A zone merging system includes a first FC networking device that is associated with one or more first FC networking device zones and a second FC networking device that is associated with one or more second FC networking device zones, wherein each of the one or more first and second FC networking device zones identifies a plurality of zone member devices. The second FC networking device performs limited zone merging operations subsequent to establishing a link with the first FC networking device. The limited zone merging operations include merging, via the link with first FC networking device zones, each of the second FC networking device zones that identifies at least one zone member device that is not local to the second FC networking device, while not merging each of the second FC networking device zones that identify only zone members that are local to the second FC networking device.

The present disclosure relates generally to information handling systems, and more particularly to merging zones in information handling systems that provide Fibre Channel (FC) communications.
As the value and use of information continues to increase, individuals and businesses seek additional ways to process and store information. One option available to users is information handling systems. An information handling system generally processes, compiles, stores, and/or communicates information or data for business, personal, or other purposes thereby allowing users to take advantage of the value of the information. Because technology and information handling needs and requirements vary between different users or applications, information handling systems may also vary regarding what information is handled, how the information is handled, how much information is processed, stored, or communicated, and how quickly and efficiently the information may be processed, stored, or communicated. The variations in information handling systems allow for information handling systems to be general or configured for a specific user or specific use such as financial transaction processing, airline reservations, enterprise data storage, or global communications. In addition, information handling systems may include a variety of hardware and software components that may be configured to process, store, and communicate information and may include one or more computer systems, data storage systems, and networking systems.
Some information handling systems are configured to provide a Fibre Channel (FC) Storage Area Network (SAN) for the storage of data. For example, FC switch device(s) may provide an FC fabric that couples storage devices providing a SAN to server devices utilizing the FC protocol. In such FC fabrics, each FC switch device may utilize FC zoning, which provides for the partitioning of the FC fabric into smaller subsets to restrict interference, add security, and simplify management, and operates to restrict zone members (e.g., target devices and initiator devices, particular ports of devices, etc.) included in a zone to communicating with other zone members included in that zone.
When FC switch devices included in two different FC fabrics are joined via a link (e.g., an Inter-Switch Link (ISL)) between the FC switch devices, zone merging operations may be performed during the initialization of the link. In conventional zone merging operations, an entire copy of a first active zone set provided for the first FC switch device will be merged with a second active zone set provided for the second FC switch device, and an entire copy of the second active zone set provided for the second FC switch device will be merged with the first active zone set provided for the first FC switch device. The zone merging operations discussed above may involve a relatively large number of zones, and thus can become a costly operation in a scaled environment that may take several minutes to complete. Furthermore, when a conflict between zones occurs, the conflict may cause the link initialization to fail, resulting in all data traffic provided on the associated link between the FC switch devices to be blocked. Further still, conventional zone merging operations only occur when a link between the FC switch devices is being established, or there is a change to the zones themselves.
Accordingly, it would be desirable to provide an FC zone merging system that addresses the issues discussed above.

Fibre channel networking device zone merging system


An optical security system enables the integrity of a container seal to be remotely interrogated. A plurality of Bragg gratings is written holographically into the core of at least one optical fiber placed about the container seal, where each Bragg grating has a predetermined location and a known frequency for reflecting incident light. A time domain reflectometer is provided with a variable frequency light output that corresponds to the reflecting frequencies of the Bragg gratings to output a signal that is functionally related to the location and reflecting frequency of each of the Bragg gratings.

There are a variety of applications where security must be assured and where such security must be ascertained from a location remote from the secured object. Older, prior art security seals were formed from metal tapes for electrical current continuity, embossed devices that were destroyed if the seal integrity was compromised, and other clasps and loops with identifiable impressions. Such devices can readily be counterfeited and/or defeated.
U.S. Pat. No. 3,854,792, issued Dec. 17, 1974, overcomes many of the problems of the prior art by using a fiber optic bundle wherein security masks provide light transmission security patterns between an input end of the fiber bundle and an output end of the bundle. The device requires, however, sufficient space to accommodate a bundle of fibers and access to both ends of the bundle to verify the optical transmission of the bundle.
These problems are addressed by the present invention and an improved fiber optic seal device is provided. Accordingly, it is an object of the present invention to provide a fiber optic seal security system that does not require access to both ends of an optical fiber for security interrogation.
Another object of the present invention is to provide a fiber optic seal device that requires only a few optical fibers, and preferably only one optical fiber, to provide the information needed to verify seal security. Additional objects, advantages and novel features of the invention will be set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.

Fiber optic security seal including plural Bragg gratings

The Regents of the University of California, Office of Technology Transfer


A method of manufacturing a semiconductor device which includes forming first and second gate patterns, forming first and second sidewall spacers on sidewalls of the first and second gate patterns respectively, implanting a first impurity into the semiconductor substrate, forming a third sidewall spacer on the first sidewall spacer and a fourth sidewall spacer on the second sidewall spacer in such a manner that the third sidewall spacer is in contact with the fourth sidewall spacer between the first and second gate patterns, implanting a second impurity into the semiconductor substrate, and removing the third and the fourth sidewall spacers.

The development of the Complementary Metal-Oxide Semiconductor (CMOS) device technology has been supporting the electronics industry and engineers are adopting finer CMOS design rules at an unprecedented pace in order to further improve the performance. As for generations of CMOS devices, which are expressed in terms of technology node, volume production of the 45-nm node has been started, the 32-nm node technology has been developed, and development of the next generation or the 22-nm node has begun. The feature sizes of devices become smaller and smaller and the gate lengths of MOS transistors are now 35 nm or less.
As the feature size of devices becomes smaller, processes such as the photolithography and etching processes are becoming more difficult to perform. Source-drain impurity profiles are designed so that devices operate even when gate pitches are reduced. Sidewalls are used primarily to set an offset for regions such as source-drain regions to gate electrodes. It is known that a problem of variations in threshold voltage arises as the gate length of a MOS gate transistor decreases. The phenomenon is called the short-channel effect.

Manufacturing method of a MOS transistor using a sidewall spacer


A chair (1), in particular a swivel office chair, is provided with a bottom chair part (2) having a column (3), a seat support (4) held on the bottom chair part (2), a seat (6) connected pivotably to the support, and a backrest support (5) holding a backrest (7) and connected pivotably to the seat support (4). The movement of the seat (6) is coupled with the movement of the backrest support (5) by a synchronizing mechanism having at least one spring (10) and coupling elements. The synchronizing mechanism is arranged essentially within the column (3).

The invention relates to a chair, in particular a swivel office chair, with a bottom chair part having a column, with a seat support held on the bottom chair part, a seat connected to this support so that it can pivot, and a backrest support holding a backrest and connected to the seat support so that it can pivot, wherein the movement of the seat is coupled with the movement of the backrest support by a synchronizing mechanism having at least one spring and coupling element.
For increasing comfort and for ergonomic sitting, swivel office chairs with synchronizing or rocking mechanisms are known, as described, for example, in EP 0 638 265 A2. This document involves a mechanism, which coordinates and simultaneously cushions the movement of the sitting surface and the backrest. In general, this mechanism part is housed underneath the seating surface in a so-called support. The cushioning is usually realized by coil springs, torque rods, or leaf springs. The restoring force can usually be set by the user.
Due to the complicated mechanism for the synchronous movement, the support is embodied as a relatively large, conspicuous box, which essentially defines the appearance of the chair and, among other things, negatively affects the handling. In addition, chairs with such a support are relatively heavy.


An arc-shaped waterproof wall is provided around a shaft to which a hearing aid main body case and a battery case are rotatably attached, and waterproof ribs are provided to the outer periphery of the installation face of the battery case and the hearing aid main body case, which improves the ability to prevent the penetration of moisture while also keep the cost low.

In the past, since the main body of a BTE (Behind-The-Ear) hearing aid was exposed to the outside, the penetration of moisture, such as rain or perspiration, was a problem.
This was a particular problem with the battery case, and because it had a structure that was opened and closed during battery replacement, there was a gap between the hearing aid main body case and the battery case, making it extremely likely that water or perspiration would penetrate into the interior of the hearing aid.
In view of this, a hearing aid has been disclosed in the past in which the battery case is rotatably fitted to the hearing aid main body case, and a gasket is installed at the grounding face between the battery case opening and the opening at the lower end of the hearing aid main body case (see Patent Literature 1, for example). Consequently, the gasket is pressed when the battery case is closed, and this prevents the penetration of rain or perspiration into the battery case.
Also, there has been a disclosure in which the entire battery case is housed inside the hearing aid main body case, a groove is formed in the inner wall face of the battery case, and a hole is provided in the lower part of this groove, which allows any moisture that does penetrate to drain away (see Patent Literature 2, for example).


The present invention provides compositions and methods for treating a myopathy. In certain embodiments, the invention provides compositions and methods for treating, improving muscle function, and prolonging survival in a subject with X-linked myotubular myopathy (XLMTM). The present invention provides a method comprising systemic administration of a composition that induces the increased expression of myotubularin in the muscle of a subject. The invention provides sustained regional and global increases in muscle function.

