An active roll control system actively controls roll of a vehicle by changing torsional rigidity of a stabilizer bar by using change in tension of a wire connected to the stabilizer bar and both lower arms according to an operation of a pulley unit mounted at the lower arm, simplifies control thereof as a consequence that an electric motor controls operation of the pulley unit, and simplifies layout thereof.

1. Field of the Invention
The present invention relates to an active roll control system. More particularly, the present invention relates to an active roll control system (ARCS) that actively controls roll of a vehicle by changing torsional rigidity of a stabilizer bar by using change in tension of a wire according to an operation of a pulley unit mounted at an lower arm, simplifies control of the ACRS as a consequence that an electric motor controls operation of the pulley unit, and has advantages in layout.
2. Description of Related Art
Generally, a suspension system of a vehicle connects an axle to a vehicle body so as to control vibration or impact transmitted from a road to the axle when driving not to be directly transmitted to the vehicle body. Accordingly, the suspension system of a vehicle prevents the vehicle body and freight from being damaged and improves ride comfort.
Such a suspension system, as shown in FIG. 1, includes a chassis spring 101 relieving impact from the road, a shock absorber 103 reducing free vibration of the chassis spring 101 and improving the ride comfort, and a stabilizer bar 105 suppressing roll of a vehicle (it means that a vehicle inclines with reference to a length direction of the vehicle body).
Both sides of the stabilizer bar 105 is mounted at the vehicle body 107, and both ends of the stabilizer bar 105 is mounted at a lower arm 109 or a strut bar (not shown). Therefore, in a case that left and right wheels 111 move to the same direction (upward direction or downward direction), the stabilizer bar 105 does not work. On the contrary, in a case that the left and right wheels 111 move to the opposite direction (one moves upwardly and the other moves downwardly), the stabilizer bar 105 is twisted and suppresses the roll of the vehicle body 107 by torsional restoring force.
That is, when the vehicle body 107 inclines toward a turning axis by the centrifugal force in a case of turning or heights of the left and right wheels is different from each other by bump or rebound of the vehicle, the stabilizer bar 105 is twisted and stabilizes position of the vehicle body by torsional restoring force.
However, a conventional stabilizer bar 105 suppresses inclination of the vehicle or restores the inclined vehicle body 107 by only using torsional restoring force of the stabilizer bar 105, it is difficult to control roll of the vehicle quickly and precisely. In order to solve above-mentioned problem, an active roll control system provided with an actuator having a hydraulic pressure cylinder 113 connected to one end of stabilizer bar 105 and controlling the roll of the vehicle actively is developed.
According to an active roll control system that controls the roll of the vehicle actively by using the hydraulic pressure cylinder 113, one lower arm 109 is connected to one end of the stabilizer bar 105 by a stabilizer link 115 and the other lower arm 109 is connected to the other end of the stabilizer bar 105 by the hydraulic pressure cylinder 113, as shown in FIG. 2. Therefore, the active roll control system stabilizer bar 105 changes torsional rigidity of the stabilizer bar 105 by changing a length between the other end of the stabilizer bar 105 and the lower arm 109.
That is, according to the active roll control system, a lower end of the hydraulic pressure cylinder 113 is connected the other lower arm 109, and an upper end of piston rod 117 of the hydraulic pressure cylinder 113 is connected to the other end of the stabilizer bar 105 by a ball joint 119.
Therefore, an ECU controls a hydraulic pressure system including a valve and a hydraulic pressure pump based on signals output from an acceleration sensor, a vehicle height sensor, and a steering sensor, and improves the roll of the vehicle according to the active roll control system.
However, according to the conventional active roll control system, a lower end of the hydraulic pressure cylinder 113 (i.e., actuator) must be assembled to the lower arm 109 through an additional bracket 121 in order to guarantee an operational stroke thereof. However, such structures have drawbacks in mass productivity.
In addition, the hydraulic pressure supply system for supplying and controlling hydraulic pressure including a hydraulic pressure pump, a hydraulic pressure valve, and a hydraulic line is very complex according to the conventional active roll control system.
The information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.


A spa enclosure apparatus has a convertible awning spanning over and spaced generally vertically from a hot tub when in use, and preferably an insulated cover assembly for covering the hot tub when not in use. Preferably, the cover assembly is engaged to and operates in conjunction with the convertible awning. The convertible awning has a canopy supported by and extending between two substantially parallel arcuate rods of the convertible awning. Each arcuate rod preferably connects to a substantially vertical shaft preferably of the cover assembly located substantially near respective rear corners of the spa. The arcuate rods extend upward from the vertical shafts, bend, and project over the hot tub to respective forward corners of the hot tub. Preferably, two substantially vertical columns of the convertible awning project upward from the vicinity of the respective forward corners to engage the distal ends of the arcuate rods.

Hot tubs and/or spas typically utilized in the outside environment of a residential home contain heated water often circulated with numerous jets, and air bubblers that sooth and relax the bather. The inside liner of the tubs and spas typically form seats or lounging areas wherein the jets are strategically placed to massage specific areas of the bather. Because the spa is often located outside, it is exposed to seasonal weather changes that can be considerably colder than the heated temperature of the spa water. Consequently, cumbersome insulated covers are placed directly over the spa to minimize heat loss, preserve energy, and prevent water evaporation.
The weight and size of the insulated covers can create cover removal and placement difficulty for the bather. Consequently, cover removal devices are known that minimize the required lifting effort by the bather. One such device is disclosed in Perry, U.S. Pat. No. 4,853,985, filed Mar. 31, 1988, and in Tudor, U.S. Pat. No. 5,974,599, filed Jan. 9, 1998, both being incorporated herein by reference in their entirety.
Unfortunately, once the cover is removed and the bather(s) are relaxing within the hot tub or spa, the degree of privacy for the outdoor bather(s) is greatly minimized. Moreover, the bather when in the spa may be exposed to the harsh rays of the sun or bothered by surrounding insects and overhead birds. Yet further, falling debris from surrounding trees can clog the spa filter.


An output section, consisting of a pair of loudspeakers disposed adjacently to each other, is installed inside a seatback of a designated seat. Sound output surfaces of respective loudspeakers face a designated person sitting on the designated seat. It is hence easy to secure a required distance for obtaining clear acoustic image localization in accordance with the size of loudspeakers cooperatively constituting the output section.

This invention relates to a sound output apparatus for an automotive vehicle which generates various acoustic or sound outputs, such as warning sounds, alarms, guide voice or speech, and others.
Conventionally, an automotive vehicle is equipped with an acoustic or sound device for generating various acoustic or sound outputs to transmit necessary information to a driver or passengers in a passenger compartment. For example, various sensors are installed on an automotive vehicle to detect dangerous or abnormal conditions of the vehicle. When these sensors detect any dangerous or abnormal conditions of the vehicle, warning sounds, alarms, and voice or speech guidance from a navigation system will be generated to evoke driver's or passenger's caution and to let the driver or passengers act or behave appropriately to avoid the encountering danger or abnormality.
However, even if warning sounds or alarms are generated, there will be the possibility that a driver or passenger cannot understand the contents or meaning of the immediately generating warning sounds or alarms and also cannot know the direction to which the driver's or passenger's caution should be directed. Hence, the action or behavior of the driver or passengers to avoid the encountering danger or abnormality will be delayed. For example, supersonic sonars may be installed at four corners of a vehicle body to detect approach of any obstacle. However, if the warning sounds or alarms notifying the approach of any obstacle are always the same, a driver or passengers will not be able to immediately know or perceive the direction from which the detected obstacle is approaching. The driver and passengers will not be able to promptly and properly respond to avoid the coming danger or increasing abnormality.
Japanese Patent Application Laid-open No. 2002-133596, in paragraph 0012 and FIG. 2, discloses a warning apparatus which produces a virtual sound source by using loudspeakers installed in a passenger compartment and changes the position of the virtual sound source or tone quality in accordance with time variation or spatial or positional change of a distance between oneself and the car ahead or behind, thereby letting a driver sense the position of other vehicle.
According to this warning apparatus, production of the virtual sound source is realized by using a multichannel surround system consisting of four channel loudspeakers disposed at four corners, i.e., right and left edges of respective front and rear ends, in a passenger compartment, or by using a stereo dipole system consisting of a pair of loudspeakers disposed adjacently to each other which is preferably incorporated in a car navigation system.
Compared with other systems, the stereo dipole system has a very wide audible area in which clear acoustic or sound image localization is attained. Furthermore, as two loudspeakers are disposed adjacently to each other, the stereo dipole system can be preferable employed as an acoustic equipment installed in a narrow or limited space available in a passenger compartment.
More specifically, to obtain clear acoustic or sound image localization according to the stereo dipole system, as shown in FIG. 13, a pair of loudspeakers SP is disposed in front of an audience with an angle θ formed between two straight lines connecting respective loudspeakers SP to the audience. In this case, the required angle θ is approximately 10°. In practice, compact loudspeakers having practically usable frequency characteristics are approximately 10 cm in diameter. If these compact loudspeakers are disposed as closely as possible, the closest distance between the centers of two loudspeakers SP will be approximately 10 cm (i.e., W=10 cm). Considering this relationship, the distance L from the audience to a plane on which sound output surfaces of two loudspeakers SP are aligned should be approximately 60 cm. If the size of loudspeakers is more reduced in the future, it may be necessary to reduce the distance L.
However, the loudspeakers incorporated in a car navigation system are usually positioned in a central region on an instrument panel or a dashboard substantially equally distant from each of a driver's seat and the next passenger's seat. In other words, the loudspeakers of a car navigation system are not positioned in direct front of the driver's seat or in direct front of the passenger's seat. Therefore, it is difficult to obtain clear acoustic or sound image localization by using a car navigation system even if the stereo dipole system is employed. If the loudspeakers are downsized in the future, the above distance L may be too long to obtain clear acoustic or sound image localization.
Furthermore, according to the stereo dipole system, it is generally known that clear acoustic or sound image localization is obtained in a wide angular range of ±70°˜90° with respect to a line (=0°) directing the front side of the audience, as shown in FIG. 13. In other words, there is an insensible angular zone at the back side of the audience in which no acoustic or sound image localization can be obtained. For example, according to the warning apparatus disclosed in the above-described prior art reference, a driver cannot obtain clear acoustic or sound image localization in an insensible region spreading at the back side of the driver when the loudspeakers of a car navigation system are positioned in front on a driver's seat.

