An aqueous hair setting composition having reduced tendency of flaking from the hair containing an alginate hair setting resin and a polymer having in a monomer unit at least one carboxylic acid moiety, said compositions preferably being in the form of an aerosol composition that produces a stable mousse upon delivery from the aerosol container.

Formulas containing alginates are known in the prior art, as exemplified by GB 1,036,497 to Schwarzkopf. The Schwarzkopf compositions are primarily aqueous systems containing an alginate. Although a hair setting effect is obtained when such compositions are applied to hair and dried, the form of these prior art compositions makes them difficult and inconvenient to apply to the head. Thus, Schwarzkopf first prepares a first composition containing the alginate which has an acidic pH above 3.6. To use the composition, it is essential that the pH of the first composition be lowered to below 3.6, to cause precipitation of the alginate. The pH may be lowered in two ways. First, an acidic solution may be applied to the hair after application of the hair setting composition. Alternately, the pH of the first composition may be lowered to below 3.6 just prior to setting the hair by adding a dilute acid solution to the first composition.
Disadvantageously, Schwarzkopf's procedure requires a two-step operation because the complete hair setting composition comprising the mixture of the first composition and the acidifying solution is inherently unstable. Necessarily, the product of Schwarzkopf would be provided in kit form comprising the first composition and the acidifying solution. Use of the product entails careful measurement of each part to obtain the right proportions of ingredients, use preferably being performed by the trained personnel of a hair styling salon. Thus, the Schwarzkopf product is greatly limited in its ease of use.
GB 1,017,843 also to Schwarzkopf discloses a hair-fixing composition containing a modified gelatine as the setting agent, in lieu of the conventional film-forming agents such as shellac, alginates, carragenates, gelatine, dextrins, polyvinyl pyrrolidone or copolymers thereof with polyvinyl acetate, dimethyl hydantoin, formaldehyde resins and polymeric acrylic acid derivatives.
As indicated above, the use of alginates in hair setting compositions has not been exploited commercially because such compositions are not particularly stable. This would be especially true with ready-to-use compositions sold over the counter to retail customers. Thus, the alginate tends to precipitate from the ready-to-use compositions, requiring the use of a kit-type product as disclosed in Schwarzkopf '497.
More recently, hair setting compositions have taken the form of hair sprays that utilize synthetic polymers as the active ingredient. These compositions are generally prepared using alcohols as the principal vehicle. However, alginates, being intolerant to alcohols present at high concentrations, have not been used in such hairspray compositions. Accordingly, an aqueous vehicle or a hydroalcoholic vehicle having a low alcohol concentration must be employed in alginate hair setting compositions.
The problem of alginate instability is of greater concern in hair spray products, typically aerosol sprays, but also pump sprays. This is because alginate, if precipitated, clogs the valve of the spray nozzle. As a further disadvantage, when applied to hair, the alginate hair setting agent present in hair setting compositions tends to flake off. As a result, the consumer has the appearance of having dandruff.
Surprisingly, it has now been found that both the flaking problem and the stability problem can be largely alleviated by incorporating a polymer material having at least one carboxylic acid moiety into the hair setting composition.


An electronics cooling system comprises a tubular fan duct and an electronics housing. The fan duct includes has a fan duct casing containing a fan with rotor blades and stator vanes. The electronics housing is mounted directly on the tubular fan duct, such that the electronics housing and the fan duct casing together enclose an interior space. A cooling airflow path extends from a high-pressure region of the tubular fan duct, through an inlet hole into the interior space, and out a bleed hole into a surrounding environment. The electronics cooling system further comprises three electronics mounts within the interior space. A first electronics mount is located immediately adjacent to the inlet hole, on the fan duct. A second electronics mount is located immediately radially outward of the stator vanes, on the fan duct. A third electronics mount is located immediately adjacent to the bleed hole, on the housing.

The present invention relates generally to electronics cooling, and more particularly to air cooling for a fan motor controller.
Fans are commonly used to dissipate heat from electronic components, thereby avoiding component failure and extending component lifetimes. Some electronic components in aircraft, including motor controllers, are commonly located in motor controller housings mounted on fan housings. Electronics installed in these motor controller housings are conventionally cooled with airflow circulated by the nearby fan. Some such cooling systems divert relatively cool air from a region of the fan duct downstream of the fan, and pass this air through the housing before releasing it into the environment at a vent in the housing. Other conventional cooling systems take in air from the environment for cooling by means of an outlet in the casing, and draw this air through the housing by means of an air passage from the housing to a region of the fan duct immediately upstream of the fan. In aircraft, the fan which provides cooling airflow may be a part of an air management system. The amount of air utilized for cooling is typically small compared to the total airflow volume of the fan—usually on the order of 2%—and thus does not disrupt normal fan functions, such as cabin or lavatory air circulation or for electronics bay cooling.
Conventional fan motor controller assemblies comprise a box-like fan motor controller housing with a flat base mounted to an adjacent cylindrical fan duct via an intervening thermal interface which adds to the cost and weight of the total assembly. In addition, many fan motor controller housings include machined fins arranged near high-heat components to increase heat dissipation surface area. These fins also increase the cost and weight of the total assembly.
It is generally desirable that the spatial footprint of fan motor controller hardware be as small as possible. Any increase to the packing density of heat generating electronics, however, necessitates corresponding improvements to heat dissipation, to avoid excessive component degradation. There exists, therefore, a need for fan motor controller housings capable of increased cooling at lower cost and weight.

Integrated fan motor and controller housing


A positive electrode material includes: a composite oxide of solid solution including Li2SnO3 and Li2NiαM1βM2γMnνO4-∈. α satisfies an equation of 0.50≤α≤1.35. β satisfies an equation of 0≤β<1.0. γ satisfies an equation of 0≤γ≤0.66. β and γ satisfies an equation of 0.33≤β+γ≤1.1. ν satisfies an equation of 0≤ν≤0.66. ∈ satisfies an equation of 0≤∈≤1.00. M1 represents at least one selected from Sn, Sb0.5Al0.5. M2 represents Sb.

With the spread of electronic devices such as notebook computers, mobile phones, and digital cameras, the demand for secondary batteries for driving these electronic devices is on the increase. In recent years, these electronic devices have increasingly high power consumption with enhancement of functionalities thereof and have been expected to be reduced in size, and hence improvement in performance of the secondary batteries has been required. Among the secondary batteries, a non-aqueous electrolyte secondary battery (particularly, a lithium-ion secondary battery) can be increased in capacity, and this battery has thus been applied to a variety of electronic devices.
Generally, a non-aqueous electrolyte secondary battery has a configuration in which a positive electrode and a negative electrode are connected via a non-aqueous electrolyte (non-aqueous electrolytic solution), and stored in a battery case. In the positive electrode, a positive electrode active material layer containing a positive electrode material typified by a positive electrode active material is formed on the surface of a positive electrode current collector. In the negative electrode, a negative electrode active material layer containing a negative electrode active material is formed on the surface of a negative electrode current collector.
In a lithium-ion secondary battery as a typical example of the non-aqueous electrolyte secondary battery, a lithium composite oxide is used as a positive electrode material (positive electrode active material). This composite oxide is described in Patent Literature 1, for example.
Patent Literature 1 describes a non-aqueous electrolyte battery having a positive electrode active material with a Sn-containing oxide deposited on the surface of a lithium nickelate-based oxide (LiNiO2-based oxide).
In the non-aqueous electrolyte secondary battery, there has been a possibility that a crystal structure of a lithium composite oxide used for the positive electrode active material is destructed due to a kind of over-heating, overcharge or the like, to release contained oxygen which would trigger abnormal exothermic reaction, ignition and fuming.
The positive electrode active material described in Patent Literature 1 was aimed at preventing the surface state from deterioration in load characteristics by coating the surface of the lithium nickelate-based oxide with the Sn-containing oxide. However, a structure of the lithium nickelate-based oxide (lithium composite oxide) in the bulk remains as it is. That is, the above-mentioned problem of deterioration in safety associated with release of oxygen from the lithium nickelate-based oxide with destruction of the crystal structure remains unsolved in the process of charge-discharge cycling as well.
Patent Literature 1: JP 2003-257434-A

Positive electrode material, positive electrode for non-aqueous electrolyte secondary battery, and non-aqueous electrolyte secondary battery


A process for preparing a solid pre-catalyst component for use in olefinic polymerization includes dissolving a magnesium chloride in an alcohol and optionally adding water to form a first solution having a water content of about 0.5 mmol water per mol MgCl2 to about 100 mmol water per mol MgCl2; contacting the first solution with a first titanium compound to form the solid pre-catalyst component; and treating the solid pre-catalyst component with a hydrocarbon or halogenated hydrocarbon solvent, optionally containing a second titanium compound.

Polyolefins are a class of polymers derived from simple olefins. Known methods of making polyolefins involve the use of Ziegler-Natta polymerization catalysts. These catalysts polymerize vinyl monomers using a transition metal halide to provide a polymer with a highly isotactic stereochemical configuration.
One type of a catalyst system includes a solid pre-catalyst component, having a magnesium dihalide (generally, a magnesium chloride) on which are supported a titanium compound and an internal electron donor compound. In order to maintain the high selectivity for an isotactic polymer product, a variety of internal electron donor compounds must be added during the pre-catalyst synthesis. Prior the polymerization reaction, the oxidation state of the titanium compound is reduced in presence of an aluminum alkyl to form the catalyst.
It is generally understood that Ziegler-Natta polymerization catalysts are extremely sensitive to even small amounts of water, which a can "poison" the catalyst and reduce polymer productivity. Accordingly, most procedures to prepare the solid pre-catalyst component go to great lengths to exclude water or dry the reagents during or prior to preparation of the pre-catalyst component.
Without being bound by theory, the present inventors have found that inclusion of water during catalyst preparation acts as a promoter for the Ziegler-Natta MgCl2 based catalyst to improve the catalyst activity and catalyst morphology.


