In general, it is preferable to use a base in a heat-developable light-sensitive material for the purpose of accelerating the heat development of said material, and it is necessary to incorporate said base in said light-sensitive material in the form of a base precursor for increasing the stability of said material. In order to use such base precursor practically, which means herein a compound capable of being decomposed under heat to be able to release a basic component, it is necessary that said base precursor must have both stability at normal temperature and rapid decomposability under heat.
Various kinds of conventional base precursors have heretofore been known including, for example, ureas as described in U.S. Pat. No. 2,732,299 and Belgian Patent No. 625,554; urea or ammonium salts of urea and weak acid as described in Japanese Patent Publication No. 1699/65; hexamethylene-tetramines or semicarbazides as described in U.S. Pat. No. 3,157,503; combinations of triazine compound and carboxylic acid as described in U.S. Pat. No. 3,493,374; dicyan-diamide derivatives as described in U.S. Pat. No. 3,271,155; N-sulfonylureas as described in U.S. Pat. No. 3,420,665; amine-imides as described in "Research Disclosure" (1977), RD No. 15776; and salts of decomposable acids such as trichloroacetic acid as described in British Patent No. 998,949.
However, image forming materials containing such conventional base precursors have serious defects. In particular, such conventional base precursors do not fully satisfy the properties desired both with respect to high stability during preservation at normal temperature (e.g., 0.degree.-30.degree. C.) and rapid decomposability during development treatment under heat. Therefore, a high and sufficient image density cannot be obtained, or the S/N (signal/noise) value of the formed image extremely decreases, as the base component tends to be released from said base precursor during preservation thereof, and these phenomena are extremely serious problems.


The present invention relates to an X-ray image intensifier.
As X-ray image intensifiers (to be referred to as "I.I."s hereinafter), a general-purpose single visual field type I.I. and a high-grade variable visual field type I.I. are frequently used. In general, an I.I. comprises a vacuum housing which includes a substantially cylindrical outer casing, and an X-ray entrance window and an X-ray exit window which are arranged to close two ends of the outer casing. In the vacuum housing, input and output surfaces are arranged along the entrance and exit windows, respectively, and a focusing electrode constituting an electronic lens is located between the input and output surfaces. The I.I.s are classified into the single visual field type and variable visual field type due to differences in the number and arrangement of focusing electrodes, and the like. In the case of a variable visual field type I.I., when a voltage distribution to the focusing electrodes is switched, an output visual field image can be enlarged like, a normal visual field, a second visual field, a third visual field,....
The input surface has a base and a phosphor screen formed on the base, and has an arcuated circular shape.
In U.S. Pat. No. 3,716,713, the thickness of the phosphor screen is increased from its center toward the periphery, and is maximized at the periphery.
According to an I.I. disclosed in Japanese Patent Disclosure No. 53-102663, the phosphor screen has the same arrangement as that in the above U.S. Pat. No., and the base has a mosaic structure having a large number of grooves for effecting a light guide function.
According to an I.I. disclosed in Japanese Patent Disclosure No. 59-207551, the thickness of the phosphor screen is decreased from its center toward the periphery, and X-ray optical path lengths passing through the phosphor screen are adjusted to be equal to each other at the center and the periphery of the phosphor screen.
In the I.I.s having the above-mentioned arrangements of the input surfaces, the characteristic of an image obtained at the output surface, in particular, a luminance distribution characteristic, is such that a luminance is high at the center of the image and is gradually decreased toward the periphery. Therefore, a luminance distribution curve obtained as a result of measurement along the diameter of an image becomes a quadratic curve. In the variable visual field I.I., the same luminance distribution characteristic is obtained either in a normal visual field operation or in an enlarged visual field operation.
The reason for the above-mentioned luminance distribution can be considered as follows.
In the I.I.s disclosed in U.S. Pat. No. 3,716,713 and Japanese Patent Disclosure No. 53-102663, in order to prolong an X-ray passage distance in the phosphor screen, which influences light emission, so as to compensate for a quantity of light emitted from the phosphor screen, the thickness of the peripheral portion of the phosphor screen is increased. However, a portion between the intermediate portion and periphery of the phosphor screen cannot provide a similar effect upon increase in thickness, and, to the contrary, the luminance of the periphery of an image is decreased. This is because an excessive increase in thickness at the peripheral portion of the phosphor screen does not contribute to light emission of the phosphor by means of X-rays but degrades a transmittance of X-rays.
In Japanese Patent Disclosure No. 59-207551, in order to obtain a constant passage distance of X-rays at respective positions in the phosphor screen, the thickness of the phosphor screen is decreased at a given rate from its center toward the periphery. However, in order to obtain a theoretical luminance, the phosphor screen must be formed to have a uniform structure and a uniform emission intensity distribution. If these conditions cannot be satisfied, the luminance at the peripheral portion of an image, in particular, an area shifted from the center of the image toward the periphery by a distance 80 to 95% of an effective image diameter, is considerably decreased as compared to the above two prior arts.
When the I.I.s having the above luminance distribution characteristic are used, the following problems are posed. In the distribution characteristic, the luminance at the center of an image is high and is decreased toward the periphery. When the I.I. is coupled to an optical system, a luminance difference between the center and the periphery of the image is emphasized due to an operation of the optical system. For this reason, a dark portion at the peripheral portion of the image has degraded discriminating ability of an object, and cannot be used for observing an object. Therefore, a virtual image area is decreased. When an object is observed upon clinical examination, a contour image of the object must be confirmed. However, when the effective image area is small as described above, the I.I. must be moved stepwise so that a portion to be observed is located at the center of the image. For this reason, the observation requires a long time, and an X-ray irradiation time is also prolonged. For example, when an observation is performed using a TV fluoroscopic imaging method, the entire object, i.e., the entire image, must be scanned, and this requires still more time.
In the enlarged visual field operation mode, e.g., in the second visual field operation mode, the luminance distribution characteristic of an output image is such that the center of an image is bright and the peripheral portion thereof is dark as in the normal visual field operation mode. In any visual field operation mode, an area of an input visual field is changed, but an image area which can be observed is almost not changed. For this reason, when the enlarged visual field operation is performed in order to microscopically observe the object after the contour image of the object is confirmed, the I.I. must be moved to locate the object at the center of image. If the object is a moving body, and is moved to the peripheral portion of an output image, the object cannot be discriminated since the luminance of the peripheral portion is low.
Since the luminance distribution characteristic is not changed in the enlarged visual field operation mode, a low luminance portion is moved upon switching of visual fields. The object is often out of sight upon switching of the visual fields, and the I.I. must be moved to confirm the object at that time. For example, upon clinical examination wherein a change in object must be immediately judged, such as blood vessel imaging, the lack of necessary data and the complicated operations as described above may cause serious problems.


