A computing device includes a charging coil for producing a charging current when placed in a magnetic field of a wireless power transmitter. A wireless charging operating frequency is associated with wireless charging of a battery of the computing device by the charging coil and the wireless power transmitter. An electrically conductive substrate has a plurality of gaps for reducing eddy currents when the electrically conductive substrate is disposed between the charging coil and the wireless power transmitter during charging of the battery. A plurality of filters each electrically bridge a respective one of the gaps. Each filter attenuates signals within a range of frequencies including the wireless charging operating frequency.

To regulate electromagnetic (EM) radiation and conduction of electronic devices, regulatory limits have been mandated by governmental agencies all over the world, such as the FCC in the U.S. and the CISPR in the E.U. In order to comply with these regulations, different techniques to mitigate EM radiation are applied to a product, ranging from board layout to filtering to shielding. One of the most common techniques to reduce EM interference (EMI) is to create some sort of metallic enclosure around the product, e.g., a Faraday cage. Such EMI reduction techniques may be difficult to deploy in a system that uses wireless charging.
A basic wireless charging system may include a wireless power transmitter unit (PTU) and a wireless power receiving unit (PRU). For example, a PTU may include a transmit (Tx) coil, and a PRU may include a receive (Rx) coil. Magnetic resonance wireless charging may employ a magnetic coupling between the Tx coil and the Rx coil. When a wireless charging module is integrated in a product, the Faraday cage approach to EMI reduction may interfere with the wireless charging.
The same numbers are used throughout the disclosure and the figures to reference like components and features. Numbers in the 100 series refer to features originally found in FIG. 1; numbers in the 200 series refer to features originally found in FIG. 2; and so on.


An apparatus for manufacturing plastics items provided with external undercuts, comprising at least one compression molding unit, which is composed of an upper male mold part comprising a plug and of a lower female mold part aligned, along a vertical axis, with the male mold part, means for actuating the mold parts between a spaced position, at which a dose of plastics sufficient to form an item is deposited in the female mold part, and a mating position for producing the compression molding of an item, the male mold part comprising a plug and an ejector that is associated with the plug in order to remove the molded item when the mold parts are in the spaced position, further comprising a bushing that is arranged externally and coaxially to the plug, a plurality of sectors for forming raised portions and undercuts on the outer surface of the item, the sectors being coupled axially to the bushing and being able to expand with respect to the plug, means for actuating the sectors between a position that produces mating with the plug in order to allow the compression molding of the item and the molding of the raised portions and undercuts, and a spaced position in order to allow to remove the molded item from the plug.

The present invention relates to a carrousel apparatus for manufacturing, by compression molding, plastics items.
Compression molding apparatuses generally comprise a carrousel, which can rotate about a vertical axis and on which a plurality of angularly spaced molding units are installed. Each unit comprises an upper male element (plug) aligned with a lower female mold part (cavity).
In order to obtain the item, a dose of semifluid plastics is introduced in the female mold part and is pressed by means of a relative movement of the two mold parts in order to obtain the item.
In the manufacture of caps for closing containers provided with internal undercuts (for example screw caps), the molded cap, after the mold parts have been opened, remains attached to the plug and is removed by means of an ejector, utilizing the elasticity of the plastics that has not yet hardened.
In the case of caps having external undercuts, it is not possible to perform removal by simply pushing downward the ejector, since the cap cannot retract inward.
The aim of the present invention is to obviate the above cited drawbacks of known devices, i.e., to provide a carrousel apparatus provided with means that allow to form items, particularly hollow items, such as caps provided with raised portions and undercuts on their outer surface.
Within this aim, an object of the present invention is to provide an apparatus in which the cap forming means assist the extraction of the molded caps from the mold.
This aim and this object are achieved by the present apparatus, whose characteristics are defined in the appended claims.

Carrousel apparatus for manufacturing, by compression molding, plastics items

Sacmi Cooperativa Meccanici Imola S.c.r.l.


A system, method, and article of manufacture for determining a productivity rate of a manufacturing system are provided. The manufacturing system has a first and second manufacturing cells. The first and second manufacturing cells has first and second machines, respectively. The method includes predicting a first cycle time indicating a time duration that a part is disposed in the first manufacturing cell. The method further includes predicting a second cycle time indicating a time duration that the part is disposed in the second manufacturing cell. The method further includes calculating a productivity rate of the first and second manufacturing system cells based on the first and second cycle times of the first and second manufacturing cells, respectively.

Manufacturing engineers generally determine a manufacturing system productivity rate by measuring a number of parts produced by a group of manufacturing cells over a predetermined time period. Accordingly, the manufacturing system productivity rate is determined after the manufacturing cells are operational. A disadvantage with this approach, however, is that if the manufacturing system productivity rate is less than a desired productivity rate, the manufacturing engineer may have to modify the manufacturing cells after the manufacturing cells have been constructed, which can delay the production date for manufacturing the part. Further, any modification to the manufacturing cells after installation thereof can result in dramatically increased expenses related to the manufacturing cells.
Accordingly, there is a need for a method of predicting a manufacturing system productivity rate prior to the construction of a group of manufacturing cells.

System, method, and article of manufacture for determining a productivity rate of a manufacturing system


A man-made caviar alternative, including granules having a gelled center in a syrup exhibiting the same organoleptic properties as caviar from sturgeon. The granules are made from a mixture of encapsulation material, salt, coloring agents and flavoring agents, and granules are formed having a size of between about 2 to 4 millimeters. The thus formed granules may be treated with firming agents, crisping agents, and antioxidants. The caviar syrup in which the granules reside is a mixture including flavoring agents, salt, and stabilizing agents.

Caviar is a popular, but rather expensive, delicacy which is often times made from the roe of sturgeon. Because of its high cost, caviar has traditionally been a food reserved mainly for the wealthy.
Unfortunately, the world""s supply of sturgeon is being depleted, due primarily to over fishing, as well as the destruction of the sturgeon""s natural habitat. Consequently, the future availability of caviar from sturgeon is uncertain; however, it seems almost certain that the price of such caviar will rise.
In light of the foregoing, many have attempted to develop an alternative dietary product similar to natural caviar. To date, these products have not been commercially successful for a variety of reasons, the most common being that these imitation products do not exhibit the same organoleptic properties, such as taste, appearance, and mouthfeel, as natural caviar. Replicating the organoleptic properties of natural caviar has proven to be difficult. For example, some imitation caviar products do not exhibit the same consistency as natural caviar or the same particle size or crispness as natural caviar. Further, some imitation caviar products are made from egg protein, a foodstuff, which is not acceptable to a large segment of the general public. Still further, problems in manufacturing non-natural caviar are frequent and include difficulty in consistently controlling the quality of the product. Lastly, many non-natural manufacturing processes are costly and are therefore not a realistic alternative to natural caviar.
It would be beneficial if a dietary man-made product could be developed which imitated the organoleptic properties of natural caviar. Such substitute or man-made caviar must be relatively easy and inexpensive to make and must maintain its organoleptic properties for extended periods of time when properly stored. It would also be beneficial if such a substitute caviar product were comprised of natural or healthy ingredients, thus increasing its appeal to a larger segment of the general public.
The present invention provides a substitute or man-made caviar whose organoleptic properties approach that of natural caviar from sturgeon. The invention also provides for a method of producing imitation caviar where the product quality is easily controlled and the cost of manufacturing is not prohibitive.
The inventive caviar is comprised of granules having shell with a gelled center, derived from an aqueous mixture containing food grade encapsulation materials, such as water-soluble carrageenans or gelatin, food grade coloring agents similar to natural caviar, food grade flavoring, water or oil having a fish flavor, and food grade sodium chloride. Other ingredients, such as food grade stabilizers, vitamins, proteins, and antioxidants may also be made a part of the granules.
The above-described mixture is introduced in the form of droplets into a food grade oil, such as mineral, vegetable, or paraffin, the temperature of which, at least in its lower layers, is below the temperature at which the droplets congeal to form granules. The thus-formed granules have an outside shell or membrane similar in hardness and crispness to natural caviar from sturgeon with a gelled center.
The granules are washed with water to remove any excess oil. The washed granules are added to an aqueous food grade solution containing water-soluble stabilizers, water or oil flavoring having the taste of fish, and sodium chloride, which form the caviar binding medium or syrup. The thus-formed, man-made caviar and binding medium in which it exists, exhibits a similar taste, mouthfeel, smell, and look of natural caviar.

Caviar alternative and method of making same


Methods, systems, and computer readable media are operable to reduce the messaging needed for efficient control of hotspot activities. A database associating hotspots, their hosting broadband home gateways and their Wireless Access Gateways (WAGs) is developed by a monitor that inspects traffic to and from the access points. The monitor provides a WAG monitoring services to the broadband home gateways that reduces the amount of network traffic, while still allowing broadband access gateways to appropriately enable to disable their hotspots with the corresponding condition of the associated WAGs.