Sound output apparatus for an automotive vehicle


A data frame synchronizer identifies frame boundaries in a serial data stream formed of a set of multi-bit frames. Selected frames in the set have a frame boundary bit at a specified location within the frame, and the frame boundary bits together form a predetermined pattern. The frame synchronizer includes a memory array having a memory data input, a memory data output and a plurality of rows and columns for storing the serial data stream. A memory control circuit is coupled to the memory array for writing successive bits of the serial data stream into the memory array through the memory data input in a sequence such that all of the frame boundary bits align in one of the rows. As each bit is being written into the memory array, the memory control circuit reads the corresponding row through the data output. A pattern detector is coupled to the memory data output for comparing the row with a predetermined pattern.

The present invention relates to a serial communication system and, more particularly, to a synchronizer for locating a frame boundary in a serial data stream.
In a typical serial communication system, data is transferred to a data stream receiver in sets of multi-bit frames. The data stream receiver includes a frame synchronizer which locates the frame boundaries and then synchronizes the receipt of information to the frame boundaries. This allows the receiver to accurately extract and process the received data. For example, a "T1" data stream is formed of a set of 193-bit frames. Each frame in the set includes one frame bit and 192 payload bits. The frame bit is located at a particular location in each frame. The payload bits can include encoded voice data, for example. A T1 data stream is transmitted in a selected format, such as Extended Super Frame (ESF) format or Super Frame (SF) format. In ESF format, data is collected in sets of 24 frames and transmitted as a continuous stream. In SF format, data is collected in sets of 12 frames and transmitted as a continuous stream. Of the 24 frame bits per set in the ESF format and the 12 frame bits per set in the SF format, six frame bits are used for frame boundary identification. These frame boundary bits are referred to as "FPS" bits in the ESF format and "Ft" bits in the SF format. The remaining frame bits are used for other purposes, such as data link bits or for Cyclic Redundancy Checks ("CRCs").
The six frame boundary bits together form a predetermined pattern, beginning with the first frame boundary bit of the set. The data stream receiver locates the frame boundary bits, and thus the boundaries between the data frames, by searching the received data stream for the predetermined pattern. A typical data stream receiver considers a number of consecutive frame boundary bits that follow a particular bit position before declaring the bit position as a possible boundary. For example, with a 24-bit qualification, the receiver will search for a bit position from which 24 consecutive frame boundary bits have been found.
In one search method, the received data stream is shifted into a large shift register. The shift register has 24 output taps spaced 193 bits apart. The first tap is typically at the first bit position in the shift register. As each bit is written into the shift register, the bits at the 24 output taps are compared to the search pattern. If there is a match, then the first bit position is a possible candidate for a frame boundary. Once a frame boundary has been located, the receiver can lock onto the received data.
A disadvantage of this method is that it requires an enormous amount of storage space. In order to compare 24 bits, the shift register must store four sets of 24 frames, with 193 bits per frame. This requires a shift register capable of holding 18,528 bits. Also, the search process may end in an incorrect result. Because the received data is random in nature, there may be more than one bit position where 24 consecutive frame boundary bits are found. This method validates the first bit position that it encounters with 24-bit qualification, and does not eliminate mimic or false patterns.

Data frame synchronizer for serial communication system


A device in a base station of a mobile communication system for power management can include a storage device to store a group of parameter sets associated with a user equipment (UE) of the mobile communication system. The device can include a processor to calculate a corresponding objective function associated with each entity of the group of parameter sets. The processor can be configured to select an entity of the group of parameter sets based on the corresponding objective function, and the selected entity of the group of parameter sets facilitates the power management for the UE.

The present disclosure relates generally to mobile communication; for example, the present disclosure relates to a device and a method for power management in a mobile communication system.
A mobile communication system that supports the third generation partnership project (3GPP) long term evolution (LTE) standard has been developed so as to enhance data rate and reduce transmission latency. However, a higher data rate may entail higher power consumption for user equipment (UE). To address the issue, power saving mechanisms have been proposed, but which are not adequate in various respects.

Power management based on discontinuous reception cycles in a mobile communication system


An outdoor heat exchanger (23), an indoor heat exchanger (24), a compression/expansion unit (30), and other circuit components are connected in a refrigerant circuit (20). The compression/expansion unit (30) includes a compression mechanism (50), an electric motor (45), and an expansion mechanism (60). In addition, the refrigerant circuit (20) has an injection pipeline (26). When an injection valve (27) is opened, a portion of high pressure refrigerant after heat dissipation flows into the injection pipeline (26) and is introduced into an expansion chamber (66) of the expansion mechanism (60) in the process of expansion. In the expansion mechanism (60), power is recovered from both high pressure refrigerant introduced into the expansion chamber (66) from an inflow port (34) and high pressure refrigerant introduced into the expansion chamber (66) from the injection pipeline (26).

Refrigeration apparatuses operable to perform a refrigeration cycle are well known in the conventional technology. Such a type of refrigeration apparatus has a variety of applications, for example, in the field of air conditioners. Patent Document I discloses a refrigeration apparatus of the type which includes an expander. In the refrigeration apparatus disclosed in Patent Document I, the expander is connected, through a single shaft, to a compressor. In the refrigeration apparatus of Patent Document I, high pressure refrigerant after heat dissipation is expanded in the expander for the recovery of power. The power recovered in the expander is used to drive the compressor, with a view to achieving improvement in the coefficient of performance (COP).
In a typical refrigeration apparatus, refrigerant is circulated in a refrigerant circuit configured in the form of a closed circuit. This produces the necessity of constantly keeping the mass flow rate of refrigerant through the expander and the mass flow rate of refrigerant through the compressor at the same value. However, the refrigeration apparatus, when in operation, undergoes variations in the operating condition (e.g., the variation in the high pressure of the refrigeration cycle and the variation in the low pressure of the refrigeration cycle). In consequence, the density of refrigerant that flows into the compressor and the compressor will vary. If, like Patent Document I, the expander is coupled to the compressor by a single shaft, the rotation speed of the expander and the rotation speed of the compressor constantly become equal. Therefore, if both the expander and the compressor are implemented by positive displacement fluid machines, this results in occurrence of an imbalance between the mass flow rate of refrigerant through the expander and the mass flow rate of refrigerant through the compressor. This might make it impossible for the refrigeration apparatus to continuously perform a stable refrigerant cycle.
On the other hand, in the refrigeration apparatus of Patent Document I, a bypass passageway is provided in parallel with the expander and a flow rate control valve is arranged along the bypass passageway. When the mass flow rate of refrigerant passable through the expander becomes excessively small relative to the mass flow rate of refrigerant through the compressor, the refrigerant is made to flow through both the expander and the bypass passageway.
Patent Document I: JP 2001-116371A

Refrigeration apparatus with expander control for improved coefficient of performance


A patient-specific cutting guide system comprises at least two instruments. One is a positioner configured to locate a fiducial marker on a patient's bone and to be secured in three axes. The second is a cutting guide that cooperates with the positioner and delineates cuts to be made. The instruments are designed from images of the bone with the marker already in place. Preferably, a positioner comprises at least three targeting apertures configured to locate at least three non-linear markers. The cutting guide comprises top surface contours that guide the depth of the cuts. A method of forming this system comprises placing at least one marker (preferably three) on a patient's bone, then imaging the bone, forming a positioner designed to incorporate the marker position, and forming a cutting guide configured to be oriented and anchored by the positioner.

This section provides background information related to the present disclosure which is not necessarily prior art.
It is often necessary in orthopedic surgery to divide a bone accurately into two or more portions. When bones are divided for the removal of a tumor, the location of these cuts is of paramount importance. Current methods for ensuring the precision of the cuts are either burdensome or subject to inaccuracy due to improper location on the bone.
There is need in the art for a system, device, and method for locating cuts so that they are made in the intended location.


The present invention involves an image-enhancing agent comprising melanin combined with an essentially non-dissociable signal-inducing metal. The signal-inducing metal has an association constant for its melanin combination of at least about 10.sup.20. Upon suspension or dissolution in water the metal remains undissociated. A preferred signal-inducing metal is paramagnetic or superparamagnetic, of course for magnetic resonance imaging. A preferred paramagnetic or superparamagnetic metals are gadolinium, iron, nickel, copper, erbium, europium, praseodymium, dysprosium, holmium, chromium or manganese. Gadolinium is the most effective metal. The metal is incorporated into the melanin in an ionic or particulate form. Metals may be utilized which are particularly useful to modify ultrasound images by the enhancement of the image obtained from emission and detection of high-frequency soundwaves. Metals emitting gamma particles may also be utilized to enhance images resulting from gamma particle emission scanning. .sup.51 Chromium, .sup.68 gallium, .sup.99m technitium and .sup.111 indium are preferred metals for gamma particle scanning. Additionally, native or synthesized melanin, in and of itself is an effective MRI image-enhancing agent.

