An offset reverse telephoto projection zoom lens 300 comprising a moving zoom group 302, a moving compensation group 304, and a fixed rear lens group 306. According to one embodiment of the projection lens, the zoom group 302 has four lenses, the compensation group 304 has four lenses, and the fixed rear group 306 has three lenses. An aperture stop 308 is located in the fixed rear group 306. The fixed rear group 306 has a small diameter which helps alleviate interference with illumination optics. Additionally, a fixed rear group 306 does not require zoom mechanisms at the rear of the lens 300 where space is at a premium.

Projection optical systems present many optical design challenges, several of which require a tradeoff between conflicting design goals. Foremost is the requirement of producing a high-quality image, characterized by low distortion, high resolution, high contrast ratio, high light throughput, and uniform screen illumination. In addition to the image quality requirement, the operational environment for many optical projectors introduces further constraints. For example, many projectors must project images large enough to be seen by many people, yet operate in a rather small conference room. This constraint requires the projection system to have a relatively wide field angle so that a large image may be produced in spite of a short projection distance.
Additionally, projection systems are rarely positioned level with the center of the projection screen. Because the projector system and the center of the screen are not located at the same elevation, the image may exhibit a keystoning effect. Keystoning occurs when an image is projected at an angle onto a screen, such as when a table-top overhead projector projects an image upward onto a wall screen. Due to the projection angle, the side of the image furthest from the projector, typically the top, is wider than the side of the image closest to the projector--causing the image to resemble the wedge-shaped keystone at the crown of a stone archway. Wide field angles exacerbate the problem of keystoning.
Furthermore, some application require a zoom lens to allow the projector to adapt to various operating environments. Projection zoom lenses are difficult to combine with reflective modulators since they must allow adequate room behind the lens to separate the incident and reflected light beams. The incident and reflected beams are nearly coincident when a reflective modulator is used. When the incident and reflected beams are so close, it is very difficult to prevent the projection optics from interfering with the illumination optics while limiting the overall size of the projector. Vignetting occurs when the illumination path is partially blocked by the projection optics.
Existing zoom lenses that have wide field angles, low distortion, high resolution, high contrast ratio, high light throughput, and uniform screen illumination are either too small format, have too short of a back focal distance to be useful for DMD based projection systems, or require too much space for the zoom mechanism near the spatial light modulator and illumination optics.
Therefore, there is a need in the art for a high resolution projection zoom lens having a long back focal distance, a wide field angle, high contrast ratio, low distortion, high light throughput, and uniform screen illumination that may be used with a reflective spatial light modulator without interfering with the illumination optics.

Offset projection zoom lens with fixed rear group for reflective spatial light modulators


The present invention is directed toward pharmaceutical compositions comprising an isolated polypeptide and a pharmaceutically acceptable carrier. The present invention also discloses an antibody or an antigen-binding portion thereof that bind to the isolated polypeptide. Methods of inhibiting cancer cells growth are also disclosed, comprising administering the isolated polypeptide or the antibody described herein to a subject in need thereof.

Stress-induced phosphoprotein (STIP1, SEQ ID NO:3) is a 62.6 kDa protein, also known as heat shock protein (HSP)-organizing protein (HOP), because it has been shown to modulate the chaperone activities of HSP 90 and HSP 70. STIP1 contains nine tetratricopeptide repeat (TPR) motifs and one nuclear localization signal (NLS) (Longshaw et al., 2004). The TPR domains of STIP1 are involved in holding HSP70 and HSP90 together in the HSP90 chaperone machinery (Odunuga et al., 2004). This formation of protein complexes participates in several cellular processes, including transcription, protein folding, protein translocation, viral replication, signal transduction, and cell division.
Cancer remains a major public health problem worldwide. It profoundly affects more than 1 million people in the U.S. diagnosed each year, as well as their families and friends. Despite the advance in chemotherapy over the last 50 years, the medical community is still faced with the challenge for curing many different types of cancer. Accordingly, there is still a need for the development of effective and safe treatments for various types of cancer. The present invention addresses this need.

CHANG GUNG MEMORIAL HOSPITAL, LINKOU BRANCH


The present invention is a narrow neck dosage device for dispensing a predetermined quantity of product. An insert is installed in a narrow neck of a container with a bottom disk protruding into the body of the container and a top device within the neck of the container. The bottom disk initially hangs within the container body, while the top device rests on a divider that separates the neck from the container body. The top device can be upward angled blades, angled blades or a circular disc. A shaft connects the top devices and the bottom disk. The shaft also can have multiple configurations, such as spiral, flat helix, or random kinks. The shaft spins, rocks or oscillates and passes through a hole in the center of the divider. The divider has pre-sized holes that allow product to pass through. When the container is tipped into a dispensing position, fluid pressure moves the insert up the neck of the container until the bottom disk reaches the divider and seals the neck off from the body of the container. The container is returned to an upright position after dispensing and the weight of the insert spins, rocks or oscillates the insert downward into the starting position.

Almost all households frequently use consumer household products, such as liquid detergents, soaps, fabric softeners and other cleaning products. Each consumer household product is packaged with some type of pouring system. Each year, millions of packages of these household products are sold around the world.
Most laundry detergents, fabric softeners and other similar products require users to measure out an appropriate dosage of product that depends on the size of a load and the amount of dirt to be removed. Human error in measuring is a common source of problems. Users often estimate the necessary dosage for a particular activity incorrectly. Underestimating results in insufficient cleaning, while overestimating results in a waste of expensive product.
The most common dosage device for these types of household products is a screw cap that fits over a spout on a bottle. Generally, the user measures an amount of product into the screw cap based on marks on the inside of the cap. This is a very inaccurate system, and often users will forgo measurements altogether and pour an estimated amount of product directly into the wash.
Other dosage devices have attempted to create a system for dispensing a recommended dosage of product. However, these systems do not create an efficient and reliable method for dispensing a predetermined amount of product. These systems can be expensive and are not easily adapted to existing packaging technology.
Needs exist for improved methods for inexpensive, efficient and easy dispensing of a predetermined amount of household product.

Doser for portable liquids and fluent materials


A multispeed drive unit (10) comprising a rotary input (27) positioned to be driven by a power source and disposed at an input side of the drive unit (10); a rotary output (28) positioned to drive a driven unit and disposed at an output side of the drive unit (10), a transmission operably interposed between said rotary input (27) and said rotary output (28), said transmission having a gear (20) moveable between a high-reduction configuration and a low-reduction configuration, a first friction clutch (40) operable to fix said gear (20) in said high-reduction configuration, whereby said transmission is operable to reduce a speed of said rotary output (28) relative to said rotary input (27) when said first friction clutch (40) is engaged, and a second friction clutch (60) operable to fix said gear (20) in said low-reduction configuration, whereby said transmission is not operable to reduce the speed of said rotary output (28) relative to said rotary input (2) when said second friction clutch (60) is engaged.

1. Technical Field
The present disclosure relates to vehicle power transmission units, and, more particularly, to remotely-actuatable multispeed transmission units.
2. Description of the Related Art
Large industrial machinery systems, such as earth moving equipment and other construction vehicles and apparatuses, may use individual power transmission units mounted at the system's driven endpoint. For example, gear reduction units mounted at the hub of each driven wheel can convert the relatively high rotational speeds of driven input shafts into lower rotation speeds, thereby accommodating the large-diameter wheels, heavy loads and low speeds frequently encountered by heavy duty construction vehicles. In another example, independent gear reduction units may be used in drilling devices such as earth augers, in order to provide the low-speed, high-torque auger rotation needed for drilling holes in tightly packed soil.
Such individual power transmission units are sometimes referred to as drive units, and include a housing which encases a transmission linking an external power source to a driven unit. Where the power source is external (e.g., a vehicle motor and/or primary vehicle transmission), the drive unit may be referred to as a nonintegrated drive unit. Alternatively, integrated drive units include an integral power input device, such as an attached hydraulic motor. For example, integrated drive units may utilize a hydraulic motor which is linked to the drive unit via a motor output shaft coupled to an input shaft of the drive unit. The drive unit has its own output shaft or output hub which links to the driven unit (such as a wheel or auger as noted above). For the purposes of the present disclosure, "drive unit" generically refers to both nonintegrated and integrated drive units.
In some cases, multispeed drive units capable of shifting between varying levels of gear reduction may be desirable. For example, in the case of heavy duty construction vehicles, a drive unit having high and low gear reduction configurations may be provided. The high gear reduction configuration provides low-speed, high-torque power transmission, such as for uneven terrain at a construction site. The low gear reduction configuration provides higher potential wheel rotation speeds, such as for driving the vehicle on maintained roads. In the case of industrial augers, the high-torque, low-speed mode (i.e., the high gear reduction configuration) may be used for drilling and deepening holes in the earth, while the lower-torque, higher-speed mode (i.e., the low-reduction configuration) may be used for quickly extracting the auger bit from a drilled hole and dislodging soil from the surface of the drill bit.
Substantial design efforts have focused on providing multispeed drive units which can be easily toggled between low and high gear reduction values. For example, hydraulically actuated wheel drive units may employ multiple hydraulic actuators which operate to engage and/or disengage internal gearing mechanisms to toggle between high- and low-reduction configurations (such as by toggling clutch mechanisms between engaged and disengaged configurations). However, such multi-actuator drive unit designs require careful synchronization of the various actuators to function properly, with the attendant cost and system complexity associated with such synchronization.
Other designs may include a mechanical shift, such as a movable or translatable gear which selectively engages higher or lower gear reduction assemblies depending on the physical location of the movable gear. However, such mechanical shift drive units require that the driven unit be stopped prior to toggling the movable gear, and may require that internal pressures on the movable gear be relieved prior to such toggling.


Holders for maintaining personal items such as dental and hygienic products are disclosed. The holders include a series of sections, particularly, holding sections having different geometrical structures related to the different items intended to be hold. In this manner, they may be assembled at the convenience of the user and its holding units may be increased or decreased as well as selected based upon the particular structure of the holding units at the will of the users. The holder may be self-standing when using a disclosed base or alternatively, it may be secured to a commonly used toothbrush supporting base or even be supported via a suction cup over a given surface.

