System for electrical energy generation from steam comprising at least one stage, each stage including: a steam-driven rotating toroidal ring; a housing comprising a toroidal cavity for containing the rotating toroidal ring, the housing further comprising at least one steam inlet, the housing further comprising a plurality of steam outlets for removing pressurized steam from the channels for at least a second portion of rotation of the rotating toroidal ring within the toroidal cavity; at least one bearing arrangement comprised by or attached to the housing within the toroidal cavity; and at least one pair of electrical coils, each electrical coil located on the outer surface of the housing at locations diagonally opposite from the other coil of each pair across the axis of the minor radius of the toroidal cavity and within the specific region where a time-varying magnetic field will occur as the rotating toroidal ring rotates.

In the contemporary electrical energy economy, a component of inefficiency in energy consumption comes from "Rejected Energy." Most rejected energy allegedly comes largely from two sources: transportation use of petroleum, and losses in centralized electricity generation and transmission. As hybridized and fully-electric transportation vehicles begin to migrate from vehicle-internal burning of petroleum-fuel to storage of at least some fraction of centralized-generated electricity, segments of the transportation use of petroleum sector shift to the centralized-generated electricity sector.
FIG. 1, adapted from the Lawrence Livermore National Laboratory report available at https://flowcharts.llnl.gov/content/energy/energy_archive/energy_flow_2012/2012newUSEnergy.pdf, depicts representative aspects of contemporary energy usage in the United States. From the fuels and source delineated on the left side the diagram, at least in 2012 the combination of Natural Gas, Coal, Biomass, and Geothermal, and Solar used for electrical generation total to 38.1% of overall energy fuel/conversion usage (38.1%) and all but a portion of Solar (overall being <0.235%) of this is directed to the powering of steam turbines for centralized electricity generation. Thus, a tremendous if not dominant opportunity to improve the efficiency of centralized electricity generation (and decentralized replacements/supplements to centralized electricity generation) could be obtained by sufficiently improving the efficiency of steam-turbine methods used for converting heat to electricity.
Thus, there is an important need for improving the efficiency of steam-driven electricity generation at centralized and medium-scale decentralized electricity generation plants.
The present invention is directed to improved-efficiency of steam-driven electricity generation at centralized and medium-scale decentralized electricity generation plants.
The present invention comprises multiple stages of shaft-less ring-shaped turbines, each ring turbine serving as a steam-driven magnetized rotor of an AC electrical generator and rotating without synchronization.
FIG. 2 depicts an example novel ring turbine rotor within a (partially cut-away) enclosing stator used to confine (and in some embodiments direct) the flow of steam. This example implementation depicted comprises spiral steam channels winding over the rotor surface as shown, although other steam channel and steam routing structures are possible, anticipated, accommodated, and provided for in the invention. Such a ring turbine rotor arrangement can, for example, be replicated as a stage in a multi-stage implementations provided for by the invention, including with varying scale from stage to stage to more optimally exploit steam energy capture as the multi-stage steam path varies from the effects of preceding stages. The novel shaft-less ring turbine can operate with much wetter steam resulting from its geometry and associated abilities to operate at lower steam velocity than traditional turbines require.
FIG. 3 depicts two perspective views of an example multistage embodiment of the present invention, illustrating example relative stage diameters varying from stage to stage as per steam energy capture design aspects of the invention.
By way of comparison, FIG. 4 depicts a representation of a traditional boiler-fed steam driven turbine arrangement comprising a heat radiator for extruding waste heat and a return pump.
In contrast, FIG. 5 depicts an adaptation of the boiler arrangement of FIG. 4 in accordance with some aspects of the present invention wherein the heat radiator and extrusion of waste heat are omitted. In some embodiments of the invention it can be advantageous to include a radiator after the turbine or turbine sequence, but such a radiator can be smaller than it would be in a traditional turbine system.
In a broader system view, FIG. 6 depicts an example schematic representation of steam, air/exhaust, water, heat, electrical, and boiler-heating fuel or thermal energy flows in an example embodiment of the present invention. It is noted, however, that the present invention typically need not involve the pressurized boiler design, and further can be invariant to the underlying heat source. Less efficient variations are possible that include a radiator to dispose of waste heat as provided for by the invention.
The boiler-heating fuel or thermal energy source can be a fossil fuel, bio-mass fuel, thermo-nuclear (fusion, fission, or other), geo-thermal capture, solar energy capture, etc. The resulting multiple-stage shaft-less ring turbine system is inherently more efficient that traditional turbine-driven electricity generation for several reasons including:                a. The novel shaft-less ring turbine can operate with much wetter steam due to its geometry and lower steam velocity.        b. Using a vacuum pump, some ring stages in the turbine can operate at vacuum pressure. Steam that is too wet to use in a ring can be converted to water by raising the pressure back to atmospheric pressure instead of cooling the steam with a radiator.        c. Waste heat can be recycled for further conversion to electricity rather than being rejected into the atmosphere.
The omission of a shaft allows the steam path to be far more constrained and alternate energy-capture geometries to be used. For example, in a representative implementation of some embodiments, a ring turbine of a stage is arranged so that steam passes through inlet nozzles, pumps or injectors into narrow channels on the surface of the ring turbine into the gap between the ring turbine (rotor) and its enveloping housing (stator). If a shaft existed, then fins, spokes or blades must extend from a center, this entire region could not be sealed from the steam movement.
Additionally, the resulting arrangement can be arranged to provide tightly constrained paths that permit intimate-co-design to optimize across physical laws of motion, electromagnetism, thermodynamics, and steam behavior in a way that energy transfers efficiently and predictably from heat to steam to kinetic energy to magnetic energy to electrical energy.
In an example embodiment, each ring-shaped rotor is rotationally-suspended within an enveloping toroidal stator chamber comprising an interior toroidal cavity to accommodate the ring-shaped rotor, with room for a gap between the exterior surface of the rotor and interior surface of toroidal cavity within the toroidal stator. Thus, each ring-shaped rotor is a toroid without an attached or otherwise associated rotation shaft employed by conventional turbines.
In an example embodiment, pairs or other pluralities of associated electrical coils can be mounted on each stator, and these electrical coils can be used to convert energy from the moving magnetic field sources into electricity. Additionally, electrically-created heat from Ohmic losses in the electrical coils can readily put back into the system.
In some embodiments, the electrical coils can be used to control aspects of the rotors rotation and rotational stability.
In an example embodiment, AC currents are independently generated by each pair or other pluralities of associated electrical coils, and can be arranged to be single-phase or phase-locked multi-phase at a frequency determined by the rotation speed of the associated ring.
In an example embodiment, power electronics can be used to convert AC currents generated by each stage into forms of DC or AC power suitable for use in standard, evolving, or future electrical power distribution.
In an example embodiment, the present invention would comprise a plurality of stages, each successive stage internally operating at consecutively lower operating steam pressures with wetter steam.
In an example embodiment, steam is passed from one stage to the next with steam nozzles, pumps or injectors, which both regulate the pressure between the stages, but also provide an angularly-directed flow of steam through the stator tubes at a moderate velocity to power the rotors without damaging them. Traditional turbine blade damage can potentially occur because of the high velocity of water droplets within the steam. The force-receiving blades comprised by the rotors can be arranged to move perpendicularly to the water droplets, while the rings are moving in the same direction as the steam, further lowering collision energy.
A traditional turbine must cool 'waste' or 'rejected' energy within the steam with a radiator before recycling it back into the boiler as water. This can also be the case in some embodiments of the present invention by design choice, although importantly in such circumstances the amount of waste steam is advantageously far lower.

Ring turbine arrangements for electricity generation and other applications


A clamp for electrically connecting a contact rail and a bus bar of a PV assembly includes a base having a first end and a second end positioned opposite the first end. Two fixing portions extend from both sides of the base and away from and perpendicular to the first surface, and adapted to detachably fix the clamp to the contact rail. An extending portion has a first bending extension extending and bent from the base, a parallel extension connected with the first bending extension and extending in parallel with and apart from the first surface, a second bending extension connected with the parallel extension and extending between the two fixing portions, and an actuating extension connected with the second bending extension and extending beyond the base. A locating protrusion is formed integrally with the base and adapted to engage within the first locating element and the second locating element.