The present invention relates to image-enhancing agents, contrast agents or spectral shift agents to enhance tissue or organ images or nuclear spectra obtained from live animals with magnetic resonance imaging (MRI) or spectroscopy (MRS), radioisotope scanning or ultrasound imaging.
Magnetic resonance imaging is a medical procedure that takes advantage of the magnetic spin properties of nuclei to create an image fundamentally like that of the more widely known X-ray procedure the CT scan. The nucleus of an atom contains neutrons and protons. Atoms which have an odd number of neutrons or protons have a non-zero spin quantum number (I). These atoms can be thought to behave like small spinning spheres. Because the nuclei have positive charges, the spinning produces a magnetic moment (U), analogous to an electric current in a closed loop of wire. When exposed to a magnetic field these dipoles align themselves with the magnetic field. The spin (magnetic moment) vectors experience a torque when subjected to a magnetic field. Due to this torque, the nuclei process about the axis of the magnetic field at a rate given by the Larmor relationship: EQU f=w/2.pi.=.gamma.Bo/2.pi.
f=resonance frequency in Hertz (Hz) PA1 w=the angular frequency in radians per second PA1 .gamma.=magnetic gyric ratio PA1 Bo=static magnetic field PA1 .gamma.=a nuclear constant characteristic of the isotope PA1 B.sub.1 =amplitude of the FR field PA1 .pi.=duration PA1 N(H)=number of protons in the discrete tissue volume (spin density); PA1 f(v)=a function of proton velocity and the fraction of protons which are moving (e.g., due to following blood); PA1 TE=time between the radio frequency (rf) pulse and the detection of signal (spin-echo); PA1 TR=the interval between repetition of the rf pulse; PA1 T1=the time interval associated with the rate of proton energy transfer to the surrounding chemical environment (spin-lattice relaxation); PA1 T2=the time interval associated with the rate of proton energy transfer, one to other (spin-spin relaxation).
The resonance frequency of a nucleus is a function of its magnetogyric ratio (a constant for the particular nucleus being studied) and the strength of an applied magnetic field (Larmor equation). The magnetogyric ratio of a nucleus relates the magnetic moment and the nuclear spin quantum number (I). The spin quantum number depicts the number of energy states that a nucleus can have; a nucleus has 2I+1 energy levels. The hydrogen nucleus (a proton) has a nuclear spin of 1/2, and thus two possible spin states. In nuclear magnetic resonance spectroscopy (NMR), the magnetic moment is shown as revolving around a fixed magnetic field (FIG. 1) at a fixed frequency. In a sample, large numbers of nuclei are revolving around this field in one of the two possible spin states, creating a "macroscopic magnetization" M parallel to the magnetic field. There are more nuclei in the low-energy spin state when there is no outside influence (FIG. 2).
Resonance is the induction of a transition between two different energy states. The nuclei that lends itself best to magnetic resonance imaging is the proton, the major isotope of hydrogen. Hydrogen has a very large abundance in biological systems in water (E10.sup.23 /cm.sup.3) as well as in other biochemical molecules and has the required magnetic moment. The energy necessary to produce a transition between the two spin states of hydrogen (+1/2 and -1/2) is the difference in energy (.DELTA.E) between these spin states. In MRI, resonance occurs when radiofrequency (RF) energy is applied at the Larmor frequency, flipping the magnetic moments from their m=+1/2 (lower energy) to their m=-1/2 (higher energy) states. Magnetic resonance absorption can only be detected by transverse magnetization (magnetization perpendicular to Bo). Only the transverse component, Mxy, is time dependent and therefore according to Faraday's law of induction, only time dependent magnetization can induce a voltage in a receiver coil. Transverse magnetization is generated when a radiofrequency (RF) field of amplitude B., rotating synchronously with the processing spins is applied.
When the RF field acts in a direction perpendicular to the main field, the effect is to rotate the magnetization away from the rest state. The macroscopic magnetization experiences a torque of the RF field, forcing the magnetization to rotate about it. If the duration of the B. field is such that the net magnetization is rotated by an angle of 90.degree., it will become transverse or perpendicular to the stated field (FIG. 3). The angle of rotation .theta., the RF flip angle, is given by the Ernst equation. EQU .theta.=.gamma.B.sub.1 .tau.
Once the RF field is removed, the magnetization is subjected to the effect of the static magnetic field and processes about it. With a detection coil positioned with its axis along the y axis, the AC voltage induced in the coil is given by EQU .gamma..delta.Mxy.degree.cos w.tau.
Mxy.degree.=initial transverse magnetization following a 90 degree RF pulse PA0 .tau.=time interval between the rotation PA0 1) inherent spin density; PA0 2) longitudinal relaxation time (T1); PA0 3) transverse relaxation time (T2); and PA0 4) flow. PA0 1) the paramagnetic concentration; PA0 2) the distance (.gamma..sup.-6); and PA0 3) a time constant describing the dynamic nature of electron-proton interactions (correlation time). PA0 1) increased effective magnetic moment; PA0 2) decreased freedom of molecular motion; and PA0 3) decreased water .sup.1 H exchange. PA0 1. They increase the specificity of MRI diagnosis. PA0 2. Smaller lesions can be identified earlier. PA0 3. Image-enhancing agents enhance tumor masses differently than surrounding edema fluid or abscesses. This allows the extent and invasion of tumor to be defined more precisely. Lesion with infiltrative-type growth (e.g., certain metastatic carcinomas and glioblastomas) will require contrast agents for demarcation between tumor and edema fluid (Felix et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 831). PA0 4. Image-enhancing agents improve the distinction between recurrent tumor and fibrous tissue resulting from surgery and radiation. PA0 5. Image-enhancing agents can decrease the time required per scan and potentially decrease the number of scans required per procedure. This increases the volume of procedures and decreases their expense. PA0 6. Body imaging has a significantly lower resolution (typically 0.5-1.0 cm) and sensitivity (decreased signal-to-noise ratio) than brain imaging (Wesbey et al. (1983) Radiology V 149, p 175). These differences result from the greater inhomogeneity of the magnetic field; the larger radio frequency coil; unequal phase-pulsing of deep versus shallow nuclei; and motion artifacts produced by respiration, cardiac systole, gastrointestinal peristalsis, and voluntary muscle movement; and PA0 7. Advanced (polymeric and microsphere) forms of contrast agents (see below) appear to be required for the optimal acquisition and interpretation of blood-flow and tissue-perfusion images and related spectral (phase) information.
The transverse magnetization decays to zero exponentially with a time constant T2*.
Therefore: EQU .gamma..delta.Mxy.degree.e.sup.-.tau./T2 * cos w.tau.
This equation represents a damped oscillation that is called the induction decay or F10 signal. As the transverse magnetization decays to zero with time, the longitudinal magnetization increases back to its equilibrium value. This return to equilibrium values is termed relaxation. RF stimulation causes the nuclei to absorb energy transferring them to the excited state. The nuclei can return to the ground state by transferring energy to their surroundings, the so called lattice. This method of relaxation is called spin-lattice relaxation (T1). (see FIG. 4) Components of M, after being rotated to the x'y' plane, (FIG. 5) return to their original magnetization values in a time (T2), the "spin-spin" relaxation time. In the T2 relaxation process, nuclei in the excited and ground state exchange energy with each other. Thus T2 measures the amount of time necessary for the nuclei to get out of phase with each other and return to the original random state. Both T1 and T2 relaxation times of a nuclei can vary widely from milliseconds to minutes depending upon the nuclei and the environment surrounding them. The primary task of magnetic resonance imaging is soft tissue contrast and the detection of low-contrast lesions. The detection of lesions depends on the inherent difference in contrast between lesions and surrounding normal tissues. The tissue or media present around a resonating nucleus have differential effects that can alter the T1 and T2 relaxation times. However, in general, organic substances such as those found in the body (tissues, organs) have a fairly uniform effect on relaxation times, largely due to the high percentage of water. MRI scans of a substance take advantage of relaxation times (T1 and T2) differences to generate an image of the object being scanned in "slices." The difference in relaxation times of, say, different organs in the body allows a visible image to be formed. However, the largely uniform effect on relaxation times of most parts of the body causes an image that is very difficult to see due to lack of contrast, hence the need for "contrast agents."
Inherent tissue contrast in MRI is determined by differences in:
Contrast agents can improve visualization of low contrast organs and lesions. The most promising agents affect signal by enhancing relaxation. A contrast agent is a substance, either 1) a paramagnetic metal ion, 2) free oxygen, or 3) a substance with free radicals (unpaired electrons), that has a far different effect on proton relaxivity than water. A good contrast agent can be either directly injected into the target area or tagged to an antibody against the target area (e.g., a cancerous tumor) and thus provide sharp contrast for aid in viewing the area by MRI.
Pharmacologic basis for relaxation enhancement is based on positive magnetic susceptibility (Bourdreaux, E. A. and Mulap, L. N.: THEORY AND APPLICATION OF MOLECULAR PARAMAGNETISM, New York, 1976, John Wiley and Sons). When a substance is placed in an external magnetic field, induced magnetization in the substance is additive to that of the applied field. The magnetic susceptibility of a substance is defined as the ratio of induced magnetization to that of the applied field. Substances can be categorized by their magnetic susceptibility (see Table I).
TABLE I ______________________________________ (David Stark and William Bradley: MAGNETIC RESONANCE IMAGING, St. Louis, 1988, Mosby) CLASS BASIS SUSCEPTIBILITY ______________________________________ Diamagnetic paired electrons- -10.sup.-6 no permanent spin moment Paramagnetic unpaired electrons +10.sup.-1 non-interacting permanent moments Superparamagnetic unpaired electrons- +10.sup.+2 non-interacting domains Ferromagnetic unpaired electrons- +10.sup.+2 interacting domains ______________________________________
Diamagnetic substances have negative susceptibilities. Most organic and inorganic compounds are diamagnetic and since all atoms experience induced magnetic affects arising from electron orbital motion, a diamagnetic component is present in all materials. Diamagnetic effects are very weak and can be overwhelmed in magnitude by relatively few unpaired electron spins. Diamagnetic materials are generally of little interest as contrast agents.
Paramagnetic, superparamagnetic, and ferromagnetic substances are characterized by the predominant magnetic effects of unpaired electron spins which produce positive susceptibilities and positive induced magnetization.
Paramagnetism is characterized by independent action of individual atomic or molecular magnetic moments. Ferromagnetism is characterized by solid phase microscopic volumes or domains in which unpaired electron spins are permanently aligned. Multiple domains in bulk can be isotropic (unmagnetized) or anisotropic (magnetized).
Superparamagnetic materials can be regarded as single domain particles. The susceptibilities per atom or mole of these substances exceed those of corresponding soluble paramagnetic species due to magnetic ordering.
Superparamagnetic and ferromagnetic susceptibilities increase linearly with field strength. Superparamagnetic substances unlike ferromagnetic substances are characterized by restoration of induced magnetization to zero upon removal of the external field.
Paramagnetic enhancement of nuclear relaxation was first described in 1946 by Bloch and co-workers (Bloch, F., Hansen, W. N., and Packard, P.: "The nuclear induction experiment", Physiol. Rev. 70:474-485, 1946) when they demonstrated a convenient practice of shortening the time needed to observe water .sup.1 H T1 by adding ferric nitrate (a paramagnetic solute).