A method of forming an electrolyte includes removably coupling a perimeter support to a temporary substrate, and electrodepositing an electrolyte composite film on the temporary substrate.

During the past several years, the popularity and viability of fuel cells for producing both large and small amounts of electricity has increased significantly. Fuel cells conduct an electrochemical reaction with reactants such as hydrogen and oxygen to produce electricity and heat. Fuel cells are similar to batteries except that fuel cells can be "recharged" while providing power. In addition, fuel cells are cleaner than other sources of power, such as devices that combust hydrocarbons. Fuel cells provide a direct current (DC) voltage that may be used to power almost any electrical device such as, motors, lights, computers, or any number of electrical appliances.
Fuel cells typically have three component parts: an anode, a cathode, and an electrolyte. The electrolyte is sandwiched between the anode and cathode. There are several different types of fuel cells, each using a different chemistry. Fuel cells are usually classified, depending on the type of electrolyte used, into one of five groups: alkaline fuel cells (AFC), phosphoric-acid fuel cells (PAFC), solid oxide fuel cells (SOFC), molten carbonate fuel cells (MCFC), and proton exchange membrane fuel cells (PEMFC). One variant of the PEMFC technology includes direct methanol fuel cells (DMFC), in which liquid methanol is directly fed to the fuel cell as fuel.
PEMFCs typically function by supplying hydrogen to the anode. The hydrogen is used by the anode to provide protons to the electrolyte and releases electrons that pass through an external circuit to reach a cathode located opposite the anode. The protons solvate with water molecules and diffuse through the membrane to the cathode where they react with oxygen that has picked up electrons thereby forming water. PEMFCs have a number of distinct advantages over other fuel cells. PEMFCs have a very high power density (40% to 60% efficiency) and a very low operating temperature (around 80 degrees Celsius). Moreover PEMFCs do not utilize dangerous chemicals that may spill or leak. These qualities make PEMFCs extremely safe and low in maintenance requirements.
Traditionally, the proton exchange membrane (PEM) of a PEMFC has been formed by applying a solid semipermiable membrane to an electrode layer with an adhesive layer between the two. The membrane-adhesion layer electrode stack would then be compressed in the presence of heat to bond the layers together. However, traditional methods of forming PEM fuel cells tend to have a low amount of mechanical stability and are susceptible to swelling of the electrolyte. This swelling of the electrolyte often leads to increased fuel crossover resulting in degraded fuel efficiency of the fuel cell.
Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements.

System and a method for manufacturing an electrolyte using electro deposition

Hewlett-Packard Development Company, L.P.


The present invention discloses a novel active insulation device and method for thermally shielding an external body from temperature fluctuations of a contained body. The method comprising providing an active thermal insulation envelope between the contained body and the external body; regulating the heat transfer from the active thermal insulation envelope to the external body; and regulating the heat transfer from the contained body to the active thermal insulation envelope, thus maintaining the temperature of the external body at a constant temperature or within a narrow temperature range.

A magnetic resonance imaging device produces a measurement of a sample which is based upon its molecular structure. The sample is subjected to a polarizing magnetic field which has the effect of aligning the spins of all the atomic nuclei of the sample. Radio waves at a frequency close to the Lamor frequency of the nuclei are then used to excite the nuclei such that their magnetic alignment is reversed. Once the excitation is removed the nuclei return to their original state by emitting characteristic radio signals. It is these radio signals that can be used to image the sample.
The exact Lamor frequency is dependent upon the precise magnetic field. By creating a magnetic field gradient within the sample cavity the source of these signals can be located such that an overall image of the sample can be constructed.
The efficiency of this process depends upon the consistency of the magnetic field strength within the sample cavity. This field is typically controlled to within 5 parts per million. The extent of the uniformity of the magnetic field determines the accuracy with which the Lamor frequency can be measured. This allows for the resolution of smaller chemical shifts.
The magnetic field is dependent to a large extent upon the ferromagnetic properties of the materials making up its magnetic assembly. These ferromagnetic characteristics are often temperature dependent and so it is important to maintain the magnetic assembly at a constant temperature. This can be particularly problematic where the temperature of the sample being imaged is itself fluctuating. In such a scenario it is necessary to introduce a means of insulating the magnetic assembly from the magnetic assembly.
Passive insulation is insufficient to stabilize a sensitive permanent-magnet magnetic resonance system. This is due to the nature of permanent magnet material that has a sensitive temperature coefficient that causes the magnetic field of the system to fluctuate beyond an acceptable range. There is thus a long felt need in the art for a means and method of maintaining a constant temperature in the magnetic assembly of a magnetic resonance device.

Means and method of maintaining a constant temperature in the magnetic assembly of a magnetic resonance device


This invention relates generally to processes for extracting iron and/or calcium from geothermal brines.

Manganese in many forms is used in a variety of industrial and other applications. It is the fourth most used metal in terms of tonnage, after iron, aluminum and copper. As a trace element, it is found in the body, and also has a variety of uses in industry. For example, manganese dioxide is used in dry cell batteries, in aluminum cans, and in the electronic components of television sets.
Manganese is most often extracted from seawater and other natural sources, but can also be separated from other metals found in aqueous solutions that are byproducts of many industrial processes. For example, geothermal steam and hot brines are found in naturally occurring, large subterranean reservoirs throughout the world. In many areas where extraction is convenient, the steam and hot brines provide a partially renewable resource for the production of power. The pressurized, hot geothermal brines are extracted from the earth to generate power by using steam flashed off from the brine to power a turbine. Thereafter, metals such as manganese can be extracted from the brine before it is returned to the ground.
One of the general problems encountered with the extraction of metals from aqueous solutions involves changes in pH associated with the exchange of metal ions for hydrogen ions in ion exchange reactions. This causes a progressive lowering of the pH which in turn impedes the efficiency of the process. Attempts to solve this problem have been reported, but their success has been limited. See, for example, U.S. Pat. No. 4,128,493, which reports the use of organic solvents and quaternary ammonium salts to extract metals from acidic solutions.
Other methods for recovering metals such as zinc from geothermal brine include precipitation with sulfides and various combinations of solvent extractions and electromagnetic stripping. However, continuous batch processes using these methods are limited due to scaling of the equipment due to the presence of large amounts of silica.
Manganese is usually extracted in the form of electrolytic manganese dioxide (EMD). Perhaps the most common process being used today for extracting manganese is by mixing the manganese-containing material with sulfuric acid to form a manganese sulfate electrolyte. This intermediate is separated from other metals by precipitation and filtration. Thereafter, the manganese sulfate is subjected to solvent extraction and electrowinning. See, for example, PCT WO 99/14403; and L. A. Mel'nik, et al., Russian J. of Electrochemistry 32:248-251 (1996).
The current sulfate process for the production of electrolytic manganese dioxide (EMD) was invented more than seventy years ago in the US. However, it was commercialized in the early 1950's in a move largely driven by the US military seeking higher quality batteries for use in Korea. The standard sulfate process is still the only commercial process for the manufacture of EMD.
The only significant market for EMD is its use in dry cell batteries (small amounts are also consumed in the production of soft ferrites for the electronics industries). Optimum battery performance is based on a combination of chemical, physical and electrical characteristics. However, the key feature of EMD which sets it apart from other manganese dioxides is its crystal structure. This all important characteristic is developed during high temperature aqueous electrolysis, the heart of the EMD manufacturing process. Although a typical specification for EMD might have about 20 components, EMD quality is defined by 4 key criteria: Crystal structure (disordered, hydrated, non-stoichiometric); Chemical purity (minimum 92% MnO2 (remainder essentially water) with key impurities at the single digit ppm level); Density (higher the better, since batteries are fixed volume devices); and Intrinsic discharge capacity (measured in mAh/g MnO2, again higher the better).
The standard sulfate process for EMD has been undergoing continual development since it was first commercialized in the 1950s. See e.g., Nathsarma, et al., Hydrometallurgy 45: 169-79 (1997); Alexperov et al., Journal of Applied Chemistry of the USSR 65: 2342-44 (1992). These developments have been largely driven by demands for improvements in product quality. However, the key elements of the process are unchanged.
One of the largest challenges facing the EMD industry is waste management. The best manganese ores available to the industry contain only 50% Mn. Insoluble gangue from the ore combined with wet filter cakes from process purification and filtration stages typically generate some 2 to 3 tons of solid waste per ton of EMD product. While manganese occurs widely in nature and is not generally considered a toxic element, solid wastes containing soluble manganese must be immobilized and contained in sealed dump sites to prevent ground water contamination. A large proportion of the worlds EMD capacity is located in environmentally sensitive regions, such as Japan, Europe, USA and Australia. Containment of waste is a major limitation to expansion for many existing producers.
A second limitation of the standard sulfate process is the low current density, typically about 55 A/m2, at which plants must operate, although some plants operate between about 50 A/m2 to 70 A/m2. This is one fifth to one tenth the current density normally associated with metal electrowinning processes. It is known that a chloride electrolyte supports higher current densities for the production of EMD, in the order of 80 to 100 A/m2, improving plant productivity and reducing capital cost per annual product ton. However, a chloride electrolyte system has not yet been adopted.
Accordingly, there is a need for a more efficient process for extracting EMD from various natural and industrial sources that is more compatible with environmental concerns and commercial needs. The present process, based on the recovery of manganese units from liquid brine and electrolysis of a chloride liquor, has the potential to overcome or minimize these two limitations of the standard sulfate process.

This patent is subject to a terminal disclaimer.

