According to some embodiments, methods and systems may include a data storage device that contains document files associated with a plurality of document line objects with attributes, the attributes including item terms and conditions. An object exchange platform processor may receive input values for a selected document line object with attributes and determine that the selected document line object contains multiple object sets. The processor may then create, for each object set, a separate executable outline document having an outline document identifier. The processor may also arrange to establish the plurality of executable outline documents at a remote external central component platform. According to some embodiments, objects within the selected document line object have a hierarchical structure such that some objects are sub-items of other objects. Moreover, attributes of the objects within the selected document line object may be distributable and configurable in accordance with the hierarchical structure.

An enterprise may utilize an object exchange platform. For example, the enterprise might establish a document line object with attributes, and the document line object may include have items with a hierarchical structure such that some objects are sub-objects of other objects. In some cases, the enterprise might want to establish a number of executable outline documents at a remote external central component platform based on such a document line object. Typically, only a single executable outline document can be established per document line object. This may force the enterprise to create a substantial number of document line objects, which can be a time-consuming, expensive, and error prone process. For example, a simple change to an attribute may need to be manually replicated across a large number of document line objects (e.g., potentially hundreds of related document line objects. It would therefore be desirable to provide for the creation of multiple executable outline documents based on a single document line item in a fast, automatic, and accurate manner.

Support hierarchical distribution of document objects


The box boom lift arm assembly of the present invention includes a single plate steel top wall and a bottom wall connected with a substantially non-transverse weld to a pair of single plate steel inner side walls and a pair of single plate steel outer side walls to define a closed box section having a rectangular cross section along the entire length, varying only in height and width. The unique configuration and shape of the plates and the use of non-transverse weld during manufacturing improve the fatigue characteristics, load distribution and strength of the box boom lift arm assembly without increasing the weight of the machine.

Present construction machines, such as wheel loaders, typically include load carrying structures, such as slab lift arms, or occasionally, a box boom lift arm, which is mounted to a frame of the machine by various connection means. The box boom lift arm is generally a hollow unitary structure made from one or more castings connected by a transversely welded midsection.
During operation of the wheel loader, it is quite common for the box boom lift arm assembly to experience a high degree of loading, some of which may be severe. Therefore, it is desirable to carry and distribute loads exerted on the box boom lift arm assembly to minimize failure of the structural elements. For improved machine performance, it is also desirable to minimize the weight of the box boom lift arm assembly while maintaining the high strength capabilities. Furthermore, it is desirable to simplify the box boom lift arm assembly manufacturing and welding processes.
Constructions of, and methods for, making load carrying structures are disclosed in the following patents. U.S. Pat. No. 3,902,295 issued to John W. Yancy on Sep. 2, 1975 and U.S. Pat. No. 4,428,173 issued to Harvey A. Knell on Jan. 31, 1984 show details of booms used on excavators. U.S. Pat. No. 4,768,917 issued to Anthony L. Garman on Sep. 6, 1988 and U.S. Pat. No. 5,152,659 issued to Toshihiko Waka on Oct. 6, 1992 show details of booms for loader type machines. In the design shown in U.S. Pat. No. 4,768,917, the boom arm is made from two hollow end castings welded together by a welded midsection. Loads on the boom arm will be experienced at the transverse welded midsection of the boom arm which may reduce overall component life. In the design shown in U.S. Pat. No. 5,152,659, the boom assembly comprises a pair of boom arms which are formed with a plurality of welded, overlapping C-channels. The overlapping of the C-channels increases the weight of the machine and complicates the welding process.
The present invention is directed to overcoming the problems as set forth above.


A haptic braking method and system is disclosed. A controller operates a pump to apply brake fluid to a brake when it is necessary to decelerate a wheel during an active cruise control mode of a vehicle. The controller further operates one or more valves to cyclically vary a pressure level of the brake fluid to cause one or more haptic movements of the brake.

1. Field of the Invention
The present invention generally relates to control systems for automotive vehicles, and more particularly relates to a haptic braking system of a vehicle in an active cruise control mode.
2. Description of the Related Art
Cruise control systems known in the art enable a driver of a vehicle to set a target vehicle speed. While such systems allow the driver to be less active in driving the vehicle, the driver must be aware of any potential rear end collision with any preceding vehicle. As such, there also exists technology in the art for providing a collision warning to the driver during an active cruise control mode. This technology includes visual indicators, tactile indicators, and audio indicators that are all designed to immediately notify the driver of a potential collision into a rear end of any preceding vehicle. Consequently, the driver has an opportunity to timely utilize a braking system of the vehicle as needed to avoid the collision. Recently, human factor research has indicated that one or more brake pulses may offer a better solution for notifying the driver of the potential collision. The automotive industry is therefore striving to incorporate haptic braking into a cruise control system of an automobile vehicle.
One form of the present invention is a haptic braking method. First, a signal indicative of a request to decelerate a wheel in a haptic manner is received. Second, brake fluid is applied to a brake adjacent the wheel in response to the signal. Third, a pressure level of the brake fluid is cyclically varied over at least one cycle.
A second form of the present invention is also a haptic braking method. First, a signal indicative of a request to decelerate a wheel in a haptic manner is received. Second, in response to the signal, a pump is operated to apply a brake fluid to a brake adjacent the wheel. Third, a valve is operated to cyclically vary a pressure level of the brake fluid over at least one cycle.
A third form of the present invention is a haptic braking system comprising a controller, a pump, and a valve. The controller is operable to provide control signals in response to a signal indicative of a request to decelerate a wheel in a haptic manner. In response to a first control signal, the pump is operable to apply a brake fluid to a brake adjacent the wheel. In response to a second control signal, the valve is operable to cyclically vary a pressure level of the brake fluid over at least one cycle.
A fourth form of the present invention is also a haptic braking system. The system comprises a means for applying a supply of brake fluid to a brake in response to a signal indicating a request to decelerate a wheel in a haptic manner. The system further comprises a means for cyclically varying a pressure level of the brake fluid over at least one cycle.
The foregoing forms, and other forms, features and advantages of the invention will become further apparent from the following detailed description of the presently preferred embodiments, read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative of the invention rather than limiting, the scope of the invention being defined by the appended claims and equivalents thereof.


A digital circuit generates a phase synchronization signal for a digital input signal coded according to a biphase modulation. The phase synchronization signal is derived from a clock signal having a higher frequency than the maximum switching frequency of the digital input signal. The frequency of the clock signal is divided with a fully digital divider circuit having a non-integer ratio. The divider is self-synchronizing with the input digital signal. Control signals are used to enable or disable switching of the frequency divider. These control signals are generated by two circuits which sample the input signal with the master clock signal and analyze triplets of consecutive sampling values.