Dental personal items, such as orthodontic retainers and/or their boxes, dentures and the like requires to be kept in a clean, dry and safe place due to its own nature in order to reduce the risk of contamination of such items with microorganisms that may transmit diseases to the user. In some instances, whenever the user is not using such items, they may be stored in a particular and hygienic place. Such care in storing such items is very important in order to promote the health of the user. In another instance the items are not used because the user forgets to use them because they are in a hidden place.
Similarly, personal care products, such as dental floss, manual razors, toothbrushes and the like also require being kept in a clean and hygienic place. Unfortunately, such items are commonly kept at the top of the bathroom's wash basin, which is a highly humid and usually a place wherein bacteria and other microorganism may found an excellent reproductive environment.
Similarly, jewelry items, such as rings, earrings and the like requires a safe place to be store, particularly whenever the user is not wearing such items. In many occasions, such items may be lost while the user is on the shower or results uncomfortable while the user is sleeping.
Thus, a particular holder may be highly convenient in order to hygienically, properly and safely, save and store such personal items in order to reduce contact of said items with bacteria and other disease related microorganisms.

Holder for dental and similar accessories


A method for monitoring the status of a plating bath purification treatment cycle. The method involves applying a swept dc measurement signal to a pretreated electrode which is in contact with the plating solution, and monitoring the resultant response current signal. The electrode potential corresponding to the peak current density in the cathodic sweep of the response current signal provides an accurate indication of the status of the purification treatment cycle. The method tracks the progress of the purification process thereby ensuring the optimal termination points for the treatment process. The method can be used in conjunction with voltammetric plating bath analysis methods and equipment, as part of an overall plating bath monitoring and control system.

1. Field of the Invention
The present invention relates to plating bath analysis methods. More particularly, the present invention relates to a method for monitoring the status of a plating bath purification treatment cycle.
2. Description of Related Art
To ensure optimal performance of a plating bath, the bath must be purified at regular intervals. The purification serves to remove organic contaminants and other impurities which can build up in the bath over time and lead to undesirable plating characteristics. In many cases, the contaminants are breakdown products resulting from the electrochemical processes within the bath. The time between purification treatments varies depending upon the contaminant buildup rate, which is a function of the nature and frequency of the plating bath processes. For example, plating baths using organic addition agents such as the acid copper plating bath generate significant levels of contaminants and require frequent purification.
Carbon treatment is one widely used plating bath purification technique. The carbon treatment process involves contacting activated carbon with the plating bath. The contaminants are adsorbed on the activated carbon and thereby effectively removed from the plating bath solution. The level of contaminants within the bath is continually reduced during the purification treatment, and when an acceptably low contaminant level is attained, the treatment can be terminated. Fresh addition agents are added to the treated bath and the plating bath is ready for use again. On continued usage organics and other contaminants will again begin to accumulate within the bath, and the purification treatment will eventually have to be repeated. Since the quality of the plating bath depends upon maintaining a low level of contaminants, it is essential that the carbon treatment cycles be initiated and terminated at the appropriate times. The same concerns apply to other plating bath purification techniques.
Under current practice, the progress of the purification treatment is typically monitored by repeated manual tests on the plating bath solution. One such manual test, disclosed in LeaRonal Application Note No. AN30009CT, uses a Hull cell plating technique to monitor carbon treatment. During the carbon treatment process, an operator will run a Hull cell plating test approximately once every three hours to determine when the process is complete. Each Hull cell test is performed at 2 amperes for 15 minutes with air agitation. When the plated Hull cell panels appear flat-matte across the entire current density range, the carbon treatment process is considered sufficiently complete. Other methods currently used involve similar repeated manual testing procedures.
The current purification treatment monitoring methods suffer from a number of problems. Repeated performance of manual tests is time-consuming and requires skilled personnel and specialized equipment. The time required to perform the tests translates into production downtime, thereby limiting plating process productivity.
In addition, presently used techniques do not usually lead to accurate and repeatable results. The manual tests often involve guess work and arbitrary interpretation, as in the case of the plated Hull cell panels. This can lead to incomplete purification treatments and resultant plating bath quality problems.
Furthermore, present techniques are not easily integrated with known voltammetric plating bath analysis methods, such as those disclosed in U.S. Pat. No. 4,631,116, and assigned to the present common assignee. Plating bath users must therefore maintain one system and set of equipment for measuring plating bath constituent concentration, and another for tracking the progress of purification treatments.
As is apparent from the above, there presently is a need for a simple and efficient method of continuously monitoring the status of a purification treatment cycle within a plating bath. The method should provide a highly accurate indication of the optimal treatment initiation and termination points. The method should provide these features and also be compatible with most on-line plating bath analysis methods and the equipment associated therewith.

Method for monitoring purification treatment in plating baths


An exercise apparatus for exercising and enhancing human agility and reaction time skills involving the mental and physical ability to act quickly and move rapidly in reacting to events and objects that invade the space immediately surrounding a person. The apparatus has one or more bases surrounding the area where the subject stands. The bases generate visible bars of light at all heights and orientations. The subject has to jump over, or duck his body to avoid intercepting the light bars. The motion of the bars is supplemented by audio which adds motion sounds as well as musical tones. The height. the rate of motion of the bars along with the orientation of their movement is settable and controllable by the user in periodic and random modes. Means are provided that enable the light bar to come to a stop against the body of the exercise subject like a physical bar. In the electronic Blocker version, an electronic Blocker with light sensors and wireless signal transmission, is used to block the light bar and restart the sweep of the light bar at a new orientation.

There are exercise machines of various kinds that are used for exercising the human body. These machines use many varieties of exercise techniques such as: lifting weight; simulating sport actions of rowing, skiing, bicycling; other means of exercise like stair climbing and walking. These and similar machines exercise the body in general and different muscle groups and parts of the body in particular.
These exercise machines do not specifically exercise and develop the agility of the human body. The human agility is the ability to act quickly and move rapidly using both mental and physical skills in reacting to events and objects that invade the space immediately surrounding a person. The agility skills when developed through an exercise apparatus are useful in improving reaction time skills and providing physical exercise. They may also be useful in improving the competition ability in some sports.


The present invention discloses a traditional Chinese medicine preparation for cardio-cerebral blood vessel diseases, it is prepared through extracting danshen and Notoginseng by lye, precipitating with alcohol, concentrating, and adding other medicine and excipients. Then using the HAPLY-MS and HAPLY fingerprint Atlas to characterize its Physicochemical properties completely. Using the fingerprint Atlas analysis method of the present invention, the structure and comparative content of biologically active component can be known. Characterization of the physical chemical properties of danshen and Notoginseng of traditional Chinese medicine preparation with this way is better than other methods of the prior art.

Cardiovascular and cerebrovascular diseases are common ones which do great harm to health of human beings. Recently, such diseases have an increasing occurrence due to the changes of works, livings, diet patterns, environments and the like with social development. The traditional Chinese medicine (TCM), in spite of its lower activity toward a single target relative to the Western medicine, is characterized by its multiple routes and targets, dynamic and holistic treatment, and low side effects, which are far beyond the effects of the Western medicine. The TCM preparation with definite therapeutic effect will have an overall therapeutic effect superior to that of the Western medicine. There have been now a plurality of TCM preparations for the treatment of cardiovascular and cerebrovascular diseases, such as compound Danshen tablets and its TCM preparations, Guanxin Danshen drop pills, and Xinkeshu tablets etc. These TCM preparations, all of which contain Radix Salviae Miltiorrhizae (also known as danshen) and Radix Notoginseng, have different therapeutic effects for their different formulations, proportions of ingredients, extraction and purification processes, or dosage forms. In addition, these TCM preparations can hardly be controlled in quality, since no effective quality detection method is available at present for completely characterizing the physical and chemical properties of these medicines, and instead, only one or two compounds, such as Danshensu or Tanshinone IIA, are used to represent the complex biologically active ingredients in these medicines. Therefore, it is necessary to improve the process for extracting and purifying such TCM preparations and also the method for controlling their qualities.

Preparation for cardio-cerebral blood vessel diseases and its preparing method


This invention relates to radiotherapeutic reagents and peptides, radiodiagnostic reagents and peptides, and methods for producing labeled radiodiagnostic and radiotherapeutic agents. Specifically, the invention relates to vasoactive intestinal peptide receptor binding peptides, derivatives and analogues of vasoactive intestinal peptide, and embodiments of such peptides radiolabeled with a radioisotope, as well as methods and kits for making, radiolabeling and using such peptides for radiodiagnostic and radiotherapeutic purposes. The invention specifically relates to vasoactive intestinal peptide receptor binding peptide derivatives and analogues of vasoactive intestinal peptide radiolabeled with technetium-99m and uses thereof as scintigraphic imaging agents. The invention also specifically relates to vasoactive intestinal peptide receptor binding peptide derivatives and analogues of vasoactive intestinal peptide radiolabeled with cytotoxic radioisotopes such as rhenium-186 (.sup.186 Re) and rhenium-188 (.sup.188 Re) for use as radiotherapeutic agents. Methods and kits for making, radiolabeling and using such peptides diagnostically and therapeutically in a mammalian body are also provided.