Process for depleting calcium and/or iron from geothermal brines


A present server transmits to a second user terminal attribute information authentication request information for requesting authentication of attribute information registered by a first user when a predetermined request is received from a first user terminal. Also, the server registers authenticated information in association with the attribute information of the first user when the authentication information, which indicates that the attribute information registered by the first user has been authenticated, has been received. When a request is made to view the attribute information of the first user, the existence of the authenticated information is determined, and if the authenticated information is registered, attribute authentication display information is generated and transmitted so as to be visually and identifiably displayed on the user terminal to indicate that authenticated information exists.

In recent years, there has been an increasing number of services for forming new friendships using community websites established on the Internet or other communication networks. Such services are referred to as social networking services (hereinafter referred to as "SNS services"). Characteristics such as name, address, birthday, hometown, alma mater (academic background), work (profession), email address, blood type, hobbies, preferred sports, and favorite foods are registered as attribute information of a user, and are used as an aid for forming new friendships.
With this SNS service, all or part of the attribute information is disclosed to other participants who have signed up for the SNS service and are forming friendships, by setting disclosure settings related to the attribute information registered during signup. The disclosure of attribute information facilitates the formation of new friendships when the range of the attribute information is increased, and when a greater amount of detail is registered, attribute information that is had in common is used as a connection that facilitates the formation of new and closer friendships.
SNS services are founded on the concept of building human networks based on existing human relationships and trusted relationships in the actual society of friends and acquaintances. Therefore, the registered attribute information must be factual as a condition for using an SNS service, as otherwise the human relationships and trusted relationships, i.e., the person-to-person connections, cannot be maintained.
Such an SNS service is a service that is accessed on a website as described above. Therefore, it is difficult to confirm personal identity using a driver license, passport, health insurance card, or the like as is performed by, e.g., financial institutions to open an account, or when purchasing a mobile phone, or in other such situations. Therefore, no form of personal identification is currently used.
As a result, pseudonyms and false information that do not match actual attribute information can be easily registered. Anonymity is maintained once false attribute information has been registered and it is not easy to identify the real person when misconduct has occurred. Therefore, by misusing the fact that the real person cannot be identified, users who carry out improper acts are sometimes permitted to slander and defame other people, to post vulgar images, or to carry out other improper activities that are contrary to good public conduct on the network service website.
There are also SNS services that cannot be used without an invitation from an existing participant who has previously registered attribute information and become a member, and there are services in which any number of unspecified persons can freely participate. Additionally, the registration of users who carry out improper activities under a pseudonym cannot be effectively removed, and there is a risk that the safe and secure maintenance and expansion of friendship relationships cannot be guaranteed.
In view of the above, a method has been proposed (see Patent Document 1) as a way to prevent impersonated contracts and other improper activities has been proposed. In the method, a confirmation terminal of an affiliated store or a confirmation terminal device at a sales finance company where the customer is present is used for providing information required to confirm intent and personal identify of a contract signatory by establishing a connection via a communication line and simultaneously transceiving audio, video, and the like in two directions.
Although for a different purpose, there has also been proposed a method (see Patent Document 2) in which a member who is introducing a new member inputs predetermined details that include the name and email address of the person being introduced, and an email containing instructions is automatically sent to the mail box of the person being introduced on the basis of the email address. The person being introduced reads the instruction email, confirms the name and other information thus inputted, makes changes if there is an error, and then adds attribute details such as address, telephone number, work address, and family.
However, the method described in Patent Document 1 is designed to prevent misconduct such as impersonation by a third party, and is not designed to prevent a person from registering false content with ill intent or the intention of carrying out improper activities.
Also, the method described in Patent Document 2 is designed so that a person can confirm and correct the details inputted by the person to be introduced, and is not designed to prevent a person from registering false content with ill intent or the intention of carrying out improper activities.
Techniques have thus been proposed for preventing misconduct such as impersonation by a third party. However, there is currently no proposed technique for preventing a person with ill intent from registering false content, and for guaranteeing the safe and secure maintenance and expansion of friendships with other participants.
[Patent Document 1] JP-A 2007-26154
[Patent Document 2] JP-A 2002-279124

Attribute information authentication apparatus, attribute information authentication method, and storage medium for storing computer program


A method of operating a multi-fuel combustion system is provided. The method includes a first phase and a second phase, wherein the first phase includes providing ignition to a combustor basket to ignite a first type of fuel, where the first type of fuel is supplied to the combustor basket through a first conduit. Also in first phase steam is also supplied to the first conduit in addition to the first type of fuel and steam is supplied to the second conduit after the ignition. In the second phase a second type of fuel is supplied to the combustor basket through the second conduit after ignition of the first fuel through the first conduit, while stopping the supply of the first fuel, and continuing to supply steam through both the first and second conduits.

Future energy demand, scarcity of available fuels and environmental regulations put pressure on power plant producers to come up with solutions for safe, efficient and clean ways to generate power. The scarcity of fuels mainly applies to oil and to a lesser extend to natural gas. With an availability of coal in abundance, electricity production from coal is mostly done using steam power plants. A cleaner and more efficient option to generate power from coals is to use them in an integrated gasification combine cycle (IGCC). In an IGCC, coals are first gasified to yield syngas, consisting mainly of CO (carbon monoxide) and H2 (hydrogen).
Syngas typically has a significantly lower calorific value as compared to conventional natural gas fuels. By removing the CO content from the syngas prior to combusting it, one also has an effective means for CO2 (carbon-dioxide) capture. The IGCC concept with pre-combustion CO2 capture is one of the most cost-effective ways to produce electricity and avoid the emission of CO2 in the future. The economical potential of the IGCC plant with CO2 capture can increase even further when natural gas prices rise faster than expected or with increased carbon tax regulation.
Due to the low calorific value and high hydrogen content, the combustion of syngas fuels requires the development of adapted or completely new combustion systems which are able to handle the wide range of syngas fuels, and produce little emissions and can handle the high reactivity of the fuels.
The syngas fuel composition depends on the type of gasifier used and on whether or not the CO is separated from the fuel. Besides syngas fuels, the combustion system might run on a second conventional fuel for backup and start up. The ideal possibility is to have all the different types of fuels combusted in a stable way by one combustion system by performing a proper combustion method to increase the efficiency and compensate for the efficiency loss due to the gasifier.

Method of operating a multi-fuel combustion system


A semiconductor device and method of making same are disclosed. In some embodiments, a method includes: forming a first thermoelectric conduction leg on a substrate; forming a second thermoelectric conduction leg on the substrate to be aligned with the first thermoelectric conduction leg along a same row; forming at least one intermediate thermoelectric conduction structure on an end of the second thermoelectric conduction leg; forming a contact structure to couple the first and second thermoelectric conduction legs via the at least one intermediate thermoelectric conduction structure; and recessing the substrate to form at least one trench substantially adjacent to a respective side edge of either the first thermoelectric conduction leg or the second thermoelectric conduction leg.

Thermoelectric power generation is a technique for converting thermal energy into electric energy with the use of the "Seeback effect." The Seeback effect is a phenomenon in which a temperature difference given to opposing ends of a substance causes a thermal electromotive force in proportion to the temperature difference, whereby electric power (e.g., a current or a voltage signal) can be taken out by externally coupling a load to the substrate. Devices operating based on such a technique (thermoelectric power generation) have been seen in various applications such as, for example, wearable electronics, wireless sensor networks, system on chip circuits, etc.
In some cases, a thermocouple device, made of either conductor or semiconductor material, can be placed across a temperature difference to generate electric power based on the above-described technique. Generally, when the temperature difference is provided across respective ends of the thermocouple device, which are typically referred to as hot and cold ends, respectively, a voltage (or current) signal (i.e., the electric power) can be measured therebetween. Such a thermocouple device is typically categorized as one of various thermoelectric energy generation (TEG) devices. In accordance with increasing needs for a high-performance and CMOS-compatible thermocouple device (e.g., a miniature size, low heat leakage, a reliable durability, etc.), various, material- and/or structure-wise, types of thermocouple devices have been proposed to further improve performance of existing thermocouple devices. However, such known thermocouple devices have not been entirely satisfactory in order to provide desired performance while being able to be fabricated using CMOS-compatible technologies.

Taiwan Semiconductor Manufacturing Co., Ltd.


An overland vehicle is provided which includes a chassis with a roll-over protection structure, a powertrain configured to generate power to drive the overland vehicle, a first suspension system configured as a chassis to ground suspension system, and an operator compartment. The vehicle may also include a second suspension system configured to pneumatically suspend the operator compartment within the chassis, where the second suspension system includes a plurality of pneumatic couplers, including at least a first pneumatic coupler suspending the operator compartment to the chassis along a first vector extending in a first direction, and a second countering pneumatic coupler suspending the operator compartment to the chassis along a second vector extending in a second direction, where the second direction is generally opposite the first direction. In another embodiment, the second suspension system may include a plurality of spaced apart pneumatic couplers, including at least a first pneumatic coupler suspending the operator compartment to a first side of the chassis, and a second pneumatic coupler suspending the operator compartment to a second side of the chassis.

Some overland vehicles are designed for rugged and/or off-road applications including, but not limited to commercial, military and construction applications. These vehicles may be tracked or wheeled vehicles and they typically include an operator compartment designed to hold one or more occupants in the vehicle.
The operator compartment is fixed to the vehicle's chassis and it may be integrally formed with the vehicle's chassis. A powertrain is coupled to the chassis to generate power to drive the vehicle. A conventional suspension system, also known as a "chassis to ground" suspension system, is designed to provide relative motion between the chassis and the ground to keep the tracks/wheels in contact with the ground while also maintaining ride quality for the vehicle's occupants.