The present invention relates to the field of signal modulation, and more particularly, to an architecture and method for decoding a biphase modulated digital signal using a phase synchronization signal generated from the digital signal.
In many applications, digitized signals or digital data are transmitted through a broadcasting medium on a carrier having frequencies or wavelengths digitally modulated. The digital coding is often based on a biphase modulation, which is also referred to as Manchester coding or Biphase Mark coding. With respect to such a modulation coding scheme, the occurrence of a transition within a given time slot corresponds to a logic xe2x80x9c1xe2x80x9d while the absence of any transition during the time slot corresponds to a logic xe2x80x9c0xe2x80x9d. In each case, there will be a transition at the beginning and another transition at the end of the reference time slot. Therefore, the information content is tied to the presence or absence of transitions from a logic state to a different logic stage during the interval between the start transition. The information content is totally independent from the logic value of the signal, i.e., whether such a signal is high or low during a certain phase.
The received digital stream to be demodulated is then decoded using a synchronizing signal (clock) generated to maintain a perfect phase synchronization with the stream of received digital data. Coding based on a Manchester biphase modulation and the relative signal of an ideal decoding clock are illustrated in FIG. 1. Coding based on the biphase Manchester modulation is used in many applications according to established and standardized protocols. A typical example of an application is with respect to the broadcast of audio signals coded according to the AES-EBU standard. This standard has been enhanced and redefined within different standardization bodies, e.g., SP-DIF, IEC958 and EIAJ. However, the biphase coding has remained unchanged.
In many systems, digital data are organized in a discontinuous manner that is exchanged in bursts. Typical applications include those in which the data is structured according to a TDMA (Time Division Multiple Access) protocol. In a TDMA application, continuity of phase synchronization between successive bursts is not guaranteed. Among these systems, wideband access systems of the passive optical network (PON) type are also included.
For example, when broadcasting digitized audio signals, two samples of the audio signal are transmitted at a prefixed sampling frequency. These two samples relate respectively to the right channel and to the left channel. Each of these samples is associated with a subframe. The subframes of channel A and of channel B are transmitted serially and alternately. Each subframe is preceded by an acknowledgment preamble, as illustrated in FIG. 2.
By way of illustration, an example is taken into consideration. This is done without intending to limit the application of the system of the invention. The ensuing description shall refer to an AES-EBU broadcasting protocol of digitized audio signals for pointing out the significant aspects of the invention. With reference to the scheme of FIG. 2, the pair of subframes A and B corresponding to the same sampling instant forms a frame. A whole set of 192 consecutive frames forms a block.
A subframe contains data relative to the audio sample, and a series of additional information. A subframe structure is represented in FIG. 3. Out of the 32 bits, the first four bits form the preamble. The following four bits transfer auxiliary data. The audio sample is represented by the following twenty bits. The last four bits contain control information, i.e., the validity bit (V), the user bit (U), the state of the channel bit (C) and the parity bit (P), respectively.
There are three different preambles that respectively identify the beginning of the subframe relative to channel A (X preamble), the beginning of the subframe relative to channel B (Y preamble), and the beginning of a new block signaled by the substitution of the X preamble with the Z preamble. FIG. 4 shows the relative waveforms of the three preambles. In addition to the three preamble sequences shown in the figure, the corresponding inverted versions are also valid since the modulation code does not depend on the signal polarity.
For the correct reception and interpretation of the digital stream, it is necessary to have a synchronizing signal that permits the signal to be sampled correctly and to apply the samples to a decoding logic. This phase synchronization signal must have an edge for each possible transition change of the broadcasted signal. Furthermore, the edge of the synchronization signal should fall as close as possible to the middle of the interval between any two possible transition variations to ensure maximum immunity to noise and jitter.
Normally, this phase synchronization signal (clock) is generated by a PLL circuit locked to the switching frequency of the broadcasted signal with a carefully controlled phase. Once the signal is sampled, the decoding logic may be designed as a state machine using the synchronization signal itself as a clock. In this, as well as in other similar applications, the synchronization signal is commonly produced by an analog PLL circuit. The analog PLL circuit extracts from the received signal its clock content using a passband filter, and a VCO is locked to the switching frequency of the received signal to generate a stable clock.
The obtained clock signal is generally used, apart for decoding the data, to drive a D/A converter downstream from the receiver. Therefore, the obtained clock signal must be very stable in terms of jitter to prevent degradation in the performances of the converter. If this function is not required, such as when a DSP is to receive the data, a completely digital approach is preferred to provide reduced integration complexity. A digital approach does not require analog components such as a VCO, filters and frequency comparators.
Furthermore, even in an analog receiver, there exist operating conditions in which the signal is not perfectly locked, i.e., at start up or during switching among different signal sources. In these cases, the receiver would sample the signal at wrong instants causing decoding errors. Normally, a receiver signals these conditions through a validity bit. However, it would be preferable to have an intrinsically more robust receiver capable of correctly interpreting the signal even under a condition of an unlocked clock.
This invention relates primarily to an improved decoding method for an input digital signal or digital stream that is coded according to a biphase modulation. Decoding is performed by sampling the input digital signal with a sampling signal in phase synchronization with the input digital signal. The phase synchronization signal is derived from a clock signal (master clock) having a higher frequency than the maximum switching frequency of the digital input signal. The frequency of the clock signal is divided by a fully digital divider circuit having an irrational or non-integer ratio. The digital divider circuit is self-synchronizing with the input digital signal.
Preferably, the master clock signal should have a frequency in the vicinity of an integer multiple of the maximum frequency of the input signal, i.e., nominally a multiple of the maximum frequency of the input signal. According to one approach, the master clock signal is divided by a certain integer number determined by the use of a divider, while enabling or disabling its switching through control signals. The control signals are generated by two circuits which sample the input signal with the master (high frequency) clock signal and analyze triplets of consecutive sampling values. The first circuit generates a first control signal upon detecting the triplet 001 or 110. The second circuit generates a second control signal upon detecting the triplet 011 or 100.
Preferably, enabling or disabling of the divider by the first circuit takes place on the rising edge of the master clock, and by the second circuit on a falling edge of the master clock. Another aspect of the invention is to provide an architecture of a fully digital frequency divider of an irrational or noninteger ratio that is self-synchronizing with an input digital signal coded according to a biphase modulation. The fully digital frequency divider is capable of generating a sampling signal of the input stream with the characteristics illustrated above. The frequency divider uses a master clock of a sufficiently high frequency, typically a multiple thereof (at least nominally) having a value in the vicinity of a multiple integer of the switching frequency of the input stream, though not necessarily synchronized with it.

Decoding of a biphase modulated bitstream and relative self-synchronizing frequency divider with noninteger ratio


It is the objective to provide a method of stabilizing hydroxylamine at a high temperature and a high concentration or in a case that metal impurities such as Fe got mixed therewith, and a stabilized hydroxylamine solution. A method for stabilizing hydroxylamine related to the present invention is characterized by adding ethylenediamine-N,N′-di(o-hydroxyphenylacetic acid) as a preservation stabilizer.

Hydroxylamines are used in wide industrial applications such as a raw material of a medical and agricultural chemical intermediate, a reducing agent, a treatment agent for surface of metal, a fiber treatment and dyeing. However, free hydroxylamine has extremely unstable characteristics, for instance, it is easily decomposed under the conditions of an existence of metal ions (particularly heavy metal ions), a high temperature or a high concentration. Consequently, a salt of hydroxylamine, which is comparatively stable, is manufactured and used in general.
However, hydroxylamine is suitable for many applications rather than a salt of hydroxylamine. In addition, in many cases, handling of a hydroxylamine aqueous solution at a high temperature or a high concentration is required. Accordingly, a trial to stabilize hydroxylamine under the conditions of a high temperature, a high concentration and metal impurities such as Fe getting mixed with has been carried out.
For instance, the patent document 1 (U.S. Pat. No. 5,808,150) describes a stabilizing method of adding diethylenetriamine-pentaacetic acid or triethylenetetramine-hexaacetic acid as a stabilizer into a solution containing hydroxylamine.
However, there is a problem in which a hydroxylamine solution that contains diethylenetriamine-pentaacetic acid or triethylenetetramine-hexaacetic acid as a stabilizer has an insufficient effect for suppressing a decomposition of hydroxylamine at a high temperature or a high concentration or in a case that metal impurities such as Fe got mixed with.
Patent Document 1: U.S. Pat. No. 5,808,150

Stabilizer and method for stabilizing hydroxylamine, and stabilized hydroxylamine solution


.alpha.-Amylase activity can be determined rapidly and precisely by using as a substrate a modified oligo-saccharide wherein a benzylozymethyl group or a halo-methyl group is bonded to the C.sub.6 position of non-reducing-end glucose residue and the reducing-end glucose residue is bonded to a group which exhibits an optically measurable change upon cleavage. Processes for producing such a compound are also disclosed.

This invention relates to a process for determining the activity of .alpha.-amylase in a sample using a modified oligosaccharide as a substrate and a process for producing such a modified oligosaccharide.
Heretofore, various processes for determining the activity of o-amylase using a modified oligosaccharide as a substrate have been proposed. For example, U.S. Pat. No. 4,649,108 to Blair discloses a method of measuring the amount of .alpha.-amylase in liquid sample comprising the steps of providing an oligosaccharide substrate for .alpha.-amylase, said substrate containing at least 3 glucose units, the reducing-end glucose residue (unit) being bonded, via a bond cleavable by .alpha.- or .alpha.-glucosidase, to a label which exhibits an optically measurable change upon cleavage of said bond, and the non-reducing-end (terminal) glucose residue being bonded to a blocking group which inhibits cleavage by exo-enzymes of the bond between said non-reducing-end glucose residue and the adjacent glucose residue; contacting said sample with said oligosaccharide substrate and with a first added exo-enzyme capable of cleaving the bond between said reducing-end glucose residue and said label, and a second added exo-enzyme capable of cleaving bonds between glucose units, to form a mixture comprising said substrate, said first exo-enzyme, and said second exo-enzyme; and measuring said optically measurable change. According to said U.S. patent, the blocking groups can be carboxylic acid esters, phosphate esters, sulfonate esters, ethers (such as benzyl, silyl, and triphenylmethyl), monosaccharides other than .alpha.-1,4 linked glucose, and acetal or ketal blocking groups such as benzylidene (column 4 lines 37-67). But the ester blocking groups are unstable since they are easily hydrolyzed in an aqueous solution. Further, when the size of the blocking group becomes larger as in the case of toluenesulfonyl, methanesulfonyl, silyl or triphenylmethyl, the solubility in water is undesirably lowered. In addition, the introduction of a blocking group into the non-reducing-end glucose residue has many problems, and the ester and ether groups as mentioned above cannot be introduced into the non-reducing-end glucose residue by the process disclosed at from column 4 line 63 to column 7 line 58 of said U.S. patent. Therefore, according to said U.S. patent, preferably the substrate has eight or fewer glucose units, and most preferably has six or seven, and preferred blocking substituents are acetals or ketals, e.g. benzylidene (column 2 lines 4-7).
When the most preferred oligosaccharide according to said U.S. patent, that is, an oligosaccharide having 6 or 7 glucose units and benzylidene as the blocking group, is used as a substrate for measuring .alpha.-amylase, there are many problems in that the hydrolysis rate by .alpha.-amylase is slow, various kinds of hydrolyzed products are produced due to many positions to be hydrolyzed, the reaction for liberating the color producing group becomes many and complicated due to many hydrolyzed products, the amount of coupling enzymes to be used becomes larger, and thus the reliability for the measurement becomes insufficient. The improvement of these disadvantages has long been desired.