1. Field of the Invention
This invention relates to radiotherapeutic agents and peptides, radiodiagnostic agents and peptides, and methods for producing such labeled radiodiagnostic and radiotherapeutic agents. Specifically, the invention relates to receptor-binding vasoactive intestinal peptides (including native vasoactive intestinal peptide (VIP) and fragments, derivatives, analogues and mimetics thereof), and embodiments of such compounds labeled with gamma-radiation emitting isotopes such as technetium-99m (Tc-99m), as well as methods and kits for making, radiolabeling and using such peptides to image sites in a mammalian body. The invention also relates to receptor binding vasoactive intestinal peptides and derivatives, analogues and mimetics thereof, labeled with cytotoxic radioisotopes such as rhenium-186 (.sup.188 Re) and rhenium-188 (.sup.188 Re), and methods and kits for making, radiolabeling and using such compounds therapeutically in a mammalian body.
2. Description of the Prior Art
Native vasoactive intestinal peptide (VIP) is a 28 amino acid peptide that was first isolated from hog upper small intestine (Said and Mutt. 1970, Science 169: 1217-1218). This peptide belongs to a family of structurally-related, small peptides that includes helodermin, secretin, the somatostatins, and glucagon. The peptide has the formula: EQU HSDAVFTDNYTRLRKQMAVKKYLNSILN.amide (SEQ. ID NO.:1) Formula I
(where single-letter abbreviations for amino acids can be found in Zubay. Biochemistry 2d ed., 1988. MacMillan Publishing: New York, p. 33).
The biological effects of VIP are mediated by the activation of membrane-bound receptor proteins that are coupled to the intracellular cyclic adenosine monophosphate signalling system. VIP regulates a variety of different biological activities in tissues and organs. It modulates cellular metabolic activities and regulates exocrine and endocrine secretions. It also induces relaxation of smooth muscle and causes vasodilatory effects. VIP is also involved in the regulation of cellular proliferation and survival in a number of different cell types, including keratinocytes, smooth muscle cells, sympathetic neuroblasts, hippocampal cells and, in vitro, NIH 3T3 cells.
VIP receptors are widely distributed throughout the gastrointestinal tract and are also found in various other cell types. Large numbers of VIP receptors are expressed in rumor cells of, for example, adenocarcinomas, breast cancers, melanomas, neuroblastomas and pancreatic carcinomas. In fact, expression of high affinity binding sites for VIP (comprising the VIP receptor protein) is a marker for these tumor cells. Specific binding of VIP to these cells can be exploited as a marker to locate and identify such tumor cells in vivo.
A variety of radionuclides are known to be useful for radioimaging, including .sup.67 Ga, .sup.99m Tc (hereinafter Tc-99m), .sup.111 In, .sup.123 I, .sup.125 I, .sup.169 Yb or .sup.186 Re. A number of factors must be considered for optimal radioimaging in humans. To maximize the efficiency of detection, a radionuclide that emits gamma energy in the 200 to 200 keV range is preferred. To minimize the absorbed radiation dose to the patient, the physical half-life of the radionuclide must be as short as the imaging procedure will allow. To allow for examinations to be performed on any day and at any time of the day, it is advantageous to have a source of the radionuclide always available at the clinical site.
Methods for radioiodinating VIP analogues at tyrosine residues in the VIP sequence (Tyr.sup.10 or Tyr.sup.22) using .sup.123 I or .sup.125 I are known in the prior art. These radioiodinated species have also been used to assess VIP binding to receptors on tumor cells.
Boissard et al., 1986, Cancer Res. 46: 4406-4413 describe radioiodination of VIP and binding to human colon adenocarcinoma cells.
El Battari et al., 1988, J. Biol. Chem. 263: 17685-17689 describe raioiodination of VIP and binding to human colon adenocarcinoma cells.
Shaffer et al., 1987, Peptides 8: 1101-1106 disclose radioiodination of VIP and binding to human small cell and non-small cell carcinoma cells.
Svoboda et al., 1988, Eur. J. Biochem. 176: 707-713 describe radioiodination of VIP and binding to rat transformed pancreatic acinar cells.
Gespach et al., 1988, Cancer Res. 48: 5079-5083 disclose radioiodination of VIP and binding to human breast cancer cells.
Muller et al., 1989, J. Biol. Chem. 264: 3647-3650 disclose radioiodination of VIP and binding to human neuroblastoma cells.
Lee et al., 1990, Peptides 11: 1205-1210 disclose radioiodination of VIP and binding to human small cell and non-small cell carcinoma cells.
Park et al., 1990, Cancer Res. 50: 2773-2780 describe radioiodination of VIP and binding to human gastric cancer cells.
Bellan et al., 1992, Exp. Cell Res. 200: 34-40 disclose radioiodination of VIP and binding to human melanoma cells.
Moody et al., 1993, Proc. Natl. Acad. Sci. USA 90: 4345-4349 disclose radioiodination of VIP and binding to non-small cell lung carcinoma cells.
Virgolini et al., 1994, Cancer Res. 54: 690-700 describe radioiodination of VIP and binding to primary tumors and tumor cell lines.
Methods for radioiodinating VIP analogues at Y.sup.10 or Y.sup.22 using .sup.131 I are known in the prior art.
Hassan et al., 1994, Nucl. Med. Biol. 21: 865-872 disclose radioiodination of VIP and in vivo distribution of radiolabel in a rat by scintigraphy.
These methods have application for enabling detection of tumor cells in vivo by radioimaging, particularly radioscintigraphy. VIP is a useful marker for such radioimaging, because many different tumor cells express a high affinity binding site for VIP (the VIP receptor protein). However, radioiodinated peptides have significant commercial disadvantages. .sup.123 I is both expensive and in limited supply. Also, approved radioiodinated radiopharmaceuticals normally cannot be prepared at the clinical site.
Tc-99m is a preferred radionuclide because it emits gamma radiation at 140 keV, it has a physical half-life of 6 hours, and it is readily available on-site using a molybdenum-99/technetium-99m generator. Other radionuclides used in the prior art are less advantageous than Tc-99m. This can be because the physical half-lives of such radionuclides are longer, resulting in a greater amount of absorbed radiation dose to the patient (e.g., indium-111). Alternatively, the gamma radiation energies of such alternate radionuclides are significantly lower (e.g., iodine-125) or higher (e.g., iodine-131) than Tc-99m and are thereby inappropriate for quality scintigraphic imaging. Furthermore, many disadvantageous radionuclides cannot be produced using an on-site generator.
Tc-99m is a transition metal that is advantageously chelated by a metal complexing moiety. Radiolabel complexing moieties capable of binding Tc-99m can be covalently linked to various specific binding compounds to provide a means for radiolabeling such specific binding compounds. This is because the most commonly available chemical species of Tc-99m, pertechnetate (TcO.sub.4.sup.-), cannot bind directly to most specific binding compounds strongly enough to be useful as a radiopharmaceutical. Complexing of Tc-99m with such radiolabel complexing moieties typically entails chemical reduction of the pertechnetate using a reducing agent such as stannous chloride.
Although Tc-99m is the preferred radionuclide for scintigraphic imaging, it has not been widely used for labeling peptides (see Lamberts, 1991, J. Nucl. Med. 32: 1189-1191). This is because methods known in the prior art for labeling larger protein molecules (i.e., >10,000 daltons in size) with Tc-99m are not suitable for labeling peptides (having a molecular size less than 10,000 daltons). Consequently, it is necessary to radiolabel most peptides by covalently attaching a radionuclide chelating moiety to the peptide, so that the chelator is incorporated site-selectively at a position in the peptide that will not interfere with the specific binding properties of the peptide.
Methods for labeling peptides with Tc-99m are disclosed in co-owned U.S. Pat. No. 5,225,180 and in co-pending U.S. patent application Ser. No. 07/653,012, now abandoned, which issued as U.S. Pat. No. 5,811,394; Ser. No. 07/807,062, now U.S. Pat. No. 5,443,815; Ser. No. 07/851,074, now abandoned, a divisional of which issued as U.S. Pat. No. 5,711,931; Ser. No. 07/871,282, a divisional of which issued as U.S. Pat. No. 5,720,934; Ser. No. 07/886,752, now abandoned, which issued as U.S. Pat. No. 5,849,260; Ser. No. 07/893,981, now U.S. Pat. No. 5,508,020; Ser. No. 07/902,935, now U.S. Pat. No. 5,716,596; Ser. No. 07/955,466, now abandoned; Ser. No. 07/977,628, now U.S. Pat. No. 5,405,597; Ser. No. 08/019,864, now U.S. Pat. No. 5,552,525; Ser. No. 08/044,825, now abandoned, which issued as U.S. Pat. No. 5,645,815; Ser. No. 08/073,577, now U.S. Pat. No. 5,561,220; Ser. Nos. 08/092,355; 08/095,760, now U.S. Pat. No. 5,620,675; and Ser. No. 08/210,822, now abandoned, and PCT International Applications PCT/US92/00757, PCT/US92/10716, PCT/US93/02320, PCT/US93/03687, PCT/US93/04794, PCT/US93/05372, PCT/US93/06029, PCT/US93/09387, and PCT/US94/01894, which are hereby incorporated by reference. However none of these references disclose specifically how to prepare technetium-99m -labeled vasoactive intestinal peptides.
Methods for preparing Tc-99m complexes are known in the art and examples are provided below for general reference:
Byrne et al., U.S. Pat. Nos. 4,434,151, 4,575,556 and 4,571,430 describe homocysteine thiolactone-derived bifunctional chelating agents.
Fritzberg, U.S. Pat. No. 4,444,690 describes a series of technetium-chelating agents based on 2,3-bis(mercaptoacetamido)propanoate.
Nosco et al., U.S. Pat. No. 4,925,650 describe Tc-99m chelating complexes.
Kondo et al., European Patent Application, Publication No. 483704 A1 disclose a process for preparing a Tc-99m complex with a mercapto-Gly-Gly-Gly moiety.
European Patent Application No. 84109831.2 describes bisamido, bisthiol Tc-99m ligands and salts thereof as renal function monitoring agents.
Davison et al., 1981, Inorg. Chem. 20: 1629-1632 disclose oxotechnetium chelate complexes.
Fritzberg et al., 1982, J. Nucl. Med. 23: 592-598 disclose a Tc-99m chelating agent based on N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate.
Byrne et al., 1983, J. Nucl. Med. 24: P126 describe homocystine-containing Tc-99m chelating agents.
Bryson et al., 1988, Inorg. Chem. 27: 2154-2161 describe neutral complexes of technetium-99 which are unstable to excess ligand.
Misra et al., 1989, Tet. Lett. 30: 1885-1888 describe bisamine bisthiol compounds for radiolabeling purposes.
The use of chelating agents for radiolabeling specific-binding compounds is known in the art and examples are provided below for general reference:
Gansow et al., U.S. Pat. No. 4,472,509 teach methods of manufacturing and purifying Tc-99m chelate-conjugated monoclonal antibodies.
Stavrianopoulos, U.S. Pat. No. 4,943,523 teach detectable molecules comprising metal chelating moieties.
Fritzberg et al., European Patent Application No. 86100360.6 describe dithiol, diamino, or diamidocarboxylic acid or amine complexes useful for making technetium-labeled imaging agents.
Albert et al., UK Patent Application 8927255.3 disclose radioimaging using somatostatin derivatives such as octreotide labeled with .sup.111 I via a chelating group bound to the amino-terminus.
Albert et al., European Patent Application No. WO 91/01144 disclose radioimaging using radiolabeled peptides related to growth factors, hormones, interferons and cytokines and comprised of a specific recognition peptide covalently linked via an amino group of said peptide to a radionuclide chelating group.
Fischman et al., International Patent Application, Publication No. WO93/13317 disclose chemotactic peptides attached to chelating moieties.
Kwekkeboom et al., 1991, J. Nucl. Med. 32: 981 Abstract #305 relates to radiolabeling somatostatin analogues with .sup.111 In.
Albert et al., 1991, Abstract LM10, 12th American Peptide Symposium: 1991 describe uses for .sup.111 In-labeled diethylene-triaminopentaacetic acid-derivatized somatostatin analogues.
Cox et al., 1991, Abstract. 7th International Symposium on Radiopharmacology, p. 16, disclose the use of, Tc-99m-, .sup.131 I- and .sup.111 In-labeled somatostatin analogues in radiolocalization of endocrine tumors in vivo by scintigraphy.
Methods for labeling certain specific-binding compounds, mainly large proteins, with Tc-99m are known in the prior art, and examples are provided below for general reference:
Hnatowich, U.S. Pat. No. 4,668,503 describe Tc-99m protein radiolabeling.
Tolman, U.S. Pat. No. 4,732,684 describe conjugation of targeting molecules and fragments of metallothionein.
Nicolotti et al., U.S. Pat. No. 4,861,869 describe bifunctional coupling agents useful in forming conjugates with biological molecules such as antibodies.
Fritzberg et al., U.S. Pat. No. 4,965,392 describe various S-protected mercaptoacetylglycylglycine-based chelators for labeling proteins.
Schochat et al., U.S. Pat. No. 5,061,641 disclose direct radiolabeling of proteins comprised of at least one "pendent" sulfhydryl group.
Fritzberg et al., U.S. Pat. No. 5,091,514 describe various S-protected mercaptoacetylglycylglycine-based chelators for labeling proteins.
Gustavson et al., U.S. Pat. No. 5,112,953 disclose Tc-99m chelating agents for radiolabeling proteins.
Kasina et al., U.S. Pat. No. 5,175,257 describe various combinations of targeting molecules and Tc-99m chelating groups.
Dean et al., U.S. Pat. No. 5,180,816 disclose methods for radiolabeling a protein with Tc-99m via a bifunctional chelating agent.
Sundrehagen, International Patent Application, Publication No. WO85/03231 disclose Tc-99m labeling of proteins.
Reno and Bottino, European Patent Application 87300426.1 disclose radiolabeling antibodies with Tc-99m.
Bremer et al., European Patent Application No. 87118142.6 disclose Tc-99m radiolabeling of antibody molecules.
Pak et al., European Patent Application No. WO 88/07382 disclose a method for labeling antibodies with Tc-99m.
Goedemans et al., PCT Application No. WO 89/07456 describe radiolabeling proteins using cyclic thiol compounds, particularly 2-iminothiolane and derivatives.
Dean et al., International Patent Application, Publication No. WO89/12625 teach bifunctional coupling agents for Tc-99m labeling of proteins.
Schoemaker et al., International Patent Application, Publication No. WO90/06323 disclose chimeric proteins comprising a metal-binding region.
Thornback et al., EPC Application No. 90402206.8 describe preparation and use of radiolabeled proteins or peptides using thiol-containing compounds, particularly 2-iminothiolane.
Gustavson et al., International Patent Application, Publication No. WO91/09876 disclose Tc-99m chelating agents for radiolabeling proteins.
Rhodes, 1974, Sem. Nucl. Med. 4: 281-293 teach the labeling of human serum albumin with technetium-99m.
Khaw et al., 1982, J. Nucl. Med. 23: 1011-1019 disclose methods for labeling biologically active macromolecules with Tc-99m.
Schwartz et al., 1991, Bioconjugate Chem. 2: 333 describe a method for labeling proteins with Tc-99m using a hydrazinonicotinamide group.
Attempts at labeling peptides have been reported in the prior art.
Ege et al., U.S. Pat. No. 4,832,940 teach radiolabeled peptides for imaging localized T-lymphocytes.
Morgan et al., U.S. Pat. No. 4,986,979 disclose methods for imaging sites of inflammation.
Flanagan et al., U.S. Pat. No. 5,248,764 describe conjugates between a radiolabel chelating moiety and atrial natiuretic factor-derived peptides.
Ranby et al., 1988, PCT/US88/02276 disclose a method for detecting fibrin deposits in an animal comprising covalently binding a radiolabeled compound to fibrin.
Lees et al., 1989, PCT/US89/01854 teach radiolabeled peptides for arterial imaging.
Morgan et al., International Patent Application, Publication No. WO90/10463 disclose methods for imaging sites of inflammation.
Flanagan et al., European Patent Application No. 90306428.5 disclose Tc-99m labeling of synthetic peptide fragments via a set of organic chelating molecules.
Stuttle, PCT Application, Publication No. WO 90/15818 suggests Tc-99m labeling of RGD-containing oligopeptides.
Rodwell et al., 1991, PCT/US91/03116 disclose conjugates of "molecular recognition units" with "effector domains".
Cox, International Patent Application No. PCT/US92/04559 discloses radiolabeled somatostatin derivatives containing two cysteine residues.
Rhodes et al., International Patent Application, Publication No. WO93/12819 teach peptides comprising metal ion-binding domains.
Lyle et al, International Patent Application, Publication No. WO93/15770 disclose Tc-99m chelators and peptides labeled with Tc-99m.
Coughlin et al, International Patent Application, Publication No. WO93/21151 disclose bifunctional chelating agents comprising thiourea groups for radiolabeling targeting molecules.
Knight et al., 1990, 37th Annual Meeting of the Society of Nuclear Medicine, Abstract #209, claim thrombus imaging using Tc-99m labeled peptides.
Babich et al., 1993, J. Nucl. Med. 34: 1964-1974 describe Tc-99m labeled peptides comprising hydrazinonicotinamide derivatives.
Radiolabeled derivatives of VIP receptor binding peptides and fragments, analogues and mimetics thereof can also be used therapeutically. For these applications, cytotoxic radioisotopes rhenium-186 and rhenium-188 are particularly advantageous.
Thus there remains a need for synthetic (to make routine manufacture practicable and to ease regulatory acceptance) VIP receptor binding peptides. derivatives, analogues and mimetics which can be radiolabeled with Tc-99m, for use as scintigraphic agents and which can be radiolabeled with rhenium-186 or henium-188 for use as radiotherapeutic agents. Small synthetic VIP receptor binding peptides, derivatives, analogues and mimetics thereof which contain chelating groups for chelating Tc-99m, Re-186 or Re-188 and their Tc-99m, Re-186 and Re-188 labeled derivatives are provided by this invention that specifically fulfill this need.

