The present invention relates to an article of clothing which has multi purpose and function. The present invention is in one form a reversible pocketed apron that converts into a general carry bag and a storage bag. The apron can be worn in several ways. The pockets are used for holding and storing items, tools and accessories. The apron can be further folded into a storage bag for convenient carry. The apron has at least one large rear pocket which forms main compartment of the bag and has carry handles on the pocket. A bib portion is provided which is retractable away from the pocket.

A number of attempts have been made in the prior art to provide multipurpose bags.
One example is disclosed in JP 2002061011 which discloses an apron capable of being transformed into a bag different in shape from the apron. However, in carrying out the transformation process from an apron to a carry bag, the design requires a number of straps or handles to be dislodged and relocated. Furthermore, the apron must be folded and clipped together in a particular manner in order to form the carry bag itself. These transformation processes are considered to be relatively complicated, and involve a relatively high level of dexterity on the part of the user to make the transformation from apron to carry bag and vis versa.
Another example is FR 2 248 001 which also discloses an apron which can be transformed into a bag. However, the design of the apron is such that the size of the bag is limited in comparison to the flap of the apron which is folded over the bag. Further, alternate, uses of the apron or bag are not considered possible due to the design disclosed.
U.S. Pat. No. 5,941,437 discloses a stroller bag which can be also converted into a carry bag. However, the bag is designed in a manner which is not considered practical nor fashionable as an apron. The design does not afford substantial protection to the user when it is worn as it's coverage is relatively limited.
Still another example is U.S. Pat. No. 6,530,089 which discloses an adjustable garment protector, which may also be fabricated as a convertible food bag. However, the food bag provided is also disposable which limits its ability to be reused. It is considered to be not suitable for carrying general goods, such as grocery items, as the bag does not have suitable handles and is adapted to provide a closed bag with a lid. This is considered to limit the use of the bag provided in this disclosure.
There is still considered to be a need for a multi-purpose garment, such as an apron which can be transformed into a carry bag.
It is an object of the present invention to alleviate at least one disadvantage of the prior art.
Any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the invention. It should not be taken as an admission that any of the material forms a part of the prior art base or the common general knowledge in the relevant art in Australia or elsewhere on or before the priority date of the disclosure and claims herein.


Balance piston assembly, apparatus, and methods are provided. The assembly includes a balance piston coupled to a rotatable shaft and configured to rotate therewith, the balance piston including a first shelf and a second shelf, the first and second shelves being axially-overlapping and radially-offset. The assembly also includes a seal including a first sealing surface configured to seal with the first shelf and a second sealing surface configured to seal with the second shelf.

Balance pistons are often used in turbomachines to manage or control axial thrust loads generally created by pressure differentials along the axial length of the turbomachine shaft. In centrifugal compressors, for example, the balance piston typically includes a disk mounted to the shaft on the outboard side of an impeller, often the final stage impeller. A reference line fluidly connects the outboard side (i.e., the side facing away from the impeller) of the balance piston with process gas provided at a reduced pressure, generally suction pressure. Accordingly, the axial forces directed from the high-pressure impeller outlet toward the low-pressure suction inlet are at least partially offset by the pressure differential being experienced in the opposite direction across the balance piston. Remaining axial thrust loads are typically taken up by one or more axial bearings, which are known and available in a variety of designs.
A challenge inherent to the balance piston solution is that it generally adds an interface between a rotating component and a stationary component. Generally, such interface is sealed using any one of a variety of different types of seals. However, the efficacy of the seal is generally a function of the sealing surface area, and the sealing surface area is limited by the axial length of the balance piston. Moreover, it is generally desirable to limit the axial length of the balance piston, and thus minimize overall shaft length and weight.
Further, gas balance seals are used to prevent contamination or fouling of sensitive seals, such as dry gas seals, with dirty process gas, while allowing sensitive seals on both ends of the shaft to operate at the same pressure. Generally, such gas balance seals are provided by a pair of seals, e.g., labyrinth seals, disposed between the dry gas seals and the balance piston. Clean seal gas is then injected between the labyrinth seals, such that the seal gas leaks across the seals. For one of the labyrinth seals, clean gas flows therepast, with an attendant drop in pressure, toward the balance piston, ensuring that no dirty gas migrates in the opposite direction, toward the dry gas seals. The other labyrinth seal acts as a blow-down seal and provides a required pressure drop, such that the dry gas seals at the high-pressure end of the machine operates at the same pressure as the dry gas seal at the low pressure end of the machine.
While balance piston seals and gas balance seals are generally suitable for a variety of applications, it is commonly desirable to reduce shaft length, thereby increasing stiffness. However, when applied to seals, such reductions in shaft length are generally limited by a trade-off with sealing ability. What is needed is a seal assembly that maximizes sealing surface length while reducing, or at least not substantially increasing, the axial length of the shaft required for the balance piston and/or gas balance seal.


There is provided a perpendicular magnetic recording and reproducing system in which the overwrite erase ratio of a perpendicular magnetic head has been improved to prevent the deterioration of an overwrite property. In the perpendicular magnetic head, a third magnetic pole composed of a soft magnetic layer is formed on the leading side of a recording magnetic pole via a non-magnetic layer, thereby reducing magnetic interference from magnetization on a medium with the recording magnetic pole and preventing the deterioration of the overwrite property.

1. Field of the Invention
The present invention relates to a magnetic head for perpendicular recording and to a perpendicular magnetic recording and reproducing system.
2. Description of Related Art
In recent years, a hard disk drive which is a magnetic recording and reproducing system used as an external recording device for an information processor, such as a computer, has been required continuously to be increased in capacity and reduced in size. To meet the requirements, improvements have been made primarily in the recording density of the hard disk drive. If the density is increased by using a conventional longitudinal recording method, however, it is necessary to reduce the thickness of a recording layer since a demagnetizing field becomes maximum on the magnetic transition zone of a recording medium upon recording magnetization. This causes the problem that the resulting thermal disorder erases recorded data. By contrast, a perpendicular recording method in which the direction of recording magnetization coincides with the direction of the film thickness of the medium is more likely to achieve a higher recording density since the demagnetizing field becomes minimum on the magnetic transition zone and therefore it is less necessary to reduce the film thickness of the medium.
When a signal is recorded on a perpendicular recording medium by using a magnetic head for perpendicular recording, i.e., a perpendicular magnetic head, an electric signal is converted to a magnetic signal by a coil so that a magnetic flux is excited in a first magnetic pole or recording magnetic pole and a second magnetic pole or auxiliary magnetic pole. The magnetic flux forms a closed loop in which it extends from the second magnetic pole through the first magnetic pole, penetrates the perpendicular recording layer of the recording medium, passes through a soft seed underlying layer under the perpendicular recording layer, and returns to the second magnetic pole. The second magnetic pole is used to return, with magnetic efficiency to the first magnetic pole, a magnetic field formed in the first magnetic pole to extend to the perpendicular recording layer and soft under layer of the recording medium. By using the flow of such a magnetic flux, the signal is recorded on the perpendicular recording medium through magnetization. An example of the magnetic head is disclosed in Transactions of the Magnetics Society of Japan, Vol. 24, 335-338 (2000).
When the writing of data is performed in a magnetic recording system, three steps of erasing, writing, and collating are required. In a hard disk drive, however, a direct overwrite method in which writing is performed simultaneously with erasing is adopted to achieve a significant improvement in writing speed. An important issue in adopting the direct overwrite method is that a residual component of old data remaining after erasing is sufficiently small when new data is written directly over the old data. As an index indicative of the write performance of a magnetic head when data is overwritten, an overwrite erase ratio can be named, which is represented by a signal ratio before and after the overwriting of the old data.
When a magnetic head for perpendicular recording performs recording with respect to a magnetic recording medium in a magnetic disk apparatus, a tangent line to a recording position in the direction of rotation of the magnetic recording medium and a tangent line in the direction of film thickness of the first magnetic pole or recording magnetic pole of a magnetic head have a given angle (skew angle) therebetween. The skew angle differs depending on a radial position on the magnetic recording medium. When a magnetic head having a recording magnetic pole with a large film thickness performs writing with a skew angle being provided, a situation occurs in which a recording magnetic field is applied also to an adjacent track. If the occurrence of the situation is frequent, thermal demagnetization is accelerated disadvantageously in the recording magnetization of the adjacent track. A problem associated with such a magnetic head having a yaw angle has been reported in Transactions of the Magnetics Society of Japan, Vol. 25 591-594 (2001).
One approach to solving the problem is a reduction in the film thickness of the first magnetic pole or recording magnetic pole. As the film thickness of the recording magnetic pole is reduced in the magnetic head, however, the recording magnetic field is reduced in size and the distance between previous history magnetization on the leading edge side (leading side) and a magnetic transition point on the trailing edge side (trailing side) in the direction of travel of the magnetic head relative to the perpendicular magnetic recording medium is also reduced. As a result, interference from the previous history magnetization with a recording point shifts the magnetic transition point (transition point shift), which degrades the overwrite erase ratio. The overwrite erase ratio degraded by the transition shift is disclosed in, e.g., IEEE Transaction on Magnetics Vol. 30, No. 6, pp. 4272 (1994) "Relationship between Overwrite and Transition shift in Perpendicular Magnetic Recording".
As shown in the report, in a perpendicular magnetic head and a perpendicular magnetic recording and reproducing system using the same, the prevention of the degraded overwrite property caused by a reduction in the film thickness of the first magnetic pole or recording magnetic pole of the magnetic head is an important issue.

