A fire door stop system for retrofitting a fire door assembly so as to bring the assembly into compliance with fire safety codes. The fire door stop system has a profile strip that is attachable to a fire door frame. An edge of the profile strip extends outward from the frame in a line with a face of the soffit against which the pull edge of the fire door closes. The fire door stop system further includes, as needed, edge protectors for a wood fire door, such as a horizontal edge protector, a vertical edge protector, and a bottom-edge extender, and a latch protector.

1. Field of the Invention
The invention relates to fire doors. More particularly, the invention relates to a fire door stop to stop the spread of smoke, hot gases, or fire from flowing between a fire door and the door frame.
2. Discussion of the Prior Art
The National Fire Protection Association (NFPA) develops codes and standards that minimize the risk and effects of fire and other hazardous situations. NFPA 80 regulates the installation and maintenance of assemblies and devices used to protect openings in walls, floors, and ceilings and as of 2007 requires that all doors and door frames that are labeled fire doors and labeled fire door frames be inspected and tested annually. This standard is herein incorporated in its entirety by reference. NFPA 80 specifies the allowable clearances or gaps between fire door and frame and the floor. Currently, the specified clearance between door and frame is ⅛ inch, plus or minus 1/16 inch, for steel doors, and shall not exceed ⅛ inch for wood doors. The clearance between the bottom of the fire door and the floor shall be a maximum of ¾ inch.
Precise standards regulating fire doors exist to ensure that a fire door assembly, which includes a fire door and a fire door frame with door frame, functions as desired to stop the flow of fire, hot gases, and smoke. The standards require that the fire door assembly, i.e., the labeled door frame and the labeled fire door, be built to a specified size and then be installed, such that about ½ inch of the edge of the door overlaps the soffit height of the frame, which is typically ⅝ inch deep, thereby creating an overlap interface between fire door and door frame. The specified clearance between door and frame is ⅛ inch, plus/minus 1/16 inch for steel doors, and shall not exceed ⅛ inch for wood doors. Clearances are always measured from the pull face of the door. This overlap is necessary in a fire condition to keep the fire door in place and together, when a fire hose water stream is put onto the fire door, and to hold back the fire, hot gases, and smoke, and also to allow for shrinkage in wood doors, as the wood edges burn away in a fire condition.
Unfortunately, the doors and door frames are built to the minimum standards and, if the installation isn't perfect, the clearance between the edge of the labeled fire door and the labeled door frame may be excessive, such that the overlap is less than specified or that a gap exists between the edge of the door and the edge of the frame. There are an estimated 150 million fire doors installed in the US today and 80% of them fail a first-time inspection. The overwhelming majority of the failures are due to excessive clearance between door and door frame. Typically, the excessive clearance is ¼ to 5/16 inch wide, with some clearances as large as ½ inch.
Also, buildings settle over the years, increasing imperfections in the installation and contributing to the formation of an excessive clearance. The remedy is to shim the door frame to eliminate the excessive clearance, or to replace the door and frame altogether. Replacing the door and/or frame is not only costly, but may be nearly impossible. In many commercial building, including hospitals and schools, the fire door frames are embedded in concrete as the building is constructed. Even the less invasive remedy of shimming the door frame can be impossible in this case. If it is possible to shim the door, this means pulling the door from the hinge side toward the lock side, which then frequently creates an excessive clearance on the hinge side.
What is needed, therefore, is a simple, reliable means of eliminating a gap between a labeled fire door and labeled fire door frame, even when both door and frame have been built to minimum standards.


Methods are provided for determining the residence age of petroleum fluids in subsurface reservoirs. The methods facilitate the determination of the geological timing of the emplacement of a petroleum fluid in a porous reservoir, as distinct from the timing of petroleum generation in, and expulsion from, a source rock.

In petroleum systems, much effort has been put into using forward basin models to estimate the times of petroleum charging into subsurface traps. There are however no independent constraints on these estimates, yet fluid residence age in a petroleum trap is a key factor in many aspects of petroleum systems evaluation. While oilfield locations and oil maturity are often used together with basin models to constrain those models, the direct testing of the locations of accumulations is provided by drilling, and estimates of the times of charging from models are non-unique and unreliable. While forward basin models provide estimates of petroleum generation timing using various kinetic models, the timing of expulsion from the source rock and the often poorly defined duration of secondary and tertiary migration to and from the reservoir, are unconstrained by real measurements made on the crude oil and may have large errors associated with them, extending to a significant portion of the age of a reservoir.
Petroleum charge times and rates are key variables in controlling hydrocarbon prospectivity, as they define volumes of trapped petroleum and the dynamics of trap integrity, including leakage and alteration phenomena. Knowledge of the timing of reservoir trap and seal development relative to the migration of crude oil accordingly reduces exploration risk.
Nuclear radiation in rocks is primarily generated from the alpha-emitting decay of uranium (238U) and thorium (232Th) isotopes, and also from the beta particle emitting decay of potassium (40K). The primary particles emitted from decaying radionuclides, however, are rapidly stopped by interactions with atoms in the host minerals and are mostly attenuated within the grains of the host minerals themselves, ultimately releasing, through a complex chain of interactions and daughter species, energized electrons and photon radiation in the form of gamma rays. Some neutrinos are also released but these do not interact significantly with reservoir media.
The main form of nuclear radiation that interacts with reservoir fluid media are primary gamma ray photons and subsequently scattered, lower energy gamma ray and x-ray photons. The interaction of gamma ray photons with atoms in fluids (or other phases) has a few possible outcomes. The photon can disappear and be absorbed completely through the photoelectric effect emitting a photoelectron, pair production, nuclear triplet production or a photonuclear reaction. Also, a gamma ray photon can be scattered and change its direction but keep its energy (Rayleigh scattering) or lose part of its energy through the Compton effect, whereby photons interact with electrons in atoms, losing energy and producing lower energy photons as a result (Bailey et al. 2015). Compton effect scattered gamma ray photons ultimately become X-rays and then finally infrared photons, and thus the energy of radionuclide fission ends up as thermal energy in the rock. Compton scattering is the primary radiation attenuation mechanism for gamma ray photons of up to a few million electron volts energy that interact with atoms typical of the major rock forming elements, such as silicon, oxygen, aluminium, calcium, magnesium, sodium, iron etc. Compton scattering also ultimately produces an avalanche of low energy electrons (10 to 80 electron volts), into the irradiated medium. Interactions of petroleum fluid with this avalanche of low energy electrons are the primary cause of the observed radiolysis chemistry effects on organic materials such as petroleum.
Crude oils are very reactive under high radiation doses, with excited hydrocarbon and heteroatomic molecules being created through non-selective bond breaking and bimolecular recombination reactions including hydrogen loss, condensation processes and reactions between any species present, including water, N2 and CO2, also occurring. Classical geochemical proxy routes to assess petroleum system variables commonly involve one or a few related precursors, converting reversibly or irreversibly, to one or a few closely related products. Specific radiolysis products are often hard to measure, as large numbers of low concentration species are produced from even simple binary compound mixtures (Larter et al., 2012).
Frolov et al. (1998) and Curiale and Frolov (1998), described the production of alkenes in crude oils from natural radiation damage (radiolysis), with radiation dose-related impacts. In petroleum mixtures, radiation-induced unsaturation has a very complex distribution with double bonds appearing through essentially all organic fractions, making detection of radiation-induced daughter species by classical geochemical approaches, such as gas chromatography-mass spectrometry (GC-MS), very challenging. Therefore, a bulk technique for measuring double bond production, such as is available using spectroscopic approaches, such as nuclear magnetic resonance (NMR), are better suited to accurately assess alkene production (Frolov and Smirnov, 1994; Frolov et al., 1996; Frolov et al., 1998).

Dating petroleum reservoir fluid residence times


A light from a light source is output uniformly in the circumferential direction even if a shift or inclination occurs in a constituent member of a sound signal transmitter. A sound signal transmitter of a microphone includes a light source that outputs a light corresponding to a sound signal from a sound source, a division part that divides the light from the light source into a plurality of divided lights, and a reflector that reflects the divided lights from the division part.