Positive susceptibility is necessary, but not sufficient, for effective relaxation. The magnitude of relaxation enhancement also depends on proximity and on correlation time. A mathematical formulation of paramagnetic enhanced solvent relaxation is described by Bloembergen (Bloembergen, N.: "Proton relaxation times in paramagnetic solutions", J. Chem. Phys. 27:572, 1957). These equations imply that nuclear relaxation results from several simultaneous mechanisms.
The paramagnetic contribution to nuclear relaxation is proportional to
The correlation time is dominated by the fastest rate of paramagnetic tumbling, electron spin flips, or chemical exchange. Due to more optimal correlation of spin motion, nuclear T1 relaxation enhancement in biologic systems is more effective with relaxation agents if large molecular weight or asymmetric shape, that is, relatively long rotational correlation times.
Solvent relaxation is the presence of superparamagnetic particles chiefly differs from that in the presence of paramagnetic solutes due to much greater weighting of the magnetic moment contribution. Compared with paramagnetic solutes, superparamagnetic particulates have
The much greater effective magnetic moment dominates these factors and results in T2 shortening caused by long range effect from magnetic field heterogeneity.
The imaging of internal structures and organs of live animals has been an important aspect of medicine since the advent of X-ray usage for this purpose. Among the techniques more recently developed for such imaging are those involving scanning for emission of particles form an internally located radioisotope. Such radioisotopes preferably emit gamma particles and are generally isotopes of metallic elements. One problem common to the diagnostic usage of such gamma particle-emitting radioisotopes concerns the localization of these materials at sites of particular interest rather than to have them randomly dispersed or rapidly excreted, by the kidney, for example. Another problem of such radioisotope mediated imaging concerns optimizing the circulating half-life of radioisotopes, for example, by preventing or accentuating their binding to serum proteins (e.g., albumin), or by prior conjugation (complexation) to polymeric carriers or receptor-binding substances.
A second class of internal body imaging which is undergoing a rapid growth in clinical use is ultrasound imaging. This is based on the detection of differences in the internal velocity (reflectivity) of directed, high-frequency sound waves. Differences in image brightness are produced at the interfaces between tissues with different native densities and ultrasound reflectivities. A present clinical problem is the difficulty of visualizing lesions in the stomach, small and large bowel, bladder, and cavities of the female reproductive tract, due to similarities of ultrasound velocity between these organs of interest and immediately adjacent tissues. Diagnostic introduction of a dense, nonradioactive metal element or ion at sufficient concentrations can confer the significant differences in ultrasound reflectivity which are required to visualize otherwise undetectable tumors and inflammatory lesions.
NMR intensity and relaxation images have been shown in recent years to provide a third important method of imaging internal structures and organs of live animals. Clinical magnetic resonance Imaging (MRI) is a rapidly growing, new form of brain and body imaging. Low-field (proton) MRI detects chemical parameters in the immediate environment around the protons because of body tissues (predominantly water protons because of their relative abundance). Changes in these parameters occur very early in disease and are independent of physical densities detected by ionizing radiation. In the brain and central nervous system, MRI has allowed detection of tumors at an earlier clinical stage and with fewer imaging artifacts than is possible with computerized axial tomography (CAT) (Runge et al., (1983) Am. J. Radiol. V 141, p 1209). Under optimal conditions, image resolution is in the submillimeter size range.
Seven factors are among those making it important to develop nontoxic MRI image-enhancing agents analogous to those available for CAT.
The discrete intensities of a two-dimensional, Fourier-transformed image are described by the following general equation (for spin-echo pulse sequences): EQU Intensity=N(H).multidot.f(v).multidot.exp(-TE/T2).multidot.(1-exp(TE-TR)/T1 ),
where
The T1 and T2 times have reciprocal effects on image intensity. Intensity is increased by either shortening the T1 or lengthening the T2 or vice versa depending upon whether proton density, T1-weighted or T2-weighted images are desired. Tissue contrast occurs naturally and is related to variations in the chemical environments around water protons (major contributor) and lipid protons (usually minor). Chemical agents have been used to enhance this natural contrast. The one most widely tested clinically is the paramagnetic metal ion, gadolinium (Gd.sup.+3) chelated to an appropriate organic chelate (Runge et al. (1983) Am. J. Radiol. V 142, p 619). Although gadolinium shortens both the T1 and T2 times, at the lower does used for clinical imaging, the T1 effect generally predominates and the image becomes brighter. Also, the rf pulse sequence can be programmed to accentuate T1 changes and diminish those due to T2 (Runge et al. (9183) Am. J. Radiol. V 141, p 1209). Hence, "T1-weighted" enhancement can be achieved by selecting the most favorable Gd dose and rf pulse sequence.
The shortening of proton relaxation times by Gd is mediated by dipole-dipole interactions between its unpaired electrons and adjacent water protons. The effectiveness of Gd's magnetic dipole drops off very rapidly as a function of its distance form these protons (as the sixth power of the radius) (Brown (1985) Mag. Res. Imag. V 3, p 3). Consequently, the only protons which are relaxed efficiently are those able to enter Gd's first or second coordination spheres during the interval between the rf pulse an signal detection. This ranges from 10.sup.5 to 10.sup.6 protons/second (Brown (1985) Mag. Res. Imag. V 3, p 3). Still, because Gd has the largest number of unpaired electrons (seven) in its 4f orbital, it has the largest paramagnetic dipole (7.9 Bohr magnetons) and exhibits the greatest paramagnetic relaxivity of any element (Runge et al. (1983) Am. J. Radiol. V 141, p 1209 and Weinman et al. (1984) Am. J. Radiol. V 142, p 619). Hence, Gd has the highest potential of any element for enhancing images. However, the free form of Gd is quite toxic. This results in part from precipitation at body pH (as the hydroxide). In order to increase solubility and decrease toxicity, Gd has been chemically chelated by small organic molecules. To date, the chelator most satisfactory from the standpoints of general utility, activity, and toxicity is diethylenetriamine pentaacetic acid (DTPA) (Runge et al. (1983) Am. J. Retail V 141, p 1209 and Weinman et al. (1984) Am. J. Retail V 142, p 619). The first formulation of this chelate to undergo extensive clinical testing was developed by Schering Ag - Berlex Imaging according to a patent application filed in West Germany by Gries, Rosenberg and Weinmann (DE-OS 3129906 A 1 (1981). It consists of Gd-DTPA which is neutralized and stabilized with the organic base, N-methyl-D-glucamine (meglumine). The Schering-Berlex agent is nearing completion of Phase III clinical testing at selected centers across the United States and abroad. The results of preliminary studies indicated that almost all human brain tumors undergo significant enhancement (Felix et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 831 and K. Maravilla, personal communication). These include metastatic carcinomas, meningiomas, gliomas, adenomas and neuromas. Renal tumors are also enhanced satisfactorily (Lanaido et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 877 and Brasch et al. (183) Am. J. Retail. V 141. p 1019). The Schering-Berlex formulation was available for general clinical use by 1989.
Despite its satisfactory relaxivity and toxicity, this formulation has four major disadvantages.
(1) Chelation of Gd markedly decreases its relaxivity (by 1/2 an order of magnitude). This happens because chelators occupy almost all of Gd's inner coordination sites which coincide with the strongest portion of the paramagnetic dipole (Koenig 1985) Proc. Soc. Mag. Res. Med. V 2, p 833 and Geraldes et al. (1985) Proc. Soc. Mag. Res. med. V 2, p 860).
(2) Gd-DTPA dimeglumine, like all small paramagnetic metal chelates, suffers a marked decrease in relaxivity at the higher radio frequencies used clinically for proton imaging (typically 5 MHz, 2T) (Geraldes et al. (1985) Proc. Soc. Mag. Res. med. V 2, p 860).
(3) Due to its low molecular weight, Gd-DTPA dimeglumine is cleared very rapidly from the bloodstream (t.sup.1/2 in 20 minutes) and also from tissue lesions (tumors) (Weinman et al. (1984) Am. J. Radiol V 142, p 619). This limits the imaging window (to ca. 30 to 45 minutes); limits the number of optimal images after each injection (to ca. 2); and increases the agent's required dose and relative toxicity.
(4) The biodistribution of Gd-DPTA is suboptimal for imaging of body (versus brain) tumors and infections. This is due to its small molecular size. Intravenously administered Gd-DTPA exchanges rapidly into the extracellular water of normal tissues, as well as concentrates in tumors and infections. This is facilitated by an absence in body organs, of the "blood-brain" vascular barrier which partly restricts the exchange of Gd-DTPA into the extracellular water of normal (versus diseased) brain. The result in body organs, is a reduced difference in the concentration of Gd-DTPA between normal and diseased regions of tissue, and hence, reduced image contrast between the normal and diseased regions of the organ. Also a disproportionate quantity (>90%) of Gd-DTPA is sequestered very rapidly in the kidneys (Weinman et al. (1984) Am. J. Radiol V 142, p 619). Of much greater interest to body MRI, are the abdominal sites involved in the early detection and staging of tumors (particularly the liver, and also the spleen, bone marrow, colon and pancreas).
Three approaches have been taken in attempts to overcome these disadvantages.
(1) Alternative, small chelating molecules have been tested. These make Gd more accessible to water protons but still chelate the metal with a sufficient affinity to potentially control its toxicity in vivo. The most effective of these chelators is DOTA, the poly-azamacrocyclic ligand, 1,4,7,10-tetraazacyclododecane-N,N',N"-tetraacetic acid (Geraldes et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 860). Its relaxivity is approximately 2 times greater than that of Gd-DTPA over a wide range of Larmor frequencies. However, it is still less active than free Gd.
(2) Gd and Gd-chelates have been chemically conjugated to macromolecules, primarily the proteins, albumin (Bulman et al. (1981) Health Physics V 40, p 228 and Lauffer et al. (1985) Mag. Res. Imaging V 3, p 11), asialofetuin (Bulman et al. (1981) Health Physics V 40, p 228), and immunoglobulins (Lauffer et al. (1985) Mag. Res. Imaging V 3, p 11 and Brady et al. (1983) Soc. Mag. Res., 2nd Ann. Mtg., Works in Progress, San Francisco , Calif.). This increases the relaxivity of Gd by slowing its rate of molecular tumbling (rotational correlation time) (Lauffer et al. (1985) Mag. Res. Imaging V 3, p 11). This improves coupling of the energy-transfer process between protons and Gd (Geraldes et aI. (1985) Proc. Soc. Mag. Res. Med. V 2, p 860, Lauffer et al. 91985) Mag. Res. Imaging V 3, p 11 and Brown et al. (1977) Biochemistry V 16, p 3883). Relaxivities are increased by multiples of 5 to 10 relative to Gd-DTPA (when compared as R1=1/T1 values at 1 millimolar concentrations of Gd) and by multiples of 2.5 to 5.0 (when compared as the molarities of Gd required to produce a specified decrease in the T1 relative to a control solution (physiologic saline).
The reasons for using the latter method of comparison are that 1) millimolar concentrations of Gd are never achieved in vivo--actual tissue concentrations achieved in the usual image enhancement are between 20 and 100 micromolar Gd; 2) the slopes of R1 graphs are frequently nonparallel for different enhancing agents; 3) the second method allows agents to be compared according to the more customary means of chemical activity ratio, in other words, as the concentration required to produce a specified percentage decrease in the T1 (or T2) relaxation time. The second method is considered preferable. A drawback of conjugating DTPA to protein carriers for use in NMR image enhancement is that it has been difficult to stably conjugate more than 5 DTPAs (and hence Gd's) to each albumin molecule (Bulman et al. (1981) Health Physics V 40, p 228, Lauffer et al. (1985) Mag. Res. Imaging V 3, p 11 and Hnatowioh et al. (1982) Int. J. Appl. Radiat. Isot. V 33, p 327 (1982).