Perpendicular magnetic recording and reproducing head

Hitachi Global Storage Technologies Japan, Ltd.


Feature values, which may be multi-dimensional, collected over successive time slices, are efficiently processed for use, for example, in known adaptive learning functions and event detection. A Markov chain in a recursive function to calculate imputed values for data points by use of a “nearest neighbor” matrix. Only data for the time slices currently required to perform computations must be stored. Earlier data need not be retained. A data selector, referred to herein for convenience as a window driver, selects successive cells of appropriate adjacent values in one or more dimensions to comprise an estimation set. The window driver effectively indexes tables of data to efficiently deliver input data to the matrix. In one form, feature inputs are divided into subgroups for parallel, pipelined processing.

Auto-adaptive systems have many applications. These applications include event recognition based on data measured over a number of successive time periods. Events take many different forms. For example, events may include detection of a target in a particular area, sensing of an out-of specification condition in a physical process environment or correspondence of processed psychometric measurements with a particular behavior prediction profile. Anomaly sensing is often an element of detecting an event. Event recognition may also comprise evaluation of sensed data to recognize or reject existence of conditions indicated by the data or to initiate a particular action.
One use of event detection is in military operations. When making critical combat decisions, a commander must often decide to either act at once or hold off and get more information. Immediate action may offer tactical advantages and improve success prospects, but it could also lead to heavy losses. Getting more data may improve situational awareness and avoid heavy losses, but resulting delays may cause other problems. Making the right choice depends strongly on knowing how much could be gained from gathering more information, and how much could be lost by delaying action. Advantages that can be achieved through the use of event detection go beyond mere friend or foe identification. A data-based, decisive inference process can help the commander to see how the operational picture might change with the arrival of more data. Seeing what to expect, in turn, will help decide if getting more information is worthwhile or whether an action should be launched at once.
Data is collected by sensors of one kind or another. In the context of the present description, a sensor is an item that provides information that may be used to produce a meaningful result. Data is collected over successive time periods, generally from an array of sensors. Depending on the conditions being analyzed and the type of sensors utilized, different types of data points may be established. For example, a data point characterizing a position of a point in a plane may be characterized by x and y coordinates. Such a point has two spatial dimensions. Other dimensions may also exist. For example, if the data point describes the condition of a pixel in a television display, the data point may be further characterized by values of luminance and chroma. These values are characterized as further dimensions of a data point.
In order to describe an environment mathematically, event recognition adaptive algorithms process successive signals in one or a plurality of dimensions to converge on a model of the background environment to maintain track of the background's dynamic change. Systems employing such algorithms are referred to as machine learning in that they are capable of learning. When an event occurs within a sensor's area of response, e.g., within a field of view of optical sensors, the adaptive algorithms determine if the return is sufficiently different from the background prediction. Domain specific event identification algorithms may then be applied to verify if an event has occurred in order to minimize the likelihood and number of false positives. An important aspect of the adaptive algorithm approach is a dynamic detection threshold that could enable these systems to find signals and events that could be lost in noise were they to be compared to fixed thresholds. Having a dynamic threshold also allows a system to maintain a tighter range on alarm limits. Broader alarm ranges decrease the ability of the system to distinguish anomalous conditions from normal conditions. Machine learning is also • readily embodied in parallel configurations to allow for extra speed afforded by parallel processing.
U.S. Pat. No. 5,835,902 discloses a system for learning from and responding to regularly arriving information at once by quickly combining prior information with concurrent trial information to produce useful learned information. Predicted values are generated, and an anomaly is indicated if a current measurement is sufficiently divergent from an expected measurement. In one form, a processing system for computing output values from input values received during a time trial comprises a processing unit receiving sequential input data values from an input vector. In order to generate the estimated values, a connection weight matrix is calculated that is the inverse of a sample covariance matrix at the beginning of the time period and the inverse of the updated sample covariance matrix at the end of the time period. While this system is effective, it has physical limitations.
To use such a system for nominal video image of 500,000 pixels, the matrix to be computed would have a size of 500,000×500,000. This is too large a number to be processed in real time by stand-alone processor circuits that are capable of inclusion on a circuit board in a remotely controlled device. Even as to tractable applications, the processor has significant minimum requirements in terms of complexity, required silicon "real estate" and operating power. Such requirements are relatively easily met when a processor is contained in a base unit such as a ship. However, tactically, there are scenarios in which it is highly desirable to use a portable device such as an unmanned underwater vehicle (UUV) to gather information and make decisions. Such devices have such limited, self powered electrical power sources that power demand becomes a critical factor. Weight and space limitations are significant in many forms of portable devices. It is desirable to provide a system better suited to operation in a remote, space limited and self powered unit.
U.S. Pat. No. 6,327,677 discloses a processor to generate values to which current values are compared. However the processor uses historical samples for comparison to currently measured values continuously on a time slice by time slice basis.
Other complex event detection systems have known drawbacks. A complex process requires powerful processors rather than simpler, less expensive field programmable gating arrays (FPGAs). FPGAs have not been used for processing of multidimensional measurements. Many systems use C++ programming, which is effective but slow in comparison to the simple instructions used for FPGAs. It is desirable to provide a processor arrangement for event detection which is simple, efficient in terms of power requirements, fast and comparatively low cost in relation to prior powerful event detection systems. It is useful to provide the capability of parallel processing in order to speed production of results.
However, as new unmanned vehicles are being developed that are smaller, more agile, and have the capability of reaching places that have not been reached before, the demands made upon the data processing capabilities of these systems have increased dramatically. An article in COTS Joumal, January 2006, http://www.cotsjournalalonline.com/home/article.php?id=100450, noted that, "The military's transformation into a more nimble and information aware fighting force means that high-demand, • compute-intensive military systems need huge amounts of processing power in a small space. Multicore processors are leading the way. . . . On the silicon side, the move to multicore processors is being driven by the limitations of single-core PUs in these high demand systems. Unmanned aerial vehicle (UAV) image recognition and collision detection processing, for example, requires many DSPs or general—purpose processors, or a combination of both. Pushing single-core processors any further in performance can't be done without drastic consequences in the heat produced and the power consumed."
Single core processors include such devices as high-powered AMD and Intel processors. Dual core processors represent new and more expensive designs for which the new architectures and programming need to be created. An example of a dual core processor is the new Intel Pentium D dual core processor. If designs can be found that can utilize older and simpler processors to perform functions such as those performed by UAVs, much redesign and power consumption can be avoided. Low level software can be utilized. Reliability will be increased and time to deployment from formulation of specifications is significantly decreased.
It is also important to formulate efficient ways of handling large arrays of data. In many typical applications, the UAV-borne processor will need to respond to outputs from a large array of sensors. The sensors will be producing consecutive outputs at a high frequency. The above-cited U.S. Pat. No. 5,835,902 successfully processes data. However, values are updated by processing the inverse of a covariance matrix. This is a complex calculation, especially when the number of covariates is large.
In order to evaluate data, it is important to provide efficient ways of presenting data to a processor. U.S. Pat. No. 6,985,779 discloses a system in which sensor output data is organized within a spreadsheet in which one column represents an output of one sensor and in which each role of the columns represents the output during a successive frequency period, or time slice. This patent does not disclose efficiently processing the values in a matrix to define imputed values.
Many prior art arrangements perform calculations for event detection and adaptive learning after entire sets of data have been collected. Often data collected by a remote vehicle must be processed at a home base. Prior arrangements have not provided for maximizing data reduction in the remote vehicle.

This patent is subject to a terminal disclaimer.

Efficient processing in an auto-adaptive network


An information reproducing apparatus includes a recording medium and a reproducing probe, and reproduces information from a signal between the recording medium and the probe. The apparatus further includes a unit for obtaining reproduced information from each of a plurality of data unit areas of the recording medium under different conditions. By obtaining a plurality of different kinds of information from scanning each recording region under the different conditions in a reproducing operation, it is possible to perform correction by discriminating a change in a tunnel current reflecting a recording bit from a tunnel current caused by projections and recesses of the surface and to remove a resulting error.