.alpha.-amylase assay using modified oligosaccharide and process for producing said modified oligosaccharide


A pen needle according to the invention comprises a needle hub having a recess for a pen injector and vial. When the pen injector is loaded into the hub, the needle cannula mounted in the hub pierces the septum of the vial. A non-patient end (non-injection end) shield positioned in the hub member engages the pen injector and travels with the pen injector when the pen injector is removed, to shield the non-patient of the needle. The shield is locked into place securing the person administering the injection from accidental injury from the non-patient end of the needle.

1. Field of the Invention
The invention is directed to a passive safety shield which may be associated with an injection pen needle to shield the non-injection end of the needle.
2. Description of the Related Art
Accidental needlestick injuries from contaminated needles expose healthcare workers to the risk of infection from blood-borne pathogens, including the viruses that cause hepatitis B and C, and HIV. According to the Centers for Disease Control and Prevention, healthcare workers in the United States experience an estimated 600,000 exposures to blood each year, with RNs being subject to an overwhelming majority of these incidents.
While the injection device of choice in the U.S. remains the syringe, the demand for pen needles is growing rapidly. The use of self-injection pen needle devices is increasing due to the relative convenience, portability, and ease of use of these devices as compared to single use syringes. Pen needles are also becoming more commonplace in the hospital/clinical setting, as certain drugs, such as human growth hormone and osteoporosis medications, are available only in pen needle format.
Healthcare workers have sustained needlestick injuries while removing and disposing of needle hubs from pen needle devices after administering an injection to patients. The needles are typically removed after each injection to minimize contamination of the medication in the cartridge and to prevent needle re-use. Removal of the needle generally requires the re-shielding of the needle using the outer protective shield in which it was supplied and it is especially during the re-shielding step where injuries can occur. Needlestick injuries also occur during the removal of pen needles that have not been re-shielded.
U.S. Pat. No. 6,986,760 B2, assigned to the assignee of the present application, the disclosure of which is herein incorporated by reference in its entirety, teaches a pen needle and safety shield system wherein a safety shield, which normally encloses the needle cannula prior to use, permits retraction of the safety shield during injection and automatically extends and locks the shield in the extended enclosed position following use. The pen needle also prevents retraction of the shield during assembly of the shield and needle cannula and hub assembly on the pen injector.
However, this prior art does not disclose a pen needle having a non-injection end passive safety shield. Thus the invention disclosed herein, which may be incorporated into prior art safety shielded pen needles, represents an advance in the art, in that novel means are provided to guard against accidental needlestick from the non-injection end of a needle in a pen needle.

Safety pen needle with non-injection end passive safety features


A system and a method for determining a break point of a plurality of hog carcasses is disclosed. The method includes establishing at least one criterion for determining whether the loin of a carcass should be boned. Data is then collected from the hog carcasses relating to the quality of the hog carcasses. Next a determination is made, based on the criteria, whether the loin of a selected carcass of the plurality of hog carcasses is appropriate for boning. If so, the break point of the selected carcass is adjusted appropriately.

The cutting floor of a typical meat packaging facility may produce meat products representing a value of several hundred million dollars each year. The value of the meat products that are produced is dependent on the way the animal carcasses are divided into primals and on the way the primals are trimmed of fat, skin and extraneous portions. The primals of a hog carcass are the shoulder (which includes the boston butt and the picnic), loin, ham, belly, and ribs. Cutting floor operations, if monitored at all, have typically been monitored on the basis of total daily production of various primals.
In commercial meat packing operations, animals, such as hogs, are slaughtered, bled, skinned, eviscerated, and the resulting carcass is then cut into halves before it is chilled. The carcasses are typically suspended from an overhead rail and are moved by a conveyor on the rail. The carcasses are then placed on a table and sent down a conveyor to a chop saw where the carcass is broken or cut at a pre-determined point between the loin portion and the shoulder portion. After the carcass is broken, the loin portion is either sent down a first line where the bones will remain in the loin or sent down a second line where the bones are removed.
A loin that is boned becomes a boneless loin. A loin that is not boned becomes a bone-in loin. A loin that is not boned is commonly referred to on the processing floor as a boxed loin.
Once the decision to bone or box the loin of the carcass has been made, the carcasses are broken between the shoulder and the loin area. This breaking point is typically located medially between the first and second rib (referred to as one and a half (1.5) ribs) from the head of the carcass. After each carcass is broken at 1.5 ribs, the carcasses that will be boned are sent down a separate line from the carcasses that will be boxed. The loins of the carcasses that go down the boning line are trimmed and the bones removed. Industry regulations require that certain muscle meat, primarily longissimus lumbarum, multifidus and spinalis dorsi complexus muscles be trimmed from the boneless pork loin. The trimmings that result from the boning process are used to make processed meat. Although the meat is not wasted, the meat would be significantly more valuable if it had remained attached to the shoulder portion instead of becoming trimmings.
Therefore, there is a need in the hog processing industry for a system and method of automatically adjusting the break point of a carcass, based on whether the loin of the carcasses will be boned or boxed to reduce the amount of the carcass which is processed as trimmings. There is a further need for such a system that operates without slowing down the speed of the processing line.

Optimal hog carcass processing system and method


Briefly, in accordance with an embodiment of the invention, a method to generate cache data is provided, wherein the method includes identifying access data transmitted from a storage device during execution of a predetermined software program and generating cache data using the identified access data.

Computing systems may include various types of memory devices having various access times. For example, a computing system may include a nonvolatile hard disk memory and a relatively faster volatile cache memory.
Several methods exist for determining which information to store in the cache memory. A cache memory may store frequently used data so that the operating system or a particular software application may access the frequently used data from the relatively faster cache memory as opposed to accessing the information from the relatively slower hard disk. Storing frequently used data in a relatively faster cache memory may improve system performance.
Determining the appropriate methods for generating cache data for a particular system may be problematic. The appropriate caching method may depend on many factors to improve performance of a particular system.
Thus, there is a continuing need for alternate ways to generate cache data.
It will be appreciated that for simplicity and clarity of illustration, elements illustrated in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements are exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals have been repeated among the figures to indicate corresponding or analogous elements.

Method and apparatus to generate cache data


Recombinant retroviruses carrying a vector construct capable of preventing, inhibiting, stabilizing or reversing infectious, cancerous or auto-immune diseases are disclosed. More specifically, the recombinant retroviruses of the present invention are useful for (a) stimulating a specific immune response to an antigen or a pathogenic antigen; (b) inhibiting a function of a pathogenic agent, such as a virus; and (c) inhibiting the interaction of an agent with a host cell receptor. In addition, eucaryotic cells infected with, and pharmaceutical compositions containing such a recombinant retrovirus are disclosed. Various methods for producing recombinant retroviruses having unique characteristics, and methods for producing transgenic packaging animals or insects are also disclosed.