A wireless microphone (hereinafter, referred to as a "microphone"), which transmits a sound signal to an external device such as an amplifier and a mixer by using infrared communication, is used for, for example, in indoor karaoke, conferences, speeches, and lectures.
In general, a microphone using infrared communication includes an electroacoustic transducer that generates a sound signal corresponding to collected sound and a transmitter that transmits a sound signal with an infrared light output from a light source (for example, a light emitting diode (LED)). The infrared light output from the transmitter is received by light receivers disposed on indoor walls and ceilings. The light receiver having received the infrared light transmits a sound signal converted from the infrared light to an external device such as a demodulator.
When a user grips and uses the microphone, the orientation of the microphone changes depending on, for example, how the user holds the microphone and rotation and inclination due to the use state of the microphone. Therefore, depending on the orientation of the microphone, the direction of the light source (transmission direction (traveling direction) of the infrared light output from the light source) may face a direction other than the direction of the light receiver. In such a case, since the infrared light does not reach the light receiver, the light receiver is unable to receive the infrared light from the microphone. As a result, infrared communication between the microphone and the light receiver is interrupted (the infrared communication is not stable).
Techniques have been proposed to stabilize the infrared communication between the microphone and the light receiver, regardless of the orientation of the microphone (the direction of the light source) (for example, see Japanese Unexamined Patent Application Publication No. H9-51279).
The microphone disclosed in Japanese Unexamined Patent Application Publication No. H9-51279 includes a transmitter using a plurality of LEDs (a plurality of light sources). The LEDs are arranged in a ring shape at equal intervals. Therefore, the transmitter uniformly transmits infrared lights, which are output from all the LEDs, in the circumferential direction of the transmitter. As a result, since the infrared light output from any one of the LEDs is received in the light receiver regardless of the orientation of the microphone, the microphone disclosed in Japanese Unexamined Patent Application Publication No. H9-51279 implements stable infrared communication.
However, when the LEDs are used in the transmitter, current consumption in the infrared communication increases as compared to conventional cases using one LED. In this regard, configurations have been proposed to uniformly output (transmit) an infrared light in the circumferential direction of the transmitter with less current consumption (less power consumption) than current consumption when a plurality of LEDs are used (for example, see Japanese Unexamined Patent Application Publication No. H9-230281).
The transmitter disclosed in Japanese Unexamined Patent Application Publication No. H9-230281 includes one laser diode and a conical reflector each as a constituent member. The laser diode is disposed with respect to the reflector such that an optical axis of a laser beam output from the laser diode is coaxial with an axis (apex) of the reflector. The laser beam output from the laser diode is incident on the reflector. Then, the laser beam incident on the reflector is reflected by the reflector and spreads in a ring shape. As a result, the laser beam is uniformly output in the circumferential direction of the transmitter.
However, in order to dispose the laser diode and the reflector such that the optical axis of the laser beam output from the laser diode is coaxial with the axis of the reflector, extremely accurate positional accuracy is required between the laser diode and the reflector. In other words, when a shift or inclination occurs in a constituent member of the transmitter due to an impact of, for example, a drop at the time of assembly and use of the transmitter, the laser beam is not uniformly output in the circumferential direction of the transmitter. As a result, stable communication is not implemented.

Sound signal transmitter and wireless microphone


The intensity of explosions as a result of hot (750-820 degrees C.) smelt from a pulp mill recovery boiler impacting cool (70-100 degrees C.) liquid in a dissolving tank is minimized by more effectively disrupting the flow of smelt from a spout free end tip into the tank. First and second nozzles which issue jets of disrupting fluid (such as steam or green liquor) are positioned on opposite sides of the center line of the spout, and are positioned and spaced from the spout tip and each other so that the jet emanating from at least one of the nozzles always intersects the flow of smelt from the spout even though the smelt flow path varies during normal operation of the recovery boiler. The first and second nozzles are preferably each spaced from the spout free end tip a distance of between about 300-700 mm, but different by at least 50 mm from the other nozzle, and are positioned downwardly and obliquely at an angle to the vertical so that the jets move downwardly and obliquely making an angle of between about 20-40 degrees with respect to the vertical. Other nozzles--e. g. in front of the smelt flow--can also be provided within a hood covering the spout area.

The present invention relates to a method and system for disrupting the flow from the smelt spout secured to the wall of a recovery boiler in a cellulose pulp mill (e. g. a kraft pulp mill), utilizing at least two properly positioned nozzles for introducing a disrupting medium for breaking up the smelt discharged from the boiler via the spout into a dissolving tank placed under the spout.
An essential apparatus in the chemical recovery circulation of sulfate and other sodium-based pulp manufacturing processes is the recovery boiler, such as a soda recovery boiler. In the recovery boiler waste liquor (e. g. black liquor) from the pulping process is combusted in order to transform cooking chemicals in the waste liquor into a form suitable for the recovery process. In a sulfate process the most important chemicals are sodium and sulfur. Organic substances dissolved in the waste liquor during digestion are combusted in the boiler producing heat which is used to convert the inorganic compounds contained in the waste liquor back into chemicals to be used in the digestion, and also for the production of steam. The inorganic matter of the waste liquor., i.e. ash, melts in the high temperature of the boiler and runs down as a primarily liquid smelt to the bottom of the furnace.
In conventional recovery boilers, the smelt is taken from the bottom of the boiler along one or more cooled smelt spouts to a dissolving tank. In the dissolving tank the smelt is dissolved into water or weak white liquor to produce soda lye, i.e. green liquor. The main components of the smelt, and the green liquor produced from it, in a sulfate process are sodium sulfide and sodium carbonate. The green liquor is then transported to a causticizing plant for white liquor production.
Hot smelt flow causes "banging" and explosions when it falls into the liquid in the dissolving tank. The "banging" noise is caused by the explosive reaction between the smelt and water when the smelt contacts the green liquor in the dissolving tank. The temperature of the smelt is on the order of 750-820.degree. C. and the temperature of the green liquor (or weak white liquor) in the dissolving tank, containing mainly water, is on the order of 70-100.degree. C.
The intensity of the explosive reactions in the dissolving tank may be controlled by breaking up the smelt flow running down the spout into small streams, droplets, flows, or pieces before it contacts the green liquor in the dissolving tank. In most cases, the smelt is disintegrated by directing a jet stream of green liquor against the smelt flow discharged from the spout. Also a jet of mist containing air and water has been suggested for this purpose. In Finland, the smelt is most commonly broken up by using low or medium pressure steam. However, the breaking up of the smelt flow using such disrupting streams is often uncertain and incomplete particularly when the flow path of the smelt between the smelt spout and the liquid surface in the dissolving tank varies. The flow path depends on the flow volume and the temperature of the smelt and other operating conditions, which inherently vary from time-to-time.
The conventional stationary breaking nozzle used for introducing disrupting media does not take into account the changing flow path of the smelt. It has been suggested that the position of the conventional breaking nozzle structure may be adjusted automatically, but such an automatic position adjustment causes problems. There is no reliable method available for adjusting the direction of the breaking nozzles with the change of the smelt flow path and the smelt volume. In practice the nozzle position (and disrupting stream direction) must be adjusted manually. However this is a dangerous job, and it is not economical or practical to assign a worker to perform this task on a continuous basis. The imperfect breaking up of the smelt pieces results in smaller or larger explosions which often cause an almost continuous loud noise in the vicinity of the dissolving tank. Liquid and smelt splashes and exhaust gases are usually prevented from escaping into the environment by a hood surrounding the smelt spout.
Usually, an excess volume of steam must be directed continuously to the smelt flow in order to secure adequate disintegration of the largest momentary smelt flow volumes. Thus, large volumes of steam may be wasted, which impairs the economy of the recovery process.
Swedish published patent application no. 381 295 discloses a method of improving the disintegration of smelt. The proposal in this reference is to cover the upper part of the dissolving tank with a semi-spherical hood having a wall thereof penetrated by the smelt spout of the recovery boiler. The smelt flow discharged from the spout hits a disc-like disrupting member inside the hood. The smelt may be further broken up by liquid jets disposed symmetrically below the disrupting member in the upper portion of the dissolving tank. A drawback of the disc-like disrupting member is that the sticky smelt may collect on its surfaces and consequently the disrupting capacity of the member is impaired. It must be cleaned manually, and the smelt lumps dislodged by cleaning fall into the dissolving tank, increasing the number of explosions. Because of the hot and chemically aggressive smelt, the life of such a disrupting member is very short even if it is made of fire-proof steel.
Japanese patent application no. 52-39575 discloses an apparatus for scattering and smashing the smelt flow. At first, the smelt arriving from the smelt spout is disrupted in an ordinary manner--by a steam jet disposed in the upper part of the dissolving tank--to produce coarse granules which then hit a cloud of water drops from horizontal nozzles, and after that impact an oblique plate before the fine smelt particles drop into the liquid in the tank.
The present invention seeks to improve the efficiency and reliability of the breakup of smelt discharged from the smelt spout of a recovery boiler to the dissolving tank and thus to minimize the number of explosive reactions between water and smelt compared to all of the prior art discussed above, in a relatively simple and inexpensive manner. The invention pays particular attention to the problems caused by variations in the smelt flow.
In order to achieve the advantages sought, the invention utilizes at least two dispersing nozzles distributing the same dispersing medium and disposed at a distance from the free end of tile spout and on different sides of a line parallel with the center axis of the spout. The nozzles are directed to apply at least one dispersing medium jet at a time obliquely downwardly to intersect the path of the smelt flow running down from the spout and thus to secure substantially uninterrupted breakup of the smelt flow during the process irrespective of the changes in the flow path.
According to the present invention, a new type of a smelt disrupting apparatus and method have been developed to reduce the noise problem of the dissolving tank. There are two or more dispersing nozzles provided in the vicinity of the smelt spout below the level of the end of the spout and directed towards the smelt flow from at least two different directions. At least two dispersing nozzles are located at the sides of the smelt flow running down from the smelt spout at a distance from a line parallel with the center line of the smelt spout (from the center line of the smelt flow). There may be one or more nozzles on both sides.
The dispersing nozzles may be arranged approximately at an equal distance from the free end of the smelt spout whereby the dispersing jets intersect the flow path of the smelt flow approximately at the same level. Preferably the dispersion nozzles are, however, disposed at different distances from the lower tip of the smelt spout. This arrangement guarantees that at least one dispersion jet hits the smelt flow from the side although the flow path of the smelt flow changes with relation to the dispersion nozzles due to smelt flow volumes and other process changes.
An additional nozzle or nozzles may also be arranged at other points by methods known per se. For example there may be an additional nozzle in front of the smelt flow and directed against the smelt flow or obliquely downwardly against the smelt flow. The nozzle may also be above the smelt flow directed approximately vertically downwardly.
According to one aspect of the present invention, an assembly for handling fluid smelt from a pulp mill recovery boiler is provided comprising the following components: A smelt spout connected to a recovery boiler, and having a free end tip, and a center line, fluid smelt downwardly flowing along the center line from said free end tip of said spout; and first and second nozzles for directing disrupting media toward the flowing smelt. The first and second nozzles are positioned on opposite sides of said center line, and so that at least one of the vertical and horizontal positions of said nozzles are different from each other so that the disrupting medium emanating from at least one of said nozzles intersects the smelt flowing downwardly from said smelt spout free end tip during normal operation even though the flow path of the smelt varies.
The first and second nozzles may each be spaced horizontally, in the dimension of smelt flow, from the spout free end tip a distance between about 200-500 mm, and the first nozzle is spaced a horizontal distance different from the second nozzle by between about 50-200 mm. Also, the first and second nozzles may both be positioned vertically below the spout free end tip a distance of between about 150-250 mm, and vertically spaced from each other a distance of at least 10 mm. For example, the first and second nozzles are each spaced from the spout free end tip a distance between about 300-700 mm, and at least 50 mm different than the other nozzle. Also, the first and second nozzles may each be spaced horizontally, in a dimension perpendicular to smelt flow, from the center line a distance between about 100-200 mm, and preferably the first and second nozzles are each positioned downwardly and obliquely at an angle to the vertical so that media emanating moves downwardly and obliquely making an angle of between about 20-40 degrees with respect to the vertical.
A third nozzle may be provided, e. g. positioned horizontally in front of the spout in the direction of smelt flow, and directing disrupting medium therefrom in a horizontal direction substantially opposite to the horizontal component of the smelt flow.
According to another aspect of the present invention, a chemical recovery assembly is provided comprising the following components: A pulp mill recovery boiler having a smelt spout extending outwardly from a bottom portion thereof. A green liquor dissolving tank positioned beneath the smelt spout to receive smelt from the smelt spout therein; the smelt spout having a free end tip, and a center line, fluid smelt downwardly flowing along the center line from the free end tip of the spout. And first and second nozzles for directing disrupting media toward the flowing smelt, the first and second nozzles positioned on opposite sides of the center line, and so that the first and second nozzles are each spaced horizontally, in the dimension of smelt flow, from the spout free end tip a distance between about 200-500 mm, and the first nozzle is spaced a horizontal distance different from the second nozzle bof between about 50-200 mm. Other details of nozzle positioning may be provided as described above.
According to another aspect of the invention there is provided a method of dissolving smelt to form green liquor while minimizing explosions as a result of hot (e. g. about 750-820 degrees C.) smelt contacting cool (e. g. about 70-100 degrees C.) liquid, using: a recovery boiler having a smelt spout extending outwardly from a bottom portion thereof; the smelt spout having a free end tip, and a center line, fluid smelt downwardly flowing along the center line from the free end tip of the spout; and a dissolving tank positioned below the spout and having cool liquid therein. The method comprises the following steps:
(a) causing fluid smelt to flow downwardly from the free end tip of the spout toward the dissolving tank, the smelt flow path inherently varying during normal operation of the recovery boiler; and
(b) before the smelt impacts the liquid in the dissolving tank, directing a disrupting medium in first and second distinct jets from opposite sides of the center line of the smelt flow toward the smelt flow to impact the smelt and break it into smaller flows, droplets, or pieces; and
wherein step (b) is practiced so that the distinct jets are differently directed so that, in combination, the disrupting medium from at least one of the jets intersects the smelt flowing downwardly from the smelt spout free end tip during normal operation even though the flow path of the smelt varies.
Step (b) is also preferably practiced so that jets are continuously emanating from both sides of the spout centerline at the same time (although based upon visual or automatic determination of the smelt flow at any particular point in time one of the jets may be turned off); and step (b) is also preferably practiced by positioning first and second nozzles which issue the jets of disrupting medium so that the first and second nozzles are each spaced from the spout free end tip a distance of between about 300-700 mm, but different by at least 50 mm from the other nozzle, and are positioned downwardly and obliquely at an angle to the vertical so that the jets move downwardly and obliquely making an angle of between about 20-40 degrees with respect to the vertical.
It is the primary object of the present invention to provide a simple yet effective method and apparatus for optimally disrupting the flow of smelt into a dissolving tank even when the smelt flow rate is inconsistent, varying during normal and inherent process changes. This and other objects of the invention will become clear from an inspection of the detailed description of the invention, and from the appended claims.