Comparably low substitution ratios (normalized for molecular weight) have been reported for immunoglobulins (Lauffer et al. (1985) Mag. Res. Imaging V 3, p 11 and Brady et al. (1983) Soc. Mag. Res., 2nd Ann. Mtg., Works in Progress, San Francisco, Calif.) and fibrinogen (Layne et al. (1982) J. Nucl. Med. V 23, p 627). This results from the relative difficulty of forming amide bonds, the comparatively low number of exposed amino groups on typical proteins which are available for coupling, and the relatively rapid hydrolysis of DTPA anhydride coupling substrate which occurs in the aqueous solvents required to minimize protein denaturation during conjugation (Hnatowich et al. (1982) Int. J. Appl. Radiat. Isot. V 33, p 327 (1982) and Krejcarek et al. (1977) Biochem. Biophys. Res. Comm. V 77, p 581). The overall effect of these suboptimal conditions is that a very large dose of carrier material is required to achieve significant in vivo effects on MR images. At this high dose, the carrier produces an unacceptable acute expansion of the recipient's blood volume by an osmotic mechanism. Indeed, low substitution ratios have generally limited the use of such protein-chelator-metal complexes to the more sensitive (low-dose), radiopharmaceutical applications (Layne et al. (1982) J. Nucl. Med. V 23, p 627).
An attempt to overcome this low substitution ratio has been made by conjugating DTPA to the non-protein carrier, cellulose (Bulman et al. (1981) Health Physics V 40, p 228), however the chemical method employed results in continued suboptimal substitution of DTPA to carrier, the nonbiodegradability of cellulose and its water-soluble derivatives and the reported molecular aggregation which results from organic-solvent conjugation (in dimethylformamide) of CNBr-activated cellulose to the diaminohexyl spacer groups which link the carrier to DTPA, have rendered this class of carrier-conjugates unacceptable for intravenous administration at the doses required for MR image enhancement.
A very important consideration in the image enhancement of solid tumors and inflammatory lesions by polymeric contrast agents is that, in order for these agents to extravasate (exit) efficiently from the microcirculation into adjacent diseased tissues, they must be completely soluble--e.g., not be contaminated by intermolecular or supramolecular microaggregates. Optimal tumor access and localization requires that the molecular size of such agents generally be less than approximately 2,000,000 daltons (ca. 2 to 3 nanometers in molecular diameter), and preferably less than 500,000 daltons (ca. 0.5 to 1.0 nanometers in molecular diameter) (Jain (1985) Biotechnology Progress V 1, p 8I). For this reason, with rare exceptions the particulate and microaggregate classes of contrast agents (which comprise the liposomes, colloids, emulsions, particles, microspheres and microaggregates, as described below) do not concentrate efficiently in most solid tumors or inflammatory lesions. Instead, following intravenous administration, these supramolecular-sized agents: a) are first circulated in the bloodstream for relatively short intervals (225 minutes to 24 hours, depending on size), potentially allowing direct image enhancement of the blood pool (plasma compartment); and b) are subsequently cleared by specialized (phagocytic) cells of the reticuloendothelial tissues (liver, spleen and bone marrow), potentially allowing selective enhancement of these normal tissues, but producing indirect (negative) enhancement of lesions within these tissues (due to exclusion of the agents from the diseased regions). Additionally, following installation into the gastrointestinal tract and other body cavities, these particulate and microaggregate classes of agents can produce direct image enhancement of the fluid within these cavities, and thereby potentially delineate mass lesions which encroach upon the lumens and cavities. Both microspheres and microaggregates are supramolecular in size. The microaggregate class of agents is produced (intentionally or unintentionally) by either a) molecular cross-linking of individual polymer molecules or b) secondary aggregation of previously single (soluble) polymers, as induce by charge attraction or hydrophobic bonding mechanisms. It is distinguished from the microsphere class of agents by virtue of its smaller particle size, which ranges from approximately 2,000,000 daltons (ca. 2 to nanometers in diameter) to 0.1 micrometers (=100 nanometers in diameter). It is important to note that microaggregates are cleared by reticuloendothelial phagocytes with significantly less efficiency and rapidity than are microspheres. In general, this property makes microaggregates a less preferred class of agents for visualizing the liver, spleen and bone marrow under the usual conditions of clinical imaging, for which prompt post-injection contrast enhancement is required.
(3) Gd-DTPA has been entrapped in liposomes (Buonocore et al. (1985) Proc. Soc. mag. Res. med. V 2, p 838) in order to selectively enhance images of the reticuloendothelial organs (liver, spleen and bone marrow) and potentially the lungs. Liver clearance is mediated by phagocytic (Kupffer) cells which spontaneously remove these small (0.05 to 0.1 um) particles from the bloodstream (Buonocore et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 838). (Particles larger than 3 to 5 um are selectively localized in the lungs due to embolic entrapment in lung capillaries.) A recent report indicates that the small-sized Gd-liposomes produce effective decrease in liever T1's (as determined spectroscopically without imaging) (Buonocore et al. (1985) Proc. Soc. Mag. Res. med. V 2, 0838). Also, insoluble GdDTPA colloids have recently been reported to enhance MR images of rabbit livers under in vivo conditions (Wolf et al. (1984) Radiographics V 4, p 66). However, three major problems appear to limit the diagnostic utility of these devices. The multilamellar, lipid envelopes of liposomes appear to impede the free diffusion of water protons into the central, hydrophobic cores of these carriers, as assessed by the higher does of Gd required for in vitro relaxivities equivalent to Gd-DTPA dimeqlumine (Buonocore et al. (1985) Proc. Soc. mag. Res. med. V 2, p 838). This increases the relative toxicity of each Gd atom.
Even more importantly, these same lipid components cause the carriers to interact with cell membranes of the target organs in a way which leads to a marked prolongation of tissue retention (with clearance times of up to several months) (Graybill et al. (1982) J. Infect. Dis. V 145, p 748 and Taylor et al., 1982 Am. Rev. Resp. Dis. V 125, p 610) . Two adverse consequences result. First, image enhancement does not return to baseline in a timely fashion. This precludes re-imaging at the short intervals (ca. 1 to 3 weeks) needed to assess acute disease progression and treatment effects. Second, significant quantities of the liposomally entrapped Gd-DTPA may be transferred directly into the membranes of host cells (Blank et al. (1980) Health Physics V 39, 913; Chan et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 846). This can markedly increase the cellular retention and toxicity of such liposomal agents. The consequences for Gd toxicity have not yet been reported. Protein (albumin) microspheres with entrapped Gd and Gd chelates have been prepared and determined (Saini et al. (1985) Proc. Soc. Mag. Res. Med. V 2, p 896) to have only modest effects on T1 relaxivity in vitro. This is because most of the Gd as well as other entrapment materials (Widder et al. (1980) Cancer Res. V 40, p 3512) are initially sequestered in the interior of these spheres and are released very slowly as the spheres become hydrated (with t1/2's of hours) (Widder et al. (1980) Cancer Res. V 40, 3512).
Emulsions of insoluble gadolinium oxide particles have been injected into experimental animals with significant image-enhancing effects on the liver (Burnett et al. (1985) Magnetic Res. Imaging V 3, p 65). However, these particles are considerably more toxic than any of the preceding materials and are thus inappropriate for human use. Because of the significant disadvantages of existing MR image contrast agents, the present applicant has formulated improved, second-generation prototype agents with reduced toxicity, phenominally increased effectiveness potentially increased selectivity of tumor and organ uptake, as well as a significant potential for enhancing blood flow images.
Many of the advantages shown for the present developments concerning NMR image-enhancing agents (also referred to herein as NMR contrast agents or MR (magnetic resonance) contrast agents) are also expandable to other areas. Gadolinium and related agents can produce characteristic changes in the NMR spectrum of adjacent NMR-susceptible nuclei. These changes include: modulation of resonance peak positions, widths, intensities, and relaxation rates (which affect intensity). Hence, perturbation of spectra by such chemical shift-relaxation agents can be used to localize and identify the source of NMR signal with respect to organ location, tissue compartment (intravascular versus extravascular), cell type within the tissue, and potentially, the specific metabolic pathways within cells which are altered by drugs and disease. Also in certain situations, ultrasound imaging or body scanning of radioisotopic emissions is particularly useful in achieving insight into internal structures. The radioisotopic emissions most frequency scanned are those of metallic radioisotopes emitting gamma particles, however, positron emission tomography is experiencing increased clinical use. The molecular formulation and mode of administering these radioisotopic metals will have significant consequences on the internal localization and body half-life of these radioisotopes, potentially leading to increased diagnostic usage of these ultrasound images and emission scannings.
The present invention includes an image-enhancing or spectral-shift agent comprising a biodegradable, water-soluble or insoluble melanin polymer, synthetic or derived from natural sources and having a signal-inducing metal or metal particle incorporated therein.
Melanins are a group of pigments derived from several different amino acid substrates in the natural world. Different types of melanins are responsible for much of the coloration in animals, plants, and bacteria. Melanins are usually classified in one of three groups: eumelanins, such as those found in hair, skin, feathers, and as a part of the coloration in reptiles and fish; phaeomelanins, which produce human red hair and the read fur of foxes; and allomelanins, which are most often present in bacteria and plants. An example of one of the most striking effects of a combination of eumelanins and phaeomelanins in the patterns found in the plumage of certain tropical birds.
Melanins are created by the action of enzymes on any of several amino acid precursors. For example, tyrosine is the precursor of most eumelanins. However, the exact process by which an amino acid is converted to melanin is unknown, and indeed, seems to vary from one pigment to another even when formed from the same substrate. In general, black pigments are formed from precursors including 3,4-dihydroxyphenylalanine (DOPA), catechol, and various other dihydroxy- substances.
______________________________________ OH CH COOH OH CH OH NH OH NH 3,4-dihydroxyphenylalanine 5,6-dihydroxyindole (DOPA) HO OH OH OH catechol 1,8-dihydroxynaphthalene ______________________________________
These substances have many active centers for polymerization. Compounds with fewer active centers are precursors to melanins of brown, reddish-brown, or yellow-brown color.
Melanins in pure form are usually insoluble in water as well as in most organic solvents, making them difficult to work with. In part due to this, not all of the chemical properties of melanins have been identified. However, recent studies using electron spin spectroscopy have identified free-radical properties of melanin.
Synthetic melanins can be created from most of the precursors used in nature by using almost any chemical oxidant or free-radical polymerizer, or, in some cases, merely leaving dissolved substrate open to the air overnight.