The present invention relates generally to retroviruses, and more specifically, to recombinant retroviruses which are capable of delivering vector constructs to susceptible target cells. These vector constructs are typically designed to express desired proteins in target cells, for example, proteins which stimulate immunogenic activity or which are conditionally active in defined cellular environments.
Although bacterial diseases are, in general, easily treatable with antibiotics, very few effective treatments or prophylactic measures exist for many viral, cancerous, and other nonbacterial diseases, including genetic diseases. Traditional attempts to treat these diseases have employed the use of chemical drugs. In general, these drugs have lacked specificity, exhibited high overall toxicity, and thus have been therapeutically ineffective.
Another classic technique for treating a number of nonbacterial diseases involves the elicitation of an immune response to a pathogenic agent, such as a virus, through the administration of a noninfectious form of the agent, such as a killed virus, thereby providing antigens from the pathogenic agent which would act as an immunostimulant.
A more recent approach for treating viral diseases, such as acquired immunodeficiency syndrome (AIDS) and related disorders, involves blocking receptors on cells susceptible to infection by HIV from receiving or forming a complex with viral envelope proteins. For example, Lifson et al. (Science 232:1123-1127, 1986) demonstrated that antibodies to CD4 (T4) receptors inhibited cell fusion (syncytia) between infected and noninfected CD4 presenting cells in vitro. A similar CD4 blocking effect using monoclonal antibodies has been suggested by McDougal et al. (Science 231:382-385, 1986). Alternatively, Pert et al. (Proc. Natl. Acad. Sci. USA 83:9254-9258, 1986) have reported the use of synthetic peptides to bind T4 receptors and block HIV infection of human T-cells, while Lifson et al. (J. Exp. Med. 164:2101, 1986) have reported blocking both syncytia and virus/T4 cell fusion by using a lectin which interacts with a viral envelope glycoprotein, thereby blocking it from being received by CD4 receptors.
A fourth, recently suggested technique for inhibiting a pathogenic agent, such as a virus, which transcribes RNA is to provide antisense RNA which complements at least a portion of the transcribed RNA, and binds thereto, so as to inhibit translation (To et al., Mol. Cell. Biol. 6:758, 1986).
However, a major shortcoming of the techniques described above is that they do not readily lend themselves to control as to the time, location or extent to which the drug, antigen, blocking agent or antisense RNA are utilized. In particular, since the above techniques require exogenous application of the treatment agent (i.e., exogenous to the sample in an in vitro situation), they are not directly responsive to the presence of the pathogenic agent. For example, it may be desirable to have an immunostimulant expressed in increased amounts immediately following infection by the pathogenic agent. In addition, in the case of antisense RNA, large amounts would be required for useful therapy in an animal, which under current techniques would be administered without regard to the location at which it is actually needed, that is, at the cells infected by the pathogenic agent.
As an alternative to exogenous application, techniques have been suggested for producing treatment agents endogenously. More specifically, proteins expressed from viral vectors based on DNA viruses, such as adenovirus, simian virus 40, bovine papilloma, and vaccinia viruses, have been investigated. By way of example, Panicali et al. (Proc. Natl. Acad. Sci. USA 80:5364, 1983) introduced influenza virus hemagglutinin and hepatitis B surface antigens into the vaccinia genome and infected animals with the virus particles produced from such recombinant genes. Following infection, the animals acquired immunity to both the vaccinia virus and the hepatitis B antigen.
However, a number of difficulties have been experienced to date with viral vectors based on DNA viruses. These difficulties include (a) the production of other viral proteins which may lead to pathogenesis or the suppression of the desired protein; (b) the capacity of the vector to uncontrollably replicate in the host, and the pathogenic effect of such uncontrolled replication; (c) the presence of wild-type virus which may lead to viremia; and (d) the transitory nature of expression in these systems. These difficulties have virtually precluded the use of viral vectors based on DNA viruses in the treatment of viral, cancerous, and other nonbacterial diseases, including genetic diseases.
Due to the nontransitory nature of their expression in infected target cells, retroviruses have been suggested as a useful vehicle for the treatment of genetic diseases (for example, see F. Ledley, The Journal of Pediatrics 110:1, 1987). However, in view of a number of problems, the use of retroviruses in the treatment of genetic diseases has not been attempted. Such problems relate to (a) the apparent need to infect a large number of cells in inaccessible tissues (e.g., brain); (b) the need to cause these vectors to express in a very controlled and permanent fashion; (c) the lack of cloned genes; (d) the irreversible damage to tissue and organs due to metabolic abnormalities; and (e) the availability of other partially effective therapies in certain instances.
In addition to genetic diseases, other researchers have contemplated using retroviral vectors to treat nongenetic diseases (see, for example, EP 243,204xe2x80x94Cetus Corporation; Sanford, J. Theor. Biol.130:469, 1988; Tellier et al., Nature 318:414, 1985; and Bolognesi et al., Cancer Res. 45:4700, 1985).
Tellier et al. suggested protecting T-cell clones by apparently infecting stem cells with xe2x80x9cdefectivexe2x80x9d HIV having a genome which could express antisense RNA to HIV RNA. Bolognesi et al. have suggested the concept of generating a nonvirulent HIV strain to infect stem cells so that T4 cells generated therefrom would carry interfering, nonvirulent forms of virus and thereby protect those cells from infection by virulent HIV. However, it would appear that the xe2x80x9cattenuatedxe2x80x9d or xe2x80x9cdefectivexe2x80x9d HIV viruses used in both of the foregoing papers could reproduce (i.e., are not replication defective) such that the resulting viruses could infect other cells, with the possibility of an increased risk of recombination with previously present HIV or other sequences, leading to loss of attenuation. Non-nonreplicative forms would necessitate a defective helper or packaging line for HIV. However, since the control of HIV gene expression is complex, such cells have to date not been constructed. Furthermore, as the infecting attenuated or defective virus is not chimeric (a xe2x80x9cnonchimericxe2x80x9d retrovirus being one with substantially all of its vector from the same retrovirus species), even if they were made replication defective, for example, by deletion from their genomes of an essential element, there still exists a significant possibility for recombination within the host cells with resultant production of infectious viral particles.
Although Sanford (J. Theor. Biol. 130:469, 1988) has also proposed using a genetic cure for HIV, he notes that due to the potential that exists for creating novel virulent viruses via genetic recombination between natural AIDS virus and therapeutic retroviral vectors carrying anti-HIV genes, retroviral gene therapy for AIDS may not be practical. Similarly, while McCormick and Kriegler (EP 243,204 A2) have proposed using retroviral vectors to deliver genes for proteins, such as tumor necrosis factor (TNF), the techniques they describe suffer from a number of disadvantages.
Briefly stated, the present invention provides recombinant retroviruses carrying a vector construct capable of preventing, inhibiting, stabilizing or reversing infectious, cancerous, auto-immune or immune diseases. Such diseases include HIV infection, melanoma, diabetes, graft vs. host disease, Alzheimer""s disease, and heart disease.
The present invention is directed, in part, toward methods for (a) stimulating a specific immune response, either humoral or cell-mediated, to an antigen or pathogenic antigen; (b) inhibiting a function of a pathogenic agent, such as a virus; and (c) inhibiting the interaction of an agent with a host cell receptor, through the use of recombinant retroviruses.
More specifically, within one aspect of the present invention, a method for stimulating a specific immune response is provided, comprising infecting susceptible target cells with recombinant retroviruses carrying a vector construct that directs the expression of an antigen or modified form thereof in infected target cells. For purposes of the present invention, the term xe2x80x9cinfectingxe2x80x9d includes the introduction of DNA sequences through viral vectors, transfection or other means, such as microinjection, protoplast fusion, etc. Where an immune response is to be stimulated to a pathogenic antigen, the recombinant retrovirus is preferably designed to express a modified form of the antigen which will stimulate an immune response and which has reduced pathogenicity relative to the native antigen. This immune response is achieved when cells present antigens in the correct manner, i.e., in the context of the MHC class I and/or II molecules along with accessory molecules such as CD3, ICAM-1, ICAM-2, LFA-1, or analogs thereof (e.g., Altmann et al., Nature 338:512, 1989). Cells infected with retroviral vectors are expected to do this efficiently because they closely mimic genuine viral infection.
This aspect of the invention has a further advantage over other systems that might be expected to function in a similar manner, in that the presenter cells are fully viable and healthy, and no other viral antigens (which may well be immunodominant) are expressed. This presents a distinct advantage since the antigenic epitopes expressed can be altered by selective cloning of sub-fragments of the gene for the antigen into the recombinant retrovirus, leading to responses against immunogenic epitopes which may otherwise be overshadowed by immunodominant epitopes. Such an approach may be extended to the expression of a peptide having multiple epitopes, one or more of the epitopes derived from different proteins. In addition, the present invention provides for a more efficient presentation of antigens through the augmentation or modification of the expression of presenting accessory proteins (e.g., MHC I, ICAM-1, etc.) in antigen presenting cells.
An immune response can also be achieved by transferring to an appropriate immune cell (such as a T lymphocyte) the gene for the specific T-cell receptor which recognizes the antigen of interest (in the context of an appropriate MHC molecule if necessary), for an immunoglobulin which recognizes the antigen of interest, or for a hybrid of the two which provides a CTL response in the absence of the MHC context.
In the particular cases of disease caused by HIV infection, where immunostimulation is desired, the antigen generated from the recombinant retroviral genome is of a form which will elicit either or both an HLA class I- or class II-restricted immune response. In the case of HIV envelope antigen, for example, the antigen is preferably selected from gp 160, gp 120, and gp 41, which have been modified to reduce their pathogenicity. In particular, the antigen selected is modified to reduce the possibility of syncytia, to avoid expression of epitopes leading to a disease enhancing immune response, to remove immunodominant, but strain-specific epitopes or to present several strain-specific epitopes, and allow a response capable of eliminating cells infected with most or all strains of HIV. Antigens from other HIV genes, such as gag, pol, vif, nef, etc., may also provide protection in particular cases.
In another aspect of the present invention, methods for inhibiting a function of a pathogenic agent necessary for disease, such as diseases caused by viral infections, cancers or immunological abnormalities, are disclosed. Where the pathogenic agent is a virus, the inhibited function may be selected from the group consisting of adsorption, replication, gene expression, assembly, and exit of the virus from infected cells. Where the pathogenic agent is a cancerous cell or cancer-promoting growth factor, the inhibited function may be selected from the group consisting of viability, cell replication, altered susceptibility to external signals, and lack of production of anti-oncogenes or production of mutated forms of anti-oncogenes. Such inhibition may be provided through recombinant retroviruses carrying a vector construct encoding xe2x80x9cinhibitor palliatives,xe2x80x9d such as: (a) antisense RNA; (b) a mutant protein analogue to a pathogenic protein, which interferes with expression of the pathogenic state; (c) a protein that activates an otherwise inactive precursor; (d) defective interfering structural proteins; (e) peptide inhibitors of viral proteases or enzymes; (f) tumor suppressor genes; or (g) a RNA ribozyme capable of specifically cutting and degrading RNA molecules corresponding to the pathogenic state. Alternatively, such inhibition is attained by a recombinant retrovirus capable of site-specific integration into pathogenic genes, thereby disrupting them.