Disrupting the flow from the smelt spout of a recovery boiler


The invention provides methods and materials related to treating HPV infections (e.g., HPV infections of cutaneous and mucosal epithelial cells) and HPV-associated conditions (e.g., cervical dysplasia, HPV-associated cervical carcinomas, oral mucosal papilloma cancers, laryngeal papilloma cancers).

1. Technical Field
The invention relates to methods and materials involved in treating human papillomavirus infections and human papillomavirus-associated conditions.
2. Background Information
Human Papillomaviruses (HPV), members of the papillomavirinea family of viruses, are recognized as a human pathogen. Various types of HPV are tropic for cutaneous and mucosal epithelial cells, and consequently they are involved in development of papillomas (including common, genital, and planter warts), and cervical carcinomas (zur Hausen, Curr. Top. Microbiol. Immunol., 186:131-56 (1994)). Types 16, 18, 31, 33, 35, 39, 45, 52, and 58 are involved in nearly 100 percent of all carcinomas of the cervix (Walboomers et al., J. Pathol., 189:12-9 (1999)), with 16 and 18 constituting "high risk" types.

Methods and materials for treating human papillomavirus infections


A bag-shaped drug container comprises a bag-shaped container body made of a flexible film, and a mouth provided at one end of the container body. The mouth is provided on a side of an open end thereof with a Luer locking means to liquid-tightly connect it with a tip of a syringe, and closed by a closing means such as cap or a male Luer portion.

The present invention relates to a small bag-shaped drug container and, more particularly, to a small bag-shaped drug container suitable for almost insoluble or insoluble drugs. Further, the present invention relates to a small bag-shaped drug container, which enables a drug to be easily and completely dissolved or suspended in spite of a small amount of a solution.
Drugs which are easily degenerated by moisture or oxygen have conventionally been administered in the form of a liquid drug prepared just before use by mixing it with a solution. In order to prepare the liquid drug, there have widely been used a so-called syringe method comprising the steps of injecting a solution into a vial containing a dried drug with a syringe, and then drawing the resultant liquid drug into the syringe, or a method employing a double ended needle to communicate a solution container with a drug container. Recently, in order to remove troublesome dispensation, double chamber type prefilled syringes have been put into practical use. Such a prefilled syringe contains a drug in a drug chamber and a solution in a solution chamber, which are adapted to be communicated with one another by communicating means such as a bypass or a built-in connecting needle to dissolve the drug in the solution.
The syringe method is used for preparation of a liquid drug less than about 10 ml, but it is troublesome in dissolving operation. Further, in case that a drug such as a subcutaneous injection is required to be dissolved or suspended in a small amount of the solution, it is extremely difficult to perform the dissolving operation in the vial. In addition, in case of insoluble or substantially insoluble drugs, it is required to repeatedly transfer a mixture of the solid medicine and the solution from the syringe to the vial, or vice versa, in order to achieve complete dissolution or suspension. However, it is very difficult to perform such dissolving operations without producing foaming.
The above troublesome dispensation can be avoided by use of the method of employing a double ended needle or the double-chamber type prefilled syringes. However, it is very difficult with the method of employing a double-ended needle to dissolve insoluble or substantially insoluble drugs in the solution without foaming, since the mixture of the solid medicine and the solution must be repeatedly transferred from the syringe to the vial, or vice versa, in order to achieve dissolution or suspending. Similarly, it is very difficult with the double-chamber type prefilled syringe to perform dissolving operation without foaming since the mixing can be performed only by shaking of the syringe.


The present invention provides compositions and methods related to equine live-attenuated influenza vaccines.

Equine influenza, currently caused by H3N8 EIV, is the most common and important respiratory infectious disease of horses (Daly et al., 2011, Vet J, 189: 7-14; Timoney, 2000, Vet. Clin. North Am. Equine Pract. 16, 537-551). H3N8 EIV is highly contagious and has the potential to spread rapidly through groups of naive horses in aerosolized droplets that are dispersed by coughing (Daly et al., 2011, Vet J, 189: 7-14; Timoney, 2000, Vet. Clin. North Am. Equine Pract. 16, 537-551). H3N8 EIV infections of horses have been responsible for disrupting major equestrian events and causing significant economic losses (Daly et al., 2011, Vet J, 189: 7-14; Timoney, 2000, Vet. Clin. North Am. Equine Pract. 16, 537-551). The equine population is highly mobile, and horses travel long distances by road and/or air for competitions and breeding purposes. When an infected horse is introduced into a susceptible population, the spread of H3N8 EIV can be explosive. Large outbreaks of H3N8 EIV are often associated with the congregation of horses at equestrian events. Their dispersal after these events can lead to further widespread dissemination of the virus. It is currently estimated that H3N8 EIV outbreaks result in economic losses of hundreds of millions of dollars.
In endemic countries, the significant economic losses caused by H3N8 EIV infections can be minimized by vaccination of highly mobile horses. Indeed, many racing and equestrian authorities have mandatory vaccination policies that serve as insurance for business. On the other hand, non-endemic countries rely on vaccination of imported horses and quarantine to prevent an incursion of H3N8 EIV. The majority of these non-endemic countries also require vaccination of their indigenous horse population to reduce the potential impact of an H3N8 EIV incursion.
Traditional vaccination strategies support that vaccine strains must represent viruses in circulation, and it is only through surveillance that vaccine companies decide on which antigens should be used. Thus, EIV surveillance and strain characterization are fundamental for H3N8 EIV control programs based on vaccination. Importantly, vaccine manufacturers need to have a dynamic vaccination approach that allows the rapid generation of novel vaccines to benefit the equine population (Cullinane et al., 2010, Influenza Other Respir. Virus. 4, 339-344; Paillot, 2014, Vaccines 2, 797-831; Paillot et al., 2016, Pathogens 5). Results from cross-protection studies indicate that the majority of the inactivated vaccines or the current commercially available LAIV Flu Avert I.N. would provide poor levels of protection if used in the face of an imminent outbreak because of the antigenic differences between the virus in the vaccine and currently circulating H3N8 EIV strains (Paillot et al., 2016, Pathogens 5). Notably, some recent H3N8 EIV outbreaks occurred in previously vaccinated animals, where the vaccine strain did not match the circulating virus (Daly et al., 2003, Equine Vet. J. 35, 458-462; Garner et al., 2011, Prev. Vet. Med. 99, 15-27; Timoney, 2000, Vet. Clin. North Am. Equine Pract. 16, 537-551). The frequency of H3N8 EIV outbreaks, the continuous antigenic variation (antigenic drift) of H3N8 EIV and examples of vaccine breakdown due to poorly antigenic match demonstrate the periodic need to update EIV vaccines to prevent equine influenza in the equine population. Moreover, EIV vaccines should include both clade 1 and clade 2 representative strains of the Florida sublineage, as recommended by the OIE (Paillot et al., 2016, Pathogens 5).
Thus, there is a need in the art for improved vaccines for EIV. The present invention satisfies this unmet need.