Radiolabeled vasoactive intestinal peptides for diagnosis and therapy


Systems and methods for simulating cyber-physical systems are disclosed. A plurality of geographic simulation layers representing respective infrastructure sectors of a real-world environment may be generated, and the layers may be linked together with one another to create a multi-layer simulation. The associations between the layers of the simulation may be adjusted, and characteristics of the simulation layers themselves may be adjusted, to ensure that the simulation conforms to characteristics of the real-world environment being simulated. In some embodiments, a multi-user simulation system allows users at separate terminals to execute attack inputs and defense inputs against the simulation to try to destabilize and stabilize the simulation, respectively. Results of the attack inputs and defense inputs may be simultaneously displayed on a plurality of terminals.

The Department of Homeland Security has identified 16 critical infrastructure sectors that are regulated under the National Cybersecurity Framework; the 16 sectors include communication, energy, and transportation. According to DHS, "incapacitation or destruction [of these sectors] would have a debilitating effect on security, national economic security, national public health or safety."
Despite the critical need for security and stability of these sectors, complex networks continue to be hacked and brought down each year under Distributed Denial of Service (DDoS) attacks, or explored for private or sensitive information. Additionally, operators of systems in these sectors are currently ill-prepared to detect, analyze, understand, and respond to disruptions that may affect multiple different critical sectors at once.
For example, in 2003, the second-largest blackout in history was caused for the northeast United States and Canada due to an undetected software bug. The bug caused the usual control room alarms not to alert during an electrical surge, allowing the server and backup server to go offline without workers' knowledge. A chain reaction caused 265 power plants to shut down, causing power outages for 55 million people. The water supply lost pressure in areas of New Jersey and Ontario, forcing residents to pump and boil water due to unsafe drinking conditions. Amtrak's northeast corridor shut down, affecting commuters from Boston to Washington. Chicago and Ontario's train systems were also shut down. Communication networks all over the northeast were dramatically affected due to loss of backup power. Millions of cell phone users could not make calls, and home phones were significantly impacted as well. The cause was eventually traced to a software bug at an Ohio power distributor. However, at the time, 55 million people were affected, with no known cause, solution, or plan. It took two days to restore power, and three months to identify the true cause of the issue. There simply was no way of knowing where the problem originated, what caused the issue, and whether or not it was intentional.
In the near future, a similar outage of internet services could hit cyber-physical systems (CPS), this time affecting the millions of devices connected to the internet, connected vehicles, automated vehicles, communication towers, and more.
Simulating a CPS before outages arise may allow operators of the systems (e.g., local governments, utility companies, emergency services providers) to plan for and respond faster to these outages, attacks, and simple system deterioration. Knowledge of how these systems fail may allow agencies to identify the cause efficiently. Incorporating electrical, communications, transportation, weather, and cyber-attacks is required to enter the next frontier of critical infrastructure management and security at an operational scale. Prior research in this area has focused on isolated systems or simple combinations of layers under average day conditions. Our approach focuses on representing outlier conditions in a rapidly emerging connected infrastructure that includes connected and automated vehicles, wireless roadside sensors, communications systems, and the underlying dynamics of the electrical grid system under stress or attack.

