A semiconductor circuit having a power supply voltage detection circuit to detect a potential level of an external power supply voltage and to output a detection signal depending on a comparison result with the potential level. A system control circuit detects the detection signal, outputs a status signal and an interrupt signal, and outputs a clock selection signal in response to an operation control signal. A CPU outputs the operation control signal to the system control circuit in response to the status signal and the interrupt signal. A clock generation circuit generates a plurality of clock signals and a clock selection circuit selects one clock signal among the plurality of clock signals in response to the clock selection signal. The clock selection circuit then outputs the one clock signal as a system clock signal.

This application claims the benefit of priority from prior Japanese Patent Application P2001-323881, filed on Oct. 22, 2001, the contents of which are hereby incorporated by reference in their entirety.
The present invention relates to a semiconductor integrated circuit and method for operating the same, where the integrated circuit is supplied with a power supply voltage having a varying potential level.
In recent years, the miniaturization in large scale integration (LSI) fabrication processes has caused a lowering of the power supply voltage. For example, integrated circuit (IC) cards and subscribers identify module (SIM) cards (an IC card used for a portable information terminal) may have power supply voltages of 5V and 3V, and lately as low as 1.8V. Accordingly, such LSI cards must cope with a wide range of power supply voltages.
While such LSI cards may be designed to be compatible with power supply voltages of 5 V, 3 V, and 1.8 V, those cards generally operate optimally at one clock frequency for a given power supply voltage. When the power supply voltage of the LSI card is lowered, the operating speed of the LSI logic circuit generally decreases. If the operating speed goes too low due to the application of a power supply voltage lower than normal, the logic operation may become unstable, and thus cause the IC card to malfunction.
If the power supply voltage to the LSI then rises (e.g., when first applying the power supply or when recovering from a low power consumption mode or sleep mode), the internal logic circuit may become indeterminate. Again, this may cause the LSI card to become unstable. This is particularly likely when, before the power supply voltage begins to rise, the power supply voltage was low enough to cause a malfunction. In such situations, the circuit components of the IC card begin operating simultaneously before the IC card""s voltage regulator or constant voltage generation circuit has a chance to stabilize. The high amount of power required to simultaneously operate these components while the voltage regulator is attempting to stabilize to the new power supply voltage, causes the operation of the regulator to deteriorate.
Accordingly, there is a need for an IC card to be compatible with a power supply voltage having a varying potential level, and to prevent malfunctioning of the IC card when the potential level of the power supply changes.
In accordance with a first exemplary implementation of the invention, a semiconductor circuit is provided comprising a power supply voltage detection circuit to detect a potential level of an external power supply voltage and to output a detection signal dependent on a comparison of the potential level. A system control circuit detects the detection signal, outputs a status signal and an interrupt signal, and outputs a clock selection signal in response to an operation control signal. A outputs the operation control signal to the system control circuit in response to the status signal and the interrupt signal. A clock generation circuit generates a plurality of clock signals and a clock selection circuit selects one clock signal among the plurality of clock signals in response to the clock selection signal and outputs the one clock signal as a system clock signal.
According to a second exemplary implementation of the invention, a semiconductor circuit is provided, comprising a plurality of circuit components and a regulator to output a predetermined constant voltage as a regulated output voltage when supplied with a first external power supply voltage higher than the predetermined constant voltage. The regulator also outputs a second external power supply voltage as the regulated output voltage when supplied with the second external power supply voltage lower than the predetermined constant voltage. A power-on reset circuit outputs an internal reset signal which remains at a first logic level until the regulated output voltage exceeds a threshold voltage value lower than the second external power supply voltage and becomes a second logic level when the regulated output voltage exceeds the threshold value. A logic circuit computes a logical product of the internal reset signal and an external reset signal and outputs the logical product as a system reset signal. A CPU receives the system reset signal and outputs a low power consumption mode signal. A sequential activation circuit receives the internal reset signal and the low power consumption mode signal, and sequentially outputs enable signals respectively activating the plurality of circuit components. The enable signals are output at different times.
According to a third exemplary implementation of the invention, a semiconductor circuit is provided, comprising a plurality of circuit components and a regulator to output a predetermined constant voltage as a regulated output voltage when supplied with a first external power supply voltage higher than the predetermined constant voltage. The regulator also outputs a second external power supply voltage as the regulated output voltage when supplied with the second external power supply voltage lower than the predetermined constant voltage. A power-on reset circuit outputs an internal reset signal which remains at a first logic level until the regulated output voltage exceeds a threshold voltage value lower than the second external power supply voltage and becomes a second logic level when the regulated output voltage exceeds the threshold value. A logic circuit computes a logical product of the internal reset signal and an external reset signal and outputs the logical product as a system reset signal. A CPU receives the system reset signal and outputs a low power consumption mode signal. A sequential activation circuit receives the internal reset signal and the low power consumption mode signal, and sequentially outputs enable signals respectively activating the plurality of circuit components, wherein the enable signals are output at different times. A power supply voltage detection circuit detects a potential level of an external power supply voltage and outputs a comparison result of the external power supply voltage with a reference voltage as a detection signal. A system control circuit detects the detection signal, outputs a status signal and an interrupt signal, and outputs a clock selection signal in response to an operation control signal. A clock generation circuit generates a plurality of clock signals from a source clock signal. A clock selection circuit selects one clock signal among the plurality of clock signals in response to the clock selection signal and outputs the one clock signal as a system clock signal to the system control circuit, wherein the CPU further outputs the operation control signal to the system control circuit in response to the status signal and the interrupt signal.
According to a fourth exemplary implementation of the invention, a memory card is provided, comprising a card substrate and a semiconductor circuit mounted on the card substrate. The semiconductor circuit has a circuit to generate a plurality of clock signals from a source clock signal and a circuit to select one clock signal among the plurality of clock signals in accordance with a potential level of an external power supply voltage. An external terminal is mounted on the card substrate and a substrate wiring is provided on the card substrate to connect the external terminal and a pad on the semiconductor circuit. Further, a cover film is provided to cover the semiconductor circuit and the card substrate.
According to a fifth exemplary implementation of the invention, a memory card is provided, comprising a card substrate and a semiconductor circuit mounted on the card substrate. The semiconductor circuit has a plurality of circuit components, a regulator which increases an output voltage with time when supplied with an external power supply voltage lower than a normal constant output voltage, and a circuit which sequentially outputs enable signals of a first logic level at different times to sequentially activate the plurality of circuit components when an output of the regulator reaches a threshold value voltage lower than the external power supply voltage. An external terminal is mounted on the card substrate and a substrate wiring is provided on the card substrate to connect the external terminal and a pad on the semiconductor circuit. Further, a cover film is provided for covering the semiconductor circuit and the card substrate.
According to a sixth exemplary implementation of the invention, a method of operating a memory card is provided, comprising: generating a plurality of clock signals from a source clock signal; detecting a potential level of an external power supply voltage supplied from an external circuit and outputting a comparison result of the external power supply voltage with a reference voltage as a detection signal; detecting the detection signal and outputting a status signal and an interrupt signal; outputting an operation control signal in response to the status signal and the interrupt signal; outputting a clock selection signal in response to the operation control signal; and selecting one clock signal among the plurality of clock signals in response to the clock selection signal and outputting the one clock signal as a system clock signal.
According to a seventh exemplary implementation of the invention, a method of operating a memory card is provided, comprising: comparing an external power supply voltage supplied from an external circuit with a normal constant voltage; increasing a regulated output voltage to drive a plurality of circuit components on a semiconductor circuit when the external power supply voltage is lower than the normal constant voltage; and sequentially outputting enable signals at different times which respectively activate the plurality of circuit components when an output voltage of the regulated voltage reaches a specified threshold voltage value lower than the external power supply voltage.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only, and should not be considered restrictive of the scope of the invention, as disclosed and claimed herein. Further, features and/or variations may be provided in addition to those set forth herein. For example, embodiments of the invention may be directed to various combinations and sub-combinations of the features described in the detailed description.

Semiconductor circuit supplied with a varying power supply voltage, and method for operating the same


A Kevlar.RTM. rope termination in which the rope is passed through an opening in a tension leg termination, is divided and laid over a rigid pin, being sealed around the pin with a resin. A flexible bearing member is located between the rope covered pin and a rigid support member contiguous with the inside of the termination, adjacent to the opening so that the rope covered pin can easily rotate within the bearing member without kinking the rope.

Parallel lay Kevlar.RTM. ropes have been proposed for use as mooring lines for tension leg platforms. For this type of rope construction, two terminations are usually used, a cone and spike type and a potted termination. The termination is usually large in size and is fabricated of metal causing a large change in bending stiffness betweeen termination and the rope. Any uncontrolled movement of the termination during handling and installation imposes a large bending of the rope end near the termination. Since Kevlar.RTM. lacks high strength in compression, bending causing kinking of the fibers results in a major reduction of the rope strength.
It is desirable to provide a termination for kinkable ropes such as Kevlar.RTM. where the rope would be free to rotate and to move laterally whereby kinking of the rope would not occur.