Melanin-based agents for image enhancement

Board of Regents, The University of Texas System


A method of treating a porous dielectric layer includes preparing a substrate on which the porous dielectric layer including an opening and pores exposed by the opening is formed, supplying a first precursor onto the substrate to form a first sub-sealing layer sealing the exposed pores, and supplying a second precursor onto the first sub-sealing layer to form a second sub-sealing layer covering the first sub-sealing layer. Each of the first and second precursors includes silicon, and a molecular weight of the second precursor is smaller than that of the first precursor.

1. Technical Field
The inventive concepts relate to a method of treating a porous dielectric layer and a method of fabricating a semiconductor device using the same. More particularly, the inventive concepts relate to a method of treating a low-k dielectric layer having a plurality of pores and a method of fabricating a semiconductor device using the same.
2. Description of the Related Art
As semiconductor devices have become highly integrated and capacity of semiconductor devices has increased, pitches of metal interconnections in semiconductor devices has been reduced. Thus, parasitic capacitances of semiconductor devices may be increased, so operation speeds of semiconductor devices may be reduced. To reduce the parasitic capacitances of semiconductor devices, various research is conducted for low-resistance copper interconnections and low-k dielectrics.

Method of treating a porous dielectric layer and a method of fabricating a semiconductor device using the same


The present invention provides a method for forming a thin film pattern having an excellent accuracy of the pattern. The method comprises the steps of:. (a) exposing a polysilane layer formed from a polysilane having a structure of the formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 indicate a group which is independently selected from the group consisting of a substituted or non-substituted aliphatic hydrocarbon residue, an alicyclic hydrocarbon residue and an aromatic hydrocarbon residue and m and n indicate an integer, provided on a substrate, to ultraviolet light selectively to form a latent image of the thin film pattern; and PA1 (b) dipping the polysilane layer in which the latent image of the thin film pattern is formed in a metal oxide sol and then drying.

A method for synthesizing a ceramic thin film using a solution reaction (referred to as a "sol-gel processing") has attracted special interest recently. The sol-gel processing is a method comprising synthesizing an inorganic polymer precursor from an organic metal compound or a metal complex in a solution by using a hydrolysis reaction or condensation reaction; applying the solution on a substrate by means of a spray method, dipping method or spin-coating method to form a thin film; and subjecting the thin film to a heat treatment to form a functional ceramic thin film. The functional ceramic thin film is used as dielectric film, insulator film, protective film, etc. in electronic devices such as thin film capacitor, LSI, electroluminescent device and the like, and a formation technique by means of the sol-gel processing have been studied intensively. On the other hand, in addition to the above electronic devices, the sol-gel processing is applied for a surface treatment of functional glass or plastic, for example, anti-diffusion film of alkali, interference colored film, anti-reflection film, reflection film and the like.
The method for forming a thin film by means of the sol-gel processing has excellent characteristics such as temperature reduction of process temperature, freedom of composition, formation of uniform thin film on a substrate having a large surface area and the like.
However, there is no method of patterning a thin film, and a method of removing a thin film by conducting etching after formation of the thin film is popular. A complicated lithography step using a photoresist is required in order to conduct etching, and simplification of the step has been required.
Further, it has been studied to use a glass as the substrate for magneto-optic disc in view of durability, however, it's practical application is falling behind because of the largest disadvantage of the glass, i.e. a pre-groove can not be formed at low cost. For example, as the practical application of the sol-gel processing, there have been proposed a method of transferring a groove by a stamper while the gel is soft (Tohge et al., J. Am. Cream. Soc. 70, C13 (1987)) and RIE (Reactive Ion Etching) method wherein a photolithography method is combined with a dry-etching method after a SiO.sub.2 film was formed (Ota et al., Electronic Material, 27, 7, 57 (1988)). However, they are merely used for long-term storage in view of cost.
On the other hand, the present inventors have already proposed a process for dyeing a pattern using a silanol group produced by exposing an organic polysilane to ultraviolet light (Japanese Laid-Open Patent Publication No. 05-188215) and a method for coloring a pattern by dipping in a colored sol solution comprising a metal alkoxide containing a dye or a pigment as a raw material (Japanese Patent Application No. 4-68243). Further, the present inventors have studied to develop a function other than a colored pattern using a sol.
As described above, the present inventors have studied intensively. As a result, the present invention has been accomplished.


The invention relates to new and known tricyclic dione derivatives of the general formula ##STR1## wherein W represents hydrogen or lower alkyl;. X represents lower alkyl; PA1 Y represents NR1; PA1 R.sup.1 represents hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl; PA1 Z represents aryl or heteroaryl optionally substituted by one or more halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents and/or on adjacent carbon atoms by lower alkylenedioxy; PA1 R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each individually represent hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 together represent the group --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; PA1 Ar represents aryl optionally substituted by one or more halo, lower alkyl, lower alkoxy or nitro substituents; PA1 Het represents heteroaryl optionally substituted by one or more halo, lower alkyl, lower alkoxy or nitro substituents; and PA1 n stands for 0, 1 or 2. and to their salts which are inhibitors of herpes simplex virus thymidine kinase.

