect the function of activity-based pulse generators by lying across the sensor-carrying face of the generator's housing.
It is believed by the inventors, therefore, that there exists a need for an alternative lead connection arrangement which is readily adaptable to smaller implantable devices. It is also believed by the inventors that it would be advantageous to provide a lead connection arrangement in which the length of the implanted lead can be customized for each patient.


An improved high pressure fuel injector and check valve disks therefore having annularly spaced passages including holes. A preferred embodiment for EMD diesel and dual fuel engines is a unit injector with a flat circular valve disk having a plurality of equally spaced holes located in a ring closely inward of the ledge of an associated valve cage and closely outward of the orifice or delivery opening of an associated valve seat. Alternative disk and injector embodiments are contemplated.

It is known in the art relating to unit fuel injectors for diesel engines to provide a positive displacement plunger pump with a controlled output to pump fuel at high pressure through a spray tip directly into an associated combustion chamber for combustion therein. A well known feature of such injectors is the provision of a flat check valve to prevent the back flow of fuel or combustion gases from the combustion chamber and spray tip into the plunger pump location. A known type of flat check valve is in the form of a small disk having the outer edges scalloped to provide flow passages for fuel when the valve is open and seated upon an annular seat open internally to a flow chamber. Such check valves have been used for many years in some of the unit fuel injectors made by General Motors and subsequently by Diesel Technology Corporation, including those supplied for use in the well known Electro-Motive Division (EMD) diesel and dual fuel engines manufactured for railroad locomotives and other applications.


A high availability on-line transaction processing (OLTP) system utilizes both hardware and software. Geographically separated primary (live) and backup (shadow) communications servers link live and shadow OLTP systems to geographically separated live and shadow Wide Area Networks and remote client computers. The remote client computers communicate with the live and shadow OLTP systems through their respective live and shadow WANs and communications servers. The live OLTP system sends "keep-alive" messages to the shadow system via the dedicated circuits on a frequent basis. If the shadow OLTP system does not receive a keep-alive message from the live system within a designated time interval, it sends "probe messages" to the live communications servers and live OLTP system, via the shadow WAN, client computers and live WAN to determine their status. If the live communications servers respond to the probe message(s) but the live OLTP system does not, the shadow OLTP system deduces that the live OLTP system failed and automatically takes over the role of the live system without operator intervention.

1. Field of the Invention
The present invention relates to computer network systems. More particularly, it relates to high availability on-line transaction processing systems.
2. The Prior Art
Alsberg and Day [1976] introduced the idea of "System Pairs" to protect against simultaneous faults through duplication and geographical separation of on-line systems. They reasoned that weather, power failures, computer operators and sabotage were unlikely to fault both systems at the same time. A fundamental problem with System Pairs is that when the backup system stops receiving data from the primary system, there is no automatic way to determine if the primary system failed, or if the circuit(s) connecting the primary and backup systems failed or both.
Gray and Reuter (Transaction Processing: Concepts and Techniques, 1993) proposed that the computer operators at the primary and backup sites consult one another to determine if the primary system failed. If it did, the operator at the backup site instructs the backup to takeover the role of the primary system. While the operators sort out the problem, the system may be down. If the operators cannot communicate for any reason, for example, fire, flood or earthquake, the system may be down for a longer period of time.
Digital Equipment Corp. markets a "Disaster-Tolerant System," which requires computer operator action or an additional computer at a third site to cast the deciding "vote" if the primary and backup systems cannot communicate. In addition, the primary and backup sites must be located within 24.8 miles of each other. This does not provide enough geographical separation to protect both sites against the effects of an earthquake, hurricane or flood.
Another important issue effecting availability is how the client computers communicate with the primary and backup systems. The system shown by Gray and Reuter depicts the client computers with separate connections to the primary and backup systems. The client computer sends all its messages to the primary system while it's operable. If the primary system fails, the backup system takes over and the client communicates with the backup system via its connection to the backup system. Unfortunately, if the circuit to the primary system fails, and the primary system is operable, the client is denied service.

High availability on-line transaction processing system


An image processing device 102 includes a background-object reference image estimation unit 1, a background-object optical flow calculation unit 2, moving-object reference image estimation units 4 and 9, moving-object heat-haze fluctuation calculation units 5, 6, 7, 10 and 11, and a motion correction unit 3. The image processing device 102 is configured such that optical flow of a background object and heat-haze fluctuation of a moving-object are obtained from input images inputted in succession, partial images of the input images are moved so as to cancel the heat-haze fluctuation, and a corrected image, which has the heat-haze fluctuation upon the background object and the moving-object within the input images removed, is generated.

Recently, there have been proposed many image processing methods for improving degradation in image quality (restoring the image quality) when an image of an object captured by a camera or the like is degraded to allow the object to be favorably perceived.
In, this regard, conventional techniques are disclosed in Patent Document 1 and Patent Document 2 (referred to as Conventional Technique 1 and Conventional Technique 2). Conventional Technique 1 discloses a fluctuation noise reduction processing method in which image deterioration such as blur of an image is small by extracting fluctuation components present in continuous images in time series as motion vectors between images, tracking the motion vectors to obtain a center of fluctuation, and rearranging partial images or pixels becoming a starting point of the fluctuation in the center position. Further, Conventional Technique 2 discloses a technique of correcting distortion of an image due to fluctuation of a monitoring camera in real time, and identifying a moving object of interest in the moving image online. Further, the inventors of the present patent application have filed, as Japanese Patent Application No. 2010-253727 (Japanese Patent Application Publication No. 2012-104018) (Conventional Technique 3), a technique for improving the quality of an image by calculating optical flow for input images and a reference image which is a time average of the input images, calculating local fluctuations (motion vectors) of the input images, and moving partial images of the input images so as to cancel the heat haze fluctuation using the motion vectors.
Patent Document 1: Japanese Patent Application Publication No. H3-95686
Patent Document 2: Japanese Patent No. 4040651
According to Conventional Techniques 1 to 3, in a case where the quality of an image is degraded due to camera shake, heat haze or the like when the image is captured by a camera, it is possible to improve the image quality degradation of a background object and obtain a favorable image. However, there is a problem that it is impossible to correct the fluctuation of the heat haze on a moving object.


Techniques for storage management involve: in accordance with a determination that an input/output (I/O) request of a storage system is received, determining a target storage device to which the I/O request is directed. The techniques further involve: in accordance with a determination that the target storage device is a storage device of a first type, processing the I/O request by accessing a memory of the storage system. The techniques further involve: in accordance with a determination that the target storage device is a storage device of a second type different from the first type, processing the I/O request without accessing the memory, the storage device of the second type having an access speed higher than that of the storage device of the first type. Accordingly, such techniques can improve performance of a storage system.

Generally, a storage system may have multiple types of storage devices, such as non-volatile storage devices. These storage devices may include traditional storage devices, for example, hard disk drive (HDD) storage devices, solid state drive (SSD) storage devices, NAND flash storage devices, and so on. In addition, storage devices in a storage system may also include storage devices employing emerging technologies. For example, 3D XPoint is a non-volatile memory (NVM) technology that has appeared in recent years. In 3D XPoint storage devices, bit storage is based on a change of bulk resistance, in conjunction with a stackable cross-gridded data access array.
As a kind of storage-level memory (SCM), a 3D XPoint storage device has the advantage of no data loss when power-down, compared with a dynamic random access memory (DRAM). In addition, compared with traditional storage devices, it not only reads and writes faster, but also supports byte-level access. Traditional storage devices normally require reading and writing according to pages and data may be erased according to a data block of several hundred pages. Therefore, 3D XPoint storage devices can implement data storage with high performance and flexibility. In theory, 3D XPoint storage devices are about 1000 times faster than traditional NAND Flash storage devices, and thus its access latency may be very low, around merely 100 nanoseconds.
However, traditional storage systems have not been designed and optimized for such storage devices that support fast access (for example, 3D XPoint storage devices, hereinafter referred to as fast storage devices for short), so that the performance advantages of such storage devices cannot be fully utilized, resulting in a poor user experience in many scenarios.