Multiple System Operators (MSOs), also known as cable companies, as well as other service providers have been expanding their service offering to include wireless services, including hotspot services. Hotspot services allow a subscribing customer to access the Internet from a mobile device when they are away from their home. An extensive system is required for hotspot operation, including broadband home gateways or access points to provide the local wireless connection, as well as a Wireless Access Gateway (WAG) that provides hotspot management services, such as authentication, authorization, DHCP services, and others.
A hotspot service may be offered to a consumer through a wireless access point. The access point might stand alone, but more commonly service providers add wireless access points to broadband home gateways. Management of hotspot services is currently distributed. The access point associated with a broadband home gateway may be configured based on the broadband home gateway's configuration data. Management of the hotspot client services may be managed separately by a WAG.
The WAG is responsible for hotspot management functions, including admission and authentication of hotspot client devices. The WAG also provides Dynamic Host Configuration Protocol (DHCP) services for hotspot clients. Traffic to and from the hotspot clients passes through the WAG. For example, the broadband home gateway encapsulates the hotspot data coming from hotspot clients then passes the traffic back to the hotspot's WAG.
When a gateway initially connects to a broadband access network using a cable modem, it first performs a local DHCP request for an IP address, then retrieves its cable modem configuration file. One part of the configuration file may cover configuration of any internal access points, including any hotspot configuration. The hotspot configuration data typically includes information allowing the gateway to communicate with the WAG associated with that hotspot. Once a gateway has received information about how to contact the WAG and how to set up the hotspot's traffic routing tunnels, it sets up the tunnels with the WAG.
A gateway may be instructed by the WAG to periodically contact the WAG to confirm to both sides that the tunnel is operational. One example of confirmation traffic is a PING. PINGs are well known in the art as a simple IP protocol message exchange that confirms a network path exists between the device initiating the PING and the target device to which the PING was sent. Because of the large number of gateways that may connect to a single WAG, the communications path between a population of broadband gateways with hotspot services enabled and the WAG managing them may be congested with confirmation traffic. Therefore, a need exists for improving methods and systems of management and control of hotspot systems with reduced messaging.

Method of providing management and control of hotspots with reduced messaging


A tool box having a reinforced door that withstands prying and resists flexing during use. The door includes a reinforced region including a first flange, a second flange and a third flange extending from the first edge of the door. At least one additional flap extends from an edge of the door adjacent to the reinforced region and is welded to the reinforced region to provide additional strength. In another embodiment, a second and a third additional flap is included on the door, and each additional flap may be welded to an adjacent flap or welded to the reinforced region. Multiple reinforced regions, each including at least one flange, may also extend from the door body to provide increased strength.

The present invention relates generally to an enclosure for storing items. More particularly, the present invention relates to a metal box for storing tools or other hardware, especially a rectangular sheet metal box with a hinged door having a reinforced region for improving the structural rigidity of the door.
Tools, hardware and other items are commonly stored in metal enclosures, generically referred to as tool boxes, for safe-keeping during periods of non-use. Tool boxes of this type are frequently placed in garages, mounted on vehicles, or kept at outdoor work sites. In these situations, public accessibility increases the likelihood of attempts by unauthorized individuals to gain access to the items stored in the tool box. Typically, to prevent theft of stored items, a tool box includes a hinged door having a locking latch for selectively restricting access to the contents of the tool box. Unauthorized individuals aimed at gaining access to the stored contents of a tool box may attempt to forcefully disengage the lock and pry the tool box open using an instrument, such as a crowbar or hammer, inserted between the edge of the tool box door and the body of the tool box. Generally, the edge of the door nearest the latch is a common target of these attempts. Such attempts may permanently deform both the tool box door and the tool box body, thereby leaving gaps between the door and tool box body, allowing theft of the stored items or permitting rain and debris to enter the enclosure, causing further damage to any remaining items.
A tool box may also be used as a work space for performing tasks, such as hammering, sanding, sawing, cutting or bending, on a work piece. Generally, these tasks involve the repeated application of force to a work piece. Such tasks are commonly performed using the edge of the tool box adjacent to the door to support the work piece. For example, at a construction site a worker may open a tool box door, remove a tool, close the tool box door and then begin hammering or cutting a work piece using the closed toolbox as a work space to support the work piece. Typically, such use takes place on the side of the tool box nearest the door because the user is naturally positioned on that side upon retrieval of a tool from inside the tool box. Further, where the tool box is mounted on a bench or vehicle, the side of the tool box including the door may be the only region accessible for use as a work space. This type of activity may be repeated multiple times, causing tool box doors to experience accelerated wear. Repeated high-impact use can cause injury to the user if the tool box door bends or flexes during such use, causing the work piece to unexpectedly move.
The ability of a tool box to withstand prying and deformation depends greatly on the mechanical strength and rigidity of the door. Others have attempted to produce tool box doors with improved strength by increasing the thickness of the door material. Although thicker material is more resistant to prying and bending, the use of thicker material increases the cost of production and adds weight to the tool box. Prior art tool boxes also include a rectangular sheet metal door bent at the edges to form a rim extending from the door. Conventional tool box doors often flex and deform when used as a work space for high-impact activities. Similarly, a single perpendicular rim does not effectively withstand attempts to pry the door open.
Thus, there is a need for a tool box with a reinforced door having increased rigidity for withstanding prying and resisting flexing during use.

This patent is subject to a terminal disclaimer.


A bladder external to a fuel tank of a vehicle that allows an operational range of the vehicle to be increased. Preferably the bladder is external to the rest of the vehicle and the vehicle is an aircraft. The external bladder allows fuel in the fuel tank to expand and contract without requiring additional space within the vehicle, thus allowing more fuel mass to be held by the vehicle and a smaller vehicle profile that is more aerodynamically efficient. More preferably, the bladder is disconnectable from the rest of the vehicle to allow increasing of aerodynamic efficiency and weight reduction during use.

Aircraft use a variety of materials to provide energy to mobilize the aircraft. Often, aircraft use fuel tanks to supply a liquid fuel to an engine that allows mobilization of the aircraft. The fuel tanks typically have a maximum capacity that is fixed while a fuel held in the fuel tank may have a variable volume that changes during transportation and use of the aircraft.
Air-breathing-engine fuels (e.g., JP-10, JP-8, JP-7, and JP-5) used in various vehicles, such as aircraft (e.g., cruise missiles, UAVs, Drones, Decoys, and Aerial Target vehicles), have densities that vary as a function of temperature. This causes the fuel volume to expand as the system is exposed to heat or contract when exposed to cold temperature extremes. For example, over a change in temperature of 111.1° C. (200° F.) (e.g., −51° C. (−60° F.) to 60° C. (140° F.)) JP-10 fuel will change in volume approximately 8%. The volumes of JP-8, JP-7 and JP-5 vary by 10% or more over the same temperature range.
In the past fuel tanks have included ullage space within a fuel tank to allow for expansion and contraction of the fuel. This generally results in fuel volume constraints on the system due to tank sizing limits. In vehicle design a goal is to maximize fuel within the available volume. At a maximum temperature the fuel may expand to the maximum capacity of the fuel tank and the ullage would be at zero. As the fuel cools the volume of the fuel reduces and the volume of the ullage space increases.
Referring to FIG. 1, in the past a fuel tank 1 included fuel 2 and a rubber inner bladder 3 to interface between the fuel tank 1 and the exterior environment. The rubber inner bladder 3 prevents leakage of fuel from the fuel tank 1 and provides for ullage volume increase and decrease resulting from temperature variation. The rubber inner bladder 3 separates atmospheric air from the fuel 2 and acts as an expanding and contracting balloon that remains within the fuel tank 1 to provide for the ullage volume changes. The rubber inner bladder 3 cannot significantly protrude outside of the fuel tank 1 past a position shown under a high temperature condition 4. Rigid walls of the fuel tank 1 and a small opening to atmospheric air prevent the rubber inner bladder 3 from significantly protruding outside, which limits the total mass of the fuel 2 the aircraft can hold when subjected to the high temperature condition 4.
Under the high temperature condition 4 the fuel 2 is at a maximum volume and the rubber inner bladder 3 is at its smallest ullage volume. Under a medium temperature condition 5 the fuel 2 is slightly contracted and the rubber inner bladder 3 expands with air to fill the volume within the fuel tank 1 that was created by the contraction of the fuel 2 due to the reduction in temperature. Under a low temperature condition 6 the fuel 2 contracts more than the medium temperature condition 5 and the rubber inner bladder 3 expands with air further filling the available volume in the fuel tank 1. In all three temperature conditions 4, 5, and 6 the mass of the fuel is the same, but the volume the fuel occupies changes and the mass of air inside the fuel tank changes due to changes in the fuel's density. The fuel tank 1 with the rubber inner bladder 3 design must be under-filled at ambient temperatures to account for fuel expansion at higher temperature conditions, such as the high temperature condition 4, because the rubber inner bladder 3 cannot expand outward of the fuel tank 2. These higher temperature conditions generally occur during transport or storage, thus resulting in wasted ullage space within the fuel tank during operation in typical environments.
Normally refuelable fuel system include venting and refuel ports and are open to the environment. In some aircraft the fuel is isolated from the surrounding environment to isolate the fuel from water and air intrusion, which can cause the fuel to develop mold or allow fuel vapor to evaporate over time.