Multi-layer cyber-physical systems simulation platform


A display apparatus according to an embodiment of the present disclosure includes: a thin plate-like display cell that displays an image; M exciters that are disposed on a back surface side of the display cell, and vibrate the display cell; and a driving section that drives the display cell and the M exciters.

Displays are rapidly becoming thinner and lighter. Accordingly, speakers are also becoming thinner and lighter, and using a flat panel speaker (FPS) in place of a cone speaker has been proposed. Moreover, using a display panel as a diaphragm in the flat panel speaker has been also proposed. For example, PTLs 1 to 3 each disclose a flat panel speaker.

Display apparatus and signal generation apparatus


Absorbent devices, and more particularly absorbent devices that are worn interlabially by female wearers for catamenial purposes, incontinence protection, or both, that have a emollient composition on their body-contacting surface are disclosed. The interlabial device has a body-contacting surface that is pre-moistened or pre-treated with an emollient to prevent drying of the wearer's labial tissue and to reduce friction of the structure against the wearer's labial tissue. The absorbent device is preferably capable of maintaining contact with the inside surfaces of the wearer's labia majora when worn. The emollient composition comprises a plastic or fluid emollient such as mineral oil, petrolatum and/or polysiloxane, an immobilizing agent such as a fatty alcohol or wax to immobilize the emollient on the body-contacting surface of the device, and optionally a hydrophilic surfactant to improve wettability of the coated surface. Because the emollient is substantially immobilized on the surface of the absorbent device, less emollient is required to impart the desired therapeutic or protective emollient coating benefits.

All manner and variety of absorbent articles configured for the absorption of body fluids such as menses, urine and feces are, of course, well known. With respect to feminine protection devices, the art has offered two basic types; sanitary napkins have been developed for external wear about the pudendal region while tampons have been developed for internal wear within the vaginal cavity for interruption of menstrual flow therefrom. Such tampon devices are disclosed in U.S. Pat. No. 4,412,833, entitled "Tampon Applicator", issued to Weigner, et al. on Nov. 1, 1983, and U.S. Pat. No. 4,413,986, entitled "Tampon Assembly With Means For Sterile Insertion", issued to Jacobs on Nov. 8, 1983.
Hybrid devices which attempt to merge the structural features of the sanitary napkins and the tampons into a single device have also been proposed. Such hybrid devices are disclosed in U.S. Pat. No. 2,092,346, entitled "Catamenial Pad", issued to Arone on Sep. 7, 1937, and U.S. Pat. No. 3,905,372, entitled "Feminine Hygiene Protective Shield", issued to Denkinger on Sep. 16, 1975. Other less intrusive hybrid devices are known as labial or interlabial sanitary napkins and are characterized by having a portion which at least partially resides within the wearer's vestibule and a portion which at least partially resides external of the wearer's vestibule. Such devices are disclosed in U.S. Pat. No. 2,662,527, entitled "Sanitary Pad", issued to Jacks on Dec. 15, 1953, and U.S. Pat. No. 4,631,062, entitled "Labial Sanitary Pad", issued to Lassen, et al. on Dec. 23, 1986.
Interlabial pads have the potential to provide even greater freedom from inconvenience because of their small size and reduced risk of leakage. Numerous attempts have been made in the past to produce an interlabial pad which would combine the best features of tampons and sanitary napkins while avoiding at least some of the disadvantages associated with each of these types of devices. Examples of such devices are described in U.S. Pat. No. 2,917,049 issued to Delaney on Dec. 15, 1959, U.S. Pat. No. 3,420,235 issued to Harmon on Jan. 7, 1969, U.S. Pat. No. 4,595,392 issued to Johnson, et al. on Jun. 17, 1986, and U.S. Pat. No. 5,484,429 issued to Vukos, et al. on Jan. 16, 1996. A commercially available interlabial device is FRESH 'N FIT.RTM. PADETTE interlabial product which is marketed by Athena Medical Corp. of Portland, Oreg. and described in U.S. Pat. Nos. 3,983,873 and 4,175,561 issued to Hirschman on Oct. 5, 1976 and Nov. 27, 1979, respectively.
However, many of these devices have not met with great commercial success. There are drawbacks associated with all of the above products. The devices described in these patents are believed to potentially be uncomfortable to wear due to frictional discomfort associated with rubbing of the product against the labial walls and sticking of the surfaces of the device to the labial walls. Furthermore, the frictional drag and sticking of the body-contacting surface of such devices against the labia can prevent these devices from being properly inserted, leading to discomfort.
The problem of drying of a female wearer's labial vestibule area has been discussed in the patent literature. For example, U.S. Pat. No. 4,846,824 issued to Lassen, et al. on Jul. 11, 1989, is directed to a labial sanitary pad that has a "physiologically hydrous" cover (that is, a cover material supposedly designed to "maintain a moist interface between the tissues of the vestibule and the pad"). Types of cover materials specified in the Lassen, et al. patent include a spunlaced polyester fiber nonwoven and a rayon cover. The Lassen, et al. patent states that the covers can be provided with various "coatings" to maintain the physiologically hydrous feature, but no specific coatings appear to be disclosed.
European Patent Application EP 0 692 263 A2, "Method of reducing the coefficient of friction of absorbent products and wax coated products produced thereby", is directed to lubricated absorbent products having a coating of a small amount of high molecular weight solid waxy substance which has a softening point above body temperature. However, there are drawbacks associated with the use of high molecular weight materials for this purpose. High molecular weight materials will not be as soothing or lotion-like to the wearer's skin as lower molecular weight materials. In addition, high molecular weight materials will not be capable of transferring to the wearer's skin to provide skin care benefits. High molecular weight waxes can also become brittle and tend to flake or chip off an absorbent article due to their lack of flexibility if the absorbent article is of a type that is required to flex and bend. Further, if the softening point of such materials is higher than room temperature, application of such materials to an absorbent article will be more difficult, and will require that the material be heated in order to coat an absorbent article with such a material.
A vaginal moisture balanced tampon and process is disclosed in European Patent Application 0 685 215 A1. However, the interlabial device of the present invention is not intended to be worn inter-vaginally as a tampon.
Thus, a need exists for an interlabial device that is small in size and that can be easily inserted and that provides protection against incontinence, menstrual discharges, and discharges of bodily exudates throughout a great range of wearer motions. A need exists for an interlabial device which is absorbent, has a reduction in frictional discomfort associated with rubbing of the product against the labial walls and sticking of the surfaces of the device to the labial walls. A need also exists for an interlabial device that has a reduced tendency to dry the inside surface of the wearer's labia.
Therefore, it is an object of the present invention to provide an interlabial device that is small in size and that can be easily inserted and that provides protection against incontinence, menstrual discharges, and discharges of bodily exudates throughout a great range of wearer motions.
It is another object of the present invention to provide an interlabial device which is absorbent, but has a reduction in frictional discomfort associated with rubbing of the product against the labial walls and sticking of the surfaces of the device to the labial walls.
It is another object of the present invention to provide an interlabial device that has a reduced tendency to dry the inside surface of the wearer's labia.
It is still another object of the present invention to provide an interlabial lo device that can be inserted into the space between the wearer's labia with less friction so that it will more easily be fully inserted into the desired wearing position.
These and other objects of the present invention will become more readily apparent when considered in reference to the following description and when taken in conjunction with the accompanying drawings.

Absorbent interlabial device treated with a polysiloxane emollient


A portable universal serial bus (USB) data exchanger device is described herein. In one embodiment, the portable USB data exchanger includes at least one flash memory chip having a multi-level cell (MLC) memory array, a flash memory controller coupled to the at least one flash memory chip, the flash memory controller having a USB on-the-go (OTG) capability and controlling reading and writing of the flash memory chip, a first extended USB (EUSB) connector coupled to the flash memory controller to be coupled to a host, and a second EUSB connector coupled to the flash memory controller to be coupled to a slave USB device. The Portable USB data exchanger can communicate with either a host or a slave USB device without polling. Other methods and apparatuses are also described.

A great variety of small portable devices such as personal digital assistants (PDA), multi-function cell phones, digital cameras, music players, etc. have become widely available. These devices use a central processing unit (CPU) or microcontroller and a mass-storage memory such as a hard drive or flash memory. These small devices are often cost and size sensitive.
These small portable electronic devices often are able to connect to a host computer such as a personal computer (PC). While a proprietary connector may be used, a connector for a standard expansion bus is preferable. Universal-Serial Bus (USB) is often used to connect such portable flash-memory card reader or Data Exchanger to a PC. USB uses one pair of differential lines that are time-duplexed, or used for transmission in both directions, but at different times. This may limit performance when data needs to be sent in both directions at the same time. The current USB 2.0 standard provides that the host, such as the PC, controls the bus as the bus master, while USB devices plugged into the host act as slave devices. A USB controller on the host PC generates data transfer transactions and waits for USB devices to respond, either by transmitting requested data to the host, or by writing host data into the USB device's memory.
Since memory on a USB device may be busy or slow, sometimes the host's request cannot be processed immediately. The host may send the request, then periodically poll the USB device to see whether the data is ready. Also, when the host is idle, the host may need to periodically poll the USB device to see if the USB device needs to transfer information to the host. This periodic polling may be used for other purposes as well, such as presence or removal of flash cards from the Card Reader device.
While polling is useful, since it allows the host to completely control the USB bus, power is consumed each time a packet is sent for polling. While this power is small, for low-power or battery-powered devices, the amount of power consumed may be significant and undesirable. Also, the USB device or host may otherwise be in a low-power sleep or suspend state, and have to wake up into a higher-power state to perform or respond to the polling. There may be significant time and energy required to wake up from the suspend or sleep state, and then to re-enter the suspend or sleep state once polling is done.
What is desired is a USB device and USB host that have lower power. A USB system that does not require polling is desirable. Bus protocols and transactions that avoid polling are desirable to be applied to USB to reduce energy consumed by polling.