Optimized access to high-speed storage device


A hard butter additive composition which comprises the middle melting point fraction of random interesterified palm stearin is provided. The hard butter additive composition of the present invention is useful for admixing with raw materials for hard butter which are not transisomerized fats nor lauric fats, and can prevent fat blooming and/or graining and improve mold removability of hard butter products such as chocolate or center cream without a tempering process.

In general, hard butter in a broad sense including cacao butter mostly used for producing chocolate, or fats used for manufacturing margarine/shortening usually exist in several polymorphic forms. Change in crystal form will proceed in hard butter products leading to crystal growth, and causes undesirable phenomena, e.g., so called blooming of the solidified product or graining which is a grainy taste development in cream type products.
Usually, a tempering treatment, a heat treatment to transfer the crystal form of the fat components uniformly, is employed in manufacturing chocolate or margarine/shortening to avoid blooming and/or graining problems. However, since the tempering is a time and energy consuming process and requires precise temperature control, it has been desired to eliminate the tempering process from confectionery manufacturing processes.
There are some fats and oils known in the art that do not need tempering, such as trans-isomerized triglyceride compositions which are high in trans fatty acids (trans fats) and triglyceride compositions high in lauric fatty acid (lauric fats).
However, trans fats are known to develop undesirable flavor due to isomerization which spoils the taste of the resulting chocolate. The lauric fats generate an undesirable "soapy" flavor under some storage conditions. In order to avoid these problems, hard butter compositions that do not need to be tempered, and that do not contain trans fats or lauric fats are desired.
Heretofore, various studies have been made to prevent or control fat blooming of non-transisomerized or non-lauric hard butter compositions. Such studies include improving the hard butter composition through addition of ester-interchanged triglycerides which have long chain and short chain fatty acid residues (U.S. Pat. No. 3,491,677), addition of a surfactant (JP-A-2-249452 and JP-A-3-247240), and addition of an anti-blooming agent comprising B.sub.2 O, wherein B represents behenic acid residue and O represents oleic acid residue (JP-A-62-6635). However, those improved hard butter compositions still require tempering.
Recently, confectionery fat compositions that do not need to be tempered and do not contain trans fats or lauric fats have been proposed. For example, JP-A-61-224934 discloses a hard butter composition containing SSU triglycerides (1,2-saturated-3-unsaturated triglycerides) in the other raw materials for hard butter exhibits good anti-blooming property when molded without tempering treatment. U.S. Pat. No. 5,424,091 discloses a non-tempered fat composition which consists of defined amounts of SSU triglycerides, trisaturated triglycerides, and 1,3-saturated-2-unsaturated triglycerides.
These prior art hard butter compositions have accomplished the improved fat blooming or graining resistance through crystal stabilization by means of a defined amount of SSU and they can provide chocolate or chocolate coating having no blooming problem without tempering. However, since solidified hard butter products, such as solid chocolate, manufactured from those prior art hard butter compositions exhibit poor contraction upon cooling, they stick in the mold and generate problems of workability. Further, SSU type triglycerides are usually made by introducing unsaturated fatty acid, such as oleic acid, selectively in the 1 or 3 position of trisaturated triglyceride through an enzymatic treatment which requires complex procedures and high costs.

Process of making a hard butter composition


A lock mechanism for use with a swinging door on hinges with no outside key involved. A fixture is affixed to the door frame opposite the hinges. A through bore allows a rod with a handle at one end and threads at the opposite end to pass through the door and be threaded into a threaded aperture in the fixture to prevent hinged movement of the door. The parts may be cadmium plated for corrosion protection.

1. Field of the Invention
The present invention provides a door locking system for providing greatly enhanced security and peace of mind.
2. Brief Description of the Prior Art
Most criminals are looking for an easy hit; a house that they can break into quickly. Dead bolts are the most common way to provide additional lock security but have not proven wholly satisfactory in use. With a dead bolt, the lock mechanism is secured to the inside of the door on the side of the door opposite from its hinged side. A dead bolt is slidably mounted within the lock mechanism and, in its locking position, extends through a strike plate and into the door jamb. One problem with dead bolts is that the security provided by the lock is limited by the short distance that the bolt extends into the jamb such that the door is subject to being kicked in or pushed open by a man running his shoulder into it.
Dead bolts are also susceptible to a practice called "lock bumping." To bump a lock, a thief will insert a special key called a bump key into the dead bolt, then tap on it with a blunt object like the handle of a screwdriver. The bump key transfers the force of the bumps into the lock's pins, jolting them into an unlocked position without damaging the lock or leaving any trace of a forced entry.
Most burglars spend only a few minutes trying to break inside. While there is no way to secure a home completely from a sophisticated or determined burglar, a locking system that makes it more difficult to break inside would be desirable.


A method of cleaning and preparing a quantity of produce for sale that includes the steps of placing the produce on a conveyor and rotating it so as to expose all sides thereof, spraying the produce with a mixture of water and ozone so as to cover the produce and so as to loosen dirt and mold, and kill bacteria, placing the produce on a rotating brush bed so as to brush the produce and remove the loosened dirt and mold, spraying the produce with a further mixture of water and ozone so as to clean, rinse and disinfect the produce, removing excess water from the produce, applying food grade wax to the produce, and drying the produce.

1. Field of the Invention
The present invention relates to a method of cleaning and preparing a quantity of produce, such as fruits and/or vegetables, the method providing a safe and sanitary cleansing process which does not excessively raise the pulp temperature of the produce and does not require the use of detergents and/or chlorine as a cleaning agent.
2. Description of the Related Art
Fresh produce, such as fruits and vegetables, will generally undergo a certain degree of processing or preparation before it is presented for sale. The primary reasons for this processing relates to the dirt and/or pesticides which may be on the produce when picked, and to a general desire to place the produce in its most presentable, appealing condition for an extended period of time during sale.
In order to provide the necessary processing, most produce processing facilities generally pass the produce through an elaborate washing and sanitizing system. Generally, however, conventionally utilized washing processes involve the use of a cleansing agent to remove dirt and/or chemicals from the surface of the food. Typically, the cleaning agents utilized include soaps or detergents, or a concentrated quantity of chlorine which is sprayed onto the food. Subsequently, the produce is rinsed and dried such that a food grade wax may be applied to the cleaned produce. In particular, the food grade wax provides a more attractive exterior appearance to the produce, and provides a certain degree of preservation and added shelf life to the produce. The food grade wax, however, which must necessarily be added in a liquefied form, must also be dried onto the produce before the produce is ready to be shipped. Along these lines, in addition to the concerns associated with utilizing detergents or chlorine in the cleansing of the produce, both due to the nature of those chemicals and the normal, limited cleansing abilities thereof, a further concern associated with conventional preparation processes relates to the drying of the produce. In particular, conventional produce washing and drying processes dry the produce utilizing heat obtained from direct gas fired heaters or steam from a boiler. Moreover, temperatures of between 115 to 125 degrees are achieved. Naturally, these high temperate, while drying the produce will also substantially raise the pulp temperature of the produce resulting in damage or other premature degradation of the produce.
Accordingly, it would be beneficial to provide a method of cleaning and preparing produce which is efficient to utilize, does not use potentially harmful detergents or chlorine, and does not excessively raise the pulp temperature of the produce in order to effectuate drying thereof.

