A method and apparatus is provided for monitoring and controlling the temperature at the heat producing portion of an electrical current carrying device without direct measurement at the heat producing site. An integrated circuit 22 is thermally attached to a plurality of heat dissipating paths; top side heat conduction path 24, bottom side heat conduction path 26, and board level heat conduction path 28. On one of the heat conduction paths exists a heat flow sensor. This sensor is comprised of an inner thermistor 32 and an outer thermistor 34. The measured heat flow is combined with a single point temperature measurement and the thermal conductivity between the heat source and the temperature measurement point to produce the temperature at the heat source. This temperature is monitored in order to keep the temperature of the electrical current carrying device below critical levels or within a specified range.

As is well known in the art, semiconductor devices are widely used in various electronic components and devices such as transistors, integrated circuits, lasers, and the like. It is also well known that the passage of current through a junction results in a certain amount of power loss and heat generation therein. Continuous operation or frequent activation with minimal off periods may result in elevating the junction temperature. This elevated temperature can cause two problems. First, some integrated circuit (IC) devices are susceptible to drift (e.g., lasers). A temperature that is a function of loading can be a source of drift that is difficult to predict. Second, many devices such as microprocessors have a high number of junctions per volume. This results in devices that have very high power densities and are susceptible to overheating. This overheating may result in the failure of the semiconductor to perform its assigned circuit function and may sometimes involve the destruction of the semiconductor device itself. It is therefore important to monitor the junction temperature and perform a control or alert function based upon the results.
Prior art has taught several different methods of determining the junction temperature of IC devices.
1. Temperature sensing directly on the die of the IC. PA1 2. Recreation of the IC into a more thermally predictable device. PA1 3. Pure computational methods (no sensing). PA1 4. Single point temperature sensing remote to the die of the IC (e.g., on the package of the IC) followed by an extrapolation of the junction temperature. PA1 5. Single point temperature sensing remote to the die of the IC (e.g., on the package of the IC) and a measurement of the ambient temperature prior to extrapolation of the junction temperature. PA1 to provide for an accurate and cost effective temperature sensing method for the junction temperature of semiconductor devices; PA1 to provide a method of junction temperature sensing that is insensitive to the configuration or quality of the thermal solution; PA1 to provide a method of junction temperature sensing that is insensitive to changes in the configuration or quality of the thermal solution throughout the life of the device; PA1 to provide a method of junction temperature sensing that is compatible with existing components. These existing components may or may not have an integrated temperature sensor; PA1 to provide a method of junction temperature sensing only where it is thermally necessary; PA1 to provide a method of junction temperature sensing that is insensitive to changes in the environment surrounding the component or its thermal solution(s); PA1 to provide a method of junction temperature sensing that can be an input to a control circuit used to regulate the same junction temperature; PA1 to eliminate the burdening of the design and manufacture of a semiconductor device with an integrated temperature sensor; and PA1 to provide a signal relating to the heat flux through a particular thermal path. Changes to this value, relative to the total heat flux being dissipated, are evidence of the state of the thermal dissipation means.
Sensing on the die itself is accomplished in a variety of different ways. Some proposals (e.g., U.S. Pat. No. 5,639,163-Davidson et al., U.S. Pat. No. 5,555,152-Brauchle et al., U.S. Pat. No. 5,422,832-Moyal, U.S. Pat. No. 5,291,607-Ristic et al., U.S. Pat. No. 3,383,614-Emmons et al., U.S. Pat. No. 4,896,199-Tsuzuki et al., U.S. Pat. No. 5,406,212-Hashinaga et al., and U.S. Pat. No. 5,206,778-Flynn et al.) include the use of a monolithically integrated environmental sensor. One typical implementation of this environmental sensor is a pair of on-chip thermally responsive diodes coupled to a remote current source. The diode pair generates differential voltage output proportional to temp. Other proposals (e.g., U.S. Pat. No. 4,896,245-Qualich, U.S. Pat. No. 3,521,167-Umermori et al., U.S. Pat. No. 4,970,497-Broadwater et al., and U.S. Pat. No. 4,039,928-Noftsker et al.) rely on the fact that the impedance of internal circuitry varies as a function of temperature. Similarly, these circuits are driven by an external source and the resulting voltage drop is correlated to junction temperature. Despite the theory, in practice, the output of these circuits varies from one manufactured on-chip circuit to another to an extent that calibration particular to each on-chip circuit is required. Differences in construction and operation between sensors and semiconductor devices such as microprocessors have led the semiconductor industry to shun their integration into the same substrate. In operation, most sensors generate analog signals that have been difficult to process in digital microprocessors. Interface circuits used to couple the analog sensor signal to a microprocessor require additional semiconductor devices and further discourage monolithic integration of sensors and microprocessors. In addition, the inclusion of a sensing circuit on an IC die naturally results in a larger die to be fabricated. The manufacturing yield of devices such as microprocessors is inversely proportional to die size. Thus, the inclusion of sensing circuits into an IC result in a circuit that is more difficult to manufacture. Another difficulty with this type of technique is that the solution must be designed into a particular device. Devices already in existence cannot be sensed with this technique since they do not have the sensor on the substrate. Even if sensors are monolithically integrated onto the substrate, some environments that those components go into may be thermally challenging while others may not. Even if the environment is not thermally challenging and no sensing or control is required, the purchaser of this device to be used in this environment is still burdened with the extra cost and size of these devices.
Squires (U.S. Pat. No. 3,502,944), Demarest et al. (U.S. Pat. No. 4,117,527), and Barker et al. (U.S. Pat. No. 4,669,025) teach methods for recreating or simulating the thermal condition of the IC in question into a different form. The goal with these techniques is to overcome the shortcomings of on-die measuring mentioned above. This simulated IC is monitored and the control circuit drives the actual IC in response to the thermal state of the simulated IC. In practice, this simulation is very difficult to achieve. The actual IC and the simulated IC cannot occupy the same space. Therefore, the simulated IC and the actual IC are operating in different environments. Often in electronic devices, the environment can vary greatly between chips that are even right next to each other. In addition, if a thermal solution (heat sink, heat pipe, heat spreader, peltier junction, etc.) is imposed upon the IC of interest, the same thermal solution must be imposed on the simulated IC. Besides generating additional cost and complexity, an identical thermal solution is difficult to achieve primarily because of thermal impedances across interfaces of different materials. In other words, an IC and a corresponding simulated IC can be attached to identical heat sinks. The surface roughness of the components and heat sinks at the interfaces can vary. In addition, the forces clamping the heat sink to the IC may not be identical to the forces clamping the heat sink to the simulated IC. These and other factors can contribute to thermal impedances that are not identical between the component in question and its simulation. These differences can be dramatically reflected in the output making the simulation inaccurate. Even if the simulation and the actual component are reasonably similar, the solution is still problematic as the simulation generates additional heat. Thus, the overall heat generated by the system is greater than the heat generated by the component itself. The total heat is a combination of the component and its simulated counterpart. This can have the adverse effect of overheating the component or other nearby components or devices.