Power electronics for electric traction motors used to drive automotive vehicles are cooled in a closed system by spraying a dielectric liquid coolant directly onto inverter circuitry. The liquid coolant changes phase and vaporizes as it absorbs heat from power transistors in inverter circuitry comprising the power electronics. The resultant vapor is condensed back to a liquid in a heat exchange arrangement having pipes carrying a second coolant from a radiator used to cool an engine or fuel cell stack in the automotive vehicle. Overspray coolant, which remains liquid, can also be cooled by the heat exchange arrangement. By utilizing the latent heat of evaporation of the dielectric coolant and increasing the rate recycling of the coolant as power output increases, temperature increases in the power electronics are controlled.

Vehicles which utilize electric traction motors to drive wheels of a vehicle, whether the electric motor is in a gas-electric hybrid vehicle or a fuel cell powered vehicle, typically use a three-phase AC motor coupled with inverter circuitry that converts direct current from a power source to alternating current. Currently, inverter circuitry generally comprises power transistors mounted on a DBC (direct bonded copper) substrate with integrated bus bars.
As automotive vehicles start, change cruising speeds, accelerate and brake, power demands of electric traction motors driving the vehicles fluctuate over a wide range. Fluctuations in power demand cause temperature changes in power electronics connected to the traction motors. The power electronics include inverter circuitry comprised of different materials with various coefficients of expansion. Accordingly, heat fluctuations can degrade inverter circuitry as the integrated components thereof expand at different rates tending to shift slightly with respect to one another as the components respond to temperature variations. It is necessary to control temperature to keep expansions and contractions of the components within acceptable levels. Currently, this is accomplished by circulating fluids through heat sinks associated with the DBC or by flowing air thereover to absorb and carry away heat. While these approaches currently appear satisfactory, there remains a need to more precisely control the temperature of inverter circuitry over the life of vehicles utilizing traction electric motors in order to sustain reliability, as well as to control power consumption.

Arrangements for and methods of phase change cooling of power electronics


A process of electronic structure is provided. First, a carrier board is provided, in which the carrier board has a first surface. Next, a first release layer is formed on the first surface of the carrier board. The first release layer has property of withstanding high-temperature and temporary adhesion capability and the first release layer entirely or mostly overlays the first surface. Then, a built-up structure is formed on the first release layer. Finally, a separating process is performed so that the built-up structure is separated from the carrier board to form an electronic structure.

1. Field of the Invention
The invention generally relates to a circuit board, and more particularly, to a process of electronic structure.
2. Description of Related Art
The process of a circuit board can be roughly divided into laminating method and building-up method. The fabrication principle of the laminating method is to form a patterned metal circuit layer on a single surface or both surfaces of a dielectric layer. Then, a bonding sheet and a metal sheet are added on the circuit layers and meanwhile the metal sheet and the bonding sheet are heated and pressed so that the metal sheet is bonded with an adjacent circuit layer. After that, conductive through vias are fabricated on the laminated layers so that each of the circuit layers and the metal sheet can be electrically connected to each other through the conductive through via. On the other hand, the fabrication principle of the building-up method is to sequentially form a circuit layer, a dielectric layer and a metal layer respectively on both opposite surfaces of a carrier board, and the adjacent circuit layer and metal layer are electrically connected to each other through conductive blind vias formed in the process.

Process of electronic structure and electronic structure


A robot system includes a container, a disposed-state detector, and a robot arm. The container is configured to accommodate a plurality of to-be-held objects and includes a reticulated portion. The disposed-state detector is configured to detect disposed states of the plurality of respective to-be-held objects disposed in the container. The robot arm includes a holder configured to hold a to-be-held object among the plurality of to-be-held objects based on the disposed states of the plurality of respective to-be-held objects detected by the disposed-state detector.

1. Field of the Invention
The present invention relates to a robot system and a method for producing a to-be-processed material.
2. Discussion of the Background
As conventionally known, some robot systems include robot arms provided with holders to hold to-be-held objects (see, for example, Japanese Unexamined Patent Application Publication No. 2011-115930).
Japanese Unexamined Patent Application Publication No. 2011-115930 discloses a robot system including a robot arm and a sensor unit. The robot arm includes a gripper (holder) to hold a workpiece (to-be-held object). The sensor unit detects (picks up an image of) a plurality of workpieces disposed in a box-shaped stocker having planar side surfaces and a planar bottom surface. In the robot system recited in Japanese Unexamined Patent Application Publication No. 2011-115930, the sensor unit picks up an image of the plurality of workpieces disposed in the stocker so as to detect a disposed state of each of the plurality of workpieces. Then, the robot arm is driven to have its gripper grip one workpiece selected from the plurality of workpieces.

Robot system and method for producing a to-be-processed material


A ceramic gas sensor for measuring a gas component in a gas mixture, which includes a sensor element, which has at least one first electrode exposed to the gas mixture to be determined, and at least one further electrode. Only one shared electrical contact is provided for the first electrode and for the additional electrode, an electrical resistor, which is situated inside the gas sensor, being preconnected to the first electrode and/or the additional electrode.

In the course of progressive environmental legislation there is growing demand for sensors with whose aid even the minutest quantities of pollutants can be reliably determined. Above all, gas sensors that allow the determination of gaseous pollutants in the ppm range, independent of the temperature of the measuring gas, play an important role. However, especially the determination of the nitrogen oxide content in the combustion waste gases poses a special challenge because of the frequently high oxygen component in exhaust gases.
U.S. Application No. 2003/0075441 describes, for instance, a gas sensor which, among other things, is used to determine nitrogen oxides. Its method of functioning is assignable to what is known as the dual-chamber limit current principle. Measuring gas that enters the sensor is selectively rid of oxygen with the aid of two electrochemical pump cells situated one after the other in the flow direction of the measuring gas, and the partial pressure of the oxygen is therefore reduced considerably in this manner. The individual pump electrodes have different potentials, so that the oxygen content of the measuring gas can be reduced in a stepwise manner without changing the nitrogen oxide component in the measuring gas to any significant degree.
However, this sensor structure requires a multitude of electrical connections for contacting pump electrodes, measuring electrodes, heating elements etc. A high number of connections, however, leads to considerable expense with regard to routing the electrical feeds out of the sensor element, the electrical contacting and routing the cables out of the sensor housing. This results in high material and production expense and an increased quality risk.

Gas sensor for measuring a gas component in a gas mixture


A piercing nut element having a strength in the range between 700 and 900 MPa which is designed to be pressed into the sheet metal part. The nut element is characterized in that the self-piercing attachment of the nut element into a sheet metal part of higher strength, or into a sheet metal part with a thickness greater than 3.5 mm, the nut element is designed in such a way that the piercing section has a peripheral extending groove below the sheet metal contact surface and in that the piercing section has a piercing edge at its free end face with the piercing edge being spaced from the boundary of the groove adjacent to the piercing section by a peripheral surface having an axial height which corresponds to at least 30% and preferably to at least 50% of the sheet metal thickness, wherein the radial wall thickness of the piercing section in the region of its free end face from the outer side of the piercing section up to the nominal diameter of the thread corresponds to a thickness between 1.2 to 1.8 and preferably 1.5 times the intended sheet metal thickness.

In the field of fastener elements which are attached during the manufacture of sheet metal parts to these by machines and distinguishes between pressing elements, on the one hand, and rivet elements, on the other hand. Pressing elements are characterized in that they are at least not intentionally be deformed on attachment to a sheet metal part but rather the sheet metal part itself is deformed and brought into engagement with features of shape of the pressing element, whereby the pressing element is attached in a manner secure against rotation and press-out at the sheet metal part. For rivet elements the element is intentionally deformed during attachment of the sheet metal part, mainly in order to form a rivet bead, whereby the sheet metal part is trapped between the rivet bead and a flange part in order to achieve a connection here which is also secured against rotation and press-out.
Furthermore, both pressing elements and also rivet elements are known as self-piercing elements. The designation self-piercing is to be understood such that the corresponding element pierces its own hole in the sheet metal part, naturally only when an adequate force is exerted on the self-piercing element, for example by a press or by a robot or by force-actuated tongs which press the self-piercing elements against the sheet metal part and which support the sheet metal part at the side remote from the element on a corresponding die button.
In vehicle construction it was hitherto customary to use self-piercing elements with sheet metal parts which have a strength below about 300 MPa. The self-piercing elements which are then used usually have a in addition strength in the range between 700 and 900 MPa and in exceptional cases of up to about 1250 MPa, which is entirely sufficient in order to pierce a hole in the sheet metal part on attaching the fastener element to the sheet metal part, in particular when the sheet metal part has a thickness of below about 3 mm. Strengths of the elements of up to about 850 MPa apply for example for elements of the class 8 whereas higher strengths apply for elements of the classes 10 and 12 which normally make a heat treatment and/or a specific material selection of the corresponding elements necessary.
With the fastener elements that are used, the material of the fastener element in the raw state normally has a strength of about 380 MPa. This strength is however increased to values in the range between 700 and 900 MPa solely by the cold deformation which is used in order to produce fastener element by cold deformation starting from the bar material.
For some purposes fastener elements are required which have a higher strength than 900 MPa. These are then manufactured from a material which can be hardened by a heat treatment, whereby a higher strength is achieved. However, such heat treatments are undesired in many cases. They represent a different process in comparison to manufacture of fastener elements with cold deformation and are normally not even carried out in the same factory in which the fastener elements are manufactured, whereby a considerable expenditure of time and money is required in order to produce heat treated elements of higher strength.
On the other hand, sheet metals with higher strength are increasingly been used in vehicle construction and partly also heat-treated sheet metal parts which have strength above the normal range of strength of 700 to 900 MPa for fastener elements. Such sheet metal parts of higher strength make it possible, on the one hand, to operate with thinner sheet metals, whereby weight can be saved, but, on the other hand, makes it extremely difficult to operate with self-piercing elements.
Sheet metal parts of higher strength are also required in vehicle construction which have larger thicknesses, since in some positions in the vehicle applications arise in which a thicker sheet metal part or a higher strength sheet metal part can be used to advantage.
Furthermore, interest exists currently in vehicle construction of operating at certain positions with sheet metal parts having a thickness larger than 3.5 mm, with the sheet metal parts then having strengths which lie in the above-named region of 300 MPa. An example for such applications is in the chassis area of trucks.

