A storage system 1 includes a channel interface (IF) unit 11 having an interface with a server 3, a disk IF unit 16 having an interface with a hard disk unit 2 , a memory unit 21 for storing data to be read/written from/to the server 3 or the hard disk unit 2 , a switching unit 51, and the hard disk group 2. The channel IF unit 11, the disk IF unit 16, and the memory unit 21 are connected to each other through the switching unit 51, and an encryption and decryption processing unit 201 is provided between a host IF unit 101 and a transfer controller 103 in the channel IF unit 11.

The present invention relates to a storage system which is capable of executing an encryption (or decryption) process (hereinafter referred to as 'encryption and decryption processes') on data and of executing a high-security (hereinafter referred to simply as 'secure') data communication with a computer (hereinafter referred to as 'a server') or another storage apparatus system (hereinafter referred to as 'a storage system').
Conventionally, fiber channel (hereinafter referred to as 'FC') interfaces have been mainly used as interfaces for effecting data communication between a server and a storage system. However, in recent years, the use of the Ethernet (a registered trademark of Fuji Xerox. Co., Ltd.) enables high-speed data communication at a speed equal to or more than that of a FC at a low cost. In addition, the advent of iSCSI (internet Small Computer System Interface) technology in which data communication by SCSI (Small Computer System Interface) protocol is realized over an IP (Internet Protocol) network makes it possible to construct a storage area network (hereinafter referred to as a 'SAN') with the IP network, such as the Ethernet, which is conventionally realized by using FC connections.
However, an FC network is commonly used in a closed environment, such as within the confinement of a company building, but an IP network is typically used inside or outside an enterprise as a general network, that is, in an open environment. Therefore, there is an increasing possibility that apparatuses connected to the IP network are susceptible to an unauthorized entry or to hostile break-in by a third party. Thus, when connecting a storage system to an IP network, it is becoming more indispensable to take necessary security measures for protection of the storage system.
One of the security measures is to apply a data encrypting technique for securing a data communication over an IP network to a storage system. Currently, IPsec (disclosed in RFC2406), which is prescribed as a standard protocol for a VPN (Virtual Private Network) by the IETF (Internet Engineering Task Force), which is one of the organizations for setting Internet standards, is widely used as a protocol for securing data communications over an IP network.
As shown in FIG. 19, in mounting encryption and decryption processing units in a storage system, encryption and decryption processing units 301 are provided in the front stages of host IFs 101 in channel IF units 12, or they are provided in the host IFs 101 (not shown).

Storage system executing encryption and decryption processing


This invention relates to a probe reagent comprising, in order from the N-terminus to the C-terminus, the amino acid sequences of a fluorescent protein I, a peptide capable of terminating protein degradation (i.e., a degradation-terminating peptide), a spacer peptide, a fluorescent protein II, and a protein to be degraded, wherein the protein to be degraded is a protein degraded by the ubiquitin-proteasome system, and the probe reagent is degraded from the C-terminus, but that the degradation of the probe reagent is terminated at the degradation-terminating peptide, a nucleic acid encoding the probe reagent, and use of the probe reagent or the nucleic acid.

The ubiquitin-proteasome system is well known as a proteolytic pathway possessed by cells. In this reaction system, linear chains comprising several molecules of a small protein called ubiquitin are attached to denatured proteins or abnormally folded proteins. The ubiquitin chains can mark the proteins for degradation, which are in turn recognized and destroyed by proteasome, a proteolytic machine. This system performs the removal of intracellular abnormal proteins. The ubiquitin-proteasome system, however, is not always a system intended only for the quality control of intracellular proteins. The system controls various cell functions by degrading even structurally or functionally normal proteins according to cell states of the moment and thereby suppressing their activities. The ubiquitin-proteasome system has been found so far to control the abundances of many proteins. These proteins have diverse functions, such as control of cell cycle, regulation of gene expression, stress response, and DNA repair. In this way, the ubiquitin-proteasome system controls many life phenomena exhibited by cells and is thus considered essential for the maintenance of normal cell activity. Therefore, the hypofunction of this proteolytic system has a critical impact on cells. The abnormal intracellular accumulation or aggregation of proteins is observed in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. It has been suggested that the onset of these diseases is caused by the abnormal function of the ubiquitin-proteasome system. Since the ubiquitin-proteasome system is also involved in cell cycle, DNA repair, and the like, the disruption of this system is also known to induce the malignant transformation of cells. In this way, the ubiquitin-proteasome system is responsible for the control of many important life phenomena. Thus, the development of an approach of precisely and conveniently measuring this reaction system would make a significant contribution not only to the elucidation of mechanisms underlying life phenomena exhibited by cells but also to the development of therapy or drugs for diseases induced by abnormality therein.
Protein degradation by the intracellular ubiquitin-proteasome system has previously been measured using a biochemical approach such as Western blotting. In this approach, many cells are collectively destroyed, and their components are recovered. Protein analytes contained therein are electrophoretically separated according to molecular weights and further detected by staining using specific antibodies. As a result, the existing levels of the proteins or proteolytic activities on the proteins can be measured. Unfortunately, this approach requires complicated operation and much time and does not permit assay in individual living cells.
In recent years, great development has been brought about in techniques of applying luciferin and luciferase involved in the bioluminescent reaction seen in firefly or the like, or fluorescent proteins obtained from Aequorea victoria or the like, to probe reagents for monitoring intracellular molecular dynamics. Such techniques have been coupled with the advance of microscopic imaging techniques to thereby popularize approaches of spatiotemporally visualizing and measuring a particular physiological activity in cells. This approach has also allowed the proteolytic activity of the proteasome to be measured in living cells. In this approach, a protein analyte is fused with luciferase or a fluorescent protein and used as a probe reagent (Patent Literature 1). When this protein exists in cells, the luminescence or fluorescence which is a label is observed; however, when this protein is degraded by proteasome, the fused luciferase or fluorescent protein is degraded together with the protein, resulting in no observable luminescence or fluorescence. Thus, change in the intensity of this light can be monitored in order to measure a proteolytic activity on this protein. The degradation of proteins such as IκBα, p27, p53, or HIF-1α has been measured so far by this approach (Patent Literature 2 and Non Patent Literatures 1 to 3). Since one type of label, such as luciferase or a fluorescent protein, is used in these probe reagents, the analyte is measured at only one wavelength of luminescence or fluorescence. Therefore, the intensity of the light is influenced by factors independent of proteolytic activity, such as the nonuniform distribution or expression level of the probe reagent, cell or tissue morphology, quenching caused by fading or the like, or nonuniform illumination with excitation light, thereby causing difficulties in quantitative measurements. In addition, when light quantity is decreased by increase of proteolytic activity, the insufficient sensitivity of a detector or a reduced S/N ratio is disadvantageously caused, thereby making precise measurements difficult.
The undesired influence of protein degradation-independent factors in the photometric method using only one wavelength can be canceled by measuring luminescence or fluorescence at two wavelengths and determining the ratio of intensities. In the approach of Davis et al., a protein analyte IκBα fused to click beetle-derived luciferase (CBG68) exhibiting green luminescence was expressed in cells. At the same time, click beetle-derived luciferase (CBR) exhibiting red luminescence was also expressed in these cells. CBG68 exhibits increase or decrease in the amount of its luminescence depending on proteasomal degradation activities on IκBα. On the other hand, the luminescence of CBR is insusceptible to proteasomal degradation and, as such, was used as a control. Davis et al. measured luminescence in a cell group cultured in a multi-well plate, and measured an IκBα-proteolytic activity as a green/red ratio of luminescence intensities in order to correct the difference in the amount of luminescence derived from, for example, different numbers of cells among wells (Non Patent Literature 4). This approach improves quantitative performance compared with the 1-wavelength photometric method, but disadvantageously, can hardly equalize the expression level ratio between two probe molecules, i.e., luminescence intensity ratio, among cells because these two probe molecules are individually expressed. In addition, the luciferase or fluorescent protein used as a label might be nonuniformly distributed in cells, depending on its properties, and thus differ in its localization among the cells. These are responsible for the degraded accuracy of proteolytic activity assay particularly at a single-cell level.

Probe reagent for measurement of proteolytic activity


An electrical connector includes a frame which supports contact modules which are equipped with connections for a corresponding number of conductors of a multi-wire cable. The contact modules and corresponding female modules can be freely combined in their selection and arrangement and can be latched together to form compact module blocks.