In a conventional PV assembly, it is necessary to electrically connect a bus bar of a solar cell panel with a contact tip of a contact rail in a PV assembly junction box (hereinafter, referred to as junction box). Usually, the electrical connection is made by using a special elastic clamp. For example, as shown in FIG. 1, an Ω-shaped clamp 80 may be used, and in the case that the contact tip 91 of the contact rail 90 is inserted between two gripping portions 81 of the clamp, or in the case that the two gripping portions of the clamp have gripped the contact tip, the tip of the bus bar is inserted between the two gripping portions to electrically connect with the contact tip.
However, the above elastic clamp cannot provide a sufficient gripping force so that it is difficult to ensure a stable electrical connection between the bus bar and the contact tip of the contact rail.
In addition, opening of the elastic clamp usually requires a special tool, which makes the operation of electrically connecting the bus bar and the contact rail complicated and inconvenient.
Therefore, it is necessary to improve the conventional elastic clamp.

Elastic clamp, contact rail assembly, and PV assembly junction box having the assembly


A system and method for creating and utilizing content is described. Content is generated which includes a query and a response to the query. A primary query may be used to generate a plurality of variant queries which may be matched to a request. A content owner or curator may review a query, a response, and/or alternate queries, and may provide access to media which may be used to generate queries and responses.

1. Field of the Invention
The present invention is related to providing a response to a request for information, more specifically providing a response to a request using resources, and human assistants associated with a target of the request.
2. Description of the Related Art
In a system which produces work for publication, it is common practice that a Wiki is established wherein users may contribute information regarding a topic, a person, a business, etc. For example, user reviews might be contributed, or wiki pages might be created and maintained, etc. Sites such as Wikipedia®, FreeBase® and others provide information to users in a full-text indexed form.
Social media sites such as MySpace®, Facebook® and Twitter™ allow a user to create a web page which includes information regarding the user. Such pages may be helpful to individuals as well as businesses in order to communicate through a social network regarding activities, special events, opinions, etc.
However both types of websites may suffer from some weaknesses. In the case of the wiki sites, content of the wiki is not necessarily accurate as the person posting the information may have a bias, or may simply not be able to obtain relevant or accurate information regarding the topic or subject matter. As such, inaccurate information may be propagated, and might cause confusion, harm, etc. In particular, an individual and/or entity may not be aware that such information is being disseminated, and might desire to make his own voice heard.
Social media websites allow a user to publish any desired information, but many users are not willing or able to create content which may be of interest. For example, a public figure might provide data such as date of birth, place of birth, marital status, etc. But people interested in the person might want to know information such as favorite books, childhood heroes, food preferences, religious views, etc. Current social networks do not allow a user to create and/or publish such information in a usable format. Ad hoc attempts to determine such affiliations by peer-to-peer messaging, etc., have not been able to bridge this gap.
In light of these and other issues, a method and system whereby affiliated content can be created, enhanced, and curated would be greatly appreciated.

Method and system of providing verified content


A method for regulating the regeneration time of an adsorption dryer, the method including the steps of: subjecting the adsorption dryer to an adsorption cycle; stopping the adsorption cycle after a preset adsorption time interval; and subsequently subjecting the adsorption dryer to a first regeneration cycle during a preset time interval. The method further includes maintaining the first regeneration cycle for an additional regeneration time interval if the measured pressure dew point or relative humidity is higher than a predetermined pressure dew point or relative humidity threshold; and/or stopping the first regeneration cycle if the outlet temperature is higher than or equal to a predetermined temperature threshold, and, if the time frame in which the adsorption dryer is subjected to the first regeneration cycle is greater than a minimum heat regeneration time interval.

Adsorption dryers are frequently used in different applications requiring a flow of dry and cooled air.
A challenge encountered is maintaining a low energy consumption of such adsorption dryers. Typically, the adsorbent material within an adsorption dryer reaches saturation and needs to be periodically regenerated. This is typically performed by either heating a regeneration gas, prior to guiding it through the adsorbent material or just by maintaining the regeneration gas flow through the dryer for a certain time interval.
While the regeneration with the help of an external heat source is efficient in terms of regenerating the adsorbent material, it is also results in increased energy consumption.
Because of this, a balance needs to be found such that the adsorption dryer is maintained in optimum parameters with the minimum required energy consumption.
Existing dryers, like the one found in US 2014/0,216,105 A, in the name of Parker Hannifin Manufacturing S.R.L., proposes a method in which the efficiency is believed to be maintained by adopting a particular layout for the two adsorption columns. More specific, a process gas is first guided through a first column, it is then heated and further guided through said second column for regenerating it. The process is maintained for a predetermined maximum time duration and as long as the temperature at the outlet of the column does not exceed a maximum value.
A drawback of such a dryer according to the above identified patent application is the fact that by applying such a method the energy consumption is not optimized throughout the complete functioning cycle of the dryer, since the method does not consider the current state of the adsorbent column, and because of this the method is not efficient.

Method for regulating the regeneration time of an adsorption dryer and adsorption dryer implementing such a method

ATLAS COPCO AIRPOWER, NAAMLOZE VENNOOTSCHAP


The invention relates to a heavy vehicle brake system and in particular, a brake system having a reduced length and an axially mounted actuator while delivering the same clamp force. A brake system for a vehicle including an actuator having a service chamber and a parking chamber and the actuator operates along an axis through the service chamber and the parking chamber. The actuator has an overall length of less than approximately 200 millimeters along the actuator axis. The brake system also includes an application unit actuated by the actuator. The application unit has a force multiplying device for generating a clamp force. The clamp force is exerted in a direction substantially parallel to the axis of the actuator.

A brake system for a vehicle, such as a bus, truck or the like, typically includes an actuator and an application unit which presses friction material into contact with a brake disc or a brake drum assembly. Conventional brake actuators have both a service brake actuator for actuating the brakes under normal driving conditions and an emergency or parking brake actuator which causes actuation of the brakes when power is removed. The parking brake actuator may include a strong compression spring which forces application of the brake when air is released. This is often referred to as the spring brake. The emergency or parking brake may be a diaphragm or piston type brake.
Application of either the service or spring brakes is accomplished via a brake application unit which is activated by the service or spring actuator to apply friction material to a hub or disc.
Typically, the spring brake actuator is paired with the service brake actuator. When full pressure is applied to the spring brake actuator, air pressure acting against a diaphragm compresses the compression spring. A spring brake actuator rod is held in a retracted position by a relatively small return spring, thus not affecting the operation of the brake. When the brake is to be applied during normal driving operation, compressed air is provided to the service brake actuator which, acting against a diaphragm, causes a service brake push rod to be extended and causes the brakes to be applied with an application force which is proportional to the air pressure applied to the service brake actuator. In the event of a loss of air pressure or an intentional exhaustion of air from the spring brake actuator, the brake will be mechanically activated by the force of the compression spring acting on the spring brake actuator rod which in turn acts upon the service brake push rod to apply the brakes. Thus, the spring brake portion may serve both as a parking brake and as an emergency brake.
Such common piggy back or combination designs lead to additional axial length of the brake actuator and the brake system. Further, air brake systems are typically designed with extra long strokes. Long stroke brakes provide heavy vehicle brakes with a greater margin of effectiveness for thick layers of friction material and to better combat brake fade. Stroke length relates to the performance of the service chamber.
Several trends in vehicle design are leading to changes in air brake actuator design. Increasingly, vehicle manufacturers are requiring additional features and capabilities in brake systems, while at the same time demanding that the brake system be provided in a smaller package while generating the same clamp force. Ideally, these demands will not necessitate a redesign of the application unit to accommodate the application of an input force at a substantial angle to the axis of operation of the application unit.
At the same time, the dimensions of the brake arrangements in the vehicle chassis are often critical. Modern brake systems for heavy vehicles often require space consuming electronic components such as onboard diagnostic sensors, electric motors and antilock brake modulators. These components, often necessary by regulation or by customer demand, occupy much of the limited space within the wheel well. In addition, suspension systems are also growing in complexity and size and in the number of components, further reducing the available space.
As wheel sizes remain constant, it is thus desirable to reduce the dimensions of the brake system. A particular requirement of vehicle manufacturers is reduction of actuator axial length. In the prior art, this has been accomplished with smaller caliper designs and reduction of excessive clearance between the pad and the disk.
As the stroke length of the actuator cylinder is reduced, the overall axial length of the brake system may also be reduced. Brakes with reduced axial dimensions are more easily adapted to different vehicles.
One approach to meet the needs of vehicle manufacturers has been to mount the actuator radially, at an angle approaching perpendicular to the application unit's axis of operation. Such radially mounted actuators may reduce the length of the brake system. A problem with this solution, however, is that it requires a redesign of the application unit in order for the application unit to generate sufficient clamp force from a radially applied input force.
While standard actuators operate along a substantially parallel axis with respect to the application unit, a radially mounted actuator operates at a greater angle with respect to the operation axis of standard application units. Further, radially mounted actuators are low volume parts compared to prior art axially mounted actuators, and are thus higher in cost. In addition to requiring a redesign of the application unit, radially mounted actuators also require alternative calipers and mounting apparatus.
The invention provides a compact brake system having a reduced axial dimension while maintaining substantially parallel axes of operation for the application unit and the actuator by shortening the stroke length of the actuator. The shortened stroke length may be as short as approximately 40 millimeters for a service brake. Similarly, the stroke length of the parking or emergency brake may be shortened to approximately 30 millimeters or less for additional reduction of axial length of the brake system.
Such a compact brake system can fit modern system architecture, and is particularly adaptive to the more restrictive space on front axle installations. Such a compact spring brake also may be suitable for sliding and fixed caliper applications and may be adapted for integrated antilock brake modulators.
Shortening the stroke length may reduce the mechanical advantage in the application unit. The mechanical ratio may be reduced to approximately 10:1 from a standard ratio of 15:1 for a conventional 24/24 spring brake chamber, an approximately 33% reduction in stroke length.
To overcome the decrease in mechanical advantage, the diameter of the actuator may be increased. A larger diameter actuator may house a larger diaphragm. A larger diaphragm is capable of generating increased actuator forces. Modifications may also be made to the application unit to compensate for the shorter stroke length and decreased mechanical advantage. The modifications could include altering the active length of the application unit lever and/or changing the eccentric ratios to alter the force multiplier ratio of the application unit.
In the past it has been normal to have a certain over-capacity regarding the stroke length of the actuator. The over-capacity provides the actuator sufficient stroke length to guarantee that the brake is actuated even as the friction material is consumed, if, for example, the adjustment mechanism fails. The over-capacity of the stroke length has meant that the actuator must also have an over-capacity with regard to the actuator dimensions. Thus, the axial length of the brake system is larger than it would have been without the over-capacity.
A sensing system to monitor the stroke of the actuator and provide a warning if the stroke differs from a reference value could reduce or eliminate the need for over-capacity. Because a possible malfunction may be detected early, the overcapacity of the stroke actuator may be reduced substantially, thus allowing the axial length of the actuator to be safely decreased.
According to the invention, the concept of having a rather large over-capacity of the stoke length of a brake actuator may be replaced by the technique of constantly monitoring the exact position of the brake actuator. Thus, the need for over-capacity of the brake actuator is avoided.