1. Field of the Invention
This invention relates to reproduction of information, and more particularly, to a recording/reproducing apparatus which records/reproduces information using a tunnel current flowing between a needle-like electrode and a recording medium having a memory effect while the electrode moves relative to the recording medium.
2. Description of the Prior Art
Recently, scanning tunnel microscopes (hereinafter termed STM's) which can directly observe the electronic structure of atoms in the surface of a conductor have been developed. The STM is expected to be used for a wide range of applications since it can measure a high-resolution real-space image of either a single-crystal sample or a non-crystalline sample, observe the sample with low electric power with little or no damage to the sample due to current, operate in the air, and can be used for various kinds of materials.
The STM utilizes a phenomenon that a tunnel current is generated if a metal probe is brought close to a conductive sample to a distance of about 1 nm (nanometer) while applying a voltage between the probe and the sample. This current is very sensitive to a change in the distance between the probe and the sample. Hence, by monitoring the tunnel current which changes when the probe scans the sample while maintaining the height of the probe constant, or by monitoring the amount of feedback for scanning with feedback control of the height of the probe so as to maintain the tunnel current constant, it is possible to depict the real-space structure of the surface of the sample, and also read various kinds of information relating to the total electronic cloud of electrons at the surface. Accordingly, it becomes entirely possible to perform a high-density recording/reproducing operation of the order as small as atomic order by applying the principle of the STM.
Recording/reproducing methods using this principle are roughly divided into two kinds. In one method, the physical shape of a surface is changed. In an apparatus using this method, physical projections and recesses are formed on the surface of a recording medium by physical deformation by a probe, fusion by a high-energy beam, such as a laser light beam, an electron beam or the like, adhesion of fine particles, or the like. In another method, an apparatus utilizes a reversible change in the electronic state of a surface or its neighborhood without changing the physical shape of the surface. The apparatus using the second method of changing the electronic state is advantageous for practical use from the viewpoint of recording density and the posibility of erasing and rewriting operations.
For example, a system has been known wherein an insulating or semi-insulating thin-film structure is provided on a substrate electrode, and recording/reproducing operation is performed using this thin-film structure, i.e., a fine structure capable of storing electric charges, such as an interface between laminated layers of a silicon oxide film and a silicon nitride film formed on a silicon substrate, or the like. Another system has been known wherein recording/reproducing operation is performed in an organic molecular film formed on an electrode, as described, for example, in a report (Journal of Vacuum Science & Technology, B9 (2), p. 1129, 1990) relating to coppertetracyanoquinodimethane (Cu-TCNQ) charge-transfer complexes by R. S. Potember of John Hopkins Univ., or in a report (Chemical Physics Letters, vol. 29, p. 277, 1988) relating to hemiquinones having a double-well potential structure of protons by A. Aviram et al of IBM.
FIGS. 7(a) and 7(b) show the principle of a recording/reproducing apparatus which uses one of the above-described recording mediums. As shown in FIG. 7(a), when a probe t scans the surface of a recording layer 2 formed on a substrate 1 while maintaining a constant height, and a voltage V having at least a predetermined threshold value is selectively applied between the probe t and the substrate 1 for respective data unit areas, a tunnel current having a barrier due to a gap between the probe t and the substrate 1 and the recording layer 2, or a gap between the probe t and the recording layer 2 is generated to form on-state bits, and binary information as shown in FIG. 7(b) is recorded.
In a reproducing operation, a tunnel current reflecting the electronic state of respective data unit areas can be read by sequentially applying a voltage less than the above-described predetermined threshold value between the probe t and the substrate 1 while scanning the surface of the recording layer 2 by the probe 1. It is also possible to reflect recorded information in the amount of feedback of the probe t in a tunnel current constant mode.
The above-described conventional approach, however, postulates an ideal state wherein no physical undulation influencing the tunnel current is present on the surface of the recording medium. If projections and recesses are actually present on the surface, a change in the tunnel current due to the projections and recesses cannot be discriminated from a change in the tunnel current reflecting recorded bits, thereby substantially increasing the error rate in a reproducing operation. The tunnel current changes exponentially in accordance with the distance between the probe t and the recording layer 2. For example, if projections and recesses of 1 angstrom are present, the value of the tunnel current changes in the range of 1 digit. Hence, even if a change in current due to a change in the electronic state of recorded bits is in the range of 3 digits, the permissible undulation of the surface is a few angstroms at most.
If the spatial frequency of projections and recesses is much larger or smaller than the frequency of the recording unit areas, it is possible to electrically separate signals. Accordingly, attention must be directed to an undulation which has projections and recesses having the same spatial frequency zone as the data unit area and which may cause a change in tunnel current of the same degree as a change in tunnel current due to the recording bits. For example, as shown in FIG. 8(a), if there exist a projection at a data unit region d3 and a recess at a data unit region d7, an off-state signal may be erroneously read as an on-state signal, and an on-state signal may be erroneously read as an off-state signal, as shown in FIG. 8(b).
In order to solve the above-described problem, it is possible to scan the surface in advance and record the state of a microscopic undulation of the surface to compensate for the influence of the microscopic undulation. This approach, however, is not practical, though possible in principle, since the amount of initial information relating to the state of undulation of data unit areas is very large, and an auxiliary storage corresponding to at least the total capacity of a storage medium is needed.
As another approach, a method of reading a modulated signal with respect to either the applied bias voltage or the distance between the probe t and the substrate 1 may also be considered. Since, in principle, the modulated value with respect to the bias voltage or the distance reflects in some cases only a particular change in the electronic state or the work function of the surface, a reproducing operation not influenced by an undulation may be performed.
It is difficult, however, to obtain a material in which a large change is produced in the above-described modulated signal by a change in recording bits. Furthermore, superposition of small noise due to thermal drift, external oscillation and the like is inevitable, greatly influencing the modulated signal. Hence, in order to obtain a measurable S/N ratio, an extremely-low-temperature and a highly anti-vibration environment is needed.

Apparatus and method for reproducing information


A method of making reproducible and accurate longitudinal studies of neuroretinal rim area establishes a reference plane based on height values of a readily established contour line at the outer rim of the optic disc. The reference plane may be used to establish a second inner contour line, between which contour lines area is measured.

Glaucoma is a chronic eye disease in which nerve axons in the retina and optic nerve progressively die and vision is lost. The axonal loss progressively alters the topography of the optic disc and its surrounding retina. Treatment can control the progression of glaucoma, but inadequate treatment leaves the disease uncontrolled and can lead to blindness. It is thus important to be able to tell if the disease is progressing and if treatments are effective. Only monitoring over time will reveal the course of the disease.
To monitor glaucoma over time, sequential testing needs to be conducted over the course of disease to try to capture its changes. The period of testing is typically months to years, and measurements yielded by repeat testing over time are expected to have variability which can be significant and unpredictable. Glaucoma is known to evolve gradually, and relatively small changes due to the disease will have to be detected above measurement variability. As such, distinguishing true glaucoma-induced change from apparent change due to variability in these longitudinal measurements can be challenging.
The optic disc, the visible portion of the optic nerve, has two anatomical parts: a peripheral region called the neuroretinal rim (NRR) surrounds a central depression called the optic cup (cup). The NRR contains neural tissue, representing axons from the retina converging on the optic nerve to exit the eye. The cup is devoid of axons.
Change in the size of the NRR and cup serves as markers of disease progression. The size of the NRR and cup can be measured once the inner margin (inner rim) and outer margin of the NRR (outer rim) are defined in optic disc images. The outer rim forms the circumference of the optic disc, and is a fixed anatomical landmark and readily identifiable. The inner rim coincides with the edge of the cup and is defined as the region in which the NRR surface's flatter slope steepens maximally as it turns into the cup. It is more difficult to identify.
Identifying the location of the cup edge/inner rim is critical to evaluating the optic disc for disease progression. As axons are lost, it is the inner, not outer, rim that recedes as the NRR gets smaller and cup concurrently gets bigger. As the changes sought are on the most part relatively small, the inner margin needs to be identified reproducibly and accurately if such minute change is to be detected.
Conventionally, the area of the NRR (rim area) and cup (cup area) have been measured in stereoscopic optic disc photographs. But detecting the inner rim in these images relies on subjective interpretation such as perceiving subtle variations in color and contour, which compromises reproducibility.
A newer innovation is scanning laser tomography, an imaging method which yields digital topography images of the fundus for quantitative analysis. It has several advantages over photography. Contour lines can be marked on the outer rim in topography images and its coordinates saved to be exported to other images of the same eye. This same contour line location is automatically maintained throughout an image series. Another advantage is that topography images permit the use of alternative analytical approaches to objectively and automatically identify the inner rim.
One such approach is to position a reference plane in the topography of the optic disc being analyzed. However, the optic disc's topography normally differs considerably between persons and eyes, and how a reference plane should be positioned so that analysis is valid, reproducible and not biased by inter-individual differences has not been determined. While reference planes of various definitions have been proposed, none has been shown to consistently fit the wide range of optic disc topographies, nor yield measurements of the inner rim that are reproducible and accurate enough to be useful for monitoring change in the size of the NRR.
Finally, measurements derived from the repeated imaging of the same eye over time will almost certainly have variability that is easily mistaken for true change. If disease progression is to be discerned in longitudinal image series, there must be a way of reliably distinguishing true change due to disease from apparent change due to measurement variability.