1. Field of the Invention
The present invention relates generally to the field of electrical connectors and more particularly to modular multi-pole connectors in which male and female contact inserts are latched into respective retaining frames to form contact insert blocks.
2. Prior Art
Electrical plug connectors of modular construction are known from EP 0 523 491 A1 as well as from various catalogs or product documents. One published product catalog November, 1992 Elektrische Bauteile (Electrical Components) from the company 2E Rolf Hiller describes a modular plug system as a board plug connector based on DIN 41612 whose modules, which can be inserted into a retaining frame, are designed as male and female strips and can be fitted with contacts of different shapes, by latching in, for the respective application. This system has no plug housing and in the male strip, which is designed as a male part, can be regarded more as a separable board connection than as an industrial plug. Depending on the fitting, the modules can be mounted on a printed circuit board, maintaining a basic grid. A retaining frame is used for mounting, and is provided on the board side as a collecting and alignment frame. The modules which are inserted into this retaining frame are available only as plug-in, crimped or soldered versions. Universal use by means of clamping or screw-clamping connection for wires and braids and PE contact-making integrated in the modular system are not provided.
The catalogs published by CONTACT Connectors 950331 EPIC Baureihe MC (EPIC MC series), Concept--Das modulare Steckverbindersystem (Concept--The modular plug connector system), INNOVATION, Title page plug connectors, Weidmuller, Amphenol C 146 Modular Catalog, euro publishing February, 1994 likewise describe modular plug connections of a common system which can be inserted and latched into a frame. In the case of this system, the individual modules are guided via side guide ribs and corresponding grooves running in the insertion direction in the retaining frame, and are attached to the latter via latching hooks. The modules are very robust and thus of a voluminous design, which leads to a considerable increase in the size of the contact grid. For bonding between the male part and the female part, early-make PE metal contacts are provided at the sides on the frame and outside the module arrangement on the narrow side of the plug connector, and these require additional installation space to allow the contact connection to spring out at the sides. In the case of plug connections which do not require bonding, this is at the expense of the number of contacts per plug connector. To this end, the fitting/base housings and the sleeve housings have been matched, in a robust configuration, to the particular requirements of rugged use and, as a rule, are made of metal. The shape of the housings in this case is matched to a mechanical hinged interlock system that is provided, and this requires additional installation space for the entire electrical plug connector.

Electrical multi-pole plug-and-socket-type connector with associated socket part


A first impurity region is formed by ion implantation of a first impurity into a first main surface of a silicon carbide substrate. A metal layer is formed in contact with the first impurity region. By annealing the silicon carbide substrate and the metal layer, an electrode is formed. The metal layer is formed such that a concentration of a first impurity at a boundary portion between the metal layer and the first impurity region becomes less than a maximum value of a concentration of the first impurity in the first impurity region. The electrode is formed such that a concentration of the first impurity at a boundary portion between the electrode and the first impurity region becomes not less than 80% of a maximum value of a concentration of the first impurity in the first impurity region in a normal direction.

1. Field of the Invention
The present invention relates to a silicon carbide semiconductor device and a method of manufacturing the silicon carbide semiconductor device, in particular, a silicon carbide semiconductor device including a silicon carbide substrate having an impurity region formed therein and a method of manufacturing such a silicon carbide semiconductor device.
2. Description of the Background Art
In recent years, in order to achieve high breakdown voltage, low loss, and utilization of semiconductor devices under a high temperature environment, silicon carbide has begun to be adopted as a material for a semiconductor device. Silicon carbide is a wide band gap semiconductor having a band gap larger than that of silicon, which has been conventionally widely used as a material for semiconductor devices. Hence, by adopting silicon carbide as a material for a semiconductor device, the semiconductor device can have a high breakdown voltage, a reduced on-resistance, and the like. Further, the semiconductor device thus adopting silicon carbide as its material has characteristics less deteriorated even under a high temperature environment than those of a semiconductor device adopting silicon as its material, advantageously.
For example, Japanese Patent Laying-Open No. 8-8210 describes a method of manufacturing a silicon carbide semiconductor element including an electrode making ohmic contact with a silicon carbide substrate. According to the method of manufacturing the silicon carbide semiconductor element, ions are implanted into a surface of the silicon carbide substrate, and then the surface layer is thermally oxidized from the surface up to a depth at which the concentration of the ion species thus implanted has a peak value. An oxide layer, which is formed by the thermal oxidation, is removed and then a metal electrode is formed on the exposed surface. In this way, an electrode having a low contact resistance can be allegedly formed on the surface of the silicon carbide substrate.

Silicon carbide semiconductor device and method of manufacturing same


A constant current driving circuit capable of performing constant current driving of a load without being influenced by power supply variation, temperature variation and process variation, while reducing the output amplitude on the high level side. The circuit includes a high-level power supply terminal, a low-level power supply terminal, a reference current source circuit, and a switching drive stage.

1. Field of the Invention
This invention relates to a constant current driving circuit which is capable of performing constant current driving of a load without being influenced by power supply variation, temperature variation and process variation.
2. Prior Art
Conventionally, to transfer signals between internal circuits of two IC chips, an off-chip driver is sometimes employed. Such an off-chip driver includes a constant current driving circuit as shown in FIG. 1, which uses current mirror circuits, and is free from the influence of power supply variation, temperature variation and process variation.
The conventional constant current driving circuit has a reference current source circuit formed of an operational amplifier OP which has an inverting input terminal thereof supplied with reference voltage VREF, a PMOS transistor P21 driven by an output from the operational amplifier OP, and a resistance R connected to a drain terminal A of the PMOS transistor P21. In the reference current source circuit, the output from the operational amplifier OP is negatively fed back by the PMOS transistor P21 such that voltage at the terminal A is always equal to the reference voltage VREF. Therefore, provided that the reference voltage VREF is free from the influence of power supply variation, temperature variation and process variation, a current I0 (=VREF/R) flowing through the resistance R is also free from the influence of power supply variation, temperature variation and process variation, which is therefore used as a reference current.
In the conventional constant current driving circuit, PMOS transistors P22 and P23 have their gates commonly connected to the gate of the PMOS transistor P21 such that they are commonly driven by the output from the operational amplifier OP, to form a current mirror circuit together with the PMOS transistor P21. If the PMOS transistors P22 and P23 have the same element size (element parameter) as that of the PMOS transistor P21, currents I1 and I2 flowing through the respective PMOS transistors P22 and P23 become equal to the current I0. An NMOS transistor N21 is connected to the drain of the PMOS transistor P22, with its source connected to a grounding terminal VSS. This transistor has its gate and drain connected to each other (diode connection), to serve as a diode. The thus connected gate and drain of the transistor N21 are connected to the gate of an NMOS transistor N22 forming an output stage of the circuit. Thus, the NMOS transistors N21 and N22 also form a current mirror circuit, and provided that they have the same element size, a current I3 flowing through the NMOS transistor N22 becomes equal to the current I0. A switching PMOS transistor P24 and a switching NMOS transistor N23 are connected between the PMOS transistor P23 and the NMOS transistor N22, for connection to a load.
With the above arrangement, when the switching transistors P24 and N23 are driven in a complementary manner by input signals IN1 and IN2, the load is driven with a constant current. That is, when the PMOS transistor P24 is on, the load is charged from the power supply VDD via the PMOS transistors P23 and P24 with the constant current I2=I0. On the other hand, if the NMOS transistor N23 is on, the load is discharged via the NMOS transistors N22 and N23 with the constant current I3=I0.
In the conventional constant current driving circuit, when the load is charged, the PMOS transistors P23 and P24 do not have voltage drops by threshold values, and consequently an output signal at a signal output terminal OUT fully swings, i.e. the output voltage rises to a level as high as the supply voltage VDD. In recent days, however, for the economy of power consumption, it is often demanded to lower the output amplitude below the power supply voltage. To cope with such a demand, it is generally effective to provide an NMOS transistor on the side of the power supply VDD. With the NMOS transistor provided on the VDD side, when the gate of the NMOS transistor is driven with the supply voltage VDD, voltage at the source of the NMOS transistor cannot rise in excess of a value VDD-Vth (where Vth represents the gate threshold voltage of the NMOS transistor). Thus, the output at the output terminal OUT is limited on the high level side.
However, if the circuit design is changed such that the reference voltage VREF is input to the non-inverting input terminal of the operational amplifier OP and at the same time the PMOS transistors P21, P22, and P23 on the VDD side are replaced by NMOS transistors N31, N32, and N33, respectively, these NMOS transistors do not form a current mirror circuit, so that a constant current characteristic is no more obtained. More specifically, in the FIG. 1 circuit, the PMOS transistors P21, P22, and P23 have their sources connected to the power supply VDD and commonly connected such that they always have the same voltage between the gate and source (gate-source voltage) to thereby satisfy current mirror circuit conditions. On the other hand, in the FIG. 2 circuit, a reference current source circuit is formed of an operational amplifier OP, the NMOS transistor N31, and a resistance R, wherein a constant reference current I0=VREF/R is obtained by the negative feedback operation of the NMOS transistor N31. However, the NMOS transistors N32 and N33 have their drains connected to the power supply VDD side and therefore they do not have always the same voltage between the gate and source. Thus, the current mirror circuit conditions are not satisfied.
Even if the circuit is designed such that a current I1=VREF/R flows through the NMOS transistor N21 with its gate and drain connected to each other under a condition that the temperature variation and process variation each fall within a standard range, the current II and a current I2 flowing through the NMOS transistors N32 and N33 cannot always be equal to the reference current I0 flowing through the resistance R when the temperature variation and/or process variation falls out of the standard range. This is the same case as the output NMOS transistor N22 of the output stage connected to the grounding terminal VSS. That is, although the connection between the NMOS transistors N21 and N22 is the same as in the FIG. 1 circuit and therefore only a relationship of I1=I3 is satisfied, the relationship of I0=I1=I3 is not always satisfied.
As described hereinabove, according to the conventional constant current driving circuit using the PMOS current mirror circuit, the output amplitude on the high level side cannot be limited, and if the PMOS transistors forming the current mirror circuit are replaced by NMOS transistors, the circuit can be influenced by temperature variation and process variation.


