An adapter for holding two fiber optic connectors in coaxial alignment. The connectors include a generally cylindrical ferrule having an axial bore and a ferrule holder having means for retaining the ferrule and a raised ridge located on its outer surface. The connector further includes a grip housing having an axial bore in which the ferrule holder is located. The grip housing also includes a cut out through which the raised ridge of the ferrule holder is exposed. The adapter comprises a unitary main body having an axial bore connecting a first opening and a second opening. The axial cavity is sized to receive an inner housing. The inner housing has at least one retaining clip which is located exterior to an axial chamber within the inner housing. The retaining clip includes means to releasably lock the raised ridge of the ferrule holder in place when said connector is inserted into the axial cavity of the adapter.

Fiber optics have revolutionized communication through out the world. Fiber optics are generally thin strings of glass designed to carry light which can be grouped together.
With the increased use of fiber optics it has become increasingly important to be able to connect and disconnect fiber optic cables from various sources. Two fiber optic cables can be optically coupled so that they are in communication with one another by using well-known SC connectors and an adapter, thereby putting each fiber optic cable in communication with the other. The SC connectors are placed on the end of each cable and then plugged into the adapter. The adapter has two openings, each one designed to receive a connector. The adapter is usually fixed to a dividing member.
The adapter of the prior art consisted of two halves, each halve being identical. Each half consisted generally of a rectangular cylinder having a flange at one end. Inside each half would be placed half of an inner housing. The inner housing being generally a round cylinder, with a flange at one end, and a pair of retaining clips, extending parallel to the cylinder from the flange. Each adapter half had a ridge located just inside from its flange so that the inner housing could be placed in the adapter through the opening proximate to the flange on the adapter half. Once the inner housing were inserted into each adapter half, the two halves were connected by ultrasonically welding the two flanges of the adapter halves together.
This design presented serious problems. The cables naturally flexed in use, while the adapter remained fixed. The related stresses of this situation caused the two halves of the adapter to separate after time. In the prior art, this problem was solved by constructing the adapter halves from metal which gave the adapter enough strength to withstand these stressed. However, this too presented a problem as metal is much more expensive to purchase and mold than the plastic it replaced.
The present invention has significant advantages over the construction of the prior art in that the present invention teaches an adapter that can be constructed out of plastic in a unitary fashion. The main body has an access opening to the interior. The access opening allows the adapter to be molded in a single piece, as with out the access opening negative draft would make it impossible to construct the adapter in a single piece. The access opening further allows an inner housing to be inserted into the main body.


A device for producing milk froth for cappuccino, having a nozzle arrangement (1,2) that is disposed downstream of a steam pipe (4)and has a vacuum chamber (3), into which a milk supply line (6) terminates, and with am air conduit (8) connected to the milk supply line (6) upstream of the vacuum chamber (3). An emulsifying chamber (9) is disposed downstream of the vacuum chamber (3), with the emulsifying chamber having a chamber wall, a floor with a central, flow-diverting protrusion and an outlet. A settling segment (16) adjoins the outlet. For the fine-pored emulsification of milk froth with the device, the emulsifying chamber (9,23,32), which is embodied without separate air inlets, has at least two free cross sections that widen step-wise in the primary flow direction (10). The central, flow-diverting protrusion is embodied as a flow trap surrounding the outlet in the floor such that the protrusion diverts a mixture essentially to a direction flowing in the primary flow direction essentially counter to the primary flow direction.

The invention relates to a device for producing milk froth for cappuccino. More particularly, the present invention relates to a device for producing milk froth for cappuccino, having a nozzle arrangement that is disposed downstream of a steam pipe and that has a vacuum chamber into which a milk supply line terminates, an air conduit connected to the milk supply line upstream of the vacuum chamber, an emulsifying chamber, having a chamber wall, a floor with a central, flow-diverting protrusion and an outlet, disposed downstream of the vacuum chamber, and a settling segment adjoining the outlet.
In a known device of this type for producing a creamy steam-milk-air emulsion for preparing cappuccino, a milk supply line, which has an air opening that is- connected to the atmosphere (U.S. Pat. No. 5,265,519), terminates into a vacuum chamber disposed downstream of a steam pipe having a nozzle. The steam-milk-air mixture produced in the vacuum chamber flows out of the vacuum chamber and into an emulsifying chamber having a closed floor with an essentially conical protrusion. The mixture flowing out of the vacuum chamber, against the central protrusion on the floor of the emulsifying chamber, is divided by the protrusion and reshaped into a new, large-surface mixture flow that impacts the floor of the side wall of the emulsifying chamber and is intended to mix thoroughly with a portion of the mixture already present in the emulsifying chamber to form a good emulsion. This process is supposed to produce a creamy mixture of fine froth that exits through a side opening of the emulsifying chamber and, from there, can flow into a further, cylindrical chamber located to the side of the emulsifying chamber. There, the emulsion settles while excess steam can escape through an upper opening of the additional chamber. This device has yet to achieve its objectives.
For more thoroughly premixing the milk suctioned into the vacuum chamber with air, it is already known to provide a premixing chamber between the vacuum chamber and the milk supply line, with the air conduit terminating into the premixing chamber (EP 0 858 757 A1). While this arrangement produces an extensively homogeneous steam-milk-air mixture in the vacuum chamber, the mixture can still be too large-pored.
Also known from the state of the technology is a device for frothing and heating liquids such as milk or the like. This device is equipped with longitudinal conduits for suctioning froth-producing air around a settling chamber having a relatively large cross ,section and a long length (EP 0 813 834 A1). In this device, first only the suctioned milk is mixed with steam in the vacuum chamber for pre-frothing. For producing the desired froth, the mixture is conducted into an acceleration segment that adjoins the vacuum chamber downstream, and is provided with openings that are connected to the air-conducting longitudinal conduits. The milk and froth are allowed to settle, and be homogeneously distributed, in the cylindrical chamber having the relatively large diameter and long length. This setup does not automatically achieve the desired fine-pore quality desired in many cases, however.
In a similar device, a second nozzle arrangement adjoins the vacuum chamber of the first nozzle arrangement. The second arrangement has air-intake openings that are more directly connected to the atmosphere than the openings connected via longitudinal conduits in the aforementioned arrangement (EP 0344 859 B1). In the second nozzle arrangement, air is suctioned and added to the milk to produce froth, which is then suctioned with the first nozzle arrangement. The froth flows out of a chamber that adjoins the second nozzle arrangement, the chamber having a relatively large diameter and long length, through lower, notably lateral, openings in the chamber, and consequently settles and is uniformly distributed. The floor of this chamber is shaped so as to prevent the froth from exiting directly at a high speed. For this purpose, the floor has a rounded protrusion. The floor has individual drip openings near the edge. This device also does not attain the desired fine-pored, homogeneously emulsified steam-milk-air mixture.
It is the object of the present invention to create a device for producing milk froth for cappuccino, with which the milk froth is homogeneously emulsified and fine-pored.
The above object generally is achieved according to the present invention with a device of the generic type described at the outset, wherein the emulsifying chamber, which is formed without separate air inlets, has at least two free cross sections that widen step-wise in the primary flow direction, and the central, flow-diverting protrusion is formed as a flow trap that surrounds the outlet in the floor such that the protrusion diverts a mixture flowing essentially in the primary flow direction essentially to a direction counter to the primary flow direction. Also disclosed are variations of the basic solution. The basic solution and vacations thereof are based on the common principle that the steam-milk-air mixture formed in the vacuum chamber after the premixing of the milk with air is mixed intensively again, and swirled, in the emulsifying chamber The mixture remains in the emulsifying chamber as long as possible, where it is emulsified into a fine-pored mixture due to the continuous flow of steam energy.
According to the basic solution, the cross sections of the emulsifying chamber, which increase step-wise in the downstream direction, strongly swirl the steam-milk-air mixture in the emulsifying chamber. The central, flow-diverting protrusion around the outlet in the floor of the emulsifying chamber, which is embodied as a flow trap, lengthens the time spent by the steam-milk-air mixture in the emulsifying chamber by diverting the mixture, which impacts the trap essentially in the primary flow direction, essentially counter to the primary flow direction. The primary flow direction is defined by the nozzle arrangement of the vacuum chamber, which changes over into the emulsifying chamber downstream. The settling segment adjoins this specially-designed emulsifying chamber by way of an outlet in the floor of the emulsifying chamber. The settling segment having the outlet can be embodied simply as a throughgoing bore.
An additional advantage of this device is its compact design.
For the basic inventive embodiment of the emulsifying chamber, it suffices to provide two segments that follow one after the other in the primary flow direction, with the first segment widening step-wise relative to an outlet of the vacuum chamber, and the second segment having a cross section that is widened, step-wise, relative to the first segment, in connection with the flow trap in the floor, i.e., the downstream end of the emulsifying chamber.
A significantly better option for attaining the desired fine-pored emulsion, according to a modification of the basic embodiment, is for the emulsion chamber to comprise three segments, whose cross sections widen, step-wise, relative to the cross section of the outlet of the vacuum chamber or the upstream adjacent segment. The flow trap is provided it the floor of the emulsifying chamber in this case as well.
According to a feature of the invention, the flow trap is embodied or formed as a blind ring having an annular trough that is open counter to the primary flow direction of the steam-milk-air mixture. The trough is embodied and oriented such that it diverts the steam-milk-air mixture, which impacts it essentially in the primary flow direction, essentially counter to the primary flow direction. This swirls the mixture again and keeps it in the emulsifying chamber longer.
In a further modification of the basic invention, a flow-diverting unit is disposed in the emulsifying chamber, at a distance from the floor. This unit is embodied such that the flow of the steam-milk-air mixture is diverted essentially counter to its primary flow direction. This flow diversion, again, effects a desired swirling of the flowing mixture in addition to the swirling effected by the flow trap that is always provided in the floor of the emulsifying chamber in accordance with the invention.
According to a preferred feature of the last mentioned embodiment, the flow-diverting unit call advantageously be embodied with an open, annular trough that surrounds a central, essentially conical protrusion. This trough can be embodied similarly to, but flatter than, the annular, open trough of the flow trap in the floor.
According to a feature of the invention, the flow-diverting unit is advantageously held in the emulsifying chamber, at a distance from the inside wall of the chamber, by radial ribs, so the flow can occur in the primary flow direction in the region of the inside wall.
In a variation of the device of the invention, the emulsifying chamber has diaphragms at the steps between its segments, with the diaphragms additionally narrowing the adjacent, smaller cross section. These diaphragms or narrow points form pronounced, turbulence-inducing edges that effect an even more vigorous swirling of the steam-milk-air mixture than the steps of the cross sections themselves.
Particularly for better cleaning, but also for the uncomplicated production of the emulsifying chamber and the adjacent regions, the emulsifying chamber has individual elements, which are cylindrical on the outside and are formed out with at least one of the stepped cross sections on the inside, and are held together by a common sleeve. All of the elements are disposed concentrically in the sleeve, which has a smooth outside surface.
According to a feature of the invention, the elements of the emulsifying chamber can comprise a half-hard synthetic material, notably chloroprene caoutchouc (brand name xe2x80x9cNeoprenxe2x80x9d). This synthetic material also has a sufficient dimensional stability when exposed to steam.
In accordance with a combination feature of the device of the invention, a premixing chamber is preferably disposed between the vacuum chamber and the milk supply line; the air conduit terminates into this chamber. This assures the homogeneous air distribution of the emulsion, namely the entry of a thoroughly premixed milk-air mixture into the vacuum chamber before steam is added to the mixture and the additional swirling takes place in the emulsifying chamber.
Three variations of the invention are explained below by way of exemplary embodiments, with reference to the four drawing figures.