Multivalent live-attenuated influenza vaccine for prevention and control of equine influenza virus (EIV) in horses


An interchangeable colored bicycle has a bicycle framework with a main bicycle frame component part, a handlebar stem component part, and a wheel fork component part. Clear transparent tube members enclose and circumscribe these component parts. Free-flowing, colored liquids fill the interior spaces between the tube members and the component parts. The colored liquids in each interior space are different, thus allowing the bicycle to assume multiple colors. The free-flowing liquids can be drained from the tube members and different colored liquids can be poured into the interior spaces to change the colors of the bicycle.

The color of a bicycle is usually important to the bicycle purchaser, especially to younger riders. However, if that color preference changes, the rider has no other option but to retain the bicycle with the less than favorable color, or purchase a new one with a different color. Further, selling a used bicycle would be easier if the bike could be available in a specific color, attractive to a potential buyer. A single bicycle which could be altered to a variety of different colors, changeable at the preference of the rider, would also be very desirable.
There is currently no means of simply and easily changing the color of a bicycle at the whim of the rider. There is also no means to permit a single bicycle to take on multiple colors, while still allowing the rider to continually change the colors.


A solid-state imaging apparatus including: a pixel section having two-dimensionally arrayed unit pixels each having a first pixel and a second pixel respectively containing photoelectric conversion devices that are located at positions regarded as the same position at which image is formed by an imaging optical system; a reset control means for simultaneously resetting respectively independently all first pixels and all second pixels of each unit pixel arrayed in the pixel section; a difference signal output means for obtaining a difference signal between signals of the first pixel and of the second pixel; a control section for rendering control such that a reset is effected of signals of all first pixels of the pixel section and, after a desired exposure time, a reset is effected of signals of all second pixels of the pixel section by the reset control means, and then signals of the first pixel and of the second pixel are read out respectively in a simultaneous or substantially simultaneous manner immediately after the reset of signal of all second pixels by the reset control means so as to output a difference signal between these as imaging signal by the difference signal output means; and a characteristic difference correction means for correcting a characteristic difference between the first pixel and the second pixel.

The present invention relates to solid-state imaging apparatus having a concurrent shutter (hereinafter referred to as global shutter) function, and more particularly relates to a solid-state imaging apparatus having a global shutter function so as to be capable of obtaining imaging data having a high image quality.
Conventionally, XY-addressing read methods are generally used to read pixel signals in MOS solid-state imaging apparatus. The construction of MOS solid-state imaging apparatus and XY-addressing read method thereof will be described below by way of FIGS. 1, 2 and 3. FIG. 1 shows a general pixel construction to be used in a MOS solid-state imaging apparatus. What is denoted by numeral 600 in FIG. 1 is a single pixel. Shown respectively therein are: 606, a photodiode serving as photoelectric conversion device; 602, a transfer transistor for transferring signal charge generated at photodiode 606 to a memory 605; 601, a reset transistor for resetting the memory 605 and photodiode 606; 604, an amplifier (amplification transistor) for amplifying and reading voltage level of the memory 605; and 603, a select transistor for selecting the pixel to transmit an output of the amplifier 604 to a vertical signal line 614. Here, these components but photodiode 606 are shielded from light.
Also referring to FIG. 1, denoted by numeral 610 is a pixel power supply, electrically connected to drain of the amplifier 604 and drain of the reset transistor 601. 611 is a reset line for resetting pixels corresponding to one row, which is electrically connected respectively to the gates of reset transistor 601 of the pixels corresponding to one row. 612 is a transfer line for transferring signal charge of the pixels corresponding to one row to the memory 605 of the respective pixels, which is electrically connected respectively to the gates of transfer transistor 602 corresponding to one row. 613 is a select line for selecting pixels corresponding to one row, which is electrically connected respectively to the gates of select transistor 603 corresponding to one row. Use of the pixel construction having four transistors in this manner (hereinafter referred to as 4-Tr pixel) achieves a photoelectric conversion function, reset function, amplification/read function, temporary memory function, and select function.
FIG. 2 shows a general fundamental construction of the solid-state imaging apparatus using XY-addressing read method. A light receiving section is constituted by a pixel array 700 where pixels 600 having the pixel construction shown in FIG. 1 are arrayed in m-rows by n-columns. A vertical scanning circuit 704 scans the pixel array 700 while outputting to the pixel array 700 a row select signal φSELi (i=1, 2, 3, . . . m), row reset signal φRSi, and row transfer signal φTxi. At this time, the row select signal φSELi is transmitted to the gate of select transistor 603 of the pixels of i-th row through the select line 613, row reset signal φRSi is transmitted to the gate of reset transistor 601 of the pixels of i-th row through the reset line 611, and row transfer signal φTXi is transmitted to the gate of transfer transistor 602 of the pixels of i-th row through the transfer line 612.
When signals of the pixels of i-th row are to be read out, row select signal φSELi of i-th row is inputted to the pixel array 700 from the vertical scanning circuit 704, and when photodiodes 606 of the pixels of i-th row are to be reset, row reset signal φRSi and transfer signal φTXi of i-th row are inputted to the pixel array 700 from the vertical scanning circuit 704. When the memory 605 of the pixels of i-th row are to be reset, row reset signal φRSi of i-th row is inputted to the pixel array 700 from the vertical scanning circuit 704. When signal charge of the pixels of i-th row is to be transferred to the memory 605, row transfer signal φTXi of i-th row is inputted to the pixel array 700 from the vertical scanning circuit 704.
Of the signals of the pixels of selected i-th row, after processing such as the canceling of FPN (fixed pattern noise) at a row parallel processing circuit 701, the results of processing are stored to a line memory 702. Subsequently, scan and read are effected while sequentially selecting through a horizontal select switch the pixel signals corresponding to one row stored at the line memory 702 based on the outputting of horizontal scanning signal φHj (j=1, 2, 3, . . . n) by a horizontal scanning circuit 703. By sequentially effecting this processing from the first row to m-th row, the signals of all pixels of the pixel array 700 can be scanned and read out.
FIG. 3 is a timing chart showing drive timing of the solid-state imaging apparatus of such XY-addressing read method. The drive operation will be described with noticing the period of T1. As row select signal φSEL1 is outputted and the reset signal φRS1 is then outputted from the vertical scanning circuit 704, pixels of the first row are selected and reset level of the pixels is read out. Further, as row transfer signal φTX1 is outputted from the vertical scanning circuit 704, signal charge generated at the photodiodes 606 of the first row is transferred to the memory 605 so that signal level of the pixels is read out. Subsequently, row reset signal φRS1 and row transfer signal φTX1 are outputted to reset the photodiode 606 and memory 605. The accumulation period of the signal to be read out here is the period indicated by Ta in the figure from immediately after the resetting of photodiode 606 in the previous frame to its transferring. Further, a differential processing between the signal level and the reset level is effected during the period of T1, and signal thereof is stored to the line memory 702. After that, signals of the first row are outputted by causing an operation of the horizontal scanning circuit 703 to output the horizontal scanning signal φHj (j=1, 2, 3, . . . n). Thereafter similar operation is effected of each row.
In such an ordinary XY-addressing read method (rolling shutter read method), since the point in time for accumulating signal is different from one row to another of the pixel array, or more specifically since a difference in the point in time corresponding to one frame at maximum exists between the first row to be read out first and the m-th row to be read out at the end, a problem of distorted image occurs when a rapidly moving object is photographed.
The global shutter read method is provided as a method for solving the above problem in the ordinary XY-addressing read method. Such read method will now be briefly described. FIG. 4 shows drive timing when global shutter operation is effected in a solid-state imaging apparatus having the same fundamental construction as the one shown in FIGS. 1 and 2.
First, as the row reset signals φRS1 to φRSm and row transfer signals φTX1 to φTXm of all the rows are simultaneously outputted from the vertical scanning circuit 704, photodiodes 606 of the pixels corresponding to all rows are reset. Subsequently, after a certain signal accumulation period, row transfer signals φTX1 to φTXm of all rows are simultaneously outputted from the vertical scanning circuit 704. The signal charges accumulated within the certain period at photodiodes 606 of the pixels corresponding to all rows are thereby transferred simultaneously for all rows to the memory 605. By such operation, the global shutter operation is effected.
A row-by-row read of the signals stored at memory 605 is then started. First, as row select signal φSEL1 is outputted from the vertical scanning circuit 704, the pixels of the first row are selected and the signal level of the pixels are read out. Further, as row reset signal φRS1 is outputted from the vertical scanning circuit 704, the memory 605 of the first row is reset so that the reset level of the pixels is read out. When read of the signal level and reset level of the pixels of the first row is complete, the pixels of the second row are selected and the signal level and reset level thereof are read out. By effecting this signal read scanning to m-th row, signals corresponding to one frame are read out. Although a horizontal scanning signal φHj of the horizontal scanning circuit 703 has not been shown for ease of explanation, the horizontal scanning signal φHj (j=1, 2, 3, . . . n) is outputted in an interval from the reading of the signals of i-th row to the reading of the signals of i+1-th row.
Japanese Patent Application Laid-Open 2002-320141 for example discloses a solid-state imaging apparatus using 4-Tr pixels, in which global shutter operation is effected.