This invention relates to an ignition system and more particularly to an ignition system for an internal combustion engine. The invention also relates to an alternative spark-plug, a drive circuit for a spark-plug and associated methods.
It is known that an ignition system for a vehicle comprises a plurality of distributed spark-plugs connected by respective high voltage power cables to a remote and central high voltage generation means. In a known capacitor discharge ignition system, the high voltage generation means comprises a capacitor connected with a power switching device, such as an SCR switch, in series with a primary winding of a transformer. A secondary winding is connected to the high voltage cables. In use, when a piston of the engine reaches a predetermined position, the power switching device is switched to the closed state. Energy in the capacitor is then transferred to the primary winding resulting in a much higher voltage on the secondary, because of the secondary to primary winding ratio. Once the voltage on the secondary reaches the breakdown voltage of a spark-gap between spark electrodes of the plug, a plasma discharge is created between the spark electrodes.
In the known systems, the switching circuit restricts the minimum inductance of the transformer that can be used. The restricting factors are the maximum current rating of the switch, Im, the switching speed of the switch ts, the switching voltage of the switch, Vs, and the cost of the switch. These limitations result in a very high secondary winding inductance, which has several drawbacks including cost. The large inductance normally requires kilometres (ten thousands of windings) of thin copper wire, which is expensive. The systems are inefficient in that the kilometres of thin copper wire have a resistance of a few kilo-ohms. To transfer enough energy for a reliable spark, a large amount of extra energy is required for each spark. Due to the large amount of energy that must be handled as well as the large amount of copper needed, the systems are bulky. The energy loss due to the copper resistance, heats the transformer. This places a severe limit on the maximum amount of energy that can be transferred to the spark and also affects the placement of the transformer for cooling. The fuel efficiency, completeness of combustion, combustion time, exhaust cleanliness and variability in cycle-to-cycle combustion are limited. Because the transformer is large and heats up, it is normally positioned a distance away from the engine. This requires high voltage cables between spark-plugs and the transformer. These high voltage cables generate a large amount of electromagnetic radiation, which may influence other electronic equipment. In order to eliminate the high voltage cables, coil-on-plug systems which comprise an ignition coil at each spark-plug are used. Because these coils are very close to the engine, normally with very little air flow around them, they overheat easily, which makes them unreliable.
Some ignition coils having a very low secondary resistance have been suggested. This is accomplished by using a magnetic path having a high permeability, to reduce the number of windings while keeping the inductance high enough for the switching circuit. The disadvantage of this approach is that the high permeability magnetic material saturates easily and that a large core is therefore required.
Some other ignition systems have a second energy transfer path on the secondary side. They all have the disadvantage that the energy must either go through the secondary winding or through a semiconductor device. If the energy goes through the secondary winding, the transfer is very inefficient due to the high winding resistance. On the other hand, the semiconductor device must be a high voltage (normally above 30 kV), high current (normally above 1 A) device. These devices are expensive and also result in energy loss.
Another disadvantage of all these systems is that the self-resonance frequency of the secondary winding is low (typically less than 20 kHz). The low self-resonance frequency is due to the long length of secondary wire and the large secondary winding inductance. When the secondary winding is connected in a secondary side circuit, the resonance frequency of the secondary side circuit is even lower than the self-resonance frequency of the secondary winding, due to the spark-plug and cable capacitance. Because of the low secondary resonance frequency, it takes some tens of microseconds to charge the spark-plug or electrode capacitance to a breakdown voltage and also some tens of microseconds to dissipate the remaining secondary energy. This limits the number of successive pulses that can be generated in multiple spark ignition systems, which limits the amount of energy that can be delivered during ignition. The efficiency and amount of energy transferred in some ignition systems are increased by placing a capacitor in parallel with the spark-plug. In these systems the secondary resonance frequency will be even lower. Even in systems where an optimal spark time is calculated (as discussed below), the spark cannot be controlled to within a few tens of microseconds. At 6000 rpm, this inaccuracy is larger than one degree in engine rotation.
It is a known technique to use the spark-plug to measure the current in or resistance of the ionized gas after ignition to gain information about the gas temperature, pressure or composition after combustion. This information is then used as one of the inputs to an engine management system to calculate an average optimal spark time. Because of the high loss of the ignition transformer, the measurement must be done on the secondary side of the transformer, which makes the secondary side circuit complex.
Due to cycle-to-cycle variations, the average optimal spark time can be quite different from the optimal spark time for a single cycle. Although there are a number of techniques available to measure the conditions inside the combustion chamber before ignition, none of them are widely used because they all require extra access points to the combustion chamber, are expensive, most have low reliability and are complex.
When using the spark-plug for measurements, the low secondary resonance frequency therefore limits the measuring frequency after ignition and also makes it very difficult, if not impossible, to measure gas properties before ignition.


Depending on the applications envisaged, thermal stabilization during shaping or during the use of the corresponding products is carried out in various ways.
French Patent FR-A-2,297,227 describes PVC compositions stabilized effectively by metal-organic salts such as, salts of zinc, calcium and barium and .beta.-diketones.
These compositions also contain common additives such as epoxidized oils, lubricants, plasticizers or impact strength enhancing agents.
For some applications, especially those for which the chlorinated polymer has to be plasticized to only a small extent, if at all, the customary presence of relatively large amounts of epoxidized oil, such as epoxidized soybean oil or epoxidized linseed oil, in the polymer, tends to lower the softening point of the polymer.
In fact, the elimination or a significant decrease in the content of these epoxidized oils decreases the thermal stability of the polymer compositions.
This manifests itself, during thermo-forming of the compositions, in a substantial yellowing of the polymer, which is unacceptable for applications requiring transparency and a colorless or only slightly colored appearance of the shaped article, for example, in the case of PVC containers.