Method and apparatus for monitoring glaucoma using scanning laser tomography


The thread gauge permits the user to determine the pitch diameter of tapered threads at the intersection of the pitch cone and the end face of the object being measured. A pair of opposed anvils having lines of threads which match the configuration and taper of the threads on the part being measured are brought into meshing engagement with the threads on opposite sides of the part. The anvils are located linearly into their proper positions by stop fingers on the anvils that are brought into abutting engagement with the end face of the part. This places predetermined reference points of the pitch cone of the thread anvils in registration with corresponding points on the end face of the part being measured, resulting in an accurate determination of the pitch diameter at that location. The thread anvils can be arranged for measuring either internal or external threads.

My prior U.S. Pat. Nos. 4,547,970 and 4,553,337 disclose and claim thread gauges for measuring the pitch diameter of cylindrical or non-tapered threads. While those gauges have proven to be extremely effective and useful for that particular type of thread configuration, they cannot be used with accuracy for parts or objects in which the pitch line of the threads forms a tapering cone instead of a straight cylinder.
Accordingly, one important object of the present invention is to provide a thread gauge which permits the user to accurately and conveniently measure the pitch diameter of an object having tapered threads. Furthermore, it is an important object to be able to measure such tapered threads whether they are on the outside or inside the object being checked.
Additionally, an important object of the present invention is to provide a thread gauge for tapered threads which carries on the general principles of use and operation provided in my earlier patents as above identified.
Still further, it is an important object of this invention to provide a tapered thread gauge which is particularly well suited for use in connection with a conventional vernier caliper, but which can also be utilized in connection with an inside micrometer without departing from the principles of operation and construction herein set forth.
In carrying out the foregoing and other objects, the present invention contemplates using a pair of thread anvils, as in my prior patents, which match the thread pitch and configuration of the part being measured. Such anvils are attached to the spreadable arms or supports of a vernier caliper, or to the opposite ends of an inside micrometer, to essentially adapt that device to take an accurate measurement of the threads on the object to be measured. The problem with measuring threads of a tapered configuration is that the pitch diameter is constantly changing over the length of the threaded portion of the object, due to its conical shape. While with straight cylinder threads it makes no difference where the measurement is taken along the length of the threaded portion, in a tapered configuration the linear point at which the measurement is taken is of critical importance.
Standard protocol requires that the pitch diameter of a tapered thread be called out at the intersection of the thread pitch cone and the end face of the object being measured. Due to the helical nature of threads, however, the exposed end face of the thread is set back or recessed away from the actual end surface of the object by a significant distance at a point that is 180.degree. around the rim from the starting point of the thread. Consequently, there are no two diametrically opposed physical points exactly in the same plane at the end of the object that can be engaged by a measuring tool to determine the pitch diameter.
In the gauge of the present invention, by designing the thread anvils so their lines of threads are caused to taper or slope at the same angle as the tapered thread on the part to be measured, such anvils will mesh properly with the threads of the part when the anvils are applied to the part. Furthermore, since the thread anvils will, in effect, have their own tapering thread cone effectively defined between the two anvils, the intersection point between that pitch cone and the end face of the anvils can be precisely located at known distances from reference surfaces on the gauge. Consequently, by then registering those pitch cone intersection points of the thread anvils with the corresponding conical intersection points of the part to be measured, the intersection points on the part will likewise come to be located at the known distances from the reference surfaces of the tool. When these known distances are then added to or subtracted from the displayed distance reading on the measuring tool for the space between its reference surfaces, the resulting figure is the distance between the two diametrically opposed cone intersection points on the part, i.e., the pitch diameter of the part.
To make sure that the thread anvils of the present invention become located on the tapered thread of the object at the proper linear position, each of the anvils is provided with a special, overhanging stop finger that projects out beyond the thread line of the anvil into position to overlie the proximal end face of the object being measured. By abutting such end face, or nearly so, with the stop fingers, the imaginary cone intersection points on the thread anvils are forced into registration with the corresponding intersection points on the object being measured, to yield an accurate measurement.
In order to permit the two anvils on opposite sides of the object to be perfectly engaged with the threads on the object, it may be necessary for slight linear shifting or adjustment of the thread anvils to occur. Accordingly, the tapered thread anvils of the present invention are provided with ball couplings that join the anvils with the measuring tool itself in essentially the same manner as set forth in my prior '970 and '337 patents. Such ball couplings allow the anvils to shift linearly through a limited amount of travel as may be necessary to best seat the anvils on the object, while also permitting a certain amount of in-and-out rocking movement to likewise assure proper seating. It will be noted that this particular ball coupling arrangement also allows the anvils of the present invention to be interchangeably attached not only to vernier calipers, but also to inside micrometers, notwithstanding the constructional differences between those two types of tools.
By providing two different types of releasable connectors for coupling the mounting balls and their anvils to the leg supports of the caliper, the caliper may be set up for checking either externally threaded parts or internally parts, as the case may be. Notwithstanding this type of flexibility and adjustment, accurate measurements are assured.


A method of preparing cyclic peptide mixtures via side chain or backbone and solid phase synthesis. The cyclic peptide mixtures form libraries that are useful for screening purposes featuring the attachment of an amino acid to a solid support through its side chain or backbone in order to mimic solution cyclization procedures with linear peptides. In the preferred embodiment, Boc chemistry is used for peptide synthesis, wherein the initial attachment of a trifunctional amino acid is by the aspartyl side chain (with OFm for alpha-carboxyl protection). Cyclization is performed using uronium reagents with racemization suppressant, and a strong acid (HF) is used for deprotection and cleavage. The strategy has been used for the preparation of a series of cyclic peptide mixtures. The procedure is expandable to include at least twenty different amino acids at each position (except the resin linked position where most attachments are by Asp, Lys, Glu, or Orn). The cyclic peptide mixtures vary in ring size from about four to about twelve residues.