Vehicle with pneumatically suspended operator compartment


A musicians telephone interface that interconnects an instant location through a telephone line to a remote location such device having inputs to receive the sound from musical instruments and/or vocalization at each location with balancing circuitry and broadcast means at each location for the musicians at each location to hear the music of one another simultaneously balanced for collaboration and production of music.

1. Field of the Invention
This invention resides in the area of telecommunications and more particularly relates to a telephone interface to interconnect the musical output of musicians at different locations so that a first musician can not only hear the music of other musician(s) at remote locations as the first musician plays but also such first musician can receive feedback of his own music. Thus each musician while playing over the telephone at remote locations from one another can contribute to the resulting musical work.
2. Description of the Prior Art
At present musicians must be in the same location in order to play together. Collaboration of musicians is highly desirable in the area of musical composition. Telephone interfacing has been utilized to interconnect game apparatuses so that two remote players can play a single game with each player receiving data over the telephone indicating the move of the other player such as disclosed in U.S. Pat. No. 4,372,558.


An automated medical instrument cleaning system is particularly adapted to provide a complete application of wet/dry detergent foam to medical instruments in a point of use cleaning operation for instrument reprocessing, in a consistent and fully adjustable manner. The system comprises a microprocessor, a user interface, and an adjustable wand for the application of foam that covers surface and internal lumens of the instruments to be cleaned, using wand applicators, to quickly and easily coat all external and internal instrument surfaces with detergent foam before the bio burden has a chance to harden.

Although medical science has made tremendous advances in the past few decades, improving greatly the quality of life and longevity of patients, infectious diseases continue to plague society, and especially these other advances. Such infections, particular in hospital settings, have become very stubborn and difficult to treat, particularly as antibiotic resistance has increased, and thus alternatives for treating infections have diminished.
Unfortunately, current cleaning approaches usually involve a manual application of detergent spray, which does not cover and invade internal lumens, or, sometimes, external surface features, such as channels or other protected areas. This shortcoming allows organic contaminants to remain embedded on or within used medical instruments, potentially causing infection problems when re-used.
Accordingly, it has become more important than ever to ensure that reusable medical instruments are thoroughly cleaned and sanitized between uses, and improved systems for ensuring same are needed.


A thermal energy storage apparatus that absorbs thermal energy from a heat-generating device is described. In one aspect, the thermal energy storage apparatus comprises a non-metal container and a phase-change material. The non-metal container is configured to receive the heat-generating device thereon. The phase-change material is contained in the non-metal container and configured to absorb at least a portion of heat from the heat-generating device through the non-metal container.

Compact heat-generating devices, such as laser diodes, light-emitting diodes (LEDs), vertical-cavity surface emitting lasers (VCSELs), integrated circuits including microprocessors, microwave chips and the like, generate thermal energy, or heat, when in operation. Regardless of which type of heat-generating device the case may be, heat generated by a compact heat-generating device needs to be removed or dissipated from the compact heat-generating device in order to achieve optimum performance of the compact heat-generating device and keep its temperature within a safe operating range. With the form factor of compact heat-generating devices (e.g., sensors or ASIC drivers in a telecom router, cellular phone tower, data communications server or mainframe computers) and the applications they are implemented in becoming ever smaller (e.g., the processor in a smartphone, a tablet computer or a notebook computer) resulting in high heat density, it is imperative to effectively dissipate the high-density heat generated in an area of small footprint to ensure safe and optimum operation of compact heat-generating devices operating under such conditions.
Many metal-based water-cooled and air-cooled cooling packages have been developed for use in compact packages to dissipate heat generated by the various types of compact heat-generating devices mentioned above. For instance, heat exchangers and heat pipes made of a metallic material with high thermal conductivity, such as copper, silver, aluminum or iron, are commercially available. However, most metal-based heat exchangers and heat pipes experience issues of oxidation, corrosion and/or crystallization after long periods of operation. Such fouling factors significantly reduce the heat transfer efficiency of metal-based heat exchangers and heat pipes. Other problems associated with the use of metal-based cooling packages include, for example, issues with overall compactness of the package, corrosion of the metallic material in water-cooled applications, difficulty in manufacturing, and so on. With increasing demand for high power density in small form factor, there is a need for a compact cooling package for compact heat-generating devices with fewer or none of the aforementioned issues.
One issue with heat dissipation in portable/mobile applications is that, even when heat generated by a heat-generating device (e.g., the processor in a smartphone, a tablet computer or a notebook computer) is removed or otherwise transferred away from the heat-generating device, the heat more or less is transferred to other portions of the portable apparatus in which the heat-generating device resides. This may not be desirable especially in portable/mobile applications. For instance, at least a portion of the heat generated by a microprocessor in a notebook computer is transferred to the casing of the notebook computer (e.g., a portion of the computer's casing closest to the microprocessor) making the casing warm or even hot to touch. As another example, some notebook computers may have a cooling fan installed therein to promote heat transfer by convection to cool off the microprocessor of the notebook computer. Still, warm air can be felt near a vent of the casing where the cooling fan blows hot air out of the casing, and the casing of the notebook computer may still be warm or even hot to touch. Consequently, user experience of such portable/mobile apparatus may be negatively impacted if not rendered dangerous.

Thermal energy storage with a phase-change material in a non-metal container


A method of computing a manufacturing yield of an integrated circuit having device shapes includes sub-dividing the integrated circuit into failure mechanism subdivisions (each of the failure mechanism subdivisions includes one or more failure mechanism and each of the failure mechanisms includes one or more defect mechanisms), partitioning the failure mechanism subdivisions by area into partitions, pre-processing the device shapes in each partition, computing an initial average number of faults for each of the failure mechanisms and for each partition by numerical integration of an average probability of failure of each failure mechanism, (the numerical integration produces a list of defect sizes for each defect mechanism, and the computing of the initial average includes setting a maximum integration error limit, a maximum sample size for a population of each defect size, and a maximum number of allowable faults for each failure mechansim), and computing a final average number of faults for the integrated circuit by iterativelly reducing a statistical error of the initial average number of faults for each of the failure mechanisms until the statistical error is below an error limit.