Method of cleaning and preparing a quantity of produce for sale


A communications system includes a first and second modem coupled together via a communications link. The first modem has at least two user devices coupled thereto, and modulates data generated by the user devices on a plurality of tone carriers for transmission to the second modem. The first modem determines the number of user devices coupled to it. Based upon the number of user devices determined, the first modem divides the plurality of tone carriers into a number of subsets corresponding to the number of user devices based upon a predetermined criterion. The first modem then allocates a subset of tone carriers to a respective user device. In one embodiment, the usage rate of each user device is determined, and the tone carriers are reallocated to different subsets as a function of the usage rate of each respective user device.

1. Field of the Invention
The present invention relates generally to modem communications, and, more particularly, to a method and apparatus for allocating tones to multiple end-users in a discrete multi-tone (DMT) modem communications system.
2. Description of the Related Art
The telecommunications industry has undergone explosive growth over the past several years. A significant contribution to this growth has been the high demand for modem communication services, such as the Internet, which extend beyond traditional voice communications. Conventional landline telephone networks, which offer xe2x80x9cPlain Old Telephone Servicexe2x80x9d (POTS), currently provide these modem services by transmitting data over a voice channel. The landline telephone network reaches nearly every household and business throughout the world, and has proven to be a relatively inexpensive medium for data transmission. Although dedicated data transmission networks also exist to provide these modern services, they are considerably more expensive to use. In addition, these data networks are not readily accessible to the general public, at least compared to the accessibility of the landline telephone network. Accordingly, a substantial portion of the public relies heavily on the landline telephone network as a cheaper alternative for providing these services.
With the increasing popularity of these modem services, however, the landline telephone network has rapidly become inefficient in handling these services due to limited bandwidth constraints. Currently, the landline network""s 56.6 kilobits per second (KBPS) data transfer rate is not fast enough to keep up with the increasing complexity of these services. In addition, projected demand for other services, such as video-on-demand, teleconferencing, interactive TV, etc. is likely to exacerbate the limited bandwidth problem.
To meet the demand for high-speed data communications, designers have sought innovative and cost-effective solutions that take advantage of the existing landline telephone network infrastructure. Of these solutions, the Digital Subscriber Line (DSL) technology, uses the existing landline network infrastructure of POTS for broadband communications, thus enabling an ordinary twisted pair to transmit video, television, and high-speed data.
DSL technology leaves the existing POTS service of the landline network undisturbed. Traditional analog voice band interfaces use the same frequency band (i.e., 0-4 kHz) for data transmission as for telephone service, thereby preventing concurrent voice and data use. Asymmetric Digital Subscriber Line (ADSL) technology, a popular version of DSL, operates at frequencies above the voice channels from 100 kHz to 1.1 MHz. Thus, a single ADSL line is capable of offering simultaneous channels for voice and data transmission. The ADSL standard is fully described in ANSI T1.413 Issue 2, entitled xe2x80x9cInterface Between Networks and Customer Installationxe2x80x94Asymmetric Digital Subscriber Line (ADSL) Metallic Interface, Rev. R4, dated Jun. 6, 1998, the entire contents of which is incorporated herein by reference.
ADSL systems utilize digital signal processing (DSP) to increase throughput and signal quality through common copper telephone wire. ADSL systems provide a downstream data transfer rate from the ADSL Point-of-Presence (POP) to the subscriber location at speeds of about 6 Megabits per second (MBPS), which is more than one-hundred times faster than the conventional 56.6 KBPS transfer rate currently available through the landline network.
The technology employed in T1.413-type ADSL modems is discrete multi-tone (DMT). The standard defines 256 discrete tones, with each tone representing a carrier signal that can be modulated with a digital signal for transmitting data. The specific frequency for a given tone is 4.3125 kHz multiplied by the tone number. Tone 1 is reserved for the voice band and tones 2-7 are reserved for the guard bands. Data is not transmitted near the voice band to allow for simultaneous voice and data transmission on a single line. Thus, the guard bands aid in isolating the voice band from the ADSL data bands. Typically, a splitter may be used to isolate any voice band signal from the data tones. Tones 8-32 are used to transmit data upstream (i.e., from the user), and tones 33-256 are used to transmit data downstream (i.e., to the user). Alternatively, all of the data tones 8-256 may be used for downstream data transmission, and the upstream data present on tones 8-32 could be detected using an echo cancellation technique, as is well established in the art. Because a larger number of tones are used for downstream communication than for upstream communication, the transfer is said to be asymmetric.
ADSL technology significantly boosts the data transfer rate of the landline telephone network to levels at least commensurate with, if not exceeding, the transfer rates of present data networks. Assuming all 256 tones are free of impairments, the data transfer rate defined by the ADSL standard is about 6 MBPS downstream and 640 KBPS upstream, significantly dwarfing today""s data transfer rate standard on the landline telephone network.
Although ADSL technology dramatically increases the available bandwidth to a single user, the user generally does not require all of the additional bandwidth for his or her own purposes. As a result, a substantial portion of the additional bandwidth is not utilized. As such, the unused bandwidth is essentially a wasted resource.
The present invention is directed to overcoming, or at least reducing the effects of, one or more of the problems set forth above.
In one aspect of the present invention, a method is provided for allocating a plurality of tone carriers in a communications system. The communications system includes a first modem and second modem coupled via a communications link. The first and second modems modulate data on the plurality of tone carriers for transmitting data over the communications link. The method includes determining a number of user devices that are to be coupled to the first modem. The plurality of tone carriers are divided into a number of subsets in accordance with a predetermined criterion, where the number of subsets corresponds to the number of user devices determined. Each subset of the plurality of tone carriers is allocated to a respective one of the determined number of user devices.
In another aspect of the present invention, an apparatus is provided that includes a first and second modem adapted to modulate data on a plurality of tone carriers. A communications link couples the first and second modem together and transfers data therebetween. The apparatus further includes at least two user devices adapted to couple to the first modem. The first modem divides the plurality of tone carriers into at least two subsets in accordance with a predetermined criterion, and allocates each subset of tone carriers to a respective one of the at least two user devices.

Method and apparatus for allocating tones to a plurality of users in a multi-tone modem communications system


Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.