The present invention relates generally to microlasers and associated fabrication methods and, more particularly, to Q-switched microlasers and associated fabrication methods.
Modern electro-optical applications are demanding relatively inexpensive, miniaturized lasers capable of producing a series of well-defined output pulses. As such, a variety of microlasers have been developed which include a microresonator and a pair of at least partially reflective mirrors disposed at opposite ends of the microresonator to define a resonant cavity therebetween. The microresonator of one advantageous microlaser includes an active gain medium and a saturable absorber that serves as a Q-switch. See, for example, U.S. Pat. No. 5,394,413 to John J. Zayhowski, which issued on Feb. 28, 1995, the contents of which are incorporated in their entirety herein. By appropriately pumping the active gain medium, such as with a laser diode, the microresonator will emit a series of pulses having a predetermined wavelength, pulse width and pulse energy.
As known to those skilled in the art, the wavelength of the signals emitted by a microlaser is dependent upon the materials from which the active gain medium and the saturable absorber are formed. In contrast, the pulse width of the laser pulses emitted by a conventional microlaser is proportional to the length of the resonator cavity. As such, longer resonator cavities will generally emit output pulses having greater pulse widths. Further, both the pulse energy and average power provided by a microlaser are proportional to the pulse width of the pulses output by the microlaser. All other factors being equal, the longer the microresonator cavity, the longer the pulse width and the greater the pulse energy and average power of the resulting laser pulses.
Conventional microlasers, such as those described by U.S. Pat. No. 5,394,413, are end pumped in a direction parallel to the longitudinal axis defined by the resonator cavity. In this regard, the longitudinal axis of the microresonator cavity extends lengthwise through the resonator cavity. Since the resonation cavity is generally a rectangular solid, the longitudinal axis is oriented so as to be orthogonal to the pair of at least partially reflective mirrors that define the opposed ends of the resonant cavity. As such, conventional microlasers are configured such that the pump source provides pump signals in a direction perpendicular to the at least partially reflective mirrors that define the opposed ends of the resonant cavity. The effective length of the resonator cavity is therefore equal to the physical length of the resonator cavity.
While the microlaser can be fabricated such that the resonator cavity has different lengths, a number of factors contribute to generally limit the permissible length of the resonator cavity. See, for example, U.S. Pat. No. 5,394,413 that states that the resonator cavity, including both the saturable absorber and the gain medium, is preferably less than two millimeters in length. In particular, a number of electro-optical applications require microlasers that are extremely small. As such, increases in the length of the resonator cavity are strongly discouraged in these applications since any such increases in the length of the microresonator cavity would correspondingly increase the overall size of the microlaser.
In addition, the length of passively Q-switched microlasers is effectively limited by the requirement that the inversion density must exceed a predetermined threshold before lasing commences. As the physical length of the resonator cavity increases, greater amounts of pump energy are required in order to create the necessary inversion density for lasing. In addition to disadvantageously consuming more power to pump the microlaser, the increased pumping requirements create a number of other problems, such as the creation of substantially more heat within the microlaser which must be properly disposed of in order to permit continued operation of the microlaser. In certain instances, the heat generated within the microlaser may even exceed the thermal capacity of the heat sink or other heat removal device, thereby potentially causing a catastrophic failure of the microlaser.
Since the pulse width and correspondingly the pulse energy and average power of the pulses output by a microlaser cavity are proportional to the length of the resonator cavity, the foregoing examples of practical limitations on the length of the resonator cavity also disadvantageously limit the pulse width and the corresponding pulse energy and average power of the pulses output by conventional microlasers. However, some modem electro-optical applications are beginning to require microlasers that emit pulses having greater pulse widths, such as pulse widths of greater than 1 nanosecond and, in some instances, up to 10 nanoseconds, as well as pulses that have greater pulse energy, such as between about 10 xcexcJ and about 100 xcexcJ, and greater average power, such as between 0.1 watts and 1 watt. As a result of the foregoing limitations on the length of the resonator cavity and the corresponding limitations on the pulse widths, pulse energy and average power of the pulses output by the conventional microlasers, conventional microlasers do not appear capable of meeting these increased demands.
A microlaser is therefore provided according to one embodiment of the present invention that is capable of supporting a zig-zag resonation pattern in response to pumping of the active gain medium so as to effectively lengthen the microresonator cavity without having to physically lengthen the microresonator cavity. As such, the microlaser of these embodiments can generate pulses having greater pulse widths and correspondingly greater pulse energies and average power levels than the pulses provided by conventional microlasers of a similar size.
According to the present invention, the microlaser includes a microresonator having an active gain medium and a Q-switch, such as a passive Q-switch proximate to and, in one embodiment, immediately adjacent to the active gain medium. In advantageous embodiments, the active gain medium and the Q-switch are integral such that the microresonator may be a monolithic structure. The microresonator extends lengthwise between opposed end faces. The microlaser also includes first and second reflective surfaces disposed proximate respective ones of the opposed end faces to define a microresonator cavity therebetween. While the first and second reflective surfaces can be coated upon respective ones of the opposed end faces of the microresonators, the first and second reflective surfaces can also be formed by mirrors that are spaced from respective ones of the opposed end faces. The microlaser can also include a pump source for introducing pump signals into the active gain medium via at least one of the end surfaces of the microresonator such that the zig-zag resonation pattern is established within the microresonator cavity.
In one advantageous embodiment, the opposed end faces are each disposed at a nonorthogonal angle xcex1, such as between about 30xc2x0 and about 45xc2x0, relative to a line perpendicular to a longitudinal axis defined by the microresonator cavity and extending between the opposed end faces. In one embodiment, the opposed end faces are each disposed at the same nonorthogonal angle xcex1 relative to the longitudinal axis such that the opposed end faces are parallel. In another embodiment, the opposed end faces are oriented in opposite directions by the same nonorthogonal angle xcex1. As a result of the nonorthogonal relationship of the opposed end faces, the microlaser of either embodiment is capable of supporting the zig-zag resonation pattern in response to pumping of the active gain medium via at least one of the end surfaces of the microresonator.
By supporting the zig-zag resonation pattern, the effective length of the microresonator cavity is increased relative to conventional microlasers having substantially the same physical size that do not support a zig-zag resonation path. In this regard, the effective length of the microresonator cavity of the present invention is the length of the zig-zag resonation path established by the microlaser which is significantly longer than the linear resonation paths established by conventional microlasers that extend parallel to the longitudinal axis of the resonator cavity. As such, the microlaser of the present invention can emit pulses having a longer pulse width and correspondingly greater pulse energies and average power levels than the pulses emitted by conventional microlasers of the same physical size.
In order to permit the pump signals to be received by the active gain medium without being reflected from the end face, the microlaser can include an antireflection coating on the end face through which the pump signals are delivered for permitting pump signals having a predetermined range of wavelengths to be received by the active gain medium. The microresonator also generally includes a plurality of side surfaces extending between the opposed end faces. In order to further facilitate resonation within the microresonator cavity, the plurality of side surfaces can be roughened, such as by grinding, to thereby diffuse light.
In order to permit the microlaser to emit signals of a predetermined lasing wavelength via one of the opposed end faces, the first reflective surface is preferably highly reflective for laser signals having the predetermined lasing wavelength. In contrast, the second reflective surface is preferably only partially reflective for laser signals having the predetermined lasing wavelength. As such, the microlaser can emit laser pulses having the predetermined lasing wavelength via the second reflective surface.
In one embodiment, the microlaser also includes a heat sink upon which at least the microresonator is mounted and a housing in which at least the microresonator is disposed. In this embodiment, the housing includes a window through which laser signals generated by the microresonator are emitted.


1. Field of the Invention
This invention relates generally to light emission devices incorporating multiple solid state emitters (e.g., light emitting diodes (LEDs)) and/or multiple phosphors as emissive components.
2. Description of the Related Art
In the illumination art, a variety of approaches have been employed to produce light of desired spectral character.
LEDs have come into widespread usage as a result of their advantages, which include small size, long life, low energy consumption, and low heat generation.
U.S. Pat. No. 6,513,949 issued Feb. 4, 2003 describes a hybrid lighting system for producing white light, including at least one LED and a phosphor-LED, in which the color and number of the LEDs and/or the phosphor of the phosphor-LED may be varied.
U.S. Pat. No. 6,600,175 issued Jul. 29, 2004 describes a light emitting assembly including an LED emitting a first, relatively shorter wavelength radiation, and a down-converting luminophoric medium, e.g., phosphoric medium, that in exposure to such first radiation, responsively emits a second, relatively longer wavelength radiation.
White LED devices have been commercialized that utilize a blue LED and a YAG phosphor (Y3Al5O12 doped with cerium) that partially absorbs blue radiation (centered on 470-480 nm) from the blue LED and emits light having a broad wavelength range with a dominant yellow characteristic (centered on ˜550-600 nm).
The commercially available LED/phosphor devices for production of white light do not provide high conversion efficiency color rendering in various spectral regimes of interest. For example, in many applications, consumers prefer white light having color (as quantifiable by color temperature and color rendering index values) that matches sunlight, conventional incandescent bulb light, or fire light such as candle light.
There is accordingly a continuing need in the art for efficient LED/phosphor illumination systems producing light having a color rendering that closely matches a predetermined spectral distribution.


1. Field of the Invention
This invention relates to an improvement in a collapsible and readily mailable accessory for desk telephones which is easily attachable to serve as a memorandum pad support and writing instrument holder and which also includes a support for a calender in upstanding position and may have a holder for a personal directory in either open or closed position.
2. Description of the Prior Art
This invention is an improvement of my quickly attachable note pad accessories for desk telephones disclosed in my prior U.S. Pat. No. 4,004,112 and corrects an instability and possible displacement of the note pad supporting platform from its intended position which is occasionally encountered when the telephone hand set is removed from the cradle or when the platform is inadvertently struck by the user. The platform of my prior accessory is constructed for manufacture by stamping from sheet metal or by molding of plastic which is then assembled with the wire brace. This results in a costly procedure for a product which is intended for merchandising primarily through the advertising and premium trade.