Recent progress raises anticipation that in vivo gene replacement will successfully treat many human genetic disorders (Epica, et al., 2002, Anim Genet 33(1):81-2; Guan et al., 2011, PM R 3(6 Suppl 1):S95-9; Forbes et al., 1985, AJR Am J Roentgenol 145(1):149-54). Nonetheless, substantial hurdles must be overcome to achieve regulatory approval for human gene therapies (Kornegay et al., 2011, Methods Mol Biol 709:105-234), such as successful treatment in predictive animal models. X-linked myotubular myopathy (XLMTM; OMIM 310400) is a fatal monogenic disease of skeletal muscle. Affected newborn boys, approximately one per 50,000 births, typically display marked hypotonia and respiratory failure (Jungbluth et al., 2008, Orphanet J Rare Dis 3:26). Survival beyond the postnatal period requires intensive support, often including gastrostomy feeding and mechanical ventilation (Herman et al., 1999, J Pediatr 134(2):206-14). No effective therapy to treat this disease exists.
XLMTM results from loss-of-function mutations in Myotubularin 1 (MTM1) (Laporte et al., 1996, Nat Genet 13(2):175-82). This gene encodes one of a family of 3-phosphoinositide phosphatases which act on the second messengers phosphatidylinositol 3-monophosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] (Rosset et al., 2004, J Digit Imaging 17(3):205-16; Yue et al., 2011, Methods Mol Biol 709:313-29; Salgado et al., 2003, JBR-BTR 86(4):215-20; Miyagoe-Suzuki and Takeda, 2010, Exp Cell Res 316(18):3087-92). Although myotubularin is expressed ubiquitously, loss of this enzyme primarily affects skeletal muscle. Myogenesis occurs, but muscle fibers throughout the body are hypotrophic and display structural abnormalities, with associated weakness (Buj-Bello et al., 2002, Proc Natl Acad Sci USA 99(23):15060-5).
The mammalian X-linked myotubularin gene is highly conserved (Laporte et al., 1998, Hum Mol Genet 7(11):1703-12; Laporte et al., 2000, Hum Mutat 15(5):393-409; Beggs et al., 2010, Proc Natl Acad Sci USA 107(33):14697-702). Genetic disruption of Mtm1 in mice causes profound abnormalities in skeletal muscle mass, structure, and function, regardless whether expression is knocked out constitutively or only in muscle (Buj-Bello et al., 2002, Proc Natl Acad Sci USA 99(23):15060-5; Al-Qusairi et al., 2009, Proc Natl Acad Sci USA 106(44): 18763-8). The phenotype resembles human XLMTM, with similar pathology and early mortality.
Thus there is a need in the art for effective and non-invasive compositions and methods for treating myopathy, including XLMTM. The present invention satisfies this unmet need.

This patent is subject to a terminal disclaimer.

Systemic gene replacement therapy for treatment of X-linked myotubular myopathy (XLMTM)


An impact-modified polyamide composition comprising from 5 wt % to 85 wt % of polyamide polymer; from 10 wt % to 60 wt % glass fiber; from 3 wt % to 30 wt % of an impact modifier; and a melt stabilizer at a concentration less than 5 wt %; wherein the weight ratio of the impact modifier to the melt stabilizer ranges from 1.0:1 to 100:1; and wherein the polyamide composition demonstrates an un-notched Charpy impact energy loss at 23° C. that is greater than 80 kJ/m2 and a tensile strength greater than 135 MPa.

Many varieties of natural and artificial polyamides have found use in various applications due to their high durability and strength. Some polyamide compositions can be formulated to have high melting points, high recrystallization temperatures, fast injection molding cycle times, high flow, toughness, elasticity, chemical resistance, inherent flame retardancy, and/or abrasion resistance. These desirable chemical and mechanical properties can make polyamide compositions suitable for use in constructing such diverse products as cable ties, sports equipment and sportswear, gun stocks, window thermal breaks, aerosol valves, food film packaging, automotive/vehicle parts, textiles, industrial fibers, carpeting, and electrical/electronic parts.
As one example, in the automotive industry there is an environmental need to reduce emissions and to increase the efficiency of fuel consumption. One approach towards achieving these goals is to reduce overall vehicle weight by substituting metal components with thermoplastic ones. And often times, polyamide compositions have been employed to provide such weight reduction in the engine compartment. Some of these polyamide compositions have also been found to be particularly well suited for automotive use due to their aforementioned heat resistance, mechanical strength, and overall appearance. Exemplary applications can include radiator tanks, charge air coolers, fans and shrouds, and push/pull cables.
In addition to the providing of mechanical strength, automotive applications also commonly require impact resistance, e.g., minimization of cabin noise, vibration, and harshness optionally via deformation. These performance characteristics, however, are often associated with conventional polyamide compositions, which have not been designed for imparting increased strength. In view of the existing art, the need therefore remains for improved polyamide compositions that effectively deliver both strength and impact resistance, e.g., toughness, as may be quantified by notched Izod and Charpy impact energy losses.

Ascend Performance Materials Operations LLC


A coated porous sheet material comprising a gas permeable sheet material selected from the group consisting of flash spun plexifilamentary nonwoven sheet, spunbonded-film-spunbonded composite sheet, spun-laced polyester/wood pulp composite sheet and paper and a polymeric coating on at least one side thereof, wherein the permeability of the coated sheet material is substantially equivalent to the permeability of an equivalent sheet material without the coating. The coated porous sheet material is suitable for use in heat sealable packages.

Conventionally practiced means for coating substrates such as fibrous nonwoven and paper sheet materials include knife coating, hot melt coating, aqueous dispersion coating, gravure coating, direct blade coating, roll coating, air doctor coating and squeeze coating. There are a number of problems with these known methods. Knife coating results in almost a complete surface coverage of the substrate, thereby altering its porosity and permeability properties. Only a small fraction of the permeability of the substrate is maintained mainly through the cracks that appear on the coating after drying. Hot melt coating, depending on how it is applied, may result in three-dimensional dots or islands of coating between the fibers of the substrates such that some of the pores of the sheet material are covered completely while some are partially covered.
The coating lines used in conventional methods are large and costly in terms of investment. These methods are not flexible in that a lot of coating material must be deposited, which is also economically unattractive in situations when less material would be sufficient for the end use application of the coated sheet. Solution or dispersion coatings must be dried by evaporation of the solvent or dispersion liquid in a way that the coating or the substrate are not damaged, or their properties are not altered due to exposure at high temperatures, which is a slow and costly step. In addition, in solvent-based coatings, solvent recovery is required which adds cost and complexity to the process. Coatings applied as hot melts often alter the thermal characteristics of the substrates resulting in a compromise of their original properties. Another problem is that the air permeability and/or the porosity of the uncoated substrate is almost always sacrificed once the coating is applied. It would be desirable to enhance or impart certain desired properties to a sheet material while leaving the air permeability or porosity of the material unaffected.
U.S. Pat. No. 6,083,628 (Yializis) discloses a hybrid film comprising a first polymer base film having at least one plasma-treated surface and at least a second thin acrylate polymer film disposed along the plasma-treated surface of the base film. The acrylate film is formed by crosslinking a functionalized acrylate monomer or oligomer. The hybrid film may additionally comprise one or more metallic or ceramic coatings. The continuous process for forming the hybrid film takes place within a vacuum chamber and it consists of plasma treatment of the base film to functionalize the film followed by vapor deposition of the acrylate monomer onto the base film and then radiation polymerization to crosslink the monomer. The hybrid film is useful in a number of applications including food packaging to improve barrier properties. In food packaging applications, the acrylate coating is disclosed to be typically 0.5 to 2 μm thick.
U.S. Pat. No. 4,842,893 (Yializis et al.) discloses a method for coating a flexible substrate with a thin, "substantially continuous" film by depositing a vapor of polyfunctional acrylate monomer, under vacuum, on a movable substrate maintained at a temperature such that the monomer condenses on the substrate. The film is then exposed to radiation in order to polymerize the film. The acrylate monomer coating may be formed having a thickness of less than 4 μm, preferably less than 2 μm and possibly as thin as 0.1 μm. Such coatings are disclosed as useful in food packaging and protective coatings for metal or other substrates used in a variety of applications. U.S. Pat. No. 5,032,461 (Shaw et al.) discloses a similar process in which the process of U.S. Pat. No. 4,842,893 (Yializis et al.) is repeated many times to form a multi-layered thin film structure having as many as 4,000 or more layers.
WO 99/59185 and WO 99/58756 disclose a process for coating a substrate in which the substrate is treated with a plasma and coated with an acrylate monomer, and the monomer is subsequently radiation polymerized. The plasma is generated using hollow cathodes and focused at the surface of the substrate using an electromagnetic or magnetic focusing means. According to WO 99/59185, the monomer coating may be applied using a capillary drip system, by immersion in a solution bath or by vapor deposition. According to WO 99/58756, the monomer is applied by vapor deposition. WO 99/58756 also discloses apparatus for treating industrial sized, continuous substrates, specifically such as papermaking fabrics.
A system and apparatus useful for vacuum deposition polymer coating in which a web surface is coated with inorganic and organic compositions is described in R. E. Ellwanger, M. G. Mikhael, A. Yializis and A. Boufelfel, "Vacuum Functionalization of Web Surfaces via Plasma Treatment and Polymer Coating," Vacuum Technology & Coating (February 2001). The system includes treating the surface with plasma to remove low molecular weight material and to functionalize the surface with polar groups, depositing materials such as radiation curable acrylates onto the surface by vacuum evaporation coating and polymerization of acrylates with either an electron beam or an ultraviolet lamp. Among the applications of the coated substrates disclosed are high barrier films, printable films and nonwoven fabrics.
U.S. Pat. Nos. 5,260,095, 5,547,508 and 5,395,644 (Affinito) disclose a process and apparatus for forming solid polymer layers under vacuum, including the step of degassing the monomer material prior to injection into the vacuum. The advantages of forming polymer layers in a vacuum are said to be that photoinitiator is not needed for polymerization, polymerization is faster, there are fewer impurities in the polymer, and the polymer has a greater density and a smoother finished surface.
WO 98/18852 discloses a process for coating substrates such as polypropylene, polyester or nylon sheet materials with crosslinked acrylate and a layer of metal. Acrylate monomer is evaporated using flash evaporators and condensing the acrylate onto the sheet as a monomer film, and subsequently polymerizing the film by irradiation by electron beam or ultraviolet light. The adhesion of the acrylate on the sheet material is enhanced by plasma treatment immediately before coating. Both the plasma treatment and the coating are conducted under vacuum. The resulting coated sheet is has low oxygen permeability and is especially useful for food packaging.
U.S. Pat. Nos. 5,811,183 and 5,945,174 (Shaw et al.) disclose sheet materials including paper and film coated with acrylate polymer release coatings made by a process in which silicon-containing and fluorine-containing acrylate prepolymer having a molecular weight between 200 and 3000 is vapor deposited on the sheet material and radiation polymerized. Coating layers of between 0.5 and 1 μm thick are disclosed.
Fiber tear is an important problem with current medical packaging in which at least one fibrous sheet, such as a nonwoven or paper, and a second sheet have been heat sealed together to form a pocket capable of containing an article such as a sterile medical device. Fiber tear occurs during the opening of a package (i.e., upon peeling the two heat sealed sheets away from each other), and begins by separating a fiber or a bundle of fibers from the surface of the fibrous sheet. Fiber tear is unacceptable in the case of medical packaging because foreign particles are thereby introduced into the sterile field of the operating room. It would be desirable to eliminate the incidence of fiber tear from heat sealed packages which include at least one fibrous sheet, without greatly affecting the permeability of the fibrous sealing sheet.
Additionally, it is often necessary to provide printed information on the surface of heat sealed sheets, especially on medical packaging. However, depending upon the nature of the substrate used as the heat sealed sheet, such printing can be rubbed off of the surface rather easily. It would be desirable to provide a coating on such substrates which would enhance ink adhesion to the heat sealed sheet/package.
Additionally, many sheet materials which are used in protective environments, such as in the medical field for use in making gowns, masks, drapes, boots, etc., are subject to contact with fluids which may present either chemical or biological hazards. Accordingly, such materials are typically rated as to their resistance to fluid strike-through, particularly blood strike-through in the medical field. It would be desirable to provide coatings for such sheet materials which would enhance fluid strike-through resistance without significantly affecting the air permeability of the sheet, such that the wearer will enjoy increased protection from fluid strike-through while still being comfortable when wearing such garments.