The present invention concerns media adapted for injection into living bodies, e.g. for the purpose of ultrasonic echography and, more particularly, injectable liquid compositions comprising microbubbles of air or physiologically acceptable gases as stable dispersions or suspensions in an aqueous liquid carrier. These compositions are mostly usable as contrast agents in ultrasonic echography to image the inside of blood-stream vessels and other cavities of living beings, e.g. human patients and animals. Other uses however are also contemplated as disclosed hereafter.
The invention also comprises dry compositions which, upon admixing with an aqueous carrier liquid, will generate the foregoing sterile suspension of microbubbles thereafter usable as contrast agent for ultrasonic echography and other purposes.
It is well known that microbodies like microspheres or microglobules of air or a gas, e.g. microbubbles or microballoons, suspended in a liquid are exceptionally efficient ultrasound reflectors for echography. In this disclosure the term of xe2x80x9cmicrobubblexe2x80x9d specifically designates air or gas globules in suspension in a liquid which generally results from the introduction therein of air or a gas in divided form, the liquid preferably also containing surfactants or tensides to control the surface properties thereof and the stability of the bubbles. More specifically, one may consider that the internal volume of the microbubbles is limited by the gas/liquid interface, or in other words, the microbubbles are only bounded by a rather evanescent envelope involving the molecules of the liquid and surfactant loosely bound at the gas to liquid junction boundary.
In contrast, the term of xe2x80x9cmicrocapsulexe2x80x9d or xe2x80x9cmicroballoonxe2x80x9d designates preferably air or gas bodies with a material boundary or envelope formed of molecules other than that of the liquid of suspension, e.g. a polymer membrane wall. Both microbubbles and microballoons are useful as ultrasonic contrast agents. For instance injecting into the blood-stream of living bodies suspensions of gas microbubbles or microballoons (in the range of 0.5 to 10 xcexcm) in a carrier liquid will strongly reinforce ultrasonic echography imaging, thus aiding in the visualization of internal organs. Imaging of vessels and internal organs can strongly help in medical diagnosis, for instance for the detection of cardiovascular and other diseases.
The formation of suspensions of microbubbles in an injectable liquid carrier suitable for echography can follow various routes. For instance in DE-A-3529195 (Max-Planck Gesell.), there is disclosed a technique for generating 0.5-50 xcexcm bubbles in which an aqueous emulsified mixture containing a water soluble polymer, an oil and mineral salts is forced back and forth, together with a small amount of air, from one syringe into another through a small opening. Here, mechanical forces are responsible for the formation of bubbles in the liquid.
M. W. Keller. et al. (J. Ultrasound Med. 5 (1986). 439-8) have reported subjecting to ultrasonic cavitation under atmospheric pressure solutions containing high concentrations of solutes such as dextrose, Renografin-76, Iopamidol (an X-ray contrast agent), and the like. There the air is driven into the solution by the energy of cavitation.
Other techniques rely on the shaking of a carrier liquid in which air containing microparticles have been incorporated, said carrier liquid usually containing, as stabilizers, viscosity enhancing agents, e.g. water soluble polypeptides or carbohydrates and/or surfactants. It is effectively admitted that the stability of the microbubbles against decay or escape to the atmosphere is controlled by the viscosity and surface properties of the carrier liquid. The air or gas in the microparticles can consist of inter-particle or intra-crystalline entrapped gas, as well as surface adsorbed gas, or gas produced by reactions with the carrier liquid, usually aqueous. All this is fully described for instance in EP-A-52.575 (Ultra Med. Inc.) in which there are used aggregates of 1-50 xcexcm particles of carbohydrates (e.g. galactose, maltose, sorbitol, gluconic acid, sucrose, glucose end the like) in aqueous solutions of glycols or polyglycols, or other water soluble polymers.
Also, in EP-A-123.235 and 122.624 (Schering, see also EP-A-320.433) use is made of air trapped in solids. For instance, 122.624 claims a liquid carrier contrast Composition for ultrasonic echography containing microparticles of a solid surfactant, the latter being optionally combined with microparticles of a non-surfactant. As explained in this document, the formation of air bubbles in the solution results from the release of the air adsorbed on the surface of the particles, or trapped within the particle lattice, or caught between individual particles, this being so when the particles are agitated with the liquid carrier.
EP-A-131.540 (Schering) also discloses the preparation of microbubbles suspensions in which a stabilized injectable carrier liquid, e.g. a physiological aqueous solution of salt, or a solution of a sugar like maltose, dextrose, lactose or galactose, without viscosity enhancer, is mixed with microparticles (in the 0.1 to 1 xcexcm range) of the same sugars containing entrapped air. In order that the suspension of bubbles can develop within the liquid carrier, the foregoing documents recommend that both liquid and solid components be violently agitated together under sterile conditions; the agitation of both components together is performed for a few seconds and, once made, the suspension must then be used immediately, i.e. it should be injected within 5-10 minutes for echographic measurements; this indicates that the bubbles in the suspensions are not longlived and one practical problem with the use of microbubbles suspensions for injection is lack of stability with time. The present invention fully remedies this drawback.
In U.S. Pat. No. 4,466,442 (Schering), there is disclosed a series of different techniques for producing suspensions of gas microbubbles in a liquid carrier using (a) a solution of, a tenside (surfactant) in a carrier liquid (aqueous) and (b) a solution of a viscosity enhancer as stabilizer. For generating the bubbles, the techniques used there include forcing at high velocity a mixture of (a), (b) and air through a small aperture; or injecting (a) into (b) shortly before use together with a physiologically acceptable gas; or adding an acid to (a) and a carbonate to (b), both components being mixed together Just before use and the acid reacting with the carbonate to generate CO2 bubbles: or adding an over-pressurized gas to a mixture of (a) and (b) under storage, said gas being released into microbubbles at the time when the mixture is used for injection.
The tensides used in component (a): of U.S. Pat. No. 4,466,442 comprise lecithins; esters and ethers of fatty acids and fatty alcohols with polyoxyethylene and polyoxyethylated polyols like sorbitol, glycols and glycerol, cholesterol; and polyoxy-ethylene-polyoxypropylene polymers. The viscosity raising and stabilizing compounds include for instance mono- and polysaccharides (glucose, lactose, sucrose, dextran, sorbitol); polyols, e.g. glycerol, polyglycols; and polypeptides like proteins, gelatin, oxypolygelatin, plasma protein and the like.
In a typical preferred example of this document, equivalent volumes of (a) a 0.5% by weight aqueous solution of Pluronic(copyright) F-68 (a polyoxypropylene-polyoxyethylene polymer) and (b) a 10% lactose solution are vigorously shaken together under sterile conditions (closed vials) to provide a suspension of microbubbles ready for use as an ultrasonic contrast agent and lasting for at least 2 minutes. About 50% of the bubbles had a size below 50 xcexcm.
Although the achievements of the prior art have merit, they suffer from several drawbacks which strongly limit their practical use by doctors and hospitals, namely their relatively short life-span (which makes test reproducibility difficult), relative low initial bubble concentration (the number of bubbles rarely exceeds 104-105 bubbles/ml and the count decreases rapidly with time) and poor reproducibility of the initial bubble count from test to test (which also makes comparisons difficult). Also it is admitted that for efficiently imaging certain organs, e.g. the left heart, bubbles smaller than 50 xcexcm, preferably in the range of 0.5-10 xcexcm, are required: with longer bubbles, there are risks of clots and consecutive emboly.
Furthermore, the compulsory presence of solid microparticles or high concentrations of electrolytes and other relatively inert solutes in the carrier liquid may be undesirable physiologically in some cases. Finally, the suspensions are totally unstable under storage and cannot be marketed as such; hence great skill is required to prepare the microbubbles at the right moment just before use.
Of course there exists stable suspensions of microcapsules, i.e. microballoons with a solid, air-sealed rigid polymeric membrane which perfectly resist for long storage periods in suspension, which have been developed to remedy this shortcoming (see for instance K. J. Widder, EP-A-324.938); however the properties of microcapsules in which a gas is entrapped inside solid membrane vesicles essentially differ from that of the gas microbubbles of the present invention and belong to a different kind of art; for instance while the gas microbubbles discussed here will simply escape or dissolve in the blood-stream when the stabilizers in the carrier liquid are excreted or metabolized, the solid polymer material forming the walls of the aforementioned micro-balloons must eventually be disposed of by the organism being tested which may impose a serious afterburden upon it. Also capsules with solid, non-elastic membrane may break irreversibly under variations of pressure.
The composition of the present invention, as defined in claim 1, fully remedies the aforementioned pitfalls.
The term xe2x80x9clamellar formxe2x80x9d defining the condition of at least a portion of the surfactant or surfactants of the present composition indicates that the surfactants, in strong contrast with the microparticles of the prior art (for instance EP-A-123.235), are in the form of thin films involving one or more molecular layers (in laminate form). Converting film forming surfactants into lamellar form can easily be done for instance by high pressure homogenization or by sonication under acoustical or ultrasonic frequencies. In this connection, it should be pointed out that the existence of liposomes is a well known and useful illustration of cases in which surfactants, more particularly lipids, are in lamellar form.