It has been found that various chemical compounds, such as, for example, nitric oxide (NO), administered during a patient inspiratory phase may provide beneficial effects.
For example, NO presents some lung vasodilator properties that may be helpful for respiratory distress conditions such as respiratory distress syndrome of newborn.
Apparatus for delivering such gaseous chemical compounds have therefore been designed to deliver the compounds during the patient's inspiratory phase.
One such apparatus is described in Canadian Patent Application No. 2,106,696, filed on Sep. 22, 1993 and published on Mar. 25, 1994 and naming Robert Briand and Marie-Hélène Renaudin as inventors. In this document, Briand et al. describe an apparatus for delivering controlled doses of NO to the respiratory system of the patient without conventional pre-mixing of the NO with oxygen supplied by a ventilator device. The apparatus therefore includes means for detecting the beginning of a patient inspiratory phase and to open an electromagnetic valve for a predetermined duration to supply a controlled dose of NO. The duration and the pressure of the NO supplied dose is adjusted so as to obtain the desired NO concentration with respect to the average inhalation volume of the patient. The NO dose supplied is therefore not directly related to the inhalation volume of the patient. Of course, there is no NO injection during the expiration phase.
A major drawback of the apparatus described by Briand et al. is the automatic opening of the electromagnetic valve for a predetermined duration each time the beginning of an inhalation phase is detected. Indeed, if the patient repetitively draws short breaths, harm may be caused by the high concentration of NO injected to the patient.
In an article entitled: “Comparison of two administration techniques on inhaled nitric oxide on nitrogen dioxide production”, published in Canadian journal of Anaesthesiology 1995, Vol. 42: 10, pages 922–927, Dubé et al. describe an injection system for delivering NO during inspiratory phase. In this injection system, an electronic circuit detects the beginning and the end of each inspiration by processing a flow signal supplied by a ventilator. At the beginning of the inspiratory phase, the electronic circuit opens a solenoid valve and NO is injected into the respiratory line. At the end of the inspiratory phase, the electronic circuit closes the solenoid valve and the injection of NO is stopped.
FIG. 1 of the appended drawings is a graph of the inspiratory gas flow 20 vs time for a conventional ventilator when the ventilator is in a first mode. When it is in this mode, the flow of inspiratory gas is constantly delivered for a predetermined duration (inspiratory phase 22) and the patient then expires (expiratory phase 24). In the injection system proposed by Dubé et al., when the gas flow reaches a predetermined threshold level 26, a solenoid valve is open, delivering NO to the patient. The line 28 illustrates the injected flow of NO in the inspiration circuit over time. It is to be noted that the scale is different for the flow of inspiratory gas 20 and the flow 28 of NO. Indeed, line 28 illustrating the flow of NO is shown scaled up for illustrative purposes.
Since the solenoid valve used by Dubé et al. is of the type fully open/fully closed, the flow 28 of NO is constant when the valve is open. As can be seen from FIG. 2, the concentration 29 of NO is essentially constant over time during the inspiratory phases. When the inspiratory gas flow 20 falls below the threshold level 26, the solenoid valve is closed, stopping the flow of NO.
FIG. 3 is a graph of the inspiratory gas flow 30 vs time for a conventional ventilator when the ventilator is in a second ventilating mode. When it is in this mode, the flow of gas is not constantly delivered for a predetermined duration but follows a particular curve during the inspiratory phase 32 and the patient then expires (expiratory phase 34). In the injection system proposed by Dubé et al., when the gas flow reaches a predetermined threshold level 36, the solenoid valve is open delivering NO to the patient. The line 38 illustrates the flow of NO over time. Again, it is to be noted that the scale is different for the flow of inspiratory gas and the flow 38 of NO. Indeed, line 38 illustrating the flow of NO is shown scaled up for illustrative purposes.
Since the solenoid valve used by Dubé et al. is of the type fully open/fully closed, the flow of NO is constant when the valve is open. As can be seen from FIG. 4, the concentration of NO (line 39) is not constant over time during the inspiratory phases but varies inversely with the flow of gas since the flow of NO is constant. When the inspiratory Gas flow 30 falls below the threshold level 36, the solenoid valve is closed.
A drawback of the injection system of Dubé et al. is that, in certain cases, the NO concentration is not constant during the inspiratory phase.
Canadian patent application No. 2,133,516 filed on Oct. 3rd, 1994 and naming Bathe et al. as inventors describes a nitric oxide (NO) delivery system monitoring the inspiratory gas flow of a patient and controlling a proportional valve to allow a calculated flow of NO to enter the inspiratory gas flow. The delivery system calculates the flow of NO in order to maintain a constant, user programmable, NO concentration in the inspiratory gas.
A drawback of the delivery system of Bathe et al. is that, while the delivery system may be programmed so that the concentration of NO in the inspiratory gas flow is constant, there are no provisions to modify the concentration of the NO during a particular inspiratory phase, or to program the variation of the concentration of NO over a number of successive inspiratory phases in view of gradually increasing or decreasing the concentration of NO supplied to the patient.


In coal and other kinds of mining by the Longwell technique, it is conventional for minerals to be removed by a single or double ended ranging shearer drum, which traverses the mineral face with a rotary cutting head carried by the, or each, ranging arm to follow the seam. Typically, each drum is provided with 50 or more locations where a cutting tool is required. A pick holder is welded in place at each location. Each pick holder supports a replaceable pick designed to engage the ground. In some constructions, each pick holder also contains a water sprayer to the rear of the pick for spraying the working end (i.e., the head) of the pick and the coal with water. In general, each pick comprises a pick shank, a securement mechanism to maintain the pick in the pick holder, a head, and a transition area between the head and the shank. The transition area often consists of a rear heel and a forward toe or shoulder.
In use, the shearer drum is rotated about its central axis. As the drum rotates the pick holders spin around with the drum so that picks engage the ground. The water sprayer within the pick holder sprays water on the pick and the coal to minimize dust and the risk of frictional ignitions.
When the pick contacts the wall while the shearer drum rotates, the picks experience forces F as the pick breaks up the material to be excavated. The force F will at times be normal N to the tip 24 with respect to the material face such as along a line 1a normal and orthogonal to the frontal direction. Line 1a goes through the forward most impact point of the pick 10a to the center of rotation of the pick assembly 8a around the excavating equipment 4. In this application, a force that is along line 1a and only has a normal component N is referred to as a normal (or inward) force and a force F that is collinear or tangent T to the cutting path (i.e., orthogonal to line 1a and only has a tangential component) is referred to as a tangential (or rearward) force.
As a pick rotates around with the drum 6, the pick will experience a force F that will at times be primarily tangential (i.e., a force that extends perpendicular to a force that extends normally through the strike point of the tip to the center of rotation of the pick assembly around the drum and has an angle α of 0 degrees). Other times the pick will experience a force at an angle α from tangential T that has a tangential component and a normal component (i.e., a force between tangential T and normal N). As the pick continues to rotate the pick will experience a force that is primarily normal (i.e., a force that is primarily inward on the pick and has an angle α of 90 degrees from tangential T and that extends normally through the strike point of the tip 24a to the center of rotation of the pick assembly around the drum 6). The transition of forces between those that are predominantly inward or normal and those that are predominantly rearward or tangential causes the pick to rock within the pick holder. The cyclic rocking causes the pick to wear the pick holder prematurely as can be seen in FIG. 4. Premature wear on the pick holder causes the pick locking system to become ineffective and leads to picks being ejected from the pick holder during use. Typically, when a pick breaks or is ejected the pick will also break the water sprayer.
Damaged holders must be cut from the drum and new holders welded in their place. Because of the risk of frictional ignitions and tight dark working areas, typically, shearer drums must be removed from the longwall (i.e., removed from service) and moved to a safe location for refurbishment, for example to the surface. Moving the shearer drum, cutting the welds between the shearer drums and the pick holder, and welding new pick holders in place is time consuming. Such refurbishment can be lengthy and expensive.