Self-piercing nut element and componet assembly consisting of the nut element and a sheet metal part


The present disclosure relates to 7-substituted pyrrolo[2,1-f][1,2,4]triazine compounds or pharmaceutically acceptable salts thereof, and preparation methods and uses thereof. These compounds show good PI3K inhibitory activity, can effectively inhibit the activity of PI3K kinase, and has significant enhancement and improvement of pharmacokinetic properties, such as bioavailability, due to the introduction of the 7-position group; furthermore, the compounds of the present disclosure exhibit an unpredictable high selectivity and strong inhibitory activity on PI3Kδ, and thus these compounds can be used for treating diseases related to PI3K pathway, especially for anti-cancer or for the treatment of tumors, leukemias and autoimmune diseases. After further optimizing and screening, the compounds are expected to be developed into a new type of anti-tumor drugs.

PI3K-Akt-mTOR signaling pathway is one of the major pathways that transmits signals from receptor tyrosine kinase and G-protein coupled receptor and plays an important role in a variety of cell functions. Recent studies have found that multiple key node proteins in the PI3K-Akt-mTOR signaling pathway are over activated due to the existence of mutation or amplification of coding genes in a variety of human tumors [Vivancod et al., Nat Rev Cancer 2 (2002), pp. 489-501]. Among them, PI3K, as a bridge molecule connecting extracellular signals and cell response effects, is a key factor that regulates growth, metabolism, and survival of cells, of which over activation is closely related to the occurrence of multiple tumors in humans [Sabbah et al., Curr Med Chem 18 (2011), pp. 5528-5544].
PI3K belongs to intracellular phosphatidylinositol kinase with a phosphatidylinositol kinase activity and a serine/threonine kinase activity. According to different gene series homology, substrate specificity and functions, the PI3K superfamily is mainly divided into three types: type I, type II, and type III [Engelman et al., Nat Rev Genet 7 (2006), pp. 606-619]. Type I PI3K is by far the most widely studied type, this type of PI3K can further be divided into four subtypes: PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ. Type I PI3K is a heterodimer enzyme consisting of a catalytic subunit of 110 kDa and a regulatory subunit of 85 kDa. Due to difference of regulatory subunits and activation mechanisms, these four subtypes can also be classified into two categories: Class IA, Class IB. Wherein PI3Kα, PI3Kβ, and PI3Kδ belong to Class IA and are activated by receptor tyrosine kinase (RTKs); while PI3Kγ belongs to Class IB and is activated by G-protein coupled receptor. The 3-position of phosphatidylinositol-4,5-phosphate (PIP2) can be phosphorylated by type I PI3K, forming phosphatidylinositol-3,4,5-phosphate (PIP3). As an important second messenger, PIP3 can bind and activate various intracellular target proteins (such as AKT and PDK1) to form a signal cascade complex and ultimately regulate the proliferation, differentiation, survival and migration of cells. The kinase domain of Type II or type III PI3K has a high homology to that of type I PI3K, and Type II and type III PI3Ks have similar phosphorylation functions as type I PI3K. However, the physiological functions of Type II or type III PI3K is poorly understood. Type II PI3K functions as a monomer without regulatory subunit and is divided into three subtypes: PI3KC2α, PI3KC2β, and PI3KC2γ, which is mainly involved in the transporting of intracellular materials, the cell survival and the internalization process of membrane receptor proteins. Type III PI3K, which consists of only one subtype, Vps34 (vacuole protein sorting defective 34), has been widely known for its endocytosis and transport function of Golgi vesicles [Backer, Biochem J 410 (2008), pp. 1-17]. Recent studies have shown that Vps34 plays an important role in the process of cell autophagy [Ma et al., Cell Res 24 (2014), pp. 912-924].
At present, there are dozens of PI3K inhibitors in clinical trials, which can be roughly divided into three categories: non-selective PI3K inhibitors, type I PI3K selective inhibitors and subtype selective type I PI3K inhibitors. From the analysis of existing clinical data, although the non-selective PI3K inhibitors were the earliest candidates which entered into clinical trial, they proceeded slowly due to dose-limiting toxicity. While subtype selective PI3K inhibitors proceeded quickly in clinic trial, especially PI3Kδ inhibitors. The first PI3K inhibitor on the market, Idelalisib, is a PI3Kδ selective inhibitor, and another γ/δ selective inhibitor, Duvelisib, is already in phase III clinical trials [Winkler et al., Chem Biol 20 (2013), pp. 1362-1372]. Among the catalytic subunits of the Class IA, the catalytic subunit p110δ of PI3Kδ, being different from the P110α and P110β which are widely expressed in various tissues throughout the body, is mainly high expressed selectively in the immune system, such as B cells, T cells, etc., closely related to the diseases of hematological malignancy and inflammation, immunity and the like [Fruman et al., N Engl J Med 370 (2014), pp. 1061-1062]. Idelalisib has been approved by the US FDA as a drug for the treatment of three hematologic tumors of recurrent chronic lymphocytic leukemia (CLL), recurrent follicular B-cell non-Hodgkin's lymphoma (FL), and recurrent small lymphocytic lymphoma. This highlights the significance of PI3Kδ inhibitors in the treatment of hematological malignancies.
Currently, the skeletons of the most inhibitors against PI3Kδ are focus on the core scaffold of Idelalisib, for example, US20140121224A1. In contrast, the toxicity of compounds with triazine as the core scaffold was significantly lower than that of Idelalisib based on the available data. Another type core scaffold that has been more studied is thienopyrimidine, whose representative compound is PI3K pan-inhibitor GDC-0941 [Folkes et al., J Med Chem 51 (2008), pp. 5522-5532]. Although thienopyrimidine compounds have been reported as selective PI3K δ inhibitors[Murray et al., J Med Chem 55 (2012), pp. 7866-7695], the core scaffolds thereof are very different from that of pyrrolotriazine in properties. At present, only a few cases of PI3K inhibitors based on pyrrolotriazine as the parent nucleus have been reported, such as those disclosed in CN102675323A, and there have been no reports about the inhibitory activity of PI3Kδ so far.

7-site substituted pyrrole triazine compounds or pharmaceutically acceptable salts thereof, and preparation method thereof and uses thereof

SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES


A method for discovering proteins and protein geometries, and a method for conducting whole proteome assays on a single test surface are disclosed. A test surface is provided featuring a surface containing a random distribution of randomly shaped features of a size from 10xe2x88x9210 meters to 10xe2x88x928 meters in width, height, depth, and spacing. A sample containing proteins is provided to interact with the test surface long enough for protein molecules to locate and adsorb to complementary sites on the test surface. Unadsorbed proteins are washed away. Protein adsorption sites are then discovered using a means such as an atomic force microscope (AFM) to identify locations where proteins are adsorbed to the surface. The topology of the protein adsorption sites is precisely measured using an AFM. Protein surface topology is deduced by determining the complementary surface to the protein adsorption sites. A device that is diagnostic for a disease is prepared by determining the disease-specific adsorption site pattern on a given test surface, in contrast to the non-disease pattern.