Brake system having a reduced length and an axially mounted actuator


An electric current balancing device includes an inverting circuit having a driving unit and one or more transformers coupled together for outputting an electric current to a load device, a detecting circuit coupled to the inverting circuit for receiving and detecting an electric current of the load device and for stabilizing and sending a stabilized and calibrated electric current to the inverting circuit, and a balancing transformer device having a primary side coupled to the inverting circuit for receiving the calibrated electric current from the inverting circuit, and a secondary side coupled to the load device for comparing an electric current of the load device with the calibrated electric current from the inverting circuit and for controlling the load device.

1. Field of the Invention
The present invention relates to an electric current balancing device, and more particularly to an electric current balancing device for coupling to a multi-loaded electric facility and for comparing the electric current of each load with a steady and calibrated or regulated or standard electric current, and for providing a stable and balancing electric current to suitably energize the loads of the multi-loaded electric facility.
2. Description of the Prior Art
Typical multi-loaded electric facilities, such as the typical liquid crystal display (LCD) light devices or display panels may comprise various kinds of discharge lamps, such as cold cathode fluorescent lamps (CCFL) as the backlight source for the display panels, and employ network to drive the discharge lamps.
In larger LCD display panels, a number of lamps or light tubes are required to be provided and installed for providing the required brightness. When a number of lamps are installed in the larger LCD display panels, a single transformer or driving or actuating circuit is not so effective on performance to actuate or drive two or more discharge lamps that are coupled parallel with each other.
For example, the impedances of the discharge lamps may be different from each other, and may seriously influence the flowing of the electricity through the discharge lamps; i.e., the electricity may not be evenly flown through the discharge lamps, such that the discharge lamps may not be suitably driven or actuated or energized.
When the electric current is less than the required amount, the discharge lamps may not be suitably driven or actuated or energized to the required brightness, and the brightness in different portions or areas of the larger LCD display panels may be different from each other, and may seriously decrease the uniformity of the display panels.
On the contrary, when the electric current is greater than the predetermined amount, the discharge lamps may be over-energized and the working life of the discharge lamps may be greatly decreased. In addition, the characteristics of the discharge lamps may be changed any time, such that the electricity may not be used to evenly energize various discharge lamps.
For example, the diameters of different discharge lamps may be different from each other, the mercury densities and/or the electrodes of different discharge lamps may also be different from each other, the pressures of different discharge lamps may also be different from each other, such that the impedances of the discharge lamps may be different from each other, and such that different discharge lamps may not be evenly energized by the typical driving or actuating circuits, and such that the discharge lamps of the typical LCD display panels may normally generate flashes and/or flickers that people may not be easily conscious of and that may hurt people or may easily fatigue people or users.
For allowing the lamps or light tubes to be suitably driven by the transformer or driving or actuating circuit, the applicant has developed a multi-lamp actuating facility for evenly and uniformly driving or actuating a number of light tubes or lamps of such as liquid crystal display (LCD) light devices or display panels or other multi-loaded electric facilities.
For example, U.S. Pat. No. 6,856,099 to Chen et al. discloses one of typical multi-lamp actuating facilities arranged for allowing the lamps or light tubes to be suitably driven by the transformer or driving or actuating circuit. However, the light tubes or lamps may include different characters, such as lengths, outer diameters, mercury densities, pressures, electrode appliances, etc. which may affect the energizing or operating of the light tubes or lamps, such that the light tubes or lamps may not be actuated or operated in the best operating modes or status.
The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional actuating devices for multi-loaded facilities.


A three-dimensional object imaging method is implemented on a computer for imaging an object. The three-dimensional object imaging method includes the steps of irradiating ultrasonic waves having two mutually different frequencies on the object which is to be imaged, measuring sound pressures of scattering waves from the object so as to obtain two acoustical holography images thereof, and obtaining a three-dimensional shape of the object based on a phase error between the two acoustical holography images.