Kenny et al. (U.S. Pat. No. 5,287,292) and Chen et al. (U.S. Pat. No. 5,422,806) teach a method of sensing and control that does not involve temperature sensing at all. These methods monitor how a device is driven during usage. In theory, by integrating this usage over time, a prediction can be made as to the current state of the junction temperature. In practice, it is very difficult to produce accurate results with an accumulated operating history because the local environmental conditions are not known. Even if the ambient conditions are well known at one point in time, they can change rapidly and dramatically. Condition changes of this type may include the sudden loss of system cooling capability, the unanticipated obstruction of the flow of device cooling medium, or the repositioning of the device. other changes over the life of the device may relate to the quality of the thermal impedances across interfaces. The thermal impedance of many thermal interface materials such as thermal greases decreases over the first few days of the life of a system. The impedances of these or other interfaces may increase over the life of a device because of handling. All of these changes can result in a device with an unknown or highly variable heat transfer capability.
The most common method of sensing and control currently in practice is the presence of a temperature sensor external to the die of the IC. Examples of this configuration can be seen in U.S. Pat. No. 5,664,201-lkedea, U.S. Pat. No. 3,906,310-Esashika, U.S. Pat. No. 3,688.295-Tsoras et al., U.S. Pat. No. 4,001,649-Young, U.S. Pat. No. 4,330,809-Stanley, U.S. Pat. No. 4,689,659-Watanabe, U.S. Pat. No. 5,008,736-Davies et al., U.S. Pat. No. 5,119,265-Qualich et al., U.S. Pat. No. 5,230,055-Katz et al., U.S. Pat. No. 5,230,074-Canova et al., U.S. Pat. No. 5,345,510-Honda, U.S. Pat. No. 5,477,417-Ohmori et al., U.S. Pat. No. 5,600,575-Anticole, U.S. Pat. No. 5,618,459-Kamiya, U.S. Pat. No. 5,712,802-Kumar et al. and U.S. Pat. No. 5,763,929-lwata. In these designs, a temperature is measured at a point X. A term commonly called .theta..sub.JX is utilized to convert this temperature to a junction temperature. The dimensions of .theta..sub.JX are Temperature/Power and the units commonly referenced in manufacturer's data sheets are .degree. C./Watt. Manufacturers of IC's often publish values for .theta..sub.JX where the X is replaced by C for case temperature and A for ambient temperature. The problem with this solution is that it assumes that all the heat flux from the component flows through the location X and the temperature of X is one definable temperature. For example, consider a component where the temperature measurement occurs on the case of the device. .theta..sub.JX is listed at 5.degree. C./W and the power delivered to the device is measured at 10W. If the maximum junction temperature, .theta..sub.JX, for this particular device is rated at 100.degree. C., then the device will go over temperature when the case measures 50.degree. C. This may be close to accurate if the vast majority of the heat flux travels through that particular portion of the case. This may be a reasonable assumption if, for example, a heat sink was also attached to the case and a fan passed cooling medium across the heat sink. However, consider if instead of being attached to the case, the heat sink device was attached to the backside of the printed circuit board (PCB) opposite the device. A large portion of the heat will be conducted through the PCB and passed to ambient via the heat sink instead of through the top case of the IC. In this situation, there will be a very small thermal gradient between the junction and the top case since the majority of the 10W are traveling the other direction. When the case reads 50.degree. C., T.sub.j is actually not much higher that 50.degree. C. Thus, T.sub.j would be dramatically overestimated in the later case compared to the former. Another problem with this solution is that the above inventions assume that .theta..sub.JX is known and does not change over time. In fact, .theta..sub.JX can change over time. The thermal impedances across interfaces may change over time due to handling or other environmental factors. Thermal greases and some interface materials used between devices and heat sinks actually decrease their thermal impedances over the first few days of their usage. In situations where X is the ambient temperature, .theta..sub.JA it is imperative that anywhere heat flux flows from the IC's thermal solution to ambient, the ambient temperature must be uniform. In practice, this is improbable. Orientation of the unit, neighboring heat producing components, cooling medium currents, external radiant energy (sunlight), etc., all contribute to making the ambient temperature a very complex function of space. Therefore, except in the most ideal conditions, T.sub.j will not be accurately estimated using this technique. In some cases, the cooling medium may be very uniform. Even in these cases, ambient measurements may not accurately predict device temperatures. For example, Kumar et al. teaches measuring of the air mass flow rate and temperature of a forced air system. Assumptions are made in that all the heat flux flows through the heat sink, which the measured air is passing over, and that the measured air properties are homogenous. These assumptions may not be reasonable as there may be other conductive, radiative and convective thermal dissipation paths present. In addition, the cooling efficiency of the heat sink may change over time. A buildup of dust, a blockage of the air, or a change to the thermal impedance properties of the interfaces material between the semiconductor device and the heat sink all contribute to a different thermal gradient between the measured point X and the junction temperature. None of these contributing factors will be indicated by the stated measurement of the air properties. Anticole teaches measuring the temperature remote, but close to, the device. Like many of the other inventions, Anticole assumes that the thermal resistance is known. The difficulties with this assumption are stated above. In addition, Anticole also assumes that the thermal time constant between the measurement point and the heat source is known. In this way, as the power delivered to the device is being monitored, the temperature at the source can be estimated more accurately and in a more timely manner during transient conditions. The difficultly is that the thermal time constants can also change over the life of a device. For example, assume that the thermal transfer material between the device and its primary thermal dissipation path decreases its thermal impedance over time. Because of this, the aggregate thermal conductivity of the system increases. As the thermal conductivity increases, the time constant decreases. In the Anticole invention, an overestimated time constant will result in an overestimated junction temperature.
Another technique that is taught is very similar to the external sensor technique above (e.g., U.S. Pat. No. 3,480,852-Hung, U.S. Pat. No. 4,823,290-Fasack et al. and U.S. Pat. No. 3,651,379-Moisand et al.). Multiple sensors are used including at least one ambient temperature sensor. The output from these devices are compared against limits and a control circuit responds accordingly. The theory has it that this device can predict the junction temperature more accurately and more rapidly in transient situations than the solution that has a single sensor alone. In practice however, measuring the ambient at a point source only determines the ambient temperature at that particular point. As mentioned, in many electronic devices, ambient temperatures can vary radically from point to point. Only if the sensor were located in a statistically average point would this solution be able to accurately determine the junction temperature. Any location other than this ideal point would generate an overestimation or an underestimation of the junction temperature.