Coated sheet materials and packages made therewith


An osteosynthetic implant for a mechanical connection of fractured elements, made of a polymeric biodegradable base material, for use in reconstructive osteosynthesis. An active ingredient assists the regeneration of bone tissue in a fracture area and acts together with the implant to assist growth in the fracture area, so that the mechanical load-bearing capability of the healing fracture increases faster or at least as fast as the load-bearing capability biodegradable implant decreases when decomposing.

1. Field of the Invention
This invention relates to a biodegradable osteosynthesis implant constructed of a polymeric biodegradable base material with active ingredients that aid regeneration of bone tissue in a fracture area.
2. Description of Prior Art
Metallic implants have been used in medicine for more than 200 years for fixation of broken bones. Success was achieved in the last decades with the selection of suitable compatible metal alloys to optimize the mechanical load-bearing capacity, and above all the tissue tolerance of these implants so that corrosion and rejection reactions rarely occur. Complications because of the metallic implants can arise in the course of X-ray and tomographic diagnostic processes. One main disadvantage associated with conventional implants is that metallic implants cannot remain in the human body over an unlimited time. It is therefore necessary to perform a second surgical procedure for removing the implant after the fracture has healed. This not only involves another stress for the patient, but also results in considerable costs for the second surgical procedure and the necessary second stay of a patient in a hospital. In addition, direct and indirect costs result from loss of work and after-treatment during the second healing of the wound. Therefore efforts have been made over a considerable period of time to replace the metallic materials with biodegradable polymers so that removal of the implant after healing of the fracture is no longer necessary.
The use of a biodegradable plate in connection with osteosynthesis was first described by D. E. Cutright and E. E. Hunsuck in the Journal of Oral Surgery, Volume 33, pages 28 to 34 (1972).
In developing novel biodegradable implants, it has been a goal to replace metallic implants. Thus the implant had to fix the bone fragments in place and support the mechanical forces acting on the bone.
However, implants made of absorbable polyesters have inferior mechanical load-bearing capabilities when compared to implants made of metal. Although it was possible using suitable production methods, for example injection molding methods, and using optimized material mixtures to produce implants, for example fiber-reinforced implants, which could resist great tensile stresses, the flexible strength of such workpieces is relatively low and far below that of metal implants. A range of applications of biodegradable osteosynthesis materials is limited to lightly stressed, rapidly healing fractures. Such fractures can occur, for example, on the skull, such as a roof of the skull, a cheek bone or an upper jaw.


A camera having a data imprinting function, includes: a motorized film transport device for winding and rewinding a film having consecutive sprocket holes; a sprocket-hole detecting device which detects that each of the sprocket holes passes a predetermined position; a memory in which photographic data of a frame of the film is stored at a shutter release; a data imprinting device which reads out one of the photographic data stored in the memory therefrom to imprint one character of the photographic data on a corresponding frame of the film between two adjacent sprocket holes of the corresponding frame; a film moving amount detector for detecting an amount of movement of part of the film which extends from the trailing edge of the last frame of the film to the end of the film, in accordance with detection of the sprocket-hole detector; wherein the amount of movement, which is detected by the film moving amount detector, is stored in the memory; a frame edge detector which detects the trailing edge of the last frame when the film is rewound by the motorized film transport device in accordance with the amount of movement stored in the memory. The data imprinting device starts imprinting each of the photographic data stored in the memory on a corresponding frame of the film with reference to the trailing edge of the last frame detected by the frame edge detector, in accordance with detection of the sprocket-hole detector.

1. Field of the Invention
The present invention relates to a camera provided with data imprinting device for imprinting photographic data such as a date, time, shutter speed, aperture value, etc., on film.
2. Description of the Related Art
A camera provided with a data imprinting device which stores photographic data such as a date, time, shutter speed, aperture value, etc., in a memory each time the shutter is released and subsequently reads out the stored data to imprint the same on film in predetermined areas thereof at the time of rewinding the film, is known in the art. In such a camera, it is necessary to detect the trailing edge of the last frame in order to imprint photographic data on each frame precisely in a predetermined area thereof. A method of detecting the trailing edge of the last frame is disclosed in Japanese Laid-open Patent Publication No.63-177120 in which two pulses of different phases are generated by a mechanism composed of a gear, a printed circuit board, and a brush which slidably contacts the printed circuit board. The gear rotates in accordance with the movement of the film to rotate the brush relative to the printed circuit board so that the levels of the two pulses become high simultaneously only at each moment the border between two adjacent frames passes a predetermined position. The trailing edge of the last frame is detected at the time of rewinding the film by monitoring the levels of the two pulses. However, since there is a certain period of time required for the levels of the two pulses to become high simultaneously, the trailing edge of the last frame cannot be detected precisely. Accordingly, such a conventional method of detecting the trailing edge of the last frame is not suitable for the case where photographic data is imprinted on film in a narrow area between two adjacent sprocket holes thereof.


A multiple wheel feed wheel assembly for wood chipper includes an infeed chute and a rotatable cutting assembly spaced from the infeed chute. The multiple wheel feed wheel assembly also includes a first feed wheel disposed between the infeed chute and the cutting assembly. The multiple wheel feed wheel assembly further includes a second feed wheel spaced longitudinally between the first feed wheel and the infeed chute to feed wood material to the first feed wheel.

1. Field of the Invention
The present invention relates generally to wood chippers and, more particularly, to a multiple wheel feed wheel assembly for a wood chipper.
2. Description of the Related Art
It is known to provide a wood chipper for chipping wood such as brush, branches, and the like to produce wood chips. An example of such a wood chipper is disclosed in U.S. Pat. No. 5, 988, 539 to Morey. In this patent, the wood chipper includes an infeed chute, feed wheel assembly, and a cutting assembly having a rotatable disc with at least one knife or blade for chipping the wood entering the wood chipper and reducing it to wood chips. Typically, the feed wheel assembly includes a feed system having a stationary lower feed wheel connected to a lower housing and a movable upper feed wheel connected to an upper housing movable relative to the lower housing for allowing wood to enter the cutting assembly. The feed wheel assembly also includes a spring interconnecting the upper housing and the lower housing to urge the upper feed wheel toward the lower feed wheel to apply a spring force against the wood entering between the feed wheels to feed the wood to the cutting assembly.
Although this type of feed wheel assembly has worked well, it is desirable to reduce a pinch point between the upper feed wheel and the lower feed wheel. It is also desirable to provide a feed wheel assembly to allow larger diameter wood to enter the wood chipper virtually effortlessly by an operator without moving a hydraulic lift. It is further desirable to provide a feed wheel assembly for a wood chipper, which increases the distance between the pinch point and the operator and reduces a kick up of the wood material when fed in by an operator under normal or extreme operating conditions. Therefore, there is a need in the art to provide a multiple wheel feed wheel assembly for a wood chipper to that meets these desires.
Accordingly, the present invention is a multiple wheel feed wheel assembly for a wood chipper including an infeed chute and a rotatable cutting assembly spaced from the infeed chute. The multiple wheel feed wheel assembly also includes a first feed wheel disposed between the infeed chute and the cutting assembly. The multiple wheel feed wheel assembly further includes a second feed wheel spaced longitudinally between the first feed wheel and the infeed chute to feed wood material to the first feed wheel.
One advantage of the present invention is that a new and multiple wheel feed wheel assembly is provided for a wood chipper. Another advantage of the present invention is that the multiple wheel feed wheel assembly is provided that has four feed wheels positioned horizontally and spaced vertically with a forward pair of feed wheels located in front of a rear pair of feed wheels to move the pinch point further away from the operator. A further advantage of the present invention is that the multiple wheel feed wheel assembly has allows the forward upper feed wheel to be spaced a predetermined distance from a forward lower feed wheel to allow large diameter wood material to be fed virtually effortlessly in feeding wood to the cutting assembly by an operator and to reduce the tendency of the wood material to kick upwardly.

Multiple wheel feed wheel assembly for a wood chipper


An ice fishing alarm and light used in a fish house for alerting a fishing person of a fish strike on a bait attached to a fish line. A fishing rod having a baitcast reel is downwardly mounted on an arm assembly pivoted to a support. A switch assembly having a movable actuator accommodates the fish line whereby when a fish pulls on the fish line the actuator allows the switch assembly to connect an alarm to an electric power source causing the alarm to produce an audible sound.