Such inhibition may also be accomplished through the expression of a palliative that is toxic for a diseased cell. Where a toxic palliative is to be produced by cells containing the recombinant viral genome, it is important that either the recombinant retrovirus infect only target cells or express the palliative only in target cells, or both. In either case, the final toxic agent is localized to cells in the pathogenic state. Where expression is targeted, the pathogenic agent controlling expression of the toxic palliative could be, for instance, a protein produced through transcription and translation of a pathogenic viral genome present in the cell.
It should be understood in the foregoing discussion, and throughout this application, that when reference is made to the viral construct xe2x80x9cexpressingxe2x80x9d or xe2x80x9cproducingxe2x80x9d any substance in a cell, or the like, this in fact refers to the action of the resulting provirus following reverse transcription of the viral RNA in the cell. In the context of a toxic palliative, the consequent killing effect may not necessarily require the permanent integration of the recombinant viral genome into the host genome, but simply a reasonably long-term expression of a toxic palliative gene, in whatever form desirable, over a reasonably long period of time (several days to one month). Thus, other nonintegrating viral vectors such as, but not limited to, adenoviral vectors may be used for this purpose. Examples of conditional toxic palliatives include recombinant retroviruses encoding (a) a toxic gene product under the control of a cell cycle-specific promoter, a tissue-specific promoter or both; (b) a gene product which is conditionally expressed and which in itself is not toxic but which processes within target cells a compound or drug from a nontoxic precursor form to an active toxic form; (c) a gene product which is not in itself toxic, but when processed by a protein, such as protease specific to a viral or other pathogen, is converted into a toxic form; (d) a conditionally expressed reporter gene product on the cell surface which identifies the pathogenic cells for attack, for example, by immunotoxins; (e) conditionally expressed gene products on the cell surface which lead to a toxic effect by interaction with extracellular factors; and (f) conditionally expressed ribozymes specific for RNA molecules essential for viability.
Within a related aspect, the present invention also provides methods for diminishing or eliminating an unwanted or deleterious immune response. Immune suppression, where appropriate, can be achieved by targeting expression of immune suppressive genes, such as the virally derived E3 gene of adenovirus.
Within another aspect of the present invention, methods are disclosed for inhibiting the interaction of viral particles with cells, cells with cells, or cells with factors. The methods generally comprise infecting susceptible cells with a recombinant, replication defective retrovirus which directs the expression of a blocking element in infected cells, the blocking element being capable of binding with a cell receptor (preferably the host cell receptor) either while the receptor is intracellular or on the cell surface, or alternatively, by binding with the agent. In either event, the interaction is blocked.
Regardless of the means by which the recombinant retrovirus exerts its immunogenic or inhibitory action as described above, it is preferred that the retroviral genome be xe2x80x9creplication defectivexe2x80x9d (i.e., incapable of reproducing in cells infected with it). Thus, there will be only a single stage of infection in either an in vitro or in vivo application, thereby substantially reducing the possibility of insertional mutagenesis. Preferably, to assist in this end, the recombinant retrovirus lacks at least one of the gag, pol, or env genes. Further, the recombinant viral vector is preferably chimeric (that is, the gene which is to produce the desired result is from a different source than the remainder of the retrovirus). A chimeric construction further reduces the possibility of recombination events within cells infected with the recombinant retrovirus, which could produce a genome that can generate viral particles.
Within another aspect of the present invention, recombinant retroviruses which are useful in executing the above methods as well as delivering other therapeutic genes are disclosed. The present invention also provides a method for producing such recombinant retroviruses in which the retroviral genome is packaged in a capsid and envelope, preferably through the use of a packaging cell. The packaging cells are provided with viral protein-coding sequences, preferably in the form of two plasmids, which produce all proteins necessary for production of viable retroviral particles, an RNA viral construct which will carry the desired gene, along with a packaging signal which will direct packaging of the RNA into the retroviral particles.
The present invention additionally provides a number of techniques for producing recombinant retroviruses which can facilitate:
i) the production of higher titres from packaging cells;
ii) packaging of vector constructs by means not involving the use of packaging cells;
iii) the production of recombinant retroviruses which can be targeted for preselected cell lines; and
iv) the integration of the proviral construct into a preselected site or sites in a cell""s genome.
One technique for producing higher titres from packaging cells takes advantage of the discovery that of the many factors which can limit titre from a packaging cell, one of the most limiting is the level of expression of the packaging proteins, namely, the gag, pol, and env proteins, as well as the level of expression of the retroviral vector RNA from the proviral vector. This technique allows the selection of packaging cells which have higher levels of expression (i.e., produce higher concentrations) of the foregoing packaging proteins and vector construct RNA. More specifically, this technique allows selection of packaging cells which produce high levels of what is referred to herein as a xe2x80x9cprimary agent,xe2x80x9d which is either a packaging protein (e.g., gag, pol, or env proteins) or a gene of interest to be carried into the genome of target cells (typically as a vector construct). This is accomplished by providing in packaging cells a genome carrying a gene (the xe2x80x9cprimary genexe2x80x9d) which expresses the primary agent in the packaging cells, along with a selectable gene, preferably downstream from the primary gene. The selectable gene expresses a selectable protein in the packaging cells, preferably one which conveys resistance to an otherwise cytotoxic drug. The cells are then exposed to a selecting agent, preferably the cytotoxic drug, which enables identification of those cells which express the selectable protein at a critical level (i.e., in the case of a cytotoxic drug, by killing those cells which do not produce a level of resistance protein required for survival).
Preferably, in the technique briefly described above, the expressions of both the selectable and primary genes is controlled by the same promoter. In this regard, it may be preferable to utilize a retroviral 5xe2x80x2 LTR. In order to maximize titre of a recombinant retrovirus from packaging cells, this technique is first used to select packaging cells expressing high levels of all the required packaging proteins, and then is used to select which of these cells, following transfection with the desired proviral construct, produce the highest titres of the recombinant retrovirus.
Techniques are also provided for packaging of vector constructs by means not involving the use of packaging cells. These techniques make use of other vector systems based on viruses such as other unrelated retroviruses, baculovirus, adenovirus, or vaccinia virus, preferably adenovirus. These viruses are known to express relatively high levels of proteins from exogenous genes provided therein. For such DNA virus vectors, recombinant DNA viruses can be produced by in vivo recombination in tissue culture between viral DNA and plasmids carrying retroviral or retroviral vector genes. The resultant DNA viral vectors carrying either sequences coding for retroviral proteins or for retroviral vector RNA are purified into high titre stocks. Alternatively, the constructs can be constructed in vitro and subsequently transfected into cells which provide in trans viral functions missing from the DNA vectors. Regardless of the method of production, high titre (107 to 1011 units/ml) stocks can be prepared that will, upon infection of susceptible cells, cause high level expression of retroviral proteins (such as gag, pol, and env) or RNA retroviral vector genomes, or both. Infection of cells in culture with these stocks, singly or in combination, will lead to high-level production of retroviral vectors, if the stocks carry the viral protein and viral vector genes. This technique, when used with adenovirus or other mammalian vectors, allows the use of primary cells (e.g., from tissue explants or cells such as WI38 used in production of vaccines) to produce recombinant retroviral vectors.
In an alternative to the foregoing technique, recombinant retroviruses are produced by first generating the gag/pol and env proteins from a cell line infected with the appropriate recombinant DNA virus in a manner similar to the preceding techniques, except that the cell line is not infected with a DNA virus carrying the vector construct. Subsequently, the proteins are purified and contacted with the desired viral vector RNA made in vitro, transfer RNA (tRNA), liposomes, and a cell extract to process the env protein into the liposomes, such that recombinant retroviruses carrying the viral vector RNA are produced. Within this technique, it may be necessary to process the env protein into the liposomes prior to contacting them with the remainder of the foregoing mixture. The gag/pol and env proteins may also be made after plasmid mediated transfection in eukaryotic cells, in yeast, or in bacteria.
The technique for producing recombinant retroviruses which can be targeted for preselected cell lines utilizes recombinant retroviruses having one or more of the following: an env gene comprised of a cytoplasmic segment of a first retroviral phenotype, and an extracellular binding segment exogenous to the first retroviral phenotype (this binding segment is from a second viral phenotype or from another protein with desired binding properties which is selected to be expressed as a peptide which will bind to the desired target); another viral envelope protein; another ligand molecule in place of the normal envelope protein; or another ligand molecule along with an envelope protein that does not lead to infection of the target cell type.
Techniques for integrating a retroviral genome at a specific site in the DNA of a target cell involve the use of homologous recombination, or alternatively, the use of a modified integrase enzyme which will recognize a specific site on the target cell genome. Such site-specific insertion allows genes to be inserted at sites on the target cells"" DNA, which will minimize the chances of insertional mutagenesis, minimize interference from other sequences on the DNA, and allow insertion of sequences at specific target sites so as to reduce or eliminate the expression of an undesirable gene (such as a viral gene) in the DNA of the target cell.
The present invention is also directed to a pharmaceutical composition comprising a recombinant virus as disclosed herein in combination with a pharmaceutically acceptable carrier or diluent.
It will be appreciated that any of the above-described techniques may be used independently of the others in particular situations, or can be used in conjunction with one or more of the remainder of the techniques.
These and other aspects of the present invention will become evident upon reference to the following detailed description and attached drawings.