The present invention generally relates to three-dimensional object imaging methods and systems, and more particularly to a three-dimensional object imaging method and a three-dimensional object imaging system which are applicable to automatic recognition systems for recognizing three dimensional objects, ultrasonic robot eye and the like.
There is active research in automatic recognition techniques for recognizing a three-dimensional shape using mainly a television camera for the purpose of improving factory automation. However, an automatic recognition system which satisfactorily processes three-dimensional information of an object has not yet been reduced to practice. The automatic recognition system which uses the television camera suffers from problems in that the quantity of input data is extremely large and it is impossible to process the three-dimensional information of objects such as a metal object having a mirror surface which reflects light and a transparent object through which light can transmit.
On the other hand, in order to realize an intelligent robot, it is desirable to develop a robot eye which can identify and measure objects and also recognize the outside. As conventional methods of recognizing the outside, various methods using light wave, X-ray, electromagnetic wave, sound wave and the like as the wave medium have been proposed, but no decisive method has emerged.
According to the method using the ultrasonic wave, it is possible to measure the general shape of the object. However, it is impossible to identify the object from the information obtained by the measurement or estimate the position and rotary angle of the object. For example, Watanabe et al., "The Ultrasonic Robot Eye System Using Neural Network", Electronic Information Communication Society, 2.22, 1989 proposes identification of a plannar object. However, when the object has a three-dimensional shape, the conventional method cannot identify the object, estimate the position and rotary angle of the object, or form an image of the object with a high definition.
The use of ultrasonic wave for recognition of the three-dimensional object has the following advantages.
First, it is possible to measure the phase of the scattering waves from the object and the change of the sound pressure with time because the propagation velocity of the sound wave is relatively slow, and as a result, it is possible to directly obtain three-dimensional information of the object. In the system which uses the light wave as the wave medium such as the system which uses the television camera, it is possible to obtain a two-dimensional image of the object relatively easily, however, it is difficult to accurately estimate information along the depth of the object since this requires a technique of analyzing the image. For this reason, even in the robot which uses the television camera as the main sensor, an ultrasonic sensor is provided in most cases for the purpose of detecting the existence of the object and measuring a distance between the robot and the object. As one application which utilizes the advantage of using the ultrasonic wave, there is a guidance system for the blind which is being developed.
Second, it becomes possible to recognize metal, transparent and black objects, fluids and the like by use of the ultrasonic wave. It is virtually impossible to recognize such objects by use of the television camera because of the large or small reflection, transparency and the like of these objects with respect to light. When the recognition system is applied to the factory automation, parts of the product may be made of a metal, and the method which uses the ultrasonic wave is thus better suited for recognizing such metal parts. Various systems which use the ultrasonic wave image for checking, recognition and the like have been reduced to practice. Examples of such systems are a system for automatically distinguishing 150 kinds of empty bottles in a supermarket, a system for automatically detecting a content level of a softdrink bottle, a system for automatically checking whether or not a straw is attached to the side of a paper container containing a softdrink and the like.
Third, by use of the ultrasonic wave, it becomes possible to make an object recognition even under difficult circumstances such as inside a turbid fluid, a dark room, a room filled with smoke and the like. To take advantages of this feature, there is research to use the ultrasonic robot eye for carrying out various tasks in deep water, for making rescue operations in fire and the like.
On the other hand, the object recognition method which uses the ultrasonic wave cannot match the high resolution obtainable on the television camera because the wavelength of the ultrasonic wave is long and there are limits to the size of the wave receiver array and the number of wave receivers. For this reason, the object recognition method which uses the ultrasonic wave is at the present confined to the use in making measurements on a living body and to the use underwater.
The so-called ultrasonic wave holography technique irradiates the ultrasonic wave on the object, measures space information of the reciprocal scattering wave from the object on a receiver transducer array, and calculates a reconstructed image of the object. However, this known technique generally introduces a large distortion in the reconstructed image and the resolution is too poor for practical use. These problems are caused mainly by the long wavelength of the ultrasonic wave, the limited size of the wave receiver array and the limited number of wave receivers in the wave receiver array.

Three-dimensional object imaging method and system


A method, a device and a computer program product for managing data backup are provided. The method comprises: obtaining a first set of performance parameters of a backup client prior to performing a data backup, the backup client being configured to transmit data to a backup server for backup and record information about the data in a cache to avoid duplicate data being transmitted to the backup server; determining, from a plurality of sets of historical performance parameters collected during multiple historical data backups performed by the backup client, at least one set of historical performance parameters similar to the first set of performance parameters; determining, from the at least one set of historical performance parameters, a set of historical performance parameters indicating the best performance; and adjusting, based on the set of historical performance parameters, an available capacity of the cache to be used in the data backup.

A data backup system generally includes a backup client and a backup server, where the backup client is configured to transmit data to be backed up to the backup server for backup. In a data backup system that supports the de-duplication function, a cache may be set in the memory of the backup client to record information about the data that has been transmitted to the backup server, so as to avoid duplicate data being transmitted to the backup server. In this way, the backup client only transmits new data to be backed up to the backup server for backup, thereby saving network traffic. The cache is usually managed by the backup client and the available capacity thereof (that is, the maximum memory size the cache occupies) is usually set to a fixed ratio relative to the total memory size of the backup client. However, such a mechanism is often unable to adapt to environmental changes and even seriously affects the performance of the data backup system in some cases.

Method, device and computer program product for managing data backup


The invention provides specific synthetic chimeric xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing crispr mediated genome editing efficiency. The invention also provides methods and compositions for inducing CRISPR/Cas-based gene editing/regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using single guide RNAs (sgRNAs) that have been chemically modified with xeno nucleic acids which enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a sgRNA that has been chemically modified with xeno nucleic acids to correct a mutation in a target gene associated with the genetic disease.

Genome engineering can refer to altering the genome by inserting, deleting, mutating, or substituting specific nucleic acid sequences. The altering can be gene or location specific. Genome engineering can use nucleases to cut a nucleic acid thereby generating a site for the alteration. Engineering of non-genomic nucleic acid is also contemplated. A protein containing a nuclease domain can bind and cleave a target nucleic acid by forming a complex with a nucleic acid-targeting nucleic acid. In one example, the cleavage can introduce double stranded breaks in the target nucleic acid. A nucleic acid can be repaired e.g. by endogenous non-homologous end joining (NHEJ) machinery. In a further example, a piece of nucleic acid can be inserted. Modifications of nucleic acid-targeting nucleic acids and site-directed polypeptides can introduce new functions to be used for genome engineering.
After the human genome project, the sequence of every gene in the human genome is now known. However, the function of most genes is still not clear. One of the most common strategies for studying the function of a particular gene is to knock it out in a model organism. However, until recently, gene knockout could only be done in certain animals, and the cost has been very high. The CRISPR-Cas9 system has now emerged as a powerful genome-editing technology that can knock out any gene in cultured cells with ease.
The use of clustered regularly interspaced short palindromic repeats (CRISPR) and associated Cas proteins (CRISPR-Cas system) for site-specific DNA cleavage has shown great potential for a number of biological applications.
This powerful and revolutionary technology has already become one of the most commonly used tools in biological research. Almost all of the major companies, including Life Technologies, Sigma, and Santa Cruz Biotechnology, provide services based on this technology. Moreover, CRISPR-Cas9 technology has been actively pursued as a therapeutic tool for treating various diseases. A CRISPR-Cas9 system with increased knockout efficiency will be of great interest. The current commonly used single-guide RNA (sgRNA) has a shortened duplex structure compared with the native bacterial crRNA-tracrRNA duplex.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a method of gene editing that utilizes the Cas9 protein and specific guide RNAs to either disrupt host genes or insert sequences of interest. Initially used in bacteria as an adaptive immunity response, CRISPR has been since utilized in the biological field as a new alternative to genome engineering. Furthermore, CRISPR provides a cheaper alternative to other gene editing techniques such as zinc fingers, and is quickly being adopted as the technique of choice.
Cas9 (CRISPR associated protein 9) is a naturally occurring enzyme found in some bacteria that is used for immunity. Cas9 works by using guide RNA with short sequences complimentary to potential foreign DNA, combating infection. This mechanism has similarities to RNA interference found in many eukaryotes. Because of its capabilities, Cas9 has been used recently in experiments to serve as a genome editing tool.
CRISPR/Cas9 systems are a versatile tool for genome editing due to the highly efficient targeting of DNA sequences complementary to their RNA guide strands. However, it has been shown that RNA guided Cas9 nuclease cleaves genomic DNA sequences containing mismatches to the guide strand. The use of chemically modified and protected nucleoside phosphoramidites for the synthesis of single guide RNAs (sgRNAs) to enhance genome editing efficiency in human primary T cells, CD34+ hematopoietic stem and progenitor cells has been reported. The researchers argued that co-delivery of chemically modified sgRNAs with Cas9 mRNA or protein is an efficient RNA- or ribonucleoprotein (RNP)-based delivery method for the CRISPR-Cas system. This approach is a simple and effective way for the development of new genome editing methods.
Additionally, genome editing with engineered nucleases is a breakthrough technology for modifying essentially any genomic sequence of interest. This technology exploits engineered nucleases to generate site-specific double-strand breaks (DSBs) followed by resolution of DSBs by endogenous cellular repair mechanisms. The outcome can be either mutation of a specific site through mutagenic nonhomologous end-joining (NHEJ), creating insertions or deletions (in/dels) at the site of the break, or precise change of a genomic sequence through homologous recombination (HR) using an exogenously introduced donor template. A recent major addition to this platform is the clustered regularly interspaced palindromic repeat (CRISPR)/Cas system consisting of an RNA-guided nuclease (Cas) and a short guide RNA (sgRNA). The guide RNA is composed of two RNAs termed CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), which are typically fused in a chimeric single guide RNA (sgRNA). sgRNAs for genome editing can consist of 100 nucleotides (nt) of which 20 nt at the 5′ end hybridize to a target DNA sequence by means of Watson-Crick base pairing and guide the Cas endonuclease to cleave the target genomic DNA.
The native prokaryotic CRISPR-Cas system comprises an array of short repeats with intervening variable sequences of constant length (i.e., clusters of regularly interspaced short palindromic repeats, or "CRISPR"), and CRISPR-associated ("Cas") proteins. The RNA of the transcribed CRISPR array is processed by a subset of the Cas proteins into small guide RNAs, which generally have two components as discussed below. There are at least three different systems: Type I, Type II and Type III. The enzymes involved in the processing of the RNA into mature crRNA are different in the 3 systems. In the native prokaryotic system, the guide RNA ("gRNA") comprises two short, non-coding RNA species referred to as CRISPR RNA ("crRNA") and trans-acting RNA ("tracrRNA"). In an exemplary system, the gRNA forms a complex with a Cas nuclease. The gRNA:Cas nuclease complex binds a target polynucleotide sequence having a protospacer adjacent motif ("PAM") and a protospacer, which is a sequence complementary to a portion of the gRNA. The recognition and binding of the target polynucleotide by the gRNA:Cas nuclease complex induces cleavage of the target polynucleotide. The native CRISPR-Cas system functions as an immune system in prokaryotes, where gRNA:Cas nuclease complexes recognize and silence exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms, thereby conferring resistance to exogenous genetic elements such as plasmids and phages.
It has been demonstrated that a single-guide RNA ("sgRNA") can replace the complex formed between the naturally-existing crRNA and tracrRNA.
Considerations relevant to developing a gRNA, including a sgRNA, include specificity, stability, and functionality. Specificity refers to the ability of a particular gRNA:Cas nuclease complex to bind to and/or cleave a desired target sequence, whereas little or no binding and/or cleavage of polynucleotides different in sequence and/or location from the desired target occurs. Thus, specificity refers to minimizing off-target effects of the gRNA:Cas nuclease complex. Stability refers to the ability of the gRNA to resist degradation by enzymes, such as nucleases, and other substances that exist in intra-cellular and extra-cellular environments. Thus, there is a need for providing gRNA, including sgRNA, having increased resistance to nucleolytic degradation, increased binding affinity for the target polynucleotide, and/or reduced off-target effects while, nonetheless, having gRNA functionality. Further considerations relevant to developing a gRNA include transfectability and immunostimulatory properties. Thus, there is a need for providing gRNA, including sgRNA, having efficient and titratable transfectability into cells, especially into the nuclei of eukaryotic cells, and having minimal or no immunostimulatory properties in the transfected cells. Another important consideration for gRNA is to provide an effective means for delivering it into and maintaining it in the intended cell, tissue, bodily fluid or organism for a duration sufficient to allow the desired gRNA functionality.
The CRISPR/Cas system has also been adapted for sequence-specific control of gene expression, e.g., inhibition or activation of gene expression. Using particular Cas9 polypeptide variants that lack endonuclease activity, target genes can be repressed or activated. Unfortunately, genome editing and modulating gene expression using the CRISPR/Cas system remains inefficient, especially in primary cells. As such, there remains a need in the art for improved compositions and methods based on the CRISPR/Cas system that can be used for gene regulation, e.g., genome editing with enhanced efficiency, inhibiting gene expression, and activating gene expression. The present invention satisfies this need and provides additional advantages as well.