The instant invention relates to a method for preparing mixtures of cyclic peptides using novel solid phase methods such that a variety of products are prepared, in groups, possessing diversity in size, length, (molecular weight), and structural elements. These are then analyzed for the ability to bind specifically to an antibody, receptor, or other ligate. Such a collection may provide a ligand library containing specific ligands for any ligate even though there are a greater number of conformations available to any one sequence. A peptide library containing known and random peptide sequences can be easily surveyed for strong ligands and provides a powerful new tool for the cell biologist for studying molecular recognition. Moreover, the present invitation provides a means for displaying the peptides in these libraries on a selected surface allowing the library to be surveyed without the need to pick through peptides one at a time. Such a tool provides a means of recognizing a new class of agonists, antagonists, enzyme inhibitors, virus blockers, vaccine development, and other pharmaceuticals.
The use of peptide libraries for generating structurally diverse compounds is impressive. Using only the 20 common amino acids, one can readily generate 400 dipeptides or 6.4.times.10.sup.6 hexapeptides. (See Table I following).
TABLE I ______________________________________ Listing of Theoretical Numbers of Cyclic Peptides of N Ring Size Using 20 Common Amino Acids. Ring Size (N) Multiples Number of peptides* ______________________________________ 3 20 .times. 20 .times. 20 8,000 4 20 .times. 20 .times. 20 .times. 20 160,000 5 20 .times. 20 .times. 20 .times. 20 .times. 20 3,200,000 6 20 .times. 20 .times. 20 .times. 20 .times. 20 .times. 20 64,000,000 ______________________________________ *Does not include redundant peptides due to summary (e.g., cyclo(AlaAla-Ala).
With nineteen other D amino acids, the number rises to over 1500 dipeptides and over 3.5 billion linear hexapeptides; the magnitude of this latter number can best be realized by calculating that if only 1 milligram of each peptide were present, the weight of the 6.5 billion peptides would nevertheless exceed three tons.
One of the first practical application of multiple peptide synthesis is attributed to Geysen, H. M., et al., Proc. Natl Acad. Sci . U.S.A., 81, 3998-4002, (1984) and is referred to as the "pin method." This procedure involves the use of Merrifield solid phase peptide synthesis, in which one end of a growing polypeptide chain is covalently linked to an insoluble support. In this case, a comb-like arrangement of dozens of pins are dipped into differentially filled aliquots of amino acids, thereby providing a defined discrete set of synthetic peptides, with a unique sequence at the head of each pin. Thus a large group of linear peptides could be rapidly synthesized and, if necessary, deprotected and assayed while still attached to the solid support. Alternatively, the peptides could be cleaved from the support and independently characterized and tested.
The second major development in multiple synthesis involved work by Houghten, R. A., Proc. Natl. Acad. Sci. U.S.A., 82, 5131-5135 (1985). In this procedure, different peptides are simultaneously prepared by solid phase methods, but individual peptide sequences are segregated from one another, when required, by being held in solvent-permeable plastic bags (the "tea-bag" method). Selected packets are removed and subjected to their own chemistries (adding different amino acids at one position) and then recombined when common amino acids are used to minimize the synthetic workload. Thus, a series of 10 linear peptides of sequence A-B-X.sub.n -D-E can be prepared with X.sub.1 -X.sub.10 merely be separating the 10 packets after adding a common amino acid, "D", then recombining the packets after adding X.sub.n to carry out couplings of B and A.
Further studies have been conducted by Houghten, Fodor and Hruby which describe the preparation of linear peptide libraries using modified peptide synthesis methods, while the synthesis group used genetic engineering techniques to prepare the peptide mixtures. The common theme of all these approaches is that literally millions of synthetic linear peptides can be prepared, more or less simultaneously, and that these peptide libraries can then be screened, collectively or in smaller groups, against specific antibodies or in bioassays for discovery of new lead compounds for various clinical problems. In this way, diversity of structures, meeting or exceeding the diversity found in natural products from rain forests or ocean dwellers, can potentially provide a rich new source of compounds for analysis by the pharmaceutical industry.
All of the above methods produce linear peptides. Most techniques use the most common twenty amino acids in their examples; however, this is not an inherent limitation. The use of unnatrual amino acids (optically active isomers) provides a new challenge in terms of product characterization. Most analytical methods for peptide structural characterization, including amino acid analysis and peptide sequencing, are most useful when applied to compounds containing only the twenty natural amino acids.
However, Kerr et al. (J. Amer. Chem Soc., 115, 2529-2531 (1993)), used a dimeric sequence formed using the trifunctional amino acid lysine with two difference sequences on each of the dimeric arms. One is composed of a least some unusual amino acids while the second arm contains a "coded" sequence composed only of common amino acids that may be readily sequenced. If the pairs of sequences in a peptide library are carefully coordinated, this approach combines the greater diversity available by using unnatural amino acids, but also contains a resident and covelantly lined reading code that can be used for sequencing. Obtaining the sequence of the unique natural amino acid arm automatically reveals the sequence of its paired arm since the molecules are prepared concomitantly.
The use of peptide libraries generates structurally diverse compounds, wherein, each of those linear hexapeptides contains at least two backbone rotatable bonds which, in linear form, are quite free to rotate. In a hexapeptide, if only 60.degree. angle increments are considered, one must incorporate another 6.sup.6 or 46,000 other variables for each peptide, since linear peptides are inherently flexible. This suggests that one is likely to see both many false positives and false negatives since conformational as well as structural diversity now plays such a major role.
While some recent versions of peptide combinational libraries may approach the theoretical maximum (Avogadro's number) of different structures in a molar unit of library product, the flexibility which is common to linear products is a significant limitation compared to the variety of conformational constraints that are found in most potent pharmaceuticals.
In order to synthesize a single defined peptide sequence those skilled in the art generally use the Merrifield method to "grow" peptide chains attached to solid supports. The process of synthesizing these individual peptides has been automated. Commercially available equipment can be used to synthesize peptides of one hundred or more amino acids in length. To obtain peptides of arbitrary length, the resulting peptides can be ligated with each other by using appropriate protective groups on the side chains and by employing techniques permitting the removal of the synthesized peptides from the solid supports without deprotecting them. Thus, the synthesis of individual peptides of arbitrary length is known in the art.
Combinatorial peptide libraries described to date have involved linear sequences. This is the case whether chemical (primarily solid phase peptide synthesis) or biological (combinatorial DNA libraries) techniques have been used for preparing the linear compunds.
Linear peptides are generally flexible molecules with entropic limitations on achieving productive biologically active conformers. For this reason many authors have described the advantages of using various types of conformational and topographical constraints to reduce these degrees of freedom (for example, see F. J. Hruby, Life Sci.,31, 189 (1982) and V. J. Hruby et al., Biochemical J., 268, 249, (1990)). These constraints may involve amide bond replacements, backbone and side chain alkyl substituents (to fix .phi., .psi., and .chi.-space), and use of heterocyclic amino acids such as proline (Pro) or tetrahydroisoquinoline carboxylic acid (Tic), among many other possibilities.
All of the above techniques focus on linear peptide mixtures; however, a preferred method of constraining peptides involves cyclization. Cyclic peptides may be prepared in which the ring is formed by oxidation of the naturally occurring cysteine residues yielding a disulfide bridged structure. This technique mimics the most common form of cyclization found among naturally occurring peptides and proteins but does not provide a convenient means of preparing other types of cyclic structures.
In order to prepare cyclic peptides, the most common technique used to employ amino acids with orthogonally protected functional groups such that some are removable selectively in the presence of others. Those skilled in the art can use these techniques to prepare peptides in solution in which the amino terminus is cyclized to the carboxyl terminus to form a ring. A naturally occurring example is the antibiotic gramicidin. Alternatively pairs of cysteine residures are oxidized to disulfide bonds to form one or more rings; the familiar naturally-occurring cyclic peptide hormone ocytocin is an example of such a structure, such as has been prepared by O'Neil et al., Protein, 14, 509-515 (1992)); however, this example is limited to cases of disulfide forming cyclic hexapeptides.
An alternate approach to solving the problem of structural diversity is to utilize other means of forming cyclic peptides include side chain-to-side amide bonds or side chain-to-backbone linkages. By combining the use of Merrifield (or related) solid phase methods with various solution cyclization procedures, it has proven possible to prepare many examples of known peptide hormones or their analogs.
If cyclization is of the head-to-tail variety, several advantages accrue. First the molecule is far more likely to have a reduced number of conformational states available to it. This can often lead to more potent and/or more selective ligands to biological receptors or to tighter binding to antibody molecules. Examples in the literature include a .delta.-selective opioid analog known as DPDPE, a mini-somatostatin cyclic hexapeptide (Merck), and a potent and selective endothelin antagonist, BQ-123 (Banyu).
A second advantage of head to tail cyclic peptides is that the molecule is virtually resistant to two of the three major types of proteolytic enzymes. Neither aminopeptidases nor carboxypeptidases are activated since cyclization simultaneously removes both amino (NH.sub.3 +) and carboxylate (COO--) termini. The molecule's resistance to endopeptidases is also likely to be affected but not in any predictable fashion.
Because of the above factors, any lead compounds obtained in a drug screening assay of cyclic peptide libraries are far more likely to resemble the final target peptide-inspired pharmaceuticals. This is especially true if D-amino acids and other unusual amino acids are incorporated into the library pool, giving rise to an even greater diversity of potential target analogs.
Finally, small cyclic compounds (with 4, 5, 6 amino acid residues) are more likely to possess decreased conformational flexibility than libraries of greater ring size. Nevertheless, the greater structural diversity inherent in the larger rings could provide more examples of lead structures and are included in the disclosure, even though the preferred embodiment involves compounds containing 408 residues in the ring, with 5 and 6 residue rings being preferred in view of their greater ease in forming cyclic structures (see Table II below).
TABLE II ______________________________________ Calculated Combinations of Cyclic Peptides (Head-to-Tail) Cyclizations); Based on Asp-Resin No. of residues Linkage With 19 amino acids With 38 amino acids in ring to resin at variant positions at variant positions ______________________________________ 4(cyclic Asp tetrapeptides) Asp;Gln 6,859 109,744 Asn;Gln 27,436 438,976 5(cyclic Asp pentapeptide) Asp;Gln 130,321 2,085,136 Asn;Gln 521,284 8,340,544 6(cyclic Asp hexapeptide) Asp;Gln 2,476,099 3,010,936,300 Asn;Gln 9,904,396 12,043,745,000 ______________________________________
Although the synthesis of a particular peptide may be routine, it is necessarily laborious. This presents a large practical problem in a situation where it is not previously known which of a mulitiplicity of peptides is, in fact, the preparation desired. While it is theoretically possible to synthesize all possible candidates and test them with whatever assay is relevant (immunoreactivity with specific antibody, interaction with a specific receptor, particular biological activity, etc.), to do so using the foregoing method would be impractical. In general, the search for suitable peptides for a particular purpose has been conducted on in cases where there is some prior knowledge of the most probable successful sequence. Therefore, methods to systematize the synthesis of a multiplicity of peptides for testing in assay systems would have great benefits in efficiency and economy, and permit extrapolation to cases where nothing is known about the desired sequence.
Three such methods have so far been disclosed. One of them, that of Houghten, R. A., Proc. Natl. Acad. Sci. U.S.A., 82, 5131-5135 (1985), is a modification of the above Merrifield method using individual polyethylene bags. In the general Merrifield methods, the C-terminal amino acid of the desired peptides is attached to a solid support and the peptide chain is formed by sequentially adding amino acid residues, thus extending the chain to the N-terminus. The additions are carried out in sequential steps involving deprotection, attachment of the next amino acid residue in protected form, deprotection of the peptide, attachment of the next protected residue, and so forth.
In the Houghten methods, individual polyethylene bags containing C-terminal amino acids bound to solid support can be mixed and matched through the sequential attachment procedures so that, for example, twenty bags containing different C-terminal residues attached to the support can be simultaniously deprotected and treated with the same protected amino acid residue to be next attached, and then recovered and treated uniformly or differently, as desired. The result of this is a series of polyethylene bags each containing a different peptide sequence. Although each bag will contain many peptides, all of the peptides in any one bag are the same. The peptides in each bag can then be recovered and individually biologically tested.
An alternative method has been devised by Geysen, H. M., et al., Proc. Natl. Acad. Sci. U.S.A., 81, 3998-4002 (1984). See also WO86/06487 and WO86/00991. This method is a modification of the Merrifield system wherein the C-terminal amino acid residues are bound to solid supports in the form of polyethylene pins and the pins treated individually or collectively in sequence to attach the remaining amino acid residues. Without removing the peptides from support, these peptides can then efficiently be effectively individually assessed for the desired activity, in the case of the Geysen work, interact with a given antibody. The Geysen procedure results in considerable gains in efficiency of both the synthesis and testing procedures, while nevertheless producing individual different peptides. It is workable, however, only in instances where the assay can be practically conducted on the pin-type supports used. If solution assay methods are required, the Geysen approach would be impractical.
A third method described by Huebner and Santi, U.S. Pat. No. 5,182,366, describes a procedure in which linear peptide mixtures may be prepared using mixed resins such that any particular resin has attached to it a single unique sequence. This is achieved by a series of splitting and recombining of resin pools such that only one amino acid is coupled at a single time in each pool, but following that completed reaction, the pools are recombined such that a large number of the statistically calculable representations are prepared by extending this through n steps.
In principle the methods of preparing linear peptide libraries might be extended to the preparation of cyclic peptide mixtures (see Table III below).
TABLE III ______________________________________ Proteced Amino Acids Used in Example 3; Total of 1296 Peptides INITIAL ATTACHMENT; Boc-Asp-OFm (bound to resin) Cycle 1 Cycle 2 Cycle 3 Cycle 4 ______________________________________ Boc-Gly Boc-Arg Boc-Lys (GlZ) Fmoc-Ala Boc-Tyr (Cl, Bzl) Boc-Gly Boc-Ala Fmoc-Phe Boc-Val Boc-Trp (For) Boc-Thr (Bzl) Fmoc-Tyr (OBut) Boc-Leu Boc-Phe Boc-Phe Fmoc-Ile Boc-Ser (Bzl) Boc-Met Boc-Pro Fmoc-His (Fmoc) Boc-Glue Boc-Gln Boc-Glue (OChx) Fmoc-Gly (OCHx) ______________________________________
But most peptide cyclizations are carried out in solutions under high dilution conditions in order to avoid dimerization and polymerization. Furthermore, attempting to cyclize mixtures of linear sequences would predictably lead to virtually intractable products with numerous unidentifiable and inseparable components.
Most peptide libraries involve the use of Merrifield solid phase synthesis to insure synthetic ease and feasibility. This approach is normally not compatible with end to end cyclization, since the C-terminal residue is usually the point of attachment, thereby precluding cyclization without first cleaving the peptide. Cleaving the peptide from the solid support creates two new problems: 1) making possible dimeric and oligomeric linear and cyclic structures, and 2) rendering the process of characterizing and retaining groups of identical peptides nearly impossible.
It is known that peptide libraries can provide a novel pool of target compounds. It is also known that there are many advantages to cyclic peptides, but most known methods of preparing peptide libraries are not amenable to the preparation of cyclic peptides. In a paper describing linear peptides (Lam et al., Nature, 354, No. 7 (1991), the authors mention the possibility of cyclic peptides, but that reference does not teach the preparation of these. In a paper by O'Neil et al., Proteins, 14, 509-515 (1992), cyclic peptide mixtures are constructed on the surfaces of phages but the compounds are not proven to be cyclic and the ring is formed by disulfide oxidation of cysteine.
Using peptide synthesis techniques, the present invention describes an innovative method for preparing libraries of cyclic peptides using resin-bound cyclization that is compatible with the presence of other peptides on accompanying beads and even on the same bead. The present invention further demonstrates the feasibility of this technique by synthesizing, both individually and collectively, cyclic peptides and by fully characterizing the products to demonstrate their structural and stereochemical integrity. This invention also solves the problem of dimerization and it is demonstrated that the resin-bound cyclization produces an monomeric cyclic components.