A method of generating a stitch file for an embroidery design selected by a user where the embroidery design includes a plurality of elements. According to one embodiment, the method includes acts of rendering an image of the selected embroidery design at a display visible to the user, receiving an order placed electronically by the user for the embroidery design; and generating, following the act of receiving, a stitch file corresponding to the embroidery design, wherein the embroidery design includes both text elements and design elements.

1. Field of Invention
Embodiments of the invention relate generally to embroidery. More specifically, at least one embodiment relates to an apparatus, system and method for generating a stitch file corresponding to an embroidery design selected by a user.
2. Discussion of Related Art
It is common for individuals and businesses to select apparel and other items with custom embroidered designs, (for example, a logo, a team name, etc.) which they distribute or sell to family, friends, employees and customers, for example, to generate goodwill, build a brand, and/or market a business product or service. Often, the embroidery design is personalized with the recipient's name. As with many other types of commercial transactions, there is an interest in allowing users to select and purchase these items on-line where the items include the selected custom designs/logos. Existing processes, however, do not provide an effective on-line ordering process for customized items that include embroidered text and/or designs because the conversion of an image selected on-line to a stitch file is a relatively complex process.
Modern embroidery machines employ software to stitch an embroidered item including selected text and design elements onto apparel or other material, e.g., a hat, a shirt, a jacket, a wall hanging, etc. Generally, the embroidered design is included in a digital stitch file which is provided to the embroidery machine for processing and execution.
Each machine may include multiple stitch heads each with a plurality of spools that may each hold a different color thread. A separate item of apparel or other material is secured in the stitching region adjacent one or more of the stitch heads and the embroidery machine processes the digital stitch file and operates one or more of the stitch heads to create the embroidered design on the items of apparel. Some embroidery machines that include multiple stitch heads are "gang operated" because the material located at each stitch head is simultaneously moved in identical x-y coordinates while being stitched.
One known approach to the on-line ordering of embroidery designs requires the real-time generation of a digital stitch file corresponding to the text and/or design before the user can finalize and order the design. In practice, the approach is not suitable for on-line selection and automatic execution of an embroidery design order. In particular, the on-line order process is delayed using current approaches because an embroidery stitch file must be created for each design before the image of the completed design can be presented to the user in their Internet browser (e.g., rendered). That is, the generation of the embroidery digital stitch file and the rendering of the graphic image both occur prior to the user finalizing and ordering the embroidered design. Such an approach generally results in poor quality embroidered designs because current approaches attempt to convert user selected images (e.g., graphic files) to digital stitch files for execution by a stitching machine. That is, some current approaches employ a process in which an image file is "digitized" to generate a digital stitch file.
Further, known approaches provide only a single style of text per font size which are based on keyboard lettering. This keyboard lettering and the corresponding stitch pattern are then "force-fit" into embroidery orders and when stitched do not provide a high quality finished look desired by customers.

Apparatus, system and method for embroidery design


According to an aspect, there is provided a method for managing elevator cars in a multi-car elevator shaft system. The method comprises determining, by an elevator control entity, the optimum number of elevator cars for a given time of a day in the multi-car elevator shaft system; and commanding, by the elevator control entity, at least one elevator car into at least one elevator car storage or back to service from the at least one elevator car storage based on the determination, wherein elevator cars in the at least one elevator car storage act as standby elevator cars for the multi-car elevator shaft system.

In a multi-car elevator shaft system, two or more cars may move in two elevator shafts independently, always in the same direction in one shaft, and change the shaft on the bottom and the top floor. In other words, the cars move upwards in one shaft and downwards in another shaft, and never move towards each other. A control system of the multi-car elevator shaft system assigns and dispatches elevator cars to serve landing or destination calls.
The multi-car elevator system has to be dimensioned so that it is able to handle both low and high traffic situations. Thus, a challenge of operating the multicar elevator system is how to operate it economically in all operating conditions.

Managing elevator cars in a multi-car elevator shaft system


A ship-to-shore interface includes a shipside ramp and a shoreside ramp. The shoreside ramp is securely fixed to the shoreline. The shoreside ramp has one or more physical adaptations that enable it to passively engage the shipside ramp. In the illustrative embodiment, the physical adaptation is a plurality of recesses that receive a lug that depends from the shoreside end of the shipside ramp.

There are a variety of situations in which passengers, troops, or vehicles must be transferred from a ship to a shoreline or vice versa. Examples of vessels that engage in this operation include roll-on/roll-off vehicle ferries and naval logistics support vessels.
The transfer requires a device that holds the ship near the shoreline and some way for passengers, vehicles, etc. to offload or onload. Offloading and onloading is typically performed using a ramp. The ramp and the holding/stabilizing device are collectively referred to as an "interface." Usually, some portion of the interface is carried by the ship ("the shipside interface") and some portion is located on the shore ("the shoreside interface").
The interface must maintain vessel position and yaw angle during offloading and onloading operations. And it must permit the vessel to resist wave, current and wind forces while accommodating pitch and heave due to tides and the transfer of vehicles.
The conventional approach to the ship-to-shore interface has been to provide a simple vehicle ramp on the shipside and to construct elaborate shoreside facilities to guide, position, and hold the vessel to the shore. But this approach has several drawbacks.
In particular, having an elaborate shoreside facility equates to high harbor infrastructure costs. Furthermore, extensive shoreside interface facilities can have a deleterious impact on the surrounding environs. For military applications, landing forces are often required to rapidly offload on unimproved or semi-improved beachheads. For such applications, an elaborate shoreside facility is not possible.
As a consequence, there is a need for an interface that is capable of creating a temporary connection between a ship and a shoreline that:                is mechanically simple on both the shipside and the shoreside; and        is capable of controlling vessel surge, sway, roll, and pitch.

Apparatus comprising a ship-to-shore interface


Disclosed herein is a method of constructing and utilizing a sound engineering evaluation and comparison process to allow for improved finished results. Such a method entails the utilization of a high-pass filter for listening evaluation of recorded music or sounds including consistency with low-frequency mixing to allow for a tool to implement changes in relation to the filtered results in order to accommodate sensitivities of the human ear (with the optional inclusion of a comparison method to provide possible further enhanced results and the avoidance of biases). In such a manner, a facilitating method for sound engineering mixing adjustments that provide such accommodations are provided for improved sound recordings for distribution within on-line or recording product frameworks.