The present invention relates generally to the field of sensors for the detection and investigation of proteins, pathogens and other biologically important molecules, and more particularly to a bionanotechnology method for rapidly determining the surface topology of protein molecules.
Determining the surface topology of proteins is vitally important to broad fields of science including pharmaceutical research and genomics, as well as fundamental research into biological processes. Surface topology determines how proteins interact with each other, since proteins of complementary shape tend to bind together while proteins of non-complementary shapes do not. This lock-and-key binding of proteins provides the mechanisms by which enzymes, antibodies and nucleic molecules accomplish their vital biological functions, as well as the mechanisms that enable viruses and bacteria to infect cells. Knowing the shape and surface characteristics of a protein can help explain its function in a cell. Also, knowing the surface topology of a protein permits the development of drugs and sensors that will bind with that particular protein, enabling more effective medications and diagnostic tests for the treatment of human diseases.
Understanding the surface topology of biologically significant proteins is an important step towards the development of new medicines and medical treatments. Once the shape and chemical structure of a protein is known, pharmaceutical researchers can design a complementary molecule that will fit into the surface folds of the protein and bind to it just as an antibody binds to an antigen. Then pharmaceutically active molecules can be attached to the binding molecule to deliver a specific medication to a particular cell, bacterium or virus.
Understanding the surface topology of proteins is also essential to the development of sensitive diagnostic and protein assay methods. With the rapid advances of biotechnology and genetic research, which are elucidating the key roles and the presence of particular proteins that can be characteristic of certain disease states, great emphasis has been placed on developing very sensitive assays and sensor methods capable of detecting minute quantities of biologically significant molecules. The detection and quantification of specific proteins associated with a given disease, such as a given cancer, may enable much earlier detection and treatment. Furthermore, the ability to detect nucleic acid sequences encoding particular proteins enables many beneficial medical and commercial applications, including agricultural product screening and development. However, in many applications, methods used to detect particular proteins still require an understanding of the binding sites and surface topology of the protein.
The primary method used to develop an understanding of protein surface topologies is protein X-ray crystallography. X-ray crystallography makes use of the diffraction of X-rays by protein crystals to determine the precise three-dimensional arrangement of atoms within the protein molecule. Sophisticated analysis software and algorithms permit researchers to translate the diffraction patterns into three-dimensional structural information, and from that to identify the surface topology of the protein.
Before a protein can be studied with X-ray crystallography, the protein must be isolated, purified and crystallized. Because of the molecular complexity of proteins, obtaining suitable crystals for crystallography can be quite difficult, extremely time consuming and labor intensive. In response, a number of methods and equipment designs have been developed for crystallizing proteins (see, for example, U.S. Pat. No. 5,961,934, issued Oct. 5, 1999; U.S. Pat. No. 5,643,540, issued Jul. 1, 1997; U.S. Pat. No. 5,597,457, issued Jan. 28, 1997; U.S. Pat. No. 5,419,278, issued May 30, 1995; and U.S. Pat. No. 5,096,676, issued Mar. 17, 1992, having methods for forming protein crystals suitable for crystallography) and for streamlining the effort required to identify and reproduce appropriate conditions for crystallization of proteins (see, for example, U.S. Pat. No. 5,641,681, issued Jun. 24, 1997, showing a method for obtaining conditions for growth of high quality protein crystals). A number of physical and chemical factors can impact upon protein formation and crystal growth, so that, for example, it has been proposed that protein crystals be produced in a satellite in earth orbit having zero gravity.
Thus, there is a need for a less time consuming and expensive method for determining the surface topology of proteins, to benefit medical and biological research and facilitate the development of new medications.
Furthermore, there is a need for a means to quickly identify potential binding sites on specific proteins. In many pharmaceutical and diagnostic commercial applications, only potential binding sites on the surface of a protein, rather than a detailed model of all atomic coordinates, are of interest. Identifying binding sites by current methods requires sophisticated analyses of the three-dimensional structure of the protein involving complex numerical modeling. Thus, a less expensive and more direct method for determining potential protein-binding sites would be of economic value.
There is also a need for reliable diagnostic devices to diagnose individuals who are infected, for example, by a new or rapidly mutating pathogen, such as human immunodeficiency virus (HIV), influenza virus, or malaria, or other disease states that have evaded simple diagnostic tests, such as certain forms of cancer or pre-cancerous conditions.
In one embodiment, the invention provides a method for discovering protein adsorption sites on a surface, comprising: providing a test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters (one Angstrom) to about 10xe2x88x928 meters (10 nanometers) in width, height, depth and spacing; exposing the test surface to a solution of a substantially purified protein, the solution remaining in contact with the surface sufficiently long to enable protein molecules to adsorb to adsorption sites; removing the solution with unadsorbed protein molecules from the test surface; and identifying the protein adsorption sites by detecting the presence of adsorbed protein molecules, to locate protein molecules adsorbed to the test surface.
A related method further includes removing the protein molecules adsorbed to the test surface, and measuring the surface topology of the identified adsorption site.
In accordance with a related embodiment, the method further comprises analyzing statistically the surface topology of a statistically significant number of identified adsorption sites to determine a most probable adsorption site topology. Measuring the surface topology further comprises using one or more of the group consisting of: a microcantilever, an atomic force microscope, a scanning tunneling microscope, a magnetic resonance force microscope, a thermomechanical atomic force microscope, a multi-tip atomic force microscope, and microparticles coupled to protein molecules adsorbed to the test surface. The method in various embodiments further comprises storing the most probable adsorption site topology in a computer database.
Another related method includes detecting the presence of adsorbed protein molecules using a microcantilever. Yet another related method includes detecting the presence of adsorbed protein molecules using, for example: an atomic force microscope; a scanning tunneling microscope; a magnetic resonance force microscope; a thermomechanical atomic force microscope; is a multi-tip atomic force microscope; or coupling a microparticle to protein molecules adsorbed to the test surface.
Another related method includes using a plurality of different surface coatings deposited on the test surface, each coating having a characteristic resiliency, and further comprising determining which of said surface coatings is deposited on the identified adsorption sites by measuring the resiliency of the deposited surface coatings using an atomic force microscope.
Another related method includes using a plurality of different surface coatings deposited on the test surface, each coating having a characteristic conductivity, and further comprising determining which of the surface coatings is deposited on the identified adsorption sites by measuring the conductivity of the deposited surface coatings using a conducting atomic force microscope.
Another related method includes providing a test surface wherein the features are not randomly distributed, and the features have a width, a height, a depth and a spacing in an identical pattern distributed regularly on the test surface.
In another embodiment, the present invention provides a method for determining a topology of protein binding sites, comprising: providing a test surface having a surface topology having a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; depositing a solution containing substantially a single type of protein molecules on the test surface, and permitting the solution to remain sufficiently long to enable the protein molecules to adsorb to protein binding sites on the test surface; removing unadsorbed proteins from the test surface; using an atomic force microscope for identifying a location of the adsorbed protein molecules on the test surface; and determining the topology that is complementary to the surface topology measurements of the identified adsorption sites. This method can further comprise, prior to depositing a solution of proteins on the test surface, using an atomic force microscope to obtain a plurality of surface topology measurements of the test surface, and recording the surface topology measurements in a computer database. This method can also further comprise analyzing a statistically significant number of the surface topology measurements of the identified adsorption sites, to determine a most probable adsorption site topology and a most probable complementary protein surface topology of the single type of protein.
In another embodiment, the present invention provides a method for determining attachment areas on a surface of a species of a micro-organism, comprising: providing a test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; depositing a sample containing a plurality of units of the micro-organism on the test surface and permitting the sample to remain in contact with the test surface sufficiently long to enable surface proteins on the micro-organism to adsorb to areas on the test surface; removing unadsorbed units of the micro-organism from the test surface; and identifying the location of attachment areas on the test surface by using a microscope by locating micro-organisms adsorbed to the test surface. The method includes an embodiment wherein the units of the micro-organism are selected from the group of virions, bacterial cells and spores.
In another embodiment, the invention provides a method for determining a topology of potential protein binding sites for a surface of an envelope of a pathogen, comprising: disrupting the pathogen, removing soluble components, and solubilizing envelope proteins of the pathogen, to obtain a sample of surface proteins of the pathogen; providing a test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; depositing the sample of surface proteins on the test surface and permitting the sample to remain in contact with the surface sufficiently long to enable proteins to adsorb to features on the test surface; removing unadsorbed proteins from the test surface; and identifying sites on the test surface by detecting the locations of adsorbed pathogen surface proteins, to locate sites on the test surface for adsorption of proteins the pathogen envelope.
In accordance with related embodiments, the method includes: identifying the adsorption sites with an atomic force microscope, to obtain surface topology measurements of the identified adsorption sites; analyzing statistically the surface topology measurements of a statistically significant number of the identified adsorption sites, to determine a most probable adsorption site topology; storing the most probable adsorption site topology in a computer database; determining a complementary topology to the most probable adsorption site topology; or storing the complementary topology in a computer database. In accordance with a related embodiment, the pathogen is a virus or a bacterium. Further, the absorbed surface proteins can be further characterized by eluting from the test surface, for example, wherein eluting protein from the test surface is characterizing the protein molecule by laser desorbing and analyzing a time-of-flight characteristic, for example, wherein analyzing the time-of-flight characteristic comprises obtaining a molecular weight. Obtaining the molecular weight further comprises comparing the molecular weight to protein sequence data predicted from a sequence of a nucleic acid of the pathogen.
In yet another embodiment, the invention provides a method for rapidly developing a diagnostic device for a disease, comprising: obtaining a first set of biological samples from each of a statistically significant number of individuals having a disease, and a second set of biological samples from each of a statistically significant number of disease-free individuals; providing a test surface having a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; depositing each of first set of the biological samples on the test surface, and permitting each sample to remain sufficiently long to enable proteins from each of the first set to adsorb to adsorption sites; removing unadsorbed proteins from the test surface; identifying adsorption sites on the surface from each of the samples of the first set by detecting the presence of an adsorbed protein, to locate proteins adsorbed to the test surface; repeating the method for each of the samples from each of the second set; and identifying a pattern of protein adsorption sites that is different in samples of the first set having the disease compared to samples of the second set lacking the disease.
Accordingly, the disease can be a type of cancer or a precancerous condition; further, the disease can be infection by a human immunodeficiency virus. In related embodiments, the invention provides a diagnostic device having a protein adsorption pattern discovered by any of these methods, for example, a diagnostic device replicating a surface topology of a protein adsorption site, using test surface topology measurements obtained by such a method. Further, related embodiments include a composition which is a protein associated with a disease, the protein being identified using any of the related embodiments of the methods.
In yet another embodiment, the invention provides a method for determining potential molecular attachment areas on a surface of a pathogen comprising: providing a test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; depositing a solution containing a preparation of units of the pathogen on said test surface and permitting said solution to remain sufficiently long to enable surface proteins on the pathogen to adsorb to adsorption sites on the test surface; removing unadsorbed pathogen from the test surface; and identifying adsorption sites on said test surface by using a microscope to locate units of the pathogen adsorbed to said test surface. For example, the units of the pathogen are virions or bacteria.
In yet another embodiment, the invention provides a diagnostic device, comprising: a test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing; a pattern of protein adsorption sites of known specificity on the test surface; and a reader capable of detecting proteins adsorbed to the pattern protein adsorption sites of known specificity. A related embodiment is provided, further comprising a fluidics cell, the fluidics cell having a fluid inlet, a fluid outlet, and a wall structure coupled to the test surface. For example, the fluid inlet and the fluid outlet are micropipettes coupled to the wall structure.
In yet another embodiment, the invention provides a protein assay apparatus, comprising: an atomic force microscope, the atomic force microscope having a multi-tip microcantilever array sensor; a positioning table coupled to the atomic force microscope and configured to position a sample for inspection by the multi-tip microcantilever array; and a test surface coupled to the positioning table, the test surface having a surface topology comprised of a random distribution of randomly shaped features of a size from about 10xe2x88x9210 meters to about 10xe2x88x928 meters in width, height, depth and spacing. In accordance with related embodiments, the protein assay apparatus further comprise a fluidics cell, the fluidics cell having a fluid inlet, a fluid outlet, and a wall structure coupled to the test surface. The fluid inlet and the fluid outlet can be micropipettes coupled to the wall structure; the positioning table can be a turntable, for example, the turntable is a miniature computer drive platform. The protein assay apparatus can further comprise a fluidics cell coupled to the test surface, the fluidics cell having a fluid inlet and a fluid outlet and comprising a wall structure coupled to the test surface.