A number of compounds encompassed within compounds of the formula: ##STR2## wherein W is hydrogen or lower alkyl;
X is lower alkyl; PA1 Y is an oxygen atom or NR.sup.1 ; PA1 R.sup.1 is hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl; PA1 Z is either aryl or heteroaryl or aryl or heteroaryl substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het, Het-lower alkyl and on adjacent carbon atoms lower alkylenedioxy; PA1 R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are individually hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 together represent the group --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; PA1 Ar is aryl or aryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; PA1 Het is heteroaryl or heteroaryl substituted by one or more halo, lower alkyl, lower alkoxy or nitro substituents; and PA1 n stands for 0, 1 or 2 PA1 X is lower alkyl; PA1 Y is oxygen or NR.sup.1 ; PA1 R.sup.1 is hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl; PA1 Z' is either aryl or heteroaryl, where the aryl and heteraryl: PA1 R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each individually are hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 taken together form --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; PA1 Ar is aryl or aryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; PA1 Het is heteroaryl or heteroaryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; and PA1 n is 0, 1 or 2, with the proviso that a) when W and X is methyl and Y is an oxygen, then Z is not 2,4-dihydroxy-phenyl, 3,4-dimethoxy-phenyl, 4-benzyloxy-3,5-dimethoxy-phenyl, 4-hydroxy-3,5-dimethoxy-phenyl, 3-hydroxy-4-methoxy-phenyl, 3,5-dichloro-2-hydroxy-phenyl, 4-hydroxy-3-methoxy-phenyl, 3,4-methylenedioxy-phenyl or 2,4,5-trimethoxy-phenyl; and PA1 X is lower alkyl; PA1 Y is an oxygen atom or NR.sup.1 ; PA1 R.sup.1 is hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl; PA1 Z is either aryl or heteroaryl or aryl or heteroaryl substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het, Het-lower alkyl and on adjacent carbon atoms lower alkylenedioxy; PA1 R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are individually hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 together represent the group --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; PA1 Ar is aryl or aryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; PA1 Het is heteroaryl or heteroaryl substituted by one or more halo, lower alkyl, lower alkoxy or nitro substituents; and PA1 n stands for0, 1 or 2 PA1 X is lower alkyl; PA1 Y is oxygen or NR.sup.1 ; PA1 R.sup.1 is hydrogen, lower alkyl, lower alkoxycarbonyl or lower alkoxycarbonyl-lower alkyl; PA1 Z' is either aryl or heteroaryl, where the aryl and heteraryl: PA1 R.sup.2, R.sup.3, R.sup.4 and R.sup.5 each individually are hydrogen, lower alkyl, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents; or R.sup.2 and R.sup.3 taken together form --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; PA1 Ar is aryl or aryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; PA1 Het is heteroaryl or heteroaryl substituted with at least one halo, lower alkyl, lower alkoxy or nitro substituent; and PA1 n is 0, 1 or 2, with the proviso that a) when W and X is methyl and Y is an oxygen, then Z is not 2,4-dihydroxy-phenyl, 3,4-dimethoxy-phenyl, 4-benzyloxy-3,5-dimethoxy-phenyl, 4-hydroxy-3,5-dimethoxy-phenyl, 3-hydroxy-4-methoxy-phenyl, 3,5-dichloro-2-hydroxy-phenyl, 4-hydroxy-3-methoxy-phenyl, 3,4-methylenedioxy-phenyl or 2,4,5-trimethoxy-phenyl; and b) when W and X is methyl and Y is --NH--, then Z is not 2,5-dibenzyloxy-4-methyl-phenyl or 2,5-dihydroxy-4-methyl-phenyl; PA1 i) two or more halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents and/or on adjacent carbon atoms by lower alkylenedioxy; or by PA1 ii) one substituent from OHet, O-lower alkyl-Het, N(R.sup.4)COHet and NR.sup.2' R.sup.3' in which R.sup.2 ' and R.sup.3 ' together represent --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--. PA1 i) two or more halo, cyano, nitro, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, COR.sup.2, OCOR.sup.2, CO.sub.2 R.sup.2, OR.sup.2, S(O).sub.n R.sup.2, NR.sup.2 R.sup.3, N(R.sup.4)COR.sup.5, Ar, Ar-lower alkyl, Het or Het-lower alkyl substituents and/or on adjacent carbon atoms by lower alkylenedioxy; or by PA1 ii) one substituent from OHet, O-lower alkyl-Het, N(R.sup.4)COHet and NR.sup.2' R.sup.3 ' in which R.sup.2' and R.sup.3 ' together represent --CH.dbd.CH--CH.dbd.CH-- or --CH.dbd.N--CH.dbd.CH--; with the proviso that a) when W and X represent methyl and Y represents an oxygen atom, then Z does not represent 2,4-dihydroxy-phenyl, 3,4-dimethoxy-phenyl, 4-benzyloxy-3,5-dimethoxy-phenyl, 4-hydroxy-3,5-dimethoxy-phenyl, 3-hydroxy-4-methoxy-phenyl, 3,5-dichloro-2-hydroxy-phenyl, 4-hydroxy-3-methoxy-phenyl, 3,4-methylenedioxy-phenyl or 2,4,5-trimethoxy-phenyl; and b) when W and X represent methyl and Y represents NR.sup.1 in which R.sup.1 represents hydrogen, then Z does not represent 2,5-dibenzyloxy-4-methyl-phenyl or 2,5-dihydroxy-4-methyl-phenyl. PA1 9-(4-Chloro-3-phenoxyphenyl)-3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl-1,8 (2H,5H)-acridinedione; PA1 9-(4-chloro-3-phenylthiophenyl)-3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl- 1,8(2H,5H)-acridinedione; PA1 9-(6-chloro-3-biphenylyl)-3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl-1,8(2H ,5H)-acridinedione; PA1 9-[4-chloro-3-(4-pyridyloxy)phenyl]-3,4,6,7,8,10-hexahydro-3,3,6,6-tetramet hyl-1,8(2H,5H)-acridinedione; PA1 9-[4-chloro-3-(4-pyridylthio)phenyl]-3,4,6,7,8,10-hexahydro-3,3,6,6-tetrame thyl-1,8(2H,5H)-acridinedione; and PA1 9-(3-benzyloxy-4-nitrophenyl)-3,4,6,7,8,10-hexahydro-3,3,6,6-tetramethyl-1, 8(2H,5H)-acridinedione. PA1 a) for the manufacture of a compound of formula I in which Y represents an oxygen atom, reacting an aldehyde of the general formula EQU Z--CHO (II) PA1 wherein Z has the significance given earlier, with a cyclohexanedione derivative of the general formula ##STR9## wherein W and X have the significances given earlier, or b) for the manufacture of a compound of formula I in which Y represents NR.sup.1 and R.sup.1 represents hydrogen, reacting an aldehyde of formula II or an acetal or hemiacetal thereof with a cyclohexanedione derivative of formula III and aqueous ammonia, or PA1 c) for the manufacture of a compound of formula I in which Y represents NR.sup.1 and R.sup.1 represents hydrogen, lower alkyl or lower alkoxycarbonyl-lower alkyl, reacting an aldehyde of formula II or an acetal or hemiacetal thereof with a cyclohexenone derivative of the general formula ##STR10## wherein W and X have the significances given earlier and R.sup.6 represents hydrogen, lower alkyl or lower alkoxycarbonyl-lower alkyl, or PA1 d) for the manufacture of a compound of formula I in which Y represents NR.sup.1 and R.sup.1 represents lower alkoxycarbonyl, reacting a compound of formula I in which Y represents NR.sup.1 and R.sup.1 represents hydrogen with a lower alkyl chloroformate, or PA1 e) for the manufacture of a compound of formula I in which Z carries an amino or NHCOR.sup.5 substituent, reducing a corresponding compound of formula I in which Z carries a nitro substituent and, where required, acylating the resulting compound of formula I in which Z carries an amino substituent and, if desired, forming a salt.
or a salt thereof are disclosed in, inter alia, U.S. Pat. Nos. 3,414,587, 3,454,577 and 3,539, 590, European Patent Publications Nos. 524 041, 369 762, 539,154 and 539,153, German Offenlegungsschrift No. 2,003,148, PCT Patent Publication No. WO 9408966 and B. Loev et al., J. Med. Chem., 1974, 17(9), 956-965 and are reported therein to have activities as anthelmintics, antibacterials, antihypertensives or agents for the treatment of urinary incontinence. No mention is made in these references with respect to their inhibition of herpes simplex virus (HSV) thymidine kinase (TK).


A method of forming an uniform interlayer insulating film on a substrate of large size is provided. A semiconductor substrate is prepared which has an interconnection pattern formed thereon. A silicon oxide film is formed on the semiconductor substrate to cover the interconnection pattern by chemical vapor deposition method using mixed gas including gas having silicon atoms and hydrogen peroxide. A molar ratio of gas having silicon atoms to hydrogen peroxide is adjusted to be within the range of from 1:2 to 1:4.