Device for producing milk froth for cappuccino


An information processing method and device are provided that relate to the field of information input. A method comprises: in response to that a user performs a touch-sensitive input operation on a touch screen of a device, acquiring contact areas between a gripping hand of the user and a side face of the device in different times; and at least in response to that the at least two contact areas satisfy a first predetermined condition, adjusting an input mode of the device. According to contact areas between a gripping hand of the user and a side face of the device, it can be inferred whether or not the user encounters inconvenient input and timely adjust an input mode of the device, which facilitates user input in the event of maintaining lower power consumption.

With popularization of electronic devices, a growing number of touch screen devices such as smartphones and tablet computers enter into people's life, which greatly enriches people's life.
On a large touch screen phone, when only one hand (the other hand is occupied by other affairs) of the user can be configured to interact with a handheld device, it is possible to result in that the input process is slow and the input efficiency is lower as a region to be touched is too distant. To increase the input efficiency, some devices, in addition to touch-sensitive input, provide more modal input manners, for example, input information is received by detecting eye movement, blowing air streams and the like.
The more modal input manners, if opened all the time, may lead to excessive device power consumption and affect endurance time.

This patent is subject to a terminal disclaimer.

Information processing method and device


A thrombectomy catheter system with occluder and method of using same for removal of tissue, such as thrombus and the like, from a vessel in the body. Multiple catheters and an occluder-bearing guidewire tube at a thrombus site provide for expandable deployment of a compliant occluder against the vasculature walls distal to the thrombus. The expanded occluder is maneuvered proximally to urge thrombus into close proximity with a retractable capture cone located distally on a capture catheter where the thrombus is dislodged, entrained, and broken into pieces by the action of a fluid jet emanator and then evacuated through the capture catheter.

1. Field of the Invention
The present invention is for a thrombectomy catheter system with occluder and method of using same.
2. Description of the Prior Art
Prior art devices for addressing and influencing thrombotic deposits often included angioplasty devices where thrombotic deposits were merely reshaped outwardly and the vessel surrounding the thrombotic material was correspondingly urged to expand to allow greater blood throughflow. Such devices were often equipped with a filter or a balloon-style occluder distal to the thrombotic occlusion to filter out or constrain any thrombotic material which may be dislodged during such reshaping angioplasty processes to prevent recirculation of such thrombotic material in the vasculature. Often an occluder-like balloon would be utilized distal to the thrombotic deposit from which a cleansing fluid would be discharged in a less than aggressive fashion in order to carry any dislodged thrombotic material proximally to a collection device. While performing angioplasty involving the reshaping of the thrombotic material, little was done to actively and aggressively cause thrombotic materials to be urged into maceration devices for breaking up and carrying away the thrombotic materials. Such a function is provided by the present invention.

Thrombectomy catheter system with occluder and method of using same


A device includes a SAR, a comparator, a DAC and a multichannel passive S/H component. The multichannel passive S/H component is able to sample and hold a plurality of analog voltages in parallel. The multichannel passive S/H component is further able to serially feed the plurality of sampled and held analog voltages to the SAR, comparator and DAC, such that each analog voltage is serially converted to a digital representation.

The present invention is generally drawn to and analog-to-digital converters (ADCs) that employ successive approximation registers (SARs).
A SAR is a type of ADC that converts a continuous analog waveform into a discrete digital representation via a binary search through all possible quantization levels before finally converging upon a digital output for each conversion. An example conventional ADC will now be described with reference to FIGS. 1A-C.
FIGS. 1A-1C illustrate a conventional ADC 100. FIG. 1A illustrates ADC 100 estimating an input voltage using a most significant bit, whereas the FIG. 1B illustrates ADC 100 estimating the input voltage using the next most significant bit, and whereas FIG. 1C illustrates ADC 100 estimating the input voltage using the least significant bit.
As shown in FIG. 1A, ADC 100 includes a sample and hold (S/H) component 102, a comparator 104, a SAR 106 and a digital-to-analog converter (DAC).
S/H component 102 is arranged to receive on analog input voltage, Vin, from an input line 110 and is arranged to output a sampled and held analog voltage, Vx, onto an output line 112. S/H component 102 samples and holds Vin until it is need.
Comparator 104 is arranged to receive Vx from output line 112 at a first input and to receive and output voltage, Vout, from DAC 108 from an output line 114 at a second input. Comparator 104 is also arranged to output a compared signal, based on a comparison of Vx and Vout, to a line 116.
SAR 106 is arranged to receive the compared signal from line 116 and to receive a clock signal from a clock line 118. SAR 106 is arranged to output SAR output values to output lines 120, 122 and 124 to ultimately provide a digital representation of an approximation of Vin.
DAC 108 is arranged to receive a reference voltage, Vref, via a reference line 111. DAC 108 provides Vout based on Vref and the SAR output values from SAR 106.
In operation, conventional ADC 100 provides a digital output corresponding to an analog input. For purposes of discussion, let Vin be 3.7 V. Initially, SAR 106 starts with the most significant bit and asks "is it greater than 4 V?" A digital value of "1" is output to output line 120, a digital value of "0" is output to output line 122 and a digital value of "0" is output to output line 124, DAC 108. In this example, let Vref be 1 V, such that Vout is in 1 V increments associated with the digital value provided by SAR 106. Accordingly, DAC 108 outputs Vout as an analog value of 4 V to comparator 104 via output line 114.
Comparator 104 compares the 4 V from DAC 108 and the 3.7 V provided by S/H component 102, and indicates that Vin "is not greater than 4 V," thus outputting a digital "0" to SAR 106.
As shown in FIG. 1B, SAR 106 then resets the most significant bit to "0" and sets the next bit to a digital "1," and asks "is it greater than 2 V?" A digital value of "0" is output to output line 120, a digital value of "1" is output to output line 122 and a digital value of "0" is output to output line 124, DAC 108.
DAC 108 then outputs Vout as an analog value of 2 V to comparator 104 via output line 114.
Comparator 104 compares the 2 V from DAC 108 and the 3.7 V provided by S/H component 102, and indicates that Vin "is greater than 4 V," thus outputting a digital "1" to SAR 106.
As shown in FIG. 1C, SAR 106 then sets the next bit to a digital "1," and asks "is it greater than 3 V?" A digital value of "0" is output to output line 120, a digital value of "1" is output to output line 122 and a digital value of "1" is output to output line 124, DAC 108.
DAC 108 then outputs Vout as an analog value of 3 V to comparator 104 via output line 114.
Comparator 104 compares the 3 V from DAC 108 and the 3.7 V provided by S/H component 102, and indicates that Vin "is greater than 3 V," thus outputting a digital "1" to SAR 106.
At this point, it is determined that Vin is less than 4 V but greater than 3 V. As such SAR 106 has gone through all bits and reached an end to the conversion, so the digital representation of the analog Vin is output as "001" on output lines 120, 122 and 124.
In some applications, analog voltages on a plurality of input lines, or multichannel inputs, may need to be converted to digital signals. Conventionally, multichannel ADCs may be used for such conversions. Some example conventional multichannel ADCs will now be described with reference to FIGS. 2-3.
In one type of conventional multichannel ADC, multiple SAR ADCs are used to simultaneously sample and convert analog voltages, in parallel. These converted signals are then provided to a central processing portion for serial output. This will be described with reference to FIG. 2.
FIG. 2 illustrates an example conventional multichannel ADC 200.
As shown in the figure, conventional multichannel ADC 200 includes a SAR ADC 202, a SAR ADC 204, a SAR ADC 206 a SAR ADC 208 and a controller component 210.
SAR ADC 202 is arranged to receive an analog input voltage, Vin1, from an input line 212 and is arranged to output a digital output voltage, Vo1, onto an output line 214. SAR ADC 204 is arranged to receive an analog input voltage, Vin2, from an input line 216 and is arranged to output a digital output voltage, Vo2, onto an output line 218. SAR ADC 206 is arranged to receive an analog input voltage, Vin3, from an input line 220 and is arranged to output a digital output voltage, Vo3, onto an output line 222. SAR ADC 208 is arranged to receive an analog input voltage, Vin4, from an input line 224 and is arranged to output a digital output voltage, Vo4, onto an output line 226.
Controller component 210 is arranged to receive Vo1 from output line 214, to receive Vo2 from output line 218, to receive Vo3 from output line 222, to receive Vo4 from output line 226 and to output a digital output voltage, Vout, onto an output line 228.
In operation, conventional multichannel ADC 200 receives Vin1, Vin2, Vin3 and Vin4 in parallel. Each analog input voltage is converted to a respective digital representation in parallel. Controller 210 then outputs digital voltages serially.
A problem multichannel ADC 200 is that the plural SAR ADC require much power and use a large amount of circuit real estate. Further, there is a higher channel to channel mismatch due to the presence of separate ADCs on each channel
In another type of conventional multichannel ADC, multiple S/H components are used to simultaneously sample analog voltages. These sampled signals are then provided to a PGA before being serially converted. This will be described with reference to FIG. 3.
FIG. 3 illustrates another example conventional multichannel ADC 300.
As shown in the figure, ADC 300 includes ADC 100 of FIG. 1 in addition to an S/H component 302, an S/H component 304, an S/H component 306, an S/H component 308 and a programmable gain amplifier (PGA) or an active sample and hold amplifier (SHA) 310.
S/H component 302 is arranged to receive an analog input voltage, Vin1, from an input line 312 and is arranged to output a sampled and held analog voltage, Vs1, onto an output line 314. S/H component 304 is arranged to receive an analog input voltage, Vin2, from an input line 316 and is arranged to output a sampled and held analog voltage, Vs2, onto an output line 318. S/H component 306 is arranged to receive an analog input voltage, Vin3, from an input line 320 and is arranged to output a sampled and held analog voltage, Vs3, onto an output line 322. S/H component 308 is arranged to receive an analog input voltage, Vin4, from an input line 324 and is arranged to output a sampled and held analog voltage, Vs4, onto an output line 326.
PGA 310 is arranged to receive Vin1 from output line 112, Vin2 from output line 318, Vin3 from output line 322 and Vin4 from output line 322. PGA 310 is additionally arranged to output an analog voltage as Vin onto line 110.
In operation, conventional multichannel ADC 300 samples and holds Vin1, Vin2, Vin3 and Vin4 in parallel with S/H component 302, S/H component 304, S/H component 306 and S/H component 308. To ensure that the sampled voltage is accurately converted, the entire voltage stored in any one of S/H components 302, 304, 306 and 308 must be transferred to S/H component 102. To ensure that the sampled voltage is entirely transferred, PGA 310 is provided.
Each analog input voltage is provided to PGA 310, which outputs amplified versions of the analog input voltages serially. Comparator 104, SAR 106 and DAC 108 then serially converts each amplified signal to digital representation in a manner similar to that discussed above with reference to FIGS. 1A-C.
A problem multichannel ADC 300 is that PGA or SHA requires much power and use a large amount of circuit real estate. Being active circuits, both the PGA and the SHA introduce more noise and other non-idealities of their own into the circuit, which leads to higher error in the precision circuit.
What is needed is a passive multi-channel ADC that uses a single SAR ADC that does not require multiple DACs (or ADC) or does not require any PGA or any SHA.