Cyclic peptide mixtures via side chain or backbone attachment and solid phase synthesis


A gateway using multiple NAT tables to translate network addresses (e.g., Internet Protocol Addresses). The gateway may comprise a service selection gateway connecting remote systems to service domains. The gateway translates local addresses of remote systems to external addresses, and vice versa. The external addresses (bound to the respective local addresses) may be provided by the service domains. The NAT information is partitioned according to service domains such that the external addresses related to the same service domain are stored in the same NAT table. If there is no overlap of external addresses provided by two service domains, the two service domains may share the same NAT table. Due to the partitioning of the NAT information, each table may be limited to be of small size, and the accesses to individual tables may be fast. As a result, a gateway may be able to process and forward packets quickly.

1. Field of the Invention
The present invention relates to gateways used in Internetworking Technologies, and more specifically to a method and apparatus for performing network address translation (NAT) in a gateway.
2. Related Art
Gateways are often used to enable users at remote locations (e.g., at homes) to access different target systems (e.g., a computer system on a local area network). A gateway provides the connectivity between remote systems (e.g., personal computers) at remote locations with the target systems of interest to enable different network applications.
A service selection gateway (SSG) is a type of gateway which facilitates a remote user to use various services provided using the Internetworking technologies. Examples of such services include access to the world-wide-web and a virtual private network (VPN) to a specific target location (e.g., to an employer site). SSGs are often integrated with routers into a single unit as is well known in the relevant arts.
Network address translation (NAT) is often performed within an SSG (or gateway in general). NAT commonly refers to replacing one network layer address in a packet with a second network layer address. In a typical application of NAT in an SSG, a packet is received from a remote location in the upstream direction. The source address field of the packet contains a local address of a system ("remote system") at a remote location The local address is substituted with an address ("external address") in the SSG, and the mapping of the local address to the external address may be referred to as a NAT operation.
The external address is usually provided from a service domain (e.g., other end of a VPN) and is unique within the service domain. The packet with the substituted external address is sent to the service domain. A reverse translation is performed from the external address to the local address when packets are received from the service domain. Thus, even if the addresses in the remote location overlap with the addresses in the service domain, remote locations can access the services.
A NAT table is often maintained to map each of the local address to a corresponding external address and vice versa. In a prior system, an SSG may maintain a single global NAT table for all the translations. One problem with such an approach is that a big table may be required to support a large number of services and the related users. The table size may lead to long lookup times and impede the throughput performance of a gateway.
Accordingly, what is required is an efficient method and apparatus to implement NAT operations within a SSG.

Network address translation in a gateway


Preparations for the sustained release of a nutraceutical are described that include a solid matrix coated with a methylcellulose-containing coating. The solid matrix contains a polyphenol and the nutraceutical. Methods of controllably releasing a nutraceutical are also described that include administering to a patient a preparation containing a solid matrix coated with methylcellulose-containing coating. The solid matrix includes a polyphenol and a therapeutically effective amount of the nutraceutical.

The present invention relates to preparations and methods for the controlled release of nutraceuticals.
The controlled release of a physiologically active agent into an individual's system from a sustained release dosage form is often a desirable alternative to repeated administrations (e.g., after a prescribed number of hours) of the agent from conventional dosage forms (i.e., one controlled release dosage may provide the full daily regimen of active agent). Sustained release formulations incorporating water soluble cellulose ethers in a hydrophilic solid core matrix have been developed for this purpose. Upon contact with an aqueous environment, such formulations hydrate to form a gel layer on the surface of the solid core matrix, which limits entry of water into the solid core, thereby establishing a diffusion-controlled sustained release of the active ingredient therein.
Alternative sustained release formulations are based on solid core matrixes that have been coated with materials that can form membranes exhibiting sustained release characteristics. Examples of such materials include hydroxypropyl methylcellulose, shellac, fats, and waxes.
In view of the importance of controlled release delivery systems for the administration of physiologically active agents, there persists a need for new preparations capable of slowly releasing an ingredient from a solid matrix in which it is contained.

Preparations for sustained release of nutraceuticals and methods of controllably releasing nutraceuticals


A branching mirror and a transfer mirror receiving a laser beam reflected on the branching mirror and outputting a laser beam in a direction parallel to the laser beam coming into the branching mirror are fixed to and mounted on one mirror holder. The mirror holder is movably provided between a branching position at which the branching mirror is located in a light path of the laser beam and an escaping position at which the branching mirror is located outside the light path of the laser beam, and while the mirror holder is located at the beam branching position, a laser beam from a laser oscillator can be introduced to the branching mirror.