1. Field of the Invention
The present invention generally relates to a method of forming an interlayer insulating film, and more particularly to an improved method thereof wherein the film can be formed uniformly on a substrate of large size.
2. Description of the Background Art
In a method of manufacturing a semiconductor device, a step of forming an interlayer insulating film is indispensable. FIGS. 5A-5C are cross sectional views of a semiconductor device in respective process steps of forming a conventional interlayer insulating film.
Referring to FIG. 5A, an aluminum interconnection pattern 12 is formed on a silicon substrate 11. A first plasma oxide film 13 is then deposited on the silicon substrate 11 such that it covers the surface of the aluminum interconnection pattern.
Referring to FIG. 5B, a silicon oxide film 14 (interlayer insulating film) is formed by chemical vapor deposition using mixed gas including silane gas (SiH.sub.4) and hydrogen peroxide to cover the aluminum interconnection pattern.
Referring to FIG. 5C, a second plasma oxide film 15 is formed on the semiconductor substrate 11 to cover the silicon oxide film 14, thereby a planar insulating film is obtained.
The silicon oxide film 14 formed by CVD using silane gas and hydrogen peroxide can fill the space less than 0.25 .mu.m between densely patterned interconnections. Further, the silicon oxide 14 is excellent in fluidity and therefore shows a self planarization feature, so that this method attracts attention as the next generation way for planarizing an interlayer insulating film alternative to the conventional way employing SOG (Spin on glass). (Technical Digest of IEDM 1994, Proceedings of DUMIC Conference, 1995)
A silicon oxide film has been formed as described above by CVD using silane gas and hydrogen peroxide. However, in the LSI process, as the diameter of a substrate wafer becomes larger, to deposit an uniform film over such a large wafer has become extremely difficult. Even if an interlayer insulating film is formed by CVD using silane gas and hydrogen peroxide as described, the CVD method still has the same problem. Although attempts have been made to improve the uniformity of film thickness by modifying the structure of a reaction chamber and adjusting the conditions of forming a film, an appropriate method has not been established.

Method of forming an interlayer insulating film


A chip assembly includes a semiconductor chip and a wirebonded wire. The semiconductor chip includes a passivation layer over a silicon substrate and over a thin metal structure, a first thick metal layer over the passivation layer and on a contact point of the thin metal structure exposed by an opening in the passivation layer, a polymer layer over the passivation layer and on the first thick metal layer, and a second thick metal layer on the polymer layer and on the first thick metal layer exposed by an opening in the polymer layer. The first thick metal layer includes a copper layer with a thickness between 3 and 25 micrometers. The wirebonded wire is bonded to the second thick metal layer.

1. Field of the Invention
The invention relates to a chip assembly, and, more specifically, to a chip assembly having a thick metallization structure formed over a passivation layer of a chip and bonded with a wire through a wire-bonding process.
2. Brief Description of the Related Art
As known in the art, wire bonding is a technology used to attach a fine wire, usually 1 to 3 mils in diameter, from one connection pad to another, completing the electrical connection in an electronic device.

Wirebond over post passivation thick metal


A method of constructing a tight mesh golf net with a support frame that returns a ball to a user, comprising routing the net around the support frame from a forward section that returns the golf ball to the user, under and around a rod between side supports, toward the forward section and upward toward top ends of the side supports.

Golf is a popular sport and in many cases it takes a long time to practice successfully. Thus, golfers often spend a lot of time practicing to improve and improve their golf skills in order to excel in this sport.
In general, golfers typically practice by hitting a golf ball at an outdoor driving range so that they can repeatedly polish their skills by hitting the golf ball. A golf driving range provides an important means for practice, but in many cases golfers must drive for 10-30 minutes to the driving range, and it takes the same time to return home. Traveling to the practice range can be time consuming. In many cases, an extra 30 minutes to 1 hour is spent traveling.
Golfers desire a solution so that golfers can practice in a smaller space (often at the golfer's home or backyard) to eliminate the need to visit an outdoor driving range and provide more practice time for the golfer This net has been invented to solve that issue. However, despite the great advantages offered when compared to golf driving ranges, golf nets on the market currently still have some drawbacks that prevent them from becoming popular practice methods for so-called average golfers.
U.S. Pat. No. 4,556,219, Tillery, is more less a box with one end open, with the open end having extensions for the golfer to hit. The golfer needs to retrieve the ball, and the net is quite large and bulky,
U.S. Pat. No. 5,492,319, Lee, is also a box with one end open, but it has a sloping floor to return the ball to the user.
U.S. Pat. No. 6,315,677, Sandin is a golf ball catching funnel, catching balls that go into a net, that drops balls down a hole in the funnel net into a bucket.
U.S. Pat. No. 7,021,630, Cho, presents a net with a back frame for support and a target on the net. This device net is not taunt and the ball drop straight into the net.
U.S. Pat. No. 7,318,777, Sells, offers a product that concentrates on a net that returns a ball to a green area where it goes through a hole and is returned to the user.
U.S. Pat. No. 10,173,117, Cho, abstract reads
"A ball-returning net comprises a vertical wire frame, a vertical net, a floor wire frame, a slope net, two side barrier nets, and a detachable strap. The vertical net is fixed to the edge portion of the vertical wire frame and blocking the opening of the vertical wire frame. The slope net is disposed over the floor wire frame so as to be tilted from an elevated lower portion. of the vertical net to a front edge portion of the floor wire frame, so as to be configured that a ball hitting the vertical net falls down on the slope net and rolls down in a direction of the front edge portion of the floor wire frame. The detachable strap holds the slope net and the vertical wire frame tightly, bending a rear portion of the slope net in a V shape."
This patent seem similar at first to the current application, it is a net with a slope that returns the ball to the user. This net has a front piece that is sloped to return the ball.
The drawback to this patent is that the slope of the net can also cause a. golf ball hit into it to go into the air. The other drawback is the sloping front part of the net doesn't cover the entire net.
The difference this application has over Cho is the method of construction. All of the patents listed above have a frame with a net attached to edges of the frame. The tautness of the frame depends on the tightness of the net When it is attached to the frame.
The method of this patent delivers a net that is more taunt and that will not allow bails to go and sit in the net. This is covered in the SUMMARY OF THE INVENTION SECTION, but the path the net covers over several support rods, adds tension and tightness to the net. The net is not simply attached to the net as is the case for all of the prior art. The other feature of construction that the device of this application is that the upward portion of the net going to the top of the side supports has wings which attach to the side support rods, a feature no other patent has.
A drawback with typical many golf nets is that golf nets often require golfers to step into the net to retrieve the balls, which may have been caught in the debt. Golf nets can be very fragile and require frequent replacement, especially when users need to step in, or reach in with a golf club to retrieve a ball. This short life and awkward use often keeps golfers away from purchasing a golf net. The method of this application produces a net that does not require any interaction with the net once a golf shot has been hit.

Method of constructing an energy absorbing and golf ball returning golf net


A method of displaying text on multiple display devices. The multiple display devices include a master device with a master display and at least one slave device with a slave display. The method includes establishing communication between the master device and the slave device, dividing the text into a first part and a second part based on a first display dimension of the master display and a second display dimension of the slave display, transmitting the second part to the slave device, and simultaneously displaying the first part on the master display and the second part on the slave display. For each individual row of text that is displayed on both the master display and the slave display, a fraction of text is displayed on the master display and a remaining fraction of text is displayed on the slave display.

1. Field of the Invention
The present invention relates to display devices, and more specifically, to a method for utilizing multiple display devices to display a single text.
2. Description of the Prior Art
The popularity of electronic devices and portable computing devices allows people to access information anywhere. Electronic devices such as mobile phones, personal digital assistants (PDAs), and other personal computing devices can be used to read documents in any location.
Please refer to FIG. 1. FIG. 1 is a diagram of a mobile phone 10 according to the prior art. The mobile phone 10 contains a display 12 such as a liquid crystal display (LCD) that is used to display text and images. As shown in FIG. 1, the display 12 currently shows a text message. Unfortunately, the dimensions of the display 12 limit the amount of text that can be displayed at one time. Typical displays have a limited number of columns and rows that can be used to display text characters. While text documents can still be read on the display 12 of the mobile phone 10, the limited dimensions of the display 12 mean that a user of the mobile phone 10 has to constantly scroll down to read a next screen of text. As an example, FIG. 1 depicts the display 12 as only being able to show the words, "The quick brown fox jumps over the lazy dog."
Although FIG. 1 shows a mobile phone 10, the small dimensions of the display 12 of the mobile phone 10 are representative of the problems of small displays used on other electronic devices such as PDAs.

Method of displaying text on multiple display devices


An iron-type golf club head comprises an upper heel-side region having a specific gravity ρ1, a lower heel-side region having a specific gravity ρ2, an upper middle region having a specific gravity ρ3, a lower middle region having a specific gravity ρ4, an upper toe-side region having a specific gravity ρ5 and a lower toe-side region having a specific gravity ρ6 which satisfy the following conditions: ρ1<ρ2, ρ3<ρ4, ρ5<ρ6, ρ4<ρ2, ρ4<ρ6, ρ3<ρ1, and ρ3<ρ5. These six regions are sectioned by a horizontal plane, a toe-side vertical plane and a heel-side vertical plane.

In recent years, an iron-type golf club head having large moment of inertia around a vertical axis passing though the center of gravity of the club head has been proposed.
(cf. The Following Patent Document 1)
Such club head is hard to rotate around the vertical axis even if a ball hits at a position off the center of the club face toward the toe or heel, therefore, directionality of the hit ball is improved.
Further, an iron-type golf club head having a lowered center of gravity of the club head has been proposed.
(cf. The Following Patent Document 2 and 3)
Such club head increases a chance to hit a ball at a position on the upper side of the sweet spot of the club face.
If a ball is hit at a position on the upper side of the sweet spot, the club head is rotated by a very small angle so as to increase the loft angle, therefore, the launch angle of the ball becomes increased. Thus, for the iron-type golf club head having a lowered center of gravity of the club head, it is easy to hit a golf ball high in the air. This helps to increase the carry.
Accordingly, an iron-type golf club head having high moment of inertia and a lowered center of gravity can improve the carry and directionality of the hit ball.    [Patent document 1] Japanese Patent Application Publication No. H09-253248    [Patent document 2] Japanese Patent Application Publication No. H10-295861    [Patent document 3] Japanese Patent Application Publication No. 2014-000410