Flash card reader and data exchanger utilizing low power extended USB protocol without polling


A method and apparatus to permit testing of Layer 2 and higher services provisioned for a port on a digital subscriber line access multiplexer (DSLAM) line card. Each line card is provisioned with a virtual port, a virtual port cross-connect function, and a virtual port tunneling function. The virtual port can be linked to any physical port on the line card. A test host can link to the virtual port from anywhere in a network to perform verification of end-to-end service provisioning and functionality throughout a network.

FIG. 1 schematically illustrates a prior art Digital Subscriber Line Access Multiplexer (DSLAM) 10 used to provide high-speed Internet (and optionally telephone service) access to service subscribers 12 in a manner well known in the art. The DSLAM 10 includes a plurality of line cards 14. Each line card 14 is provisioned with a plurality of DSL ports 16, typically 24 or 48 DSL ports 16. Each subscriber 12 is connected to one of the DSL ports 16 by a subscriber line 18 via a DSL modem 19, also in a manner well known in the art. The line cards 14 are further provisioned with interworking functions 22, which perform interworking feature processing 24. The line cards 14 are connected to a Local Area Network (LAN) switch 26, which is in turn directly or indirectly connected to a service provider network 28. The communications path 30 to the administrative workstation 20 may include multiple service provider networks (e.g. Service Provider A 28, Service Provider B 29, and Service Provider C 31).
As understood by those skilled in the art, subscriber services provided to the subscriber 12 by the DSLAM 10 must be provisioned using an administrative workstation 20, which is typically not connected directly to the DSLAM 10. Service provisioning can be complex and frequently requires verification or troubleshooting. Traffic flows bidirectionally between the subscriber 12 and the service provider 28 via a communications path 30. Provisioned interworking features are processed by interworking feature processing 24. If an error is made during service provisioning, service to the subscriber 12 may be denied, or the service provided may not accord with their service subscription.
In order to verify service provisioning, test heads 32 have been invented. The test head 32 is designed to be connected to a test bus interface on the line cards 14 of the DSLAM 10, as schematically shown. Any DSL port 16 can be administratively connected to the test bus (not shown) and thereby to the test head. Although the test heads 32 were originally designed to test only the physical layer of connectivity to the subscriber 12, the functionality of some test heads 32 has been enhanced to permit testing of higher layer functionality via the integration of reference DSL customer premise equipment (CPE), which can verify the service provisioning. However, the capital cost of such test heads can be prohibitive. Furthermore, there is a growing trend toward locating DSLAMs remotely in Fiber to the Neighborhood (FTTN) deployments. These deployments typically support fewer DSL customers thereby further increasing the cost per subscriber of deploying a test head.
In order to reduce operating costs, equipment self-testing for verifying physical layer connections has been invented. An example of this is built-in single-ended line testing (SELT) and dual-ended line testing (DELT) in DSL transceivers. However, Layer 2 and higher provisioning can still only be tested using a specially equipped test head, as explained above.
There therefore exists a need for a method and apparatus for verifying end-to-end service provisioning and functionality throughout a network used to provide DSL services.

Method and apparatus for verifying service provisioning in networks used to provide digital subscriber line services


The present invention relates to a lighter which a user actuates by at least two different modes of operation. In the first mode, a biasing member is positioned to oppose movement of an actuating assembly so that a user releases fuel and ignites the lighter only if a high-actuation-force is applied to the actuator. In this first mode, the lighter resists operation by unintended users by requiring a user to have a predetermined level of strength to actuate the lighter. In the second mode, the biasing member is moved to a different position which does not oppose movement of the actuating assembly to the same extent as the first mode so that a user may release fuel and ignite the lighter if a low-actuation-force is applied to the actuator. Moving the biasing element from the first position to the second position preferably requires the user to have a predetermined level of cognitive abilities and/or physical characteristics in order to resist use by unintended users.

The present invention generally relates to lighters such as pocket lighters used to light cigarettes and cigars or utility lighters used to ignite candles, barbecue grills, fireplaces and campfires, and more particularly to such lighters which resist inadvertent operation or undesirable operation by unintended users.
Lighters used for igniting tobacco products, such as cigars, cigarettes, and pipes, have developed over a number of years. Typically, these lighters use either a rotary friction element or a piezoelectric element to generate a spark near a nozzle which emits fuel from a fuel container. Piezoelectric mechanisms have gained universal acceptance because they are simple to use. U.S. Pat. No. 5,262,697 (xe2x80x9cthe ""697 patentxe2x80x9d) to Meury discloses one such piezoelectric mechanism, the disclosure the ""697 patent is incorporated by reference herein in its entirety.
Lighters have also evolved from small cigarette or pocket lighters to several forms of extended or utility lighters. These utility lighters are more useful for general purposes, such as lighting candles, barbecue grills, fireplaces and campfires. Earlier attempts at such designs relied simply on extended actuating handles to house a typical pocket lighter at the end. U.S. Pat. Nos. 4,259,059 and 4,462,791 contain examples of this concept.
Many pocket and utility lighters have had some mechanism for resisting undesired operation of the lighter by young children. Often, these mechanisms are on/off switches which may shut off the fuel source or may prevent movement of an actuator, such as a push-button, on the lighter. On/off switches which a user positively moves between xe2x80x9conxe2x80x9d and xe2x80x9coffxe2x80x9d positions can be problematic. For example, an adult user may forget to move the switch back to the xe2x80x9coffxe2x80x9d position after use and thereby render the feature ineffective.
Other pocket and utility lighters include a spring-biased blocking latch which arrests or prevents movement of the actuator or push-button. U.S. Pat. Nos. 5,697,775 to Saito and 5,145,358 to Shike et al. disclose examples of such lighters.
There remains a need for lighters which resist inadvertent operation or undesirable operation by unintended users, but which provide each intended user with a consumer-friendly method of operating the lighters so that the lighters appeal to a variety of intended users.
The present invention is directed to a lighter with at least two modes of operation. In either mode of operation, the lighter preferably is operational with no blocking mechanism(s) which arrests or prevents movement of an actuating member.
The present invention in one embodiment relates to a lighter which generally comprises a housing which contains fuel, an actuating member for actuating the lighter, and a movable biasing member. The biasing member preferably moves between a high-actuation-force position and a low-actuation-force position. More specifically, in the high-actuation-force position, the biasing member provides a first opposing force which opposes actuation of the lighter and preferably, when the user moves or repositions the biasing member to the low-actuation-force position, the biasing member provides a second different opposing force which opposes actuation of the lighter.
Preferably the first opposing force provided by the movable biasing member is greater, and optionally significantly greater, than the second opposing force. Optionally, the second opposing force may be substantially zero. The biasing member in the low-actuation-force mode may not oppose movement of the actuating member when the user applies a force thereto to the same extent as in the high-actuation-force mode. In one embodiment, the biasing member in the high-actuation-force position may be operatively associated with, engaged or in contact with, or coupled to the actuating member, and in the low-actuation-force position, the biasing member may be in contact with or disengaged from the actuating member.
In accordance with one embodiment, the actuating member may selectively dispense fuel, activate the ignitor assembly or perform both functions. The lighter optionally may have an ignitor assembly actuated by the actuating member. The ignitor assembly may include a piezoelectric unit. The actuating member may be at least one trigger. In the high-actuation-force position the movable biasing member may resist movement of the trigger to an actuation position by increasing the force necessary to actuate the trigger.
In yet another embodiment, the actuating member may be part of an actuating assembly that includes the trigger, a linking rod, and a pivoting member. The linking rod may be operatively connected to the ignitor assembly, and selectively activates the ignitor assembly. In such an embodiment, the actuating member can be the trigger or the linking rod. The pivoting member may be connected to the housing, disposed between the trigger and the linking rod, and selectively dispense fuel to the nozzle. In the high-actuation-force position the biasing member may contact the linking rod and apply the first opposing force to the linking rod to oppose movement of the linking rod. In the low-actuation-force position, the biasing member may be moved or repositioned and applies a second opposing force which preferably is less than the first opposing force, and optionally may be substantially less than the first opposing force or substantially zero.
In a further aspect, a latch member may be operatively associated with the biasing member. The latch member can be coupled to the housing in a number of ways, such as pivotally, slidably or in a cantilevered fashion. In the cantilevered coupling, one end of the latch member is fixed to the housing while the other end is free to move. Movement of the latch member may move the biasing member between the high-actuation-force position and the low-actuation-force position. The latch member may be separate from or integral with the biasing member, or the biasing member may be moved or repositioned directly by the user.
In an alternate embodiment, the lighter further includes a biasing member with an engaging portion and an actuating assembly with an engaging portion. The biasing member is movable between a first, at rest state and a second state. In the first state, the biasing member engaging portion is associated with the engaging portion of the actuating assembly. In the second state, the engaging portion of the actuating assembly moves the engaging portion of the biasing member. Less than about 10 kg applied to the trigger changes the biasing member from the first state to the second state and activates the ignitor.
This embodiment may further include a valve for dispensing fuel which is biased into a closed position and moveable to an open position. The actuating assembly selectively moves the valve. When in the high-actuation-force position, the biasing member resists or opposes movement of the actuating assembly. If the user applies a force equal to or greater than a first trigger force to the actuating assembly when the biasing member is in the high-actuation-force position, the valve moves from the closed position to the open position. When the biasing member is in the low-actuation-force position, the user may apply a lower second trigger force to the actuating assembly in order to move the valve between such positions.
One preferred aspect of the multi-mode lighter according to at least one embodiment is that after multiple actuations of the lighter, the first and second trigger forces required to operate the lighter in either mode, and more preferably the first trigger force, remains substantially constant. Thus, the first and second opposing forces exerted by the movable biasing member preferably do not substantially decrease with use of the lighter.
According to yet another embodiment of the present invention, the movable biasing member is configured and adapted in the high-actuation-force position to resist movement of the actuating assembly to an operative position and has a predetermined, at rest, length which upon movement of the actuating assembly may change between a first length and a second length. In one embodiment, the biasing member is configured such that its length in a first position is less than its length in a second position such as in, for example, a tension or extendable spring. In another embodiment, the biasing member is configured such that its length in its first position is greater than the length in its second position, as in, for example, a compression spring.
According to yet another embodiment, the lighter comprises a housing having a supply of fuel, an ignitor assembly for igniting the dispensed fuel, an actuating member associated with the housing, and a repositionable biasing member disposed to the housing. A predetermined actuating force is necessary to move the actuating member to an actuation position to actuate the lighter. In a first position, the biasing member is associated with the actuating member such that a first actuating force greater than said predetermined actuating force is required to move the actuating member to the actuation position.
According to a preferred aspect of the multi-mode lighter, the first or high-actuation-force mode preferably relies more on the user""s physical characteristics, and more specifically strength characteristics, while the second or low-actuation-force mode preferably relies more on the user""s cognitive abilities and dexterity. In yet another preferred, but optional, aspect of this lighter, the user may actuate the lighter in the high-actuation-force mode with a single finger. Moreover, according to another preferred, but optional, aspect of this lighter, the user may actuate the lighter in the low-actuation-force mode with two fingers. One further preferred, but optional, feature of the lighter is that actuation of the lighter in the high-actuation-force mode may occur by a different actuation sequence or movement than the actuation sequence or movements which may occur in the low-actuation-force mode.