1. Field of the Invention
This invention generally relates to the prediction of electrical test yield for semiconductor integrated circuits (IC), or of electronic packages, and the influence of design and process characteristics upon those tests; more particularly, to an efficient procedure for the prediction of random defect yields which are practical for large chips.
2. Description of the Related Art
Electrical test yield is the most variable productivity component from product to product, and through the evolution and development of a process technology. Electrical test yield, Y, is defined as the product of systematic (gross) yield, Y0, and random defect yield (usually the dominant component), YR. Defects may be randomly introduced during the various steps of IC fabrication. Some of these defects will cause electrical failures (faults), and similar electrical failures are collectively referred to as a failure mechanism. The random defect yield is a function of average number of faults per IC, or xcex9, which is the summation of the average faults for each of the failure mechanisms, i.e. xcex9=xcexa31 xcexi). The electrical test yield can therefore be mathematically defined as
Y=Y0xc2x7YR=Y0xc2x7(1+xcex9/xcex1)xe2x88x92xcex1,xe2x80x83xe2x80x83(Equation 1)
which is known as the negative binomial distribution. Other widely published yield models, such as Poisson, Seeds, Murphy, and Boltz-Einstein, may be used in place of the negative binomial distribution (Charles H. Stapper, et al.,xe2x80x9cIntegrated Circuit Yield Statisticsxe2x80x9d, Proceedings of the IEEE, Vol. 71, Number 4, April, 1983, incorporated herein by reference), however, the mathematics defining the average faults for a particular IC remains the same. Alternatively, some IC manufacturers compute the average faults as the product of the chip area with the average fault density; however, the fault density must be empirically determined, and varies because of diverse IC functional content.
For a given failure mechanism, numbered i, the average number of faults, xcexi, is defined as the product of the critical area, ACi, which is dependent upon physical layout and the defect density, DDi. In Equation 2, critical area is shown as the product of the average probability of failure, xcex8i, or percent critical area, and the area of the chip, A.
xcexi=ACixc2x7DDi=(xcex8ixc2x7A)xc2x7DDixe2x80x83xe2x80x83(Equation 2)
Critical area has been defined as the area in which the center of a defect must fall to cause an electrical failure in an integrated circuit (Stapper, et al, supra, and Wojciech Maly, et al, xe2x80x9cYield Estimation Model for VLSI Artwork Evaluationxe2x80x9d, Electronics Letters, Vol. 19, Number 6, March, 1983, incorporated herein by reference). Thus, a key distinction exists between defects and faults. While all faults are presumed to be caused by defects, not all defects cause faults. In this invention, defect size will be characterized by the radius of the defect, denoted r. The average probability of failure is defined as an infinite integral (which is an integral from a minimum defect radius, r0, to an infinite radius, ∞) over the defect radii:
xe2x80x83xcex8i=∫Pi(r)xc2x7S(r)drxe2x80x83xe2x80x83(Equation 3)
where Pi(r) is the probability of failure function for a given failure mechanism, and is a function of defect radius, and S(r) is the size distribution, which is also a function of defect radius. While any size distribution function may be used, frequently fabricator defect inspection data is fit to equation 4:
S(r)=SK/rxcex2xe2x80x83xe2x80x83(Equation 4)
The inventive methods described herein center around the computation of the probability of failure function for a given failure mechanism, Pi(r). This function depends on the detail design of the IC, which is generally described in the form of a database of 2D geometries or shapes. The formal definition of the probability of failure function is:
Pi(r)=∫X∫Yxcex4i(x,y,r)dy dyxe2x80x83xe2x80x83(Equation 5)
where the values of the function xcex4i(x,y,r) is a 1 if a defect of radius r at location (x,y) causes a fault, and 0 otherwise.
Other approaches to model electrical test yield depend upon design shape algorithms calculating probability of failures by failure mechanism for a particular IC, (Sean Fitzpatrick, et al, xe2x80x9cA Comparison of Critical Area Analysis Toolsxe2x80x9d, IEEE/SEMI Advanced Semiconductor Manufacturing Conference Proceedings, September, 1998, and Gerard A. Allen, xe2x80x9cA Comparison of Efficient Dot Throwing and Shape Shifting Extra Material Critical Area Estimationxe2x80x9d, IEEE Defect and Fault Tolerance in VLSI System Proceedings, December, 1998, each incorporated herein by reference). One approach is the widely published Monte Carlo technique which simulates defects of predetermined sizes randomly falling on the design. Geometric (shape shifting) techniques allow a direct computation of a probability of failure for a given defect size. This method may be combined with sampling small portions of the design to ease the enormous compute resource requirements. All of these approaches are targeted at the specific problem of calculating the probability of failure for a predetermined defect size. Since it is not practical to calculate a probability of failure for every possible defect size, the defect size distribution must be approximated, introducing error into the larger problem of projecting electrical test yield. Consequently, all of the yield estimation techniques require the analyst to make some assumptions, either about the physical design characteristics, the defect size distribution, or the distribution of defects across failure mechanisms and process levels. The result is a yield estimate in which the error is not clearly understood, and there was likely an excessive amount of computer resource spent on the problem. For a fabricator making multiple ICs, the problem quickly becomes self-limiting. This application details a procedure that allows for optimization of the computer resources required for the calculation of the probability of failure for a particular failure mechanism at a specific defect size. This optimization is based upon an integrated approach, with complete error management and computational time controls, for projecting electrical test yield of a particular IC. Moreover, this procedure is practical for a manufacturing environment where multiple ICs of complex function are fabricated.
It is, therefore, an object of the present invention to provide a structure and method for computing the electrical test yield of an IC. The present invention takes as input an IC in the form of a database of shapes, and a fabrication process described in terms of failure mechanisms, defect densities per failure mechanism, defect size distribution, and a yield model. The present invention computes an estimate of the electrical test yield, including the average number of faults per IC, the average number of faults per failure mechanism of the IC, and an estimate of the error in the computation of these quantities.
The present invention computes a predicted yield of an IC that will be manufactured with a given manufacturing technology through the following processes:
1. Subdivide the IC into subdivisions, each of which contains multiple layers, each layer relating to a different failure mechanism. These subdivisions are called failure mechanism subdivisions.
2. Optionally, partition the failure mechanism subdivisions by area. The objective of these two partitioning steps is to reduce the computational effort of the remaining steps.
3. Pre-process the shapes in each partition to apply manufacturing process simulation steps such as layer biasing (shrinks or expands), optical proximity effects, etc.
4. Compute an initial estimate of the average number of faults for each failure mechanism (e.g., short, open, etc.) and each area partition by numerical integration of the percent critical area (e.g., numerical integration of a failure mechanism""s average probability of failure). This initial integration will produce a list of defect sizes for each failure mechanism (and each partition of each failure mechanism). The computational effort of this step is controlled by a maximum integration error limit, a sample size for the population of defects of each defect size (radius), and a maximum number of allowable faults.
5. Compute the final estimate of the average number of faults per IC by iteratively reducing the statistical error of the computation resulting from step 4 by repeating steps 6-10 until the statistical error is below the desired error limit.
6. Select the total number of defects (or total sample size) to be analyzed.
7. Distribute the total sample size among all the defect sizes of all the failure mechanisms. The sample sizes for each defect size of each defect mechanism are selected to maximize the reduction in the statistical error.
8. Compute probability of fault for each defect size and each defect mechanism with the selected sample size.
9. Compute the average number of faults for the current samples and the statistical error of the current sample.
10. Combine the results of this sample with the results of previous samples.
11. Compute the yield estimate using equation 1 or a similar equation.
It is a further object of the present invention to compute the average number of faults for a failure mechanism by predicting defect sizes and the number of defects by defect size (sample size), selecting a location and size for each defect, computing whether each defect results in a fault, summing the number of faults to compute the probability of failure by defect size, thus producing a probability of failure function, and integrating the product of the probability of failure function with the defect size distribution function to obtain the average number of faults as shown in Equation 2.
This invention controls the error in the integration that computes the average number of faults by a controlled selection of the number of defect sizes and of the specific defect sizes.
This invention also controls the statistical error of the average number of faults per IC by a controlled selection of the number of defects per defect size for each failure mechanism. The controlled selection of sample sizes takes into account the relative importance of the individual statistical errors of each defect size of each failure mechanism in the total statistical error of the average number of faults per IC.
The invention may also include partitioning the IC, computing the average number of faults per failure mechanism for each partition, and combining the average number of faults for all partitions and all the failure mechanisms to produce the average faults for the IC. The method for the control of the statistical error is extended to include partitioning of the IC.
The invention may also comprise a system for computing the electrical test yield of an IC that includes a computational unit which determines whether a defect causes a fault on the IC, another computational unit for computing a probability of failure for each defect size of each failure mechanism, and a further computational unit that selects defect sizes for a failure mechanism, computes the average number of faults for each failure mechanism, and then selects the sample sizes for each defect size.
The inventive system may also include a plurality of computational units simultaneously computing the average number of faults for each failure mechanism in each partition of the IC. The inventive system may further include a plurality of the computational units simultaneously computing a probability of failure for each of the defects and/or a sample size selector controlling statistical error of the probability of failure for the IC by controlled selection of a sample size of the defects in the predicting step. The sample size selector can also control integration error of the probability of failure for the IC by controlled selection of sizes of the defects and controlled selection of a number of the sizes.

Method for prediction random defect yields of integrated circuits with accuracy and computation time controls

International Business Machines Corporation


A method of storing electronic data in a system having a mobile terminal (8) and a remote system (1), the mobile terminal (8) and the remote system (1) interacting with each other to exchange electronic data. In order to prevent data loss at the mobile terminal (8), data storage capacity and storage requirements are monitored at the mobile terminal (8). If a risk exists that the data storage capacity of the mobile terminal (8) is likely to be exceeded, electronic data from the mobile terminal (8) is uploaded to the remote system (1), and stored there. The previously uploaded data is subsequently downloaded from the remote system (1) to the mobile terminal (8) in the event that that data is required by the mobile terminal (8) or a determination is made that the risk of exceeding the data storage capacity of the mobile terminal (8) no longer exists.

The present invention relates to memory requirements for mobile hosts and in particular, though not necessarily, to the memory requirements of mobile telephones and smart phones.
The recent growth in the use of mobile telephones has resulted in a large number of proposals being made as to how the role of such telephones can be extended beyond that of merely making and receiving telephone calls. Indeed, a number of these proposals have already been implementedxe2x80x94the ability to send and receive text messages and faxes and to browse the WWW are but two examples.
Definite steps are also being made in the use of mobile electronic terminals (with a particular emphasis on mobile telephones) to allow users to interactively control local systems such as parking meters and vending machines. For example, a number of major companies are currently involved in the development of a standardised interface for this application, under a project termed xe2x80x9cBluetoothxe2x80x9d.
What most of these proposals have in common is the requirement for the transfer of relatively large amounts of electronic data between the mobile terminals and the interacting systems (be that a local system or a telephone network). Much of this data must be stored at the mobile terminal even if only as a temporary measure. In addition, advanced applications running at a mobile terminal will themselves generate a large amount of data which must be stored at the mobile terminal. This need to store data at a mobile terminal will inevitably place considerable demands on the memory available at the mobile terminal which is always going to be limited due to both size and cost constraints.
In the event that data requiring storage at a mobile terminal exceeds the available memory space, one or more applications running at the terminal are likely to crash, or at least the running of the application(s) will be suspended. In a worst case scenario, valuable data may be lost. This is particularly serious where an electronic commerce application is running at the mobile terminal and where financial transaction data may be lost.
It is an object of the present invention to overcome or at least mitigate the disadvantage noted above. In particular, it is an object of the present invention to prevent or reduce the risk of memory overload at a mobile terminal when the terminal is interacting electronically with other equipment or systems.
These and other objects are achieved, at least in part, by enabling a mobile terminal to upload electronic data to the equipment or system with which it is interacting in the event that a risk of memory overload is recognised. The uploaded data can then be retrieved by the mobile terminal when this risk is reduced or eliminated.
According to a first aspect of the present invention there is provided a method of storing electronic data in a system having a mobile terminal and a remote system, the mobile terminal and the remote system interacting with each other to exchange electronic data, the method comprising:
transmitting from the remote system to the mobile terminal a notification including an identification of the amount of data to be downloaded;
determining at the mobile terminal when a risk of exceeding a data storage capacity of the mobile terminal exists;
uploading electronic data from the mobile terminal to the remote system in the event that such a determination is made, and storing the uploaded data at the remote system; and
subsequently downloading the previously uploaded data from the remote system to the mobile terminal in the event that the uploaded data is required by the mobile terminal or a determination is made that the risk of exceeding the data storage capacity of the mobile terminal no longer exists.
Embodiments of the present invention assist in preventing the overloading of memory at a mobile station and therefore reduce the risk of applications crashing and/or data being lost at the mobile terminal.
Preferably, said exchange of data between the mobile terminal and remote system is carried out at least in part via a wireless interface. Most preferably, the wireless interface is a radio interface although other interfaces, such as infra-red or ultrasonic, may be used.
In certain embodiments of the invention, said remote system is a local system, for example a parking meter or a vending or sales machine, and the local system interacts with the mobile terminal using a local radio air interface protocol RI1. In other embodiments however, the remote system may be a radio network or a system coupled to the radio network.
Preferably, the mobile terminal is or comprises a mobile telephone arranged to communicate with a mobile telephone network. Said exchange of electronic data, including said uploading and downloading of data, may occur via a link between the terminal and the network or may occur via a second distinct wireless interface.
The electronic data uploaded from the mobile terminal to the remote system may include application software (i.e. executable code), state information, and user data. Preferably, the uploaded data is converted into a serial format for transmission to the remote system.
According to a second aspect of the present invention there is provided apparatus for storing electronic data in a system having a mobile terminal and a remote system, the mobile terminal and the remote system interacting with each other to exchange electronic data, the apparatus comprising:
transmitting means at the remote system for transmitting to the mobile terminal a notification including an identification of the amount of data to be downloaded
processing means at the mobile terminal for determining when a risk of exceeding a data storage capacity of the mobile terminal exists;
first data transfer means for uploading electronic data from the mobile terminal to the remote system in the event that such a determination is made;
memory means at the remote system for storing the uploaded data at the remote system; and
second data transfer means for subsequently downloading the previously uploaded data from the remote system to the mobile terminal in the event that the uploaded data is required by the mobile terminal or a determination is made that the risk of exceeding the data storage capacity of the mobile terminal no longer exists.
According to a third aspect of the present invention there is provided a mobile terminal arranged in use to interact with a remote system by way of the exchange of electronic data, the terminal comprising:
receiving means for receiving a notification including an identification of the amount of data to be downloaded
processing means for determining when a risk of exceeding a data storage capacity of the mobile terminal exists;
data transmission means for uploading electronic data from the mobile terminal to the remote system in the event that such a determination is made; and
data reception means for subsequently downloading the previously uploaded data from the remote system to the mobile terminal in the event that the uploaded data is required by the mobile terminal or a determination is made that the risk of exceeding the data storage capacity of the mobile terminal no longer exist.