Method of junction temperature determination and control utilizing heat flow


Adenosine analogues which act selectively at adenosine receptors and which act in general as adenosine antagonists are disclosed. From in vitro studies it is known that specific physiological effects can be distinguished as a result of this selectivity and that adenosine receptor activity in vitro correlates with adenosine receptor activity in vivo.. Pharmaceutical preparations of the subject compounds can be prepared on the basis of the selective binding activity of the compounds disclosed herein which will enhance certain physiological effects while minimizing others, such as decreasing blood pressure without decreasing heart rate.

The profound hypotensive, sedative, antispasmodic, and vasodilatory actions of adenosine were first recognized over 50 years ago. Subsequently, the number of biological roles proposed for adenosine have increased considerably. The adenosine receptors appear linked in many cells to adenylate cyclase. A variety of adenosine analogues have been introduced in recent years for the study of these receptor functions. Alkylxanthines, such as caffeine and theophylline, are the best known antagonists of adenosine receptors.
Adenosine perhaps represents a general regulatory substance, since no particular cell type or tissue appears uniquely responsible for its formation. In this regard, adenosine is unlike various endocrine hormones. Nor is there any evidence for storage and release of adenosine from nerve or other cells. Thus, adenosine is unlike various neurotransmitter substances.
Adenosine might be compared as a physiological regulator to the prostaglandins. In both cases the enzymes involved in the metabolic formation are ubiquitous and appear to be responsive to alterations in the physiological state of the cell. Receptors for adenosine, like those for prostaglandins, are proving to be very widespread. Finally, both prostaglandins and adenosine appear to be involved with the regulation of functions involving calcium ions. Prostaglandins, of course, derive from membrane precursors, while adenosine derives from cytosolic precursors.
Although adenosine can affect a variety of physiological functions, particular attention has been directed over the years toward actions which might lead to clinical applications. Preeminent has been the cardiovascular effects of adenosine which lead to vasodilation and hypotension but which also lead to cardiac depression. The antilipolytic, antithrombotic, and antispasmodic actions of adenosine have also received some attention. Adenosine stimulates steroidogenesis in adrenal cells, again probably via activation of adenylate cyclase. Adenosine has inhibitory effects on neurotransmission and on spontaneous activity of central neurons. Finally, the bronchoconstrictor action of adenosine and its antagonism by xanthines represents an important area of research.
It has now been recognized that there are not one but at least two classes of extracellular receptors involved in the action of adenosine. One of these has a high affinity for adenosine and, at least in some cells, couples to adenylate cyclase in an inhibitory manner. These have been termed by some as the A-1 receptors. The other class of receptors has a lower affinity for adenosine and in many cell types couples to adenylate cyclase in a stimulatory manner. These have been termed the A-2 receptors.
Characterization of the adenosine receptors has now been possible with a variety of structural analogues. Adenosine analogues resistant to metabolism or uptake mechanisms have become available. These are particularly valuable, since their apparent potencies will be less affected by metabolic removal from the effector system. The adenosine analogues exhibit differing rank orders of potencies at A-1 and A-2 adenosine receptors, providing a simple method of categorizing a physiological response with respect to the nature of the adenosine receptor. The blockade of adenosine receptors (antagonism) provides another method of categorizing a response with respect to the involvement of adenosine receptors. It should be noted that the development of antagonists specific to A-1 or A-2 adenosine receptors would represent a major breakthrough in this research field and in the preparation of adenosine receptor selective pharmacological agents having specific physiological effects in animals.


Wavelength multiplexed optical communication systems include a channeled chromatic dispersion compensator coupled to receive modulated optical beams associated with a plurality of optical channels at respective communication wavelengths. The channeled chromatic dispersion compensator applies independently selected dispersion compensations to each of the optical channels by identifying a dispersion compensation associated with a preferred bit error rate, inter-symbol interference, or other signal quality metric, or determined using optical fiber properties such as dispersion slope and zero dispersion wavelength. Chromatic dispersion compensation can be coupled with channel power equalization, and can be performed at a receiver or a transmitter or in the middle of a fiber span.

High speed data links can use optical fibers to communicate optical data signals over significant distances with low signal loss. Single mode optical fibers having losses of less than 0.20 dB/km at wavelengths near 1550 nm are typical, and optical transmitters and receivers are readily available that can be simply coupled to optical fibers. Such low losses have led to the implementation of optical fiber based communication systems in data center communications.
To take advantage of the high bandwidths available with optical fiber links, so-called coherent communication systems have been developed that encode data onto amplitude, phase and polarization of an optical beam in a dense wavelength division multiplexing (DWDM) technique and achieve per wavelength data rates of 10 Gbit/s and higher. Such systems typically use dual polarization-quadrature phase shift keying (DP-QPSK) modulation and coherent optical detection. Higher order quadrature amplitude modulation (QAM) formats have also been used with coherent detection.
Other approaches for high speed data communication on optical fibers use direct detection. One problem in direct-detection systems for use in DWDM is fiber chromatic dispersion (CD) and fiber nonlinearities that can cause interference and channel degradation and limit communication distances. As data rates increase, both signal bandwidth and modulation format can produce increased optical signal bandwidth, increasing the likelihood of signal degradation due to CD. Multi-level pulse-amplitude-modulation (PAM) formats have been proposed for high data rate data center applications. In such PAM modulation, optical power is modulated to multiple levels with each level representing multiple bits. These systems can be cost-effective and are promising candidates for metro-reach applications. However, in multi-level PAM systems, signal levels are typically much closer to each other than in simple on-off keying (OOK) systems, and are significantly more prone to errors produced by CD and fiber nonlinearities. Even though some tunable CD compensators are available for fiber CD compensation on DWDM channels, conventional tunable CD compensators typically exhibit multiple deficiencies: (i) CD inaccuracies remain over all channels as CD cannot be individually compensated on a per-channel basis, (ii) fixed channel frequency grids are required, limiting the channel plan, and (iii) limited CD compensation resulting in communication bandwidth limitations.