A method of diagnosing the occurrence or non-occurrence of a blood vessel blockage or hemorrhage comprises non-invasively applying ultrasound to a location on a patient's body, where the ultrasound is applied in an alternating and pulsed fashion, administering acoustic amplifiers to the patient, monitoring a feedback acoustic response signal of the acoustic amplifiers triggered by the ultrasound, and determining a diagnosis based at least in part on a relationship between an acoustic response signature of the acoustic response signal and a baseline acoustic response signature.

Stroke is the second leading cause of death worldwide and the third leading cause of death in the United States, between cardiac diseases (the number one worldwide common cause of death) and tumor diseases (the number three worldwide common cause of death). Neuronal brain cells (neurons) are very sensitive to oxygen supply, which may be interrupted, for example, due to a sudden arterial vessel occlusion. As a result, neurons turn into apoptosis within the first 60 seconds of oxygen deprivation. Apoptosis is defined as a programmed cell death, which means that neurons start to die irreversibly already at this very early point in time if recanalization, and therefore providing an oxygen supply, does not occur.
In the case of acute ischemic stroke, it has been shown that an average of 1,900,000 neurons die every minute due to intracranial arterial vessel occlusion. Hence, it is a worldwide, common understanding that therapeutic options to recanalize the affected brain artery should be applied as early as possible. Recent advances in stroke care, such as the installation of specialized Stroke Centers/Units or TeleMedicine concepts, have improved stroke care in selected areas. However, all of these activities are either initiated or coordinated mainly by well known academic centers in developed countries, and the overall impact of these improvements on stroke care are negligible. The cause of the worldwide growing incidence of stroke may be attributed to 3 main causes. First, there is a lack of public awareness of the disease and its symptoms. Second, all conventional therapeutic interventions require hospitalization of the patient. Third, and among people of all ages, more than 85% of global deaths from stroke occur in either low or middle-income countries, where approximately 85% of the world's total population resides, as illustrated in FIG. 1.
Currently, tissue Plasminogen Activator, abbreviated tPA, is the worldwide accepted first choice therapeutic intervention in case of acute ischemic stroke. Globally, only about 3% of all stroke victims receive tPA. In the U.S., tPA is the only drug for acute stroke treatment approved by the Food and Drug Administration (FDA). One of the major limitations why only a very limited amount of stroke victims are eligible for tPA therapy is the limited treatment window of 4.5 hours after initial onset of clinical stroke symptoms. If this treatment window is exceeded, tPA will typically not be administered, due to a significant higher risk of harmful events caused by the drug itself. The vast majority of tPA treatment delays are caused by either failure to recognize stroke like symptoms in time and/or delayed transport times to the appropriate hospital where tPA therapy can be provided. Therefore, the diagnosis of ischemic vs. hemorrhagic stroke at the earliest time point possible, means having the capability to do so either at the site of the emergency or during patient transport in ambulances and helicopters, would potentially contribute to a higher referral rate of tPA candidate patients or patients who might benefit from neuro-intervention. The time delay between a '911' call, arrival at the site of the emergency, recognition/interpretation of stroke symptoms and their cause, and transport to the appropriate hospital are limiting factors determining whether a patient survives, suffers from lifelong invalidity or fully recovers without deficits.

Methods and devices for diagnosis of blood vessel blockage or hemorrhage

The Regents of the University of California


A holographic recording system with a simple structure is provided that can make a holographic recording beam follow a recording medium traveling even at high speed. The holographic recording system 10 includes a chopper lens 30 that travels in synchronization with and in a same direction as the holographic recording medium 14. The chopper lens 30 is formed so as to move the axes of incident information and reference beams relative to the recording medium and the chopper lens, and to irradiate them to an identical information recording region 15 in the holographic recording medium 14.

In holographic recording that utilizes holography to record information into a recording medium, an information beam and a reference beam are superposed each other in a holographic recording medium and an optical interference pattern formed by these beams is written as a diffraction grating.
As one of holographic recording systems, there is a system that modulates a recording beam comprising the information and reference beams in time and space and irradiates it to a recording medium while continuously moving the recording medium with respect to the optical axis of the recording beam. This includes, for example, a holographic recording system that irradiates the recording beam from an optical head while rotating a disc-shaped recording medium.
In this case, to prevent an aberration of the diffraction grating to be recorded in the recording medium moving relative to the recording beam, a light pulse as short as several tens nanoseconds is necessary to perform recording, causing the sensitivities in both recording and reproducing to decrease.
Alternatively, as described in, for example, Japanese Patent Laid-Open Publication No. 2002-183975, there is another holographic recording system that drives an optical head along tracks formed in the circumference direction of a disc-shaped recording medium by using an elastic arm, an electromagnetic coil, and a magnet to change the position of the recording beam.
This is the so-called stop-and-go recording method, in which recording is performed so that the variation of the relative position of the recording beam with respect to an information recording region in the recording medium will not occur when the recording medium rotates, and then the optical head is moved back to the original position while the recording beam (laser beam) turns off.
In the holographic recording system described in the above Japanese Patent Laid-Open Publication No. 2002-183975, irradiation position moving means comprising an elastic arm, an electromagnetic coil, and a magnet is provided as described above and is controlled by a follow-up control circuit so as to make the irradiation position of the recording beam follow an information recording region in the recording medium for a predetermined time and move it back to the original position. Therefore, the structure is complicated, the fabrication cost is high, and there is a risk that the recording beam cannot reliably follow the recording medium when the recording medium is rotated at high speed.

Holographic recording system and optical chopper


Universal running equation of time mechanism including a differential device outputting a running equation minute, the running equation minute driving a true minute which, via a true equation motion work drives a true hour, the civil time minute cannon-pinion driving, via a motion work wheel set, a civil hour wheel, a jumper spring, integral with the civil hour wheel, cooperating with a star having twelve teeth connected to an arbor carrying a civil hour hand, a time zone wheel also being integral with the arbor, a time difference and display train applying the time difference linked to the longitude position of the user relative to the center of the time zone to the true running equation hour, the time zone wheel applying to the civil hour wheel, in forward or backward one-hour steps, the time difference between the civil time at the place where the user is situated and the time at the center of the time zone.