Rapid method for determining potential binding sites of a protein


The invention relates to a punch rivet for connecting two workpieces. The rivet includes a head and a hollow shank having a shank internal diameter (D3), a shank external diameter (D1) and a shank end face. Located at the shank end face is an annular cutting edge with a diameter (D4) that is smaller than the shank external diameter (D1). The shank internal diameter (D3) merges with the annular cutting edge via a cutting edge radius (R2); and the ratio of the cutting edge radius to the shank external diameter R2/D1 is greater than 0.3.

The present invention relates to a punch rivet for connecting two workpieces, with a head and a shank, the shank being embodied as a hollow shank having a shank internal diameter, a shank external diameter and a shank end face, there being embodied at the shank end face an annular cutting edge, the diameter of which is smaller than the shank external diameter, and the shank internal diameter merging with the annular cutting edge via a cutting edge radius.
A punch rivet of this type is known from document DE 10 2005 052 360 B4.
The invention further relates to a method for producing a punch rivet connection of at least two workpieces, of which one is made, in particular, of a high-strength material having a strength of at least 800 MPa and has, in particular, a thickness of at least 0.5 mm. The present invention further relates to a workpiece arrangement made up of at least two workpieces which are connected by means of at least one punch rivet of this type or by means of a punch riveting method of this type.
Punch riveting is a reshaping joining method and can be carried out by means of what are known as solid rivets and what are known as semitubular rivets. The present case relates to punch riveting with a semitubular rivet which is embodied with a hollow shank. This method is characterized in that the semitubular rivet is driven into an arrangement of two workpieces (in particular two metal sheets), the top workpiece being punched through (pierced) by the hollow shank. A die plate on which the bottom workpiece rests is designed in such a way that the hollow shank is subsequently radially spread and is driven radially into the lower workpiece, thus forming an undercut. In this case, the lower workpiece is generally not severed, so that the side of the lower workpiece that faces the die plate remains closed and accordingly has low susceptibility to rusting. This punch riveting method with a semitubular rivet has for years increasingly been used in the automotive industry. The punch riveting method is suitable, in particular, for connecting workpieces made of different material (for example steel and aluminium). As, in particular in body construction, there is a trend toward a combination of different materials adapted to the respective purpose of application, the punch riveting method is for this case a joining method which is preferable over welding methods.
It will in this case be understood that at least the material of the lower, die plate-side workpiece should be readily cold formable and have material properties which are as homogeneous as possible.
As, in the above-described field of application, there is a trend toward high-strength materials (for example materials of the upper, swage-side workpiece of greater than 1,000 MPa), the punch rivets used for this purpose have to have a correspondingly higher strength (rivet hardness), in particular in order to be able to punch through a workpiece of this type made of a high-strength material. At the same time, the punch rivet should be sufficiently deformable in its shank region to ensure a sufficient undercut in the finished punch rivet connection.
In the field of semitubular rivets there are various types, for example what is known as the C rivet such as is known from document WO 95/09307. The semitubular rivet described therein has a cylindrical hollow shank, a sharp annular cutting edge being formed at the outer edge of the end face of the shank. For this purpose, the internal diameter merges with the shank external diameter via a cutting edge radius. However, this C rivet is less suitable for the punch riveting of high-strength materials, as the C rivet has a tendency to spread intensively during the punch riveting process, so that only little material is present in the undercut region of the lower workpiece. The strength which may be achieved is accordingly relatively low. A modified C rivet with a sharp annular cutting edge, which is however set apart from the shank external diameter, is known from document DE 203 19 610 U1.
Furthermore, what is known as a P rivet is known in the art, for example from document DE 10 2005 052 360 B4.
In this punch rivet there is formed at the shank end face an annular cutting edge, the diameter of which is smaller than the shank external diameter. The annular cutting edge is embodied as a planar annular surface which is oriented in the radial direction, merges with the shank external diameter via a shank outer chamfer and is thus set apart from the shank external diameter. The shank internal diameter merges with this annular surface via a relatively small radius.
Although the P rivet has better properties than the C rivet in the punch riveting of high-strength materials, there is nevertheless still a need for improvement even over the P rivet in this regard.

Punch rivet, method for producing a punch rivet connection, and workpiece arrangement


A drain strainer includes a base body defining a chamber with opposite water inlet and water outlet, a straining unit disposed in the chamber, and a cover unit including a cover body connected to the straining unit. The straining unit includes a bottom straining member having a plurality of bottom straining holes, and a main straining member disposed on one side of the bottom straining member and including a main straining surrounding wall formed with a plurality of spaced-apart main straining holes. The bottom and main straining holes communicate with each other and with the chamber.

An existing strainer generally includes a seat body connected to a drain pipe, and a drain cover covering the seat body and provided with a plurality of through holes for filtering hair and other foreign objects when water flows therethrough so as to prevent the same from being discharged into the drain pipe which can cause blockage or clogging.
However, the existing strainer is usually made of stainless steel, which is different from the stone, tile or other floor materials often used in interior design, and thus affects the integrity and consistency of the interior design appearance. Further, the filtered hair and other foreign objects are exposed on the drain cover, thereby making the environment appears more dirty. Additionally, water will accumulate on top of the drain cover because it is covered with the filtered hair and other foreign objects, so that there is need to frequently clean the existing strainer.
For the existing strainer to operate smoothly, the through holes in the drain cover are usually made large. However, the hair and the smaller foreign objects can flow along with the water into the drain pipe, thereby clogging the drain pipe. Further, when removing the hair, because a portion of the hair will flow along with the water to the bottom of the drain cover, and the remaining portion thereof will be left on the drain cover, the hair are easily entangled or stuck in the through holes, thereby causing inconvenience during cleaning of the existing strainer.
Currently, a commercially available strainer for a wash basin is provided with an openable water storage cover disposed above a drain hole of the wash basin to provide a water storage function. When it is necessary to store water, the water storage cover is closed; and, when it is necessary to allow flow of the water, the water storage cover is opened, and the water will flow through a gap between the water storage cover and the wash basin. However, this kind of strainer for the wash basin almost has no filtering function, so that it is easy to cause clogging. Generally, the wash basin in an outdoor or public place rarely use the water storage function, so that the commercially available strainer for the wash basin does not meet the requirements of the outdoor or public place.
A drainage head, as disclosed in Taiwanese Patent No. M479329U, includes a seat body, a drain plate disposed on the seat body, and a drain cover connected to and covering a large portion of the drain plate. When water passes through the drainage head, hair and other foreign objects will be filtered and accumulated between the drain plate and the drain cover, and are covered by the drain cover, so that a clean appearance can be maintained. Further, a top surface of the drain cover may be made of a marble or ceramic tile which can improve the overall appearance. However, the drainage head cannot solve the problem of easy clogging of the drain pipe, so it still has room for improvement.