Optical power and chromatic dispersion equalization system


A coal formation may be treated using an in situ thermal process. A mixture of hydrocarbons, H2, and/or other formation fluids may be produced from the formation. Heat may be applied to the formation to raise a temperature of a portion of the formation to a pyrolysis temperature. Pressure within the formation may be controlled as a function of temperature or temperature within the formation may be controlled as a function of pressure to yield a desired mixture.

1. Field of the Invention
The present invention relates generally to methods and systems for production of hydrocarbons, hydrogen, and/or other products from coal formations. Certain embodiments relate to in situ conversion of hydrocarbons to produce hydrocarbons, hydrogen, and/or novel product streams from underground coal formations.
2. Description of Related Art
Hydrocarbons obtained from subterranean (e.g., sedimentary) formations are often used as energy resources, as feedstocks, and as consumer products. Concerns over depletion of available hydrocarbon resources have led to development of processes for more efficient recovery, processing and/or use of available hydrocarbon resources, for example coal. In situ processes for coal formations may be used to remove hydrocarbon materials from subterranean formations. Chemical and/or physical properties of coal within a subterranean formation may need to be changed to allow coal to be more easily removed from the subterranean formation. The chemical and physical changes may include in situ reactions that produce removable fluids, composition changes, solubility changes, phase changes, and/or viscosity changes of the hydrocarbon material within the formation. A fluid may be, but is not limited to, a gas, a liquid, an emulsion, a slurry and/or a stream of solid particles that has flow characteristics similar to liquid flow.
Examples of in situ processes utilizing downhole heaters are illustrated in U.S. Pat. No. 2,634,961 to Ljungstrom, U.S. Pat. No. 2,732,195 to Ljungstrom, U.S. Pat. No. 2,780,450 to Ljungstrom, U.S. Pat. No. 2,789,805 to Ljungstrom, U.S. Pat. No. 2,923,535 issued to Ljungstrom, and U.S. Pat. No. 4,886,118 to Van Meurs et al., each of which is incorporated by reference as if fully set forth herein.
A heat source may be used to heat a subterranean formation. Electrical heaters may be used to heat the subterranean formation by radiation and/or conduction. An electrical heater may resistively heat an element. U.S. Pat. No. 2,548,360 to Germain, which is incorporated by reference as if fully set forth herein, describes an electrical heating element placed within a viscous oil within a wellbore. The heater element heats and thins the oil to allow the oil to be pumped from the wellbore. U.S. Pat. No. 4,716,960 to Eastlund et al., which is incorporated by reference as if fully set forth herein, describes electrically heating tubing of a petroleum well by passing a relatively low voltage current through the tubing to prevent formation of solids. U.S. Pat. No. 5,065,818 to Van Egmond, which is incorporated by reference as if fully set forth herein, describes an electrical heating element that is cemented into a well borehole without a casing surrounding the heating element.
U.S. Pat. No. 6,023,554 to Vinegar et al., which is incorporated by reference as if fully set forth herein, describes an electrical heating element that is positioned within a casing. The heating element generates radiant energy that heats the casing. A granular solid fill material may be placed between the casing and the formation. The casing may conductively heat the fill material, which in turn conductively heats the formation.
U.S. Pat. No. 4,570,715 to Van Meurs et al., which is incorporated by reference as if fully set forth herein, describes an electrical heating element. The heating element has an electrically conductive core, a surrounding layer of insulating material, and a surrounding metallic sheath. The conductive core may have a relatively low resistance at high temperatures. The insulating material may have electrical resistance, compressive strength and heat conductivity properties that are relatively high at high temperatures. The insulating layer may inhibit arcing from the core to the metallic sheath. The metallic sheath may have tensile strength and creep resistance properties that are relatively high at high temperatures.
U.S. Pat. No. 5,060,287 to Van Egmond, which is incorporated by reference as if fully set forth herein, describes an electrical heating element having a copper-nickel alloy core.
Combustion of a fuel may be used to heat a formation. Combusting a fuel to heat a formation may be more economical than using electricity to heat a formation. Several different types of heaters may use fuel combustion as a heat source that heats a formation. The combustion may take place in the formation, in a well and/or near the surface. Combustion in the formation may be a fireflood. An oxidizer may be pumped into the formation. The oxidizer may be ignited to advance a fire front towards a production well. Oxidizer pumped into the formation may flow through the formation along fracture lines in the formation. Ignition of the oxidizer may not result in the fire front flowing uniformly through the formation.
A flameless combustor may be used to combust a fuel within a well. U.S. Pat. No. 5,255,742 to Mikus, U.S. Pat. No. 5,404,952 to Vinegar et al., U.S. Pat. No. 5,862,858 to Wellington et al., and U.S. Pat. No. 5,899,269 to Wellington et al., which are incorporated by reference as if fully set forth herein, describe flameless combustors. Flameless combustion may be accomplished by preheating a fuel and combustion air to a temperature above an auto-ignition temperature of the mixture. The fuel and combustion air may be mixed in a heating zone to combust. In the heating zone of the Blameless combustor, a catalytic surface may be provided to lower the auto-ignition temperature of the fuel and air mixture.
Heat may be supplied to a formation from a surface heater. The surface heater may produce combustion gases that are circulated through wellbores to heat the formation. Alternately, a surface burner may be used to heat a heat transfer fluid that is passed through a wellbore to heat the formation. Examples of fired heaters, or surface burners that may be used to heat a subterranean formation, are illustrated in U.S. Pat. No. 6,056,057 to Vinegar et al. and U.S. Pat. No. 6,079,499 to Mikus et al., which are both incorporated by reference as if fully set forth herein.
Coal is often mined and used as a fuel within an electricity generating power plant. Most coal that is used as a fuel to generate electricity is mined. A significant number of coal formations are, however, not suitable for economical mining. For example, mining coal from steeply dipping coal seams, from relatively thin coal seams (e.g., less than about ≢1 meter thick), and/or from deep coal seams may not be economically feasible. Deep coal seams include coal seams that are at, or extend to, depths of greater than about 3000 feet (about 914 m) below surface level. The energy conversion efficiency of burning coal to generate electricity is relatively low, as compared to fuels such as natural gas. Also, burning coal to generate electricity often generates significant amounts of carbon dioxide, oxides of sulfur, and oxides of nitrogen that are released into the atmosphere.
Synthesis gas may be produced in reactors or in situ within a subterranean formation. Synthesis gas may be produced within a reactor by partially oxidizing methane with oxygen. In situ production of synthesis gas may be economically desirable to avoid the expense of building, operating, and maintaining a surface synthesis gas production facility. U.S. Pat. No. 4,250,230 to Terry, which is incorporated by reference as if fully set forth herein, describes a system for in situ gasification of coal. A subterranean coal seam is burned from a first well towards a production well. Methane, hydrocarbons, H2, CO, and other fluids may be removed from the formation through the production well. The H2 and CO may be separated from the remaining fluid. The H2 and CO may be sent to fuel cells to generate electricity.
U.S. Pat. No. 4,057,293 to Garrett, which is incorporated by reference as if fully set forth herein, discloses a process for producing synthesis gas. A portion of a rubble pile is burned to heat the rubble pile to a temperature that generates liquid and gaseous hydrocarbons by pyrolysis. After pyrolysis, the rubble is further heated, and steam or steam and air are introduced to the rubble pile to generate synthesis gas.
U.S. Pat. No. 5,554,453 to Steinfeld et al., which is incorporated by reference as if fully set forth herein, describes an ex situ coal gasifier that supplies fuel gas to a fuel cell. The fuel cell produces electricity. A catalytic burner is used to bum exhaust gas from the fuel cell with an oxidant gas to generate heat in the gasifier.
Carbon dioxide may be produced from combustion of fuel and from many chemical processes. Carbon dioxide may be used for various purposes, such as, but not limited to, a feed stream for a dry ice production facility, supercritical fluid in a low temperature supercritical fluid process, a flooding agent for coal bed demethanation, and a flooding agent for enhanced oil recovery. Although some carbon dioxide is productively used, many tons of carbon dioxide are vented to the atmosphere.
As outlined above, there has been a significant amount of effort to develop methods and systems to economically produce hydrocarbons, hydrogen, and/or other products from coal formations. At present, however, there are still many coal formations from which hydrocarbons, hydrogen, and/or other products cannot be economically produced. Thus, there is still a need for improved methods and systems for production of hydrocarbons, hydrogen, and/or other products from various coal formations.