Within the same time zone, the sun is at its zenith at a different time depending on whether one is at the extreme east, at the center or extreme west of the time zone. There is a time difference of 59 minutes between the two extreme positions.
Moreover, the country in which the user is situated may not be aligned with the official time zone time. This is, for example, the case of Switzerland, which although within the Greenwich Time zone, has a one hour time difference with England.
Other countries have only one official time but their territory covers several time zones.
Finally, some countries change time according to the season (summer time/winter time).
By way of example, for someone in Neuchâtel (Switzerland) on 23 July, the sun will be at its zenith at 13:38 hours in civil time, namely: 12 hours (time zone time), +2 hours (summer time)−28 minutes (longitude of Neuchâtel: 7°)+6 minutes (difference from running equation of time). Conversely, for someone in London on the same day, the sun will be at its zenith at 13:06 hours in civil time, namely: 12 hours (time zone time)+1 hour (summer time)+0 minutes (longitude of London: 0°)+6 minutes (difference from running equation of time). Yet Neuchâtel and London are in the same time zone.
FIGS. 1, 2 and 3 annexed to this patent application illustrate the prior art differential device to which the universal running equation of time mechanism of the invention applies.
This differential device is described in detail in European Patent Application No 1286233 in the name of the Applicant. Let us recall that FIGS. 1, 2 and 3 annexed to this patent application and taken from the aforementioned European Patent Application, show, in particular, the equation of time cam 1 whose profile is determined by the difference, for each day of the year, between mean solar time or civil time and true solar time.
Indeed, as is well known, there is a difference between true solar time, which is the time that elapses between two consecutive upper passages of the sun at the meridian of the same location, and mean solar time or civil time which is the mean duration in a year of all the true solar days. This difference between civil time and true time reaches +14 minutes 22 seconds on 11 February and −16 minutes 23 seconds on 4 November. These values vary very little from year to year.
The equation of time cam 1 is driven in rotation at the rate of one revolution per year from the simple or perpetual date mechanism comprised in the timepiece. Cam 1 carries a month disc 2 which rotates at the same speed and which matches the position of said cam 1 to the date indicated by the date mechanism so that the solar time minute hand 4 indicates the exact solar time.
The simple or perpetual date mechanism may be of any known type and will not be described in its entirety here. For a clear understanding, it is sufficient to know that this date mechanism drives equation of time cam 1 at the rate of one complete revolution per year. However, purely for the purpose of illustration, a date wheel set 6 driving a hand 8 which indicates the date (from 1 to 31) is shown. This date wheel set 6 rotates at the rate of one complete revolution per month. It is actuated by the date mechanism via an intermediate date wheel 10 for reversing the direction of rotation, and a reduction wheel set 12 for reducing the rotational speed from one complete revolution per month to one complete revolution per year.
The solar time minute hand 4 is driven by a differential gear 14 which has as respective inputs a gear train 16 driving a civil time minute hand 18 and a rack 20 which cooperates with equation of time cam 1 (rack 20 is shown in FIG. 1 in both of its end positions, once in a full line and the other time in dot and dash lines). More specifically, as seen in FIG. 1, differential gear 14 includes at least one and preferably two planetary wheels 22 driven by the motion work of the watch movement. These two planetary wheels 22 are capable of rotating on themselves and rolling over the inner toothing 24 of an equation of time wheel 26. The latter also has, on the external periphery thereof, a toothed sector 28 via which it cooperates with a toothed sector 30 comprised on one of the ends of rack 20. This rack is subjected to the return action of a spring (not shown) which is fixed to the watch frame and which tends to apply a feeler spindle 32, forming the other end of said rack 20, against the periphery of running equation of time cam 1. The solar time display train includes a pinion 34 placed at the center of differential gear 14 and carried by an arbour 36. This solar time display pinion 34 meshes with planetary pinions 22. It also carries a display wheel 38 which meshes with a cannon-pinion 40 onto the pipe of which there is driven the solar time minute hand 4. This gear train 38, 40 returns the solar time display to the center 42 of the watch movement, so that the solar time minute hand 4 is concentric with civil time minute hand 18.
The running equation of time mechanism which has just been described operates as follows.
In the normal operating mode of the watch, equation of time cam 1, equation of time rack 20 and thus equation of time train 26 are immobile. However, planetary pinions 22 are driven by the watch movement. Thus, they rotate on themselves and roll over the inner toothing 24 of equation of time wheel 26, driving solar time display pinion 34 in rotation, which permits the solar time minute hand 4 to rotate in a concomitant manner with civil time minute hand 18. The difference between solar time hand 4 and civil time hand 18 thus remains constant over a period of 24 hours.
Once per day, at around midnight, the running equation of time cam 1 pivots, driven by the date mechanism which changes the date from one day to the following day. At that precise moment, feeler spindle 32, which is in contact with the periphery of cam 1, in turn pivots rack 20. Said rack 20, in pivoting, drives equation of time wheel 26 in rotation. Planetary pinions 22, which are substantially immobile during this brief time interval (they make one complete revolution in one hour), rotate on themselves, driven in rotation by equation of time wheel 26 and in turn drive solar time display pinion 34 so as to precisely set the position of solar time minute hand 4 again.
Thus, the running equation of time mechanism described above can, at any time, display the time difference between mean solar time and true time, by means of a civil time minute hand and a solar time minute hand. This running equation of time mechanism does not, however, indicate the civil time at which the sun is at its zenith according to the position, in terms of longitude, of the user within the time zone.

This patent is subject to a terminal disclaimer.

Universal running equation of time mechanism and method of setting the same


The invention provides methods of using sequence based analysis and rational strategies to improve the solubility of immunobinders, and in particular of single chain antibodies (scFvs). The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions with hydrophilic residues identified by analysis of a database of selected, stable scFv sequences. The invention also provides immunobinders with optimized solubility prepared according to the engineering methods of the invention.

Antibodies have proven to be very effective and successful therapeutic agents in the treatment of cancer, autoimmune diseases and other disorders. While full-length antibodies typically have been used clinically, there are a number of advantages that use of an antibody fragment can provide, such as increased tissue penetration, absence of Fc-effector function combined with the ability to add other effector functions and the likelihood of less systemic side effects resulting from a shorter in vivo half life systemically. The pharmacokinetic properties of antibody fragments indicate that they may be particularly well suited for local therapeutic approaches. Furthermore, antibody fragments can be easier to produce than full-length antibodies in certain expression systems.
One type of antibody fragment is a single chain antibody (scFv), which is composed of a heavy chain variable domain (VH) conjugated to a light chain variable domain (VL) via a linker sequence. Thus, scFvs lack all antibody constant region domains and the amino acid residues of the former variable/constant domain interface (interfacial residues) become solvent exposed. An scFv can be prepared from a full-length antibody (e.g., IgG molecule) through established recombinant engineering techniques. The transformation of a full length antibody into an scFv, however, often results in poor stability and solubility of the protein, low production yields and a high tendency to aggregate, which raises the risk of immunogenicity.
Accordingly, attempts have been made to improve properties such as solubility of scFvs. For example, Nieba, L. et al. (Prot. Eng. (1997) 10:435-444) selected three amino acid residues known to be interfacial residues and mutated them. They observed increased periplasmic expression of the mutated scFv in bacteria, as well as a decreased rate of thermally induced aggregation, although thermodynamic stability and solubility were not significantly altered. Moreover, in their publication, they expressively state they did not observe any solubility improvement of the native protein state of the engineered scFvs as determined by the PEG precipitation method. Other studies in which site directed mutagenesis was carried out on particular amino acid residues within the scFv also have been reported (see e.g., Tan, P. H. et al. (1988) Biophys. J. 75:1473-1482; Worn, A. and Pluckthun, A. (1998) Biochem. 37:13120-13127; Worn, A. and Pluckthun, A. (1999) Biochem. 38:8739-8750). In these various studies, the amino acid residues selected for mutagenesis were chosen based on their known positions within the scFv structure (e.g., from molecular modeling studies).
In another approach, the complementarity determining regions (CDRs) from a very poorly expressed scFv were grafted into the framework regions of an scFv that had been demonstrated to have favorable properties (Jung, S, and Pluckthun, A. (1997) Prot. Eng. 10:959-966). The resultant scFv showed improved soluble expression and thermodynamic stability.
Progress in the engineering of scFvs to improve solubility and other functional properties is reviewed in, for example, Worn, A. and Pluckthun, A. (2001) J. Mol. Biol. 305:989-1010. New approaches, however, are still needed that allow for rational design of immunobinders, in particular of scFvs with superior solubility. Moreover, methods of engineering scFvs, and other types of antibodies, to thereby impart improved solubility—especially solubility of the native protein—, are still needed.

Solubility optimization of immunobinders

ESBATech, an Alcon Biomedical Research Unit LLC


A woven laminate for sound absorption that includes a first woven layer, a second woven layer, and a third woven layer. The first woven layer has a coarse structure. The second woven layer has a fine structure. The third woven layer has a medium structure. Each of the first, second, and third woven layers are composed of metallic wires that are woven to each other or interlaced as a fleece. At least one of the first, the second, and the third woven layers are superimposed in order to form the woven laminate. The woven layers are placed in the layer order fine-coarse-medium. The woven layers are welded together at least partially.

Woven laminates of the initially mentioned type are known from the state of the art. So called microporous cover materials are used for the sound absorption in hot gas flows. This is in particular always the case when the frequencies to be absorbed are comprised in the range above 800 Hz up to 6000 Hz, as they occur in turbines or other fast running rotary systems, such as for example in auxiliary gas turbines (APUs) of aeroplanes or the like.
The functioning of the microporous materials is to convert the energy of sound pressure waves into thermal energy. For this, it is necessary to cause a certain pressure loss by means of the microporous material. The partially high temperatures of the combustion gases of gas turbines of up to 900° C. require a corresponding material on metallic or ceramic base. The large field of metallic materials offers different possibilities for this.
One of the most famous solutions is the use of sintered metal fibre fleeces, such as they are also used for the purpose of the solid/liquid filtration. Such metal fibre fleeces are inserted in cylindrical form as a lining into a sound absorber section of an APU. Herein, the high weight of these fleeces as well as also their further processing by welding, which is extremely complicate, presents a substantial disadvantage. Another disadvantage are the long sintering times which lead to high costs and the brittle behaviour of the sintered material. This is essentially caused by the material to be selected, which always comprises a strong oxide forming alloying addition due to the high temperatures. A typical material for this is an alloy of FeCrAlY. A metal fibre fleece having sound absorbing properties is known from DE 102004018810 A1.
Therefore, new developments intend to substitute these metal fibre fleeces by woven textiles or woven laminates. These ones are single or multi-layer woven wires that are combined to solid woven laminates by means of a sintering process. Typically, one of the woven layers acts as acoustically active layer because of the selected microporous mesh.
Furthermore, reinforced metal fibre mats are known from the state of the art, such as for example from DE 12 98 507 A. The here described metal fibre mat consists of overlapping metal fibres that are arbitrarily distributed in a mated body and connected to each other by in particular sintering, wherein the particularity is that a permeable metal insert, that is provided with a greater free screen section than the mat, is embedded in and metallurgically connected to at least one surface of the metal fibre mat. The thus formed metal fibre mat serves in particular as insert for liquid filters.
Furthermore, a combined band for sound absorption, filter and padding purposes is known from the German Utility Model 19 68 840. This band is composed of two or more types of appropriate fleece-like material or wire mesh, wherein the inner core region is formed by glass, mineral or rock wool and the outer zone is formed by steel wool and/or wire mesh.

Woven laminate as lining for sound absorption of inlet and outlet sound absorbers and method of production of an acoustic insulation unit