This patent is subject to a terminal disclaimer.


A first indicator of a first number of cache misses to a cache memory of a multicore processor for a first application over a first time period is received. The first application executes on a first core of the processor and a second application simultaneously executes on a second core of the processor during the first time period. The first and second cores share the cache memory. A second indicator of a second number of cache misses to the cache memory for the first application over a second time period is received. During the second time period, the first application executes on the first core and the second application does not execute on the second core. A degree of contention among the first and second applications is determined based on the first and second indicators, and execution of the second application is adjusted based on the determined degree of contention.

Multicore processor architectures are widely used in modern computing systems. These architectures dominate in many domains, including those with quality of service (QoS) and low latency requirements. A multicore processor architecture includes two or more processing cores, on which two or more software applications may execute in parallel. When two or more applications are executing in parallel on separate cores of a single multicore processor, the applications are said to be co-located on the processor.
The processing cores of the multicore processor often use both private resources and shared resources to perform tasks associated with the executing applications. Private resources are generally replicated across each of the processing cores, for exclusive use by a corresponding individual processing core. Shared resources, by contrast, may generally be used by any of the processing cores of the multicore processor. When two or more applications that are simultaneously executing on separate cores each attempt to use a shared resource, contention for the shared resource can result. Often, contention for shared resources can result in reduced performance, or cross-core application interference, for one or both of the applications competing for the shared resource.

Cache contention management on a multicore processor based on the degree of contention exceeding a threshold


A two-piece safety cap for a container including a valve assembly having a valve rim thereon is disclosed. The safety cap comprises a collar having an inner surface and an outer surface and top and bottom portions. The collar is securably seatable on the valve rim so that the inner surface is arranged adjacent the valve rim. The bottom portion of the collar is sized and shaped so that the collar can be arranged on the valve rim regardless of the diameter of the barrel of the associated container without any interference occurring between the bottom portion of the collar and the container. The safety cap also comprises a cover adapted to be mounted between a removable position and a non-removable position on the collar. Additionally, a locking mechanism is arranged between the cover and the collar so that the cover can be selectively locked thereon.

Childproof caps for preventing children from gaining access to potentially dangerous products stored within different types of containers are generally known within the safety closure art. Many inventors have devoted large amounts of effort to developing childproof caps. Despite the great effort expended by such inventors, the structure and operation of known childproof caps which are adapted to prevent children from gaining access to products stored within a container have many drawbacks which render them ineffective and undesirable.
Thousands of unnecessary emergencies arise every year because of young children who accidentally come into contact with potentially dangerous products stored within various types of containers. For example, a wide variety of household products such as cleaners, insecticides, paints, cosmetic aids, and the like are stored within aerosol cans. These products are generally used by spraying them directly onto their intended target. This can be a quick and efficient way for dispensing such products from a container. However, these types of dispensers can also be extremely dangerous since many of the products can cause serious injuries if they are improperly applied to the eyes, lungs or skin of a person or an animal. This danger becomes even greater when unprotected aerosol cans are left within the reach of young children.
Many other potentially dangerous products are stored within containers which dispense such products through a valve and which have a valve rim thereon. These products include various gels, hair products such as mousse, and other cosmetic products which are retained in pressurized containers other than aerosol containers. Since these products may also be toxic, it is desirable to prevent young children from having unsupervised access to them.
As can be appreciated, the size of the barrel of the pressurized containers in which many of the foregoing products are stored can vary from relatively small to relatively large. For example, some products, such as oven cleaner, are stored in aerosol cans having a relatively large diameter barrel. On the other hand, mousse and other hair gels are often stored in a pressurized container having a relatively small diameter barrel. Despite the differences in the barrel sizes, the valve rim is generally one standard size. In particular, a well known standard size valve rim has an outer diameter of approximately 1.29 inches.
Thus, there is a great need for a universally adaptable childproof cap to prevent young children from gaining access to the potentially harmful products stored within pressurized containers having a standard sized valve rim and various sized barrels. Efforts have been made, prior to this invention, to develop childproof caps for placement over the dispensing mechanism of various pressurized cans. However, these efforts have been largely unsuccessful because the known safety caps are not universally adaptable, are too expensive to manufacture, are too difficult to remove from an associated container, or are ineffective for a variety of other reasons. Examples of known prior art safety caps having one or more of the foregoing drawbacks include U.S. Pat. Nos. 5,092,493 to Pehr; 5,040,694 to Gambello; 4,662,542 to Vitale; 4,576,315 to Vitale; 4,353,483 to Pehr; 4,133,448 to Balfanz; and 3,964,634 to Jasinski et al.
It is evident from all of the drawbacks that exist in the safety cap art, that there is a considerable need for a new and improved universally adaptable childproof cap to prevent young children from gaining access to potentially harmful contents stored within various sized pressurized containers having a standard sized valve rim thereon.
The present invention solves all of the aforementioned problems and will greatly benefit all individuals who are concerned that young children may injure themselves by dispensing various contents from pressurized containers.


A mounting device for a camera with automatic exposure mode to an optical system is disclosed. An adapter tube has a first and a second end, wherein the first end is attached to the camera and the second end is attached to the optical system. A mounting element, provided at the first end, provides the mechanical connection to the camera. A plurality of electric contact pins, located at the first end, cooperates with respective electric contacts provided at the camera.

It is important for users to attach a digital or conventional camera to an optical system in order to take pictures with the camera. In order to do so the lens of the camera needs to be removed and an adapter is used to mount the camera to the optical system. An additional feature for the user is to use the automatic mode of the camera for taking the pictures. The user should not be bothered with any manual settings of the camera. It would be extremely inconvenient for a user if he has to interrupt the observation in order to set the camera.
U.S. Pat. No. 4,478,212 shows an adapter for coupling a camera adapted to receive power from an endoscope to which the camera is coupled. The adapter is coupled between the ocular section of the endoscope and the mounting of the taking lens of the camera. The adapter has electric power terminals for providing the camera with electric power. The adapter can have a built in power source or a plug-in power source. There is no indication that the adapter simulated the presence of an objective to the camera.
German Utility Model DE 200 10 421 U1 discloses an adapter for attaching a camera to the photo tube of a microscope. Between the camera and the pipe like photo tube the adapter is provided. The mounting means enables an alignment between the optical axis of the camera and the optical axis of the microscope.
U.S. Pat. No. 6,462,771 discloses a still-picture acquisition method and device. A still-picture acquisition section in a computer selects a brightness-periodically-varying portion of image data of a living cell like a cardiac cell, as a sample, which makes a self-ordered periodic motion, monitors a change in brightness, and generates a trigger signal at the timing at which the value of the brightness exceeds a specific threshold value. This causes a camera body to repeatedly pick up the image of the living cell after a predetermined delay time and then averages the picked-up images. There is no indication of the use of a conventional camera to pick-up the images from the microscope.

Mounting device for a camera with automatic exposure mode to an optical system


The invention pertains to a method for the production of a biologically active modified protein derived from a starting protein having essentially the same kind of biological activity with an attendant modulation effect on, particularly increase of, the stability as compared with that of the starting protein. The method comprises substituting an arginine residue for a lysine residue of the starting protein at a site that can sterically accommodate the substitution, without substantially altering the biological activity of the starting protein, said site being preferably of low solvent accessibility, at interfaces between domains or sub-units of the starting protein.