Memory requirements for mobile terminals


A method of manufacturing a multi-tooth fir-tree or bulbous form milling cutter, by the grinding of a blank with a grinding wheel, wherein, a flat clearance angle Θ of between 0° and 20° is generated on each tooth (13) by the path (14) of the grinding wheel (10), with each tooth (13) having a width (X) from tip to point of maximum clearance (see FIG. 5), calculated as follows: —X={[(R tan Θ)cos Θ] cos Θ}±0.25% (being calculation (A)) where R=radius of cutter, and where Θ=clearance angle measured from a tangent to the tooth tip, and furthermore, wherein, each tooth (13) has a variable depth (Y) around the cutter, calculated as follows: —Y={[πD]/[180/Θ]}0.5±0.2. (being calculation (B)) where D=maximum diameter of the form at any given point along the form. The invention also includes fir tree and bulbous milling cutters produced by the above defined method.

Complex, small, fir tree or bulbous root form geometry milling cutters are difficult to make, having a relatively small number of cutting edges—typically 3 to 5 cutting edges—and hence have correspondingly restricted cutting rates. A recent development of Applicants, is a milling cutter described in WO 2008/090301, but whilst providing substantial advantages in the cutting sphere for which it was designed, is impossible to make in complex profiles containing a mixture of concave and convex shapes on the periphery.
The result is that, in order to machine roots of desired profile for turbofan components, extensive broaching operations from roughing to finishing are unavoidable, involving all manufacturers, worldwide, in a substantial broaching machine investment programme, with capital costs typically £2-3 million per machine, resulting in substantial installation costs, maintenance costs, floor area requirements, machining time, and hence significant manufacturing costs.
Although it is self-evident that the rate of metal removal of course increases with the number of teeth of a rotary cutter, and a broaching tool has numerous cutting teeth for both roughing and finishing operations in a single tool, the performance of form milling cutters is, as indicated above, constrained by the number of teeth that can be manufactured within a given tool diameter.
Whilst the range of cutters of WO 2008/090301 starts to address this issue on parallel or ball nosed tools, the production of a range of form milling cutters of both dovetail and bulbous forms, with a substantially increased number of teeth/flutes has been impossible to date. This has resulted in current industry use, worldwide, of form milling cutters incorporating between 4 and 6 teeth of a given tool diameter of 25 mm as exemplified in FIGS. 1A to 1C in fir-tree form and in FIGS. 2A and 2B in bulbous form, with the current constraints limiting the number of teeth that can be produced in existing form milling cutters.
Because, in prior art proposals, clearance on each tooth is generated by the arc of the grinding wheel, the diameter of the grinding wheel is the limiting factor during manufacture of form milling cutters, which diameter defines the number of teeth that can be produced. This is due to the current manufacturing process, where, as the tool is rotated to produce the necessary clearance, the grinding wheel fouls the following tooth and thus damages the form. Reducing the diameter of the wheel therefore allows for more teeth to be produced, but is impractical beyond a certain diameter of grinding wheel. Therefore, restriction of the number of teeth in the cutter normally is unavoidable.
In US 2008/020600 (SASU) is described a ball nose cutter, of relatively simple geometry for the machining of integrally bladed rotors, rather than being a form milling cutter with which the invention is concerned, and is a cutter that scans across a shape and is tapered for ready re-grinding.
In WO 2009/070424 (TDY Industries) is described a landless i.e. sharp toothed, burr rather than a form milling cutter with which the invention is concerned, and produced by the method of U.S. Pat. No. 5,868,606 (Martin), the latter describing a ball end cutter, with grinding by a wheel having an axis of rotation different to the cutter axis of rotation.
In U.S. Pat. No. 6,164,877 (Kamata) is described a fir-tree, formed milling cutter with but three cutting edges, supporting the comments above on the inability of any manufacturer to produce more than 3, 4 or at most 6 cutting edges on a fir-tree etc root form milling cutter, such that all turbofan manufacturers have been obliged to include a broaching step.

Form milling cutter for the machining of titanium alloys etc


A predictive model method (and structure) includes receiving an input data into an initial model to develop an initial model output and receiving both of the input data and the initial model output as input data into a first transform/regression stage.