Liposome solutions are aqueous suspensions of microscopic vesicles, generally spherically shaped, which hold substances encapsulated therein. These vesicles are usually formed of one or more concentrically arranged molecular layers (lamellae) of amphipatic compounds, i.e. compounds having a lipophobic hydrophilic moiety and a lipophilic hydrophobic moiety. See for instance xe2x80x9cLiposome Methodologyxe2x80x9d, Ed. L. D. Leserman et al, Inserm 136, May 2-8, 1982). Many surfactants or tensides, including lipids, particularly phospholipids, can be laminarized to correspond to this kind of structure. In this invention, one preferably uses the lipids commonly used for making liposomes, for instance the lecithins and other tensides disclosed in more detail hereafter, but this does in no way preclude the use of other surfactants provided they can be formed into layers or films.
It is important to note that no confusion should be made between the present invention and the disclosure of Ryan (U.S. Pat. No. 4,900,540) reporting the use of air or gas filled liposomes for echography. In this method Ryan encapsulates air or a gas within liposomic vesicles: in embodiments of the present invention microbubbles or air or a gas are formed in a suspension of liposomes (i.e. liquid filled liposomes) and the liposomes apparently stabilize the microbubbles. In Ryan, the air is inside the liposomes, which means that within the bounds of the presently used terminology, the air filled liposomes of Ryan belong to the class of microballoons and not to that of the microbubbles of the present invention.
Practically, to achieve the suspensions of microbubbles according to the invention, one may start with liposomes suspensions or solutions prepared by any technique reported in the prior art, with the obvious difference that in the present case the liposomic vesicles are preferably xe2x80x9cunloadedxe2x80x9d, i.e. they do not need to keep encapsulated therein any foreign material other than the liquid of suspension as is normally the object of classic liposomes. Hence, preferably, the liposomes of the present invention will contain an aqueous phase identical or similar to the aqueous phase of the solution itself. Then air or a gas is introduced into the liposome solution so that a suspension of microbubbles will form, said suspension being stabilized by the presence of the surfactants in lamellar form. Notwithstanding, the material making the liposome walls can be modified within the scope of the present invention, for instance by covalently grafting thereon foreign molecules designed for specific purposes as will be explained later.
The preparation of liposome solutions has been abundently discussed in many publications, e.g. U.S. Pat. No. 4,224,179 and WO-A-88/09165 and all citations mentioned therein. This prior art is used here as reference for exemplifying the various methods suitable for converting film forming tensides into lamellar form. Another basic reference by H. C. Woodle and D. Papahadjopoulos is found in xe2x80x9cMethods in Enzymologyxe2x80x9d 171 (1989), 193.
For instance, in a method disclosed in D. A. Tyrrell et al, Biochimica and Biophysica Acta 457 (1976), 259-302, a mixture of a lipid and an aqueous liquid carrier is subjected to violent agitation and thereafter sonicated at acoustic or ultrasonic frequencies at room or elevated temperature. In the present invention, it has been found that sonication-without agitation is convenient. Also, an apparatus for making liposomes, a high pressure homogenizer such as the Microfluidizer(copyright), which can be purchased from Microfluidics Corp., Newton, Mass. 02164 USA, can be used advantageously. Large volumes of liposome solutions can be prepared with this apparatus under pressures which can reach 600-1200 bar.
In another method, according to the teaching of GB-A-2,134,869 (Squibb), microparticles (10 xcexcm or less) of a hydrosoluble carrier solid (NaCl, sucrose, lactose and other carbohydrates) are coated with an amphipatic agent; the dissolution of the coated carrier in an aqueous phase will yield liposomic vesicles. In GB-A-2,135,647 insoluble particles, e.g. glass or resin microbeads are coated by moistening in a solution of a lipid in an organic solvent followed by removal of the solvent by evaporation. The lipid coated microbeads are thereafter contacted with an aqueous carrier phase, whereby liposomic vesicles will form in that carrier phase.
The introduction of air or gas into a liposome solution in order to form therein a suspension of microbubbles can be effected by usual means, inter alia by injection, that is, forcing said air or gas through tiny orifices into the liposome solution, or simply dissolving the gas in the solution by applying pressure and thereafter suddenly releasing the pressure. Another way is to agitate or sonicate the liposome solution in the presence of air or an entrappable gas. Also one can generate the formation of a gas within the solution of liposomes itself, for instance by a gas releasing chemical reaction, e.g. decomposing a dissolved carbonate or bicarbonate by acid. The same effect can be obtained by dissolving under pressure a low boiling liquid, for instance butane, in the aqueous phase and thereafter allowing said liquid to boll by suddenly releasing the pressure.
Notwithstanding, an advantageous method is to contact the dry surfactant in lamellar or thin film form with air or an adsorbable or entrappable gas before introducing said surfactant into the liquid carrier phase. In this regard, the method can be derived from the technique disclosed in GB-A-2,135,647, i.e. solid microparticles or beads are dipped in a solution of a film forming surfactant (or mixture of surfactants) in a volatile solvent, after which the solvent is evaporated and the beads are left in contact with air (or an adsorbable gas) for a time sufficient for that air to become superficially bound to the surfactant layer. Thereafter, the beads coated with air filled surfactant are put into a carrier liquid, usually water with or without additives, whereby air bubbles will develop within the liquid, by gentle mixing, violent agitation being entirely unnecessary. Then the solid beads can be separated, for instance by filtration, from the microbubble suspension which is remarkably stable with time.
Heedless to say that, instead of insoluble beads or spheres, one may use as supporting particles water soluble materials like that disclosed in GB-A-2,134,869 (carbohydrates or hydrophilic polymers), whereby said supporting particles will eventually dissolve and final separation of a solid becomes unnecessary. Furthermore in this case, the material of the particles can be selected to eventually act as stabilizer or viscosity enhancer wherever desired.
In a variant of the method, one may also start with dehydrated liposomes, i.e. liposomes which have been prepared normally by means of conventional techniques in the form of aqueous solutions and thereafter dehydrated by usual means, e.g. such as disclosed in U.S. Pat. No. 4,229,360 also incorporated herein as reference. One of the methods for dehydrating liposomes recommended in this reference is freeze-drying (lyophilization), i.e. the liposome solution is frozen and dried by evaporation (sublimation) under reduced pressure. Prior to effecting freeze-drying, a hydrophilic stabilizer compound is dissolved in the solution, for instance a carbohydrate like lactose or sucrose or a hydrophilic polymer like dextran, starch, PVP, PVA and the like. This is useful in the present invention since such hydrophilic compounds also aid in homogenizing the microbubbles size distribution and enhance stability under storage. Actually making very dilute aqueous solutions (0.1-10% by weight) of freeze-dried liposomes stabilized with, for instance, a 5:1 to 10:1 weight ratio of lactose to lipid enables to produce aqueous microbubbles suspensions counting 108-109 microbubbles/ml (size distribution mainly 0.5-10 xcexcm) which are stable for at least a month (and probably much longer) without significant observable change. And this is obtained by simple dissolution of the air-stored dried liposomes without shaking or any violent agitation. Furthermore, the freeze-drying technique under reduced pressure is very useful because it permits, after drying, to restore the pressure above the dried liposomes with any entrappable gas, i.e. nitrogen, CO2, argon, methane. FREON (a gaseous fluorocarbon or chlorofluorocarbon.) etc., whereby after dissolution of the liposomes processed under such conditions suspensions of microbubbles containing the above gases are obtained.
Microbubbles suspensions formed by applying gas pressure on a dilute solution of laminated lipids in water (0.1-10% by weight) and thereafter suddenly releasing the pressure have an even higher bubble concentration, e.g. In the order of 1010-1011 bubbles/ml. However, the average bubble size is somewhat above 10 xcexcm, e.g. in the 10-50 xcexcm range. In this case, bubble size distribution can be narrowed by centrifugation and layer decantation.
The tensides or surfactants which are convenient in this invention can be selected from all amphipatic compounds capable of forming stable films in the presence of water and gases. The preferred surfactants which can be laminarized include the lecithins (phosphatidyl-choline) and other phospholipids, inter alia phosphatidic acid (PA), phosphatidyl-inositol phosphatidyl-ethanolamine (PE), phosphatidyl-serine (PS), phosphatidyl-glycerol (PG), cardiolipin (CL), sphingomyelins, the plasmogens, the cerebrosides, etc. Examples of suitable lipids are the phospholipids in general, for example, natural lecithins, such as egg lecithin or soya bean lecithin, or synthetic lecithins such as saturated synthetic lecithins, for example, dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline or distearoyl phosphatidyl choline or unsaturated synthetic lecithins, such as dioleyl phosphatidyl choline or dilinoleyl phosphatidyl choline, with egg lecithin or soya bean lecithin being preferred. Additives like cholesterol and other substances (see below) can be added to one or more of the foregoing lipids in proportions ranging from zero to 50% by weight.
Such additives may include other surfactants that can be used in admixture with the film forming surfactants and most of which are recited in the prior art discussed in the introduction of this specification. For instance, one may cite free fatty acids, esters of fatty acids with polyoxyalkylene compounds like polyoxypropylene glycol and polyoxyethylene glycol; ethers of fatty alcohols with polyoxyalkylene glycols; esters of fatty acids with polyoxyalkylated sorbitan; soaps; glycerol-polyalkylene stearate; glycerol-polyoxyethylene ricinoleate; homo- and copolymers of polyalkylene glycols; polyethoxylated soya-oil and castor oil as well as hydrogenated derivatives; ethers and esters of sucrose or other carbohydrates with fatty acids, fatty alcohols, these being optionally polyoxyakylated mono-, di- and triglycerides of saturated or unsaturated fatty acids; glycerides of soya-oil and sucrose. The amount of the non-film forming tensides or surfactants can be up to 50% by weight of the total amount of surfactants in the composition but is preferably between zero and 30%.