This patent is subject to a terminal disclaimer.

Specific synthetic chimeric Xenonucleic acid guide RNA; s(XNA-gRNA) for enhancing CRISPR mediated genome editing efficiency


A combination file folder and fastener for securing loose papers to the folder. The folder has a flap cut along a hinge line about which the flap is pivotable. There is a cover strip which covers a portion of the outside of the folder including the flap. A central portion of the fastener is sandwiched between the cover strip and the flap with the ends or prongs of the fastener extending into the interior of the folder such that loose papers may be positioned over the prongs and thereby secured within the folder.

File folders are commonly used in combination with metal fasteners for securing papers within the folder. Those metal fasteners generally comprise an elongate body with projecting prongs. The fasteners and folders are supplied separately, and when they are to be used, the prongs of the fastener are bent over and pushed through slits in the folder so that the body of the fastener is outside the folder and the prongs are inside. The loose papers are punched and placed over the prongs on the inside of the folder, after which the prongs are bent down against the inside of the folder. But, this type of folder and fastener combination are subject to the criticism that the bodies of the fasteners are exposed and tend to catch and damage other adjacent file folders when the folders are filed. These exposed portions of the fasteners can also damage furniture.


An inking pump for an offset printing press has a cylinder defining a bore in which a plunger is received for both rotation and linear reciprocation, creating a first and a second opposed fluid chamber. The cylinder has formed therein a first and a second suction port with a spacing therebetween axially of the bore, and, angularly spaced 180 degrees from the suction ports, a first and a second discharge port with an axial spacing therebetween. The plunger has formed in its surface a first recess for placing the first fluid chamber in successive communication with the first suction port and the first discharge port during each complete revolution of the plunger, and a second recess for placing the second fluid chamber in successive communication with the second suction port and the second discharge port during each complete revolution of the plunger. The first and second recesses are angularly spaced 180 degrees from each other about the plunger axis, so that the ink is delivered twice during each complete revolution, with concurrent one complete linear reciprocation, of the plunger.

1. Field of the Invention
This invention relates generally to pumps, and more particularly to a pump well adapted for use in an inking mechanism of the offset printing press, among other applications. Still more particularly, the invention pertains to a pump of the kind having a piston or plunger slidably received in a bore in a pump housing for joint rotation and linear reciprocation, featuring provisions for making the pump as constant as feasible in the rate of ink or other fluid delivery therefrom.
2. Description of the Prior Art
The inking pump of the kind in question differs from the so-called piston pump or reciprocating pump in that the plunger not only reciprocates linearly but rotates, too, at the same time. This type of pump is per se not new, however. Japanese Patents Nos. 2,864,447 and 3,095,744 are hereby cited as teaching pumps with a reciprocating and rotating plunger. Both of these prior art pumps are alike in requiring two plunger strokes and one revolution to complete a cycle; that is, the fluid is drawn in while the plunger is both traveling linearly in one direction and rotating a half revolution, and forced out while the plunger is both traveling linearly in the other direction and rotating another half revolution.
An objection to these known pumps, particularly in their use as inking pumps in an offset printing press, is that the suction stroke and discharge stroke of the plunger alternate, resulting in intermittent ink discharge. The ink density of the image is the highest at the end of the discharge stroke, diminishes during the ensuing suction stroke, and restarts rising upon commencement of the next discharge stroke. Such cyclic change in ink density presents a bar to the production of high-quality printings. Even totally defective printings may occur depending upon the images being printed, for some such images may be printed densely, and others thinly, to an unacceptable degree.
The present seeks to make a pump of the kind defined, far more constant than heretofore in the rate of fluid delivery during each cycle of operation and hence, in its intended typical use as an inking pump in an offset printing press, to enable the latter to produce printings of unfluctuating ink density.
Briefly, the present invention may be summarized as a pump suitable for use in an inking mechanism of a printing press, among other applications. Included is a plunger received in a bore in housing means for both angular and linear motion relative to the same, defining a first and a second opposed fluid chamber in the bore. The housing means has formed therein a first and a second suction port with a spacing therebetween axially of the bore, and a first and a second discharge port with a spacing therebetween axially of the bore, there being a preassigned angular spacing about the axis of the bore between the first and second suction ports and the first and second discharge ports, all of the first and second suction ports and the first and second discharge ports being open to the bore. The plunger has formed therein a first recess adjacent a first end thereof and in a first preassigned angular position thereon for placing the first fluid chamber in successive communication with the first suction port and the first discharge port during each complete revolution of the plunger, and a second recess adjacent a second end thereof and in a second preassigned angular position thereon for placing the second fluid chamber in successive communication with the second suction port and the second discharge port during each complete revolution of the plunger.
The plunger is driven for joint angular and linear travel relative to the housing means, making one complete linear reciprocation (i.e. one to-and-fro travel) during each complete revolution, or turning half a revolution during each stroke. During plunger travel from the first toward the second fluid chamber, the fluid will be drawn from the first suction port into the first fluid chamber via the first recess in the plunger and, at the same time, delivered from the second discharge port by being forced out of the second fluid chamber via the second recess in the plunger. During the return stroke of the plunger from the second toward the first fluid chamber, the fluid will be drawn from the second suction port into the second fluid chamber via the second recess in the plunger and, at the same time, delivered from the first discharge port by being forced out of the first fluid chamber via the first recess in the plunger.
Thus the pump draws in the fluid twice, and forces it out twice, during each cycle of operation. Therefore, through appropriate determination of the relative sizes and locations of the suction and discharge ports and the plunger recesses, fluid delivery will continue at all times but when the plunger is at its xe2x80x9cdead centerxe2x80x9d positions at both extremities of its stroke.
Constructed and operating as briefly outlined in the foregoing, the pump according to the present invention is particularly well suited for use in an inking mechanism of an offset printing press, in which application a plurality or multiplicity of pumps, each configured according to the invention, may be juxtaposed for conjoint operation in conformity with the usual practice in the art. The inking pump arrangement according to the invention will cause no such fluctuations in the ink density of the printings as have been conventionally experienced. No overly dense or overly light printings will be produced either, as the pumps are readily adjustable for optimum ink density according to the images being printed, making possible the printing of products that meet the most stringent demands of the clients.
The above and other objects, features and advantages of this invention and the manner of realizing them will become more apparent, and the invention itself will best be understood, from a study of the following description and appended claims, with reference had to the attached drawings showing the preferred embodiment of the invention.