System and method for multi channel sampling SAR ADC


A pin removal mode signal generation circuit includes: a set signal generation unit configured to activate a set signal when an activated test mode signal pulse is generated by a mode register set and an activated flag signal pulse is applied, and a pin removal mode signal generation unit configured to activate a pin removal mode signal when the set signal is activated, and deactivate the pin removal mode signal when a reset signal is activated.

1. Technical Field
The present invention relates to semiconductor design technology, and more particularly, to a pin removal mode signal generation circuit and a semiconductor apparatus including the same.
2. Related Art
In order to test a packaged semiconductor apparatus, a test board and I/O pins are utilized. For memory chips, a plurality of memory chips are connected to a test board to perform tests concurrently, during which addresses and commands are inputted to the respective memory chips. Output signals of the memory chips are then measured to determine whether the corresponding memory chips failed or passed.
FIG. 1 is an address input waveform diagram of a conventional semiconductor apparatus during a test mode.
A packaged semiconductor memory apparatus has a plurality of pins defined in the specification. Referring to FIG. 1, the semiconductor memory apparatus receives addresses address0 to address14 corresponding to a plurality of address input pins A0 to A14 during the test mode. The semiconductor memory apparatus latches the addresses address0 to address14 in synchronization with a rising edge of a clock signal received through a clock input pin CLK.
FIG. 2 is a timing diagram when the conventional semiconductor memory apparatus enters the test mode.
With the diversification of functions, semiconductor memory apparatuses are designed to implement various operation modes. In particular, a semiconductor memory apparatus such as synchronous DRAM includes a mode register set circuit to set various operation modes. FIG. 2 illustrates an example of a method for activating a test mode signal TSET such that the mode register set circuit provided in the semiconductor memory apparatus enters the test mode.
A plurality of test set commands TMRS0 to TMRS2 are received through a command input pin CMD in synchronization with a clock signal received through a clock input pin CLK. When preset addresses are received through address input pins A7 to A10 when the plurality of test set commands TMRS0 to TMRS2 are received, an activated test mode signal pulse TSET is generated. Accordingly, the semiconductor memory apparatus enters the test mode.
Various methods for reducing test time required for a semiconductor memory apparatus have been proposed. The methods may include an address pin removal mode in which only a part of a plurality of address pins is used to connect a plurality of semiconductor memory apparatuses to a test board. In the address pin removal mode, only a part of the address pins are connected to the test board, and addresses are sequentially inputted to the connected address pins to perform tests. As a result, since a larger number of semiconductor memory apparatuses may be connected to the test board than during a normal test mode, more tests may be performed at the same time.
The standardization of a method for controlling a semiconductor memory apparatus to enter the address pin removal mode, as well as hardware developments to minimize additional area and to allow the method to occur in a stable manner, is in the process of being developed.

Pin removal mode signal generation circuit and semiconductor apparatus including the same


An apparatus and method for performing early correction of a conditional branch instruction in a pipeline microprocessor is disclosed. Early branch correction logic examines early status flags to detect a branch misprediction. The early status flags are generated in response to an instruction preceding the branch instruction earlier in the pipeline than the architected status flags are generated and may or may not be valid. If the early status flags are valid and indicate a misprediction, the early correction logic corrects the misprediction. If the pipeline stages below the early correction logic stage become void of uncompleted flag-modifying instructions, such as after a pipeline flush, the early status flags are re-validated by copying to the architected status flags to the early status flags. Late branch correction logic corrects the misprediction if the architected status flags indicate a misprediction and if the early correction logic did not correct the misprediction.

Modern microprocessors are pipelined microprocessors. That is, they operate on several instructions at the same time, within different blocks or pipeline stages of the microprocessor. Hennessy and Patterson define pipelining as, "an implementation technique whereby multiple instructions are overlapped in execution." Computer Architecture: A Quantitative Approach, 2nd edition, by John L. Hennessy and David A. Patterson, Morgan Kaufmann Publishers, San Francisco, Calif., 1996. They go on to provide the following excellent illustration of pipelining:    A pipeline is like an assembly line. In an automobile assembly line, there are many steps, each contributing something to the construction of the car. Each step operates in parallel with the other steps, though on a different car. In a computer pipeline, each step in the pipeline completes a part of an instruction. Like the assembly line, different steps are completing different parts of the different instructions in parallel. Each of these steps is called a pipe stage or a pipe segment. The stages are connected one to the next to form a pipe—instructions enter at one end, progress through the stages, and exit at the other end, just as cars would in an assembly line.
Synchronous microprocessors operate according to clock cycles. Typically, an instruction passes from one stage of the microprocessor pipeline to another each clock cycle. In an automobile assembly line, if the workers in one stage of the line are left standing idle because they do not have a car to work on, then the production, or performance, of the line is diminished. Similarly, if a microprocessor stage is idle during a clock cycle because it does not have an instruction to operate on—a situation commonly referred to as a pipeline bubble—then the performance of the processor is diminished.
A potential cause of pipeline bubbles is branch instructions. When a branch instruction is encountered, the processor must determine the target address of the branch instruction and begin fetching instructions at the target address rather than the next sequential address after the branch instruction. Furthermore, if the branch instruction is a conditional branch instruction (i.e., a branch that may be taken or not taken depending upon the presence or absence of a specified condition), the processor must decide whether the branch instruction will be taken, in addition to determining the target address. Because the pipeline stage that ultimately resolves the target address and/or branch outcome (i.e., whether the branch will be taken or not taken) is typically many stages below the stage that fetches the instructions, bubbles may be created.
To address this problem, modern microprocessors typically employ branch prediction mechanisms to predict the target address and branch outcome early in the pipeline. Microprocessor designers are continually striving to design branch predictors with greater prediction accuracy. However, branch predictors mispredict branch instruction outcomes a non-trivial percentage of the time. As alluded to above, the mispredictions must be detected and corrected in a subsequent stage of the pipeline below the branch prediction stage. The penalty associated with the misprediction is a function of the number of pipeline stages between the branch predictor and the branch misprediction correction stage. Therefore, what is needed is an apparatus and method for correcting conditional branch instruction mispredictions earlier in the pipeline.
Furthermore, conditional branch instructions specify a branch condition which, if satisfied, instructs the microprocessor to branch to the branch target address; otherwise, the microprocessor continues to fetch the next sequential instruction. The microprocessor includes status flags that store state of the microprocessor. The status flags are examined to determine whether the condition specified by the conditional branch instruction is satisfied. Thus, in order to finally determine whether a conditional branch instruction has been mispredicted, the microprocessor must examine the most current state of the status flags. However, currently, it is not until late in the pipeline that the status flags are examined in order to determine whether the branch condition is satisfied and whether the branch prediction was incorrect. Therefore, what is needed is an apparatus and method for generating the status flags earlier in the pipeline.
Finally, the state of the status flags is typically affected by the results of instructions preceding the conditional branch instruction. For example, the condition may be whether the carry flag, which is one of the status flags, is set. The state of the carry flag may be determined by the most recent add instruction result, for example. However, the results of instructions that affect the status flags are currently generated in execution units located in lower pipeline stages of the microprocessor. Therefore, what is needed is an apparatus and method for generating instruction results earlier in the pipeline.