External-bladder fuel system fluidly connectable to a fuel tank to receive excess


Method and apparatus for drip irrigation having a water supply tank connected to a constant water level tank by a drain pipe having a drain opening. A supply tube extends from the constant water level tank and is connected to a supply tank with an open top located inside of an air tight casing. The casing contains fillers and has its bottom open to the soil. The system is applicable to irrigate farms and potted plants.

Irrigation has been considered as one of the important keys for the maintenance of races since olden days. However, the majority of water secured by hard labor, has been returned back into the soil uselessly.
Recently, dripping methods of irrigation have been used in foreign countries where dry regions occupy the greater part of land. However, since these methods require electric power and special equipment, these methods are employed in limited places.
Miscellaneous devices have been realized since olden days in the effectual utilization of irrigated water in order to maintain the prosperity of races.
However, in order to maintain the population which is increasing day by day, the development of effective irrigated water is now keenly urged in consideration of the limited efficiency of prior irrigated water.
The dripping method of irrigation was practically used for the first time by Symcha Blazs in 1930 and has greened many deserts and barren lands.
However, since the dripping method of irrigation requires flow control equipment, electrical solenoid valves, and timers, it still has problems and troubles unavoidable in such a system and also economical burdens.


A portable seat assembly for safely securing an occupant such as a child within a vehicle is provided. The portable seat assembly readily converts between an expanded state and a collapsed state. In the expanded state, the portable seat assembly can secure the occupant in the vehicle. In the collapsed state, the portable seat assembly is readily carried and/or stowed by a user.

Child seats for safely securing a child occupant inside a vehicle are known in the art (see, e.g., U.S. Pat. No. 7,954,895 assigned to Britax Excelsior Limited (GB), the entire disclosure of which is herein incorporated by reference). Typically, child seats are situated on and secured to seats that are installed in the vehicle. These installed seats and/or their restraints (e.g., belts) are generally not sized appropriately for the child occupant, thereby necessitating use of the child seats. Given their construction, child seats are often rigid, heavy, bulky items that are not readily portable over a considerable distance. Thus, there is a need for an improved child seat for safely securing a child occupant inside a vehicle, wherein the child seat is also readily portable.


An LED epitaxial structure includes a substrate, a buffer layer, a functional layer and a light generating layer. The buffer layer is located on a top surface of the substrate. The functional layer includes a plurality of high-temperature epitaxial layers and low-temperature epitaxial layers alternatively arranged between the buffer layer and light generating layer. A textured structure is formed in the low-temperature epitaxial layer. A SiO2 layer including a plurality of convexes is located on the textured structure to increase light extraction efficiency of the LED epitaxial structure. A manufacturing method of the LED epitaxial structure is also disclosed.

1. Technical Field
The disclosure is related to a light emitting diode (LED) epitaxial structure and a manufacturing method of the same, and particularly to an LED epitaxial structure having good light emitting efficiency and the manufacturing method of the same.
2. Description of Related Art
Light emitting diodes (LEDs) are technologically and economically advantageous solid state light sources. LEDs are capable of reliably providing light with high brightness, hence in the past decades they have come to play a critical role in numerous applications, including flat-panel displays, traffic lights, and optical communications. The conventional procedures for producing LEDs are primarily to epitaxy a layered light emitting structure with pn junction on a sapphire substrate. The performance of such LEDs is seriously degraded by the presence of threading dislocations, which thread vertically through the epitaxial layers. In particular, when a sapphire substrate is used, it does not dissipate heat efficiently and there is a strong tendency of light emission efficiency not to increase linearly in proportion to an input, but to be saturated halfway. It is known in the art that the light emission from electroluminescent devices or from LEDs is limited by the total internal reflection occurring at the surface between the semiconductor substrate wherein the device is fabricated and the surrounding medium. Therefore, what is needed is an LED structure that reduces the amount of emitted light that is lost through various loss mechanisms, thereby increasing the overall output of the device.

Light emitting diode epitaxial structure and manufacturing method of the same

Advanced Optoelectronic Technology, Inc.


A closed bioreactor for high organic carbon removal and ammonia conversion in high-strength wastes under microgravity conditions. Oxygen is provided to the bioreactor by diffusion through a non-porous hydrophobic membrane in a recirculation line, allowing a high rate of oxygen transfer while minimizing the opportunity for formation of bubbles. Operating the bioreactor as a closed unit at elevated pressures keeps the oxygen in the dissolved phase. The oxygen transfer within the reactor is thus much more efficient and uniform than in similar reactors having both a liquid and gaseous phase.