Sound engineers must provide high quality to achieve success. Quality largely relates to how decisions are made and how recordings are evaluated. In the earliest days of recording, sound engineers were working to find ways to improve recordings by taking care in their evaluation processes and the factors that affected them. Acoustic architecture, carefully crafted listening systems, and even the hearing ability of the engineer all were and have continued to be factors of consideration.
Classic recording techniques may have been effective because of reasons that were not accurately recognized at their inception. After recognition, the reasons could be made more effective, and formed into powerful, simple tools for sound engineers. For instance, there has occurred research in the area of sound engineering about the sensitivity of the human ear, evaluation of recorded audio, and about details of tools that could be deployed in evaluation. However, there is not a body of research that describes the totality of recent understandings together with classic techniques. Also, the underlying reason that the classic techniques have been so effective they may have been, again, misunderstood.
In the past, for instance, there have been systems that allow for adjustments of the loudness of a signal in real time. However, in such a situation, such an adjustment is not based on another signal and it is not used for comparison to improve the recorded sound in relation to human hearing issues. This type of system is thus limited to adjusting loudness depending on a flow of audio through the system itself, rather than adjusting it to match another source subsequent to recording. Additionally, such a system does not contain the audio comparison methods including blind and randomized testing.
Another type of system includes the adjustment of loudness of at least one channel of audio, depending on another, with filtering to approximate the human hearing system. This is accomplished by comparing phase and samples of phase, and primarily for voice or background noise. This does not cover specifics in terms of comparisons between frequencies, nor does it contain audio comparison methods including blind and randomized testing.
Another type of system provides consistent loudness across one or more input tracks, however it uses a modified limiter, where the loudness adjustment portion of the comparison method only uses a gain control. This system thus does not actually minimize any potential artifacts in the signal that might be introduced by limiting, maintaining signal purity for high quality evaluations, rather than direct comparisons, nor does it contain the audio comparison methods including blind and randomized testing.
Yet another system involves monitoring of sound pressure levels at the ear using an ear canal microphone, ostensibly to preserve ear health. It calculates data to detect such potential damage levels. This system does not measure signal coming through it to measure simple ear fatigue in order to help sound engineers avoid making misjudgments in sound levels during mixing.
Additionally, there are systems that monitor SPL levels with a transducer placed in the ear. This system, however, does not do anything to detect audio flowing through it for the purpose of combining with timers to provide visual feedback about when ear fatigue may be a factor in sound engineering decisions.
Geoff Emerick was an audio engineer who worked with The Beatles, on albums including Sgt. Pepper's Lonely Hearts Club Band, Revolver, Magical Mystery Tour and Abbey Road. Emerick has described techniques of sounds mixing wherein all tracks would be mixed without the bass guitar track, allowing for such a bass track to be brought up and mixed only as the final step. He would start by bringing the mix without the bass guitar to −2 on the VU meter. Later, when the bass would be mixed in, the VU meter would be pushed up to 0. Emerick explains that in this way, at the final step, the bass was 2 dB VU above everything else. The Beatles are generally known for having recordings that had a prominent sound for their time and this technique may have been central to the difference in recording quality.
Bruce Swedien is one of the most noted engineers in the recording industry. He worked with Michael Jackson on many albums including Thriller, the best-selling album of all time. Mr. Swedien has stated that his work always checked everything on speakers called Auratones, devices he has repeatedly referred to as "truth speakers". Mr. Swedien has further repeatedly noted that he has never liked headphones, or car stereos, and he has always felt it is foolish to check professional mixes on such implements. To him and his level of expertise, the ability to achieve a good sound mix on Auratones is an indication such will sound great anywhere. Thus, to him, the mark of a good recording is to sound good anywhere, without requiring high-volume playback over high-end speakers. Auratones do not produce much bass, as shown in its frequency response in Prior Art FIG. 1.
Yamaha NS10 speakers are a studio classic and perhaps the most widely-recognized studio speaker of all time. The NS10 speakers, when designed and launched in 1978 were technically unremarkable, having been designed for consumer listening at home. These speakers did not become popular for such home listening purposes and the product all but disappeared from the marketplace. However, artist turned engineers started using them, and perhaps most influential of all, famed engineer Bob Clearmountain began publicizing his use of them. Clearmountain wanted a speaker he could take from studio-to-studio and he chose the NS10 because it was "the worst-sounding speaker" he could find. Virtually all professional engineers have heard of Clearmountain's use of tissue paper over the NS10 tweeters to dull their brightness. Yamaha NS10s do not produce much bass, as shown in its frequency response in Prior Art FIG. 2.
Next, we consider the frequency response of the human ear. The frequency sensitivity of the ear is such that we are most sensitive around 3 kHz, and we are least sensitive to bass, as well as the highest frequencies as we approach the human hearing limit at 20 kHz. The frequency sensitivity of the ear was first outlined as the Fletcher-Munson curves in 1933, re-determined and published as Robinson-Dadson curves in 1956, and most recently revised by the International Standards Organization in (ISO 226:2003). The human ear is not very sensitive to bass, as shown in its frequency sensitivity in Prior Art FIG. 3, recreated from (ISO 226:2003).
Noted audio engineer Paul Frindle, has worked over 40 years as a designer at the famed SSL Corporation, on the Sony Oxford processors and is the sole creator of the Dynamic Spectrum Mapper. Past descriptions exists regarding the effect of high pass filtering on a generated tone of approximately 100 Hz. He shows that it changes significantly when high pass filtering is applied, even though it is of a range that would not show to be affected by the filter in an FFT representation of the filter's frequency response curve. He discusses that because NS10s have a roll-off that they are essentially functioning as a high-pass filter and thus would impart similar characteristics shown using the digital pass filter in his illustration. Importantly, however, these high pass filter actions are undertaken while recording; applications to fully recorded tracks have never been mentioned or performed.
To filter out bass frequencies, a high pass filter is used. There are several types of high pass filters and many ways they can function and be constructed. Different filter types are compared to each other. This source covers them for their use in crossover design. The finding is that Bessel type has the widest, most gradual crossover region and a gentle dip in the summed response. The Linkwitz-Riley type has a moderate roll-off and a flat sum. The Butterworth type has the sharpest initial cutoff and a +3 dB sum at the crossover.
Filters have a type and also have an order, which in digital filter architecture involves the number of samples a filter "looks back" and mixes with the new input. The benefits of high-order parametric filtering are present in certain past systems, as well. Higher order filtering can give more accuracy, especially around the passband with the potential for 4th or at most 6th order filtering to gain accuracy.
It is well-known and widely quoted research that explains that we can detect differences in loudness of approximately 0.41 dB SPL at a threshold of over 30 dB SPL and above.
There is a device described in the past regarding an audio comparison device which includes a voting element and the details of a hardware device to accomplish the comparison. It does not appear that the claims cover devices that would not include voting elements. No loudness matching algorithm is included in this device.
Loudness matching devices have been described, as well, with a limiter having a target threshold with signals below the target threshold are adjusted upwardly and a second copy is output based on the analysis.
Issues with ABX testing are discussed in other situations, particularly showing that there are more sophisticated analysis schemes such as signal detection theory that could prevent false conclusions and account for certain biases. There is a caveat that the foundation of any good experiment is the experimental design and that the statistical analysis itself will not overcome issues with such design. Certain reporting should thus go with all listening tests, including the details of any apparatuses used should be included in all listening tests as well as the environment, test setup and listening material. It has been determined, now, that testing should be double blind and include a third x "random" element, aside a simple A/B test. These elements are great for conducting statistical research but may not be the very best for the recording studio user workflow.
The concept that visual stimuli affects human judgment of auditory loudness has been considered, as well, in the past. Testing was conducted on individuals in this regard and found that prediction error is a factor of "crossmodal interplay" between vision and audition. The conclusion is that what we see can affect what we hear.
Three categories may be used to classify sound during evaluation, particularly three main divisions for evaluation (1) stimulus-response (2) Pleasantness of sounds and (3) identifiability of sounds or sound sources. With the instant research we are concerned with the pleasantness of sounds, for which this research indicates is done by means of rating scales.
The evaluation of audio in terms of its spatial sound quality is has been considered in the past. Such concerns intend to supersede the International Telecommunication Union (ITU) recommended test methods, as they do not take into account the spatial dimension of sound. When working in professional sound engineering, the spatial aspect of a recording is of prime importance.
In any case, the important considerations in the past were the separate capabilities of such prior devices to seek either a means to achieve audio results for non-bass tracks that either maximize in relation to human ear sensitivity levels (as recorded) or the capability of providing linear low-distortion audio effects within the final recorded format. Thus, such prior art standards were one or the other with the utilization of a high pass filter (HPF) providing linear audio effects without unintended qualities (including a too-loud vocal, a too-soft snare, a problematic cymbal, as mere examples), possible low-distortion (due to a filter utilization, rather than a speaker system basis as in the prior art), linear results or standard mixing boards providing maximum ear sensitivity levels at the specific frequency but with large amounts of audio distortions (and/or unintended sound qualities as noted above). In either situation, the resultant recordings provided the consumer market would either have low distortions at the non-bass track level or high distortion levels at the non-bass track level, but with maximum ear sensitivity frequency levels, leaving much to be desired and no understood means to overcome the clear deficiencies in these respects.
As it pertains to bass levels in market-supplied recordings, there are also problems with the currently standard operations. Bass tracks are typically honed after recording has been undertaken through single audio filtering, ostensibly providing such action to the overall recorded track alone. In this situation, thus, such single bass track filtering results in noticeably limited effects, particularly with dominant bass lines in comparison with the remaining non-bass track results. In other words, such standard bass treatments singularly focus on single frequency effects, lacking complementary mixing results for reintroduction with the non-bass track lines components of a recording. Such a common situation creates a bass-dominating, rather than overall blended bass and non-bass recording mix, resulting in rather harsh audio finishing, particularly when combined with the aforementioned non-bass filtered components that are limited to maximized ear sensitivity levels or low distortions, not both. Improvements in such recording results within the marketed recorded music industry would be desired, certainly, but are lacking within the current state.
Additionally, it has been understood that sound engineers, particularly, are susceptible to ear fatigue when continuously subjected to recorded music, whether in terms of individual tracks or combined mixed tracks. If such a sound engineer suffers too much ear fatigue at a single sitting, such a person would lack a proper perspective to genuinely judge the levels of mixing adjustments needed to correctly provide finished recorded products for market. Thus, the ability to alert a subject sound engineer of music exposure time period durations in order to determine the needed rest time between effective mixing operations would be helpful for overall optimization of such considerations, as well. To date, some alerts are undertaken through setting external clocks. However, there is nothing provided integrated within an overall recorded music mixing program. Thus, overall there is nothing in the art providing any recorded music mixing capabilities of any of these three bases.
To the contrary, the present system provides totally divergent methods and processes from the state of the art present today. Here it was discovered how to construct an optimal high-pass filter for listening evaluation, a bass leveling two-frequency method, an ear fatigue reminder system, and, optionally, the construction of a comparison tool to overcome human ear fatigue in relation to recorded sounds and/or music.