Pipelined microprocessor, apparatus, and method for performing early correction of conditional branch instruction mispredictions


A method of manufacturing an optical fiber including drawing an optical fiber preform and forming a bare optical fiber, disposing a coating layer formed of a resin on an outer circumference of the bare optical fiber, and curing the coating layer and obtaining an optical fiber is provided. A direction of the bare optical fiber is changed by a direction changer in any position from drawing the optical fiber to disposing the coating layer. In a flow rate of a fluid from a blowout port, an average flow rate or a highest flow rate in an inlet wire portion and an outlet wire portion is higher than a lowest flow rate of the fluid in an intermediate portion.

Field of the Invention
The present invention relates to a method of manufacturing an optical fiber and an apparatus of manufacturing the same.
Description of Related Art
In manufacturing of an optical fiber, a method in which an optical fiber is drawn toward a vertically lower direction from an optical fiber preform along a linear path is generally adopted.
In the manufacturing method, there is a restriction on the height of the entire system as a factor affecting productivity. The reason that the height of the system is a main factor which restricts productivity is because it is necessary to ensure a distance for sufficiently cooling a bare optical fiber which is obtained by drawing the optical fiber preform.
When a new facility including a building is built, the restriction can be relaxed; however, an enormous cost is required for building a new facility, and when it is required that productivity is further improved in the future, it is necessary that a new facility will be built at higher cost.
As a method of relaxing the restriction, a method is included in which a direction changer including a fluid bearing is used.
The fluid bearing is for holding a target to be in a noncontact state using the pressure of a fluid such as air, and in the direction changer including the fluid bearing, it is possible to perform direction change with respect to the bare optical fiber without being in contact with the bare optical fiber (a bare fiber).
By using the direction changer, it is possible to change the direction of the bare optical fiber which is subjected to the fiber drawing from the optical fiber preform along the first path to conform to a second path (for example, refer to Japanese Patent No. 5571958 and Japanese Unexamined Patent Application, First Publication No. S62-003037).
In Japanese Patent No. 5571958, a manufacturing method is disclosed in which an apparatus for direction change including a groove into which an optical fiber is introduced and an opening formed in the groove is used. In this method, gas introduced to the apparatus is blown out from the opening through one inflow port, and the direction of the optical fiber is changed in a state where the optical fiber is floated due to the pressure of the gas.
A direction changer disclosed in Japanese Unexamined Patent Application, First Publication No. S62-003037 includes a guide groove which guides a bare optical fiber, and a blowout port for gas which is formed on a lower surface and both side surfaces of the guide groove (refer to Examples, and FIGS. 3A to 4). In the manufacturing method using the direction changer, the direction of the optical fiber is changed in a state where the optical fiber is floated due to the pressure of the gas blown out from four blowout ports.
However, in the manufacturing method disclosed in Japanese Patent No. 5571958 and Japanese Unexamined Patent Application, First Publication No. S62-003037, positioning accuracy of at least a μm order is required at the time of disposing the apparatus for direction change (for example, refer to Claim 8 in Japanese Patent No. 5571958).
The reason that an accurate position adjustment is required for disposing the apparatus is because the bare optical fiber is damaged when the bare optical fiber is in contact with an inner surface of the groove of the apparatus, and the strength of the bare optical fiber decreases.
For this reason, it is necessary that the bare optical fiber is floated by maintaining a narrow gap of approximately a few dozen μm between the bare optical fiber and the inner surface of the groove. In addition, it is necessary to accurately adjust the position of a central axis (a path line) before and after the direction change. However, since the gap is small, it is very difficult to adjust the position.
The present invention has been made in consideration of the above-described circumstances and an object of the present invention is to provide a method of manufacturing an optical fiber and an apparatus of manufacturing an optical fiber capable of relaxing a requirement for accuracy in a disposing position of an apparatus for direction change.

Method of manufacturing optical fiber and apparatus of manufacturing the same


A carbon dioxide electrolytic device comprises: an electrolysis cell including a cathode, an anode, a carbon dioxide source to supply carbon dioxide to the cathode, a solution source to supply an electrolytic solution, and a separator separating the anode and the cathode; a power controller connected to the anode and the cathode; a refresh material source including a gas source to supply a gaseous substance, and a solution source to supply a rinse solution; and a controller to control the carbon dioxide source, the solution source, the power controller, and the refresh material source in accordance with request criteria of a performance of the cell and thus stop the supply of the carbon dioxide and the electrolytic solution, and apply the voltage therebetween while supplying the rinse solution thereto.

In recent years, depletion of fossil fuel such as petroleum or coal has been concerned, and expectation for sustainably-usable renewable energy has been rising. As the renewable energy, a solar cell, wind power generation, and the like can be cited. Because a power generation amount of these depends on weather and a natural situation, there is a problem that it is difficult to realize stable supply of electric power. For this reason, there has been made an attempt to store the electric power generated by the renewable energy in a storage battery, to thereby stabilize the electric power. However, when the electric power is stored, there are problems that a cost is required for the storage battery, and a loss occurs at a time of the storage.
With respect to such points, attention is focused on a technology in which water electrolysis is performed by using the electric power generated by the renewable energy to produce hydrogen (H2) from water, or carbon dioxide (CO2) is electrochemically reduced to be converted into a chemical substance (chemical energy) such as a carbon compound such as carbon monoxide (CO), formic acid (HCOOH), methanol (CH3OH), methane (CH4), acetic acid (CH3COOH), ethanol (C2H5OH), ethane (C2H6), or ethylene (C2H4). When these chemical substances are stored in a cylinder or a tank, there are advantageous points that a storage cost of energy can be reduced, and a storage loss is also small, when compared to a case where the electric power (electric energy) is stored in the storage battery.
As a carbon dioxide electrolytic device, for example, a structure in which an Ag nanoparticle catalyst is used as a cathode, a cathode solution and CO2 gas are brought into contact with the cathode, and an anode solution is brought into contact with an anode is being studied. As a concrete configuration of the electrolytic device, for example, there can be cited a configuration which includes a cathode solution flow path disposed along one surface of the cathode, a CO2 gas flow path disposed along the other surface of the cathode, an anode solution flow path disposed along one surface of an anode, and a separator disposed between the cathode solution flow path and the anode solution flow path. When a reaction of producing, for example, CO from CO2 is performed for a long period of time by using the electrolytic device having such a configuration and, for example, by making a constant current flow through the cathode and the anode, there is a problem that a deterioration over time of a cell performance such that a production amount of CO is reduced or a cell voltage is increased occurs. For this reason, there has been demanded a carbon dioxide electrolytic device capable of suppressing the deterioration over time of the cell performance.

Carbon dioxide electrolytic device and method of electrolyzing carbon dioxide


An electric power tool (100) includes a power source (102) enclosed in a casing (104). The power source (102) is a brushless DC motor (202) which drives a drive mechanism (106) for a cutting device. Further, an oil pump is at least partly housed in the casing (104) of the electric power tool (100). The oil pump is also driven by the brushless DC motor (202).

Hand-held power tools, for example, but not limited to, chainsaws, trimmers and hedgetrimmers are extensively used in garden and forestry applications. These power tools are required to be made compact and light weight for easy handling during operation. Typically, a power tool includes a power source which is drivably connected to a cutting device. Further, one or more handles are provided on the power tool to facilitate manual gripping during operation.
Typically, most of the power tools known in the art use a brush type DC motor as the power source. The brush type motor includes an electromagnetic rotor and a permanent magnet stator. During operation of the brush type DC motor, a brush assembly provides commutation between the rotor and the stator which is necessary for a continuous rotation of the rotor. Though, the power tools using the brush type DC motor are small and compact, the speed of the brush type DC motor is limited to a pre-determined range depending on the design and material of the brush assembly. Thus, these power tools typically utilize a gear assembly between the brush type DC motor and the cutting device.
The gear assembly not only increases the overall cost and weight of a power tool, but also the components of the gear assembly may require periodic maintenance and the overall running cost of the power tool increases. Further, an oil pump is provided to supply lubricant to the gear assembly and also to other moving parts of the power tools. Typically, the oil pump is driven by an auxiliary electric motor which further increases weight, running costs, and power and space requirements.
Moreover, in the brush type DC motor, the brushes may tend to wear out over a period of time due to constant friction and thus, need to be replaced periodically. This increases the maintenance requirements and requires regular disassembling of the power tool. Furthermore, at high speeds, the brush assembly may cause sparks during commutation, which is highly undesirable.
In light of the foregoing, there is a need for an improved method and system which addresses the above problems in a power tool, for example chainsaws, trimmers, hedgetrimmers etc.