A switching element and methods thereof are provided. The switching element includes a port from among a plurality of ports, which when configured to operate as a network protocol port sends and receives network information and when configured to operate as a storage protocol port sends and receives storage information. The port includes a control segment for generating a control signal for setting an operating mode of a serial and de-serializer (SERDES). The operating mode of the SERDES is selected based on whether the port is configured to operate as a network protocol port or as a storage protocol port.

The present disclosure relates to networks.
Networking systems are commonly used to move network information (may also be referred to interchangeably, as frames, packets, commands or others) between computing systems (for example, servers) or between computing systems and network devices (for example, storage systems). Various hardware and software components are used to implement network communication. Different network and storage protocols may be used to handle network information and storage information. Continuous efforts are being made to enhance the use of networking and storage protocols.

Configurable switch element and methods thereof


Anionically polymerizable monomers containing at least one silicon or titanium atom form polymeric photoresists having good dry etch resistance for use in microlithography. The monomers are of the formula ##STR1## wherein A is --H or --CH.dbd.CH.sub.2 ; X is a strong electron withdrawing group;. Y is a strong electron withdrawing group containing at least one silicon or titanium atom.. Preferably Y is ##STR2## wherein n is 1-5 and R.sup.2, R.sup.3 and R.sup.4 are C.sub.1 -C.sub.10 alkyl. A particularly preferred monomer is 3-trimethylsilylpropyl 2-cyanoacrylate.. Methods for applying a resist coating by vapor deposition of these monomers and exposure to radiation are described. A positive or negative tone image can be produced, depending upon the imaging method employed. The imaging layer may be applied over a planarizing layer to form a multilayer photoresist.

1. Field of the Invention
This invention relates to anionically polymerizable monomers containing at least one silicon or titanium atom, polymers thereof, and use of such polymers in photoresists, particularly for the microelectronics industry. In one aspect this invention also relates to vapour deposition and polymerization of silicon-functionalised cyanoacrylates.
2. Description of the Related Art
The use of anionically (or zwitterionically) polymerisable monomers as resist materials for microlithography is known in the art, as discussed in U.S. Pat. Nos. 4,675,273 Woods et al. and 4,675,270 Woods et. al. both assigned to Loctite (Ireland) Limited, the contents of which are incorporated herein by reference. Such resist materials are usually applied to or formed as a coating on an etchable substrate; the coated substrate is then imaged using high energy radiation; the image is developed by a development process, normally using a solvent; and the image is etched using a suitable plasma or chemical etching process.
Chemical etching has a significant disadvantage in that it is isotropic, i.e. the etching can affect the substrate below the photoresist. To achieve anisotropic etching, it is preferred to use dry etching by radio frequency glow discharge or large area ion beam methods. The most preferred methods are:
(i) plasma etching, e.g. using oxygen or a halocarbon, particularly a fluorocarbon such as CF.sub.4 or CH.sub.2 F.sub.2 with chlorine or argon; or PA1 (ii) reactive ion etching. PA1 (1) coating a substrate with a film that contains a cationic photoinitiator; PA1 (2) exposing the film in an imagewise fashion to radiation and thereby generating cationic initiator in the exposed regions of the film; PA1 (3) treating the exposed film with a cationic sensitive monomer to form a film of polymer resistant to plasma etching; and PA1 (4) developing the resist image by etching with a plasma. PA1 Y is a strong electron withdrawing group containing at least one silicon or titanium atom.
(See "Plasma Etching" by J. A. Mucha and D. W. Hess in "Introduction to Microlithography"(L. F. Thompson, C. G. Willson and M. J. Bowden Ed.) ACS Symposium Series 219, Am. Chem. Soc. (1983), 216-285; and "Multilayer Techniques and Plasma Processing" by A. Reiser in "Photoreactive Polymers--the Science and Technology of Resins", John Wiley & Sons (1989), 359-393).
However in plasma etching the photoresist itself is vulnerable to being etched away. There is a need therefore for polymeric photoresist films which have a good dry etch resistance. It is known to increase the plasma resistance of a resist material by including silicon in it (see the Reiser reference mentioned above, pages 375-381). U.S. Pat. No. 4,551,418 Hult et. al. describes a process for generating a negative tone resist image comprising the steps of:
The cationic sensitive monomer may be an organometallic monomer wherein the organometallic elements include silicon, germanium and tin. Particular examples of monomers include an epoxy substituted siloxane or silane or a silyl substituted vinyl ether. The monomer may be dissolved in a solvent or may be in the vapor state.
However there is no teaching concerning improving the dry etch resistance of anionically polymerizable resist materials.

Anionically polymerizable monomers, polymers thereof and use of such polymers in photoresists


The present disclosure is related to pharmaceutical compositions and methods for treating and/or preventing oxalate-related disorders. More particularly, the present disclosure pertains to compositions comprising an oxalate-degrading bacteria Oxalobacter formigenes particularly suitable for the treatment and/or prevention of late stage hyperoxaluria characterized by high plasma-oxalate levels and a progressing decrease in kidney function.