Ice fishing in winter is a popular outdoor activity in northern United States and Canada. Walking onto a frozen lake, drilling a hole in the ice, and sitting on a bucket or chair with a jig stick in hand in temperatures below freezing zero degrees is ice fishing, a therapeutic experience. Out on the ice the hassles of work, the to-do lists, taxes, wars and politicians all fade away into the background. A field of ice is a landscape that sears the sin from the soul. Parkas, insulated pants and boots and bulking gloves are the ice fishing attire to maintain at least some body heat. Ice fishing houses and shelters have been used to escape the cold and windy environments on the ice. Fish houses are portable buildings that are located on the ice for the duration of a period of time determined by ice conditions and government regulations. The interiors of fish houses range from simple rooms to rooms having heaters, furniture, and communication devices. The floors of fish houses have one or more openings that allow augers to drill fishing holes in the ice.
Ice fishing persons use jig sticks or ice fishing rods to retain fish lines and bobs in open holes in the ice in sub-zero temperatures. The ice fishing rods are handheld and periodically moved up and down or jigged to move the bait to attract fish. Signal devices known as tip-ups are used to alert a fishing person that a fish has taken the bait. Audible and visual alarms have been used with signal devices to alert a fishing person remote from the fishing rod. An example of a tip-up ice fishing alarm is disclosed in U.S. Pat. No. 4,996,788. There are numerous alarm devices for use with fishing tackle that respond to the pull of baits by fish. Some of these devices are mounted directly on the fishing rod and other devices are separate from the fishing rods. A fishing alarm mount on a fishing rod is disclosed in U.S. Pat. No. 4,398,185. A fishing alarm and light apparatus remote from a tip-up is disclosed in U.S. Pat. No. 6,408,561.


A pre-prepared mesh-film web is used on a conventional vertical form-fill-seal packing machine to form a plurality of mesh-film bags.

Mesh bags are used to package many different products, for instance, children""s toys, small hardware items, flower bulbs, nuts, fruits and vegetables. Plastic bags made with thermal sealable films (both solid and perforated) are also used to package many of these same items. Mesh bags and perforated film bags allow air to flow through the package. Perishable items such as flower bulbs, nuts, fruits, and vegetables are often packaged in mesh or perforated film because they benefit from the airflow.
Vertical form, fill and seal machines are widely used in the packaging industry. They are widely used because they reduce packaging costs, especially labor costs associated with loading or filling premade bags.
Thermoplastic films, both solid and perforated, have been widely used on vertical form, fill, and seal machines for more than 20 years. Mesh materials have generally not been used on vertical form, fill, and seal machines because they are difficult to process on vertical form, fill, and seal equipment.
Typical mesh materials have a significantly higher degree of open air space between strands (openness) than do perforated films. This is true because typical mesh films are composed of thin strands. This is also true because there is a limit to the size and number of perforation holes that can be used before a perforated film loses its tensile strength, tear resistance, and dimensional stability. For example, a typical 10 lb. plastic bag having a length of 18xe2x80x3 and a width of 10xe2x80x3 for fresh whole potatoes might have 12 holes punched for ventilation approximately 0.375xe2x80x3 diameter. This is equivalent to 0.4% is the surface area of the plastic film on both-sides of the bag. Whereas a mesh material such as the preferred CLAF mesh is at least 50% open. The resultant step change in openness for mesh materials significantly increases airflow through the mesh package compared to a perforated film package.
The thin strands of typical mesh materials also reduce the surface area inside the package where moisture and condensation can be trapped and collect. Entrapped moisture and condensation inside the package are generally believed to increase spoilage and/or decrease shelf life for most perishable items, particularly whole potatoes and onions packed fresh or from storage.
The combination of increased airflow through the package is and reduced entrapment of moisture inside the package is desired by most packinghouse operators, distributors, and marketers of perishable fruit and vegetables.
Heretofore, the use of mesh materials on vertical form-fill-seal machines has been limited due to concerns about heat seal failures and overall package integrity. The most common failures are in either (1) the mesh-to-mesh transverse fin seals, and/or (2) the mesh-to-mesh longitudinal lap (or fin) seals. Failures of mesh-to-mesh heat seals are common in the predominant package weights ranging from one pound to ten pounds. In the majority of attempts to use mesh materials on vertical form-fill-seal machines, the package either fails at or adjacent to the transverse fin seal, at or adjacent to the longitudinal lap (or fin) seal, or both. The primary reason for mesh-to-mesh heat seal failures is the lack of an adequate and consistent mass of thermal sealable plastic material in the desired heat seal area.
Although there are distinct advantages to the use of mesh materials for such packages, for many of the above-described reasons, perforated films are typically chosen over mesh for use on vertical form-fill-seal machines when perishable items are being packed.
The grower-shippers and packing facilities that package perishable items have also imposed additional demands for increased packing and filling speeds for pre-made bag filling equipment and automated form-fill-seal packing equipment. In either case, filling premade bags or filling on vertical form, fill, and seal machines, the larger the fill opening for the items to be packed, the greater the filling speed.
Typically, the length of a bag is greater than its width. That being the standard, there is an advantage to filling the bag through the side as opposed to filling through the top. Regardless of the filling method employed (manual, semi-automatic, or fully automatic) the vast majority of all bags are filled through the top of the bag, thus the 10 opening size for placing articles in the bag is limited by the top circumference dimension of the premade bag or vertical form, fill, and seal package. Thusly, the speed of packing is also limited.
Fox U.S. Pat. No. 6,190,044 indicates examples of typical premade bag sizes indicating horizontal (width) and vertical (length) dimensions of the side walls (sides) for various produce weights as follows:
It is clear from the cross sectional area that the openings for filling through the sides are significantly greater the openings for filling top. Those skilled in the art of operating packaging equipment would easily recognize the advantages of being able to automatically fill packages with articles through the larger side opening of the package rather than through the smaller top opening of the package.
Grower-shippers and packing facilities that package perishable items have also imposed additional demands on packing equipment manufacturers for reduced equipment cost, increased packing and filling speeds, increased efficiency, increased flexibility, and reduced waste during the packing processes. This is true for packing machines designed and used for packing pre-made bags, as well as for vertical form, fill, and seal 1 packing machines.
In recent years, particularly in Europe, new vertical form, fill, and seal machines designed to run mesh materials have been introduced to the market by Pannekeet Machine Techniek of The Netherlands, Sorma Netpack of Italy, and Affeldt Verpackungsmaschinen GmbH of Germany. For the most part, these are machines that are designed for the primary purpose of running mesh with large labels front and back, the use of labels being advantageous to reinforce the mesh-to-mesh transverse heat seals. The fact that they require large labels, however, adds significant cost to the final package. There is also the burden of added capital investment for the packing house operator if he has to purchase special vertical form, fill and seal machines designed primarily to run mesh material only.
WO9914121 (EP 0 677 450 A1) is directed to the utilization of a mesh web on vertical form, fill, and seal machines made by Pannekeet Machine Techniek of The Netherlands and Affeldt Verpackungsmaschinen GmbH of Germany specifically for improved packaging of perishable items. WO9914121 (EP 0 677 450 A1) provides that the top and bottom mesh-to-mesh heat seals of the vertical form, fill, and seal package are reinforced by positioning a large film label on both the front and back of the package sandwiching a mesh tube in-between. The front and back labels run the full length and nearly the full width of the lay-flat package. Aside from advertising, the primary purpose of the front and back label is to reinforce and prevent the top and bottom heat seals from failing. While this method may reduce heat seal failures typical of most mesh-to-mesh seals, it falls short because its advantages are offset by the following deficiencies:
(1) the bag must be filled through the narrow top opening; thereby, limiting filling speeds;
(2) the finished bag must be gusseted on both sides in order to eliminate any mesh-to-mesh transverse direction fin seals top and bottom that would likely fail in most practical applications over 1.0 lb.;
(3) the front and back label panels dictate the finished bag width;
(4) the finished bag requires very large labels front and back in addition to the tube of mesh material; thereby, increasing the total packaging materials required by as much as 60% to 70% as compared with alternative packages for the same application, for example Fox 6,190,044 81; and,
(5) the finished bag cost is significantly greater than alternative premade bags made for the same purpose, for example Fox 6,190,044 B1.
Likewise, Sorma Netpack EP 0 788 974 A3 is also directed to the utilization of a mesh web on-vertical form, fill, and seal machines for improved packaging of perishable items. EP 0 788 974 A3 requires that a pre-pared mesh-film web be utilized consisting of five parts, three parts label (comprising the front and back label panels of the bag) and two parts mesh (comprising the side gussets of the bag) This web can only be processed on a vertical form, fill, is and seal machine specifically designed to run this pre-pared mesh-film web. The bag must be formed by forming a mesh gusset on both sides of the bag by tucking a substantial part, apparently 90% or more, of the mesh material between the front and back label panels on both sides of the bag prior to transverse heat sealing. Like EP 0 677 450 A1, EP 0 788 974 A3 utilizes large film labels front and back to sandwich the mesh between the label panels in order to achieve sufficient heat seal strength of the top and bottom transverse seams of the bag. While this method reduces heat seal failures typical of most mesh-to-mesh seals, it falls short because its advantages are offset by the following deficiencies:
(1) the bag must be filled through the narrow top opening; thereby, limiting filling speeds;
(2) the finished bag must be gusseted on both sides in order to preclude mesh-to-mesh transverse direction fin seals top and bottom that would likely fail in most practical applications over 1.0 lb.;
(3) the front and back label panels dictate the finished bag width;
(4) the back label consists of two parts that must be heat sealed longitudinally in the center of the back label panel thereby interfering with the printing of the backside label; and,
(5) the finished bag cost is significantly greater than alternative premade bags made for the same purpose, for example Fox U.S. Pat. No. 6,190,044 B1.
Madderom U.S. Pat. No. 6,105,908 is directed to the utilization of a pre-pared mesh web based upon Rusert-Antonacci patent application dated Sep. 22, 1998, Ser. No. 09/158,307. Madderom U.S. Pat. No. 6,105,908 is directed to the utilization of a pre-pared mesh web with a plurality of sequentially spaced filler strips on vertical form-fill-seal equipment for improved packaging of perishable items. Madderom U.S. Pat. No. 6,105,908 directs that a pre-pared web consisting of a pre-printed fixed length label and precisely sequentially spaced thermoplastic filler strips be applied to a 100% mesh web. The thermal sealable filler strips must be precisely located and sequentially spaced on the pre-pared mesh web at the exact length of the pre-printed label applied to the 100% mesh web. If done correctly, the pre-pared web will process on a vertical form, fill, and seal machine in such a manner that the thermal sealable filler strips are located precisely in the same location as the transverse side heat seals of the finished bag. To date, Madderom U.S. Pat. No. 6,105,908 has not been economically or commercially viable and falls short because its advantages are offset by the following deficiencies:
(1) the process to make the pre-pared web is capital intensive
(2) the process to make the pre-pared web requires special proprietary equipment be purchased in order to produce the pre-pared web;
(3) the process to make the pre-pared web requires special component materials because:
a. the mesh web must have very high tensile strength and low elongation properties to insure the precise location and sequential spacing of the thermal sealable filler strips within approximately +/xe2x88x92 0.125xe2x80x3;
b. the pre-printed label applied to the mesh web must also have very high tensile strength and low elongation properties to insure the precise location and sequential spacing of the thermal sealable filler strips; and,
c. the thermal sealable filler strips have to be a special blend of metallocine Linear Low Density Polyethylene (LLDPE) in order for the process and the finished bag to be successful;
(4) the finished pre-pared web can only be used for a specific predetermined bag size on the vertical form, fill, and seal machine; and,
(5) the finished bag cost is significantly greater than alternative premade bags made for the same purpose, for example Fox U.S. Pat. No. 6,190,044 B1.
The present invention solves the above-described deficiencies within the known prior art by providing for the use of a pre-prepared mesh-film web on conventional form, fill and seal machines. According to the present invention, the pre-prepared mesh-film web is made up of approximately 50% thermal sealable plastic mesh and approximately 50% unprinted or printed film that can be either solid or perforated. The pre-prepared mesh-film web may be processed on conventional vertical form-fill-seal equipment without the need for major modifications or special equipment added to the machine, for instance, label unwinds for the front and back labels. The items may be placed in the bag through the side or the top of the bag.
The prepared mesh-film web may be printed or unprinted prior to being processed on the vertical form-fill-seal packing machine. The majority of vertical form-fill-seal machines have the ability to advance an unprinted continuous web a predetermined length as it is being processed through the vertical form, fill, and seal machine. This enables the operator adjust bag length at any time by resetting that criteria on the control panel. Likewise, the majority of vertical form, fill, and seal machines have the ability to print a continuous web while the web is being processed. This is typically done in-line prior to introduction to the forming mandrel and subsequent formation of a tube. Vertical form-fill-seal machines also enable the operator to process a printed continuous web to make a bag at a predetermined length in accordance with the bag printing or graphics. Thus, the combined options of being able to (1) process a pre-pared printed mesh-film web or (2) print an unprinted pre-pared mesh-film web in-line and (4) change bag length at any time on the unprinted pre-pared mesh-film web provides the vertical form, fill, and seal operator the ability to run a multitude of bag designs and bag sizes without having to change the unprinted pre-pared mesh-film web.
Different types of bags can be formed on different types of vertical form, fill and seal machines by modifying the specific configuration of the pre-prepared mesh-film web of the present invention for the particular package requirements or by modifying the specific configuration of the vertical form, fill, and seal machine.
For example, in some applications, it may be desirable to provide a thermal sealable zipper tape applied during the form, fill and seal process as the longitudinal fin seal is formed, and, thereafter, thermally attaching each side of the tape to the respective free longitudinal edges of the pre-pared mesh-film web.
The primary features and advantages of the invention will be apparent to those skilled in the art upon inspecting the following drawings and description thereof. Importantly, the inventive pre-pared mesh-film webs and the inventive mesh-film bags derived from these webs can be made with relative ease and without any special modifications on commercially available vertical form, fill, and seal equipment.