A method and an apparatus for recommending information to users within a social network. The method builds a recommendation list with at least one two-tuple, where each two-tuple comprises a target user name and an information item and ranks the recommendation list by using two-tuples in the recommendation list as a basic unit. By selecting a two-tuple in the recommendation list, the user can recommend a corresponding information item to a user represented by a target user name. An apparatus is also provided by using a builder for building for a user a recommendation list comprising at least one two-tuple and a sorter for ranking the recommendation list by using two-tuples in the recommendation list as a basic unit, such that, by selecting a two-tuple in the recommendation list.

With the evolution of computer technology, communications technology, and various other multimedia transmission technologies, manners of providing information become increasingly diverse. Therefore, an information provider (such as an advertiser, a news provider, a manufacturer, etc) starts providing information to potential recipients in various manners, for example, publishing information to the public via a computer network, television network, a broadcast network, etc.; sending emails, MMS (Multi-media Message Service), and SMS (Short Message Service) to a particular recipient; and offering phone promotion directly via a fixed phone or a mobile phone. Common recipients start focusing on how to manage various information which they have received and recommend useful information to other people who can require such information.
For common recipients of information, they generally recommend information to other people manually. For example, a user receives an email from other users via the Internet, while this email comprises information about IBM software products. When the user intends to provide information about these new products to other friends, he/she usually needs to select email addresses of other users from the contact list to forward this email to the desired users. If the same user finds a technical article about an IBM hardware product published or forwarded by a certain user in a social website, the user can opt to repost the technical article about the IBM hardware product to different users within the social website, or opt to repost it to all other users.
Accordingly, a user can receive information in various manners, while the user can further recommend information to other users in a manner identical to or different from the manner in which he or she receives the information. Managing the recommended information manually is a time-consuming and complex work, and the user has to consider various aspects of factors: to whom the information is provided, what information to be provided, how to provide the information, whether to initiatively search information of other user's interest based on their preferences, etc. For a user who reads little information every day and has a few friends, manually recommending information can be realistic. However, when the user is within a gigantic social network and faces a considerable amount of information every day, it can become unfeasible to recommend information to other people manually.
In a real world, a user can have multiple aspects of attribute such as age, gender, address, graduate school, occupation, hobbies, etc., which will affect the types of information of the user's interest. The user further intends to provide information to other users in a plurality of manners (such as via the internal message within the website, email, SMS, instant message, MMS, paging service, and even directly using voice telephone).
There is a proposed a solution which can facilitate sharing of particular information from one user to other users (for example, through "group"), in which a user can quickly share some information he/she has accessed to other users in a group where he/she is in. Additionally, the user can participate in a plurality of groups across a plurality of social websites, or intend to recommend information to users in the plurality of groups. Those skilled in the art can know that groups are provided with respect to a particular social website, and the basis for sharing information between users in a group is that these users are registered users of the same social website (for example, a web community or an instant messenger, etc.), so that they can share group services provided by the social website.

Method and apparatus for recommending information to users within a social network

International Business Machines Corporation


A method, computer program product, and computer system for receiving, by a processor, an initiation indication that a test is initiating on a computing device. A logging process is activated to record to a log one or more log messages generated as a result of the test in response to receiving the initiation indication that the test is initiating. A completion indication is received that the test is complete. The logging process is deactivated to stop recording to the log in response to receiving the completion indication that the test is complete. The one or more log messages are associated with the test in response to receiving the completion indication that the test is complete.

Recording events that take place on a computing device may be accomplished by, e.g., using log files. Log files may be a tool used for, e.g., diagnosing problems with one or more components of the computing device, such as applications that may be running on the computing device. When a problem is detected, a person (e.g., system administrator) may attempt to review the log to find the appropriate section where the problem may have occurred so that a solution may be developed.
However, finding the appropriate section of the logs may be arduous and time consuming, especially if the administrator is not familiar with the technical internals of, e.g., the product code, or when multiple tests have been run on the same computing device. As a result, productivity may be lost, since, e.g., the wrong section of the logs may be provided to a development team that is tasked to remedy the problem, and the developers may spend substantial amounts of time finding the correct section of the logs before they can start their analysis.
A technique that may be used to address the cumbersome task of finding the appropriate section of the logs may be to enhance the application being tested to have it dynamically control the location to which log messages are written. However, the technique may have a substantial impact on the application product code. Additionally, the technique may also result in a failure to record all of the appropriate log messages, and may also introduce a divergence from regular product code.

System and method for capturing logging information


The invention is directed to sterilant gas compositions of pentafluorodimethyl ether and ethylene oxide which possess improved environmental properties.

This invention relates to novel compositions comprising ethylene oxide and pentafluorodimethyl ether which possess improved environmental and nonflammability characteristics. These compositions are useful in the gaseous sterilization of heat and/or moisture sensitive materials.
Sterilization with a germicidal agent, such as ethylene oxide gas or ethylene oxide containing gas mixtures, has played an increasingly important role in sterilizing heat or moisture sensitive materials. Rapid growth in the use of sterile, disposable medical devices is just one consequence of gaseous sterilization with agents such as ethylene oxide. Gaseous sterilization of reusable medical and surgical equipment using a nonflammable mixture of ethylene oxide and a carrier gas has also proven to be reliable, cost effective technology for many hospitals.
The basic gaseous sterilization process consists of evacuating the sterilization chamber containing the articles to be sterilized, preconditioning the articles at an optimal relative humidity, generally between 20-70% relative humidity, admitting the sterilizing gas at an appropriate pressure and temperature, maintaining contact between the sterilizing atmosphere and the articles to be sterilized for an appropriate time, and finally discharging and evacuating the chamber to remove the sterilant gas.
Although there are many variations on the basic process, the major factors which have to be controlled in order to effect the sterilization are exposure time, temperature, ethylene oxide pressure or partial pressure, and relative humidity. The following prior art references provide a good description of the standard sterilization processes and apparatus with which the gaseous sterilizing agents of the invention are useful: J. J. Perkins, Principles and Methods of Sterilization 2nd. Ed. 501-530 (1969) and "Ethylene Oxide Gaseous Sterilization For Industrial Applications" Industrial Sterilization International Symposium, 181-208 (1972), U.S. Pat. No. 3,068,064 and U.S. Pat. No. 3,589,861.
By itself, ethylene oxide is an extremely flammable gas. Its flammability range extends from about 3.0% by volume to 100% by volume in air. Thus, when ethylene oxide is used alone as a sterilizing gas, precautions such as explosion proof equipment are mandatory.
A preferable practice is to blend the ethylene oxide with another fluid which serves to dilute the ethylene oxide and render the mixture as a whole, nonflammable. Two such blends which have been used as sterilizing gases are dichlorodifluoromethane (chlorofluorocarbon (CFC)-12)/ethylene oxide and carbon dioxide/ethylene oxide. Inert carrier gases like CFC-12 and carbon dioxide inhibit the flammability of ethylene oxide and provide sufficient autogeneous pressure to deliver the liquid mixture from the source cylinder to the heat exchanger of the sterilizer vessel where the liquid mixture is vaporized.
The CFC-12/ethylene oxide blend is generally supplied as a liquid mixture consisting of 88% by weight CFC-12 and 12% by weight ethylene oxide. This composition is below the critical flammability composition of about 14-15% by weight ethylene oxide in CFC-12, and is therefore nonflammable. A typical hospital sterilization process which utilizes the CFC-12/ethylene oxide blend is performed by evacuating the chamber to about 20-24 inches of mercury vacuum, preconditioning the articles at an optimal relative humidity, and filling the chamber to about 10 psig pressure with the gas mixture. Sterilization is generally performed around 130.degree. F. The 88/12 by weight CFC-12/ethylene oxide mixture produces a gas mixture containing 72.8 volume or mole percent CFC-12 and 27.2 volume or mole percent ethylene oxide. This composition provides about 630 milligrams of ethylene oxide per liter at the stated typical operating condition. The concentration (mg/liter) of ethylene oxide present in the sterilization chamber is critical in determining the required exposure time and ultimate sterilization efficiency. The Association for the Advancement of Medical Instrumentation (AAMI) recommends a minimum ethylene oxide concentration of 400 mg/liter.
The nonflammable carbon dioxide/ethylene oxide blend is also supplied as a liquid mixture consisting of about 90% by weight carbon dioxide and about 10% by weight ethylene oxide. This blend produces a gas mixture containing 90% by volume or mole carbon dioxide and 10% by volume or mole ethylene oxide. The available ethylene oxide concentration (mole percent) is significantly less than that obtained from the 88/12 by weight CFC-12/ethylene oxide blend. Sterilization using carbon dioxide/ethylene oxide is generally performed at a greater pressure than that used with CFC-12/ethylene oxide to increase the concentration of ethylene oxide, or is performed for greater exposure times which decreases productivity.
Although the major purpose of the inert carrier gas component in these sterilizing gas mixtures is to mask the flammability characteristics of ethylene oxide, simple substitution of an arbitrary nonflammable gas does not necessarily ensure a useful sterilizing gas mixture. First, the flammability properties of the blend must be such that sufficient ethylene oxide (mg/liter at a typical pressure and temperature) is delivered by the blend to effect the sterilization in an appropriate time. If the carrier gas does not mask the flammability to a sufficient extent, a lower concentration of ethylene oxide must be used to ensure nonflammability. In such cases, either a longer exposure time is required to perform the sterilization, which affects productivity, or greater operating pressures are required to increase the effective ethylene oxide density in the sterilization chamber. Increasing the operating pressure is generally not a viable option because existing sterilization chambers may not be rated for the increased pressure, and as pointed out by Gunther in U.S. Pat. No. 3,589,861, increased pressure can lead to swelling and rupture of the sealed plastic bags commonly used to package disposable medical devices. Indeed, lower operating pressures are advantageous in this respect. The requirement for a greater operating pressure or increased exposure time has limited the acceptance of the 90/10 carbon dioxide/ethylene oxide mixture in comparison to the 88/12 CFC-12/ethylene oxide mixture.
A candidate inert diluent or carrier gas must also be miscible with ethylene oxide in the liquid phase and must not segregate from the ethylene oxide to any great extent during vaporization. Segregation or fractionation can lead to potentially flammable or explosive situations. The degree of segregation that may occur during evaporation is related to the relative volatility of the components of the mixture. The vapor pressure of ethylene oxide at 70.degree. F. is 22 psia while the vapor pressures of CFC-12 and carbon dioxide at 70.degree. F. are 85 and 850 psia, respectively. The vapor pressure data indicate a very large difference in volatility between carbon dioxide and ethylene oxide and, hence, a susceptibility for carbon dioxide/ethylene oxide blends to fractionate.
Because CFC's like the fully halogenated CFC-12 have been implicated in causing environmental problems such as stratospheric ozone depletion and global warming they are not preferred diluents. The trend in the industry is toward the use of stratospherically safer (i.e. hydrogen containing) materials as the flame suppressing diluent. Hydrochlorofluorocarbon (HCFC)-based diluents such as 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124) and a blend of chlorodifluoromethane (HCFC-22)/HCFC-124 are currently being used. These materials are available from AlliedSignal Inc. of Morristown, N.J. Even though these materials possess significant environmental advantages over perhalogens (lower ozone depletion potentials), because they contain some chlorine they are viewed as temporary solutions with limited lives.
Materials such as the hydrofluorocarbons or HFC's, which contain fluorine, hydrogen and no chlorine, are more acceptable. Examples of these materials are HFC-125 and HFC-227. They have zero or essentially zero ozone depletion potentials and atmospheric lifetimes of substantially less than the CFC's. Other materials that contain fluorine, hydrogen but no chlorine such as ethers are also candidate diluents. Pentafluorodimethyl ether is one such compound. It is essentially non-ozone depleting and has an atmospheric lifetime of about 17 years, which is significantly lower than that of most CFC's (CFC-12/116 year lifetime)