A pneumatically operated hoist system including a load support is disclosed, wherein the system is capable of sensing an overload and preventing the raising of the load support.

Many industrial applications utilize air operated hoist systems to enable loads to be lifted. Air hoists are equipped with air motors which are sized to provide a specific maximum lifting capacity (i.e., ¼ Ton, ½ Ton, 1 Ton, etc.). The hoist controls typically control the vertical movement of the lifting mechanism. When in a lifting mode, the hoist will have the capability to lift up a predetermined rated lift capacity.
Many applications require a tool or lifting device, suspended from the hoist to engage the load. These devices are called "End-Effectors" or "Below the Hook Tooling". It is very common for the end-effector tooling and load to weigh less than the rated lifting capacity of the air hoist. Therefore, excess capacity remains for the hoist to lift a greater load. This can create an unsafe environment in many industrial applications.
Examples of safety related issues may be:
1. Attempting to lift heavier objects than the rated capacity of the end-effector tool, which may be less than the hoist. The hoist could continue to lift and the tool be placed in an unsafe condition. A further problem may occur wherein the hoist applies a maximum lift force against a load to be lifted, where the load is too heavy for the hoist to lift. Upon removing the load from the hoist, the hoist may continue to supply the maximum lift force, causing the end-effector tool to abruptly lift upward with the maximum lift force, possibly damaging equipment, tooling, or placing the operator in an unsafe situation.
2. The tool and/or load contacting an obstacle such as an adjacent shelf or a machine component. The hoist may have the lifting capacity to continue an upward movement possibly damaging equipment, tooling, or placing the operator in an unsafe situation.
It is an object of the present invention to produce a pneumatically operated hoist system which is capable of sensing an overload and preventing any further flow of the supply of pressure operating fluid.

Lifting system with overload protection circuit


An irrigation control system and method for controlling irrigation based on weather data. Weather data such as wind, temperature, solar radiation, humidity, and rainfall, may be collected at one or more weather stations for a region. The weather data may be compiled on a computer and transmitted to a paging broadcast service. The weather data may then be transmitted by the paging broadcast service to controller interfaces associated with irrigation systems throughout the region. The controller interfaces may adjust irrigation controllers associated with the irrigation systems based on the weather data such that the proper amount of water is applied. This allows the water to be used more efficiently and the health of the landscape to be improved.

1. The Field of the Invention
The present invention relates generally to irrigation control systems, and more particularly, but not necessarily entirely, to systems that utilize weather data for irrigation control.
2. Description of Background Art
Water conservation is a major issue in many parts of the world. In particular, population growth is putting fresh water supplies under tremendous strain. Notably, landscape water usage consumes more than half of the potable water supplies in some areas. Landscape water usage refers to the artificial application of water to promote the growth of desired plants. This is especially true in agricultural areas where crops require frequent watering in order to achieve maximum yield. However, residential, governmental and commercial water usage also significantly taps the available water supply, i.e., yards, golf courses, and parks also demand significant amounts of water to maintain healthy foliage.
A well known device to conserve and apply water during landscape watering is an irrigation system which controls the application of the water. A typical irrigation system comprises an irrigation controller, valves, pipes, and sprinkling heads. The irrigation controller, customarily also known as a clock or timer, automatically regulates the opening and the closing of the valves. The valves allow water to pass into the pipes and out of the sprinkling heads thereby irrigating the desired location. Properly configured, an irrigation controller can achieve some conservation of water. Irrigation controllers are commonly employed in the agricultural, commercial, governmental and residential settings albeit the scale of the operation can vary dramatically. The irrigation controller is often set to water "automatically" on preset days and times. Thus, the user can at least be assured that the watering occurs so that at least a predetermined amount of water is dispensed but often without any adjustment being made if a reduced amount of water would be optimum.
One great disadvantage to using an irrigation controller preset to water at specified days and times is the inability to automatically adjust for changing water requirements of the landscape. For example, during a rainy period, many previously available irrigation controllers still water even though no watering may be needed due to rainfall. Likewise, during a hot and windy period, additional water may be needed but because of the preset schedule, it is not provided. Also, because of the changing seasons in many areas, one preset watering schedule usually will not effectively water the landscape over a period of several months, i.e., less water may be needed in the spring than the hot summer months.
Furthermore, because the lack of water is potentially more harmful than too much water (except in the extreme case), the previously available irrigation controllers are typically programmed to "over water" to provide a margin of safety to the landscape and avoid death of the landscape due to dehydration. While this ensures that the landscape has sufficient water to maintain a viable landscape, it commonly results in wasteful water consumption.
In order to overcome the aforementioned problems, recently developed irrigation controllers are capable of receiving electronic input to improve the watering of the landscape based upon the estimated water needs of the landscape. The water requirement for the landscape can be determined through several methods, including visual inspection, soil moisture sensors, evaporative pan measurements or by calculating the evapotranspiration. Evapotranspiration is the most popular method for determining the water needs of the landscape.
Evapotranspiration is defined as the water lost to the atmosphere by two processes-evaporation and transpiration. Evaporation is the loss from open bodies of water, such as lakes and reservoirs, wetlands, bare soil, and snow cover; transpiration is the loss of water from living-plant surfaces. Several factors other than the physical characteristics of the water, soil, snow, and plant surface also affect the evapotranspiration process. The more important factors which impact evapotranspiration include net solar radiation, relative humidity, wind speed, density and type of vegetative cover, availability of soil moisture, elevation above sea level, reflective land-surface characteristics, and season of year. Because of the importance of solar energy to evapotranspiration, the evapotranspiration which is actually experienced also varies with latitude, season of year, time of day, and cloud cover. Evapotranspiration is typically expressed in either millimeters or inches of water per hour, per day or week.
The seasonal variability in evapotranspiration differs greatly and is similar to the seasonal trend in air temperature. Daily fluctuations in evapotranspiration can also occur. On clear days, the rate of transpiration increases rapidly in the morning and reaches a maximum usually in early afternoon or midafternoon. The midday warmth can cause closure of plant stomata, which results in a decrease in transpiration.
Numerous formulas have been developed, tested and refined over the years to calculate evapotranspiration. The formulas typically have been developed to reference either alfalfa or cool-season turf grass. To adapt the results to a specific plant, the reference value is modified by a crop coefficient. Each crop has its own crop coefficient curve, which is based upon plant physiology, height, density and growth stage. Research is ongoing to provide crop coefficient data for various crops and seasonal changes. The estimated potential evapotranspiration may differ from actual evapotranspiration based on water stress of the plants, and based on the margin of error of the model or equation used for the estimate.
Due to the large number of evapotranspiration equations in use today, the Evapotranspiration in Hydrology and Irrigation Committee of the American Society of Civil Engineers developed the "Standardized Reference Evapotranspiration Equation." Two equations were actually developed, one for short clipped grass and the other for tall crop. The landscape industry has also generally accepted a formula referred to as the FAO Penman-Monteith equation as a reliable means of calculating the potential evapotranspiration. Further information regarding evapotranspiration and the FAO Penman-Monteith equation can be found in Crop Evapotranspiration: Guidelines for Computing Crop Water Requirements published by Food & Agriculture Organization of the United States (June 2000) and also located at http://www.fao.org on the internet, both of which are hereby incorporated by reference in their entirety. It should be noted that as used herein, the term evapotranspiration refers to the actual evapotranspiration or the potential evapotranspiration determined from any of the methodologies now known or may become known in the future. Other methodologies, without limitation, include the Blaney-Criddle, radiation, and pan evaporation methods.
Most estimates of evapotranspiration are derived from studies of areas where climate, available moisture, and plant cover are relatively uniform. In order to calculate evapotranspiration for an area, a weather station collects data that can be used in the equation. For example, temperature, wind, solar-radiation and humidity values are collected and logged hourly by the weather station and are retrieved by a computer. The evapotranspiration can then be used to determine if an adjustment to the preset water schedule is warranted.
Once the evapotranspiration has been calculated, a crop coefficient is used to modify the reference evapotranspiration to reflect the water use of a particular plant or group of plants particularly with reference to the plant species. In some areas, the crop coefficient values changes seasonally.
One major problem with the previously available systems is that once the evapotranspiration has been calculated for an area based upon the measurements obtained from a weather station, the irrigation controllers must still be adjusted based upon that information. This is problematic because the irrigation controller may be located some distance from the weather station or central control computer where the evapotranspiration was initially calculated. Placing a weather station and computer to calculate the evapotranspiration near each irrigation controller is cost prohibitive in all but a few cases.
An attempt to overcome this drawback has been developed to utilize two-way communications, an on-site water manager, and an operator to monitor every irrigation controller. The operator communicates to a water manager by radio or cell phone the required information obtained from a weather station to adjust the watering schedule. The water manager can then make the appropriate adjustments to the irrigation controller. It has been recognized that the need for human intervention has prevented implementation of such systems on a wide scale basis.
Another attempt to overcome the aforementioned drawbacks, utilizes the step of having a user manually phone a commercial radio paging station to generate a paging signal for transmission to a receiver connected to a specific irrigation controller. The user first obtains the weather data and calculates the evapotranspiration to determine the appropriate adjustment to the watering schedule. Once the paging signal has been received by the receiver, it interfaces with the irrigation controller to control the watering schedule. A problem with this system is that the user of the system must manually call the paging station to send a signal to control the irrigation system. Further, each irrigation controller has a separate paging number, thereby requiring a separate call and page for each irrigation controller. Again, the described system disadvantageously requires intervention by a human and is therefore not fully automated.
In still another attempt to overcome the aforementioned drawbacks, coded evapotranspiration values and corresponding evapotranspiration zones are broadcast to a collection of microprocessor-based irrigation sprinkler controllers located within a geographic area. The controllers produce an adjustment value responsive to the evapotranspiration data which is broadcast for a particular zone. However, this particular system calculates the evapotranspiration values at one location prior to broadcasting, and only the evapotranspiration data and evapotranspiration zones data are broadcast. Thus, each irrigation site receives weather data which may be, or may not be, applicable to the location of a particular irrigation site. This previously available system still is disadvantageous because each site may have distinct characteristics from the other sites and the application of evapotranspiration zone data may be inapplicable to the location of that particular irrigation site.
In view of the foregoing, it will be appreciated that the previously available systems are characterized by significant drawbacks and disadvantages. For example, the decision to irrigate is made at the central computer and not on-site providing inaccurate watering. In addition, the previously available systems do not transmit the weather data but only evapotranspiration values calculated by the central computer which prevents on-site adjustments from being made. Thus, it would be a great advance in the art to provide a system and method which overcomes the aforementioned drawbacks and disadvantages.