Pre-prepared mesh-film web for use on form, fill and seal machines


An apparatus minimizes stress on un-moulded IC devices by use of an airflow system. A vacuum urges the DUT's into contact with the pivoted test fingers, thereby reducing damage to the IC. A fitting is connected to a vacuum pump which draws out air and creates a vacuum chamber in the area created by the lift/support and the test socket, thereby causing the supported un-moulded DUTs to move upward towards the test socket and into physical contact with the test pins. The index time is decreased in order to improve overall operating efficiency and costs of the test apparatus.

Conventional IC device tests are generally carried out by picking up the IC molded dies with a using vacuum picker arms. DUTs are then placed on a test site with pivoted gold test fingers to test on the IC dies.
U.S. Pat. No. 5,894,217 shows a test handler having a turn table in which IC devices where a suction force is used to pick and place the said IC devices. U.S. Pat. No. 6,031,384 describes an IC testing method and apparatus where IC devices are carried and tested using a loader arm, an unloader arm and a contact arm without creating a vacuum for testing the said DUTs.
In testing IC devices, an automatic test handler is frequently used in combination with an IC tester to automatically move IC devices (DUT) to a test position at the test head of the IC tester. There are generally two types of test handlers. A vertical transfer type handler transfer the DUTs in a vertical direction by use of gravity. A horizontal transfer type handler places DUTs on a tray or carrier module for transfer in a horizontal direction to the test position. The test apparatus/test handler of the present invention is directed to a vertical transfer type handler.
In a typical horizontal type testing apparatus test handler, IC devices are aligned on a tray in a loading area and picked up, one by one, transferred to a test head of an IC tester and placed on a test socket of the test head by a pick and place mechanism or a robot hand of the test handler. The tested IC devices are taken from the test head and transferred to an unloading area and placed on a tray based on the test results.
In this type of test handler, the overall path of movement of the DUTs is lengthy and complicated. A relatively long time is required for positioning the DUT with the test socket, testing the DUT, and returning the tested IC device to the unloading area.
Index time, as defined in semiconductor industry, is the overall time required for handling IC device other than the time required for device testing. Since the index time is not the actual time for testing of the DUT, it is generally considered that the shorter the index time, the higher the test efficiency of the testing apparatus. A conventional test handler requires a relatively long index time because of the length of device transfer paths and complicated movements of the test handler.
A modem IC device has a large number of pins with a small pitch. Each pin is very small in size and is mechanically weak. Thus, precise positioning is required to accurately place the IC device in a test position to match with the test socket with a large number of corresponding contact pins during testing. As fine positioning of the IC devices needs complicated adjustments and synchronization of various components, errors tend to arise in placing or extracting the IC devices with respect to the test socket. This may deform the pins of the DUTs and thereby make the test unreliable.
An example of a conventional type test handler is shown in FIG. 2.
FIG. 2 is a schematic diagram showing a plan view of a test handler (100). A tray (20) having the IC devices to be tested is transferred from the loading area to a transfer station (21) (dotted line) where each of the IC devices is picked up by a suction end (10) of a pick and place mechanism and transferred to a test socket (31) positioned at the test head of an IC tester.
The suction end (10) is movable along the arm (50) in a back and forth direction (Y). The contact arm (50) can move in a right and left direction (X) along rails (40). Thus, the suction end (10) can freely take a position by the movement in the X and Y directions on a surface of the test handler (100).
By placing the IC device on the test socket (31), an IC tester (not shown) supplies test signals to the IC device on the test socket (31) and the resulted output signals from the IC device are evaluated by the IC tester. The suction end (10) picks up the DUTs that have been tested and transferred to a tray on a receiving station (22) (dotted line). It then places the IC devices depending on the test results. The IC devices on the tray are transferred to an unloading area (23) where the IC devices are unloaded with the trays for the next process, such as a molding, burning, packing and shipping for customers.
FIG. 1 is a side view showing an example of a suction end used in the pick and place mechanism of FIG. 2. In this example, the suction end (10) is provided with an air pipe (not shown) connected to an air cylinder to provide a suction air force. When a suction is applied, the suction end (10) attracts the IC device below and picks up the IC device by the suction air force. The suction end (10) is movable in the X and Y directions on the testing apparatus. The suction end (10) transfers each IC device from the transfer area (21) to the test socket (31) and from the test socket (31) to the receiving station (22).
During the process involved in the conventional testing apparatus/handler, the operation of placing the IC device on the test socket (31) sometimes fail because of an inaccurate positioning of the IC device with respect to the test socket. Such inaccurate positioning may occur when the suction end (10) picks up the IC device while moving in the X and Y directions at a relatively high speed. Suction end (10) may therefore not accurately place the DUT in the desired position when placing the IC device. The suction end (10) also may fail to accurately position the DUT due to the poor surface condition of an IC device, mechanical vibrations, or other factors.
Therefore, in the conventional testing apparatus/handler as exemplified in FIGS. 1 and 2, a relatively large index time is needed for supplying IC devices to the IC socket. As a result the test efficiency is limited by the index time. In addition, positioning errors sometimes occur because of the inaccuracy of the pick and place mechanism of the testing apparatus/handler.
Moreover, all dies must be molded during testing on apparatus/handler in order to conduct tests. This wastes the die casting materials. Physical contact with pivoted gold test fingers or test sockets may also cause severe damage to the IC.