This patent is subject to a terminal disclaimer.

Situ thermal processing of a coal formation using pressure and/or temperature control


A process for preparing 3- or 4-formyltricyclo-[5,2,1,0.sup.2,6 ]-decene-8 which comprises contacting dicyclopentadiene with carbon monoxide and hydrogen in the presence of a rhodium catalyst at 110.degree. to 150.degree. C. and 50 to 400 atmospheres, said catalyst being present in an amount of 1 to 30 ppm of rhodium, based upon the amount of dicyclopentadiene employed, said rhodium being present in the form of an organic phosphine-carbon monoxide containing complex.

1. Field of the Invention
The present invention relates to a process for preparing 3- and 4-formyltricyclo-[5,2,1,0.sup.2,6 ]-decene-8 by hydroformylating dicyclopentadiene. By virtue of the presence of two double bonds, dicyclopentadiene can form both monoaldehydes and dialdehydes when reacted with carbon monoxide and hydrogen in the presence of carbonyl-forming metals of Group VIII of the Periodic System.
2. Discussion of the Prior Art
The preparation of the dialdehyde, namely, the chemical compound tricyclodecane-dialdehyde from dicyclopentadiene, is described in German Pat. No. 928,645. Cobalt compounds yielding cobalt carbonyl hydrogen are used as catalysts in this case, optionally in the presence of metallic cobalt or iron. The conversion is carried out at 140.degree. C. and at a synthesis gas pressure of 180 atmospheres.
UK Pat. No. 801,734 describes the use of rhodium-containing catalysts, which are present dissolved in the reaction mixture under the process conditions, for the hydroformylation of dicyclopentadiene. An unsaturated tricyclodecene-monoaldehyde having a structure not described in more detail is obtained in a yield of 68 percent as reaction product under the reaction conditions employed, namely, a temperature of 100.degree. C. and a pressure of approximately 197 atmospheres.
Of the two double bonds in the cyclopentadiene molecule, the double bond in the norbornene ring is generally the more reactive. It is therefore to be expected that hydroformylation will preferentially result in the formation of 8- and 9-formyltricyclo-[5,2,1,0.sup.2,6 ]-decene-3.
It therefore became desirable to provide a process which yields the isomeric compounds 3- and 4-formyltricyclo-[5,2,1,0.sup.2,6 ]-decene-8 in good yields by hydroformylation of the cyclopentene ring.

Process for preparing 3-(4)-formyltricyclo-[5,2,1,0.sup.2,6 ]-decene-8


A kit and method of predicting a refractory response in a subject diagnosed as having periodontal disease by measuring serum concentrations of actinomyces antibodies, streptococcal antibodies and lysine decarboxylase antibodies and using the measurement along with other subject information in a set of derived equations.