The total amount of surfactants relative to the aqueous carrier liquid is best in the range of 0.01 to 25% by weight but quantities in the range 0.5-5% are advantageous because one always tries to keep the amount of active substances in an injectable solution as low as possible, this being to minimize the introduction of foreign materials into living beings even when they are harmless and physiologically compatible.
Further optional additives to the surfactants include:
a) substances which are known to provide a negative charge on liposomes, for example, phosphatidic acid, phosphatidylglycerol or dicetyl phosphate;
b) substances known to provide a positive charge, for example, stearyl amine, or stearyl amine acetate;
c) substances known to affect the physical properties of the lipid films in a more desirable way: for example, capro-lactam and/or sterols such as cholesterol, ergosterol, phytosterol, sitosterol, sitosterol pyroglutamate, 7-dehydro-cholesterol or lanosterol, may affect lipid films rigidity;
d) substances known to have antioxidant properties to improve the chemical stability of the components in the suspensions, such as tocopherol, propyl gallate, ascorbyl palmitate, or butylated hydroxy toluene.
The aqueous carrier in this invention is mostly water with possibly small quantities of physiologically compatible liquids such as isopropanol, glycerol, hexanol and the like (see for instance EP-A-52.575). In general the amount of the organic hydrosoluble liquids will not exceed 5-10% by weight.
The present composition may also contain dissolved or suspended therein hydrophilic compounds and polymers defined generally under the name of viscosity enhancers or stabilizers. Although the presence of such compounds is not compulsory for ensuring stability to the air or gas bubbles: with time in the present dispersions, they are advantageous to give some kind of xe2x80x9cbodyxe2x80x9d to the solutions. When desired, the upper concentrations of such additives when totally innocuous can be very high, for instance up to 80-90% by weight of solution with Iopamidol and other iodinated X-ray contrast agents. However with other viscosity enhancers like for instance sugars, e.g. lactose, sucrose, maltose, galactose, glucose, etc. or hydrophilic polymers like starch, dextran, polyvinyl alcohol, polyvinyl-pyrrolidone, dextrin, xanthan or partly hydrolyzed cellulose oligomers, as well as proteins and polypeptides, the concentrations are best between about 1 and 40% by weight, a range.of about 5-20% being preferred.
Like in the prior art, the injectable compositions of this invention can also contain physiologically acceptable electrolytes; an example is an isotonic solution of salt.
The present invention naturally also includes dry storable pulverulent blends which can generate the present microbubble containing dispersions upon simple admixing with water or an aqueous carrier phase. Preferably such dry blends or formulations will contain all solid ingredients necessary to provide the desired microbubbles suspensions upon the simple addition of water, i.e. principally the surfactants in lamellar form containing trapped or adsorbed therein the air or gas required for microbubble formation, and accessorily the other non-film forming surfactants, the viscosity enhancers and stabilizers and possibly other optional additives. As said before, the air or gas entrappment by the laminated surfactants occurs by simply exposing said surfactants to the air (or gas) at room or super-atmospheric pressure for a time sufficient to cause said air or gas to become entrapped within the surfactant. This period of time can be very short, e.g. In the order of a few seconds to a few minutes although over-exposure, i.e. storage under air or under a gaseous atmosphere is in no way harmful. What is important is that air can well contact as much as possible of the available surface of the laminated surfactant, i.e. the dry material should preferably be in a xe2x80x9cfluffyxe2x80x9d light flowing condition. This is precisely this condition which results from the freeze-drying, of an aqueous solution of liposomes and hydrophilic agent as disclosed in U.S. Pat. No. 4,229,360.
In general, the weight ratio of surfactants to hydrophilic viscosity enhancer in the dry formulations will be in the order of 0.1:10 to 10:1, the further optional ingredients, if any, being present in a ratio not exceeding 50% relative to the total of surfactants plus viscosity enhancers.
The dry blend formulations of this invention can be prepared by very simple methods. As seen before, one preferred method is to first prepare an aqueous solution in which the film forming lipids are laminarized, for instance by sonication, or using any conventional technique commonly used in the liposome field, this solution also containing the other desired additives, i.e. viscosity enhancers, non-film forming surfactants, electrolyte, etc., and thereafter freeze drying to a free flowable powder which is then stored in the presence of air or an entrappable gas.
The dry blend can be kept for any period of time in the dry state and sold as such. For putting it into use, i.e. for preparing a gas or air microbubble suspension for ultrasonic imaging, one simply dissolves a known weight of the dry pulverulent formulation in a sterile aqueous phase, e.g. water or a physiologically acceptable medium. The amount of powder will depend on the desired concentration of bubbles in the injectable product, a count of about 108-109 bubbles/ml being generally that from making a 5-20% by weight solution of the powder in water. But naturally this figure is only indicative, the amount of bubbles being essentially dependent on the amount of air or gas trapped during manufacture of the dry powder. The manufacturing steps being under control, the dissolution of the dry formulations will provide microbubble suspensions with well reproducible counts.
The resulting microbubble suspensions (bubble in the 0.5-10 xcexcm range) are extraordinarily stable with time, the count originally measured at start staying unchanged or only little changed for weeks and even months; the only observable change is a kind of segregation, the larger bubbles (around 10 xcexcm) tending to rise faster than the small ones.
It has also been found that the microbubbles suspensions of this invention can be diluted with very little loss in the number of microbubbles to be expected from dilution, i.e. even in the case of high dilution ratios, e.g. 1/102 to 1/104, the microbubble count reduction accurately matches with the dilution ratio. This indicates that the stability of the bubbles depends on the surfactant in lamellar form rather than on the presence of stabilizers or viscosity enhancers like in the prior art. This property is advantageous in regard to imaging test reproducibility as the bubbles are not affected by dilution with blood upon injection into a patient.
Another advantage of the bubbles of this invention versus the microcapsules of the prior art surrounded by a rigid but breakable membrane which may irreversibly fracture under stress is that when the present suspensions are subject to sudden pressure changes, the present bubbles will momentarily contract elastically and then resume their original shape when the pressure is released. This is important in clinical practice when the microbubbles are pumped through the heart and therefore are exposed to alternating pressure pulses.
The reasons why the microbubbles in this invention are so stable are not clearly understood. Since to prevent bubble escape the buoyancy forces should equilibrate with the retaining forces due to friction, i.e. to viscosity, it is theorized that the bubbles are probably surrounded by the laminated surfactant. Whether this laminar surfactant is in the form of a continuous or discontinuous membrane, or even as closed spheres attached to the microbubbles, is for the moment unknown but under investigation. However the lack of a detailed knowledge of the phenomena presently involved does not preclude full industrial operability of the present invention.
The bubble suspensions of the present invention are also useful in other medical/diagnostic applications where it is desirable to target the stabilized microbubbles to specific sites in the body following their injection, for instance to thrombi present in blood vessels, to atherosclerotic lesions (plaques) in arteries, to tumor cells, as well as for the diagnosis of altered surfaces of body cavities, e.g. ulceration sites in the stomach or tumors of the bladder. For this, one can bind monoclonal antibodies tailored by genetic engineering, antibody fragments or polypeptides designed to mimic antibodies, bioadhesive polymers, lectins and other site-recognizing molecules to the surfactant layer stabilizing the microbubbles. Thus monoclonal antibodies can be bound to phospholipid bilayers by the method described by L. D. Leserman, P. Machy and J. Barbet (xe2x80x9cLiposome Technology vol. IIIxe2x80x9d p. 29 ed. by G. Gregoriadis, CRC Press 1984). In another approach a palmitoyl antibody is first synthesized and then incorporated in phospholipid bilayers following L. Huang, A. Huang and S. J. Kennel (xe2x80x9cLiposome Technology vol. IIIxe2x80x9d p. 51 ed. by G. Gregoriadis, CRC Press 1984). Alternatively, some of the phospholipids used in the present invention can be carefully selected in order to obtain preferential uptake in organs or tissues or increased half-life in blood. Thus GM1 gangliosides- or phosphatidylinositol-containing liposomes, preferably in addition to cholesterol, will lead to increased half-lifes in blood after intravenous administration in analogy with A. Gabizon, D. Papahadjopoulos, Proc. Natl Acad. Sci USA 85 (1988) 6949.
The gases in the microbubbles of the present invention can include, in addition to current innocuous physiologically acceptable gases like CO2, nitrogen, N2O, methane, butane. FREON (a gaseous fluorocarbon or chlorofluorocarbon.) and mixtures thereof, radioactive gases such as 133Xe or 81Kr are of particular interest in nuclear medicine for blood circulation measurements, for lung scintigraphy etc.
The following Examples illustrate the invention on a practical stand point.
Echogenicity measurements were performed in a pulsexe2x80x94echo system made of a plexiglas specimen holder (diameter 30 mm) and a transducer holder immersed in a constant, temperature water bath, a pulser-receiver (Accutron M30105) with for the receiving part an external pre-amplifier with a fixed gain of 40 dB and an internal amplifier with adjustable gain from xe2x88x9240 to +40 dB. A 10 MHz low-pass filter was inserted in the receiving part to improve the signal to noise ratio. The A/D board in the IBM PC was a Sonotek STR 832. Measurements were carried out at 2.25, 3.5, 5 and 7.5 MHz.