This invention relates to medical guidewires typically used by physicians to gain access to restricted regions of the body and over which therapeutic devices are passed for insertion to a site of interest. Specifically, the invention relates to an ultrasound imaging guidewire with a detachable imaging guidewire body and a stationary central core.
Many surgeries involve the insertion of guidewires into a patient""s body. The guidewire may be inserted into the digestive tract, urethra, blood vessels, heart chamber, a body cavity such as the abdominal cavity, or a hollow organ. Typically, an artery is the vessel of interest. The artery could be a relatively large peripheral vessel, a relatively small proximal coronary artery, or an artery of any size in between. The guidewire may include an imaging portion that permits close examination of the site of interest by means of ultrasonic waves. An ultrasonic imaging guidewire may permit the user to obtain 360 degree (i.e., cross-sectional) acoustic images of the vessel wall to, for example, determine the tissue morphology state of a site of interest, position a therapeutic device, monitor the progress of treatment or observe the site after treatment to determine the course of further treatment.
Often, the guidewire must be Positioned at a predetermined site after passing through a complex network of blood vessels. Such placement may require a considerable amount of time. Furthermore, the difficulty and time required for guidewire placement increases with increasing vessel occlusion at later stages of disease. Thus, placement of the guidewire can be a time-consuming and difficult task.
Accordingly, once the physician has taken the time to correctly place the guidewire, it is preferable to maintain the guidewire position. However, it is also desirable to obtain images of the diseased area which may require that the guidewire be axially translated to view the site of interest. Hence, after the physician places the guidewire, the physician needs to move the imaging guidewire back and forth to make a correct diagnosis of the lesion morphology. The problem with advancements and pullbacks of the imaging guidewire is that the physician may lose the correct placement of the guidewire, and have to spend additional time repositioning the guidewire. Thus, there currently exists a need to maintain guidewire positioning while permitting multi-position, real-time imaging.
Furthermore, the back-and-forth movement of the guidewire may damage the patient""s vessels. Therefore, there currently exists a need to provide safer guidewire imaging.
A significant problem encountered by physicians is the proper positioning of stents. Stents are often used to prevent lumen closure following bypass surgery and to treat acute vessel closure after angioplasty. It is often extremely difficult for a physician to accurately determine the correct location to deploy a stent, particularly at a bifurcating vessel. Incorrect placement of a stent can lead to xe2x80x9cstent jailxe2x80x9d and is demonstrated in FIG. 3. As shown in FIG. 3, if the stent 100 is incorrectly placed at a bifurcating vessel location 102, the stent 100 may block the vessel 102 and the physician can no longer access that vessel 102. This is particularly dangerous if the vessel 102 becomes diseased, such as at 104, and access is needed for therapy. Thus, there currently exists a need for easier, multi-position, ultrasonic imaging of the site of interest to assist in accurate placement of a stent.
There also currently exists a need to provide improved imaging capabilities, without losing proper guidewire positioning, so as to efficiently locate the site of interest, to properly position therapeutic catheters such as an angioplasty balloon, and to observe continuously the site or sites of interest. There also exists a need to decrease the complexity and to save time associated with the ultrasonic imaging procedure.
Accordingly, a general object of the present invention is to provide an apparatus and method for permitting multi-position, ultrasonic imaging without losing correct guidewire positioning.
A further object of this invention is to provide a faster imaging guidewire procedure, and to eliminate the complexity associated with the ultrasonic imaging guidewire procedure.
Another object of this invention is to prevent harm to a patient""s vessels by eliminating the back and forth movement of the guidewire tip.
In order to achieve the above objects of the present invention, an ultrasound imaging guidewire is provided with a connector to permit a static central core to be temporarily detached from an imaging guidewire body of a guidewire. A method is also provided to permit efficient and accurate imaging of the site of interest. The method includes the step of inserting a guidewire with an imaging guidewire body and a static central core into a patients body at a particular site of interest. Next, the imaging guidewire body is rotated at the site of interest to obtain acoustical images. Finally, the imaging guidewire body of the guidewire is axially translated to further obtain images of the site or sites of interest, without axially translating the static central core.
Additional objects, advantages, aspects and features of the present invention will further become apparent to persons skilled in the art from a study of the following description and drawings.


An example of prior art chip capacitors is shown in FIG. 1. The chip capacitor shown in FIG. 1 includes a solid-state tantalum capacitor element 2 with a cathode layer 4 disposed on its outer surface. An anode lead 6 is led out from one end surface of the capacitor element 2. A flat cathode terminal 8 is connected to the cathode layer 4 with an electrically conductive adhesive (not shown). Also, a flat anode terminal 10 is welded to the tip end of the anode lead 6. An encapsulation 12 is provided by transfer molding with epoxy resin. Outer end portions of the flat anode and cathode terminals 10 and 8 are bent to extend along the end surfaces of the encapsulation 12 and, then, further bent to extend along the bottom surface of the encapsulation 12.
It is seen that a large proportion of the cathode terminal 8 is within the encapsulation 12, and the proportion of the volume occupied by the cathode terminal 8 to the entire volume of the encapsulation 12 is large. Further, both the cathode terminal 8 and the anode terminal 10 include portions extending on the side surfaces of the encapsulation 12. Accordingly, the length of the capacitor is increased by the thickness of these portions. In mounting such chip capacitor on a printed circuit board, the side surfaces of the cathode and anode terminals 8 and 10 are connected to the board by solder 14. Accordingly, when a number of such chip capacitors are to be mounted on a board side by side, as shown in FIG. 2, the spacing between adjacent chip capacitors must be large enough to prevent short-circuiting of adjacent capacitors, which prevents dense packing of the capacitors. Recently, smallsized, portable electric and electronic devices, such as cellular phones, have been remarkably improved, and chip capacitors to be used in such devices are required to be down-sized. For down-sizing prior art chip capacitors like the ones described above, the volume occupied by the capacitor element 2 in the chip capacitor including the encapsulation 12 should be as small as possible, which sometimes prevents the chip capacitor from having desired capacitance.
Therefore an object of the present invention is to provide a chip capacitor which makes high density packing possible, and can have desired capacitance, while being small in size.


A large and growing population of users is enjoying entertainment through the consumption of digital media items, such as music, movies, images, electronic books, and so on. The users employ various electronic devices to consume such media items. Among these electronic devices (referred to herein as user devices) are electronic book readers, cellular telephones, personal digital assistants (PDAs), portable media players, tablet computers, netbooks, laptops and the like. These electronic devices wirelessly communicate with a communications infrastructure to enable the consumption of the digital media items. In order to wirelessly communicate with other devices, these electronic devices include one or more antennas.
The conventional antenna usually has only one resonant mode in the lower frequency band and one resonant mode in the high-band. One resonant mode in the lower frequency band and one resonant mode in the high-band may be sufficient to cover the required frequency band in some scenarios, such as in 3G applications. 3G, or 3rd generation mobile telecommunication, is a generation of standards for mobile phones and mobile telecommunication services fulfilling the International Mobile Telecommunications-2000 (IMT-2000) specifications by the International Telecommunication Union.