Proteins are chemical compounds endowed with tiological functions. Proteins with the ability to catalyze chemicaI reactions are designated enzymes.
Many proteins, especially enzymes from microbial sources, have found an extensive use in a variety of industrial applications. Enzymes have a number of advantages over purely chemical processes. They are highly specific, and can efficiently catalyze reactions which might otherwise require extreme conditions of e.g. temperature, pressure, pH, etc.
The following list is intended as a non-exhaustive list of particular examples. For a more detailed treatment of these and other industrial enzymes, reference is made to Godfrey and Reichelt (1983).
Amylases, glucose isomerases, glucoamylases, isoamylases, invertases, pullulanases, etc. are used in the starch conversion technology which is applied in the preparation of a great variety of products (Van Beynum and Roels, 1985). PA1 Beta-galactosidases, catalases, chymosines, lipases etc. are used in the dairy industry. PA1 Cellulases find an application in waste treatment industry. PA1 Proteases are used in the detergent, the leather and baking industries. PA1 Pectic enzymes are applied in the fruit juice industry PA1 Glucose oxidase is used as an antioxidant in brewing and wine-making industries and in the food industry in general, and also finds applications in clinical diagnostics and analytical assays. PA1 Most industrial enzymes are used preferably at elevated temperatures so that contamination and viscosity are reduced while reaction rates are increased. However, at industrially preferred temperatures, proteins are bound to undergo inactivation. Therefore, industrial enzymes are often best derived from thermophilic microorganisms. PA1 pH considerations must take into account the pH optimum of specific enzymes, the stability of substrate and products, and conditions further imposed by upstream and/or downstream operations in the industrial process. PA1 Enzyme activators and coenzymes present a problem to the extent that they create additional costs e.g. for their elimination from the product during down-stream processing. PA1 Inhibitors are a problem in as much as they can be difficult to remove from the reaction mixture or may be even essential for the reaction (e.g. in the case of substrate inhibition). Inhibitors can act through a variety of mechanisms, one of which is chemical modification of the protein. PA1 1 Hydrophobic interactions, which are thought to be the most important contribution favoring the folded state in aqueous environment (Kauzmann, 1959; Privalov, 1979). PA1 2. Chain entropy, i.e. the number of conformational states, which is the most important single contribution favoring the unfolded state. PA1 3 Specific non-covalent interactions between protein atoms in the folded state, which at least compensate for similar interactions made with the solvent in the unfolded state. These are hydrogen bonds, Van der Waals interactions, and other electrostatic interactions between charges (ionised groups) and/or dipoles (Creighton, 1983). PA1 1. The residue to be replaced should be directly involved in electrostatic interactions, preferably in the interface between subunits an/or domains. PA1 2. The mutation should occur at a site that can sterically accommodate the amino acid residue that is introduced. PA1 3. The residue should occur at a site of low solvent accessibility and, preferably be part of an interface between subunits and/or domains.
For industrial purposes either whole microbial cells or purified enzymes may be used. Purified enzymes, although more costly, are preferred because they can generally convert a higher proportion of substrate, while displaying fewer side reactions.
The use of enzymes in industry, and of proteins in general, is still restricted in many cases. The greatest technical difficulty is the finding of suitable proteins which are stable under industrially desired conditions such as temperature, pH, requirements of activators, and/or the presence of inhibitors.
The use of proteins for therapeutic applications is rapidly increasing, mostly due to developments in recombinant DNA technology. Recombinant tissue Plasminogen Activator, human serum albumin, human growth hormone, interferons, and insulin for instance are already well known in this respect (Watson et al., 1983; Roskam, 1987). Other examples are L-Asparaginase which finds an application in the treatment of acute lymphocytic leukemia, and superoxide dismutases which have been proposed for the treatment of oxidative damage in a wide variety of applications.
Last, but not least, a large variety of proteins are used for clinical or analytical assays (Bergmeyer, 1983), or as diagnostics (Dodet, 1987).
In all these applications where particular proteins are used, one is often confronted with the problem of protein stability Indeed, many proteins, particular enzymes, become unstable and inactivated when they are isolated from their natural environment.
Proteins commonly consist of combinations of some or all of twenty monomeric building blocks called amino acids. The amino acids are conventionally represented by either a three-or a one-letter code as shown in Table I.
The amino acids are linearly linked together by a special type of covalent bond termed the peptide bond. The order or sequence of the amino acids so linked is the primary structure of a protein. The primary structure is important for at least three reasons. First, it determines the three-dimensional (3D) structure of a protein. Second, it confers the latter three-dimensional conformation with one or more biological functions via the choice of amino acids necessary for the conformational structure yet bestowed with the appropriate chemical physical characteristics to fulfill the desired functionality. Third, essential information regarding the DNA sequence can be ascertained from the primary structure of a protein and vice versa.
A polypeptide is the amino acid chain that is translated from a single messenger RNA (mRNA) which, in turn, is transcribed from a single structural gene. Proteins are composed of one or more polypeptide chains. Monomeric proteins are composed of a single polypeptide chain (and in some cases, e.g. insulin, of a few covalently linked polypeptide chains). Oligomeric proteins are composed of two or more polypeptide chains, termed "subunits", which are structurally similar to monomeric proteins without necessarily possessing separate biological functions.
The three-dimensional structure of a protein comprises its secondary, tertiary, and quaternary structures. Secondary structure refers to structural elements that involve the relationship or interaction of the main-chain atoms of neighboring amino acids of the primary chain. Tertiary structure is the spatial arrangement of all atoms of the amino acids making the polypeptide chain. Many proteins may associate into super-assembly structures; in such multi-subunit proteins, the term quaternary Structure refers to the arrangement of subunits in the protein and quaternary interactions are those which occur between atoms belonging to different subunits.
Owing to secondary, tertiary, and quaternary structure, many complex interactions may occur between amino acids, whether they are close or far remote from each other within the amino acid sequence.
In the native state --i.e. the state associated with biological function--, the polypeptide chain adopts one, or a small number of, well defined conformations. In the denatured state, the protein is devoid of biological function; in this so-called "unfolded" state, the three-dimensional structure is not well defined in that the polypeptide chain assumes a large number of different conformations (Anfinsen & Sheraga, 1975).
The native state is stable under well defined conditions of pH, temperature, ionic strength and pressure. Where unfolding --denaturation-- is shown to be reversible, it is verified that the free energy of the native state is lower than that of the denatured state. In such instance, the difference in free energy (delta G) between the two states provides a direct measure of protein stability (Privalov, 1979).
In addition to covalent interactions, the native conformation results from a complex interplay of different forces (Janin,1979):
Folding is the process that leads to the formation of the native state, whereas denaturation is the process which leads to the denatured (or unfolded) state starting from the native conformation.
The kinetics of the unfolding --or of the folding-- process is, under given physical conditions, a function of the energy barrier encountered by the system during the transition process (Creighton, 1983). It is not a function of the difference in free energy between the native and denatured states.
In multi-subunit (oligomeric) proteins, individual subunits often display an appreciable degree of folding prior to their assembly into the final quaternary structure. The structure of the isolated subunits, however, need not be absolutely identical to that observed in the final oligomeric state. Upon recognition and association, further structural adjustments may indeed occur so that the final quaternary conformation acquires its most thermodynamically favored state (Jeanicke, 1987).
In polypeptide chains above a certain size (about 100 amino acid residues), the presence of globular sub-structures, termed "domains", has been recognized. Based on the analysis of a number of protein 3D structures (see review by Janin & Wodak, 1983), as well as on experimental data on protein renaturation (Goldberg, 1969), and on the discovery that such domains could be isolated by limited proteolysis (Porter, 1973), it is believed that domains could play an essential role in folding (Wetlaufer, 1973).
Structural domains can be identified in proteins with known 3D structures using the procedure described by Wodak and Janin (1981). In case the structure of a protein is not known, indications of domains can be obtained by studies on limited proteolysis (Porter, 1973).
It has been inferred from the above considerations that interactions between subunits or between domains contribute to increase the stability of the folded native state (Miller et al., 1987), and that folded individual domains, or subunits, can be folding intermediates. The early steps in protein denaturation are thus likely to involve the disruption of interactions between subunits or domains (Ptitsyn, 1987).
Such contention is in general widely and largely accepted by those experts in the art as a result of numerous observations derived from the study of naturally occurring protein mutants (Perutz, 1978; Walker et al., 1980; Mrabet et al., 1986).
Enzymes are proteins which have the ability to catalyze biochemical reactions. Enzymes are very specific for their substrate, a consequence of the 3D structure and of the physical-chemical properties of their "active site" where the substrate binds and the chemical reaction takes place (Fersht, 1985).
The partial or total loss of enzymatic activity (or of biological activity in proteins, in general) is termed inactivation. As a result of the above-mentioned considerations, any alteration of the native conformation of the enzyme may influence the enzymatic activity, and, in particular, lead to inactivation.
Thermal inactivation of enzymes, i.e. the loss of enzymatic activity as induced by temperature, may be either reversible or irreversible, depending on whether return to ambient temperature results in the recovery of biological activity within a reasonable period of time (Klibanov, 1983). The most common causes of irreversible denaturation are believed to be either non-covalent (aggregation or folding into a stable non-native conformation) or covalent (chemical modification of the covalent structure of the polypeptide chain). The latter has been shown to prevail in lysozyme (Ahern & Klibanov, 1985). A number of chemical reactions can take place in proteins at high temperature (Zale & Klibanov, 1986), but the most frequently studied ones are deamidation (Asn and Gln are converted to Asp and Glu, respectively), hydrolysis (e.g. cleavage of the acid-labile peptide bond following an Asp residue (Inglis, 1983), and oxidation of methionine to the sulfoxide form.
Covalent alterations of the protein structure --in particular, the introduction of chemical cross-links-- can also impart protein stability. It has indeed been the most common means for increasing protein (thermo)stability in the past (Torchilin, 1983; Sadana & Henley, 1986; Gottschalk & Jaenicke, 1987). The success of this approach has however been limited because (1) the protocols rely on exhaustive screening of cross-linking agents of variable lengths and/or chemistry, (2) the chemical reactions cannot be reliably targeted to specific amino acid residues of the protein and may therefore occur at unwanted sites, such as those which may interfere with biological function.
More recently, with the advent of protein engineering, it has been possible, by site-directed mutagenesis (SDM) of the gene, to modify a given protein amino acid sequence at will, and thereby produce enzymes with improved properties (for reviews see Knowles, 1987, and Dill, 1987).
In some of the early examples, SDM has been used to engineer non-native disulfide bonds in proteins. Only in a limited number of cases, however, has this approach been successful (Perry & Wetzel, 1984; Wetzel, 1985; Sauer et al., 1986; Villafranca et al., 1983 and 1987; Wells & Powers, 1986; Pantoliano et al., 1987). Reasons for this modest success are reviewed and discussed by Wetzel (1987) and Creighton (1988).
A more stable variant of T4 phage lysozyme has also been obtained by substitutions of the type X for Gly and of the type Pro for X where X is any other amino acid, attributing that effect to the reduced conformational freedom of the mutant due to the presence of "stiffer" residues (Matthews et al., 1987).
SDM has been used recently to study hydrophobic stabilization of bacteriophage T4 lysozyme resulting in one variant with increased stability (Ile to Leu substitution at position 3 (Matsumura et al., 1988).
SDM has also been used to probe the nature of electrostatic interactions --hydrogen bonds and interactions between charged groups-- and their influence on the pH dependence (Russel et al., 1987) and enzyme kinetic parameters of subtilisin (wells et al., 1987). But their influence on protein stability has not been investigated by this technique, nor has a more stable enzyme been produced as a result of specific modulation of electrostatic interactions.
The role of non-covalent interactions between protein subunits and/or domains has seldom been assessed by means of SDM. In a first example, Casal et al. (1987) could show that substitution of asparagine at position 78 by aspartic acid in dimeric yeast triosephosphate isomerase produced more labile protein. This result has been rationalized on the basis that deamidation of asparagine into aspartic acid is found to occur in proteins at elevated temperature. In a second example, simultaneous replacement of asparagine residues in the same model protein at positions 14 and 78 by threonine and isoleucine, respectively, was found to result in improved thermostability (Ahern et al., 1987). The doubling of the half-life of the mutant enzyme was, however, accompanied by a two-fold reduction in catalytic activity.
Temperature-sensitive mutations in bacteriophage T4 lysozyme were found to occur at sites of low solvent accessibility in the folded protein (Alber et al., 1987).