Apparatus for testing un-moulded IC devices using air flow system and the method of using the same


A system and methods for detecting intrusions in the operation of a computer system comprises a sensor configured to gather information regarding the operation of the computer system, to format the information in a data record having a predetermined format, and to transmit the data in the predetermined data format. A data warehouse is configured to receive the data record from the sensor in the predetermined data format and to store the data in a SQL database. A detection model generator is configured to request data records from the data warehouse in the predetermined data format, to generate an intrusion detection model based on said data records, and to transmit the intrusion detection model to the data warehouse according to the predetermined data format. A detector is configured to receive a data record in the predetermined data format from the sensor and to classify the data record in real-time as one of normal operation and an attack based on said intrusion detection model. A data analysis engine is configured to request data records from the data warehouse according to the predetermined data format and to perform a data processing function on the data records.

1. Field of the Invention
This invention relates to systems and methods for detecting anomalies in a computer system, and more particularly to an architecture and data format for using a central data warehouse and heterogeneous data sources.
2. Background
As sensitive information is increasingly being stored and manipulated on networked systems, the security of these networks and systems has become an extremely important issue. Intrusion detection systems (IDSs) are an integral part of any complete security package of a modem, well managed network system. An IDS detects intrusions by monitoring a network or system and analyzing an audit stream collected from the network or system to look for clues of malicious behavior.
Many widely used and commercially available IDSs are signature-based systems. As is known in the art, a signature-based system matches features observed from the audit stream to a set of signatures hand crafted by experts and stored in a signature database. Signature-based methods have some inherent limitations. For example, a signature-based method is designed to only detect attacks for which it contains a signature in the database. Therefore, the signature-based methods cannot detect unknown attacks since there is no signature in the database for them. Such unknown attacks can be dangerous because the system is completely vulnerable to them. In addition to the expense in time and human expertise of manually encoding a signature for each and every known attack
Data mining-based methods are another paradigm for building intrusion detection systems. The main advantage of these methods is that they leverage the generalization ability of data mining methods and in order to detect new and unknown attacks. Data mining IDSs collect data from sensors which monitor some aspect of a system. Sensors may monitor network activity, system calls used by user processes, or file system access. They extract predictive features from the raw data stream being monitored to produce formatted data that can be used for detection. Machine learning and data mining algorithms are used on a large set of such data (e.g., "training data") to build detection models. New data (e.g., "sensor data") gathered by sensors is evaluated by a detector using the detection model. This model determines whether or not the sensor data is intrusive. These models have been proven to be very effective. (See, W. Lee, S. J. Stolfo, and K. Mok, "Data Mining in Work Flow Environments: Experiences in Intrusion Detection," Proceedings of the 1999 Conference on Knowledge Discovery and Data Mining (KDD-99), 1999; and Christina Warrender, Stephanie Forrest, and Barak Pearlmutter, "Detecting Intrusions Using System Calls: Alternative Data Models," Proceedings of the 1999 IEEE Symposium on Security and Privacy, pages 133-145. IEEE Computer Society, 1999).
These algorithms are generally classified as either misuse detection or anomaly detection. Misuse detection algorithms model known attack behavior. They compare sensor data to attack patterns learned from the training data. If the sensor data matches the pattern of some known attack data, the observed data is considered intrusive. Misuse models are typically obtained by training on a large set of data in which the attacks have been manually labeled (See, W. Lee, S. J. Stolfo, and K. Mok. Data mining in work flow environments: Experiences in intrusion detection. In Proceedings of the 1999 Conference on Knowledge Discovery and Data Mining (KDD-99), 1999.) This data is very expensive to produce because each piece of data must be labeled as either normal or some particular attack.
Anomaly detection algorithms learn a model of normal activity by training on a set of normal data. Anomaly detection models compare sensor data to normal patterns learned from the training data. Anomaly detection algorithms then classify as an attack activity that diverges from this normal pattern based on the assumption that attacks have much different patterns than do normal activity. In this way new unknown attacks can be detected. (See, e.g., D. E. Denning, "An Intrusion Detection Model," IEEE Transactions on Software Engineering, SE-13:222-232, 1987; T. Lane and C. E. Brodley, "Sequence Matching and Learning in Anomaly Detection for Computer Security," Proceedings of the AAAI-97 Workshop on AI Approaches to Fraud Detection and Risk Management, pages 43-19. Menlo Park, Calif.: AAAI Press, 1997; Christina Warrender, Stephanie Forrest, and Barak Pearlmutter, "Detecting Intrusions Using System Calls: Alternative Data Models," Proceedings of the 1999 IEEE Symposium on Security and Privacy, pages 133-145. IEEE Computer Society, 1999; and T. Lane and C. E. Brodley, "Temporal Sequence Learning and Data Reduction for Anomaly Detection," Proceedings of the Fifth ACM Conference on Computer and Communications Security, pages 150-158, 1998.) Anomaly detection models are popular because they are seen as a possible approach to detecting unknown or new attacks. Most of these algorithms require that the data used for training is purely normal and does not contain any attacks. This data can be very expensive because the process of manually cleaning the data is quite time consuming. Also, some algorithms require a very large amount of normal data which increases the cost.
As discussed above, data mining-based IDSs have their own disadvantages. Data to train the models is costly to generate. The data must be collected from a raw audit stream and translated into a form suitable for training. In addition, for misuse detection, each instance of data must be labeled either normal or attack. In the case of anomaly detection, each instance of data must be verified to be normal network activity.
Since data-mining based IDSs in general do not perform well when trained in one environment and deployed in another, this process of preparing the data must be repeated at every deployment of data mining-based IDS system. Furthermore, for each type of audit data that is to be examined (network packets, host event logs, process traces, etc.) the process of preparing the data needs to be repeated as well. Because of the large volumes of data that needs to be prepared, the deployment of a data mining-based IDS system involves a tremendous amount of manual effort.
Many of parts of these manual proms can be automated, including the collection and aggregation of the data and translating it into a form appropriate for training the data mining-based detection models. In addition, many of these processes are the same across types of audit data. Some of the processes still require some manual intervention such as labeling the data, but even these can be semi-automated.
The work most similar to adaptive model generation is a technique developed at SRI in the Emerald system. (See, e.g., H. S. Javitz and A. Valdes, "The NIDES Statistical Component: Description and Justification," Technical Report, SRI International, 1993.) Emerald uses historical records to build normal detection models and compares distributions of new instances to historical distributions. Discrepancies between the distributions signify an intrusion. One problem with this approach is that intrusions present in the historical distributions may cause the system to not detect similar intrusions in unseen data.
Related to automatic model generation is adaptive intrusion detection, Teng et al. perform adaptive real time anomaly detection by using inductively generated sequential patterns. (See, H. S. Teng, K. Chen and S. C. Lu, "Adaptive Real-Time Anomaly Detection Using Inductively Generated Sequential Patterns," Proceedings of the IEEE Symposium on Research in Security and Privacy, pages 278-284, Oakland, Calif., May 1990.) Also relevant is Sobirey's work on adaptive intrusion detection using an expert system to collect data from audit sources. (See, M. Sobirey, B. Richter and M. Honig, "The Intrusion Detection System Aid, Architecture and Experiences In Automated Audit Analysis," Proc. of the IFIP TC6/TC11 International Conference on Communications and Multimedia Security, pages 278-290, Essen, Germany, 1996.)
Many different approaches to building anomaly detection models have been proposed. A survey and comparison of anomaly detection techniques is given in Christina Warrender, Stephanie Forrest and Barak Pearlmutter, "Detecting Intrusions Using System Calls: Alternative Data Models," Proceedings of the 1999 IEEE Symposium on Security and Privacy, pp. 133-145, IEEE Computer Society, 1999. Stephanie Forrest presents an approach for modeling normal sequences using look ahead pairs (See, Stephanie Forrest, S. A. Hofmeyr, A. Somayaji, and T. A. Longstaf, "A Sense of Self For UNIX Processes," Proceedings of the 1996 IEEE Symposium on Security and Privacy, pp. 120-128, IEEE Computer Society, 1996) and contiguous sequences (See, S. A. Hofmeyr, Stephanie Forrest, and A. Somayaji, "Intrusion Detection Using Sequences of System Calls," Journal of Computer Security, 6:151-180, 1998). Helman and Bhangoo present a statistical method to determine sequences which occur more frequently in intrusion data as opposed to normal data. (See, P. Helman and J. Bhangoo, "A Statistically Base System for Prioritizing Information Exploration Under Uncertainty," IEEE Transactions on Systems, Man and Cybernetics. Part A: Systems and Humans, 27:449-466, 1997.) Lee et al. uses a prediction model trained by a decision tree applied over the normal data. (See, W. Lee and S. J. Stolfo, "Data Mining Approaches For Intrusion Detection," Proceedings of the Seventh USENIX Security Symposium, 1998; and W. Lee, S. J. Stolfo, and P. K. Chan, "Learning Patterns From UNIX Processes Execution Traces For Intrusion Detection," Proceedings of the AAAI-97 Workshop on AI Approaches to Fraud Detection and Risk Management, pages 50-56. Menlo Park, Calif.: AAAI Press, 1997.) Ghosh and Schwartzbard use neural networks to model normal data. (See, Anup Ghosh and Aaron Schwartzbard, "A Study in Using Neural Networks for Anomaly and Misuse Detection," Proceedings of the Eighth USENIX Security Symposium, 1999.) Lane and Brodley examine unlabeled data for anomaly detection by looking at user profiles and comparing the activity during an intrusion to the activity under normal use. (See, e.g., T. Lane and C. E. Brodley, "Sequence Matching and Learning in Anomaly Detection for Computer Security," Proceedings of the AAAI-97 Workshop on AI Approaches to Fraud Detection and Risk Management, pages 43-19. Menlo Park, Calif.: AAAI Press, 1997; T. Lane and C. E. Brodley, "Temporal Sequence Learning and Data Reduction for Anomaly Detection," Proceedings of the Fifth ACM Conference on Computer and Communications Security, pages 150-158, 1998; and T. Lane and C. E. Brodley, "Temporal Sequence Learning and Data Reduction for Anomaly Detection," ACM Transactions on Information and System Security, 2:295-331, 1999.)
In intrusion data representation, related work is the IETF Intrusion Detection Exchange Format project ("Internet Engineering Task Force: Intrusion Detection Exchange Format," http://www.ietf.org/html.charters/idwg-charter.html, 2000) and the CIDF effort (S. Staniford-Chen, B. Tung and D. Schnackenberg. "The Common Intrusion Detection Framework (CIDF)", Proceedings of the Information Survivability Workshop, October 1998).
The challenge in automating these processes is the need to support different types of data and different types of detection models. In a typical network environment there are many different audit streams that are useful for detecting intrusions.
What is needed is an architecture to automate the processes of data collection, model generation and data analysis, and to solve many of the practical problems associated with the deployment of data mining-based IDSs.