Inflammatory adult periodontitis is a major cause of tooth loss in the middle aged and elderly. The gingival sulci of teeth become infected with a complex mixture of bacteria that impair tooth attachment. Mechanical debridement of the teeth surfaces (scaling and root planing, SRP) is the current basis of prevention. Many patients preserve tooth attachment with regular SRP and home care, but some such patients are defined as having a refractory response. The refractory response is defined as continued loss of tooth attachment even after treatment with antibiotics (e.g., tetracycline), surgery and SRP. The severity of prior attachment loss increases the likelihood that a patient will be refractory to therapy [3,4], as also does attachment loss in response to initial SRP [5]. The ability to identify refractory subjects at initial examination would provide several functions that are currently lacking in periodontics. It would indicate how patients should be divided to determine differences in host response or bacterial flora a priori, which patients would benefit most from new and experimental therapies, and provide an objective criterion for periodontists to warn patients of the potential for failure before treatment is begun.
Although patients develop antibody responses to various bacterial antigens, responses to specific bacteria have not been related to disease severity or progression except in a general way. The odds ratio of being refractory increased from 3-fold to 19-fold as the number of bacterial taxa with an antibody concentration >50 μg/ml increased from 3 to 17, out of a total of 85 bacterial taxa examined [6]. Measuring antibody levels to 85 taxa is difficult. A more specific response was the antibody to Hemophilus aphrophilus being >50 μg/ml, but the rationale for measuring antibodies to this organism is not clear and a second, more complex laboratory procedure, measuring bacterial DNA to Streptococcus constellatus, is also required [6]. The proposed procedure requires only antibody levels, and clinical measurements that all periodontists obtain prior to therapy.
Recent findings suggest that, of 40 bacterial species detected in the sulci pre-therapy, 37% of the variance in attachment level change after initial SRP was predicted by only the amount of Actinomyces naeslundii serotype 2 and Treponema denticola [5]. A. naeslundii extrudes an ornithine-rich antigen that contains an epitope to which an IgG antibody is directed in human serum [7,8]. An antibody response to this Actinomyces antigen is increased in subjects with less plaque, gingivitis and caries [9]. The sulci of refractory patients contain increased numbers of constellatus/anginosus streptococci [2] that possess a streptococcal antigen (e.g., D-alanyl lipoteichoic acid (D-alanyl-LTA)), whereas mitis/oralis streptococci do not possess D-alanyl LTA and increase in healthy sulci [10,11].
Capnocytophaga sputigena and Capnocytophaga ochracea are indigenous bacteria which, in addition to Eikenella corrodens, make lysine decarboxylase. When one or other of these bacteria comprise more than 2.5% of the total bacterial DNA from sulci, the odds ratios that the patient will be refractory is respectively increased 16-fold or 5.8 fold [6]. Lysine decarboxylase activity in healthy or recently cleaned sulci creates inflammation by irritating the dentally attached (DAT) cells of the oral epithelial attachment. Because therapy does not remove indigenous bacteria, increased numbers of bacteria such as E. corrodens or Capnocytophaga spp. in the indigenous flora will infect sulci after cleaning and their lysine decarboxylase production will prevent healthy DAT cells from becoming re-established. E. corrodens and Capnocytophaga spp. form most of a bacterial cluster group that colonizes healthy and recently cleaned sulci [12].
Subjects with advanced periodontitis (>4 mm attachment loss) are difficult to treat becasue of anatomical difficulties in keeping a low bacterial load [1], whereas subjects with mild disease are easy to treat successfully and, inexpensively. The therapeutic response of subjects with moderate periodontitis is unpredictable. At present, the fraction of sulci that bleed when gently probed is the only criterion for whther a patient will be refractory. It is so unsatisfactory that, when periodontists are faced with treatment failure, they do not know whether this was inherent in the patient or the result of an overlooked problem [5]. The object of the present invention is therefore to enable prediction of which patients will be refractory after initial therapy so they can be warned that there is a high risk of treatment failing within two years thereby potentially enabling other treatment options to be identified or at least anticipated.

Kit for use in predicting refractory periodontal disease


An orthopedic apparatus and footwear for distributing weight evenly so as to relieve pressure and discomfort from the ball, arch and heel region of the wearer's foot. This is accomplished by first and second embodiments in which two substantially parallel plates are mounted between an inner sole and an outer sole. The parallel plates are spaced apart by a spacer which is located at a point or region of attachment between the two plates in the arch region of the footwear. The lower plate is rigid and the upper plate is flexible. A layer of easily deformable foam material is provided between the two plates. In the first embodiment, sole spacers are provided in the toe region of the footwear. As a result of the attachment configuration, the plates are cantilever mounted both extending forward and rearward from the arch region. In operation, the flexing of the forward cantilever portion of the flexible plate relative to the rigid plate cushions the ball region and redistributes weight rearward from the ball of the foot and the flexing of the rearward cantilever portion of the flexible plate relative to the rigid plate cushions the heel region and redistributes weight forward from the heel of the foot. A third embodiment also uses a flexible plate and a rigid plate which are attached at an acute angle in the arch region and extend forward toward the ball region. A wedge is provided between the two plates. The flexing of the flexible plate relative to the rigid plate cushions the ball region and redistributes weight rearward from the ball of the foot. The first and second embodiments can be modified as in the third embodiment to provide parallel plates which only extend forward from the arch region, with spacers provided in the rearward region behind the arch.

1. Field of the Invention
The present invention is directed to shoes or footwear worn by humankind, and more particularly to the support the shoes or footwear provide for the foot.
2. Description of the Prior Art
Problems with the foot, especially the condition known as "fallen arches" have been addressed in various shoe or footwear constructions. Included among these are two patents issued to the present inventor, U.S. Pat. Nos. 5,159,767 and 5,203,095. The disclosures of each of these patents are hereby incorporated by reference herein. The emphasis in these prior art patents and in the other prior art embodiments known to the inventor are directed to providing relief by distributing weight from the arch toward the ball of the foot and also away from the heel.
For example, in the inventor's prior art patents, the embodiments were directed to an orthopedic apparatus and shoe incorporating the apparatus including a structure which cooperates to distribute weight from the arch area and heel of the foot toward the ball of the foot. This is accomplished by a combination of rigid and flexible members which cooperate with each other and the foot of the wearer. More particularly, in first and second embodiments, a first rigid reinforcing member is disposed inside of the shoe and located under the arch region of the foot and extends in the direction of the ball of the foot. A flexible supporting member is attached to the bottom of the shoe. A second rigid mounting member extends at an acute angle from the flexible member with the apex at the arch region back toward the heel region and forms the base for mounting of the heel to the shoe if a heel is to be provided. The flexible member, the second rigid member and the inside first rigid member are commonly attached by fasteners such as bolts or pop rivets in the arch region. The result is a pivot axis substantially transverse to the longitudinal axis of the shoe. The flexible member functions as a spring plate which is compressed toward the second rigid member. This serves to support and cushion the heel region of the foot. The first rigid member, extending forwardly toward the ball of the foot, in cooperation with the flexible spring member and second rigid member, serves to provide arch support and to distribute weight over the length of the foot.
In a third embodiment of the prior art orthopedic apparatus by the same inventor, the first rigid reinforcing member is eliminated from the inside of the shoe and replaced by a rigid reinforcing member in the form of a sole wedge which is disposed forward of the apex formed by the acute-angle connected mounting member and supporting member. The acute angle is maintained by a wedge disposed between the mounting member and supporting member. In the third embodiment, the apparatus is attached or bonded to an inner sole and an outer sole is placed over the orthopedic apparatus and bonded to the apparatus and the inner sole. A heel, also bonded to the apparatus, can be provided, or, alternatively, the heel can be eliminated.
In the second and third embodiments, a reinforced resin is used to provide either a flexible plate or a substantially rigid plate, depending upon the number of laminations of vinyl ester resin and graphite fabric employed.
The above corrective measures, while highly effective in addressing fallen arches, do not in themselves address problems people have in the ball of the foot. Therefore, it would be desirable to provide an orthopedic stabilizer attachment or sole design which distributes weight away from the ball of the foot toward the arch and/or the heel of the foot, thereby more evenly distributing the wearer's weight to alleviate pain or discomfort in the ball region, as well as in other regions of the foot.