Biochemical oxidation of carbonaceous and nitrogenous substrates, in aqueous waste streams, is typically mediated by microorganisms capable of catalyzing the oxidative processes under conditions ranging from strict aerobiosis to strict anaerobiosis. The selection of the specific process environment depends on the nature of the substrates, their concentration and treatment objectives. High strength wastewater is characterized by high substrate concentrations, as measured by the chemical oxygen demand (COD) or the five-day biochemical oxygen demand (BOD5), and high nitrogen content, as measured by ammonia-, nitrite- or nitrate-nitrogen. Conversion of BOD5 to carbon dioxide and water, and transformation of ammonia to nitrite and nitrate in a process termed nitrification, requires a supply of oxygen sufficiently high to satisfy the stoichiometric requirements of these processes.
Biological processing of high strength wastewater in terrestrial or space environments presents serious challenges, stemming mainly from mass transfer limitations of substrate and oxygen. Further, a major issue in space applications is the absence of gravity which introduces problems associated with separation between solid-liquid and liquid-gas phases.
Immobilized, cell packed bed bioreactors (ICPB) have been used extensively for the treatment of wastewater on earth and can provide solutions to problems associated with microgravity. Conceptual models of advanced life support (ALS) integrated systems design mandate approximately 100% closure with respect to the water loop Drysdale A. E., et al., xe2x80x9cA More Completely Defined CELSSxe2x80x9d, SAE Paper 941292, 24th International Conference on Environmental Systems and 5th European Symposium on Space Environmental Control System, Friedrichshafen, Germany, Jun. 20-23, 1994.). Water reclamation from various aqueous streams and reuse is thus imperative. Water rich liquid streams in space/space vehicle habitats include washwater, utility water (food preparation, laundry), urine and condensate water. Mixtures of the first two streams (washwater, utility water) are commonly termed greywater. Estimated quantities of urine and greywater vary in the range of between 1.3-2.1 liters of urine waste and 20-30 liters of greywater waste per person per day. (Wieland P. O., xe2x80x9cDesigning for Human Presence in Space: An Introduction to Environmental Control and Life Support Systemsxe2x80x9d, NASA Reference Publication 1324, 1994.; Wydeven T. and Golub M. A., xe2x80x9cGeneration Rates and Chemical Composition of Waste Streams in a Typical Crewed Space Habitatxe2x80x9d, NASA Technical Memorandum 102799, Ames Research Center, 1990). With the exception of condensate water which is low in organic content, the other liquid streams contain varying amounts of organic loads and require treatment prior to any possible reuse. Various reuse scenarios include utilization of the reclaimed water as hydroponic solution water, utility water, or potable water. Evidently, each of these reuse scenarios dictates and sets the desired treatment objectives. These objectives include, but are not limited to: organic carbon removal, nutrient reclamation and reuse in hydroponic solutions, and water reclamation. Essentially the first two objectives can be summarized as carbon oxidation and nitrification. Research conducted over the last ten years has shown that biological processes for treatment of urine, condensate, and grey water combined streams have a demonstrated potential for use as a primary water processor (Petrie G. E., et al., xe2x80x9cDevelopment of Immobilized Cell Bioreactor Technology for Water Reclamation in a Regenerative Life Support Systemxe2x80x9d, SAE Paper 911503, 21st International Conference on Environmental Systems, San Francisco, Jul. 15-18, 1991; Petrie G. E., et al., xe2x80x9cImmobilized Cell Bioreactors for Water Reclamation: Process Stability and Effect of Reactor Designxe2x80x9d, SAE Paper 921227, 22nd International Conference on Environmental Systems, Seattle, Jul. 13-16, 1992.) or a trace polisher in an integrated bioregenerative life support water recovery system (Miller G. P. et al., xe2x80x9cFurther Applications of the Use of Biological Reactors to Remove Trace Hydrocarbon Contaminants from Recycled Waterxe2x80x9d, SAE Paper 921273, 22nd International Conference on Environmental Systems, Seattle, Jul. 13-16, 1992; Miller G. P. et al., xe2x80x9cUsing Biological Reactors to Remove Trace Hydrocarbon Contaminants from Recycled Waterxe2x80x9d, SAE Paper 911504, 21st International Conference on Environmental Systems, San Francisco, Jul. 15-18, 1991). Because of the well established performance reliability, small energy and volumetric requirements, various configurations of immobilized cell bioreactors have been preferred over their suspended growth counterparts. Collaborative work performed by NASA and aerospace contractors has focused on immobilized cell bioreactors operating as plastic media packed beds. Two-stage packed bed bioreactors containing porous and non-porous plastic media accomplishing carbon oxidation in the first stage and nitrification in the second were initially studied (Verostko C. E., et al., xe2x80x9cA Hybrid Regenerative Water Recovery System for Lunar/Mars Life Support Applicationsxe2x80x9d, SAE Paper 921276, , 22nd International Conference on Environmental Systems, Seattle, Jul. 13-16, 1992). The performance of these reactors with respect to both chemical oxygen demand (COD), and urea degradation at hydraulic retention times (HRT) in the range of 24-48 hr was satisfactory (greater than 97% and 99%, respectively) but decreased significantly for HRTs in the range of 12-24 hr (65% and 91%, respectively) (Petrie G. E., et al., xe2x80x9cImmobilized Cell Bioreactors for Water Reclamation: Process Stability and Effect of Reactor Designxe2x80x9d, SAE Paper 921227, 22nd International Conference on Environmental Systems, Seattle, Jul. 13-16, 1992). An immobilized cell bioreactor (ICB) essentially consisting of a foam covered plate reactor was also studied in parallel. The parallel plate reactor performance was over 95% and 99% total organic carbon (TOC) and urea reduction for all HRTs in the range of 12-24 hours. Full-scale experiments for both bioreactor types verified previous findings (Nacheff-Benedict M. S. et al., xe2x80x9cAn Integrated Approach to Bioreactor Technology Development for Regenerative Life Support Primary Water Processorxe2x80x9d, SAE Paper 941397, 24th International Conference on Environmental Systems and 5th European Symposium on Space Environmental Control System, Friedrichshafen, Germany, Jun. 20-23, 1994).
Immobilized cell bioreactors with packed or fluidized bed, provide a unique environment for microbial growth resulting in high biomass concentrations. Packing materials commonly used include ceramic saddles, stainless steel wire spheres, polypropylene toroids, reticulated polyester foams, matted reticulated polypropylene sheets, polypropylene strands and sand. The main features of immobilized cell bioreactors are the support media for microbial attachment with larger surface area which are better for conversion efficiency; the absence of a microbial wash-out flow-rate, and the elimination of the need for concentrated biomass recycle from a clarifier. The advantages of these reactor configurations over conventional, completely stirred tank reactors (CSTR) systems for organic removal and nitrification/denitrification are well established. Biomass concentrations as high as 5-40 g/L of reactor volume have been reported when using solid support particles (Cooper, R. F. and B. Atkinson. Editors of: Biological Fluidized Bed Treatment of Water and Wastewater. Ellis Horwood Limited Publishers, 1981). High biomass concentrations greatly enhance process efficiency resulting in substantial reductions in treatment time and reactor volume. ICBPs can operate both in aerobic and oxygen limiting modes. A major problem with the operation of such aerobic reactors is oxygen distribution and gaseous by-product formation. Phase separation in packed beds under microgravity conditions, has been a major problem.
Greywater generated in closed environments such as a space station, a space vehicle or a submarine contains high concentrations of biodegradable carbon compounds and nitrogen in the form of various amino acids and urea. Liquid wastes generated from various farming activities also have high levels of carbon and nitrogen and are difficult to treat by conventional aerobic processes. For instance, liquid swine wastes are characterized by high BOD5 and COD strengths. This high strength wastewater exerts a high oxygen demand on the treatment system if complete conversion to innocuous products is to be realized. Typical concentrations of carbon and nitrogen in greywater are in excess of 800 mg/L BODS, and 500 mg/L of ammonia-nitrogen(NH3-N), respectively. These concentrations are substantially higher than the corresponding BOD5 and ammonia concentrations observed in municipal wastewater. Conventional attached growth systems such as trickling filters and packed bed bioreactors, operating at atmospheric conditions, cannot effectively cope with the mass transfer demands, in terms of substrate and oxygen, that are required for efficient treatment of high strength wastewater. In addition, these systems operate in a three phase mode meaning that the solid, liquid and gaseous phases coexist in the packed bed bioreactor unit, which makes phase contact and separation impossible under microgravity conditions. Most biological processes currently in operation require a solid-liquid separator after the bioreactor, in order to separate the biomass from the treated effluent prior to discharge.
U.S. Pat. Nos. 5,403,487, 5,463,176, 5,543,039, 5,686,304, and 6,132,602 describe various approaches which enhance oxygen transfer and process performance in attached growth packed bed bioreactors. U.S. Pat. No. 5,543,143 describes generation of microbubbles for enhanced oxygen transfer. U.S. Pat. No. 5,997,736 describes nitrogen conversion by specific microorganisms. U.S. Pat. No 4,192,742 describes a system wherein wastewater is passed through a pressurization tank and a gas tight biological filter bed. The liquid in the first tank comes into direct contact with an oxygen-containing gaseous phase above it. The oxygenated wastewater is then introduced to the biological filter, which also operates under pressure, and is subsequently discharged to the environment. Both the oxygenation tank and the biological filter operate with a gaseous headspace, thus forming a two-phase system, which makes them unsuitable for microgravity operation. Moreover, the single-pass of the wastewater through the biological filter limits the performance of the system for the treatment of high strength streams. Another limitation of this system is that oxygen exchange occurs through the interface of the liquid and gas phases which is fixed by the dimension of the chamber.
Another method widely used in the biological treatment of wastewater by attached growth bioreactors, is the recycling of a portion of the effluent to a point upstream of the oxygenation device. This approach also enhances oxygen transfer and improves the overall performance of the system, but becomes uneconomical for the treatment of large volumes of wastewater when the operation is carried out using air at atmospheric pressure. Further, this approach suffers from similar limitations to pressurized two-phase systems during treatment of high strength streams and in the absence of gravity.
Therefore, there is a need for an improved biological method and apparatus for treatment of high strength wastewater in terrestrial and microgravity environments.
An object of the present invention is to provide an apparatus for wastewater treatment comprising at least one immobilized cell packed bed bioreactor, and at least one membrane oxygenation module attached to an external recirculation line.
Another object of the present invention is to provide a system for treating wastewater comprising at least one immobilized cell packed bed bioreactor, and at least one membrane oxygenation module attached to an external recirculation line.
A further object of the present invention is to provide a method of treating wastewater containing organic carbon and ammonia using the apparatus of the present invention by removing organic carbon and nitrifying high strength wastewater.

Method and apparatus for treatment of wastewater

Trustees of Stevens Institute of Technology


Water-soluble supramolecular complexes formed from a water soluble block copolymer and at least one associative gelling adjuvant. The copolymer includes at least two blocks of polyethylene oxide and at least one block of polypropylene oxide. The adjuvant has a water solubility less than 0.5 g/100 ml at 20° C. When combined with water, the complexes form a transparent reversely thermo-reversible hydrogel or solution that may be repeatedly hydrated and dehydrated. The hydrogel exhibits improved gelling efficiency and enhanced solubility and/or stability for sparely soluble and insoluble pharmaceutical agents. The complexes are useful in a variety of pharmaceutical and cosmetic products and applications and may be combined with an effective amount of a cosmetic, medicament, or diagnostic in a solid dosage form.