Sterilant gas mixtures of pentafluorodimethyl ether and ethylene oxide


In one embodiment, a calibration apparatus includes a jig body, a camera, an elongated strip which is deflectable and resilient, a lower groove which is disposed in the jig body, and is configured to receive and grasp the camera therein, an upper groove, which is disposed in the jig body above the lower groove, and is configured to receive and grasp the elongated strip therein so as to position the elongated strip above, and in a fixed relation to, the camera, the upper groove being wider than the lower groove, and an alignment element, which is disposed in the jig body, and is configured to align an end of the camera with an end of the elongated strip.

Medical instruments, for example, but not limited to, catheters, probes, and other instruments such as ENT tools, may include miniature cameras for capturing images within the body of a living subject. In order to provide useful data, the image capture equipment often needs to be calibrated after the medical instrument has been assembled prior to initial use.
US Patent Publication 2013/0281821 of Liu, et al., describes a surgical navigation system employs an endoscope and an imaging unit. The endoscope includes an electromagnetic tracker within a working channel of the endoscope for generating electromagnetic sensing signals indicative of one or more poses of the endoscope within an anatomical region, and an endoscopic camera within an imaging channel of the endoscope for generating endoscopic images of the anatomical region. The imaging unit executes an intraoperative calibration of the electromagnetic tracker and the endoscopic camera as a function of an image registration between the preoperative scan image of a calibration site within the anatomical region and one or more endoscopic images of the calibration site within the anatomical region.
U.S. Pat. No. 9,188,973 of Tenney, et al., describes systems and methods that determine a mapping between a first camera system's coordinate system and a second camera system's coordinate system; or determine a transformation between a robot's coordinate system and a camera system's coordinate system, and/or locate, in a robot's coordinate system, a tool extending from an arm of the robot based on the tool location in the camera's coordinate system. The disclosed systems and methods may use transformations derived from coordinates of features found in one or more images. The transformations may be used to interrelate various coordinate systems, facilitating calibration of camera systems, including in robotic systems, such as an image-guided robotic system for hair harvesting and/or implantation.


An apparatus includes a conductive or semiconductive substrate and a dielectric layer located directly thereon. A semiconductor layer is located directly on the dielectric layer. The semiconductor layer includes a ridge waveguide and a heater strip extending parallel to the ridge waveguide. The heater strip is electrically isolated from the ridge waveguide and is doped to carry a current therein about parallel to the ridge waveguide.

Various optical devices rely on interference generated between two optical signals propagating in two optical paths when the optical paths and signals are combined. In some cases the optical path length of one or both of the optical paths may be varied to change the degree of interference between the optical signals. In this way, among other effects, the intensity of the combined signal may be varied.

Thermally controlled semiconductor optical waveguide


Provided is a pick-up hitch assembly for connection to a vehicle. The pick-up hitch assembly includes a swing frame having a first end configured to be coupled to the vehicle and a second end, a slide frame movable relative to the swing frame between a retracted position and an extended position, and an electrically powered actuator assembly configured to be coupled to the vehicle and being coupled to the swing frame at the second end of the swing frame. The actuator assembly is configured to move the swing frame between a raised position and a lowered position independent of movement of the slide frame and of a three-point hitch.

A tractor or utility vehicle used for agricultural work may be used for transport tasks and for carrying out tasks in the field. The tractor or utility vehicle can be coupled to an implement that has electoral couplers, hydraulic couplers, and/or a power takeoff that is connected to the tractor couplers and to the tractor power takeoff. Implements attached to a tractor or utility vehicle are generally not utilized full time, and thus a coupling mechanism is provided to allow for convenient connecting and disconnecting of the implement.


A test pattern generating apparatus that generates a test pattern to be communicated with a device under test having a plurality of terminals, the test pattern generating apparatus comprising a primitive generating section that generates a cycle primitive indicating a signal pattern to be communicated with each of the terminals during a base cycle, based on instructions from a user; a device cycle generating section that generates a device cycle indicating signal patterns of a plurality of base cycles, by arranging a plurality of the cycle primitives based on instructions from the user; and a sequence generating section that generates a sequence of the test pattern to be supplied to the device under test, by arranging a plurality of the device cycles based on instructions from the user.

1. Technical Field
The present invention relates to a test pattern generating apparatus, a test program generating apparatus, a generation method, a program, and a test apparatus.
2. Related Art
Conventionally, when testing a device under test with a test apparatus, the user creates a test program corresponding to the test using a programming language for the test apparatus, and this test program is used for testing after being debugged (for example, see Patent Documents 1 and 2).    Patent Document 1: Japanese Patent Application Publication No. 2006-323706    Patent Document 2: Japanese Patent Application Publication No. H11-118889
However, in order to create a test pattern, particularly one for communicating with a device under test, for this test program, the user must have programming experience and knowledge of programming languages for the test apparatus and hardware specifications of the test apparatus, and therefore it is difficult to create the test pattern easily.

Test pattern generation apparatus, test program generation apparatus, generation method, program, and test apparatus


A crossover tool that resists the erosive forces of high velocity slurry streams of gravel in downhole fracturing and gravel packing operations employs hardened inserts that protect the inside face of the housing as well as the openings through the crossover housing wall. The inserts have an extending portion that goes through housing openings preferably to the outer surface of the housing. The inserts also have inboard flanged surfaces that preferably abut or overlap to give preferably full inner wall protection to the housing from the flow of abrasive slurry. The inserts can be secured to each other or to the interior of the housing to hold them firmly in place.