Methods and means for controlling the stability of proteins


This invention relates to a new use of stilbene derivatives or pharmaceutically acceptable salts thereof, especially in the manufacture of medicament for the prevention and treatment of diabetes or retrovirus associated diseases.

Diabetes is a common metabolic disorder in human beings. Recently, along with the improvement of living standard, and the changing of foodstuff structure, the incidence of diabetes are increasing rapidly. In the world there are around 0.12 billion of patients suffering from this disease. It is a serious threat to mankind. Therefore the prevention and treatment of diabetes is a hot focus in the field of medicinal research work.
Now the anti-diabetic medicament used in clinics such as sulfanylureas, biguanidins etc are effective yet with some side effects. Some formulation derived from Chinese traditional herbs are effective, less toxic. Up to now no hypoglycemic monomer derived from natural plants which is used in clinics is reported.

Use of stilbene compounds in the manufacture of medicament for the prevention and treatment of diabetes or retrovirus-associated diseases

Institute of Radiation Medicine, Academy of Military Medical Sciences, PLA

Beijing Luyin Lihua Pharmaceutical Science and Technology Development Company Ltd


A high-impact, energy-absorbing vehicle barrier system generally includes a substantially rigid outer containment wall coupled via strap assemblies with an energy-absorbing inner impact wall, and energy-absorbing cartridges strategically positioned between the impact wall and containment wall. The impact wall is constructed of a number of tubes coupled with one another to present a substantially smooth, uniform surface to passing vehicles. The energy-absorbing cartridges generally consist of a foam member or a number of foam sheets which compress and crush between the containment wall and impact wall to absorb energy from an errant vehicle striking the face of the impact wall, while the deflection and deformation of the impact wall tubes dissipates additional energy to reduce peak decelerations and mitigate the severity of high-energy vehicular impacts. Internal splice units and the strap assemblies provide for relatively easy and quick replacement of damaged impact wall sections and energy-absorbing cartridges.

In recent years, automobile racing has become one of the most popular sporting events in the United States and abroad. Auto racing's popularity is evidenced by the number of weekend auto races, extensive fan support and corporate sponsorship, and 24-hour cable television coverage. In addition, the sport's popularity is seen in the wide variety of race series available for drivers and spectators, including the Indy Racing League (IRL), NASCAR's car and truck series, FORMULA 1, CART, and IROC.
In automobile racing, high-performance vehicles travel many times around an oval track at very high speeds. Many of these tracks utilize outer retaining or containment walls, typically in the form of substantially rigid concrete barriers, to prevent race vehicles from leaving the track. Unfortunately, race vehicles frequently lose control and impact the rigid outer containment wall, resulting in high-impact energies and, occasionally, driver injuries and fatalities. Errant vehicles and driver injuries and fatalities do not occur only on race tracks, but on highways, interstates, autobahns, and other public roadways in the United States and abroad. An improved barrier system can mitigate the severity of high-speed, high-energy automobile accidents and potentially reduce the number of injuries and fatalities on race tracks and public roadways.
Over the years, there have been many efforts to advance the state of the art of safety barrier design and construction. Some of the simpler proposed solutions consisted of loosely-stacked foam blocks placed around the outer, exterior walls of the track or roadway to reduce the severity of impact between the errant vehicle and the rigid wall. An impacting vehicle, however, can penetrate these foam blocks and strike the retaining wall with little or no impact energy having been absorbed by the blocks. Further, portions of the foam blocks can be knocked onto the track or roadway by the impacting vehicle, creating a hazard for other vehicles that follow. Other barrier designs have incorporated used rubber automobile tires banded together at selected regions of road courses. Although these tire barriers offer significant impact attenuation, these systems capture virtually all impacting vehicles, significantly increasing the total velocity change during the crash and greatly increasing the risk of driver injury or fatality. Further, tire barriers can allow vehicles to under-ride the barrier and lead to intrusion into the vehicle's occupant compartment. This type of system is generally appropriate only for locations where vehicle redirection is not practical, such as the gore areas created at tight hairpin turns.
In the late 1990's, a barrier system known as the FLAG barrier was developed. The FLAG barrier was a compression-type barrier consisting of large diameter, thick-walled resilient cylinders attached to a rigid concrete racetrack wall. The cylinders were placed adjacent one another, forming a longitudinal row of cylinders positioned along the track side. Smaller diameter cylinders were placed on the traffic-side face of the longitudinal barrier and positioned and attached at the recessed regions between the larger cylinders to minimize the potential for vehicle pocketing. This barrier system was crash tested using a 1,248 kg vehicle impacting at a speed of 121.0 km/hr and an angle of 20.8 degrees. After compressing several of the cylinders, the test vehicle was smoothly redirected, exiting the system at a speed of 70.0 km/hr and an angle of 15.0 degrees. However, the vehicle's velocity change and exit angle were both relatively high.
In 1998, a polyethylene energy dissipating system (PEDS) was developed for use on oval racetracks. The PEDS barrier system was configured using high-density polyethylene (HDPE) cylinders covered by a thick HDPE skin on the front and top of the cylinders. To expedite construction and repair of the PEDS system, the barrier was designed and fabricated in modular units attached to the concrete wall using a cable restraint system. The cover skin was used to reduce the potential for vehicle pocketing in the front face and reduce or eliminate the potential for the driver's extremities becoming caught in the openings between the cylinders. During the running of an IROC race at the Indianapolis Motor Speedway in August, 1998, driver Arie Luyendyk was involved in a crash which resulted in his IROC car impacting rearward on the PEDS barrier installed downstream from the inside corner of turn four. The estimated impact condition for this event consisted of a 1,633 kg car striking the barrier at a speed of 209 km/hr and an angle of 32 degrees. Remarkably, the driver sustained no serious injury from this severe impact event. These relatively positive results were attributed to the PEDS barrier and the excellent energy management of IROC vehicles during rearward impacts. The PEDS barrier, however, sustained significant damage, and debris was spread across the racing surface. Based on the impact performance of the PEDS barrier, several modifications were made to increase its energy-absorbing capabilities and prevent the units from becoming dislodged.
Beginning in 1999, researchers at the Midwest Roadside Safety Facility (MwRSF) in Lincoln, Nebr. in cooperation with IRL and NASCAR, investigated several energy-absorbing barrier concepts for use in high-speed racetrack and roadway applications using both computer simulation modeling and full-scale vehicle crash testing. The energy-absorbing properties and potential of both HDPE and foam materials were investigated. This testing and simulation indicated that HDPE barrier systems allowed impacting vehicles to gouge into the material and create snagging and pocketing, indicating to the MwRSF researchers that HDPE barrier faces offered no improvements or advantages over concrete barriers.
Simulation and testing of vehicle barriers indicates that lateral accelerations imparted to impacting vehicles and their occupants can be greatly reduced by adding even modest amounts of energy dissipation to rigid barrier systems. Further, testing has indicated that the utilization of relatively stiff longitudinal barrier elements would minimize vehicle rebound from the barrier. Subsequently, an energy-absorbing barrier system utilizing rubber energy absorbers with steel reinforced fiberglass fender panels was developed. This barrier design included a cable and strut mechanism by which the fender panels were attached to the vertical concrete backup structure to allow the barrier to deflect rearward with limited longitudinal motion. However, the relatively short "fish scale" fender panels and the soft energy absorbers utilized in this barrier caused the system to deform around the front of the impacting vehicle, increasing the potential for snagging and/or high rebound angles at increased impact speeds. Further, the cables and struts used to mount the barrier to the backup structure also posed potential snagging problems during high-speed impacts.