The field of applying active ingredients to humans and animals is, of course, wide ranging and comprises for example, the delivery and application of active ingredients for pharmaceutical and cosmetic purposes. It is specifically desirable to provide such compositions that are capable of solubilizing and stabilizing water insoluble or sparely soluble active ingredients in water.
Supramolecular Chemistry has expanded the scope of Chemistry allowing for the design and development of smart and functional materials. While traditional synthetic molecules are covalently-linked molecules or macromolecules, supramolecular complexes contain non-covalent binding on the association of two or more building blocks which are held together by intermolecular bonds, such as hydrogen bonding, dipole-dipole interactions, van der Waals forces, cation-pi interactions, pi-pi bonds, CH/pi interactions, or hydrophobic effects, and etc. showing inclusion, selectivity and other functionality.
Reversely thermo-reversible gelling systems are known in which the solution viscosity increases and decreases with an increase and decrease in temperature, respectively. Such system exhibits a solution to gel (sol-gel) transition which transforms a low viscosity solution to a higher viscosity gel form as the temperature increases, with continued increases in temperature, the gelled system then experiences a gel to solution (gel-sol) transition which transforms the gelled system back to a liquid solution. Such reversely thermo-reversible gelling systems are useful wherever it is desirable to handle a composition in a liquid state, and/or the performance of the composition in a gel form.
A known material with these properties is a reversely thermo-reversible hydrogel using water soluble block copolymers of polyethylene oxide and polypropylene oxide available commercially as Pluronic® from BASF (Ludwigshafen, Germany) and generically known as Poloxamers. Generally, about 20% w/w Pluronic® F127 aqueous solution is liquid when at or below about 25° C. or heated to temperatures exceeding 70° C., but turns into gel form and exhibits maximum viscosity in the range of 30-60° C. (see 2006 BASF Technical Bulletin entitled "Pluronic® F127 surfactant viscosity as a function of temperature & concentration"; and April 2010 "Lutrol® L and Lutrol® F-Grades"). Typically, concentrations of Pluronic® F127 polymer of at least 18-20% by weight are needed to produce a sol-gel transition temperature at about 25° C., room temperature range. To decrease the desired sol-gel transition temperature further below 25° C., a higher concentration of Poloxamer polymer has to be used which in turn increases the viscosity of solution and results in unfavorable physiological interaction during use. The freedom to use Poloxamer polymers with adjustable sol-gel transition temperatures, specifically, at temperatures below about 25° C. without employing higher concentrations of polymer, is limited.
U.S. Pat. Nos. 4,188,373, 4,478,822 and 4,474,751 disclose the use of nonionic block copolymers of polyethylene oxide and polypropylene oxide Poloxamers in aqueous pharmaceutical compositions. In these systems, the concentration of polymer is adjusted to give the desired sol-gel transition temperature. However, concentrations of the poloxamer polymer of at least 18-20% by weight are needed to produce a composition which exhibits such a transition at commercially or physiologically useful temperatures. Also, solutions containing more than 18-20% by weight of block copolymer at the desired sol-gel transition temperature are typically very viscous even in the "liquid" state. In addition, the high polymer concentrations may cause unfavorable physiological interactions with target tissue during use.
U.S. Pat. No. 5,256,396 to Piechota et al. discloses an oral composition of a water dispersible active ingredient with the use of Pluronic F127. These compositions are flowable liquids below 82° F. (27.8° C.), and gels when heated to 82° F. (27.8° C.).
U.S. Pat. No. 5,252,318 to Joshi et al. discloses reversible gelling compositions which comprise a blend of a pH-sensitive gelling polymer and a thermo-sensitive gelling polymer, such as Pluronic F 127. The sol-gel transition temperature adjustment has been achieved at relatively low Pluronic F127 polymer concentrations upon simultaneous change in temperature and pH.
U.S. Pat. No. 6,316,011 to Ron et al. discloses a reversely thermo-sensitive gelling composition comprising an end-modified block copolymer of polyethylene oxide and polypropylene oxide, the composition reversibly gelling at a temperature in the range of 22° C. to 40° C.
The references cited above are generally concerned with reversely thermo-reversible hydrogel compositions which are in a liquid state at room temperature or below, subsequently transform to a gel form when warmed to body temperature after application, and have to employ a high concentration of polymer. However, for many pharmaceutical and cosmetic products and applications, a gel form hydrogel composition is more preferred under use conditions, i.e. in the form of a gel at room temperature. In addition, the liquid state of such systems at room temperature presents a lot of challenges in regard to the solubility and/or stability of sparely soluble or insoluble active ingredients in such aqueous liquid solutions. For example, the use of salicylic acid or its derivatives for treating dandruff, acne, skin wrinkling, skin pigmentation, warts, freckles, or skin-related problems is well known in the preparation of dermatologic and cosmetic formulations. Salicylic acid and its derivatives are usually in crystalline form and are not sufficiently soluble in water or oils traditionally used in dermatological and cosmetic preparations. Typical problems that occur when using salicylic acid or its derivatives in making dermatologic and cosmetic products are that the salicylic acid and its derivatives tend to crystallize out within various compositions, which significantly reduces the bioavailability of salicylic acid and its derivatives for treating or preventing the aforementioned skin problems. Further, salicylic acid and its derivatives provide formulations that form crystals on standing and precipitate out within the solution, which is unpleasant with regard to texture and appearance from the consumer's viewpoint.
U.S. Pat. No. 8,865,143 to Lu et al. discloses reversely thermo-reversible hydrogel compositions comprising water soluble block copolymers of polyethylene oxide and polypropylene oxide and at least one associative gelling adjuvant in a temperature range of 4-45° C. The hydrogel compositions disclosed in this reference have substantial water weight, which make shipping and handling difficult and expensive, and it is not known from this reference how to overcome this disadvantage.
Accordingly, there remains a need for improved delivery compositions comprising water soluble block copolymers of polyethylene oxide and polypropylene oxide for solubilizing water insoluble or sparely soluble active ingredients, particularly reversely thermo-reversible hydrogel or solution compositions comprising such block copolymers of polyethylene oxide and polypropylene oxide, which have extended gel form under use conditions, specifically at below room temperature, and have acceptable or improved solubility and/or stability for sparely soluble or insoluble active ingredients at relatively low polymer concentration, useful for pharmaceutical and cosmetic products and applications.


An electro-optical device includes: a first substrate; a second substrate having one surface opposite to the first substrate; a support member configured to hold the first and second substrates with the second substrate located outside the first substrate, and to include a frame portion surrounding the first and second substrates; a first conductive film formed on the other surface of the second substrate; and a conductor layer placed between the frame portion and the first and second substrates, and electrically connected to the first conductive film. The first conductive film is held at a constant potential via the conductor layer.

The present application relates to an electro-optical device including an insulating opposite substrate, a surface of which is opposite to a device substrate and formed with no wiring or electrode, and electronic equipment including the electro-optical device.
Electro-optical devices, in which no wiring or electrode is formed on an opposite substrate arranged opposite to a device substrate formed with signal lines, pixel electrodes, and pixel switching elements, include a liquid crystal device based on the IPS (In Plane Switching) system or the FFS (Fringe Field Switching) system. In the liquid crystal device, the opposite substrate is arranged outside the device substrate, i.e., on the output side of display light. Therefore, the opposite substrate is easily charged, and the charging disturbs the orientation of liquid crystal. In view of this, a method has been proposed which forms a front surface-side conductive film on the outer surface of the opposite substrate and brings the front surface-side conductive film into contact with a metal outer frame, to thereby have the opposite substrate held at the ground potential and prevented from being charged (see Japanese Unexamined Patent Application Publication No. 2005-43901).

Electro-optical device and electronic equipment


Cardiac ablation systems include vacuum-stabilized, irrigated ablation devices that have ablating elements capable of providing regions of relatively low pressure to maintain the ablating element in a stable position relative to the tissue, or minimize relative movement of the ablating element relative to the tissue. The ablation elements have integrated structures for vacuum-stabilization. The devices also include one or more electrodes for both orienting the ablating element as well as for diagnostic purposes.

a. Field of the Invention
The present disclosure pertains generally to an electrophysiological device and method for providing energy to biological tissue and, more particularly, to an ablation system that uses vacuum stabilization to provide greater contact between an ablation element and tissue.
b. Background Art
The heart beats or contracts when an electrical impulse originating from the sinoatrial node (SA node) travels through the right and left atria, and then activates the atrioventricular node (AV node). From the AV node, the electrical impulse travels through the right and left ventricles via a group of specialized fibers called the His-Purkinje fibers. The impulse causes synchronized contraction of the chambers of the heart. Cardiac conduction irregularities, or any change from the normal sequence of electrical impulses, can cause various arrythmias, such as atrial fibrillation, atrial flutter and certain ventricular arrhythmias. These conditions can decrease cardiac output and reduce tissue perfusion to the detriment of a subject.
Cardiac ablation is a procedure for treating various arrythmias by selectively damaging heart tissue in the region where aberrant or abnormal electrical activity is occurring. The damaged tissue blocks the aberrant pathways and restores normal heart rhythm. Various energy delivery schemes may be used, including, but not limited to, cryogenic ablation, radiofrequency (RF) ablation, laser ablation, ultrasound ablation, and microwave ablation. Ablation devices are used to create linear lesions or tiny scars that cut-off or disconnect the abnormal electrical pathway.
Ablation procedures rely on stable contact between the medical device and the cardiac tissue. For certain ablation procedures, such as a left atrial pulmonary vein isolation (PVI) procedure, the epicardial surfaces of posterior portions of a heart must be accessed. To reach such surfaces from an anterior location (e.g., via a minimally invasive subxiphoid incision) requires the catheter, in particular the distal portion of an elongate catheter, to traverse a tortuous route to reach target tissue. Establishing adequate contact with the target tissue to successfully perform a PVI (i.e., create a continuous lesion or set of connected lesions around one or more pulmonary veins) presents challenges to the practitioner. Furthermore, in some transvenous catheter applications, the point of electrode-tissue contact is as far as about 150 cm away from the point of application of force. In some catheter applications, the point of electrode-tissue contact is as far as about 150 cm away from the point of application of force. These challenges give rise to functional and theoretical challenges associated with conventional devices, and thus, the ability to accurately stabilize the device at the point of contact with a line of target tissue is increasingly important. Applying a vacuum at the point of contact has been contemplated for adhering the device to tissue.
There is a need for electrophysiological devices that provide greater contact stability for control of medical treatments.
There is a need for improved RF electrode ablation elements that provide greater stability, i.e., limit relative motion between the ablating element and the tissue at the point of contact.