1. Field of the Invention
The present invention generally relates to data mining and knowledge discovery of computer databases. More specifically, an output of the first stage becomes an input to a second stage in a predictive model in which nonlinear transformations of input variables are automatically discovered and in which such transformed inputs are then combined via linear regression to stage-wise produce predictions/forecasts.
2. Description of the Related Art
Data mining is emerging as a highly advantageous application of computer databases that addresses the problem of extracting useful information from large volumes of data. Predictive modeling is an area of data mining and knowledge discovery that is specifically directed toward automatically extracting data patterns that have predictive value. Constructing accurate predictive models is a significant problem in many industries that employ predictive modeling in their operations.
For example, predictive models are often used for direct-mail targeted-marketing purposes in industries that sell directly to consumers. The models are used to optimize return on marketing investment by ranking consumers according to their predicted responses to promotions, and then mailing promotional materials only to those consumers who are most likely to respond and generate revenue.
The credit industry uses predictive modeling to predict the probability that a consumer or business will default on a loan or a line of credit of a given size based on what is known about that consumer or business. The models are then used as a basis for deciding whether to grant (or continue granting) loans or lines of credit, and for setting maximum approved loan amounts or credit limits.
Insurance companies use predictive modeling to predict the frequency with which a consumer or business will file insurance claims and the average loss amount per claim. The models are then used to set insurance premiums and to set underwriting rules for different categories of insurance coverage.
On the Internet, predictive modeling is used by ad servers to predict the probability that a user will click-through on an advertisement based on what is known about the user and the nature of the ad. The models are used to select the best ad to serve to each individual user on each Web page visited in order to maximize click-though and eventual conversion of user interest into actual sales.
The above applications are but a few of the innumerable commercial applications of predictive modeling. In all such applications, the higher the accuracy of the predictive models, the greater are the financial rewards.
Because the data-mining/knowledge-discovery problem is broad in scope, any technology developed to address this problem should ideally be generic in nature, and not specific to particular applications. In other words, one should ideally be able to supply a computer program embodying the technology with application-specific data, and the program should then identify the most significant and meaningful patterns with respect to that data, without having to also inform the program about the nuances of the intended application.
The development of application-independent predictive modeling technology is made feasible by the fact that the inputs to a predictive model (i.e., the explanatory data fields) can be represented as columns in a database table or view. The output(s) of a predictive model can likewise be represented as one or more columns.
To automatically construct a predictive model, one first prepares a table or view of training data comprising one or more columns of explanatory data fields together with one or more columns of data values to be predicted (i.e., target data fields). A suitable process must then be applied to this table or view of training data to generate predictive models that map values of the explanatory data fields into values of the target data fields. Once generated, a predictive model can then be applied to rows of another database table or view for which the values of the target data fields are unknown, and the resulting predicted values can then be used as a basis for decision making.
Thus, a process for constructing a predictive model is essentially a type of database query that produces as output a specification of a desired data transformation (i.e., a predictive model) that can then be applied in subsequent database queries to generate predictions.
To make predictive modeling technology readily available to database applications developers, extensions to the SQL database query language are being jointly developed by the International Organization for Standardization (ISO) and the International Electrotechnical Commission (IEC) to support the construction and application of predictive models within database systems (see, for example, ISO/IEC FCD 13249-6:200x(E), "Information technology—Database languages—SQL Multimedia and Application Packages—Part 6: Data Mining," Document Reference Number ISO/IEC JTC 1/SC 32N0848, Jun. 20, 2002, (Final Draft International Standard) http://www.jtc1sc32.org/sc32/jtc1sc32.nsf/Attachments/39E375F33B51135788256BDD00835045/$FILE/32N0848.PDF.
For an overview, see J. Melton and A. Eisenberg, "SQL Multimedia and Application Packages (SQL/MM)," SIGMOD Record, Vol. 30, No. 4, pp. 97-102, 2001, http://www.acm.org/sigmod/record/issues/0112/standards.pdf). This ISO/IEC standard aims to provide SQL structured types and associated functions for creating data mining task specifications, executing data mining tasks, querying data mining results, and, in cases where the results are predictive models, applying data mining results to row data to generate predictions.
For example, the ISO/IEC standard requires that both data mining task specifications and data mining results be stored as Character Large Objects (CLOBs), using an encoding format that is consistent with the Predictive Modeling Markup Language (PMML) standard that is being developed separately through the Data Mining Group (http://www.dmg.org). The ISO/IEC standard likewise specifies sets of functions to be used for manipulating these database objects. By providing a standard application programming interface (API) for utilizing data mining technology with database systems, the standard is expected to promote wide use of data mining technology by enabling database application developers to readily apply such technology in business applications simply by writing SQL queries. In so doing, the standard effectively makes data mining a component technology of database systems.
The ISO/IEC data mining standard likewise serves a clear acknowledgment that predictive model technology produces useful, concrete, and tangible results that have specific meaning with respect to the input data and the user-specified modeling objectives (i.e., which data field to predict in terms of which other data fields). Indeed, if this were not the case, there would be no reason to create an international database standard for utilizing such technology. From a pragmatic database perspective, the specification of the input data and the modeling objectives constitutes a query, and the predictive model that is produced as output constitutes a query result. The processes provided by predictive modeling technology are utilized by the query engine in order to produce the query results.
Decision-tree classifiers provide a convenient illustration of the usefulness of predictive modeling technology. Well-known procedures exist for constructing such models. The usual method is summarized as follows by Quinlan (see J. R. Quinlan, "Unknown attribute values in induction," Proceedings of the Sixth International Machine Learning Workshop, pp 164-168, Morgan Kaufmann Publishers, 1989):
"The 'standard' technique for constructing a decision tree classifier from a training set of cases with known classes, each described in terms of fixed attributes, can be summarized as follows:                If all training cases belong to a single class, the tree is a leaf labeled with that class;        Otherwise:                    select a test, based on one attribute, with mutually exclusive outcomes;            divide the training set into subsets, each corresponding to one outcome; and            apply the same procedure to each subset."
Details on the individual method steps can be found, for example, in the on-line statistics textbook provided over the Internet as a public service by StatSoft, Inc.
The usefulness of decision tree technology is best illustrated by means of a concrete example. Table 1 below shows the data field definitions for a data set commonly known within the predictive modeling community as the "Boston Housing" data (D. Harrison and D. L. Rubinfield, "Hedonic prices and the demand for clean air," Journal of Environmental Economics and Management, Vol. 5, pp 81-102, 1978). Table 2 below shows twelve exemplary of the rows from this data set. A complete copy of the data set can be obtained over the Internet from the UCI Machine Learning Repository (http://www.ics.uci.edu/˜mlearn/MLRepository.html).
TABLE 1(Data definition for the Boston Housing data set.Data fields have been assigned more intuitive names.The original names appear in the "a.k.a." column.)Data Fielda.k.a.DescriptionPRICEMEDVMedian value of owner-occupied homes(recoded into equiprobable HIGH,MEDIUM, and LOW ranges)ON_RIVERCHASCharles River indicator (value is 1 if tractbounds Charles River; else 0)CRIME_RTCRIMPer capita crime rate by town%BIGLOTSZNPercentage of residential land zoned for lotsover 25,000 square feet%INDUSTYINDUSPercentage of non-retail business acres pertownNOXLEVELNOXConcentration of nitric oxides (recoded intoequiprobable high, medium, and low ranges)AVGNUMRMRMAverage number of rooms per dwelling%OLDBLDGAGEPercentage of owner-occupied units builtprior to 1940DIST2WRKDISWeighted distances to five Bostonemployment centersHWYACCESRADIndex of accessibility to radial highwaysTAX_RATETAXFull-valued property tax rate per $10,000CLASSIZEPTRATIOPupil-teacher ratio by town%LOWINCMLSTATPercent lower status of the population
TABLE 2(a)(Twelve sample rows from the Boston Housing data set (Part 1 of 3).)%BIG-ROWPRICEON_RIVERCRIME_RTLOTS%INDUSTY1HIGH00.00618.002.312MEDIUM00.0270.007.073HIGH00.0320.002.184MEDIUM00.08812.507.875LOW00.21112.507.876MEDIUM00.6300.008.147MEDIUM00.15425.005.138MEDIUM00.1010.0010.019LOW00.2590.0021.8910LOW13.3210.0019.5811LOW00.20622.005.8612LOW18.9830.0018.10
TABLE 2(b)(Twelve sample rows from the Boston Housing data set (Part 2 of 3).)ROWNOXLEVELAVGNUMRM%OLDBLDGDIST2WRK1medium6.5865.204.092low6.4278.904.973low7.0045.806.064medium6.0166.605.565medium5.63100.006.086medium5.9561.804.717low6.1429.207.828medium6.7181.602.689high5.6996.001.7910high5.40100.001.3211low5.5976.507.9612high6.2197.402.12
TABLE 2(c)(Twelve sample rows from the Boston Housing data set (Part 3 of 3).)ROWHWYACCESTAX_RATECLASSIZE%LOWINCM1129615.304.982224217.809.143322218.702.944531115.2012.435531115.2029.936430721.008.267828419.706.868643217.8010.169443721.2017.1910540314.7026.8211733019.1012.50122466620.2017.60
Harrison and Rubinfield collected and analyzed these data to determine whether air pollution had any effect on house values within the greater Boston area. One approach to addressing this question is to build a model that predicts house price as a function of air pollution and other factors that could potentially affect house prices.
FIG. 1 shows a decision tree 100 generated from the Boston Housing data using the CART algorithm (L. Breiman, J. H. Friedman, R. A. Olshen, and C. J. Stone, Classification and Regression Trees, New York: Chapman & Hall, 1984) as implemented in STATISTICA for Windows (STATISTICA for Windows [Computerprogram manual], Version 5.5, 1995, StatSoft, Inc., 2300. East 14th Street, Tulsa, Okla., 74104-4442). The STATISTICA program was told to construct a decision tree model that predicts PRICE (i.e., the median value of owner-occupied homes broken down into high, medium, and low ranges) using all of the other columns in the data table as potential inputs to the model (i.e., as explanatory data fields).
Each node 1 through 13 in the tree shown in FIG. 1 corresponds to a data segment (i.e., a subset of the data). Illustrated at each node are histograms of the proportions of high-, medium-, and low-priced neighborhoods that belong to the corresponding data segments. The price range that corresponds to each histogram bar is indicated by legend 14. Each node in FIG. 1 is also labeled with the dominant price range within the corresponding segment (i.e., the price range that has the largest histogram bar). Thus, for node 1, the dominant price range is medium, whereas for nodes 2 and 3 the dominant price ranges are high and low, respectively.
Tree branches correspond to tests on the values of the inputs to the predictive model and it is these tests that define the data segments that correspond to each node in the tree. For example, in FIG. 1, node 1 is the root of the tree and it corresponds to the entire set of data. Test 15 (i.e., % LOWINCM≦14.4) defines the data segments that correspond to nodes 2 and 3.
Left-going branches in FIG. 1 are followed when the outcome of the corresponding test is "yes" or "true." Right-going branches are followed when the outcome of the test is "no" or "false." Thus, node 2 corresponds to the subset of data for which % LOWINCM is less than or equal to 14.4, and node 3 corresponds to the subset of data for which % LOWINCM is greater than 14.4. Similarly, node 4 corresponds to the subset of data for which % LOWINCM is less than or equal to 14.4 and AVGNUMRM is less than or equal to 6.527, and so on.
The leaves of the tree (i.e., nodes 4, 5, 7, 8, 10, 12, and 13) correspond to the subsets of data that are used to make predictions in the decision tree model. In this example, the predictions are the dominant price ranges at the leaves of the tree. Thus, at node 4 the prediction would be "medium," at node 5 it would be "high," at node 7 it would be "low," etc.
FIG. 1 demonstrates the ability of decision tree programs to automatically extract meaningful patterns from collections of data. As the tree model indicates, air pollution does have an effect on house prices, but only for neighborhoods that have a sufficiently large percentage of low-income housing (i.e., % LOWINCM>14.4). For all other neighborhoods, house prices are primarily affected by the size of the house, as indicated by the average number of rooms per house in the neighborhood (i.e, AVGNUMRM).
When air pollution is a factor, but the air pollution level is sufficiently small, then the next most predictive factors that affect house prices are crime rate, the percentage of non-retail industrial land, and the distance to a major center of employment, with the more desirable (i.e., higher-priced) neighborhoods being those with low crime rates (i.e., node 8) and those with sufficiently large percentages of non-retail industrial land located away from centers of employment (i.e., node 13).
To demonstrate that decision tree algorithms are not application-specific, but can be applied to any application simply by providing application-specific data as input, the STATISTICA program was executed again, but this time it was told to predict the air pollution level (i.e., NOXLEVEL) using all of the other data columns as explanatory variables, including PRICE. FIG. 2 shows the resulting tree model 200. As this tree illustrates, the majority of neighborhoods that have the highest levels of air pollution (i.e., node 28) are those with sufficiently large percentages of non-retail industrial land, sufficiently large percentages of older buildings, and sufficiently high tax rates.
Not surprisingly, these factors characterize downtown Boston and its immediate vicinity. The majority of neighborhoods that have the lowest levels of air pollution (i.e., node 26) are those with sufficiently small percentages of non-retail industrial land, sufficiently large percentages of houses on large lots, and that are sufficiently far from centers of employment. These characteristics are typical of outlying suburbs. The majority of neighborhoods that have moderate levels of air pollution (i.e., node 29) are those with sufficiently small percentages of non-retail industrial land, sufficiently small percentages of houses on large lots, and easy access to radial highways that lead into Boston. These characteristics are typical of urban residential neighborhoods favored by commuters.
For both FIGS. 1 and 2, the relationships described above make intuitive sense, once the tree models are examined in detail. However, it is important to keep in mind that the STATISTICA program itself has no knowledge of these intuitions nor of the source of data. The program is merely analyzing the data to identify patterns that have predictive value.
Nevertheless, the program produces meaningful results. The decision tree models that are produced as output are useful, concrete, and tangible results that have specific meaning with respect to the input data and the user-specified modeling objectives (i.e., which data field to predict in terms of which other data fields). From a database perspective, the specification of the input data and the modeling objectives constitutes a query, and the decision tree model that is produced as output constitutes a query result.
The usefulness of decision tree algorithms, in particular, and automated predictive modeling technology, in general, derives from the fact that they can perform their analyses automatically without human intervention, and without being told what kinds of relationships to look for. All that they need to be told is which data values are to be predicted, and which data values can be used as inputs to make those predictions. The generic nature of such technology makes the technology extremely useful for the purpose of knowledge discovery in databases. Moreover, it is the generic nature of predictive modeling technology that permits the technology to be incorporated into general-purpose database systems.
Note that, once a decision tree has been constructed—or, for that matter, once any type of predictive model has been constructed—the step of applying that model to generate predictions for an intended application is conventional, obvious, and noninventive to those skilled in the art of predictive modeling.
Although decision tree methods yield models that can be interpreted and understood for the purposes of knowledge discovery, the predictive accuracy of decision tree models can be significantly lower than the predictive accuracies that can be obtained using other modeling methods. This lower accuracy stems from the fact that decision trees are piecewise-constant models; that is, within each data segment defined by the leaves of the tree, the predictions produced by the model are the same for all members of that segment.
FIG. 3 illustrates this effect 300 in the case of regression trees, which are decision trees used to predict numerical values instead of categorical values. As FIG. 3 indicates, the output 39 of a piecewise-constant model (such as one produced by conventional decision tree algorithms) is stair-like in nature and is therefore inherently inaccurate when used to model data 38 that exhibits smooth variations in values relative to the inputs of the model. The strength of decision tree models, however, is that they are quite good at modeling any nonlinearities that might exist, as FIG. 3A demonstrates.
To overcome the deficiencies of the piecewise-constant aspect of decision trees, Natarajan and Pednault have developed a method for constructing tree-based models with multivariate statistical models in the leaves—specifically, linear regression models and naive-Bayes models (R. Natarajan and E. P. D. Pednault, "Segmented Regression Estimators for Massive Data Sets," Proceedings of the Second SIAM International Conference on Data Mining (on CD-ROM), Arlington, Va., April 2002), the contents of which are hereby incorporated by reference.
This method is further described in the above-identified copending patent application. FIGS. 3B and 3C show how this segmented regression method works. In the initial model 301 shown in FIG. 3B, a first linear estimation 302 of the data is modeled. As shown in FIG. 3C, the linear model 301 is refined into a linear segmented model 303 by calculating linear estimates 304-307 for a number of segments. The number of segments and the segment boundaries are determined by applying a top-down process for building decision trees in which the tree branches define segment boundaries and the leaves of the decision trees contain linear regression models.
However, the above segmented regression method is limited by another deficiency of tree-based predictive modeling methods, which is that one quickly runs out of data as a result of dividing data into numerous subsets that correspond to the leaves of a tree. Less data implies greater estimation errors in the parameters of the leaf models, and these estimation errors can in turn lower the predictive accuracy of the resulting model relative to what could be achieved using other modeling techniques.
Thus, the problem remains in predictive modeling to provide an accurate model via a process that quickly converges, using limited amounts of data.