1. Field of the Invention
Generally, the present disclosure relates to integrated circuits, and, more particularly, to the manufacture of field effect transistors in complex circuits including memory areas, for instance, in the form of a cache memory of a CPU.
2. Description of the Related Art
Integrated circuits comprise a large number of circuit elements on a given chip area according to a specified circuit layout, wherein transistor elements represent one of the major semiconductor elements in the integrated circuits. Hence, the characteristics of the individual transistors significantly affect overall performance of the complete integrated circuit. Generally, a plurality of process technologies are currently practiced, wherein, for complex circuitry, such as microprocessors, storage chips, ASICs (application specific ICs) and the like, MOS technology is currently one of the most promising approaches due to the superior characteristics in view of operating speed and/or power consumption and/or cost efficiency. During the fabrication of complex integrated circuits using MOS technology, millions of transistors, i.e., N-channel transistors and/or P-channel transistors, are formed on a substrate including a crystalline semiconductor layer. A MOS transistor, irrespective of whether an N-channel transistor or a P-channel transistor is considered, comprises so-called PN junctions that are formed by an interface of highly doped drain and source regions with an inversely or weakly doped channel region disposed between the drain region and the source region. The conductivity of the channel region, i.e., the drive current capability of the conductive channel, is controlled by a gate electrode formed above the channel region and separated therefrom by a thin insulating layer. The conductivity of the channel region, upon formation of a conductive channel due to the application of an appropriate control voltage to the gate electrode, depends on the dopant concentration, the mobility of the majority charge carriers and, for a given extension of the channel region in the transistor width direction, on the distance between the source and drain regions, which is also referred to as channel length. Hence, in combination with the capability of rapidly creating a conductive channel below the insulating layer upon application of the control voltage to the gate electrode, the conductivity of the channel region substantially determines the performance of the MOS transistors. Thus, the latter aspect renders the reduction of the channel length, and associated therewith the reduction of the channel resistivity, a dominant design criterion for accomplishing an increase in the operating speed of the integrated circuits.
On the other hand, the drive current capability of the MOS transistors also depends on the transistor width, i.e., the extension of the transistor in a direction perpendicular to the current flow direction, so that the gate length and thus the channel length, in combination with the transistor width, are dominant geometric parameters which substantially determine the overall transistor characteristics in combination with “transistor internal” parameters, such as overall charge carrier mobility, threshold voltage, i.e., a voltage at which a conductive channel forms below the gate insulation layer upon applying a control signal to the gate electrode, and the like. On the basis of field effect transistors, such as N-channel transistors and/or P-channel transistors, more complex circuit components may be created, depending on the overall circuit layout. For instance, storage elements in the form of registers, static RAM (random access memory), may represent important components of complex logic circuitries. For example, during the operation of complex CPU cores, a large amount of data has to be temporarily stored and retrieved, wherein the operating speed and the capacity of the storage elements have a significant influence on the overall performance of the CPU. Depending on the memory hierarchy used in a complex integrated circuit, different types of memory elements are used. For instance, registers and static RAM cells are typically used in the CPU core due to their superior access time, while dynamic RAM elements are preferably used as working memory due to the increased bit density compared to registers or static RAM cells. Typically, a dynamic RAM cell comprises a storage capacitor and a single transistor wherein, however, a complex memory management system is required so as to periodically refresh the charge stored in the storage capacitors which may otherwise be lost due to unavoidable leakage currents. Although the bit density of dynamic RAM devices may be very high, a charge has to be transferred from and to the storage capacitors in combination with periodic refresh pulses, thereby rendering these devices less efficient in terms of speed and power consumption compared to static RAM cells. Thus, static RAM cells may be advantageously used as high speed memory with moderately high power consumption, thereby, however, requiring a plurality of transistor elements so as to allow the reliable storage of an information bit.
FIG. 1a schematically illustrates a circuit diagram of a static RAM cell 150 in a configuration as may typically be used in modern integrated circuits. The cell 150 comprises a storage element 151, which may include two inversely coupled inverters 152A, 152B, each of which may include a couple of transistors 100B, 100C. For example, in a CMOS device, the transistors 100B, 100C may represent an N-channel transistor and a P-channel transistor, respectively, while, in other cases, transistors of the same conductivity type, such as N-channel transistors, may be used for both the transistors 100B and 100C. A corresponding arrangement of N-channel transistors for the upper transistors 100C is illustrated at the right-hand side of FIG. 1a. Moreover, respective pass or pass gate transistors 100A may typically be provided so as to allow a connection to the bit cell 151 for read and write operations, during which the pass transistors 100A may connect the bit cell 151 to corresponding bit lines (not shown), while the gate electrodes of the pass transistors 100A may represent word lines of the memory cell 150. Thus, as illustrated in FIG. 1a, six transistors may be required to store one bit of information, thereby providing a reduced bit density for the benefit of a moderately high operating speed of the memory cell 150, as previously explained. Depending on the overall design strategy, the memory cell 150 may require the various transistor elements 100A, 100B, 100C to have different characteristics with respect to drive current capability in order to provide reliable operational behavior during read and write operations. For example, in many design strategies, the transistor elements are provided with minimum transistor lengths, wherein the drive current capability of the transistors 100B, which may also be referred to as pull-down transistors, may be selected to be significantly higher compared to the drive current capability of the pass transistors 100A, which may be accomplished by appropriately adjusting the respective transistor width dimensions for the given desired minimum transistor length.
FIG. 1b schematically illustrates a top view of a portion of the memory cell 150 as a hardware configuration in the form of a semiconductor device. As illustrated, the device 150 comprises a silicon-based semiconductor layer 102, in which an active region 103 is defined, for instance, by providing a respective isolation structure 104 that laterally encloses the active region 103, thereby defining the geometric shape and size of the transistors 100A, 100B. As illustrated, the transistors 100A, 100B may be formed in and above the same active region 103 since both transistors may have the same conductivity type and may be connected via a common node, as is for instance illustrated as nodes 153A, 153B in FIG. 1a. As previously explained, the transistors 100A, 100B, i.e., the pass transistor and the pull-down transistor, may have substantially the same length so that respective gate electrodes 106 may have substantially the same length 106L, whereas a transistor width 103B of the pull-down transistor 100B may be greater compared to a transistor width 103A of the pass transistor 100A, in order to establish the different current capabilities of these transistors.
FIG. 1c schematically illustrates a cross-sectional view taken along the line 1c of FIG. 1b. As illustrated, the device 150 comprises a substrate 101 which may typically be provided in the form of a silicon substrate, possibly in combination with a buried insulating layer (not shown) if a silicon-on-insulator (SOI) is considered. Above the substrate 101 and a possible buried insulating layer, the semiconductor layer 102, in the form of a silicon layer, is provided, in which the isolation structure 104 (see FIG. 1b) may be formed according to the desired shape so as to define the active region 103 according to the configuration as shown in FIG. 1b. That is, the active region 103 has the width 103B in the transistor 100B and has the width 103A in the transistor 100A. In this respect, an active semiconductor region is to be understood as a semiconductor region having an appropriate dopant concentration and profile so as to form one or more transistor elements in and above the active region, which have the same conductivity type. For example, the active region 103 may be provided in the form of a lightly P-doped semiconductor material, for instance in the form of a P-well, when the semiconductor layer 102 may extend down to a depth that is significantly greater than the depth dimension of the transistors 100A, 100B, when the transistors 100A, 100B may represent N-channel transistors. Similarly, the active region 103 may represent a basically N-doped region when the transistors 100A, 100B represent P-channel transistors. Furthermore, in the manufacturing stage shown in FIG. 1c, the transistors 100A, 100B may comprise the gate electrode 106, for instance in the form of a polysilicon material, which is separated from a channel region 109 by a gate insulation layer 108. Furthermore, depending on the overall process strategy, a sidewall spacer structure 107 may be formed on sidewalls of the gate electrodes 106. Additionally, drain and source regions 110 may be formed in the active region 103 and may connect the transistors 100A, 100B. Typically, metal silicide regions 111 are provided in the gate electrode 106 and an upper portion of the drain and source regions 110 so as to reduce contact resistance of these areas.
The device 150 is typically formed on the basis of the following processes. First, the isolation structure 104 may be formed, for instance, as a shallow trench isolation by etching respective openings into the semiconductor layer 102 down to a specific depth, which may even extend to a buried insulating layer, if provided. Thereafter, the corresponding openings may be filled with an insulating material by deposition and oxidation processes, followed by a planarization such as chemical mechanical polishing (CMP) and the like. During the process sequence for the isolation structure 104, advanced lithography techniques may have to be used in order to form a corresponding etch mask, which substantially corresponds to the shape of the active region 103, which requires the definition of a moderately narrow trench to obtain the desired reduced width 103A of the transistor 100A. Thereafter, the basic doping in the active region 103 may be provided by performing respective implantation sequences, which may also include sophisticated implantation techniques for introducing dopants for defining the channel doping and the like. Next, the gate insulation layers 108 and the gate electrodes 106 may be formed by depositing, oxidizing and the like an appropriate material for the gate insulation layer 106, followed by the deposition of an appropriate gate electrode material, such as polysilicon. Subsequently, the material layers are patterned by using advanced lithography and etch techniques, during which the actual length 106L of the gate electrodes 106 may be adjusted, thereby requiring extremely advanced process techniques so as to obtain a gate length of approximately 50 nm and less. Next, a part of the drain and source regions 110 may be formed by implanting appropriate dopant species followed by the formation of the spacer structure 107, or at least a portion thereof, followed by a subsequent implantation process for defining the deep drain and source areas, wherein a corresponding implantation sequence may be repeated on the basis of an additional spacer structure if sophisticated lateral concentration profiles may be required in the drain and source regions 110. Thereafter, appropriate anneal processes may be performed to re-crystallize implantation-induced damage in the active region 103 and also to activate the dopant species in the drain and source areas 110. It should be appreciated that, for a reduced gate length in the above-defined range, the sophisticated geometric configuration of the active region 103 may result in process non-uniformities, for instance during the deposition and etching of a spacer material for forming the sidewall spacer 107. Typically, the spacer structure 107 is formed by depositing an appropriate material, for instance a silicon dioxide liner (not shown) followed by a silicon nitride material, which may subsequently be selectively etched with respect to the silicon dioxide liner on the basis of well-established anisotropic etch recipes. However, at areas indicated as 112 in FIG. 1b, irregularities may be observed which may even be increased due to respective non-uniformities created during previously performed lithography processes, such as the lithography process for patterning the gate electrodes 106 and the like. Consequently, the areas 112 may have a significant influence on the further processing of the device 150, which may finally result in non-predictable behavior of the transistor 100B and thus the overall memory cell 150. For example, during the further processing, the metal silicide regions 111 may be formed by depositing a refractory metal, such as nickel, cobalt and the like, which may then be treated to react with the underlying silicon material, wherein typically the isolation structure 103 and the spacer structure 107 may substantially suppress the creation of a highly conductive metal silicide. However, due to the previously generated irregularities, respective leakage paths or even short circuits may be created, thereby undesirably influencing the final drive current capability of the transistor 100B, which may result in a less stable and reliable operation of the memory cell 150, thereby significantly contributing to yield loss of sophisticated semiconductor devices including static RAM areas.
The present disclosure is directed to various methods and devices that may avoid, or at least reduce, the effects of one or more of the problems identified above.