Systems and methods for adaptive model generation for detecting intrusions in computer systems

The Trustees of Columbia University in the City of New York


A WDM ring configuration having a central office node is provided in which each channel has substantially the same loss and no single channel has a disproportionately high loss. Thus, the diameter of the WDM ring in accordance with the present invention can be increased and/or the number of filters provided along the ring can be increased to accommodate additional channels.

The present invention is directed toward a wavelength division multiplexed (WDM) ring system.
Optical communication systems are a substantial and fast growing constituent of communication networks. The expression "optical communication system," as used herein, relates to any system which uses optical signals to convey information across an optical waveguiding medium, for example, an optical fiber. Such optical systems include but are not limited to telecommunication systems, cable television systems, and local area networks (LANs).
Currently, many optical communication systems are configured to carry an optical channel of a single wavelength over one or more optical waveguides such as optical fibers. To convey information from multiple sources, time-division multiplexing (TDM) is frequently employed. In TDM, a particular time slot is assigned to each signal source with the complete signal constructed from portions of the signal collected from each time slot. While this is a useful technique for carrying plural information sources on a single channel, it is prohibitively expensive to continue to increase the TDM data rate.
While the need for communication services increases, the current capacity of existing waveguiding media is limited. Although capacity may be expanded (e.g., by laying more fiber optic cables), the cost of such expansion is prohibitive. Consequently, there exists a need for a cost-effective way to increase the capacity of existing optical waveguides.
Wavelength division multiplexing (WDM) is being explored as an approach for economically increasing the capacity of existing fiber optic networks. WDM systems typically include a plurality of transmitters, each respectively transmitting signals on a designated wavelength. As a result, fiber capacity can be increased by a multiple equal to the number of channels.
WDM systems have been deployed in long distance networks in a point-to-point configuration consisting of end terminals spaced from each other by one or more segments of optical fiber. In metropolitan areas, however, WDM systems having a ring or loop configuration are currently being developed. Such systems typically include a plurality of nodes located along the ring. At least one optical add/drop element, associated with each node, is typically connected to the ring with optical connectors. The optical add/drop element permits both addition and extraction of channels to and from the ring. One of the nodes, referred to as a hub or central office node, typically has a plurality of associated add/drop elements for transmitting and receiving a corresponding plurality of channels to/from other nodes along the ring.
Each channel in a WDM system is typically transmitted at a unique wavelength.
Conventional filters, such as dielectric filters, can be provided within the add/drop elements in order to facilitate adding and/or dropping of individual channels, while allowing the remaining channels to continue along the ring. Each filter and its associated optical connectors, however, imposes an incremental loss on optical signals propagating along the WDM ring. Accordingly, a particular channel traversing a given number of filters along the ring can incur significantly more loss than other channels traversing fewer filters. As a result, the "worst-case" loss for one channel passing through a maximum number of filters can be so high as to limit the ring circumference.


A preparation method of inverse opal material for visible-light-driven photocatalytic degradation of organic pollutants includes 1) using titanium dioxide precursor as raw material, preparing nitrogen-doped titanium dioxide inverse opal by one-step process in the presence of nitrogen source, and 2) in the presence of reducing agent, using the nitrogen-doped titanium dioxide inverse opal, selenium precursor, and cadmium precursor as raw materials to prepare the cadmium selenide sensitized nitrogen-doped titanium dioxide inverse opal.

With the development of science and technology, dyes are closely related to human daily life. Today, synthetic dyes are widely used in food, printing and dyeing, cosmetics and pharmaceutical industries. Throughout the world, about 12% of the dyes used are lost in their processing and handling operations. Of which, 20% pass through wastewater into the environment, resulting in pollution of the water environment. It can be seen that dye wastewater seriously endangers the water environment. These dyes are usually biologically toxic and carcinogenic, and difficult to degrade by microorganisms in the environment. Therefore, the search for cheap, efficient and energy-saving methods to degrade dye wastewater has become a hot issue in environmental research.
Since Honda et al. used TiO2 electrodes for hydrogen production by photolysis of water in 1972, the research on semiconductor photocatalysts has developed rapidly. Photocatalysis refers to that by light irradiation, semiconductor generate carriers and undergoes the separation of photogenerated carriers. And then photogenerated electrons and holes combine with ions or molecules to produce reactive radicals with oxidative or reductive properties. These reactive radicals can degrade organic macromolecules into carbon dioxide and water. Therefore, the photocatalytic technology has the advantages of high efficiency and low cost.
Nowadays, the research on photocatalytic performance of ZnO, TiO2, CdS and SnO2 is becoming more and more important. Among them, titanium dioxide has many advantages, such as good photocatalytic activity, high stability, acid and alkali resistance, non-toxic to the biological, rich sources and low cost, so it is the most frequently used for photocatalytic research. However, the application of titanium dioxide in the field of photocatalysis has been limited by the following factors: 1), the recombination of photo-generated electrons and holes leads to low quantum yield. 2), TiO2 has a wide band gap of 3.2 eV and exhibits photocatalytic activity under ultraviolet excitation. 3), the mass transfer rate between TiO2 and pollutant is low.

Inverse opal material for visible-light driven photocatalytic degradation of organic pollutants, and preparation method thereof


A method includes acquiring a plurality of sample level values of a received current frame signal; determining a current power of the current frame signal based on the plurality of sample level values; determining a current traffic signal ratio of the current frame signal based on the plurality of sample level values; taking the current power as a current pilot power of the current frame signal if it is determined that the current traffic signal ratio is less than or equal to a predetermined ratio; and determining the current pilot power of the current frame signal based on the current power, the current power floating upper limit and the current power floating lower limit if it is determined that the current traffic signal ratio is greater than the predetermined ratio. Thus, the pilot power can be accurately determined for different traffic signal ratios.

With the development of communication technology, 5G has been widely deployed and applied. However, in practice, the amplitude of real-time power jitter of 5G NR (New Radio) signal is large, which brings trouble for openness and maintenance of communication equipments. In addition, in the 5G NR signals, control resource blocks (RBs) and traffic resource blocks are interleaved in a physical frame structure, so that the real-time powers will be read with large errors.

Method for determining pilot power, communication device, and storage medium


A telemark ski binding has a toe retainer pivotally coupled to a base. A lock assembly of the binding has an actuator assembly. The lock assembly is adjustable between a locked configuration and an unlocked configuration. The binding further has a heel retainer rotatably coupled to the toe retainer. When the lock assembly is in the unlocked configuration, the toe retainer is unlocked, and the toe retainer and heel retainer are both rotatable together substantially inline, relative to the base, around a first center point. When the lock assembly is in the locked configuration, the toe retainer is locked, and the toe retainer is restrained from rotating relative to the base. The heal retainer is rotatable relative to the toe retainer around a second center point. The second center point is at a different location from said first center point.

Telemark ski binding systems are well known.
U.S. Pat. No. 9,566,498 discloses a ski binding comprising a first recess for receiving a ski shoe pin, a locking member movable between a locking position and an open position, a biasing means to bias the locking member towards the locking position, and an activation member rotatably attached to the housing for rotation around a transversal rotational axis of the binding. The locking member has at least one outer portion that allows a ski shoe pin to force the locking member from the locking position towards the open position when the ski shoe pin enters the first recess. The activation member has an arm extending radially away from its transversal rotational axis. The activation member and the locking member are operatively connected such that when the arm rotates in the first rotational direction through a predetermined lower operational range, the activation member forces the locking member from the locking position to the open position.
U.S. Pat. No. 9,526,972 discloses a front unit for a ski binding, comprising a front jaw for fixating a ski boot in a downhill position and engagement members for pivotably supporting the ski boot about a horizontal pivot axis (S) perpendicular to a longitudinal axis of a ski in a climbing position, wherein the front jaw is disposed slidably in the direction of the longitudinal axis of the ski relative to the engagement members for switching between the downhill position and the climbing position, wherein the engagement members are each disposed on a first end of two opposing guiding arms which substantially extend in the direction of the longitudinal axis of the ski and each are guided by a front jaw member of the front jaw.
U.S. Pat. No. 7,246,812 discloses a ski binding of the cross-country type in which a ski boot's heel may be elevated with respect to the ski's top surface while in the act of skiing. The binding includes a toe piece associated with a heel retainer through a spring-biased linkage. A linkage typically includes a pre-loaded compression spring mounted external to a core element. A preferred linkage includes a plurality of rigid link elements defining a plurality of intermediate pivot axes between an anchor and the heel retainer. Certain preferred linkage systems permit unfettered boot flexion, but transversely maintain the heel retainer in a zone over the ski to facilitate step-in engagement. Desirably, the core is adjustable along the linkage, to change a spacing between the toe piece and heel retainer independent of spring pre-load. Preferred embodiments of the binding include a rear frame adapted to permit step-in engagement of a ski boot. Certain frames may carry a televator. A frame may function as a rear shim to permit adjusting a binding to fit boots of different sizes without necessitating adjustment of the position of a rear shim installed on a ski.
U.S. Pat. No. 8,328,225 discloses a ski binding adaptor for alpine ski touring and downhill, including a floating heel lock assembly and multifunctional rotatable locking arms. Ski bindings are mounted on an adaptor mounting plate, channel or beam assembly that pivots at the toe. The heel lock mechanism "floats" on a rail or rails to accommodate ski flex, and includes a multi-position climbing bar or heel riser. The floating heel block and locking mechanism are interconvertible for different ski modes: in fixed heel-mode—the locking arms act to firmly secure the heel to the ski for aggressive downhill conditions or riding style, and in free heel mode—the locking arms may be configured to support touring and climbing configurations. The ski binding adaptor with floating heel lock mechanism is optionally compatible with a range of alpine ski touring and downhill bindings.