Orthopedic apparatus and footwear for redistributing weight on foot


A template for positioning small format films on the platen of a flatbed scanner for reducing flare during scanning, the template comprising: a thin rectangular member of opaque material, the member having a plurality of rectangular apertures for receiving small format films; and indicia associated with each aperture for assisting in the proper placement of a small format film in the aperture.

Film digitization using flatbed scanners can be a practical alternative to direct digital image capture or other means of digital image acquisition such as storage phosphor computed radiography. For example, hybrid imaging systems can provide an expedient and low cost imaging solution for both dentists and insurance companies. Without the more significant capital investment required for other digital devices, the dental practitioner can have the advantages that the digital modality can offer, such as imaging capability to support practice management and electronic insurance claims. Insurance companies are also motivated to incorporate imaging into electronic claims in order to reduce overhead associated with manual claims submission.
An important step in any hybrid imaging system is the initial image capture, which for film digitization is the scanning process. Exposure conditions should be carefully controlled during image acquisition so that any subsequent processing steps can be implemented in a more desired fashion. In practice this means controlling unwanted exposure or flare and maintaining proper alignment of the scanned image with the optical configuration of the scanner. Because the relative size of the platen on a flatbed scanner is great compared to a small format film such as a smaller format dental radiograph, the concern over unwanted flare becomes an issue.
Dental radiographs vary greatly in practice. X-ray exposure levels and processing of these films contribute to variability of dental films. A dental film can range from a very light "under-exposed" image to a very dark in appearance "over-exposed" image. Where there is too much exposure on the platen when scanning an under-exposed radiograph, for example, the captured image will not have enough gray value content. Another important consideration during image capture is the alignment of the radiograph on the platen in the correct horizontal and vertical directions to maintain consistency with, for example, the CCD array of a scanner. If the image does not correspond to this alignment when placed on the platen, image rotation may be required, which can alter the aspect ratio of the original image.
One other consideration in the placement of dental radiographs on the platen relates to the actual viewing of the image so that the anatomical structures will be seen digitally in the same orientation as seen on the original radiograph. Smaller format dental films contain a dimple that, when observed properly, points outward toward the viewer in a position corresponding to standard practices in dentistry. Placing the film on the platen in a manner corresponding to this practice can avoid flipping the digital image so that the perspective remains the same as in the radiograph.
U.S. Pat. No. 5,483,325 describes an accessory frame that can be mounted on a photocopier or electronic flatbed scanner that facilitates location and removal of small originals like business cards. This patent does not address the problems described above relating to digitization of small format films using a flatbed scanner, such as regulating exposure and aligning the films on the platen consistent in a manner that is useful to the dental practitioner. This patent does not address the problem of flare in copying transparent originals.

Template for digitizing small format films


The present invention relates to a class of heptapeptide analogs of LHRH. These compounds are useful in the treatment of disease conditions which are mediated by reproductive hormones, including benign prostate hyperplasia, prostate tumors, breast and ovaries tumors, cryptorchidism, hirsuitism, gastric motility disorders, dysmenorrhea, and endometriosis.