Authenticating a client device to a service to allow the client device to access a resource provided by the service. A client device obtains a secondary credential that is associated with a primary credential and that is generated as being usable by a particular set of devices including the client device to indirectly gain access to the service through the primary credential. While outside of an enterprise network, the client device requests access to the service, including sending the secondary credential to an enterprise gateway. Based at least on sending the secondary credential to the enterprise gateway, the client device receives a resource from the service. The resource is received based at least on the enterprise gateway having forwarded the primary credential to the service after verifying that the secondary credential is valid and that the client device is in the particular set of client devices.

Background and Relevant Art
Computers and computing systems have affected nearly every aspect of modern living. Computers are generally involved in work, recreation, healthcare, transportation, entertainment, household management, etc.
Further, computing system functionality can be enhanced by a computing systems ability to be interconnected to other computing systems via network connections. Network connections may include, but are not limited to, connections via wired or wireless Ethernet, cellular connections, or even computer to computer connections through serial, parallel, USB, or other connections. The connections allow a computing system to access services at other computing systems and to quickly and efficiently receive application data from other computing system.
Current networks have allowed many new and different types of devices to be networked. Additionally, there is a desire to have mobility with networked devices. Mobility continues to evolve, as smartphones and tablets are more prevalent on business enterprise networks. Many organizations that wish to leverage the opportunity to increase employee productivity are embracing the mobile work style, and enabling information workers to access enterprise resources from their mobile devices.
While this trend brings new opportunities to improve employee effectiveness, it also creates new security risks for IT administrators as in many cases an employee can store enterprise credentials (e.g. a username and password pair) on their mobile devices. For example, most mobile email clients that use Active Sync available from Microsoft Corporation of Redmond Wash. require enterprise credentials. These credentials can be easily extracted from the mobile device. For example, the device may be stolen, the device may host a mobile application that turns out to be Trojan horses that collects saved passwords or log keystrokes. This can be particularly dangerous given that often an enterprise user may use the same credentials to access most, if not all, of the resources available to the enterprise user.
The subject matter claimed herein is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one exemplary technology area where some embodiments described herein may be practiced.

This patent is subject to a terminal disclaimer.

Resource protection on un-trusted devices


The invention relates to a starter (10) for an internal combustion engine, comprising a starter motor (12), which can be connected to a direct voltage network (30, 31) by means of a switching device (27). In order to improve the process of meshing a starter pinion (22) into a ring gear (26) of an internal combustion engine, it is proposed that the excitation winding (37) of the starter motor (12) be divided into several partial windings (a-f), which can optionally be connected to the direct voltage network (30, 31) by the switching device (27) in a staggered manner.

The invention relates to a starter for an internal combustion engine. By way of example, one such starter is described in the "Kraftfahrttechnisches Taschenbuch", a book on motor transport technology issued by the Robert Bosch Corporation, 25th edition, p. 986, in the form of a pre-engaged Bendix starter, which is actuated via a so-called pull-in relay. This relay carries out the pulling-in functions, that is to say meshing the pinion of the starter motor into the ring gear of an internal combustion engine and switching the main current of the starter motor. When meshing the pinion into the ring gear, a tooth of said pinion can strike against a tooth of said ring gear, which is why the engagement process is assisted by a meshing spring. This starter design, which is known from prior art, admittedly requires only a single relay and can therefore be produced at relatively low cost, but on the other hand it results in very difficult working conditions for the process of meshing said starter pinion into said ring gear and for the switching process for the high motor current. Working conditions are particularly difficult in this embodiment of the switching device for the main current of the starter, the maximum possible torque of which is already produced during start-up from rest. If the pinion of the starter motor is not thereby completely engaged into the ring gear of the internal combustion engine, at the least inadmissibly large loads on the toothing of the ring gear can occur over the service life of the starter. This gives rise to the danger of one or a plurality of teeth breaking off.
In order to improve the process of meshing a starter pinion into a ring gear of an internal combustion engine, particularly in the case of high-power starters, it is furthermore known from the aforementioned reference for the motor current to be switched on in two stages in so-called pre-engaged starters. In a first stage, the pinion of the starter is moved against the ring gear of the engine and the armature of the starter motor is at the same time fed with a reduced current; thus enabling said armature and, with it, said starter pinion to rotate when meshing into said ring gear. In so doing, the meshing process is made easier. The meshing mechanism is in this case provided with a ratchet, which only at the end of the process of meshing the starter pinion closes a further switching contact of the relay and via said contact closes the main current circuit of the motor. As a result, the meshing process and the switching of the main current of the motor can take place in two separate operating stages; however, the design of the pull-in relay is thereby more complicated and more susceptible to defects from the mechanical and electrical points of view. The main current of the starter motor is, however, likewise powered up in one switching operation; thus enabling the maximum torque of the starter to already be present at the pinon/gear ring interface while the internal combustion engine with its large mass is still at rest.

Starter having a switchable number of pole pairs


A system on chip (SOC) is provided according to an embodiment of the invention. The SOC includes a storage system, a network on chip (NOC) adapted to communicate with a communication network, and a processing system in communication with the storage system and with the NOC. The processing system is configured to conduct operations of the SOC and perform communication operations using the NOC. The SOC further includes an integrated test processor (ITP) in communication with the processing system, the storage system, and the NOC. The ITP is configured to generate a logical function test instruction for testing one or more logical functions of the SOC and generate a physical link test instruction for testing one or more physical links of the SOC.