Mixable combination for generating a suspension of stable microbubbles for ultrasonic imaging


To provide a method of recording information to an optical recording medium comprising recording a mark of time length nT (n: natural number of 3 or more, T: clock cycle) in an optical recording medium capable of supporting different recording speeds and having constant information line density, and irradiating the optical recording medium, the optical recording medium irradiated with light of alternating m1 heating pulses of power Pw and m1 cooling pulses of power Pc (where m1 is a natural number smaller than n) provided v<v0 (where v is a scanning speed and v0 is a scanning speed unique to each optical recording medium), the optical recording medium irradiated with light of alternating m2 heating pulses of power Pw and m2 cooling pulses of power Pc (where m2 is a natural number smaller than n) provided v≧v0, wherein the condition n/m1≧n/m2 is satisfied.

1. Technical Field
This disclosure relates to an optical recording medium (hereinafter referred to as an "optical recording medium," "information recording medium," or "optical disc" in some cases) more particularly to a method of recording to rewritable optical discs such as CD-RWs, DVD-RWs, DVD+RWs and DVD-RAMs in which a phase-change material is used as a recording layer, and to an optical recording medium to which the recording method can be applied.
2. Description of the Related Art
Rewritable optical discs applied with a phase change technology, as typified by CD-RWs, DVD+RWs and DVD-RWs, are widely used for audio-visual purpose and information recording purpose in computers. With an increase in the digital capacity in recent years, the recording speed for these optical discs is also expected to be increased.
High-speed recording for these optical discs using the phase-change technology requires excellent rewriting performance both at higher scanning speeds and in a broader scanning speed range—the former corresponds to the maximum recording speed and the latter to the speed range inside of which recording is possible. For the latter, in particular, a speed ratio of about 2.4:1 (maximum speed: minimum speed) is required to support the CAV (Constant Angular Velocity) recording, a technology that is necessary for the acceleration of random access recording. In the CAV recording, the scanning speed v varies with the recording radial position r, i.e., v/r=constant, and thus recording needs to be possible at any recording speed below the maximum recording speed. Furthermore, the higher the maximum speed, the broader the scanning speed range, inevitably, e.g., 4×DVD+RW discs require a scanning speed range of 5.8 m/s to 14.0 m/s to support the CAV recording. Thus, further development is required for optical recording media and recording methods, so that recording is possible in an extremely broader speed range from 11.6 m/s to 27.9 m/s to support 8× recording.
Meanwhile, for the increased maximum recording speed, a recording layer material needs to be changed to a material that is more suitable for high-speed recording. Phase-change materials are generally used as the recording layer material of optical discs typified by DVD-RWs and CD-RWs. For such phase-change materials, alloys that can switch between an amorphous state and a crystalline state in a reversible manner are generally used. To achieve speed up, phase-change materials that rapidly switch from an amorphous state to a crystalline state, i.e., those with high crystallization rates need to be used. Increasing the crystallization rate, however, makes the control of the crystalline state at low-speed recording very difficult. For this reason, a major recording method (or write strategy) change needs to be made between the speed range close to the maximum and the speed range close to the minimum. Thus, using recording layer materials that support high-speed recording makes it very difficult to achieve recording at any recording speed below the maximum speed.
Examples of related art which may be associated with the present invention are as follows: for example, Japanese Patent Application Laid-Open (JP-A) No. 2005-78662 discloses an optical information recording method and an apparatus, where the delay amount of the first pulse is changed in the CAV recording by using a 2T strategy, and also discloses the fact that parameters are set for recording speed using linear functions; JP-A No. 2000-322740 discloses a method of recording to an optical recording medium, where parameters are set for recording speed using linear functions; and JP-A No. 2001-118245, JP-A No. 2001-243626, "DVD+ReWritable 4.7 Gbytes Basic Format Specifications System Description version 1.2" and "Recordable Compact Disc Systems Part III, volume 2, version 1.1" disclose an information recording method for setting parameters for recording speed using linear functions, an apparatus, and a technology for changing the parameters stepwise.
The related arts described above all fail to describe discontinuous pulse change, which is the feature of the present invention.
In addition, although JP-A No. 2003-281722 discloses a technology for changing the pulse number depending on the speed range for recording, its setting is totally opposite of the setting disclosed in the present invention; therefore it never reveals the present invention.