Luteinizing hormone releasing hormone (LHRH) is released from the hypothalamus and binds to a receptor on the anterior pituitary gland causing the release of gonadotropin hormones. The gonadotropin hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), secreted from the anterior pituitary gland, regulate fundamental reproductive processes, such as ovarian release and gamete maturation. These play a major role in regulating the synthesis of the steroidal reproductive hormones from the gonads, ie. estrogen and progesterone in females and testosterone in males.
The ongoing system of feedback between hypothalamus, the anterior pituitary gland, and the gonads modulates the fundamental processes related to the reproductive cycle. The feedback process, described by A. V. Schally et al., Fertility and Sterility, 22:11 (1971), provides a web of complex relationships related to reproductive functions. Pulsatile release of the gonadotropin hormones controls levels of steroidal hormone circulating in the mammalian reproductive cycle. Manipulation of the release of these hormones provides an avenue for the design of novel agents useful in treating various conditions related to dysfunction of the reproductive cycle and hormone dependent diseases. Several agonists of natural LHRH have been shown to be clinically useful.
Natural mammalian releasing hormone LHRH isolated and purified from porcine and human hypothalami has been characterized as having the sequence:
(Pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH.sub.2 PA1 R.sup.1 is of the formula R.sup.3 (C.dbd.O)--, wherein R.sup.3 is lower alkyl; PA1 A is an amino acyl residue selected from the group consisting of: PA1 B is an amino acyl residue selected from the group consisting of: PA1 C is an amino acyl residue selected from the group consisting of: PA1 D is seryl; PA1 E is an acyl group selected from the group consisting of: PA1 F is an amino acyl residue selected from the group consisting of: PA1 G is an amino acyl residue selected from the group consisting of: PA1 R.sup.2 is of the formula --NR.sup.4 R.sup.5 ; wherein PA1 R.sup.4 is selected from the group consisting of: PA1 R.sup.5 is selected from the group consisting of: PA1 R.sup.6 is selected from the group consisting of amino, guanidino, hydrogen, hydroxy, phenyl, morpholinyl, piperidinyl, pyrrolyl, pyridyl, pyrrolidinyl, pyrrolidinonyl, and quinuclidinyl; and wherein the piperidinyl, pyrrolyl, pyrrolidinyl, and pyrrolidinonyl groups are optionally substituted with a methyl group. PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH-nBu; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-N(CH.sub.2 CH.sub.3).sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.6 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.4 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 OH; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -phenyl; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 NH-isopropyl; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.7 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.6 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.5 NH-isopropyl; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.5 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.5 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.3 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.10 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.8 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 NHCH.sub.3 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.8 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.10 NH-isopropyl; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.4 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.4 NH(C.dbd.NH)NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 -(2-pyridine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 -(3-pyridine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(3-quinuclidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 -(1-piperidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 -(1-morpholine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 -(2-pyridine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 -[2-(1-methyl)pyrrole]; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 -[2-(1-methyl)pyrrolidine]; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 CH.sub.2 -(1-morpholine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 CH.sub.2 --N[(2-methyl)piperidine]; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 CH.sub.2 -(1-pyrrolidin-2-one); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH--CH.sub.2 CH.sub.2 --CH.sub.2 CH.sub.2 OH; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DLys(Nic)-Leu-NH(CH.sub.2).sub.9 NH.sub.2 ; PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Tyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Tyr-DCit-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Tyr-DCit-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DCit-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-DLys(Nic)-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Arg-DTrp-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Tic-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMePhe-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcSar-D4ClPhe-D1Nal-Ser-NMeTyr-DLys(Nic)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMeTyr-DArg-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMePhe(4-NAc)-DPhe(4-NAc)-Leu-NH--(CH.sub.2). sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMePhe(4-NO.sub.2)-DCit-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Phe(4-Atza)-DPhe(4-Atza)-Leu-NH--(CH.sub.2).sub. 2 -(1-pyrrolidine); PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-NMePhe(4-Atza)-DPhe(4-Atza)-Leu-NH--(CH.sub.2). sub.2 -(1-pyrrolidine); and PA1 NAcD2Nal-D4ClPhe-D3Pal-Ser-Phe(4-NAc)-DPhe(4-NAc)-Leu-NH--(CH.sub.2).sub.2 -(1-pyrrolidine).
as described in A. V. Schally, Science, 202:6 (1978). Substitutions and derivatizations of amino acyl residues have been developed to achieve novel compounds useful in treating various disorders related to mammalian reproductive systems.
Synthetic analogs of LHRH have been described in a number of U.S. patents for exhibiting activity as LHRH agonists or as antagonists of LHRH. For the most part, these compounds contain nine or ten amino acyl residues, substituting naturally-occurring or non-naturally occurring amino acid residues at one or more positions in the natural sequence of LHRH. U.S. Pat. No. 5,110,904 describes nonapeptide and decapeptide LHRH antagonists wherein the nitrogen atom of at least one of the amide bonds has been alkylated. The decapeptide and undecapeptide analogs described in U.S. Pat. No. 5,502,035 have an acyl-substituted N-terminal nitrogen atom.
Truncated peptide compounds have been developed as series of smaller peptide analogs also exhibiting biological activity and having the added advantage of possibly improved oral bioavailability. These reduced-size peptides, described in U.S. Pat. No. 5,140,009, exhibit effective LHRH agonist or antagonist activity. They are "pseudo" hexapeptide, heptapeptide, octapeptide and nonapeptide analogs of LHRH, which have 1 to 3 amino acids eliminated from the N-terminus of a decapeptide antagonist sequence to achieve activity as LHRH antagonists. Distinctively, the peptides described in this invention have the 10 to 8 amino acids eliminated from the C-terminus. Copending U.S. application Ser. No. 09/373,180 discloses and claims a class of pentapeptide LHRH analogs wherein the 1 to 3 amino acids are eliminated from the N-terminus and the 10 to 8 amino acids from the C-terminus of a decapeptide LHRH antagonist.
The development of synthetic LHRH antagonists truncated from the C-terminus having biological activity provides novel compounds for treatment of hormone dependent diseases in male and female mammals. Smaller synthetic peptide sequences provide significant advantages when compared to decapeptide LHRH analogs. These LHRH antagonists are useful in the treatment of a variety of clinical condition in which the suppression of sex steroids plays a major therapeutic role, including delay of puberty, treatment of benign prostatic hyperplasia, palliative treatment or remission of hormonal-dependent tumors of breast and ovaries, palliative treatment or remission of hormonal-dependent tumors of the prostate, the treatment of cryptorchidism, hirsutism in women, gastric motility disorders, dysmenorrhea, and endometriosis.

C-terminus modified heptapeptide LHRH analogs


An intermittent injection type fuel injection valve including a nozzle body comprising a hollow cylindrical member and having a valve seat and an injection port, valve comprising a movable member having a valve seat interposed into the nozzle body and intermittently reciprocated therein; a compressed air supply passage communicating with a compressed air supply source and having an air opening provided on or near at least one of the valve seats of the nozzle body and movable member; and a compressed fuel supply passage communicating with a compressed fuel supply source and having at least one fuel opening provided on the valve seat of the nozzle body and movable member, the valve intermittently controlling the on-off communication of the air and fuel openings of the compressed air and fuel supply passages, and the fuel opening of the compressed fuel supply passage being positioned closer to the injection port than the air opening of the compressed air supply passage. Thus, compressed fuel is supplied to the flow of the compressed air between the valve seats of the nozzle body and movable member, and the mixture of the compressed fuel and air in the form of extremely fine fuel droplets is injected from the injection port at a preset timing in a stable manner under any driving condition of an engine.

1. Field of the Invention
The present invention relates to an intermittent injection type fuel injection valve for an internal combustion engine and particularly for a gasoline engine.
2. Description of the Prior Art
As the demand for the fuel economy and purification of exhaust gases of an internal combustion engine of an automobile is being increased more and more, carburetors are being replaced by an increasing number of electric type fuel injection devices (which will be shortly referred to as an EFI injection valve) which can delicately control the flow rate of fuel.
However, the atomizing characteristics of the EFI injection valve being used are not sufficient. In a manifold injection system, more specifically, the atomized fuel will wet the inner walls of a manifold and combustion chambers so that the fuel mixing operation cannot be accomplished satisfactorily. This results in an increase in the hydrocarbon contents which is detrimental to the exhaust gas emission control. Especially during the cold starting of the automobile, the fuel injected has a small evaporation rate so that the fuel consumption rate and the exhaust purification percentage at cold start are deteriorated in comparison with those of a carburetor.

Intermittent injection type fuel injection valve


Producing high purity lithium solution from a lithium source containing dissolved Na+, Ca2+, and Mg2+, by: passing the source into and out of a bed of sorbent composed of hydrated alumina intercalated with LiX, preferably LiCl, to extract lithium from the lithium source into the sorbent; washing the bed of sorbent with dilute aqueous LiCl to remove lithium from the sorbent to obtain a lithium eluent of increased Li+ concentration; subjecting this eluent to nanofiltration to produce a lithium permeate from which Ca2+, Mg2+, and other nanofilterable components are concurrently removed, yielding a permeate solution with 25% or less, and a retentate solution with 75% or more Ca2+ and Mg2+, as compared to the eluent from washing; and subjecting the permeate solution to a particular forward osmosis yielding a solution having 13,000-25,000 ppm dissolved lithium. Specified optional steps and new features can be used to increase lithium concentrations and purity.

As is well known, in recent years a need has arisen for more economical and efficient technology enabling production of high purity lithium or its salts from suitable sources. This is reflected by an increase in research activities devoted to this subject. And it appears that this need has not been fulfilled yet by any published prior art.

Processes for recovering lithium values from lithium-containing brines