1. Field of the Invention
The invention relates to a drive unit, in particular for an injection unit or an ejector of an injection molding machine.
2. Description of Related Art
Recently, one has provided injection molding machines with electric and hydraulic drives, wherein actuations at high speed are exerted by the electric drive with relatively low forces, while the hydraulic drive is particularly advantageous if high axial forces have to be applied with comparatively minor actuations.
In the case of a closing unit of a plastics injection molding machine, for instance, the drive unit moves a movable tool faceplate of the machine. In so doing, the drive unit has to fulfill two important, different objects. On the one hand, it is to move the tool faceplate as quickly as possible for closing and for opening the mould so as to keep the cycle time of the manufacturing of an injection-molded component as short as possible. On the other hand, it is to impact the tool faceplate with a high clamping force, so that the tool can be kept shut against the high inner pressure during injection molding. The drive unit therefore has to be configured such that it is adapted to perform actuations at high speed and to apply high forces with a comparatively minor stroke. Requirements of this kind are posed, except with a closing unit, also with the actuation of ejectors or the injection unit of an injection molding machine.
DE 101 21 024 A1 (cf. in particular FIGS. 26, 34) of the Applicant discloses a drive unit that is adapted to fulfill the afore-mentioned requirements. This drive unit comprises a hydraulic force transmitting element, the smaller piston unit of which is actuated via an electrically actuated stroke spindle device for closing a tool. This smaller piston unit may consist of one single smaller piston, or of a plurality of small pistons. These confine, along with a cylinder or interface and one or several large pistons of the force transmitting element, a pressure chamber, wherein, by the moving of the small piston unit into the pressure chamber, a high pressure can be generated, which acts, via the large active surface of the large pistons (power pistons) on the movable tool faceplate which may then be kept shut with high force. During the quick closing of the tool with comparatively low force, the interface is indirectly connected with a spindle nut of the spindle device, so that the piston unit with smaller diameter, the power piston, and the interface are jointly shifted by the spindle device. For applying the high force, the interface is fixed at the frame of the injection molding machine, so that the further closing movement of the tool is determined by the moving of the smaller piston unit into the pressure chamber and the corresponding axial movement of the large piston of the force transmitting element.
In one embodiment described in DE 101 21 024 A1 (FIG. 34), the coupling of the cylinder to the stroke spindle device is performed hydraulically. To this end, a chamber confined by a section of the small piston unit and the cylinder is impacted with pressure from a high pressure storage means, so that the pressure medium incorporated in the chamber acts like rigid pulling mechanics and the cylinder participates in the closing stroke of the stroke spindle device and thus of the small piston unit.
In an embodiment illustrated in FIG. 26 of DE 101 21 024 A1, the small piston unit is, during rapid motion, connected with the large piston via an electromagnetic coupling. This large piston is in turn centered with respect to the cylinder by a prestressed centering spring arrangement. The prestressing of this centering spring arrangement is chosen such that the axial shifting of the small piston unit is, during rapid motion, transferred to the large piston via the coupling, and from there via the centering spring arrangement to the cylinder so as to take it along.
In both known solutions the force transmitting element is designed to be double-acting, so that, for tearing open the tool, a high tear-open force acts on the tool via the force transmitting element as the small piston unit moves in opening direction. This movement of the small piston unit in opening direction is performed during the application of the tear-open force against the force of a prestressed pressure spring.
A disadvantage of the initially mentioned known construction (FIG. 34) is that, for applying the high pressure in the chamber during rapid motion, a comparatively complex circuitry with high pressure storage means and electrically controlled direction control valve is required, so that this circuitry variant is very expensive and also requires substantial construction space.
In the solution illustrated in FIG. 26 of DE 101 21 024 A1, the large piston has to be designed with a very large surface due to the integrated coupling, so that a compact solution cannot be realized with such a construction.