St. Jude Medical, Artial Fibrillation Division, Inc.


The invention relates to methods of making modular chimeric protein expression products and compositions utilized in the methods. In particular, the invention relates to sequential, directional cloning of polynucleotides encoding polypeptide modules. Each clonable element or module contains an open reading frame of interest flanked by predetermined restriction sites. The methods include using modules and vectors containing these modules as starting materials for recombinant DNA techniques. One advantage of the invention is that it allows for many variations of fusion proteins to be made quickly and easily without needing to design and evaluate each subsequent cloning step.

Recombinant DNA technologies and molecular biological methods of cloning nucleic acids are known in the art. Such methods include manipulating nucleic acids using restriction endonucleases, ligases, nucleotide/nucleoside kinases and phosphatases, polymerases, and other molecular biology tools to generate desired recombinant nucleic acids. Several laboratory manuals have been written as reference books for molecular biology researchers. Examples of these reference manuals include, Sambrook, J., E. F. Fritsch and T. Maniatis, 1989. Molecular Cloning: A Laboratory Manual, 2nd. ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press; and Joseph Sambrook and David Russell, 2001. Molecular Cloning: A Laboratory Manual, 3rd ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press.
A problem in the art is the lack of methodology to engineer chimeric protein expression products where modular elements can be easily inserted at desired positions within a chimera. In general, while hybrid or chimeric proteins have been made successfully, the goal of synthesis has been towards final endpoint products, without building-in a predetermined mechanism to add more modules. An aspect of the invention addresses this problem by contemplating the future need for chimeras and variations thereof and making it possible to build them without starting from scratch for each one. One embodiment of the invention generally relates to methods of making fusion protein expression products. Another embodiment of the invention relates to methods of making fusion protein expression products with pre-engineered modules. Another aspect of the invention relates to building block molecules or modules, where modules are pre-designed to be capable of insertion into a chimeric protein expression cassette. The instant invention also contemplates libraries of engineered modules that can be utilized in the disclosed methods. In one embodiment, modules are made with predetermined restriction sites.

Methods of making modular fusion protein expression products


A magnetoresistive head having a structure based on a two-layer film having a first film exhibiting a magnetoresistive effect and a second film comprising Nb and at least one element selected from the group consisting of Ti, Cr, Mo, Zr, W, Pt, Re, V, Hf, Ta, Rh, Ni and Ru as an additive element.

The present invention concerns a magnetic head for magnetic recording apparatus and, particularly, it relates to an improvement in Nb materials used therefor and provides a magnetoresistive head suitable for reading for high density magnetic recording.
The Nb material in the present invention is used, particularly, for a shunt film of a magnetic head using a shunt bias type magnetoresistive device having a shunt film for the application of bias. Further, it is also used as an intermediate film between a soft magnetic film and a magnetoresistive film of a magnetic head using a soft bias type magnetoresistive device having a soft magnetic film for the application of bias.
For the shunt film in existent shunt bias type magnetoresistive heads, there have been used, for example, Ti, Ta, Mo, Nb or the like as described in U.S. Pat. No. 4,663,684, Ti, Cr, Ta, Zr, Hf, TiW alloy or the like as described in U.S. Pat. No. 4,914,538 and Cr, Ta, W, Nb or the like as described in U.S. Pat. No. 5,005,096.
For a magnetoresistive film, a Ni-Fe alloy film, Ni-Co alloy film or Ni-Fe-Co film is used usually, and a shunt film is used together with the magnetoresistive film in the state of a dual layer film. Usually, an electric current greater than 10.sup.6 A/cm.sup.2 is supplied and shunted into each of the films, to generate a bias field in the shunt film and cause a resistance change in the magnetoresistive film due to magnetic resistance.
As the properties required for the shunt film, it has to satisfy such conditions that it has an appropriate electric resistance value relative to the magnetoresistive film so as to provide current shunting that causes an optimum bias field in the dual layer film with the magnetoresistive film, causes no reaction as deteriorating the magnetoresistive film in the manufacturing step of a magnetoresistive device, has excellent corrosion resistance and an easy film forming property and shows less scattering of the electric resistance.
Further, as a bias field generation means, there is a soft bias type magnetoresistive head using a soft magnetic film and having a three-layer structure consisting of a soft magnetic film, a spacer metal film and a magnetoresistive film. As the prior art, there can be mentioned U.S. Pat. Nos. 4,663,685 and 5,001,586.
However, in such a three-layer structure, it is useless that a current flows to the soft magnetic film, and high specific resistivity is desired for the spacer metal film in order to prevent the reduction of the current flowing in the magnetoresistive film. Further, It is of course required also for the spacer metal film that the film has reaction resistance, corrosion resistance and easy film forming property, and has no scattering of the electric resistance as described above.


The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, the present invention relates to immunogenic compositions and vaccines comprising detoxified pneumolysin adsorbed onto aluminium phosphate and an improved process for the adsorption of detoxified pneumolysin onto aluminium phosphate. It additionally relates to the use of the immunogenic compositions and vaccines in the treatment or prevention of Streptococcu pneumoniae infection.