Battery driven electric power tool with brushless motor


The invention relates to a bioreactor (1) comprising a reactor vessel (41) having a mixing chamber (3) separated by a partition (44) from a reaction chamber (2) located generally above the mixing chamber (3), the mixing chamber (3) having an inlet system (4) for influent or a mixture of influent and recycled material, wherein the inlet system (4) has an outlet opening (60-64) in the mixing chamber (3). In an embodiment the partition (44) has an opening (66) forming a connection between the mixing chamber (3) and the reaction chamber (2), wherein the outlet opening (60-64) of the inlet system (4) is directed at the opening in the partition. In an embodiment the mixing chamber (3) has a skeleton for reinforcing the mixing chamber.

From EP 0 539 430-B1 a bioreactor is known having a reaction chamber and a mixing chamber. An inlet system allows influent and/or recycled material to enter the reactor vessel through a mixing chamber separated from the reaction chamber by a partition, the partition having slits. The mixing chamber is conically shaped and comprises steel plates welded to the interior of the reactor vessel near a bottom thereof. The inlet system provides a tangential flow in the mixing chamber.
Much of the energy necessary to bring the influent and/or recycled material in the mixing chamber is dissipated with the cyclone flow in the mixing chamber according to EP 0 539 430-B1. Still, the pressure difference over the partition is limited because of strength limitations of the partition material which causes unequal distribution of the influent in the mixing chamber and eventually in the reaction chamber. Further the pressure difference over the partition increases the level in the degassing tank connected downstream with the bioreactor.


A group of embodiments for enabling the replacement of damaged shackles for multiple types of portable locks is disclosed. The embodiments have the ability to alter the shackle size and configuration for multiple types of portable locks by substituting one type of shackle with a different shackle, with no tools or special skills required.

When using portable locks, cable locks and other types of portable locks, it is sometimes necessary to break or cut the shackle in order to remove the lock. A very common example of this scenario occurs frequently when a portable lock is used as a Lock Out Tag Out device as required by OSHA regulation 1910.147 to prevent inadvertent or deliberate release of energy from a system undergoing maintenance or inspection. Specifically, OSHA regulation 1910.147 states that there be a "one employee, one key and one lock relationship'. If a project or repair is completed, an employee who placed a personal Lock Out Tag Out portable lock to protect personnel performing this project must be present to remove the portable lock when it is no longer required. If the owner of the lock and its unique key is not present, the lock must be cut off in order to restore the repaired system to an operable state. The damaged lock is then either sent back to the manufacturer for repair, or scrapped.
The proper selection of a portable lock depends upon matching several characteristics, such as shackle specifications including but not limited to shackle material, rigid shackle versus flexible cable shackle, shackle clearance and shackle diameter. If a purchaser desired to purchase a portable lock for multiple purposes that have different shackle requirements, they must purchase a separate lock for each specification. If high reliability and availability of a particular lock shackle type is required, it would be necessary to purchase a backup lock's of any required configuration.
The approaches described in this section are approaches that could be pursued, but not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated, it should not be assumed that any of the approaches described in this section qualify as prior art merely by virtue of their inclusion in this section.


A high-voltage AC-DC converter is provided that converts alternating current into high-voltage direct current to be provided to a load, e.g. for use as an electrostatic precipitator. The converter includes at least one transformer, wherein the transformer includes at least one primary winding on the AC-side and at least two secondary windings on the DC-side. The converter further includes at least one rectifier rectifying alternating input current, comprising at least one transistor bridge converting the resulting direct current into alternating current, the transformer transforming the resulting alternating current, and comprising at least two high-voltage rectifiers connected to each of the secondary windings, wherein the output voltage of the high-voltage rectifiers is connected in series.

In many contexts, especially in flue gas cleaning, electrostatic precipitators (ESP) are highly suitable dust collectors. Their design is robust and they are very reliable. Moreover, they are most efficient. Degrees of separation above 99.9% are not unusual. Since, when compared with fabric filters, their operating costs are low and the risk of damage and stoppage owing to functional disorders is considerably smaller, they are a natural choice in many cases. In an electrostatic precipitator, the polluted gas is conducted between electrodes connected to a high-voltage rectifier. Usually, this is a high-voltage transformer with thyristor control on the primary side and a rectifier bridge on the secondary side.
This arrangement is connected to the ordinary AC mains and thus is supplied at a frequency, which is 50 or 60 Hz.
The power control is affected by varying the firing angles of the thyristors. The smaller the firing angle, i.e. the longer conducting period, the more current supplied to the precipitator and the higher the voltage between the electrodes of the precipitator.
Modern power supplies for these ESP are so-called series loaded resonant converters (SLR), which allow to have high-power (typically in the range of 10-200 kW) and high-voltage (50-150 kV DC) while at the same time keeping switching losses at a minimum. The focus of the R&D is higher output power.
The used topology is a series loaded resonant converter, SLR, e.g. as given in FIG. 1. The three phase main with the three phases 1-3 which can be individually switched by switches 4, is rectified by a six-pulse rectifier 6 e.g. comprising diodes 5. This rectifier may however also be an actively switched rectifier. The rectified voltage is smoothed by a DC-link capacitor 13 in the DC-link 6. The DC link voltage is fed to a transistor bridge 8 (H-bridge), comprising four transistors 14, 14′, 15, 15′. The output of the bridge 8 (high frequency AC voltage) is connected, via a resonant tank 9, to the primary of a transformer 10. The resonant tank 9 comprises an inductor 16 and a capacitor 17 in series and together with the primary winding 18 these elements basically define the resonance frequency of the resonant tank, which correspondingly can only reasonably be operated around this resonance frequency. The transformer 10, consisting of the primary winding 18 and the secondary winding 19, adapts the input voltage (mains) to the load 12 (ESP, 50-150 kV). The secondary alternating voltage of the transformer 10 is rectified by a high voltage rectifier 11 and fed to the load 12. The output voltage is normally negative.
In order to increase the power handling capability and to establish a scaleable design, modularizing is used. The fundamental issue when modularizing is to control the load sharing i.e., to secure that different modules take equal or well defined shares of the load.
The high voltage transformer 10 is a key component in the system. Due to the high frequency operation the transformer 10 can be made small. Thus, compared to low frequency designs, the power density is high, leading to high electric fields and to the demand of a high efficiency.
Normally, a transformer for an ESP power supply is immersed in oil to get the appropriate electrical insulation. Also solid insulation materials are in use, in order to strengthen the system where needed.
The presences of high voltage, high frequency AC-fields gives raise to partial discharges (PD) in the insulation system, which will by time deteriorate the system.
The high operation puts focus on the parasitic components of the transformer, these are: leakage inductor, winding capacitor, and magnetizing inductor. The first affect the operation the most. The leakage inductor is connected in series with the resonance tank inductor and has to be considered in the design, as a circuit element. Hence, it has to be controlled and defined by the design.

Power supply for electrostatic precipitator


The disclosure generally describes a chaise longue having a base structure that supports a backrest section, a footrest section and an intermediate section. The intermediate section is connected between the backrest section and the footrest section. The base structure can include a first movable support that supports the backrest section and can articulate about a first stationary transverse axis. The base structure can also include a second movable support that supports the footrest section and can articulate about a second stationary transverse axis.

1. Field of the Invention
The present invention relates to a chaise-longue recliner.
2. Description of the Related Art
A chaise-longue is a reclining chair with anatomical shape which allows the user to assume a semi-reclined resting position. A chaise-longue is traditionally formed by three sections with different inclination: a backrest section, an intermediate section and a footrest section. When the user sits on a chaise-longue, his/her knees are usually at a greater height than his/her hips and feet.
The chaise-longue with continuous adjustment designed by Le Corbusier in 1927 is a furnishing element that has become a part of the design history. The chaise-longue with continuous adjustment is formed by a structure bearing down on the ground, which bears a seating structure that includes two arched support elements able to slide relative to the stationary base structure, so that the user can vary the inclination of the seating structure at will.


The invention concerns a manual resuscitation bag having a first PEP exhaust valve (4) arranged in a first conduit element (3) and fluidly communicating with the ambient atmosphere for venting gas to the atmosphere when the gas pressure, into the first conduit element (3), exceeds a given pressure threshold. The first PEP exhaust valve (4) has a valve body (5) and a calibration mechanism (6, 12; 7-10) for setting a desired pressure threshold. The calibration mechanism (6, 12; 7-10) is a rotatable member (6), actuatable by a user, arranged on the valve body (5) and cooperating with a pressure adjusting device (7-10) arranged into the valve body (5), and a support member (12) comprising several markings (11) corresponding to several settable pressure values, arranged between the rotatable member (6) and the valve body (5).