Optical recording medium and method of recording to the same


A display device which can ensure the correction of a black spot, for example, in forming an opening portion in a portion of a scanning signal line where the scanning signal line intersects a video signal line and forming a semiconductor layer and a conductor layer by a resist reflow method is provided. A conductor layer includes a video signal line, a drain electrode, a source electrode, and a connecting line. A semiconductor layer is formed so as to cover at least a region of the insulation film which is larger than a region where the video signal line and the connecting line are formed. The connecting line is connected with the video signal line over an opening portion which is formed in the scanning signal line. A cutout portion, a projecting portion or an enlarged-width portion is formed on the video signal line and/or the connecting line in a region which corresponds to the opening portion or in the vicinity of the region.

1. Field of the Invention
The present invention relates to a display device which performs a display control of pixels using thin film transistors (TFTs) and a manufacturing method thereof.
2. Description of the Related Art
For example, among various display devices including a liquid crystal display device, there has been known a display device which performs a display control of respective pixels by an active matrix drive method using thin film transistors. In such a display device, a plurality of scanning signal lines and a plurality of video signal lines are arranged on a substrate (hereinafter, referred to as a TFT substrate) in a stereoscopically intersecting manner. Here, respective intersecting points of the scanning signal lines and the video signal lines correspond to the pixels of the display device. A portion of the scanning signal line functions as a gate electrode of the thin film transistor, and either one of a drain electrode and a source electrode (the drain electrode in the explanation made hereinafter) of the thin film transistor is connected to the video signal line. Further, a pixel electrode is connected to the electrode of the thin film transistor which is not connected to the video signal line (source electrode in the explanation made hereinafter). Due to such constitution, by applying voltages to both of the scanning signal line and the video signal line corresponding to the pixel to which a display control is applied, the voltages are applied to the corresponding pixel electrode via the thin film transistor which functions as a switching element so that a display control of the pixel can be performed.
To form such a thin film transistor, it is necessary to stack the scanning signal lines, insulation layers, semiconductor layer, and a conductor layer on the TFT substrate in this order. Here, the conductor layer is a layer which includes the video signal lines, the drain electrodes and the source electrodes. To form these scanning signal lines, semiconductor layers and conductor layer having desired patterns respectively on the TFT substrate, a so-called photolithography technique can be used. According to this technique, a resist material is applied to a surface of a material film for forming an object by coating, the resist material is processed in a pattern of an object to be formed by exposure and development, and a film to be formed is etched using the processed resist material as a mask thus forming the scanning signal lines, the semiconductor layer and the conductor layer having desired patterns.
Further, in forming the semiconductor layers and the conductor layer by performing exposure one time, a resist reflow method may be adopted (see JP-A-2002-90779 (corresponding US patent; U.S. Pat. No. 6,933,989B2) (patent document 1), for example). In this method, a film made of a semiconductor material and a film made of a conductor material are sequentially stacked on a TFT substrate on which scanning signal lines and an insulation film are formed, the film made of the conductor material is formed into conductor layers of a desired pattern by the above-mentioned technique and, thereafter, a resist material remaining on the conductor layers is melted. Due to such steps, the resist material covers a region which is larger than a region on which the conductor layer is formed. By further etching the film made of the semiconductor material using the spread resist material as a mask, the semiconductor layer is formed into a shape which includes a region where the conductor layer is formed without exposing the resist material.
Further, in a display device having the above-mentioned type of thin film transistor, an opening portion may be formed in a portion of a scanning signal line where the scanning signal line intersects with the video signal line (see JP-A-9-258244 (patent document 2), for example). By forming the opening portion in the scanning signal line, the scanning signal line is bifurcated at the portion where the opening portion is formed so that, as viewed in a plan view, the respective branched or bifurcated scanning signal lines intersect with the video signal line. Due to such constitution, even when the scanning signal line and the video signal line are short-circuited with each other at an intersecting portion during a manufacturing process by a chance, by cutting one scanning signal line on a side where the scanning signal line is short-circuited with the video signal line out of these bifurcated or branched scanning signal lines using, for example, laser beams such that portions of one scanning signal line on both sides of the video signal line are cut, it is possible to cut off only the portion which is short-circuited with the video signal line from the whole scanning signal line. Further, the conductor layer may be formed such that a connecting line which connects the video signal line and the drain electrode of the thin film transistor is branched from the video signal line above the opening portion. Due to such constitution, when it is necessary to correct a black spot of a certain pixel, it is possible to separate the video signal line and the thin film transistor from each other by cutting the connecting line which connects the drain electrode of the thin film transistor corresponding to the pixel and the video signal line above the opening portion using laser beams, for example.

Display device and manufacturing method of display device

Panasonic Liquid Crystal Display Co., Ltd.


Goggles for providing interchangeable transparent and mesh screen eye shields on a goggle frame. The device includes a frame shaped to fit on the face of a wearer and having a front and inner and outer surfaces. The inner surface of the frame defines a central space. The ends of a flexible strap are coupled to the frame. The flexible strap is adapted for looping around the back of the head of a wearer to hold the frame to the face of the wearer. A mesh screen eye shield substantially covers the central space at the front of the frame. The mesh screen eye shield has a plurality of generally uniform apertures therethrough. Each of the apertures has a predetermined area and is designed for preventing objects greater than the predetermined sized passing therethrough. The apertures of the mesh screen eye shield are also designed for permitting the passage of moisture therethrough.

1. Field of the Invention
The present invention relates to goggles and more particularly pertains to a new goggles for providing interchangeable transparent and mesh screen eye shields on a goggle frame.
2. Description of the Prior Art
The use of goggles is known in the prior art. More specifically, goggles heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art goggles include U.S. Pat. No. 4,901,374; U.S. Pat. No. 5,184,354; U.S. Pat. No. 3,104,508; U.S. Pat. No. 4,494,251; U.S. Pat. No. 3,663,959; and U.S. Pat. No. 2,871,642.
While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not disclose a new goggles. The inventive device includes a frame shaped to fit on the face of a wearer and having a front and inner and outer surfaces. The inner surface of the frame defines a central space. The ends of a flexible strap are coupled to the frame. The flexible strap is adapted for looping around the back of the head of a wearer to hold the frame to the face of the wearer. A mesh screen eye shield substantially covers the central space at the front of the frame. The mesh screen eye shield has a plurality of generally uniform apertures therethrough. Each of the apertures has a predetermined area and is designed for preventing object, greater than the predetermined size from passing therethrough. The apertures of the mesh screen eye shield are also designed for permitting the passage of moisture therethrough.
In these respects, the goggles according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of providing interchangeable transparent and mesh screen eye shields on a goggle frame.