Streptococcu pneumoniae (S. pneumoniae) is a Gram-positive bacterium responsible for considerable morbidity and mortality (particularly in infants and the elderly), causing invasive diseases such as bacteraemia and meningitis, pneumonia and other non-invasive diseases, such as acute otitis media. About 800,000 children die annually due to pneumococcal disease, especially in emerging countries (O-Brien et al. 2009 Lancet 374:893-902). The increasing number of antibiotic-resistant strains (Linares et al. 2010 Cin. Microbiol. Infect. 16:402-410) and the severity of pneumococcal diseases make vaccination the most effective intervention.
The major clinical syndromes caused by S. pneumoniae are widely recognized and discussed in standard medical textbooks (Fedson D S, Muscher D M. In: Plotkin S A, Orenstein W A, editors. Vaccines. 4th edition. PhiladelphiaWB Saunders Co, 2004a: 529-588). For instance, Invasive Pneumococcal Disease (IPD) is defined as any infection in which S. pneumoniae is isolated from the blood or another normally sterile site (Musher D M. Streptococcu pneumoniae. In Mandell G L, Bennett J E, Dolin R (eds). Principles and Practice of Infectious diseases (5th ed). New York, Churchill Livingstone, 2001, p2128-2147). Chronic obstructive pulmonary disease (COPD) is recognised as encompassing several conditions (airflow obstruction, chronic bronchitis, bronchiolitis or small airways disease and emphysema) that often coexist (Wilson et al., Eur. Respir. J. 2001; 17: 995-1007). Patients suffer exacerbations of COPD that are usually associated with increased breathlessness, and often have increased cough that may be productive of mucus or purulent sputum (Wilson, Eur Respir J 2001 17:995-1007). COPD is defined physiologically by the presence of irreversible or partially reversible airway obstruction in patients with chronic bronchitis and/or emphysema (Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med. 1995 November.; 152(5 Pt 2):S77-121). Exacerbations of COPD are often caused by bacterial (e.g. pneumococcal) infection (Sethi S, Murphy T F. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev. 2001 April; 14(2):336-63).
Streptococcu pneumoniae, also referred to as pneumococcus, is encapsulated with a chemically linked polysaccharide which confers serotype specificity. There are more than 90 known serotypes of pneumococci, and the capsule is the principle virulence determinant for pneumococci, as the capsule not only protects the inner surface of the bacteria from complement, but is itself poorly immunogenic. An anti-polysaccharide antibody level has been regarded as predictive of the protection against invasive pneumococcal disease (Jodar et al. Vaccine, (21) 2003, p. 3264-3272). After initial licensure of a 7-valent conjugate vaccine containing serotypes 4, 6B, 9V, 14, 18C, 19F, 23F (PCV7), two pneumococcal conjugate vaccines (PCVs) designed to broaden coverage have been licensed. The 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) contains serotypes 1, 4, 5, 6B, 7F, 9V, 14 and 23F conjugated to nontypeable H. influenzae protein D, plus serotype 18C conjugated to tetanus toxoid and serotype 19F conjugated to diphtheria toxoid. The 13-valent pneumococcal conjugate vaccine (PCV13) contains the PCV7 (4, 6B, 9V, 14, 18C, 19F, 23F) serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A, conjugated to cross-reactive material CRM197. It is an object of the present invention to develop improved Streptococcu pneumoniae vaccines.
Pneumolysin (ply) is a 53 kDa thiol-activated cytolysin found in all strains of S. pneumoniae, which is released on autolysis and contributes to the pathogenesis of S. pneumoniae. It is highly conserved with only a few amino acid substitutions occurring between the ply proteins of different serotypes. Pneumolysin is a multifunctional toxin with a distinct cytolytic (hemolytic) and complement activation activities (Rubins et al., Am. Respi. Cit Care Med, 153:1339-1346 (1996)). The toxin is not secreted by pneumococci, but it is released upon lysis of pneumococci under the influence of autolysin. Its effects include, for example, the stimulation of the production of inflammatory cytokines by human monocytes, the inhibition of the beating of cilia on human respiratory epithelial, the decrease of bactericidal activity and migration of neutrophils, and in the lysis of red blood cells, which involves binding to cholesterol. Expression and cloning of wild-type or native pneumolysin is described in Walker et al. (Infect Immun, 55:1184-1189 (1987)), Mitchell et al. (Biochim Biophys Acta, 1007:67-72 (1989) and Mitchell et al (NAR, 18:4010 (1990)).
The present invention provides detoxified pneumolysin adsorbed onto aluminium phosphate having improved properties and an improved process for the adsorption of detoxified pneumolysin onto aluminium phosphate. The present inventors have found that by admixing detoxified pneumolysin and aluminium phosphate at a specific pH range a high level of completeness of adsorption may be obtained (greater than 85%), and an adsorbed detoxified pneumolysin having desirable properties, for example in relation to particle size, can be produced. The particle size of the adsorbed detoxified pneumolysin and level of adsorption can affect immunogenicity; therefore, a particle size <10 μm and a high level of adsorption (greater than 85%) are desirable. Furthermore, the present inventors have found that it is advantageous to pre-adsorb detoxified pneumolysin onto aluminium phosphate according to the method of invention prior to mixing with other antigens. For example, pre-adsorbed detoxified pneumolysin may be mixed with pre-adsorbed PhtD which has been adsorbed onto aluminium phosphate under different conditions.


An adjustable stylet includes a core wire having a portion surrounded by a compression member preferably comprised of a flat wire spring. Depending upon the configuration, compression or relaxation of the compression member in response to forces at the tip or handle of the stylet results in adjustments to the characteristics of the stylet. In a first embodiment, the stiffness of the stylet is adjustable. In a second embodiment, the length of the stylet is adjustable. In a third embodiment, both the stiffness and the length of the stylet are adjustable.

The present invention relates generally to the field of intravascular leads and catheters. More specifically, the present invention relates to an adjustable stylet for use in positioning such leads and catheters.
Stylets and guidewires are used to control the manner in which intravascular leads and catheters are introduced into the veins or arteries of the body. Although both kinds of devices are often thought of as simply very small wires, the purpose and operation of stylets is significantly different as compared to guidewires.
Conventional intravascular procedures typically involve an initial step of introducing and routing a guidewire through a patient""s vascular system to provide a rail or track along which additional intravascular devices may be introduced. Once a guidewire is in place, a sheath is routed over at least a portion of the guidewire to provide a larger opening into the vein or artery and sometimes to protect the inside walls of the vessels along the route of the guidewire. With the sheath in place, the guidewire may be removed or may remain in place as additional intravascular devices such as intravascular leads and catheters are introduced into the patient""s vascular system.
To better accomplish the purpose of a guidewire of providing a track along the patient""s vascular system for other intravascular devices, it is desirable that the guidewire have a region at the tip of the guidewire, referred to as the distal end, that is extremely flexible. Preferably, the guidewire has the ability to vary the flexibility of the distal tip and/or deflect the distal tip so as to aid in routing the guidewire through the patient""s vascular system. U.S. Pat. Nos. 4,215,703, 4,456,017, 4,719,924, 4,886,067 and 5,060,660 describe designs for guidewires that use an internal tensioning member or pull wire to alter the characteristics of the non-expandable distal tip and/or to deflect the distal tip. U.S. Pat. Nos. 4,271,845 4,822,345, 5,605,162, 5,762,615, 5,851,203, 5,957,903 and 6,183,420 describe various designs for guidewires with adjustable stiffness by moving a core member axially within the distal region of the guidewire. U.S. Pat. Nos. 5,938,623 and 6,039,743 describe a guidewire with adjustable stiffness that is controlled by running electricity through a memory metal wire tip. U.S. Pat. No. 5,341,817 describes a guidewire extension arrangement in which a smaller inner extension can be pushed out of a larger core segment to extend the distal end of the guidewire. U.S. Pat. Nos. 4,846,174 and 5,338,301 describe guidewires with a core member that can be extended to axially stretch an angioplasty balloon at the distal tip. In a similar manner, U.S. Pat. Nos. 3,841,308 and 4,759,748 describe catheters that utilize a core member to axially stretch a coiled section at the distal end of the catheter for purposes of controlling delivery of a fluid.
In contrast to the guidewire which serves as a track over which other intravascular devices are routed, a stylet is used within an internal lumen of an intravascular device both to push that device through the vascular system and to steer the device as it is being pushed. Although some intravascular devices are designed to steer themselves using internal pull wires, almost all leads, most catheters and some guidewires have an inner channel or lumen into which a stylet is inserted. In addition to pushing the intravascular device through the vascular system by engaging the distal end of the device, the stylet also serves to deflect the distal end of the intravascular device so as to steer the distal end through the vascular system. Unlike the lead, catheter or guidewire, which has a distal region that is flexible and floppy, the stylet must be stiffer and more rigid so as to enable the stylet to push the lead or catheter through the patient""s vascular system. Conventionally, stylets having different bends on the distal end are used at different points of advancing the lead or catheter to a desired location. For straight segments of a vessel a straight stylet is used, whereas a stylet with a curved distal tip is used to navigate the lead or catheter through a curved portion of a vessel. U.S. Pat. No. 2,118,631 shows an early stylet formed of coils of flat wire welded to plugs at both ends that could be bent by the physician into either a straight or curved configuration at its distal end prior to insertion into the lumen of a catheter or the like. In a more recent type of stylet, an operator controls the direction of deflection of the tip of the stylet while it is in place in the lumen, which in turn controls the direction of the cardiac lead or catheter as it is moved along the veins or arteries. An example of a stylet with such a deflecting tip is shown in U.S. Pat. No. 5,824,031. Other examples of steerable stylets can be found in U.S. Pat. No. 5,873,842 and PCT Publ. No. WO 00/22981.
The more control and flexibility an operator has over an intravascular device, the easier it is to operate that device. In the case of stylets, the physical demands of engaging the distal end of a lumen of an intravascular device so as to push that device through the vascular system impose constraints on the beam strength of the device that are much different than the constraints encountered for a guidewire, catheter or lead. Most guidewires are constructed from a tapered core wire with a coiled round wire wrapped around this tapered core wire in order to achieve the necessary flexibility in the distal region of the guidewire. Stylets, on the other hand, are generally constructed of a solid wire of uniform diameter without any coils around this wire in order to achieve the necessary strength and rigidity required over the entire length of the device so as to function as a stylet. Because of these differences, the techniques for improving control and flexibility that have been utilized for guidewires, catheters and leads are not generally applicable for the design of stylets. It would be desirable to provide for a stylet with improved flexibility and control without the need for changing stylets during a procedure to obtain different orientations of the distal tip of the stylet.
The present invention is an adjustable stylet. The stylet includes a core wire having a portion surrounded by a compression member preferably comprised of a flat wire spring. Depending upon the configuration, compression or relaxation of the compression member in response to forces at the tip or handle of the stylet results in adjustments to the characteristics of the stylet. In a first embodiment, the stiffness of the stylet is adjustable. In a second embodiment, the length of the stylet is adjustable. In a third embodiment, both the stiffness and the length of the stylet are adjustable.
Unlike most guidewires that are so flexible the guidewire will fall over when grasped only by the ends, the stylet in accordance with the present invention requires a much greater rigidity such that the stylet forms an arc that generally stands up and does not fall over when the stylet is grasped only by the ends. The present invention utilizes a core wire that has a relatively uniform beam strength over its axial length so as to provide the necessary rigidity and strength required for a stylet. The compression member augments the characteristics of the core wire in a manner that is adjustable so as to also be able to more closely emulate the desired characteristics of an adjustable guidewire.