1. Field of the Invention
The invention is related to a system on chip (SOC) that includes a network on chip (NOC), and in particular, to a SOC that includes a network on chip (NOC) and further includes an integrated test processor (ITP).
2. Description of the Prior Art
Computers and computerized devices have become increasingly more complex. As a result of modern fabrication technology, integrated circuits (i.e., chips) have become smaller and smaller. This has been achieved while including larger number of components and while achieving more and more functions.
This increased complexity has lead to increased cost and difficulty in manufacturing. The increasing number of components and circuits require more and more testing to ensure functionality and reliability. Many computers and computerized devices employ specialized on-chip circuitry in order to perform testing on the chip before it can be approved and sold to customers.
One area of electronics in which chip complexity has dramatically increased is in the area of communication chips. The increased reliance on communication networks, such as packet-based networks and public switched telephone networks (PSTNs), for example, has lead to the development of more powerful communications circuits and functions on chips. Such communications continue to demonstrate a need for increased methods and devices for testing the chips. Rigorous and complete testing is needed in order to test a chip design for proper and efficient operation before manufacture, in order to test chips during manufacture to ensure that quality meets acceptable levels, and in order to test the chips during operation in order to ensure continued proper operation.

Integrated test processor (ITP) for a system on chip (SOC) that includes a network on chip (NOC)


An improved method and apparatus as disclosed for measuring the permeability of multiple phases through a rock fracture. The improvement in the method comprises delivering the respective phases through manifolds to uniformly deliver and collect the respective phases to and from opposite edges of the rock fracture in a distributed manner across the edge of the fracture. The improved apparatus comprises first and second manifolds comprising bores extending within porous blocks parallel to the rock fracture for distributing and collecting the wetting phase to and from surfaces of the porous blocks, which respectively face the opposite edges of the rock fracture. The improved apparatus further comprises other manifolds in the form of plenums located adjacent the respective porous blocks for uniform delivery of the non-wetting phase to parallel grooves disposed on the respective surfaces of the porous blocks facing the opposite edges of the rock fracture and generally perpendicular to the rock fracture.

This invention relates to a method and apparatus for measuring the permeability of a rock fracture to two or more immiscible fluids. More particularly, this invention relates to a method and apparatus for measuring the permeability of a rock fracture to two flowing phases such as a liquid and a gas.
Data on the relative permeability of a rock fracture to two or more immiscible fluids, such as a liquid and a gas, is needed in predicting fluid flow in such processes as nuclear waste isolation, petroleum reservoir engineering, and exploitation of geothermal energy. When two phases occupy a porous medium or a fracture, in general one phase wets the surface better than the other. The non-wetting phase must, therefore, be at a higher pressure; and the difference in pressure is called the capillary pressure.
In measuring two-phase flow, the capillary pressure must be uniform throughout the flow field, or errors result which are difficult to compensate for. A method to achieve uniform capillary pressure, when measuring the permeability of porous bodies, is disclosed in Hassler U.S. Pat. No. 2,345,935, wherein the wetting phase is fed to and from the porous sample body through solid end blocks placed respectively against the opposite ends of the porous sample body. A circular distribution groove, intersecting a bore passing through the end block, is formed in the respective face of each end block facing the porous sample body, and porous material is respectively placed in each of these circular distribution grooves so that the wetting phase must pass through this porous material in the end blocks before reaching the face of the porous sample body. The non-wetting phase (e.g., a gas) is fed directly to the face of the porous sample body through a bore which passes through the end block to the face of the porous sample body.
A somewhat similar system for measuring the relative permeability of fluids in a porous body is described in Rose U.S. Pat. No. 4,506,542, wherein the end blocks, however, are made of porous material, and the distribution grooves of Hassler are eliminated, with the wetting phase passing directly through the porous end blocks to and from the respective faces of the porous sample body.
However, while the distribution grooves containing porous material in the end blocks of Hassler and the porous end blocks of Rose do provide some distribution of the wetting phase into the porous body to be measured, the use of a single port in the end block of either Rose or Hassler to deliver the non-wetting phase to the face of the porous body leaves something to be desired, particular when one attempts to measure the permeability of a fracture in a rock structure, rather than the permeability of a porous body wherein the porous nature of the body being studied may itself provide a certain degree of distribution means for the non-wetting phase.
Osaba et al., in an article entitled "Laboratory Measurements of Relative Permeability", published in Petroleum Transactions, AIME, Volume 192 (1951), at pages 47-56, describe the measurement of the relative permeabilities to oil and gas on small core samples of reservoir rock and illustrate apparatus for making measurements by the Hassler method using semi-permeable discs at each end of the core sample to allow oil, but not gas, to pass. Provision is made for gas to enter and leave the core sample through radial grooves in the respective faces of the semipermeable discs.
In the study of porous materials, the distribution of the wetting and non-wetting phases to the face of the porous sample is not critical, because the three-dimensional network of pores within the sample ensures that essentially all pores have access to either phase, and will be occupied by one phase or the other as determined by capillary pressure. For a fracture, however, there is no such three-dimensional network of pores to accomplish the detailed distribution of the phases, so the uniform delivery of both the wetting and non-wetting phases to all parts of the fracture edge is necessary to obtain accurate results.
Measurement of fluid flow through a rock fracture has been previously measured. Jones et al. U.S. Pat. No. 4,884,438 describes the measurement of flow of a single phase through a fracture using inlet and outlet blocks which respectively contain inlet and outlet ports for transporting the fluid to and from the fracture face.
The determination of fluid saturation within a fracture is taught in Jones et al. U.S. Pat. No. 4,907,442, by establishing a functional relationship between fluid saturation and electrical capacitance for a multiple component fluid and then, after introducing the fluid between the fracture faces of the fractured media, the fluid saturation is determined from electrical capacitance measurements.
However, it would be desirable to provide a reliable method and apparatus for measuring multiple phase flow in a single fracture wherein both wetting and non-wetting phase are delivered to, and uniformly distributed across, opposite edges of a fracture in a manner which will permit accurate determination of the flow rates and pressure drops of the respective phases through the fracture to determine the permeability of the fracture, and measurement of the capillary pressure at the inlet and outlet edges of the fracture.
In a paper entitled "Two-Phase Flow Visualization and Relative Permeability Measurements in Transparent Replicas of Rough-Walled Rock Fractures", published by Lawrence Berkeley Laboratory as LBL-30161, and the contents of which were distributed in a printed publication in January, 1991, we discussed the use of porous end blocks placed against opposite edges of a rock fracture for delivery of a wetting phase to the rock fracture and grooves alternate with flats on the face of the porous block facing the fracture edge to deliver a non-wetting phase to the fracture edge.

Method and apparatus for determining two-phase flow in rock fracture

The United States of America as represented by the United States Department of Energy


A process for making N-vinyl-2-pyrrolidone (NVP) is disclosed. The process comprises dehydrating N-(2-hydroxyethyl)-2-pyrrolidone (HEP) in the presence of a catalyst and added water. Adding an effective amount of water into the dehydration process reduces the amount of N-ethyl-2-pyrrolidone (NEP) formed compared with the amount produced in the absence of the added water. Adding water can also sustain high conversions of HEP, minimize heavies formation, and improve selectivity to NVP. The process provides high-purity NVP and avoids a costly crystallization step.

N-vinyl-2-pyrrolidone (NVP) is a monomer used for making crosslinked or uncrosslinked polyvinylpyrrolidones, vinyl pyrrolidone-vinyl ester copolymers, and other valuable polymers. The polymers are used in beverage clarification, hair care, pharmaceutical tablet binding, and other industrial applications.
NVP is commonly manufactured by reacting 2-pyrrolidone with acetylene, but non-acetylenic routes to NVP are available. In one approach, NVP is made by dehydrating N-(2-hydroxyethyl)-2-pyrrolidone (HEP), which is easily obtained by reacting gamma-butyrolactone with 2-aminoethanol.
The dehydrations are normally performed by passing a vaporized mixture of HEP and a diluent gas, usually nitrogen, through a heated reactor tube containing a catalyst. NVP is collected along with water, unreacted HEP, and by-products. The by-products usually include 2-pyrrolidone ("2-Py," a hydrolysis product), N-ethyl-2-pyrrolidone (NEP), and nonvolatile materials ("heavies"). NEP is particularly undesirable because unlike 2-Py, it is not easily converted back to NVP. Moreover, pharmaceutical-grade NVP must be substantially free of NEP, and because NEP and NVP have similar boiling points, an expensive crystallization step is usually needed to separate them. NEP is seldom mentioned in the literature. However, there is at least one report of NEP being observed in an HEP dehydration process catalyzed by alumina (see U.S. Pat. No. 3,821,245 at column 4, line 17).
As noted above, an inert gas such as nitrogen or argon is commonly used to dilute the HEP in the dehydration process. U.S. Pat. No. 5,410,170 teaches (column 2, lines 6–10) that "inert gases, such as hydrogen, nitrogen, or steam, or the addition of inert organic solvents, or the use of reduced pressure can be advantageous." The reference does not say what advantage is expected from using the inert gases, and Table 1 (columns 3–4) shows no examples in which the HEP is combined with nitrogen, steam, or any other diluent.
Despite the availability of a well-known non-acetylenic route to NVP from HEP, the industry would benefit from a process that delivers and sustains higher HEP conversion, better NVP selectivity, reduced NEP formation, and a lower level of non-volatile by-products. An ideal process would be easy to perform using conventional equipment and would use cheap, readily available starting materials.