High-impact, energy-absorbing vehicle barrier system

Board of Regents of University of Nebraska


An elevator arrangement includes first and second movable elevator units, the first unit being an elevator car and the second unit being a counterweight, and a roping system including a first roping portion suspending the first and second elevator units, and being locked at least to the second elevator unit, a second roping portion being suspended by the first elevator unit and the second elevator unit, and being locked at least to the second elevator unit. The first and the second roping portions are successive portions of a roping passing unbroken via a locking arrangement provided at the second elevator unit, the locking arrangement locking the roping to the second elevator unit between the first and the second portions. In a method in constructing an elevator, the locking arrangement is unlocked and thereafter the roping is repositioned with respect to the locking arrangement and thereafter the locking arrangement is relocked.

During initial construction of an elevator or in any later elevator modification a situation may arise where repositioning of elevator components that have been installed earlier is beneficial or even necessary. A need to reposition arises for instance in construction-time elevators, particularly in connection with a process for extending the service zone to reach higher in the elevator hoistway. In this type of elevator arrangements, which are also known as jump-lifts, the bottom part of an elevator hoistway is put to use already before the building has been completed. The top part of the elevator hoistway can be under construction at the same time as an elevator car moving in the bottom part of the elevator hoistway already serves people on the lower floors of the building. Generally in jump-lifts the elevator car moving in the lower parts of the elevator hoistway is supported by a movable supporting structure positioned above the car in the hoistway. The installation work in parts of the elevator hoistway above this support structure is performed from a working platform movable in the elevator hoistway above the support structure. The installation work may comprise, among other things, the installation of guide rails and electrification in the elevator hoistway. When the elevator hoistway under construction above the supporting structure has reached a sufficient stage of completion, the completed part of the elevator hoistway can be put to use. At this stage a jump-lift is performed, where the supporting structure is lifted and mounted in a higher position in the elevator hoistway. These steps may be repeated until the desired height has been reached. Elevators often comprise a roping system having one roping suspending the elevator car and the counterweight, and another roping which is suspended by the elevator car and counterweight. This type of setting of the roping system is desirable for numerous reasons, for example because it provides rope weight compensation and it may be used for tie-down function. In jump-lift type elevators having this type of roping system, however, the lifting stage poses challenges. The lifting of the support structure may cause a need to adjust the relative position of the movable elevator units and the roping system. Particularly, in order to maintain the lowest landings within the service zone of the elevator car, a longer roping is needed for suspending the elevator car and the counterweight. Typically, each of said two separate ropings has had a rope supply at an end thereof so as to enable the feeding of more roping to the roping system. The existing solutions have the drawback that they necessitate several ropings the route of which cannot be freely chosen. Also, several rope supplies are needed, the location of which cannot be freely chosen. In particular, the existing solutions are not flexible with regard to the suspension ratios during the construction time. This often means that the elevator must undergo radical changes when converting the construction time elevator into a final elevator, because often the construction time suspension ratio cannot be chosen to be the same as that of the final elevator. The drawbacks related to the suspension ratio are usually caused by the need to position the rope supply separately from the moving elevator units, for example to save energy and space. For this reason the suspension ratio for the elevator car and/or counterweight needs to be 2:1, which leaves the rope ends free to pass to the rope supply which is positioned for example in the pit or on the landing or on the support structure. A later conversion of the elevator into 1:1 suspension ratio then necessitates changing routes of the ropes. It may also necessitate major changes to the shaft layout and structure of the car frame and/or counterweight frame.


A rotary connector includes: a first housing; a second housing; a bayonet ring including a locked portion to be locked to a locking portion of the first housing, which forms a bonded state by rotating by a predetermined angle in a ready state, so that its rotation is prevented; and a connector position assurance that is prevented from moving from a first position in the ready state, and in the bonded state, that is moveable to a second position and maintains a state in which the locked portion is locked to the locking portion.

As a rotation fitting connector (rotary connector) of a first known example, one including a male connector, a female connector, and a meshing ring (bayonet ring) is known (see JP 2005-267930 A).
In the rotary connector of the first known example, a temporary locking projection and a detection locking projected portion are provided on the outer peripheral wall portion of the male connector.
In the rotary connector of the first known example, an axial wall portion that engages with the temporary locking projection and a flexible locking arm having, on an inner surface of its tip, a locking claw that engages with the detection locking projected portion are provided on an outer surface of the meshing ring.
In the rotary connector of the first known example, a contact surface that contacts the flexible locking arm is formed at the projected tip of the detection locking projected portion, and a step portion having a contacted surface that contacts the contact surface is formed in the flexible locking arm.
And, the completely fitted state between the male connector and the female connector can also be recognized visually and aurally, in addition to the rotation feeing of the meshing ring, whereby the reliability of the fitting between the male connector and the female connector is improved.
Also, as a rotation fitting connector (rotary connector) of a second known example, one including a lock key (CPA: connector position assurance), in addition to the male connector, the female connector, and the bayonet ring, is known (see JP 2009-505343 A).


A frequency synthesizer is provided in the present invention. The frequency synthesizer includes a single phase-locked loop having a reference frequency signal input, a first output, a second output and a pair of divide-by-N circuits coupled with each other and electrically connected to the second output; a multiply-by-M circuit having a first input electrically connected to the first output and a third output; and a combination of a buffer and a mixer having a second input electrically connected to the second output and a third input electrically connected to the third output generating a frequency signal output.

Please refer to FIG. 1, which is a diagram illustrating a frequency synthesizer according to the prior art. The frequency synthesizer is a kind of component used for providing various kinds of frequencies in one or many reference frequency circuits. Usually, in the frequency synthesizer, the multiply phase locked loop would be adopted therein in order to obtain a series of frequency signals. Take it as the example the frequency synthesizer architecture 1 illustrating in FIG. 1, where a phase locked loop 80 receives a reference frequency 81; a UP and DN signal are outputted by a phase frequency detector 91 in the phase locked loop 80; a digital comparison signal is transformed into an analogy current signal by a charge pump 92; a control voltage Vctrl is then obtained by filtering the analogy current signal through a loop filter 93 (low-pass filter); and this control voltage Vctrl is used for controlling a signal output of a voltage controlled oscillator (VCO) 94 and the signal output then passes a specific frequency divider. Finally, in accordance with the aforementioned, signals from different frequency bands could be generated via a single sideband mixer 82.
Please keep referring to FIG. 1. For the present state of the art, the phase locked loop 80 illustrated in FIG. 1 includes a loop filter 93, a frequency divider 95/96 and a voltage control oscillator 94, wherein the loop filter 93 is a low-pass filter that is usually consisted of the resistances and the capacitors etc. so that it would occupy more area for the circuit.
The frequency divider could be categorized into two types, one is an injected locked frequency divider (ILFD) and the other is a digital frequency divider. The former type has a lower power consuming when a higher operation frequency is adopted thereby, and it could be used to define a more precise phase relationship. Please keep referring to FIG. 1. Since the orthogonal signals 83/84 of a I-channel and a Q channel are required to be involved in the mixer 82 of the multiply bands system so as to synthesize the signal 85 of a specific wave band and the phase deviation will determine whether the other frequency signals could be suppressed in order to provide a smaller spur wave on the outputted frequency band, a precise phase could helpfully enhance the performance of the in-band spur wave; and the latter type has a lower workable frequency, could provide a fractional frequency divider ratio, has no static power consuming and could further reduce the dynamic power consuming through the True-Signal-Phase-Clock (TSPC) technique, but the phase relationship could not be guaranteed. Therefore, in this conventional way, the ILFD would be chosen to be used following the VCO, for instance a first frequency divider 95, but the digital frequency divider would be chosen to be used in front of the phase detector, for instance a second frequency divider.
The VCO 94 could be a coupled looped VCO 200 (referring to FIG. 2(a)) and since it has a lesser order, it saves energy and could perform better in the aspect of the noise than the conventional looped VCO 942 (referring to FIG. 3). However, due to the improvement of the technology, the scale of the circuit becomes more and more miniature and the magnitude of the power source are also decreased so that the permitted oscillating amplitude is also decreased thereaccording. In order to deal with the variation of the manufacturing process, for the VCO, a smaller range of the control voltage is required and simultaneously the required bandwidth must also be covered thereby. (referring to FIG. 2(b)) for a conventional single order VCO circuit 943, a fixed resistive load 944 is used to adjust the characteristic curve of the VCO voltage with respect to the frequency so as to raise the Kvco (the variation of the frequency/the control voltage to the linear portion of the curve and magnitude of the slope to the linear portion of the curve). But the raise of the Kvco would influence the performance to the spur wave. Besides, it frequently needs to generate a series of frequencies with fractional ratio in the orthogonal frequency division multiply super wideband, but the first frequency divider 95 of the injected locked type could merely generate an integer ratio. Hence, a fractional type circuit shall be therefore provided, for instance the multiplication circuit 86. In prior art, the fractional type circuit is usually consisted of a multiplier and a divider. In terms of the multiplication circuit 86, it is consisted of a multiplier 87 that is combined with a divider 88. For example, in the conventional technique, a divided-by-2 circuit 98 (referring to FIGS. 5(a), 5(b)) is merged with a multiply-by-3 circuit 97 (referring to FIG. 4) in order to complete the purpose to multiply by 1.5. Nevertheless, since these two circuits are usually operated with a higher workable frequency that consumes massive power and the multiply-by-3 circuit includes the passive component, these two circuits occupy more circuit area.
To overcome the mentioned drawbacks of the prior art, a surface treatment method and device thereof are provided.

Frequency synthesizer, coupled divide-by-N circuit, current-reuse multiply-by-M circuit