A fluid decontamination apparatus is provided having a container body with a plurality of three-dimensional open structure (3DOS) substrates spaced about therein, wherein a contaminated fluid flowing through the container body will contact the 3DOS substrates. Nozzles can be inserted and secured within inlet apertures disposed about the container body, configured to inject the contaminated fluid with/without air to induce the occurrence of hydrodynamic cavitation. The substrates can be porous and permeable enabling the contaminated fluid to flow therethrough, wherein the fluid flow passageway through the pores extends the volume of contaminated fluid exposed to turbulent and cavitation inducing flow conditions. Moreover, the 3DOS substrates may be coated with one or more types of catalysts so as to initiate chemical reactions. As such, the extended exposure of the contaminated fluid to hydrodynamic cavitation forming conditions, along with the chemical reactions carried out on the porous surfaces, enable an increased number of toxic species and unwanted organic compounds to be destroyed and/or altered, thereby enhancing the decontamination of the flowing fluid.

Fluids, particularly liquids such as water, are susceptible to being contaminated with toxic species and other unwanted organic compounds. As such, there are several methods used in various industries to decontaminate and treat such contaminated fluids. These methods include sonication, hydrodynamic cavitation and/or the use of chemical reactions, particularly aided with a catalyst.
However, several of these existing methods are often limited in their effectiveness due to physical and/or spatial constraints. For example, hydrodynamic cavitation, which relies on the increase in fluid flow turbulence and occurrence of cavitation, or gas voids/bubbles, is often limited to decontaminating the specific localized areas where cavitation occurs. Thus, a significant portion of the fluid flow would need to be exposed to cavitation in order for effective decontamination to occur. Another example is the use of catalysts to initiate chemical reactions that destroy or modify such unwanted chemicals to render them safe. Often, a single or uniform type of catalyst is employed which may only be effective in targeting a fraction of the unwanted compounds.
It should therefore, be appreciated that there remains a need for effectively decontaminating liquids, including enhancing existing decontamination methods to improve the destruction of toxic species and other unwanted organic compounds. The present invention addresses this need and others.


A pressure resistant plastic bottle for containing and dispensing an aerosol composition. The plastic bottle is designed to reduce deformation by a local reinforcement to the neck and shoulder regions. The reinforcement preferably comprises the provision of a wall thickness for a lower portion of the neck as compared to the wall thickness of the upper portion of the neck to be increased by a ratio of from about 1.25:1 to about 2.5:1.

The present invention relates to dispensers for aerosols or other pressurized products, and more particularly to a pressure resistant plastic bottle containing a reinforced neck and shoulder region for dispensing an aerosol or other comparably pressurized product.
The term "aerosol" will be understood herein to encompass both aerosols, literally, and other liquid or flowable products that can be dispensed from pressurized containers in a manner comparable to aerosolized products. Such products may include but are not limited to foamed or gel preparations or to liquid products delivered in a non-aerosol stream.
Pressurized containers for dispensing aerosols are well known in the art, and are typically constructed of metal in order to withstand the inherent internal pressures of aerosols. However, it is desirable to provide a plastic container capable of withstanding the internal pressures generated by an aerosol because plastic has many advantages over metal. Some of these advantages include the ease and economy of manufacture, and the aesthetic appeal to an end user.
Despite the desirability of using plastic containers for aerosols, there are some inherent disadvantages to utilizing plastic materials in such an environment. For example, it is desirable to avoid plastic containers that have abrupt changes in configuration. The areas of such abrupt changes are stress concentration points which are inherently weak. Another disadvantage is that when the container is subject to internal pressure, certain features of a plastic container may deform. Depending on the wall thickness of the container, the internal volume may change between 3% to 5%. As a result of such stress, slight bulging and/or skewing of a container may occur causing the container to become unsightly, and depending on the location of the deformation, the container could become unstable and may not rest properly on a table or other flat surface. It is thus necessary to provide a container design or shape which, when made of a plastic material, can most effectively resist the internal pressures generated by an aerosol without rupturing or becoming unduly distorted.
A successful plastic bottle design is required to hold internal pressure without fracture or distortion under both room temperature and elevated temperature encountered during shipping and storage (for example, at about 55° C. (131° F.)) for an extended period of time equivalent to the product manufacturing and use cycle (about 6 months). For economic reasons, it is also desirable to design such a plastic bottle from relatively inexpensive plastic material such as stretch blown polyethyleneterephtalate (PET) or polyethyleneterephtalate/polyethylene-naphthalate (PEN) copolymer. Blow molding techniques of such plastic materials are well known in the art, and typically a plastic bottle may be formed by any conventional two-stage blow molding technique. In two-stage blow molding, a preform of a plastic is made by injection molding. The preform provides the mass of material that eventually is blown into the final desired shape. The preform is reheated, enclosed within the halves of a blow mold, and thereafter expanded in such mold. Under such a process, the plastic bottle may be formed integrally in a one-piece construction which is typically the preferred construction. The final bottle usually includes an externally concave neck region which, because of limited material stretching during the blow molding process results in the neck region being virtually "as-injection-molded." When PET is used as the material of construction, the neck region is composed of primarily amorphous PET. The externally convex region below the neck is the shoulder and waist regions which, due to material stretching during the blow molding process, will consist of partially crystalline PET.
Conventional PET or PET/PEN aerosol bottles tend to be unable to hold pressure without distortion at elevated temperatures due to two fundamental weaknesses. First, the neck region is amorphous and will undergo large, irreversible, time-dependent deformations known as "creep." Secondly, the neck region is composed of an externally concave shell configuration which is inherently unstable under internal pressure. The accumulated creep deformation will effectively lower the material stiffness over time until it is at or below the level required to withstand the internal pressure contained by the bottle. When this occurs, the geometric instability of the concave neck region will result in the concave neck region "inverting" to an external convex configuration, i.e. a distorted externally convex configuration that under internal pressure and in the presence of external chemical agents develops micro crazes and voids, which phenomenon is generally known in the industry as "stress crazing." The crazes elongate and propagate with time and finally cause a rupture through the thickness. The shoulder and waist regions, by virtue of the partial crystalinity imparted by the stretch blowing process, will undergo far less creep deformation and will not experience instability since they are inherently stable due to the fact that these regions are externally convex configurations.
As noted above, stress crazing of pressurized plastic containers is commonly observed in stretch blown molded PET containers having regions of high amorphous content with externally concave configurations. The stress crazing will typically occur in the neck region slightly above the shoulder of a molded PET container because this region does not achieve enough orientation during the blow molding process. On the other hand, each of the shoulder, skirt and body regions of stretch blow molded PET containers typically has a high level of molecular orientation caused by the stretching process, and as a result provides better mechanical properties. The stress, designated by the Greek letter sigma, developed in a cylindrical bottle of diameter D and thickness t is given by the equation σ=P(D/2t) where P is the internal pressure. Thus, for a container of diameter 5.08 cm (2 inches) with sidewall thickness of 0.0355 cm (0.014 inches) and 9.843 kg/cm2 (140 psi) internal pressure, the stress is approximately 703.1 kg/cm2 (10,000 psi). If this stress is higher than the yield stress of the material, structural deformation and failure may occur. Orientated PET (such as that found in the shoulder, waist and body regions of a bottle) typically has a Youngs modulus of 35,155 kg/cm2 (500,000 psi) and a yield strength of 914.03 kg/cm2 (13,000 psi) at 5% strain. However, for amorphous PET (such as that found in the neck region) the yield strength and Youngs modulus is about ⅛ that of orientated PET, which as noted above, results in poor mechanical properties.
To compensate for lower mechanical properties, one can reduce the container diameter or increase sidewall thickness. Reducing the diameter of the container, however, provides other disadvantages because such a container becomes more difficult to injection and blow mold, and may provide a product container of undesirable dimensions and volume. Likewise, increasing sidewall thickness creates its own unique problems, such as undesirably increasing cycle time and propensity to crystallize the PET due to slow cooling of thicker sidewalls. Thus, a delicate balance of design criteria must be undertaken in order to achieve an aerosol bottle design which can sustain pressure for an extended period of time by reducing the stress levels generated in PET and PET/PEN copolymers at relatively high pressures (at least 8.437 kg/cm2 (120 psi)) and temperatures (at least 50° C. (122° F.)).

Pressurized plastic bottle with reinforced neck and shoulder for dispensing an aerosol