Method and structure for transform regression

International Business Machines Corporation


The present disclosure generally relates to modified relaxin polypeptides, such as modified human relaxin 2 polypeptides, comprising a non-naturally encoded amino acid which is linked to a pharmacokinetic enhancer, and therapeutic uses of such polypeptides, such as for the treatment of cardiovascular conditions (such as heart failure) and/or conditions relating to fibrosis.

The present disclosure generally relates to modified relaxin polypeptides, such as modified human relaxin 2 polypeptides, comprising a pharmacokinetic enhancer, and therapeutic uses of such polypeptides, such as for the treatment of cardiovascular conditions (such as heart failure) and/or conditions relating to fibrosis. In exemplary embodiments, the pharmacokinetic enhancer is linked to a non-naturally encoded amino acid, which may be ribosomally incorporated into the relaxin polypeptide.
Heart failure (HF) represents a tremendous burden on today's health care system with an estimated United States prevalence of 5.8 million and greater than 23 million worldwide (Roger et al., 2012. Circulation, 125(1): e2-e220). The symptoms of HF are the result of inadequate cardiac output and can be debilitating depending upon the advanced stage of the disease. Major symptoms and signs of HF include: 1) dyspnea (difficulty in breathing) resulting from pulmonary edema due to ineffective forward flow from the left ventricle and increased pressure in the pulmonary capillary bed; 2) lower extremity edema occurs when the right ventricle is unable to accommodate systemic venous return; and 3) fatigue due to the failing heart's inability to sustain sufficient cardiac output to meet the body's metabolic needs (Kemp & Conte, 2012. Cardiovascular Pathology, 21:365-371).
Many contributory diseases, risk factors, and pathological changes may ultimately lead to heart failure (Jessup & Brozena, 2003. N Engl J Med, 348(20): 2007-2018). Injurious events thought to be involved in the pathophysiology of HF range from the very acute such as myocardial infarction to a more chronic insult such as life-long hypertension. The death rate remains high with ˜50% of people with HF dying within 5 years of diagnosis (Roger et al., 2012. Circulation, 125(1): e2-e220; Roger et al., 2004. Jama, 292(3): 344-50). Heart failure clearly presents a significant unmet medical need.
The human relaxin 2 hormone (also called H2 relaxin) is a 6-kDa peptide composed of 53 amino acids which was known to be responsible for remodeling the reproductive tract before parturition, thus facilitating the birth process. While predominantly a hormone of pregnancy, relaxin has also been detected in the non-pregnant female as well as in the male. Human relaxin is a member of the insulin peptide family which includes insulin, a number of insulin like peptides (INSL3-6), and the insulin-like growth factors (IGFI and IGFII) (Van Der Westhuizen et al., 2007. Curr Drug Targets, 8(1): 91-104). These heterodimeric peptides are all structurally related with each comprised of two peptide chains (A & B) that are connected by two disulfide bonds, and with the A-chain containing a single intramolecular disulfide bond. The receptor for relaxin 2 (H2), called the Relaxin Family Peptide Receptor 1 (RXFP1), is conserved between mouse and human with 85% amino acid identity and is essentially ubiquitously expressed in humans and in other species (Halls et al., 2007. Br J Pharmacol, 150(6): 677-91).
During human gestation, in order to meet the nutritional demands imposed upon it by the fetus, the female body undergoes a significant ˜30% decrease in systemic vascular resistance (SVR) and a concomitant ˜50% increase in cardiac output (Jeyabalan, 2010: Renal and Electrolyte Disorders. Lippincott Williams & Wilkins. 462-518; Clapp and Capeless, 1997. Am J Cardiol, 80(11): 1469-73). Additional vascular adaptations include an ˜30% increase in global arterial compliance that is important for maintaining efficient ventricular-arterial coupling, as well as an ˜50% increase in both renal blood flow (RBF) and glomerular filtration rate (GFR), important for metabolic waste elimination (Jeyabalan, 2010: Renal and Electrolyte Disorders. Lippincott Williams & Wilkins. 462-518; Poppas et al., 1997. Circulation, 95(10): p. 2407-15). Both pre-clinical studies in rodents as well as clinical studies performed in a variety of patient settings provide evidence that relaxin is involved, at least to some extent, in mediating these adaptive physiological changes (Conrad, 2011. Am J Physiol Regul Integr Comp Physiol, 301(2), R267-275; Teichman et al., 2009. Heart Fail Rev, 14(4), 321-329.). Many of these adaptive responses would likely be of benefit to HF patients in that excessive fibrosis, poor arterial compliance, and poor renal function are all characteristics common to heart failure patients (Mohammed et al., 2015. Circulation, 131(6), 550-559), (Wohlfahrt et al., 2015. Eur J Heart Fail, 17(1), 27-34; Dammon et al., 2011. Prog Cardiovasc Dis, 54(2), 144-153). As an estimated 30% of patients with HF suffer from moderate to severe renal impairment (Triposkiadis and Skoularigis, 2012. Curr Heart Fail Rep, (4):354-62), an agent such as relaxin by improving both vascular flow and electrolyte handling, may be of particular benefit to HF patients.
The relaxin peptide has a short pharmacokinetic half-life: Serelaxin, a recombinant human relaxin peptide, which was developed for the treatment of HF, has a short first-phase pharmacokinetic half-life of 5-15 minutes, and necessitated 48 hours continuous intravenous infusion for therapeutic utility (REASANZ (serelaxin) Briefing Document Prepared by Novartis for FDA Cardiovascular and Renal Drugs Advisory Committee Meeting. Feb. 26, 2014). For chronic diseases like heart failure, a relaxin molecule with an improved pharmacokinetic profile provides the opportunity for alternate routes of drug administration, beyond continuous intravenous infusion, likely to be more amenable as a therapeutic for patients suffering from chronic diseases.

Modified relaxin polypeptides comprising a pharmacokinetic enhancer and pharmaceutical compositions thereof