The present invention relates to a manual artificial respiration device or system, commonly called a manual resuscitation bag or the like, with a PEP exhaust valve that can be used for resuscitating a person, i.e. a patient, in state of cardiac arrest, comprising improved means for easily setting a desired pressure threshold of the PEP exhaust valve.
Cardiac arrest is a condition affecting hundreds of thousand people every year with a very poor prognosis. One of the main life-saving actions is to apply thoracic compressions or 'TCs' along with brief intervals of lung ventilation with a resuscitation bag. TCs are successive compressions and decompressions exerted by a rescuer on the thoracic cage of the person, i.e. the patient, in cardiac arrest. TCs aim at partially restoring inhalation and exhalation phases and therefore gas exchanges in the lungs, as well as promoting or restoring blood circulation in the body and toward the organs, especially in the brain of the patient.
As the compressions and decompressions exerted by the rescuer mobilize only small volumes of gas, in and out of the patient's airways, it is advocated to perform regularly further gas insufflations to bring a fresh O2-containing gas into the lungs, such as air or O2-enriched air, thereby enhancing the gas exchanges.
The flow of respiratory gas delivered to the patient, at a positive pressure, helps keeping the alveoli of the lungs open thereby promoting and/or enhancing gas exchanges. In addition, the positive pressure creates a resistance to gas expulsion during the TC phases, which improves the energy transmission to the heart thereby promoting a better cardiac output.
It is recommended to interpose 2 gas insufflations every 30 chest compressions, whereas the ideal rate of compressions is of between 100 and 120 compressions per minute (c/min).
Usually, the flow of respiratory gas is delivered by an manual resuscitation bag, also called "resuscitation bag system", "resuscitation bag device" or similar, that is fluidly connected to ambient air and, if need be, to an oxygen source.
A manual resuscitation bag generally comprises a deformable bag on which a rescuer can exert a manual-pressure, i.e. he/she can manually squeeze it, for sending the respiratory gas to the patient. The respiratory gas flowing out of the deformable bag is subsequently delivered to the patient's airways, by means of a respiratory interface, such as a facial mask, a laryngeal mask, an endotracheal tube or the like.
Examples of such manual resuscitation bags are given by documents WO-A-2017/096286, WO2015/041396, WO2005/035065 and EP-A-0743075.
For avoiding overpressures in the manual resuscitation bag, in particular overpressures in the conduit element fluidly connected to the gas inlet of the deformable bag, it has been proposed to arrange upstream of the deformable bag of the manual resuscitation bag, namely in said conduit element fluidly connected to the gas inlet, a PEP exhaust valve that is in fluid communication with the ambient atmosphere for venting gas, i.e. gaseous overpressures, to the atmosphere when the gas pressure exceeds a given pressure threshold into said conduit element.
However, a problem is that setting a desired pressure threshold can be difficult for the rescuer, while the manual resuscitation bag is used, i.e. while compressions and decompressions are provided by the rescuer to the patient in cardiac arrest, as existing PEP exhaust valves comprise side or lateral pressure markings carried by the peripheral surface of the valve body. Such a lateral or side positioning of the pressure markings is not convenient as it obligates the rescuer to tilt his head for reading the markings and setting the desired pressure, which is neither comfortable nor convenient, and further may result in parallax issues leading to wrong pressure settings.

Manual resuscitation bag with improved PEP exhaust valve


A stove carrier including a base frame for carrying a baking stove, and a rack for carrying the cover of the baking stove, the base frame having two parallel horizontal bars and two vertical supporting frames symmetrically connected between the horizontal bars at two opposite ends. Each vertical supporting frame having a heat-resisting grip horizontally disposed at the top and two legs vertically disposed at the bottom for supporting the stove carrier on a flat surface. The rack having two opposite ends terminated to respective hooks for hooking on either vertical supporting frame. A pair of bars horizontally disposed at equal elevation relative to the parallel horizontal bars for carrying the cover of the baking stove.

The present invention relates to a stove carrier for carrying a baking stove which has a detachable rack for holding the cover of the baking stove being carried thereon.
Various baking stoves are manufactured and widely accepted by housekeepers. A baking stove is generally comprised of a cylindrical housing and a cover with a built-in electric heater covered on the cylindrical housing at the top. As a baking stove is opened after cooking, the cover must be carefully handled. A baking stove user tends to place the baking stove on the dinner table and simultaneously prepare a heat-resisting pad on the dinner table for holding the cover of the baking stove. However, placing a baking stove on the dinner table occupies much table space.


The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

CD137 (4-1BB, TNFRSF9) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family. CD137 is a co-stimulatory molecule on CD8+ and CD4+ T cells, regulatory T cells (Tregs), natural killer (NK) and NKT cells, B cells and neutrophils. On T cells, CD137 is not constitutively expressed, but induced upon T-cell receptor (TCR)-activation. Stimulation via its natural ligand 4-1BBL or agonist antibodies leads to signaling using TNFR-associated factor (TRAF)-2 and TRAF-1 as adaptors. Early signaling by CD137 involves K-63 poly-ubiquitination reactions that ultimately result in activation of the nuclear factor (NF)—KB and mitogen-activated protein (MAP)-kinase pathways. Signaling leads to increased T cell co-stimulation, proliferation, cytokine production, maturation and prolonged CD8+ T-cell survival. Agonistic antibodies against CD137 have been shown to promote anti-tumor control by T cells in various pre-clinical models (Murillo et al. 2008 Clin. Cancer Res. 14(21): 6895-6906). Antibodies stimulating CD137 can induce survival and proliferation of T cells, thereby enhancing the anti-tumor immune response. Antibodies stimulating CD137 have been disclosed in the prior art, and include urelumab, a human IgG4 antibody (WO2005035584) and utomilumab, a human IgG2 antibody (Fisher et al. 2012 Cancer Immunol. Immunother. 61: 1721-1733).
Programmed death ligand 1 (PD-L1, PDL1, CD274, B7H1) is a 33 kDa, single-pass type I membrane protein. Three isoforms of PD-L1 have been described, based on alternative splicing. PD-L1 belongs to the immunoglobulin (Ig) superfamily and contains one Ig-like C2-type domain and one Ig-like V-type domain. Freshly isolated T and B cells express negligible amounts of PD-L1 and a fraction (about 16%) of CD14+ monocytes constitutively express PD-L1. However, interferon-γ (IFNγ) is known to upregulate PD-L1 on tumor cells.
PD-L1 obstructs anti-tumor immunity by 1) tolerizing tumor-reactive T cells by binding to its receptor, programmed cell death protein 1 (PD-1) (CD279) on activated T cells; 2) rendering tumor cells resistant to CD8+ T cell and Fas ligand-mediated lysis by PD-1 signaling through tumor cell-expressed PD-L1; 3) tolerizing T cells by reverse signaling through T cell-expressed CD80 (B7.1); and 4) promoting the development and maintenance of induced T regulatory cells. PD-L1 is expressed in many human cancers, including melanoma, ovarian, lung and colon cancer (Latchman et al., 2004 Proc Natl Acad Sci USA 101, 10691-6).
PD-L1 blocking antibodies have shown clinical activity in several cancers known to overexpress PD-L1 (incl. melanoma, NSCLC). For example, atezolizumab is a humanized IgG1 monoclonal antibody against PD-L1. It is currently in clinical trials as an immunotherapy for several indications including various types of solid tumors (see e.g. Rittmeyer et al., 2017 Lancet 389:255-265) and is approved for non-small-cell lung cancer and bladder cancer indications. Avelumab, a PD-L1 antibody, (Kaufman et al Lancet Oncol. 2016; 17(10):1374-1385) has been approved by the FDA for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma, and is currently in clinical trials in several cancer indiciations, including bladder cancer, gastric cancer, head and neck cancer, mesothelioma, NSCLC, ovarian cancer and renal cancer. Durvalumab, a PD-L1 antibody, is approved for locally advanced or metastatic urothelial carcinoma indications, and is in clinical development in multiple solid tumors and blood cancers (see e.g. Massard et al., 2016 J Clin Oncol. 34(26):3119-25). Further anti-PD-L1 antibodies have been described in WO2004004771, WO2007005874, WO2010036959, WO2010077634, WO2013079174, WO2013164694, WO2013173223 and WO2014022758.
Horton et al (J Immunother Cancer. 2015; 3 (Suppl 2): 010) discloses combination of an agonistic 4-1BB antibody with a neutralizing PD-L1 antibody.
Combination therapy of utomilumab and avelumab is currently being tested in the clinic (Chen et al., J Clin Oncol 35, 2017 suppl; abstr TPS7575, and clinical trial NCT02554812).
However, despite advances in the art, there is a need for multispecific antibodies that can bind both PD-L1 and CD137. These will give simultaneous binding to PD-L1-expressing antigen-presenting cells (APCs) or tumor cells and CD137-expressing T cells, resulting in conditional activation of (cytotoxic) T cells. PD-L1 binding to PD1 expressed on activated T cells will result in T cell inhibition. Accordingly, it is an object of the present invention to provide PD-L1×CD137 bispecific binding agents such as bispecific antibodies which block the PD1-(PD-L1) inhibitory signaling and at the same time co-stimulate T cells via trans binding to the CD137 molecule expressed on activated T cells, with the activation occurring through the trans binding. This can lead to efficient induction of anti-tumor immunity. It is a further object of the present invention to provide a PD-L1×CD137 bispecific binding agent with an inert Fc region or alternatively without an Fc binding region, thereby providing a bispecific binding agent which does not induce complement-dependent cytotoxicity (CDC) or other Fc-mediated effector functions on the T cells when binding to CD137. It is a further object of the present invention to provide a PD-L1×CD137 bispecific binding agent suitable for activating T cells. It is a further object of the present invention to provide a PD-L1×CD137 bispecific binding agent suitable for activating tumor-specific T cells such as tumor infiltrating T cells. It is a further object of the present invention to provide a bispecific binding agent with an improved toxicology profile compared to current treatment options in the field. It is yet a further object of the present invention to provide a binding agent with improved efficacy profile compared to current treatment options in the field.

Binding agents binding to PD-L1 and CD137 and use thereof


An actinic radiation curable composition, comprising a photo-acid generating agent selected from the group consisting of sulfonium represented by General Formulas (I)–(III).