Oxalate is a metabolic end product which cannot be broken down by humans. The human body has two main excretory organ pathways for oxalate; the kidney and the intestine. Both pathways are controlled by transporter proteins abundant in the tubular and intestinal epithelium. It is of utmost importance that excretion of oxalate through urine and through the intestinal lumen is sustained.
Primary and Secondary hyperoxaluria are two distinct clinical expressions characterized for example by abnormal excretions of oxalate in the urine. Primary hyperoxaluria is an inherited genetic disorder with defective enzyme activities. In contrast, Secondary hyperoxaluria may be caused by a number of factors including increased dietary ingestion of oxalate or precursors of oxalate, or alterations in intestinal absorption or excretion of oxalate or fat and, alterations in intestinal microbiota or genetic variations of intestinal or tubular oxalate transporter protein expression. Hyperoxaluria is a known complication of Inflammatory Bowel Disease (IBD) and hyperoxaluria with hyperoxalemia is a common consequence of resection of parts of the small intestine and Roux-en-Y gastric bypass surgery. The symptoms of these diseases range from unique kidney stones, recurrent kidney stones and nephrocalcinosis to chronic kidney disease (CKD) and end stage renal disease (ESRD).
Secondary Hyperoxaluria
Oxalate-related CKD due to secondary hyperoxaluria is a health problem throughout the world. It is e.g. characterized by progressively increasing concentrations of oxalate in urine leading to kidney stones.
Secondary hyperoxaluria does normally not lead to ESRD unless hyperoxalemia has occurred. This is mostly common in patients with a resected small bowel such as SBS-patients and bariatric surgery patients.
The liver, the major metabolic organ in the body, is the main site of oxalate production. Oxalate is however not further metabolized and must therefore be excreted. This excretion occurs by two routes; through renal tubular excretion and through intestinal excretion; both excretion routes mediated by active transporter proteins from the SLC26 family. The concentration of oxalate in plasma and hence in tubular fluids is critical, e.g. during renal excretion, where increased oxalate concentrations cause risks for the formation of calcium oxalate crystals in the distal tubules and the connecting duct with subsequent formation of calcium oxalate depositions or calcification of the kidney. The intestinal excretion route is particularly important in preventing pathological conditions that involve elevated plasma oxalate concentrations and calcification of soft tissue.
Secondary hyperoxaluria may be caused by a number of factors including increased dietary ingestion of oxalate or precursors of oxalate, or alterations in intestinal absorption or excretion of oxalate or fat and, alterations in intestinal microbiota or genetic variations of intestinal oxalate transporters. Hyperoxaluria is a known complication of Inflammatory Bowel Disease. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease (Bhasin, 2015). This typically happens in diseases with impaired intestinal excretion due to inflammation such as Inflammatory Bowel Disease, vulvodynia, small intestine bacterial overgrowth (SIBS), gastroenteritis, gastritis, enteritis, enterocolitis, ulcerative colitis, Crohn's disease, and oxalate-related disorder in patients treated with a gastrointestinal lipase inhibitor.
When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in all body fluids and soft tissue. This is mostly common in patients with a resected small bowel such as Short Bowel Syndrome (SBS) patients, some IBD patients, intestinal cancer patients and bariatric surgery patients.
Also ESRD-patients on dialysis tend to build up plasma oxalate as a consequence of the kidney failure and may also suffer from oxalosis that could affect graft survival in kidney transplantation.
Primary Hyperoxaluria
Primary hyperoxaluria (PH) is a paediatric, seriously debilitating and life-threatening genetic disease with a high unmet medical need. PH is a rare autosomal recessive inborn error of glyoxylate metabolism, with significant morbidity and mortality, especially in young children. PH occurs as a consequence of an increased hepatic production of oxalate and is characterised by widespread calcium oxalate crystallization, progressing hyperoxalemia followed by reduced kidney function. As a result of renal oxalate excretion, patients with PH have high levels of urinary oxalate (>0.5 mmol/24 h/1.73 m2 vs. <0.5 mmol/24 h/1.73 m2 in healthy patients) [Hoppe, 2012]. Patients with PH have a wide range of oxalate production, reflected by hyperoxaluria ranging from slightly to highly elevated (>0.5-4.5 mmol/day, 1.73 m2). The extent of oxalate over-production is partly connected to specific genotypes, of which more than 140 are known. Progression to ESRD has been shown to correlate with age at diagnosis (time for exposure to high oxalate), the level of urinary oxalate excretion and kidney function at diagnosis [Zhao et al., 2016]. Patients with a high urinary oxalate excretion and low estimated glomerular filtration rate (eGFR) at diagnosis tend to progress more quickly to ESRD. In PH patients, plasma oxalate gradually increases from 1-3 μmoles/L at early stages to 45-50 μmoles/L at early ESRD. It is common that plasma oxalate rises as high as 150-300 μmoles/L during ESRD and dialysis treatment, leading to systemic accumulation of oxalate and systemic oxalosis.
Often, the first clinical symptoms of PH are renal tubular disorders, manifested by flank pain and kidney stones. The symptoms are primarily caused by calcium oxalate crystal-mediated inflammation of the tubular epithelial cells and growing calcium oxalate crystal deposition gradually causing calcification of the kidney. Progressive renal damage is caused by a combination of tubular toxicity from oxalate, nephrocalcinosis and renal obstruction by stones, or stone removal procedures [Cochat and Rumsby, 2013; Tang et al., 2015]. There is currently no approved pharmaceutical therapy for treatment of PH. Eventually the only curative therapy, only for PH type 1, is a combined kidney and liver transplantation at ESRD (Cochat et al., 2012). Overall, the median renal survival is 24-33 years [Lieske et al., 2005, Harambat et al., 2010].
There are three known types of PH (Type 1, 2 and 3) with Type 1 being the most severe and most widespread (70-80% of known cases) [Hoppe et al., 2009]. The three types of PH are caused by a deficiency or a mislocalisation of different enzymes affecting the hepatic production of oxalate: Type 1 is caused by a deficiency of liver-specific peroxisomal alanine-glyoxylate aminotransferase, Type 2 by a lack of glyoxylate reductase-hydroxypyruvate reductase and Type 3 by a lack of the liver-specific mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase [Cochat and Rumsby 2013, Belostotsky et al., 2010]. The estimated incidence of PH Type 1 is one case per 120,000 live births per year in Europe and the prevalence is one to three per million population [Cochat et al., 1995; Kopp and Leumann, 1995; van Woerden et al., 2003]. Incidence and prevalence may have been underestimated because of underdiagnosis [Leumann and Hoppe, 2001, Hopp et al., 2015].
Declining kidney function results in progressive hyperoxalemia and plasma calcium oxalate supersaturation. The increasing plasma oxalate concentrations cause calcium oxalate deposits to build up in the body. Deposits may be located in the bone, soft tissue, arterial media, peripheral nerves, skin, eyes and the heart [Beck et al., 2013]. Already at early stages in the disease, hyperoxalemia damages cells in the heart, causes calcification (stiffness) and causes inflammation in the myocardium leading to progressive reduced left ventricular strain leading to heart arrhythmia and heart failure (Lagies et al., 2013, Lagies et al., 2014, Lagies et al., 2015).
The interplay between biological molecules and crystal formation is an emerging field of research (see e.g. Aggarwal et al., 2013). In plasma, oxalate may be present as free oxalate, divalent metal-bound free oxalate, protein and lipid-associated oxalate and as solid divalent metal oxalate crystals. The ratio between total oxalate and free oxalate increases with time and disease progression.
After combined liver-kidney transplantation where the new liver produces normal levels of oxalate, an initial decrease of free oxalate is observed. However, when the plasma oxalate concentration is reduced under the saturation limit, calcium oxalate deposits in proteins and lipids, in vessel walls and soft tissue start to dissolve, which results in a new increase of the plasma oxalate concentration. Urinary and plasma oxalate can be elevated for many months to years following transplantation and may lead again to deterioration of the new kidneys (Leumann and Hoppe, 2001). Thus, the prevention of oxalate build-up before and during dialysis and enhancement of excretion of oxalate through the small bowel and through urine is highly beneficial for PH patients. Also for patients with maintained kidney function it is crucial to delay or stop accumulation of calcium oxalate deposition to prevent kidney deterioration.
Secondary Hyperoxaluria with Hyperoxalemia
Gregory et al, 1975, showed that Jejuno-Ileal Bypass (JIB) surgery in otherwise healthy bariatric patients caused renal failure. The elimination of the major intestinal excretion pathway caused high plasma oxalate concentrations, which in turn lead to renal failure. The procedure was discontinued in 1979. Today the dominant procedure for bariatric surgery is Roux-en-Y, a smaller resection of the jejunum/ileum. Although this procedure is associated with recurrent kidney stones, it does not cause ESRD.
Short Bowel Syndrome, SBS, is defined as a disease status where a patient has resected the small bowel and has less than 200 cm bowel left. Similarly to JIB patients, SBS patients have a 45% risk of kidney failure (ESRD) caused by increased concentrations of plasma oxalate.
Zellweger's disease, or the Zellweger spectrum disorders (ZDS) are characterized by a general loss of peroxisomal functions caused by deficient peroxisomal assembly. The disease is heterogeneous in its presentation and survival. Despite a normal level of the enzyme AGT (Alanine:glyoxylate aminotransferase) which is deficient in primary hyperoxaluria, severe hyperoxaluria has been reported in several ZSD patients (van Woerden et al, 2006).
Aspergillus niger infection is a rare fungus infection. A niger is an oxalate producing organism and can cause plasma oxalate at levels that can lead to ESRD.
Oxalobacter formigenes
Oxalobacter formigenes is a strict anaerobic bacterium that relies exclusively on oxalate as a substrate to obtain energy for its survival and growth. It is currently believed to be the most efficient oxalate-reducing enzymatic system that operates at neutral pH. Not all humans carry populations of O. formigenes in their intestinal tract. For example, there is a low or a complete lack of oxalate-degrading bacteria in the fecal samples of persons who have had jejunoileal bypass surgery. Administration of O. formigenes to a subject in need thereof has been shown to have an effect on dietary oxalate absorption, but it has also been shown to have effect on the elimination of oxalate from plasma to the intestine, promoting the natural intestinal oxalate excretion pathway. O. formigenes has furthermore been shown to promote active elimination of oxalate, possibly through interaction with SLC26 transporter proteins that enhance the oxalate flux from plasma to small bowel (Hatch et al., 2011; Hatch and Freel, 2013).
Compositions comprised of oxalate-degrading bacteria, such as O. formigenes for use in methods for reducing urinary and plasma oxalate for treating oxalate-related conditions have previously been disclosed in the art, such as in U.S. Pat. Nos. 6,200,562, 6,355,242, WO2007075447, and WO2005123114.
There is however still a need for improved compositions for treating oxalate-related disorders, particularly for treating or preventing calcium-oxalate deposition related disorders, such as calcium-oxalate deposition related disorder(s) involving hyperoxalemia as well as treating ESRD patients on dialysis. There is also a need for pharmaceutical compositions that may enhance or increase the excretion of oxalate to reduce the systemic oxalate burden and the related inflammation in patients with calcium oxalate deposition.