Certain completions use screens and fill the annular space around the screens with particles known as proppant as an aid to controlling production of sand or other particulates from the formation and fracturing the formation. The proppant is prepared at the surface as a slurry and pumped downhole into a bottom hole assembly that extends through an isolation packer to the zone of interest. The bottom hole assembly has a series of screens. Inside the screens is a tool called a crossover that allows the slurry pumped down from the surface to get through the packer and then exit into an annular space below the packer and outside the screens. The gravel remains in the annular space outside the screens and the carrier fluid for the slurry enters a wash pipe inside the screen and goes into different porting in the crossover tool to get to the upper annulus above the set packer for the return trip back to the surface.
While proppant slurry is abrasive, its erosive effects are also directly related to its velocity which is also related to the pumped pressure. When delivery rates were lower, such as with gravel packing at lower flow rates and pressures, the erosion problem was present but manageable. More recently, the need for higher delivery rates and higher operating pressures such as when proppant delivery was also combined with formation fracturing has made the erosion problem more acute. The evolution to higher flow rates and operating pressures has also caused erosion to an outer tubular that extended around the crossover exit ports and which supported the screens below. The slurry had to impact this tubular before making an exit to the annular space around the screens. To protect this outer tubular from direct impingement from the high flow and high pressure slurry, abrasive resistant liners were placed inside made of a hardened material to extend the operating life of the assembly.
One response to the erosion problem, which is generally more severe at the location where the slurry is forced to change direction, has been to use inserts that are hardened and which are positioned literally in the ports where the slurry has to exit. This design is shown in U.S. Pat. No. 6,491,097 FIGS. 4A-4E. This approach was offered as an alternative to an earlier design that used a hardened ported sleeve inside the crossover with the sleeve ports aligned with ports in the crossover housing but having a smaller periphery so as to protect the edges of the crossover body ports from erosion by flowing slurry. This design is shown in U.S. Pat. No. 5,636,691. Other downhole valve designs have used inserts in ported sleeves that are shifted into and out of alignment with ports in a surrounding housing. One such design is shown in FIG. 4 of U.S. Pat. No. 6,973,974. Other designs of crossovers have attempted to reduce erosion after the exiting flow goes through the crossover ports and into an annulus defined by an outer tubular by reducing the energy of the flowing stream in that annular space by placing a hardened rotating member that is turned by the slurry stream as shown in U.S. Pat. No. 7,096,946. Protective sleeves at an inlet to a crossover have been used as shown in U.S. Pat. No. 5,597,040.
One of the issues with using an internal hardened sleeve is that it left the actual ports in the crossover housing unprotected in the portion of those ports that extended through the crossover wall. While an internal sleeve protected the crossover housing port interior edge at the inside housing wall, once the slurry got into the housing wall, the peripheral surface of the port through the wall and at the outer surface of the housing wall was left unprotected and suffered from erosion. That early design shown in U.S. Pat. No. 5,636,691 had these issues. The later design that put the inserts into the wall such as U.S. Pat. No. 6,491,097 protected the inside of the housing wall as the slurry passed through it but it had other disadvantages. The older internal sleeve design protected the inside surface of the crossover housing and going to just inserts in the ports through the wall of the crossover housing left the entire inside surface of the crossover housing exposed to erosive flow. Not only that but since the inserts were at most just flush with the internal housing wall at the housing ports and the interior housing wall was exposed, it left open an erosion path to start by removal of the interior housing wall around the periphery of the insert that was only in the wall. This opens a possibility of starting a bypass stream on the outside of the wall insert as the surrounding wall was eroded away. In severe cases the housing port could be enlarged enough to undermine the support for the insert.
The present invention seeks to overcome these shortcomings of the prior design by allowing an insert assembly to be employed that protects the passage through the housing wall where the slurry exits through ports and also affords interior wall protection to the housing inside wall and inside edges of the wall ports in the housing. A series of erosion resistant inserts are inserted into wall openings. The inserts include a segment that extends through the wall opening and an interior flange that straddles the wall opening on the inside surface and in the preferred embodiment covers the inside wall from erosive effects. The inserts can be configured to keep each other in position or they can be secured to the housing or to each other. Edges of the inserts can be made to overlap inside the crossover housing to hold them in place or to better secure the interior housing wall from erosion from slurry that might otherwise work a path to the inside housing wall between abutting inserts. These and other features of the present invention will become more clear to those skilled in the art from a review of the discussion of the preferred embodiment and the associated drawings while recognizing that the full scope of the invention is determined from the associated claims.

Crossover sub with erosion resistant inserts


Embodiments disclosed herein relate to methods, systems, and computer programs for automatically determining an outcome associated with a reasoning graph, based on one or more data sets. The methods, systems, and computer programs compare hash values associated with different data sets to determine if they match to assign the outcome associated with a pre-existing hash to the later provided hash and data set associated therewith.

Data is referenced and used by computer programs. Data may be used or incorporated in any number of formats. Data is typically incorporated into an executable program and used by the program as necessary. For example, the data can be queried by one or more functions to provide answers or determinations.
Some queries examine relative amounts of data, a type of data, a state or status indicated by the data, or some other variable relative to some standard or threshold. Such queries may include functions that are performed utilizing the data.
When large amounts of data are processed, the computing power of a computing system may be a limiting factor in the speed at which the data is processed.


A tire comprises at least first and second working plies (16, 18) respectively comprising first and second reinforcing elements (50, 52) in which at least one of the following relationships is satisfied:−4053×E1+4720≤(D14×d1×1000)/E1  (I)−4053×E2+4720≤(D24×d2×1000)/E2  (II)where D1, D2 are the diameter of each reinforcing element (50, 52) made up of a metallic monofilament (66, 68), and D1 and/or D2 ranges from 0.34 to 0.38 mm, d1, d2 are the density of the reinforcing elements (50, 52), expressed in monofilaments per decimetre, and E1, E2 are the mean thickness of the working ply (16, 18), expressed in mm.

The invention relates to a tyre comprising an improved crown reinforcement. A tyre is understood to mean a structure of substantially toroidal shape. For preference, the invention relates to a pneumatic tyre. A pneumatic tyre is understood to mean a tyre intended to form a cavity in collaboration with a support element, for example a rim, this cavity being able to be pressurized to a pressure higher than atmospheric pressure. In contrast, a non-pneumatic tyre is not able to be pressurized.
The invention relates to the field of tyres intended to be fitted to rolling vehicles. The tyre is preferably designed for passenger vehicles but can be used on any other type of vehicle, such as two-wheeled vehicles, heavy-duty vehicles, agricultural vehicles, construction plant vehicles or aircraft or, more generally, on any rolling device.
A first prior art described in WO2013117476 is known. WO2013117476 describes a radial pneumatic tyre comprising a crown reinforcement comprising a working reinforcement comprising first and second working plies. Each working ply respectively comprises first and second reinforcing elements arranged substantially parallel to one another in each first and second working ply and respectively embedded in first and second elastomeric matrices. Each first and second reinforcing element is made up of a metallic monofilament of a diameter equal to 0.30 mm. In each first and second working ply, the density of the reinforcing elements, measured in a direction perpendicular to the main axis of the metallic monofilaments, is equal to 160 monofilaments per decimetre. The mean thicknesses, measured in the radial direction, of each first and second working ply are equal to 0.75 mm. Because of the significant thickness of each first and second working ply, the tyre described in WO2013117476 has a relatively high resistance to buckling. Because of this relatively great thickness, the mass, the hysteresis of the crown reinforcement and therefore the rolling resistance of the tyre leave room for improvement.
A second prior art described in WO2012175305 is known. WO2012175305 describes a pneumatic tyre having a crown reinforcement similar to that of WO2013117476 and in which the diameter of the metallic monofilaments is likewise equal to 0.30 mm. In contrast with the first prior art described in WO2013117476, the density of the reinforcing elements, measured in a direction perpendicular to the main axis of the metallic monofilaments, in WO2012175305 is far lower and equal to 110 monofilaments per decimetre and the mean thicknesses, measured in the radial direction, of each first and second working ply are equal to 0.48 mm. Such a pneumatic tyre was marketed by the company BARUM in 2015. Nevertheless, such a pneumatic tyre, because of its small thickness, has mediocre resistance to buckling. Furthermore, because of the low density of the reinforcing elements, the mechanical strength of the crown reinforcement is relatively low.
It is an object of the invention to propose a tyre that offers, on the one hand, better resistance to buckling than the second prior art and, on the other hand, a better compromise between the resistance to buckling and the mass of the or each ply than the first and second prior arts.

COMPAGNIE GENERALE DES ETABLISSEMENTS MICHELIN


Techniques describe preventing sensitive data from being misappropriated during an operation performed by a cloud synchronization application. A request from a cloud sync application to upload a file to a cloud storage service is intercepted. The file is currently stored on a client computer of an enterprise network. An account associated with the request is identified. The file is evaluated based on a data loss prevention policy and the account associated with the request. The request is blocked based on the evaluation.

Field
Embodiments presented herein generally relate to data loss prevention (DLP) in a computer system, and more specifically, to techniques for providing DLP in cloud synchronization applications.
Description of the Related Art
Data loss prevention (DLP) refers to a variety of techniques for protecting sensitive data. In endpoint DLP, a DLP agent can monitor and control activity occurring within a client computing system according to a policy, usually specified by an administrator (e.g., of an enterprise network). The DLP agent can block attempted transmissions of sensitive data and generate incident reports describing such attempts.
One issue that DLP addresses is preventing sensitive data from being leaked by a client computing system to a cloud storage service. Many enterprise networks rely on a cloud storage services (e.g., Box, Dropbox, Google Drive, etc.) to store data. Cloud storage services also facilitate online collaboration on documents. For example, an enterprise network may maintain a list of customer information on a cloud storage service. Users may collaborate to edit the list in real-time. Each user may download the list on a client computer, e.g., through a storage interface on the web, a cloud synchronization ("sync") application, or a cloud storage-integrated productivity application. When a given user modifies the listing, the modifications can be saved to cloud storage via an enterprise account associated with the user on the service, e.g., through a cloud sync application on the client computer, a web interface on a browser, or a productivity application that is integrated with the cloud storage service.
However, using cloud services also risks leaking sensitive data to a user's personal account. Continuing the previous example, it is undesirable if a user saves the listing of customer information to a personal account (instead of the enterprise account) on the cloud storage service.

Technique for data loss prevention for a cloud sync application