Process for making N-vinyl-2-pyrrolidone


A jig mounting apparatus has a detection optical system that detects reference marker of an eyeglass lens, is configured so as to determine an mounting point based on the reference marker detected by the detection optical system and position the mounting center of jig, which is used in processing the eyeglass lens, on the mounting point to mount the jig on the surface of the eyeglass lens, in which the detection optical system includes: a focusing optical system that focuses a light-emitting optical flux from a light source on the surface of the eyeglass lens, where hidden marks are formed, via an aperture stop; a reflection plate that reflects an optical flux focused by the focusing optical system and passed through the eyeglass lens; and an imaging device that is provided on a position optically approximately conjugate with the aperture stop and configured to focus on a space portion along an optical axis direction from the surface of the eyeglass lens.

Generally, an eyeglass lens such as a progressive multi-focal lens, for example, is provided with print marks or hidden marks as a reference marker that are used in mounting a jig, which is used in processing the eyeglass lens, on the eyeglass lens.
Conventionally, the following Patent documents 1 to 8, for example, disclose a jig mounting apparatus that detects an identification marker such as the hidden marks by a detection optical system, determines an mounting point based on the identification marker detected by the detection optical system to position the jig used in processing the eyeglass lens at the mounting point, and mounts the jig on the eyeglass lens.    Patent document 1: Japanese Utility Model Registration No. 3077054 gazette    Patent document 2: Germany Patent Publication No. 3829488 gazette A1    Patent document 3: The United States Patent Publication No. 2003-15649 gazette    Patent document 4: Japanese Patent Laid-Open No. 2002-296144 gazette    Patent document 5: Japanese Patent Laid-Open No. 2000-19058 gazette    Patent document 6: Japanese Patent Laid-Open No. 2002-139713 gazette    Patent document 7: Japanese Patent Laid-Open No. 2002-1638 gazette    Patent document 8: European Patent Registration No. 856728 gazette B1
The jig mounting apparatus disclosed in each of these documents binarizes an image which is obtained by imaging the identification markers formed by printing, engraving or the like on the eyeglass lens, to detect the identification markers.
However, there were cases where each jig mounting apparatus doubly images the identification markers such as the hidden marks and print marks or the like, and in such a case, there was a problem that it was difficult to discriminate which of the doubly imaged identification markers should be used as a reference to determine the mounting point.
The present invention has been created in view of the above-described problem of the prior art, and an object of the present invention is to provide a jig mounting apparatus that is capable of detecting hidden marks as identification markers more accurately and capable of surely determining an mounting point, and thus capable of surely attaching a jig on an eyeglass lens with good accuracy.


A single, large-scale satellite access communication network may be configured as infrastructure for many small-scale subnets, wherein each subnet may be configured to serve a different organization (e.g. an SME) as a private network. Each subnet may be configured as a small star and/or mesh satellite data access network from the end-user perspective, yet all subnets may be configured to be part of the total large-scale network and share satellite bandwidth resources. Such configuration may yield significantly higher bandwidth efficiency, lower operation and equipment costs, minimized latency and ease of network operations for each of the small organizations sharing the large-scale network.