FIG. 10 shows a laser processing machine having a laser beam branching apparatus based on the conventional technology. This laser processing machine has two machining heads 1a and 1b, and laser beams are given to the machining heads 1a and 1b respectively from one unit of laser oscillator 2.
The laser oscillator 2 has an excitation light source 3, a solid state laser element 4 as an excitation medium, a cavity 5 incorporating therein the excitation light source 3 and the solid state laser element 4, and an optical resonator 8 comprising a total reflection mirror 6 and a partial reflection mirror (output mirror) 7 provided opposite to each other in both side of the cavity 5, and a laser beam L is outputted from the partial reflection mirror 7 to a laser optical system.
The laser optical system has a laser beam branching apparatus 9 for selectively branching the laser beam L outputted from the optical resonator 8 into two light paths, magnifying lenses 10a, 10b provided in parallel to each other at midpoints in the branched two light paths (parallel light paths) respectively, collimator lenses 11a, 11b, and converging lenses 12a, 12b, and laser beams La, Lb in the two light paths are propagated to the machining heads 1a, 1b through optical fibers 13a, 13b respectively.
Provided on each of incident end faces of the optical fibers 13a, 13b are optical fiber incident beam converging lenses 14a, 14b, and laser beams La, Lb converged by the converging lenses 12a, 12b are given to the optical fiber incident beam converging lenses 14a, 14b respectively.
It should be noted that converging lens systems each comprising a collimator lens 15a (15b) and a converging lens 16a (16b) are provided in the machining heads 1a, 1b respectively, and the laser beams La, Lb are converged to nozzle sections 17a, 17b provided at tips of the machining heads 1a, 1b, respectively.
The laser beam branching apparatus 9 has a branching mirror holder 21 holding the branching mirror (partial reflection mirror) 19 and enabling pivotal displacement of 180 degrees at a center axial line of a pivot 20 as well as a transfer mirror (total reflection mirror) 22 located and fixed in the light path of the laser beam Lb at a slope of 45 degrees.
The branching mirror 19 is positioned at either a position A (a beam branching position) located in a light path between the laser beams L and La (an optical axis of the laser beam L and that of the laser beam La are an identical axial line) at a slope of 45 degrees or a position B (an escaping position) pivotally displaced from the position A by 180 degrees and escaping outside the light paths between the laser beams L and La according to rotation by 180 degrees of a branching mirror holder 21 around a central axis of a pivot 20, and at the position A the branching mirror branches the laser beam L into the laser beams La, Lb directing to the machining heads 1a and 1b respectively, and stops branching of the laser beam at the position B so that only the laser beam La is allowed to go to the machining head 1a.
As the other type of laser beam branching apparatus, there is the one as disclosed in Japanese Patent Laid-Open Publication No. HEI 7-294833, in which total reflection mirrors each having a form like a right-angled triangle located opposite to each other in a main laser beam light path are provided movably in parallel to each other in the direction of crossing the optical axis at right angles to the main laser beam optical axis, the branching mirror branches the main laser beam into two beams by refracting the main beam to both sides of the mirror by 90 degrees in opposite directions when an apex (ridgeline) of the total reflection mirror having a form like a right-angled triangle is positioned on the optical axis (central position) of the main laser beam, and the main laser beam is refracted only to one side by 90 degrees when the total reflection mirror having a form like a right-angled triangle is located where the main laser beam is introduced into only one of slants of the mirror and the laser beam is not branched.
As shown in FIG. 10, in an apparatus in which a light path is switched (branched) to the other by pivotally displacing the branching mirror holder 21 holding only one piece of the branching mirror 19, when there occurs angle displacement in the branching mirror holder 21 at the position A, an incident angle of the laser beam into the transfer mirror 22 is changed and a position of the incident light into an optical system to be converged to the optical fiber 13b is also displaced, and for this reason converging performance of the laser beam Lb outputted from the optical fiber 13b is reduced, and at the worst the laser beam Lb is not introduced into the optical fiber 13b, which sometimes causes the optical fiber 13b to be burnt and resultantly processing to be impossible.
For this reason, in order to prevent generation of angle displacement in the branching mirror holder 21, a driving system of the branching mirror holder 21 for realizing selection of a light path is required to have high-angular positioning accuracy, which causes the structure to be complicated and so much cost to be required.
In the laser beam branching apparatus as shown in Japanese Patent Laid-Open Publication No. HEI 7-294833, the above problem does not occur, but the laser beam is branched at the optical axis (beam center) of the main laser beam as an interface therebetween, so that a position of maximum light intensity of the branched laser beam is not located at the center of the beam, and the light intensity is distributed on one side, and for this reason a high-quality branched laser beam can not be obtained.


A vehicle body structure is provided. The vehicle body structure includes a hood provided at a vehicle body; and a transfer mechanism configured to move the hood relative to the vehicle body, the transfer mechanism including: a main actuator configured to move a vehicle-widthwise center portion of the hood relative to the vehicle body; and driven actuators configured to move the hood relative to the vehicle body on left and right sides of the main actuator.

Conventionally, such a vehicle body structure as disclosed in JP5907193B has been known.
JP5907193B discloses a pop-up hood device used to lift a front end portion of a hood provided at a front section of a vehicle body. The pop-up hood device includes a hood locking device for locking the hood and a pair of left and right actuators. When a collision detection sensor detects a collision with a protection target, a control unit of the pop-up hood device actuates the pair of left and right actuators. Upon the actuation of the actuators, the hood locking device unlocks the hood. This enables the hood to be lifted, thereby reducing an impact when the protection target collides with the vehicle body.


A backlight module includes at least a light source generator, a housing, at least a thermal detector, and an inverter. The thermal detector is disposed in the housing for measuring the temperature within the housing when the light source generator is operating, and the inverter is electrically connected to the thermal detector and the light source generator for adjusting the electrical current of the light source generator according to the temperature measured by the thermal detector.

1. Field of the Invention
The invention relates to a backlight unit and method for equalizing brightness of the backlight unit, and more particularly, to a means of utilizing thermal detecting devices and a feedback system to improve the brightness equalization of the backlight unit.
2. Description of the Prior Art
As technology advances, liquid crystal displays (LCDs) have been widely utilized in digital cameras, PDAs, satellite navigation systems, and flat panel televisions. Being one of the key components of the liquid crystal displays, backlight units are optical devices utilized for providing a light source to the liquid crystal displays.
According to the location of the light source, backlight units are typically divided into two major categories: direct-type, in which the light source is generated from directly underneath the display panel, and edge light type, in which the light source generator is located adjacent to the edge of the display panel. The direct-type backlight units are able to provide a higher intensity of light and are thus more suited for large size display panels such as computer monitors and TV panels while the edge light type backlight units are poorly suited for these larger panels.
Please refer to FIG. 1. FIG. 1 is a cross-sectional view of a conventional backlight unit 10. As shown in FIG. 1, the backlight unit 10 includes a housing 12 serving as the supporting platform of the backlight unit 10, a housing 14, a plurality of light generators 16 for generating lights, a reflecting plate 18 disposed on the surface of the housing 12, a light guiding structure 20, such as a diffusing plate, disposed on the opening of the housing 14 for diffusing the light produced by the light source generator 16 upward to the liquid crystal display panel (not shown) and for providing uniformly scattered lights, and a plurality of reflectors 22 embedded on the edge of the housing 14 and the housing 12 for reflecting the light produced by the light source generator 16 along a horizontal direction to the light guiding structure 20. Additionally, an optic film is typically provided above the light guiding structure 20 for enhancing the backlight unit 10 so as to output light beams with uniform luminous intensity to the housing 12, in which the number and the position of the optical film can be varied according to the requirements of the products.
In general, the light source generator 16 in the backlight unit 10 is typically composed of a plurality of light tubes, such as cold cathode fluorescent lamps (CCFL) or external electrode florescent lamps (EEFL). To meet the requirements of high brightness and low weight, the aforementioned light source generator 16 is often installed in a very narrow and small closed chamber. Thus, the heat generated during operation will accumulate rapidly, leading to a high temperature near the light tubes after operating for a period of time. Consequently, the high temperature will interfere with the normal operation of the backlight unit 10 and deteriorate the illumination efficiency of the lamps.
Please refer to FIG. 2. FIG. 2 is a diagram showing the relationship between the brightness of the cold cathode fluorescent lamp and the ambient temperature. As shown in FIG. 2, the brightness of common cold cathode fluorescent lamps utilized for light source generators will only achieve a maximum value under certain ambient temperature. However, the interior of the direct-type backlight unit 10, especially the type utilized for large-scale liquid crystal displays will generate large amount of heat due to long hours of operation and the large quantity of cold cathode fluorescent lamps, such that the interior temperature of typical backlight units will often reach 50° C. or above and seriously decrease the illumination efficiency of the backlight unit and influence the uniformity of the brightness of the liquid crystal display. Additionally, the high temperature within the backlight unit 10 will also decrease the quality of the display, result in a flickering phenomenon in some regions of the display. This has the effect of reducing the life expectancy of the surrounding devices.
Hence, maintaining and adjusting the illumination efficiency of the backlight unit, increasing the uniformity of the brightness of the unit, and at the same time achieving satisfactory heat dissipation and maintaining the life expectancy of surrounding devices has become a critical task.