Method and system for audio critical listening and evaluation


A method of manufacturing a capacitor by highly etching a foil sheet, and at selected relief portions of the sheet, reducing the surface area coefficient. An anode sheet is cut from the foil sheet and assembled with other capacitor components. The surface area coefficient may be reduced by coining or mechanically compressing at the selected relief portions, and an oxide layer may be formed on the sheet after coining.

Electrolytic capacitors are normally formed with a conductive anode sheet and a conductive cathode sheet with paper separator sheet between to form a thin sandwich. An electrolyte impregnated in the separator sheet functions as the cathode in continuity with the cathode sheet, with an oxide layer on the anode functioning as a dielectric.
In cylindrical capacitors, the sandwich is tightly rolled along with another separator sheet; in flat capacitors, multiple sandwiches are stacked with insulating sheets between. Where a high capacitance per unit volume is needed, highly etched anode foil has been employed. Highly etched foil has a deeply microscopically contoured surface having a total surface area much greater than the flat area of a given sheet. A surface area coefficient, the ratio of the microscopic true surface area to the macroscopic apparent area, may be as high as 100 in current devices, permitting miniaturization of capacitor components.
In manufacturing such miniature capacitors, a dielectric oxide layer is formed on the etched anode sheets to function as a dielectric for the capacitor. However, this embrittles the sheet, leading to several disadvantages. In rolled capacitors, the brittle sheet does not readily roll to a tight radius; too tight of a radius leads to unacceptable cracking and fractures, and too loose of a roll radius leaves a large vacant core in the finished capacitor, increasing component volume. In both rolled and flat capacitors, cutting the desired shapes from the etched and oxidized master anode sheet can lead to fractures and chipping at the edges of the cut sheets. These may contribute to shorts, or require additional tolerances to be built into the component design, increasing volume. In some cases, sharp edge fragments may penetrate the separator material and cause a shorting component failure.
It is also difficult to connect the anode sheet to a component lead, as conventional welding and compressive techniques may damage the fragile material. Flat capacitors in particular have extending tabs that must flex in order to be brought together for welding; brittle material is poorly suited for this. Even in routing handling during manufacturing, oxidized anode layer sheets are vulnerable to damage that reduces manufacturing yields.
Past efforts to reduce these problems have employed selectively etched master sheets, with critical regions masked to prevent etching, and thereby limiting brittleness after oxide formation. However, such efforts increase the cost of procuring anode sheet material, impede design changes, and complicate inventory management.
The present invention overcomes the limitations of the prior art by providing a method of manufacturing a capacitor by highly etching a foil sheet, and at selected relief portions of the sheet, reducing the surface area coefficient. An anode sheet is cut from the foil sheet and assembled with other capacitor components. The surface area coefficient may be reduced by coining or mechanically compressing at the selected relief portions, and an oxide layer may be formed on the sheet after coining.

Electrolytic capacitor and method of manufacture


A receiver for use in a wireless communication system includes a voltage controlled oscillator and estimating means for obtaining a frequency estimate to adjust the voltage controlled oscillator, thereby correcting an oscillator frequency error. The estimating means performs a number of block correlations on a received signal with a known midamble reference. The output of the block correlators are conjugately multiplied and summed to produce a low-variance estimate of the phase change between correlators. A number of the largest summed values are located, and the located values that exceed a detection threshold are summed to provide a single complex number whose angle is an estimate of the phase change between the correlators.

In typical wireless communications systems, a frequency difference between the transmitter and receiver local oscillators can prevent the transmission of data. Additionally, because many systems utilize the same Local Oscillator (LO) for both receiver and transmitter functions, a large frequency offset can cause significant out-of-band interference.
In order to overcome this problem, prior systems have utilized differential detection of phase or applied the Discrete Fourier Transform to estimate the frequency error and apply an update to the Local Oscillator. However, these prior systems either ignored the effects of multipath interference or combined the automatic frequency control (AFC) with a RAKE receiver. Therefore, these prior techniques were not applicable for systems that use Multi-user Detection without a RAKE receiver.

Automatic frequency correction method and receiver for time division duplex modes of 3G wireless communications


Precipitated silica with a sodium sulphate content of 4 to 18 wt. %, particularly with the physical-chemical data:. ______________________________________ Sodium sulphate content: 4-14 wt. % BET surface area (DIN 66131): 100-190 m.sup.2 /g DBP absorption (anhydrous) 208-250 g/100 g (DIN 53601, ASTM D 2414): 3.0-6.5 wt. % (DIN ISO 787/II) Oversize with >63 .mu.m .ltoreq. 10.0 wt. % ALPINE air-jet sieve >150 .mu.m .ltoreq. 0.1 wt. % >250 .mu.m .ltoreq. 0.01 wt. % ______________________________________. It is prepared by introducing hot water into a precipitation vessel, with stirring, adding water glass, then heating the mixture and maintaining the temperature throughout the remainder of the precipitation period. Water glass and sulphuric acid are added simultaneously during this process. The precipitated silica is then separated from the suspension and the filter cake containing sodium sulphate is dried in a spray drier and ground. The precipitated silica may be used in the production of battery separators.

The present invention relates to a precipitated silica, the process for the preparation thereof, and to its use in battery separators.
It is known to use precipitated silicas for the production of microporous polyethylene battery separators (U.S. Pat. No. 3,351,495, U.S. Pat. No. 4,024,323, U.S. Pat. No. 4,681,750). A common feature of the known silicas is that the salt produced during the precipitation reaction is removed from the filter cake during filtration to a salt content as low as <2.5 wt. % by washing with water. The salt content of .ltoreq.2.5 wt. % refers to the salt content determined in the dried silica. In the filter cake, this corresponds to a salt content of 0.625% (see, for example, U.S. Pat. No. 4,681,750, column 8, Example 1, lines 20-23 and Table 1, Examples 1-3).
An object of the present invention is to reduce the amount of water needed to obtain an acceptable product. Another object is to lessen the amount of salt discharged with the effluent of the process. Further objects of the invention include obtaining improved products containing the precipitated silicas and improved processing of compositions containing precipitated silicas.