Small-Medium Enterprises (SMEs) as well as other organizations (e.g. large corporations, government agencies, etc,) continuously use communication networks to enable remote branches and/or offices to access both an enterprise data center, typically located at the enterprise's headquarters (HQ), and the Internet. Accessing the enterprise data center may be required for example for intranet data processing, accessing central servers of various types (e.g. file storage facilities, electronic mail servers, etc), performing management tasks, conducting conference calls or video sessions within the enterprise or using Enterprise Resource Planning/Customer Relationship Management (ERP/CRM) systems or any other enterprise unique applications. Access to the Internet may be required since the Internet is a major source for information and data and provides connectivity on a global scale for numerous applications, such as access to web content, electronic mail exchange, etc. In some cases, connectivity to a wide area network (WAN) other than the Internet via the enterprise's head office (HO) may also be required, either instead of connectivity to the Internet or in addition to such, for example in order to provide services which might not be available at the enterprise HQ but may be available at the HO.
FIG. 1a illustrates a hierarchical topology of an enterprise network 100, comprising a plurality of small networks (120, 130 and 140) and a corporate head office (HO 101). A small network, such as small network 120, may comprise a headquarters (HQ 121), which may act as a data center and host central servers as previously described, and plurality of branches (122 to 124). Network 120 may be connected to HO 101, which may act as a major source of information and data for several small networks (120 to 140). HO 101 may provide WAN connectivity to a corporate network or to the Internet. HO 101 may also be connected to a plurality of stand-alone branches (151, 152), which might not be part of any small network. HO 101 may provide these branches connectivity to the corporate network for example for accessing corporate data, accessing the Internet or conducting multimedia sessions with users either inside or outside the corporate network.
FIG. 1b illustrates connectivity options of a single branch 122 within a small network 120. Link 110 may illustrate connectivity of branch 122 to HQ 121, for example for accessing data servers or conducting multimedia sessions (e.g. voice and/or video) with other users of small network 120. Link 111 may illustrate WAN connectivity of branch 122 via HO 101, for example for accessing the Internet, accessing corporate data or conducting multimedia sessions with users either inside or outside the corporate network. Link 112 may illustrate connectivity of branch 122 to another branch, e.g. branch 124, which may also be part of network 120, for example for data transfer between branches or for conducting multimedia sessions between the branches. Link 113 may illustrate connectivity of HQ 121 to the corporate WAN via HO 101, for example for accessing the Internet, accessing corporate data or conducting multimedia sessions with users either inside or outside the corporate network.
In some scenarios, enterprise network 100 may be configured as a satellite based communication network, for example in order to provide connectivity between the various offices where terrestrial infrastructure is unavailable or for backup and disaster recovery purposes (e.g. after earthquakes or other disasters which may affect terrestrial infrastructure). Furthermore, in some parts of the world, lack of Internet infrastructure results in gateways to the Internet (or to any other WAN) to be located very far from the corporate facilities, in some cases even in a different continent. For example, small networks in Africa may be connected to the Internet via gateways located in Europe, where the Internet backbone is easily accessible. In such networks, using connectivity over satellite is practically the only available option. In many of these cases, these satellite communication networks may be based on demand-assignment-multiple-access (DAMA).
A DAMA satellite network may support remote terminals with ambiguous data profiles, wherein the ambiguity may be manifested by a large data rate peak to average ratio. For example, a remote terminal may be used most of the time for exchanging electronic mail messages (which may be transmitted at relatively low rate regardless of message size) or for voice connectivity, but occasionally it may be required to transmit a high rate video stream. In order to achieve efficient use of bandwidth, such networks may be designed with sufficient bandwidth to support an average network data rate, while assuming oversubscription for remote terminals' peak rates over high throughput channels. If the network is large enough (hundreds of remote terminals) utilizing a statistical approach may be justified, as normally only a small number of remote terminals require their peak rate at any given time.
When attempting to apply DAMA techniques to a small-scale satellite network (for example tens of remote terminals), wherein a considerable volume of traffic may be exchanged between remote sites, inherent limitations of the topology may lead to utilizing bandwidth less efficiently (and perhaps even to cost ineffectiveness). The low number of terminals and a higher correlation between bandwidth requests from those remote terminals may render the statistical approach unjustified, resulting in less oversubscription (i.e. more bandwidth per remote terminal). Furthermore, a relatively high volume of traffic sent from remote terminals (i.e. over return channels to a hub or to other remote terminals, e.g. in mesh topology) compared to the volume of traffic sent from a hub to remote terminals (e.g. over a forward channel) also negatively affects the bandwidth efficiency. Inbound and mesh traffic may be transmitted using bursts over return channels (e.g. in accordance with DVB-RCS recommendations), which are less efficient than a continuous, statistically multiplexed carrier as the forward channel may be (e.g. in accordance with DVB-S2 recommendations). In addition, any overhead of management and control (hardware and bandwidth) may be divided between fewer users hence the overhead per user is higher. Consequently, in terms of bits per Hz, a small-scale DAMA network may be much less efficient than a regular DAMA network.
A network topology of small-scale networks using satellite access, for example like the one illustrated for example in FIG. 1a, poses several technological challenges, including the inherent latency over satellite links, the cost of equipment and operation of a satellite network (e.g. bandwidth efficiency), operation simplicity (as operation of a satellite network may require expertise not always existing in small organizations), broadband requirements, availability requirements, user experience requirements and support of interactive applications (e.g. VoIP or video conferencing).
According to the current state of the art of satellite communication networks, several solutions and technologies exist and may be used in order to support the above described topology, in varying degree of adequacy.
A widely used solution may be a VSAT (Very Small Aperture Terminal) network in star topology, comprising a hub and plurality of remote terminals (VSATs), for example as illustrated in FIG. 8a. The hub may be configured to aggregate all the traffic to and from the remote terminals and perform all network management and control tasks. The hub may be located at a data center and/or close to an Internet backbone access point in order to provide the required connectivity to the Internet and/or intranet. In some embodiments, the outbound link (hub to remote terminals) is a point to multipoint link, based on a continuous carrier with statistical multiplexing of data frames (for example in accordance with the DVB-S2 standard recommendations) and the inbound links (from remote terminals to the hub) are point to point links, based on burst transmissions over shared bandwidth media managed using an appropriate access scheme, for example, Multi-Frequency Time Division Multiple Access (MFTDMA).
A VSAT network in star topology may be typically used in networks where the number of VSATs is measured in hundreds or more. In such systems, relatively small VSAT antennas are often used (sub-meter for Ku-band in many cases) along with a DAMA (Demand Assigned Multiple Access) satellite access scheme, which enables providing a service for a large number of users over relatively small bandwidth.
However, a VSAT network in star topology fails to meet several key requirements of the small-scale network topology previously presented. In one aspect, the bandwidth utilization efficiency expected from DAMA access schemes may be achieved only with a relatively large install base (hundreds of sites). Most SME networks may comprise only a tenth of that number of sites or even less than that. In another aspect, the star topology is efficient where almost all traffic is exchanged between the remote terminals and the data center via the hub and almost no traffic is exchanged between remote sites (e.g. branches or a second data center). Any data exchanged between VSATs travels twice via the satellite (in double hop) hence requiring approximately twice the satellite bandwidth compared to data exchanged with a data center at the hub. Since in the small-scale network topology previously presented a considerable portion of the total traffic may be exchanged between remote sites (especially between branches and their headquarters), a star topology network may be much less efficient than usually expected for such networks. In yet another aspect, any data exchanged between two VSATs is subjected to longer latency due to the additional satellite hop in each direction, hence user experience (e.g. for voice and video sessions) might be significantly compromised. In a further aspect, installing a hub for a satellite network at an SME's data center may require SME personal to operate the satellite network hence the operational simplicity requirement presented above is not satisfied as well.
In another variant of a VSAT network in star topology, a small hub may be located at each HQ of the enterprise and connectivity to the HO may be provided from each HQ via a single channel per carrier (SCPC) link. While offering efficient connectivity between branches and their HQ, the connectivity between branches and the connectivity to the Internet via the HO is in two satellite hops per direction, hence the problems of latency and user experience are not resolved but rather relocated from one link to another. In addition, the issues of bandwidth efficiency (due to network size) and operation simplicity were already presented above and are applicable in the same way to this type of solution as well.
Consequently a VSAT network in star topology, where the hub is located either at the HO or at the HQ, is an inadequate solution for a small-scale network topology as previously presented.
Another solution known in the art may be a fully meshed VSAT network, for example as illustrated in FIG. 8b. In certain networks, this topology may provide certain advantages over a star topology network, such as more efficient exchange of data between VSATs (in single satellite hop) and better user experience (lower latency). In some embodiments, as shown in FIG. 8b, a mesh network may be configured without a hub. However, such embodiments often use static channel assignments hence the total bandwidth efficiency is limited (i.e. network operation costs are higher) and the task of managing the network (e.g. adding additional sites) may be more complicated (i.e. network operation might not be simple).
However, a VSAT network in fully meshed topology fails to meet several key requirement of the small-scale network topology previously presented. In one aspect, mesh links are usually point to point links. In a topology where a VSAT may be configured to support a data center or an HQ of an SME, that VSAT may be required to concurrently maintain multiple point-to-point mesh links with plurality of other VSATs, both for transmission and reception. Since each remote terminal may be configured to have a single receiver and a single transmitter, the satellite links must be designed for aggregating the total traffic of all point-to-point links used concurrently between the data center and the other sites. This means that all VSATs in the network may be configured to transmit and receive at relatively high rate, though the throughput for each VSAT may be much lower. Achieving high throughput between remote sites (e.g. due to the above or due to broadband requirements or for video conferencing) requires a larger (and more expensive) VSAT antenna and a more powerful (and expensive) transmission equipment at each site in order to insure a sufficient link budget between any two VSATs. Consequently, the entire solution may be cost ineffective and/or face regulatory obstacles due to high transmission power. In other aspects, issues such as bandwidth efficiency (due to network size) and operation simplicity (assuming the network has a hub) were already presented above in context with the star topology network and are applicable in a similar way to this type of solution.
Consequently a VSAT network in fully meshed topology is an inadequate solution for a small-scale network topology as previously presented.
Yet another solution known in the art may be a VSAT network in a hybrid star and mesh topology, for example as illustrated in FIG. 8c, comprising a hub and plurality of remote terminals (VSATs), at least some of them configured for mesh connectivity as well as connectivity with the hub (e.g. through comprising a second inbound receiver as well as a first outbound receiver). In certain networks, a hybrid star and mesh topology may enable more efficient and lower latency connectivity between remote terminals compared to star topology.
However, a VSAT network in hybrid topology fails to meet several key requirement of the small-scale network topology previously presented. In one aspect, the issues of bandwidth efficiency (due to network size) and operation simplicity previously presented for the star topology are applicable in the same way to this type of solution. In another aspect, since the network is basically a star network and the VSATs comprise relatively small antennas and low power transmission equipment, mesh connectivity may be supported only for low throughput applications. Hence a hybrid topology may be used where the traffic between remote terminals consists for example of low-rate data transfer and/or a telephony application (which have low-rate traffic requirements), as the link rate is limited by the antenna sizes from both ends. Therefore, a hybrid topology may be inadequate for supporting a second data center at a location other than the hub, which is a key requirement in the small-scale network topology previously presented. In yet another aspect, any attempt to increase the throughput over mesh connectivity may require a larger VSAT antenna and/or a more powerful (and expensive) transmission equipment at least at one end of the mesh link. This may introduce the deficiencies of the fully meshed network, as previously presented, back into this topology.
Consequently a VSAT network in a hybrid star and mesh topology is an inadequate solution for a small-scale network topology as previously presented.
Another approach known in the art toward satellite communication networks is based on a single channel per carrier (SCPC) topology. In this approach, for example as illustrated in FIG. 8d, each link between a remote terminal and a data center requires a separate channel over a fully dedicated carrier. Those links might not be shared or multiplexed hence require permanent satellite resources, as also illustrated in FIG. 8d.
An SCPC approach fails to meet several key requirement of the small-scale network topology previously presented. In one aspect, perhaps some of the biggest disadvantages of this approach are its inherent bandwidth inefficiency while working with non-continuous traffic (e.g. as in the case of IP networks) and its rigidness and inflexibility from satellite resources point of view. In another aspect, in a network containing more than very few sites, perhaps with one site being configured as a data center to which all the other sites may be connected and with requirements for single hop connectivity between at least some of the other sites, the necessary equipment required for implementation of such a network may be cost-ineffective, as a dedicated transceiver (transmitter and receiver) may be required for each link.
Over the years, several enhancements to the SCPC approach were introduced such as the MCPC (Multiple Channels Per Carrier) approach. Although an MCPC approach may enable time division multiplexing (TDM) of several data streams over a single carrier, this approach does not cure any of the other deficiencies previously presented with respect to the SCPC approach.
Consequently the SCPC approach is an inadequate solution for a small-scale network topology as previously presented.