Backlight unit and method for equalizing brightness thereof


An induction-type loopset is provided that is connectable to a wireless device. The loopset contains a first coil electromagnetically coupled to a t-coil hearing aid and an impedance-matching device coupled to the first coil. The impedance-matching device is responsive to an audio signal from the wireless device. The induction-type loopset is powered from the power source of the wireless device. The power source is responsive to an activation state of the wireless device.

1. Field of the Invention
This invention relates to providing a power source for an inductive loopset. More particularly, this invention relates to providing operating power to an inductive loopset using battery power provided by a wireless phone.
2. Description of Related Art
Telecoil (T-coil) hearing aid users commonly experience interference from the high-frequency electromagnetic signal emitted by wireless phones when the phone is placed in close proximity to the t-coil. The interference—a "buzz" or "hum" in the hearing aid—makes the use of wireless phone handsets difficult. To assist these users, audio induction systems were created. Audio induction systems operate using the principles of electro-magnetics. When an electrical current is amplified and passed through a wire loop, an electromagnetic field is generated around the wire that varies in direct proportion to the amplitude and frequency of the signal. If another wire (or wire loop) is placed in proximity to this field, an identical current will be passed (induced) to the wire. Finally, the current representative of the original audio signal is amplified for hearing.
Personal loopsets were created to apply the audio induction principle to wireless devices so that the wireless phone could be used with t-coil hearing aids. As shown in FIG. 1, the coil 40 of loopset 5 is worn around the user's neck. The coil 40 is coupled to an impedence-matching device 33 inside the housing 30. The impedance-matching device 33 receives a voice signal from the wireless phone 10, transmits the corresponding electromagnetic field to the coil 40, and ultimately to a hearing aid placed in proximity to the coil 40.
Current designs of loopsets use small cell batteries to power the electronics of the loopset. As shown FIG. 2, the battery 34 provides operating power to the loopset 5 when the terminal 41 has been inserted into the jack 42. The insertion of the terminal 41 completes an electrical path, which allows the loopset 5 to produce an induction current.
The current designs have inherent problems that, if removed, would make major strides in the loopset technology. First, in order for the loopset 5 to operate, the terminal 41 must be plugged into the jack 42. Using this approach, a hearing impaired user is almost forced to constantly wear the loopset to hear an incoming call to the wireless phone 10. This means that the coil 40 is constantly emitting an electromagnetic magnetic field if the loopset is being worn and the battery power is constantly being depleted. This leads to inconvenience and a short battery life. Thus, a user is forced to replace the battery often. However, if a user decides to keep the loopset in a pocket or a bag, to conserve battery power, a user must fumble to put the loopset on if a call is received while the loopset is not being worn.
Thus, the inventors have discerned that there is a need to address the above-mentioned problems by providing a loopset that is more user friendly than current configurations and overcomes the problems identified above.

Wireless phone powered inductive loopset


The present invention relates to novel salts and crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate for use in treating viral infections. In some embodiments, the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.

Prevention and treatment methods for some Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae viruses present challenges due to a lack of vaccine or post-exposure treatment modality for preventing or managing these infections. In some cases, patients only receive supportive and resource intensive therapy such as electrolyte and fluid balancing, oxygen, blood pressure maintenance, or treatment for secondary infections. Thus, there is a need for antiviral therapies having a potential for broad antiviral activity.
The compound (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate, referred herein as Compound 1 or Formula I, is known to exhibit antiviral properties against Arenaviridae, Coronaviridae, Filoviridae, and Paramyxoviridae viruses as described in Warren, T. et al., Nature (2016) 531:381-385 and antiviral activities against Flaviviridae viruses as described in U.S. provisional patent application No. 62/325,419 filed Apr. 20, 2016.
(S)-2-Ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino) propanoate or 2-ethylbutyl ((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate, (Formula I), has the following structure:

It is desired to have physically stable forms of the compound that are suitable for the therapeutic use and the manufacturing process.

Crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy) (phenoxy) phosphoryl)amino)propanoate


An interface module having a receiving section and a sending section, the receiving section being provided with a low pass filter, an isolation transformer and a common mode choke transformer, and the sending section is provided with a low pass filter, an isolation transformer and a common mode choke transformer and they are integrated with each other, wherein the receiving section and the sending section are independently formed on a board of the interface module, and the low pass filter at the receiving section and the low pass filter at the sending section are respectively covered by shield cases.

1. Field of the Invention
The present invention relates to an interface module, and more particularly to an interface module used to transmit a digital signal in a communication between LANs (Local Area Networks), computers, data terminals or the like.
2. Description of the Related Art
FIG. 9 is a circuit diagram showing a conventional interface circuit. A reference numeral 1 denotes a whole interface circuit. Reference numerals 2, 3 denote low pass filters. Reference numerals T1, T2 denote isolation transformers. Reference numerals T3, T4 denote common mode choke transformers. A reference symbol RE denotes a receiver. And, a reference symbol DR denotes a driver.
The whole interface circuit 1 is provided with a receiving slide, or section and a sending slide, or section. The receiving section is composed of the low pass filter 2, the isolation transformer T1 and the common mode choke transformer T3. The sending section is composed of the low pass filter 3, the isolation transformer T2 and the common mode choke transformer T4.
The low pass filter 2 removes noise (harmonic element) mixed on a transmission line. One end of a coil L1 and one end of a coil L2 are connected to each other through a capacitor C1. The other end of the coil L1 and the other end of the coil L2 are connected to each other through a capacitor C2. The low pass filter 3 removes harmonic element (noise at a normal mode). One end of a coil L3 and one end of a coil L4 are connected to each other through a capacitor C3. The other end of the coil L3 and the other end of the coil L4 are connected to each other through a capacitor C4.
The isolation transformers T1, T2 electrically separate between an input side and an output side (insulate between the input side and the output side). The common mode choke transformers T3, T4 remove common mode noises (noises having same phases on two lines).
An input signal on a receiving side input has a wave substantially identical to a sine wave, and is converted by the isolation transformer T1 after the common mode noise is removed by the common mode choke transformer T3. This signal is outputted to the receiving side output via the receiver RE after the noise mixed on the transmission line is removed through the low pass filter 2.
An input signal on a sending side input is a digital signal having a rectangular wave outputted by the driver DR. Then, this signal is inputted to the low pass filter 3 at the sending section. The wave of the signal inputted to this low pass filter 3 becomes substantially identical to the sine wave, since the harmonic element is removed. This signal is transmitted through the isolation transformer T2 to the common mode choke transformer T4, and then the common mode noise is removed and the signal is outputted to the sending side output.
Up to now, such an interface circuit is integrated as shown in FIG. 10. Namely, electronic parts, such as a bobbin around which coils L1, L2 of a low pass filter 2 are wound, a bobbin around which coils L3, L4 of a low pass filter 3 are wound, isolation transformers T1, T2, common mode choke transformers T3, T4 and the like are mounted on a front surface of a printed circuit board 101, and capacitors C1, C2, C3 and C4 (not shown in FIG. 10) of the low pass filters are mounted on a rear surface of the printed circuit board 101.
The interface module in which such an interface circuit is integrated is required to have an abrupt attenuation characteristic to attenuate signals not included in a predetermined frequency band because a fast response is necessitated.
In the conventional interface module, since the coils L1, L2, L3 and L4 constituting the low pass filter are formed in an open magnet circuit, an inputted signal having a high frequency is radiated as noise. Thus, in the conventional interface module, the noise radiated from the coil of the low pass filter is mixed into the isolation transformer or the common mode choke transformer, or the noise radiated from the coil of the one low pass filter is mixed into the other low pass filter. This results in a problem that it is impossible to obtain the sufficient attenuation characteristic.
In a case that other electronic parts which generate noise are mounted adjacently to the interface module, the external noise resulting from the electronic parts is mixed into the low pass filter, and thereby this results in the problem that it is impossible to obtain the sufficient attenuation characteristic. Moreover, in a case that the low pass filter 2 at the receiving section and the low pass filter 3 at the sending section are formed adjacently to each other, the coils L1, L2 constituting the low pass filter 2 and the coils L3, L4 constituting the low pass filter 3 at the sending section are electro-magnetically coupled to each other. Hence, this results in a problem that cross talk is generated.
In order to solve these problems, the low pass filter 2 at the receiving section, the low pass filter 3 at the sending section, the isolation transformers T1, T2 and the common mode choke transformers T3, T4 are formed so as to have intervals between them. However, this results in a problem that the size of the interface module becomes large. Moreover, even if having the above mentioned configuration, it is impossible to prevent the external noise from being mixed into the low pass filter. Hence, it is impossible to obtain the sufficient attenuation characteristic.
On the other hand, recently, it is desirable that such an interface module and the like are miniaturized, associated with the miniaturization of the apparatus comprising them. However, the conventional interface module can not be miniaturized because of the above mentioned problems.

Interface module for a sending section and a receiving section