In recent years, ink-jet recording systems have been applied to various printing fields such as photography, various printing, marking, and special printing such as color filters due to its capability of forming images simply and easily. It has become possible to achieve image quality comparable to silver salt photography, specifically by employing recording apparatuses which eject minute dots under control, inks which exhibit an enhanced color reproduction range as well as enhanced durability, and improved ejection adaptability, and special sheets which exhibit markedly improved ink absorbability, color forming properties of colorants and acceptable surface gloss. Enhancement of image quality of the current ink-jet recording system is achievable only by simultaneously improvement of all the recording apparatuses, inks and special sheets.
However, ink-jet systems, which require special sheets, results in problems such as limitations of recording media as well as an higher cost of the aforesaid recording media. As a result, a number of trials have been made in which recording is carried out on image receiving media different from such special sheets, while employing various ink-jet systems. Specific examples include a phase change ink-jet system using a wax ink which is solid at room temperature, a solvent based ink-jet system using an ink comprised of rapid drying organic solvents as a main component, and a UV ink-jet system in which after image recording, crosslinking is carried out employing ultraviolet radiation (UV radiation).
Of these, in recent years, the UV ink-jet system has received attention due to relatively low generation of unpleasant odors, rapid drying properties, and recording capability onto recording media exhibiting no ink absorbability. Ultraviolet radiation curing ink-jet inks are disclosed, for example, in Japanese Patent Publication No. 5054667, Japanese Patent Publication Open to Public Inspection No. 6-200204, and Japanese Patent Publication Open to Public Inspection (under PCT Application) No. 2000-504778.
However, even though these inks are employed, it is very difficult to form highly detailed images on all the recording materials due to large changes of ink dot diameter after the impingement, depending on the types of recording materials and operation environments.
On the other hand, it is known (e.g., Japanese Patent Application Open to Public Inspection No. 2000-186071, pages 4–7) that sulfonium salts are incorporated in the aforesaid ultraviolet radiation curing ink-jet ink as an initiator. However, the ultraviolet radiation curable ink, employing such sulfonium salt initiators results in the problems described below.
Namely, the aforesaid ultraviolet radiation curable ink is divided mainly into a radical polymerization type ultraviolet radiation curable ink mainly comprised of an acryl based composition, and a cation polymerization type ultraviolet radiation curable ink. The radical polymerization type ultraviolet radiation curable ink exhibits problems in which from the standpoint of the polymerization mechanism, its curability is degraded due to the presence of oxygen which hinders curing. On the other hand, the cation polymerization type ultraviolet curable ink does no exhibit degradation of curability due to the presence of oxygen. However, problems occur in which curing tends to be adversely affected by water (humidity) at a molecular level from the standpoint of its polymerization reaction.

Actinic radiation curable composition and actinic radiation curable ink, and image forming method as well as ink jet recording apparatus using the same


[Problem] A viscoelasticity measuring method and a viscoelasticity measuring apparatus are provided which can measure viscoelasticity of a sample substance even when the quantity of the sample substance is minute.

A measuring apparatus using a QCM (Quartz Crystal Microbalance) in the related art is disclosed, for example, in PTL 1.
On the other hand, viscoelasticity measuring methods in the related art can be broadly classified into methods of a static viscoelasticity measuring method such as a steady flow measuring method or a uniform up and down method and a dynamic viscoelasticity measuring method in which a frequency function is deformed. Particularly, the dynamic viscoelasticity measuring method has been widely used, because information on viscosity or viscoelasticity can be acquired in a minutely-deformed state in which the measurement sample is not structurally destroyed.
However, when viscoelasticity is measured using a general viscoelasticity measuring apparatus, a measurement sample of at least 0.5 mL to 50 mL is necessary. A measuring method suitable for measuring viscoelasticity of substances, which cannot be taken in large quantity, such as substances taken in minute quantity from a human body or grease used in a machine actually working does not exist.

Viscoelasticity measuring method and viscoelasticity measuring apparatus

Abstract: [Solution] A solution or semisolid sample substance is brought into contact with an electrode of a sensor formed of a quartz crystal oscillator, a variation ΔFs of a resonance frequency Fs of the quartz crystal oscillator and a variation ΔFw of a half-value half frequency (F1-F2)/2 of a first frequency F1 and a second frequency F2 having conductance ½ Gmax which is a half of conductance Gmax of the resonance frequency Fs are measured, and any of a storage elastic modulus G′ of the sample substance based on the difference of squares of the variation ΔFs of the resonance frequency and the variation ΔFw of the half-value half frequency and a loss elastic modulus G″ of the sample substance based on the multiplication of the variation ΔFs of the resonance frequency and the variation ΔFw of the half-value half frequency is calculated.


A non-vented shell earplug for insertion into the ear canal has multiple chambers configured as coupled acoustic resonators. Each chamber is provided with an acoustic element having inertia and resistance coupling the chamber to its neighbor to form multiple resonant chambers. The dimensions of the individual acoustic elements set the frequency response of the earplug, and determine the attenuation characteristics of the resonators. Unlike the single chamber resonator of the prior art, the multiple-resonator earplug provides attenuation in both low and high frequency segments of the noise spectrum.

1. Field of the Invention
This invention relates to an earplug, and in particular to a non-vented, multiple-resonator, noise attenuating earplug for insertion into the ear canal.
2. Description Relative to the Prior Art
The deleterious effects on the hearing capability of a person subjected to a high amplitude ambient noise field are well known. Personnel such as miners, construction workers, aircraft maintainers, military tank operators, pilots, as well as many industrial employees are routinely and necessarily subjected to loud noise environments while performing their duties. Preventing ambient sound from entering the ear canal protects users from excessive ambient noise that causes hearing damage. In addition, attenuating ambient noise is beneficial in communications systems because higher speech intelligibility results.
When an earplug is inserted into an ear canal, ambient sound is transmitted into the canal through movement of the earplug, through air leaks around the earplug, by sound impinging on the body and by traveling through skin tissue and bone into the canal, as well as by sound transmission through the earplug itself. Solid earplugs constructed of polymeric foam, wax, rubber, acrylic are currently available, and have no internal resonators. The attenuation of a well-sealed solid earplug generally increases monotonically as a function of rising frequency.
U.S. Pat. No. 3,047,089, issued to J. J. Zwislocki, discloses a non-vented passive earplug having a single internal resonator. A sound chamber along with its sound opening into the ear canal form an acoustic resonating system, known as a Helmholtz resonator. The resonant frequency, F0, of such a resonator is determined by the following formula:F0=1/(2π✓(M1C1))where M1 is the acoustic inertance at the sound opening and C1 is the compliance of the chamber volume. As an example, for a chamber volume of 2.5 cc with a compliance of 1.76×10−6 cm4 s2/g and the acoustic inertance is 0.01 g/cm4; the resonance frequency is 1200 Hz. Above the resonance frequency, the acoustic impedance at the sound opening is relatively high, and the earplug attenuation matches that of a solid earplug. Below resonance, the impedance is relatively small, and the chamber of the earplug increases the occluded ear canal volume. This results in enhanced attenuation at frequencies below resonance. The improvement in the attenuation, in decibels (dB), is calculated fromI=20 log((C1+Cc)/Cc)where Cc is the acoustic compliance of the occluded ear canal, which is approximately 8.60×10−7 cm4 s2 when using an earplug. Therefore, in this example the improved attenuation below resonance is approximately 10 dB. The resonance of the system is primarily damped by viscous losses associated with movement of air through the sound opening. A problem with the single-chamber earplug is its limited high-frequency attenuation performance. Also when a loudspeaker, or other sound transmitting means is used with the earplug to provide communications for the user, the sound pressure level developed using the loudspeaker is significantly reduced compared to a solid earplug also having an attached loudspeaker.
U.S. Pat. No. 2,347,490, issued to Watson et al, discloses an earplug made of flexible resilient material having two chambers separated by a partition containing a cotton-packed cylindrical insert having a minute hole in its endplate to allow static pressure equalization between the chambers. Watson et al do not disclose chambers having the structure of multiple acoustic resonators because the chamber coupled to the ear canal does not employ an inertial element, and accordingly, the disclosed earplug does not exhibit the attenuation characteristic of multiple acoustic resonance.
U.S. Pat. No. 5,832,094, issued to Le Her discloses an earplug with an acoustic valve. The earplug disclosed by Le Her is vented, in that there is an acoustic path provided through the earplug to the ear canal under normal operating conditions. The invention of Le Her selectively transmits ambient sound through the earplug and into the ear canal at all times. This sound transmission increases the unwanted sound level in the ear canal and diminishes the hearing protection function of the earplug.

Abstract: Additionally, the present invention teaches placing loudspeaker and/or sound sensing transducer for sound communication purposes and active noise control within the earplug, with their sound field patterns directed into a chamber for coupling to the ear canal. The use of multiple resonators enhances the high frequency communications response of the earplug.


Method and apparatus to treat unwanted dermatological conditions on a specific area of the body. The area of treatment is exposed to a specific pattern of multi-wavelength light which may have an added infusion of a particular wavelength from a unique non-collimated laser rod optical insertion. The light is generated by specific gas mixture multiple flashlamps that allow simultaneous, overlap, or consecutive firing with quasi-logarithmic spacing between pulses. Pre/Post low level optical heating increases lesion temperature to optimize pulsed treatment. The optimum fixed specific wavelength distribution pattern allows the treatment of various skin conditions by adjusting the intensity of light, and delay between pulses. The need for skin cooling and damage to skin treatment areas is eliminated by the quasi-logarithmic pulse spacing in conjunction with optimum length and characteristic shape of the individual pulses of light.