Statistical multiplexing in satellite communication networks


Disclosed are 3-aryl-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and related compounds thereof, represented by the Formula I:

1. Field of the Invention
This invention is in the field of medicinal chemistry. In particular, the invention relates to 3-aryl-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and related compounds, and the discovery that these compounds are activators of caspases and inducers of apoptosis. The invention also relates to the use of these compounds as therapeutically effective anti-cancer agents.
2. Related Art
Organisms eliminate unwanted cells by a process variously known as regulated cell death, programmed cell death or apoptosis. Such cell death occurs as a normal aspect of animal development, as well as in tissue homeostasis and aging (Glucksmann, A., Biol. Rev. Cambridge Philos. Soc. 26:59-86 (1951); Glucksmann, A., Archives de Biologie 76:419-437 (1965); Ellis, et al., Dev. 112:591-603 (1991); Vaux, et al., Cell 76:777-779 (1994)). Apoptosis regulates cell number, facilitates morphogenesis, removes harmful or otherwise abnormal cells and eliminates cells that have already performed their function. Additionally, apoptosis occurs in response to various physiological stresses, such as hypoxia or ischemia (PCT published application WO96/20721).
There are a number of morphological changes shared by cells experiencing regulated cell death, including plasma and nuclear membrane blebbing, cell shrinkage (condensation of nucleoplasm and cytoplasm), organelle relocalization and compaction, chromatin condensation and production of apoptotic bodies (membrane enclosed particles containing intracellular material) (Orrenius, S., J. Internal Medicine 237:529-536 (1995)).
Apoptosis is achieved through an endogenous mechanism of cellular suicide (Wyllie, A. H., in Cell Death in Biology and Pathology, Bowen and Lockshin, eds., Chapman and Hall (1981), pp. 9-34). A cell activates its internally encoded suicide program as a result of either internal or external signals. The suicide program is executed through the activation of a carefully regulated genetic program (Wyllie, et al., Int. Rev. Cyt. 68.251 (1980); Ellis, et al., Ann. Rev. Cell Bio. 7:663 (1991)). Apoptotic cells and bodies are usually recognized and cleared by neighboring cells or macrophages before lysis. Because of this clearance mechanism, inflammation is not induced despite the clearance of great numbers of cells (Orrenius, S., J. Internal Medicine 237:529-536 (1995)).
It has been found that a group of proteases are a key element in apoptosis (see, e.g., Thornberry, Chemistry and Biology 5:R97-R103 (1998); Thornberry, British Med. Bull. 53:478-490 (1996)). Genetic studies in the nematode Caenorhabditis elegans revealed that apoptotic cell death involves at least 14 genes, 2 of which are the pro-apoptotic (death-promoting) ced (for cell death abnormal) genes, ced-3 and ced-4. CED-3 is homologous to interleukin 1 beta-converting enzyme, a cysteine protease, which is now called caspase-1. When these data were ultimately applied to mammals, and upon further extensive investigation, it was found that the mammalian apoptosis system appears to involve a cascade of caspases, or a system that behaves like a cascade of caspases. At present, the caspase family of cysteine proteases comprises 14 different members, and more may be discovered in the future. All known caspases are synthesized as zymogens that require cleavage at an aspartyl residue prior to forming the active enzyme. Thus, caspases are capable of activating other caspases, in the manner of an amplifying cascade.
Apoptosis and caspases are thought to be crucial in the development of cancer (Apoptosis and Cancer Chemotherapy, Hickman and Dive, eds., Humana Press (1999)). There is mounting evidence that cancer cells, while containing caspases, lack parts of the molecular machinery that activates the caspase cascade. This makes the cancer cells lose their capacity to undergo cellular suicide and the cells become cancerous. In the case of the apoptosis process, control points are known to exist that represent points for intervention leading to activation. These control points include the CED-9-BCL-like and CED-3-ICE-like gene family products, which are intrinsic proteins regulating the decision of a cell to survive or die and executing part of the cell death process itself, respectively (see, Schmitt, et al., Biochem. Cell. Biol. 75:301-314 (1997)). BCL-like proteins include BCL-xL and BAX-alpha, which appear to function upstream of caspase activation. BCL-xL appears to prevent activation of the apoptotic protease cascade, whereas BAX-alpha accelerates activation of the apoptotic protease cascade.
It has been shown that chemotherapeutic (anti-cancer) drugs can trigger cancer cells to undergo suicide by activating the dormant caspase cascade. This may be a crucial aspect of the mode of action of most, if not all, known anticancer drugs (Los, et al., Blood 90:3118-3129 (1997); Friesen, et al., Nat. Med. 2:574 (1996)). The mechanism of action of current antineoplastic drugs frequently involves an attack at specific phases of the cell cycle. In brief, the cell cycle refers to the stages through which cells normally progress during their lifetime. Normally, cells exist in a resting phase termed Go. During multiplication, cells progress to a stage in which DNA synthesis occurs, termed S. Later, cell division, or mitosis occurs, in a phase called M. Antineoplastic drugs, such as cytosine arabinoside, hydroxyurea, 6-mercaptopurine, and methotrexate are S phase specific, whereas antineoplastic drugs, such as vincristine, vinblastine, and paclitaxel are M phase specific. Many slow growing tumors, e.g. colon cancers, exist primarily in the Go phase, whereas rapidly proliferating normal tissues, for example bone marrow, exist primarily in the S or M phase. Thus, a drug like 6-mercaptopurine can cause bone marrow toxicity while remaining ineffective for a slow growing tumor. Further aspects of the chemotherapy of neoplastic diseases are known to those skilled in the art (see, e.g., Hardman, et al., eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, Ninth Edition, McGraw-Hill, New York (1996), pp. 1225-1287). Thus, it is clear that the possibility exists for the activation of the caspase cascade, although the exact mechanisms for doing so are not clear at this point. It is equally clear that insufficient activity of the caspase cascade and consequent apoptotic events are implicated in various types of cancer. The development of caspase cascade activators and inducers of apoptosis is a highly desirable goal in the development of therapeutically effective antineoplastic agents. Moreover, since autoimmune disease and certain degenerative diseases also involve the proliferation of abnormal cells, therapeutic treatment for these diseases could also involve the enhancement of the apoptotic process through the administration of appropriate caspase cascade activators and inducers of apoptosis.
C-Myc is a proto-oncogene and encodes the c-Myc transcription factor. Physiologically, cMyc expression correlates with cell proliferation in various cells and tissues of the body. cMyc is implicated in various biological processes including cell growth, proliferation, loss of differentiation and apoptosis. Deregulated expression of c-Myc occurs in a wide range of cancers and is often associated with poor prognosis suggesting an important role for this oncogene in tumor progression. Initially it was discovered in Burkitt's lymphoma as causative for the progression of the disease due to a translocation between chromosome 8 and the antibody-containing genes. More recently, cMyc has been detected in a wide range of cancers that include breast, colon, cervical, small-cell lung carcinomas, osteocarcomas, glioblastomas, melanoma and myeloid leukemias (Nesbit, C E et al. Oncogene, 18, 3004-3016 (1999); Blackwood, E. M et al. Science 251, 1211-1217 (1991); Mo H. & Henriksson M. PNAS, 103: 6344-6349 (2006)) Inactivation of c-Myc was found to cause tumor regression with rapid proliferation arrest and apoptosis in hematopoietic malignancies and osteosarcoma. Therefore inactivating cMyc or downstream targets of cMyc may provide important therapeutic advantages.
JP2004010548 disclosed fluorinated triazolothiadiazole compounds as electron-transporting agents.
The fluorinated triazolothiadiazole compounds as represented by I (R, R′=pentafluoroalkyl, pentafluoroaryl) were disclosed to have excellent electron-transporting property.
Xu et al. (Journal of the Chinese Chemical Society (Taipei, Taiwan), 51: 315-319 (2004)) reported the synthesis of heterocyclic derivatives, such as I (R=2-, 3-, 4-Cl, 3-, 4-F, 4-iodo, 3-, 4-Me, 3-, 4-Br). Some of the representative compounds were screened for antibacterial and fungicidal activity.

Invidiata et al. (Farmaco 46: 1489-95 (1991)) reported the synthesis and pharmacological properties of 6-substituted 3-(pyridin-4-yl)-1,2,4-triazole[3,4-b][1,3,4]thiadiazoles. A number of 6-substituted 3-(pyridine-4-yl)-1,2,4-triazole[3,4-b]thiadiazoles I (R=alkyl) were synthesized and evaluated for their pharmacological activity. Some of them exhibited moderate MAO, antimalarial and in vitro antitumor activity.

Zhang et al. (Huaxue Xuebao, 49: 513-20 (1991)) reported the synthesis and antibacterial activity of 3-(4-pyridyl)-6-aryl-s-triazolo[3,4-b]-1,3,4-thiadiazoles I (R=Me, MeO, NO2, Br, Cl, F, I). Some of these compounds were screened for antibacterial activity against Bacillus subtilis, Escherichia coli, Proteus vulgaris and Staphylococcus aureus.

Abstract: wherein Ar1, Ar2, and X are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.