Compositions and methods for the treatment or prevention of oxalate-related disorders


In one aspect, a magnetic field sensor includes a plurality of tunneling magnetoresistance (TMR) elements that includes a first TMR element, a second TMR element, a third TMR element and a fourth TMR element. The first and second TMR elements are connected to a voltage source and the third and fourth TMR elements are connected to ground. Each TMR element has a pillar count of more than one pillar and the pillar count is selected to reduce the angle error below 1.0°.

Magnetic field sensors are used in a variety of applications, including, but not limited to, an angle sensor that senses an angle of a direction of a magnetic field, a current sensor that senses a magnetic field generated by a current carried by a current-carrying conductor, a magnetic switch that senses the proximity of a ferromagnetic object, a rotation detector that senses passing ferromagnetic articles, for example, magnetic domains of a ring magnet or a ferromagnetic target (e.g., gear teeth) where the magnetic field sensor is used in combination with a back-biased or other magnet, and a magnetic field sensor that senses a magnetic field density of a magnetic field.
Various parameters characterize the performance of magnetic field sensors and magnetic field sensing elements. With regard to magnetic field sensing elements, the parameters include sensitivity, which is the change in the output signal of a magnetic field sensing element in response to a magnetic field, and linearity, which is the degree to which the output signal of a magnetic field sensor varies linearly (i.e. in direct proportion) to the magnetic field.
Some magnetic field sensors include magnetoresistance (MR) elements, such as giant magnetoresistance (GMR) elements and tunneling magnetoresistance (TMR) elements. Generally, GMR and TMR elements have a relatively high sensitivity compared, for example, to Hall effect elements. GMR and TMR elements have moderately good linearity, but over a restricted range of magnetic fields. However, even in the restricted range of magnetic fields, the linearity of the GMR or TMR element can suffer from irregularities, such as due to high temperatures.
Further, angle sensors using GMR and TMR elements can experience angle error due to phenomena such as spin flop (i.e. alteration of reference direction at high magnetic fields or anisotropy field (e.g., magnetocrystalline anisotropy or shape anisotropy)). For example, the angle obtained with GMR elements can experience error up to several degrees.

Reducing voltage non-linearity in a bridge having tunneling magnetoresistance (TMR) elements


The present disclosure describes techniques for detecting and mitigating a spoof communication within a network, such as a Session Internet Protocol (SIP) network. More specifically, a SIP server, may receive a call request to initiate a Voice over Internet Protocol (VoIP) communication between an originating device and a recipient device. In response, the SIP server may analyze registration data associated with a subscriber account of the originating device, and in doing so, infer whether the call request is a spoof communication.

Today, the use of mobile devices is widespread. Continual advancements in mobile device technology can improve the productivity and quality of life for users by enhancing accessibility to real-time communications in a variety of environmental settings, such as a home, workplace, school, and/or so forth. However, mobile devices are highly susceptible to nuisance concerns by unspecified individuals that target some users for unwanted or ill-intentioned purposes. Unspecified individuals may include telephone marketers or spammers that initiate nuisance concerns. Unspecified individuals may also include individuals that impersonate a known person's identity (i.e. phone number) for fraudulent or nuisance purposes.
Therefore, the continual growth and advancement of mobile device technology can burden legitimate subscribers of a telecommunication service account in their attempt to trust that those voice communications received at their mobile device are from specified individuals with known identities, rather than unspecified individuals that spoof a known identity.

Mitigation of spoof communications within a telecommunications network


A process and apparatus is provided in which improved control of gas phase radicals is provided. In one embodiment, a system generating atomic oxygen is provided in which gases which generate the atomic oxygen are mixed prior to injection in a process space. The mixing may occur within a showerhead or prior to entrance into the showerhead. In another embodiment, a showerhead is provided which includes multiple zones. Some of the zones of the showerhead may inject the mixture of gases which generate the atomic oxygen into the process space, while other zones do not inject that mixture. In one embodiment, the mixture of gases which generates the atomic oxygen is injected into a main zone, while a subset of those gases is injected into inner and outer zones of the showerhead. The process and apparatus provides a uniform density of atomic oxygen across the substrate being processed.

The present disclosure relates to the processing of substrates. In particular, it provides an apparatus and method for treating surfaces of substrates.
Atomic layer deposition is a known technique for forming layers on a substrate. In atomic layer deposition, substrates are cyclically exposed to alternate gaseous species (or precursors). The gaseous species react with the substrate surface in a self-limiting or near self-limiting manner. A thin film may be slowly formed by repeating the cycles of alternating gaseous species. A variety of process tools may be utilized in atomic layer deposition processes. For example, batch furnace type systems may be utilized. Single substrate systems in which a process chamber is filled with gas and evacuated for a single substrate may also be utilized. Yet another system is a spatial atomic layer deposition system. In spatial atomic layer depositions systems, substrates travel at relatively high speeds past gas injectors or past a gas showerhead, or past a showerhead with injector outlets, which inject the necessary gases proximate the substrate surface to accomplish the atomic layer deposition process steps as the substrate passes in a cyclical manner.
One known atomic layer deposition process is the formation of atomic layer deposition oxide films, for example, silicon oxide. An exemplary process may include sequentially exposing the substrate surface to a silicon containing gas followed by exposure of the substrate surface to atomic oxygen (O). Atomic oxygen may be preferred due to excellent oxidation properties that result in a high quality silicon oxide deposited film. Exemplary spatial atomic layer deposition processes may include first exposing the substrate to silicon containing gas, such as for example, dichlorosilane (DCS), trichlorosilane, etc.). Next, the substrate may be exposed to atomic oxygen. Typical techniques for producing atomic oxygen include injecting a gas combination of oxygen (O2) and hydrogen (H2) above the substrate surface individually, where upon the O2 and H2 mix and react to form gas phase byproducts such as atomic oxygen (O). The atomic oxygen (O) may react with the silicon on the substrate to form silicon oxide. Such techniques are known as low pressure radical oxidation (LPRO). Typically the process occurs with the substrate heated and the injection of O2 and H2 at desired ratios at a low pressure (sub 10 Torr). The chemistries described above are merely exemplary known chemistries for atomic layer deposition of silicon oxide and it will be recognized that other chemistries may exist and atomic layer deposition of other materials may exist.
The creation of atomic oxygen in systems like a spatial systems may have other uses in addition to atomic layer deposition processes. For example, other uses of atomic oxygen surface treatments are known. In one embodiment, atomic oxygen may be provided at a surface so as to diffuse into the surface to form a diffused silicon oxide layer.
A problem that exists in systems utilizing atomic oxygen is providing a uniform density of the atomic oxygen across the surface of the substrate. A non-uniform density of atomic oxygen may result in a non-uniformly deposited film and other problems. For example, the non-uniformity of atomic oxygen will change the amount of atomic oxygen that diffuses into the substrate and change the formation of a diffused silicon oxide film. Such diffused films are generally undesirable in atomic layer deposition process due to consumption of the underlying material as opposed to forming a deposited film. Further, non-uniform atomic oxygen density will result in a non-uniform oxidation of the adsorbed silicon species. For example, if the adsorbed molecule is DCS, the DCS may not be fully oxidized and converted to silicon oxide. Subsequent cycles of DCS exposure may result in less DCS adsorption and thereby non-uniformities in the silicon oxide ultimately deposited.
Thus, it would be desirable to provide a system and method that provides for the improved uniformity of the density of gas phase radicals above a substrate.

Multiple zone gas injection for control of gas phase radicals