This invention relates to a method and device for treating and removing various skin conditions and lesions using flashlamps. There exists a multitude of common skin problem which can be caused by many reasons. Conditions such as excessive hair, age spots, freckles, superficial veins, wrinkles, acne, rosacea and collagen shrinkage due to old age to name just a few. There are many products and methods for treating such skin conditions. The methods can include one or a combination of external creams, chemicals, internal medications, laser devices, mechanical devices, and surgery.
These methods vary in effectiveness, pain, term of benefit, side effects, duration of treatment, and cost of procedure. Unfortunately, to treat all the various skin conditions generally requires multiple devices and/or treatment modalities. Because of this need for multiple devices and modalities to treat numerous skin conditions, a single device that could treat a great number of skin conditions would make treatments more accessible to the public.
Prior art methods such as Altshuler et al. U.S. Pat. No. 6,511,475 utilizes continuous wave light as apposed to a pulsed light system. The Altshuler device does not create high peak temperatures in a short time span due to its continuous wave nature. This inability to create high peak temperatures in a short time span prohibits its use in a wide variety of skin conditions.
While another prior art method disclosed in Eckhouse et al. U.S. Pat. No. 6,514,243 utilizes pulsed light. Its particular spectrum distribution pattern requires the use of a cooling gel to prevent discomfort to the patient. Unfortunately, the spectrum distribution pattern of the Eckhouse device may cause damage to the treatment area skin. Further, the lack of multiple lamps severely limit the range of skin conditions that the Eckhouse device is able to treat.

Dual filter multiple pulse photo-dermatological device with pre/post optical heating, quasi-logarithmic spacing, and laser rod spectrum infusion


According to an aspect of the present invention, once the mode setting device sets the person photographing mode, and the face zooming instruction device instructs zooming to the face of the person, the detection device detects the size of the face of the person captured by the image pickup device. The zooming device is then controlled so as to capture the face of the person in a certain size based on the detection result. Subsequently, the photographer instructs zooming in the telephoto direction or the wide direction using the zooming instruction device as necessary to thereby allow fine adjustment of the composition. This enables to easily and quickly photograph an image in a user's desired composition.

1. Field of the Invention
The present invention relates to an image taking apparatus, and more particularly to an image taking apparatus with a zoom function.
2. Description of the Related Art
When photographing a person as an object, such as in the portrait photographing, the composition is usually adjusted so that the person is photographed in a proper size.
The composition is usually adjusted using a zoom function in a camera having a zoom function. However, an opportunity to press the shutter may be missed during the zooming operation.
Under the circumstances, Japanese Patent Application Laid-Open Nos. 6-217187, 2004-320286, and 6-153047 propose technologies for automatic zooming when photographing moving images of a person. The face of a person is identified from the photographed images, and the size and the position of the face is found such that the face of the person is always photographed in a certain size.
Japanese Patent Application Laid-Open No. 11-84481 proposes a technique for obtaining an image with a proper face size when photographing an ID photo. The size of the face of an object is detected from the photographed image, and the image is automatically contracted or expanded such that the size of the detected face becomes a standard size.


Optically-activated systems and methods for reducing the appearance of dark under eye circles are provided. The systems comprise a complex of a fluorescent compound and a substrate for the fluorescent compound which are affixed to one another by covalent bonding, hydrogen bonding, Van der Waals forces, or a combination thereof. After absorption of ambient light, the fluorescent compound in the complex re-emits visible light of longer wavelength. The re-emitted light provides an illuminating radiant effect and is particularly useful in improving the appearance of skin imperfections.

Field of the Invention
The present invention relates to optically-activated systems and cosmetic and/or dermatological compositions thereof. More particularly, the optically-activated systems absorb ambient light and re-emit visible light to reduce the visual perception of skin imperfections including, dark under eye circles, hyperpigmentation, rosacea, lines, wrinkles, enlarged pores, cellulite, uneven skin tone, and the like. The optically-activated systems may take the form of lotions, creams, gels, mousses, sticks, powders, and so forth, and may be used in various cosmetic or dermatological preparations, for example, make-up foundations and concealers, and skin treatment products, such as moisturizers.
Description of the Prior Art
A wide variety of personal care compositions has been developed to improve skin appearance; that is, to reduce the appearance of wrinkles, fine lines, enlarged pores, and so forth, to achieve natural, translucent, more even-toned and youthful appearing skin. Such compositions have traditionally utilized light subtraction materials (pigments), fluorescent brighteners, soft focus technology, and/or biologically active anti-aging ingredients.
Reducing the appearance of dark under eye circles in particular has proved a particularly difficult challenge in the cosmetic and dermatological industries. Typical make-ups and concealers do not provide a natural appearance to the skin under the eyes, but only mask the appearance of skin imperfections. For example, current products on the market for targeting dark under eye circles (often referred to as DUEC) contain one or more of metal oxide pigments, dyes and/or lakes, mica, peptides, and botanicals.
The use of a combination of light scattering with fluorescent light emission to camouflage skin imperfections is known from U.S. Pat. No. 7,306,809 which discloses optically-activated particles for use in cosmetic compositions. The optically-activated particles comprise a solid nylon substrate having a synthetic fluorescent compound trapped therein. The fluorescent compound-treated substrate is coated with cross-linked polyvinyl alcohol (PVA). The optically-activated particles emit and diffuse visible blue light which is said to illuminate shadows in skin and/or camouflage fine lines, creating the illusion that such imperfections do not exist. Nevertheless, treatment of DUEC remains a challenge. Most desired by consumers are natural looking compositions which do not mask the skin but which nevertheless reduce the visual perception of skin imperfections, and dark under eye circles, in particular.
Accordingly, there remains a need in the art for improved cosmetic and dermatological systems which are capable of obscuring discolorations and uneven surface texture by imparting a perception of natural, smooth and even-toned skin to observers. The systems of the present invention meet this need by harnessing ambient light and concentrating the increased light reflection in the area of the skin imperfection, and in particular, under the eye.

Method of making an optically-activated system


This invention provides a method that combines a checkpoint inhibitor and a glucocorticoid receptor modulator to treat cancer, e.g., a checkpoint inhibitor sensitive cancer.

Cancer is a group of varied diseases characterized by uncontrolled growth and spread of abnormal cells. The pathways regulating cell division and or cellular communication become altered in cancer cells such that the effects of these regulatory mechanisms in controlling and limiting cell growth fails or is bypassed. Through successive rounds of mutation and natural selection, a group of abnormal cells, generally originating from a single mutant cell, accumulates additional mutations that provide selective growth advantage over other cells, and thus evolves into a cell type that predominates in the cell mass. As the cancer cells further evolve, some become locally invasive and then metastasize to colonize tissues other than the cancer cell's tissue of origin. This property along with the heterogeneity of the tumor cell population makes cancer a particularly difficult disease to treat and eradicate.
Traditional cancer therapies take advantage of the higher proliferative capacity of cancer cells and their increased sensitivity to DNA damage: Ionizing radiation, including γ-rays and x-rays, and cytotoxic agents, such as bleomycin, vinblastine, cyclophosphamide, 5′-fluorouracil, and methotrexate rely upon a generalized damage to DNA and destabilization of chromosomal structure which eventually leads to destruction of cancer cells. These treatments are particularly effective for those types of cancers that have defects in cell cycle checkpoint, which limits the ability of these cells to repair damaged DNA before undergoing cell division. The non-selective nature of these treatments, however, often results in severe and debilitating side effects. The systemic use of these drugs may result in damage to normally healthy organs and tissues, and compromise the long-term health of the patient.
Recently, immunotherapy targeting immune checkpoint signaling pathways has been shown to be effective in treating cancer. These pathways suppress immune response and are crucial for maintaining self-tolerance, modulating the duration and amplitude of physiological immune responses in peripheral tissues, and minimizing collateral tissue damage. It is believed that tumor cells can activate the immune checkpoint signaling pathways to decrease the effectiveness of the immune response against tumor tissues. Many of these immune checkpoint signaling pathways are initiated by interactions between checkpoint proteins present on the surface of the cells participating in the immune responses, e.g., T cells, and their ligands, thus they can be readily blocked by agents or modulated by recombinant forms of the checkpoint proteins or ligands or receptors. The agents blocking the immunosuppression pathway induced by checkpoint proteins are commonly referred to as checkpoint inhibitors and a few have been commercialized. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies, blocking the immunosuppression pathway by the checkpoint protein CTLA4, were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD-1), indicate broad and diverse opportunities to enhance anti-tumor immunity with the potential to produce durable clinical responses.
Glucocorticoid receptor (GR) mediated signaling pathways have dynamic biologic effects involving different components of the immune system and their in vivo effects are unpredictable. For example, glucocorticoids have been reported to have both immunosuppressive effects such as, suppression of proflammatory cytokines, promotion of anti-inflammatory cytokines, inhibition of dendritic cells, suppression of natural killer cells, promotion of T-regulatory cells, and induction of T cell apoptosis,—and immune-enhancing effects, See Hinrichs J. Immunother. 2005: 28 (6): 517-524. The effects of GR mediated signaling pathway on cancer cells is likewise elusive. On one hand, it is believed that activating the GR signaling pathways induce apoptosis in certain types of cancer cells, for example, malignant lymphoid cancers. See Schlossmacher, J. Endocrino. (2011). On the other hand, it has also been reported that agents blocking the GR signaling pathway can potentiate chemotherapy in killing cancer cells. See U.S. Pat. No. 9,149,485. This current invention uses a novel combination therapy that targets both the checkpoint signaling pathway and GR signaling pathway to treat patients suffering from a tumor load.

Use of glucocorticoid receptor modulators to potentiate checkpoint inhibitors