An antimycobacterial combination and composition for treating tuberculosis are described. The compounds used are N-(3-[[4-(3-trifluoromethylphenyl)piperazinyl]methyl]-2-methyl-5-phenyl-pyrrolyl)-4-pyridylcarboxamide of formula (I) or a pharmaceutically acceptable non-toxic salt thereof

Worldwide, tuberculosis remains a leading cause of death. There are approximately 8 million active cases of tuberculosis per year, with 3 million deaths annually. About 1.7 billion people (one-third of world's population) are estimated to harbor the latent Mycobacterium tuberculosis infection [Kochi, A. Tubercle. 1991, 72, 1-6]. Individuals with latent tuberculosis carry 2 to 23% lifetime risk of reactivation of the disease later in life [Parrish, N M., Dick, J D., and Bishai, W R., Trends. Microbial. 1980, 6, 107-112]. In addition, immunosuppressive conditions including human immunodeficiency virus (HIV) infection has dramatically increased the risk of reactivation of tuberculosis.
The emergence of drug resistant pathogens renders the current mode of treatment very difficult and in many cases completely ineffective. Treatment of multi-drug resistant varieties of tuberculosis is difficult, and the disease often carries a high rate of mortality, particularly in developing countries. It is estimated that in the next twenty years over one billion people will be newly infected with tuberculosis with nearly 35 million people succumbing to the disease [WHO Fact Sheet No. 104, Global Alliance For TB Drug Development: Executive Summary of the Scientific Blueprint for TB Development; http://www.who.int/inf-fs/en/fact104.html]. With the emergence of HIV related tuberculosis, the disease is assuming alarming proportions as one of the killer diseases in the world today. The World Health Organization (WHO) has declared as a priority the need to immediately control tuberculosis infection for prevention of the spread of drug resistant strains.
One problem with current tuberculosis therapies is the shift of M. tuberculosis into a dormant or latent state. Thus, while the treatment of active tuberculosis with the currently prescribed combination drug regimen reduces the bacterial burden by a substantial amount, a proportion of bacilli shift into dormancy and survive in the host for months or years without producing any overt disease. However, later the bacilli can reactivate resulting in active tuberculosis once again. The recurrence of tuberculosis these days is considered to be the result of the reactivation of latent organisms which survive in the host [Stead, W W., Am. Rev. Respir. Dis., 1982, 95, 729-745; Stead, W W., Kerby, G R., Schleuter, and Jordahl, C W., Ann. Intern. Med., 1968, 68, 731-745].
The first drug used to combat M. tuberculosis was streptomycin in 1944, which was found to inhibit the growth of M. tuberculosis. A few classes of compounds have been introduced into clinical practice in the last 30 years, such as:
a) Long acting rifamycins e.g., rifapentine, rifabutin, and rifalazil [Javis, B., Lamb, H M., Drugs, 1998, 56, 607-616; McGregor, M M., Olliaro, P., Wolmarans, L., Am. J. Respir. Crit. Care Med., 1996, 154, 1462-1467; Shoen, C M., DeStefano, M S., Cynamon, M H., Clin. Infect. Dis., 2000, 30(Suppl. 3), S288-S29];
b) Fluoroquinolone compounds e.g. levofloxacin, moxifloxacin, and gatifloxacin [Ji, B., Lounis, N., Truffot-Pernot, C., Grosset., Antimicrob. Agents Chemother., 1995, 39, 1341-1344; Miyazaki, E., Miyazaki, M., Chen, J M., Chaisson, R E., Bishai, W R., Antimicrob. Agents Chemother., 1999, 43, 85-89; Fung-Tomc, J., Minassian, B., Kolek, B., Washo, T., Huczko, E., Boner, D., Antimicrob. Agents Chemother., 2000, 45, 437-446];
c) Oxazolidinone compounds [Cynamon, M H., Klemens, S P., Sharpe, C A., Chase, S C., Antimicrob. Agents Chemother., 1999, 43, 1189-1191]; and
d) Niroimidazopyrans [Strover, C K., Warrener, P., VanDevabter, D., Nature, 2000, 405, 962-966].
However, none of these compounds has shown the desired potential to effectively treat multi-drug resistant and/or latent tuberculosis.
Rifapentine and rifalazil have shown effectiveness in treating tuberculosis through administration of lesser (intermittent therapy) doses of the drugs and a combination of the two drugs is also reported to be more effective in preventing latent tuberculosis than rifampicin. However, since these drugs have the same pharmacophore as rifampicin their activity spectrum against the resistant strains has not improved significantly. These molecules are rather ineffective against multi-drug resistant strains of M. tuberculosis. Further, many of these compounds have proved to be toxic.
A number of drugs, such as p-aminosaliscyclic acid, isoniazid, pyrazinamide, ethambutol, ethionamide, rifampicin etc. have been used either alone or in combination for treatment of tuberculosis. These drugs were found to be more effective than streptomycin in treating patients infected with the streptomycin resistant strains, thereby ushering in an era of effective treatment of tuberculosis.
Currently, the treatment of tuberculosis consists of administering a combination of four first line drugs, viz. isoniazid, rifampicin, ethambutol and pyrazinamide, administered individually as a single drug formulation or as a fixed dose combination. For effective treatment the abovementioned four first line drugs are given to a patient in the initial or induction phase, during which the drugs are used in combination to kill the rapidly multiplying population of M. tuberculosis as well as to prevent the emergence of drug resistance. This is followed by a continuation phase during which sterilizing drugs, viz. isoniazid, rifampicin, and pyrazinamide are given to kill the intermittently dividing population of M. tuberculosis [Jindani, A., Aber, V R., Edwards, E A., Mitchison, D A., Am. Rev. Respir. Dis., 1980, 121, 39-49; Grosset, J., Tubercule., 1978, 59, 287-297; East African/British Medical Research Council Study in Am. Rev. Respir. Dis., 1977, 115, 3-8; Singapore Tuberculosis Service/British Medical Research Council in Am. Rev. Respir. Dis., 1979, 119, 579-585; British Thoracic Society and Tuberculosis Association in Am. Rev. Respir. Dis., 1982, 126, 460-462; Snider, D E., Rogowski, J., Zierski, M., Bek, E., Long, M W., Am. Rev. Respir. Dis., 1982, 125, 265-267].
While the abovemenioned combination of first line drugs together provide treatment against sensitive M. tuberculosis infection in 4 to 6 months time, such a combination therapy is not always successful, especially in patients harbouring multi-drug resistant strains. Also the long duration of treatment consisting of six months, more often than not, leads to unpleasant side effects. Further, compliance with the relatively long course of treatment is generally poor. Such non-compliance leads, more often than not, to treatment failure resulting in development of drug resistance.
The second line drugs, such as cycloserine, clofazimine, capreomycin etc. used for treatment, on the other hand, are more expensive, may cause severe side effects and are inferior to the first line drugs.
Substituted pyrrole derivatives constitute another class of compounds, which hold promise as antimycobacterial agents. Many pyrrole derivatives have been synthesized and tested for antitubercular activity [Deidda, D., et. al., Antimicrob. Agents Chemother., 1998, 3035-3037; Biava, M., et. al., J. Med. Chem Res., 1999, 19-34; Biava, M., et. al., Bioorg. & Med. Chem. Lett., 1999, 2, 2983-2988; Cerreto, F., et. al., Eur. J. Med. Chem., 1992, 27, 701-708; Gillet, C., et. al., Eur. J. Med. Chem.-Chimica Therapeutica., 1976, 11(2), 173-181; Raagno. R., et. al., Bioorg. & Med. Chem., 2000, 8, 1423-1432]. At best, the compounds disclosed therein are drug candidates not drugs since the reports contain no mention of in vivo activity and toxicity of the compounds disclosed therein against experimental tuberculosis in animal models. Hence, the compounds are more of academic rather than any commercial interest.
Hence, there is an urgent need to develop newer regimens that can be used to prevent, treat and/or reduce tuberculosis and/or eliminate the threat of multi-drug resistant tuberculosis and/or latent tuberculosis.
An alternative regimen should be superior to the existing regimen so as to:
a) shorten the total duration of treatment and/or significantly reduce the total number of doses;
b) provide an effective treatment of the multi-drug resistant varieties;
c) provide more effective treatment of latent tuberculosis; and
d) minimize or prevent side effects.
In our PCT Application No. PCT/IN02/00189 (WO 04/026828 A1) we have described several substituted pyrrole derivatives and pharmaceutically acceptable salts thereof, which have demonstrated good to excellent inhibitory activity against the susceptible and drug resistant strains of M. tuberculosis. The MIC value of some of the most active compounds against sensitive and multi-drug resistant strains of M. tuberculosis were in the range of 0.12 to 0.5 μg/ml. Further, some of the compounds have also demonstrated therapeutically significant in vivo activity against M. tuberculosis infected animals and also found to be safe having an LD50 value of about 700 mg/kg in mice as against 133 mg/kg for isoniazid. Moreover, the pharmacokinetic profile of the compounds are excellent. The subject matter of PCT Application No. PCT/IN02/00189 (WO 04/026828 A) is incorporated herein by reference.
The present inventors have found that a number of the pyrrole derivatives disclosed in PCT Application No. PCT/IN02/00189 (WO 04/026828 A1) provide a synergistic effect when used in combination with some of the front line drugs, thereby providing a new treatment of tuberculosis, including multi-drug resistant varieties and latent tuberculosis. The treatments described herein are superior to the drug regimens known in the prior art.

Abstract: and an amount of one or more first line antitubercular drugs.