A semiconductor module has been extensively used in a power converter, such as an electrical system of a hybrid vehicle or an electrical vehicle. The semiconductor module configuring an energy-saving controller has a power semiconductor element for controlling a high current.
The heat generated by such a power semiconductor element when controlling a high current tends to increase especially as miniaturization and power boosting of the power semiconductor element advance. Therefore, a major problem is to cool a semiconductor module having a plurality of power semiconductor elements.
A liquid cooling cooler has conventionally been used in such a semiconductor module. The power semiconductor elements need to be cooled efficiently in order to improve the cooling efficiency of the semiconductor module. The liquid cooling cooler is designed in various ways to improve its cooling efficiency thereof, by increasing the flow rate of its refrigerant, shaping heat radiating fins (cooling body) into a shape to provide good heat-transfer efficiency, and increasing heat-transfer efficiency of materials configuring the fins.
Increasing the flow rate of refrigerant supplied to the cooler or adopting the fin structures providing good heat-transfer efficiency can easily increase a pressure loss of the refrigerant inside the cooler. Especially in a cooler that uses a plurality of heat sinks to cool a large number of power semiconductor elements, the pressure loss of the refrigerant is significant in a passage structure where refrigerant passages are connected in series. To reduce the pressure loss of the refrigerant, it is ideal to construct a cooler in which its cooling efficiency can be enhanced with a low refrigerant flow rate. However, adopting a new fin material for improving the heat-transfer efficiency of the fin material configuring the cooler can lead to increases in costs of the entire cooler.
In a recent cooler, a refrigerant introducing passage for introducing a refrigerant and a refrigerant discharge passage for discharging the refrigerant are arranged parallel to each other, and a plurality of heat sinks are disposed therebetween in a refrigerant circulation direction so as to be substantially perpendicular to the abovementioned passages (for example, Japanese Patent Application Publication No. 2001-35981, Japanese Patent Application Publication No. 2007-12722, Japanese Patent Application Publication No. 2008-205371, Japanese Patent Application Publication No. 2008-251932, Japanese Patent Application Publication No. 2006-80211, Japanese Patent Application Publication No. 2009-231677, Japanese Patent Application Publication No. 2006-295178). In this case, the refrigerant can flow parallel between fins configuring each heat sink, increasing the cooling performance per pressure loss and reducing the pressure loss of the refrigerant inside the passages, as shown in Japanese Patent Application Publication No. 2006-80211.
Japanese Patent Application Publication No. 2009-231677 describes a liquid cooling cooler in which the entire rear-side wall of the casing is smoothly inclined forward from the right-side wall toward the left-side wall and in which the cross-sectional area of the passage of the entrance header part decreases gradually from the cooling liquid entrance side toward the left-side wall (see the paragraphs [0024] and [0031] and FIG. 2). Japanese Patent Application Publication No. 2008-205371 describes a liquid cooling cooler in which the connection water paths for introducing and discharging a refrigerant are disposed on the same side surface of the module and in which each of the paths is disposed in a direction perpendicular to the fins without changing the cross-sectional areas thereof (see FIG. 1).
Japanese Patent Application Publication No. 2006-295178 describes a heat sink apparatus for use in a computer electronic device and the like. In this heat sink apparatus, the shape of the inflow guide plate extending toward the plurality of passages is configured so as to be inclined into the shape of a curve of a convex surface toward the plurality of passages, as it moves away from the inflow port. In addition, the cross-sectional area of the inflow guide part becomes small gradually from the inflow port. Moreover, the shape of the inflow guide plate is same as that of the inflow guide plate (see the paragraph [0030] and FIG. 6).
In the conventional cooling technologies, however, a drift distribution in which the refrigerant drifts away occurs due to the shapes of the heat sinks and refrigerant passages, the method for disposing the heater elements, or the shapes of the refrigerant introduction/discharge ports, etc. Such drift distribution caused in the conventional coolers disturbs the balance of the cooling performance. Therefore, a uniform and stable cooling performance cannot be accomplished. Another problem is that only the temperatures of heat generated in the semiconductor elements disposed opposing the refrigerant discharge port increase significantly, reducing the lives of the elements or damaging the elements.
As in the coolers disclosed in Patent Documents 6 and 7 in which the cross-sectional areas of the entrance header parts decrease gradually in a direction in which the entrance header parts extend, their flow rate distributions are improving, but the increase in the temperatures of the sections near the refrigerant introduction ports cannot be prevented.


Arrows conventionally include fletchings mounted on their rear ends to provide flight stability. Usually three and sometimes four fletchings are mounted in a circumferentially spaced relationship about the rear end of the arrow shaft. In addition, two fletchings and a single fletching have also been utilized on arrow shafts in the past but have never received any significant commercial acceptance by archers.
Feathers were the only type of fletchings conventionally utilized by archers until about five years or so ago when "rubber" fletchings gained acceptance. Actually, the designation "rubber" fletching is now somewhat of a misnomer since this type of fletching is presently made from synthetic plastic, although such plastic does have some rubber-like characteristics. Usually rubber fletchings are extruded with a mounting foot and a vane projecting from the foot, and the fletching is cut after the extrusion to the required length with the vane having the desired shape. In addition to feather and rubber fletchings, sheet plastic has also been previously utilized to make fletchings but has never received any significant commercial acceptance by archers.
Arrow spin or rotation is desirable to maintain flight stability and is usually achieved by mounting fletchings on the arrow shaft either at a slight angle with respect to the elongated axis thereof or in a helical configuration thereabout such that a screw action takes place during forward flight through the air. The consequent rotation stabilizes the arrow flight even when subjected to head, side, and tail winds that would otherwise significantly alter the flight trajectory. Such arrow rotation is particularly important with hunting arrows whose flat blade type points can tend to "sail" if there is not sufficient stabilizing rotation.
Prior art arrow fletchings of the type described above are illustrated by U.S. Pat. Nos.: 2,193,397; 2,277,743; 2,525,332; 3,106,400; 3,539,187; 3,595,579; 3,749,403; 3,895,802; 4,003,576; and 4,088,323.
My prior U.S. Pat. Nos. 3,756,602 and 4,012,043 disclose arrow fletchings made by sharply bending sheet plastic to the desired shape. The arrow fletching disclosed by my U.S. Pat. No. 3,756,602 patent includes vanes that are spaced outwardly from the shaft an increasing extent in the forward direction so as to provide a construction that compensates for cross-winds by steering the arrow into the wind. The arrow fletching disclosed by my U.S. Pat. No. 4,012,043 patent includes vanes that each define a pocket of decreasing volume from front to rear to effect a pressure buildup that causes stabilizing rotation of the arrow during flight.
Frictional drag generated by arrow fletchings during flight is affected by wind changes and thus alters the flight trajectory. Wind changes are a much greater problem with the longer distances involved in target shooting as compared to hunting, since any change in the frictional drag due to wind changes is effective over a greater period of time with the higher trajectory required for longer distances. Also, arrow fletchings heretofore have not had a construction capable of compensating for wind changes in order to maintain the desired flight trajectory.


1. Field of the Invention
The present invention relates to a procedure for the production of enantiomerically pure monomeric and dimeric C-10 non-acetal derivatives of natural trioxane artemisinin having high in vitro antimalarial, antiproliferative and antitumor activities. The present invention further relates to the formation of a novel trioxane aldehyde compound produced via a chemoselective C--C bond formation at the C-10 position upon reaction of artemisinin trioxane lactone with lithiothiazole or lithiobenzothiazole. This trioxane aldehyde may then be reacted with organolithium, Grignard, and phosphorus ylide nucleophiles exclusively via carbonyl addition.
2. Description of the State of Art
Each year approximately 200-300 million people experience a malarial illness and over 1 million individuals die. In patients with severe and complicated disease, the mortality rate is between 20 and 50%.
Plasmodium is the genus of protozoan parasites which is responsible for all cases of malaria and Plasmodium falciparum is the species of parasite that is responsible for the vast majority of fatal malaria infections. Malaria has traditionally been treated with quinolines such as chloroquine, quinine, mefloquine, and primaquine and with antifolates such as sulfadoxine-pyrimethamine. Unfortunately, most P. falciparum strains have now become resistant to chloroquine, and some, such as those in Southeast Asia, have also developed resistance to mefloquine and halofantrine; multidrug resistance is developing in Africa also.
The endoperoxides are a promising class of antimalarial drugs which may meet the dual challenges posed by drug-resistant parasites and the rapid progression of malarial illness. The first generation endoperoxides include artemisinin and several synthetic derivatives, discussed in further detail below.
Artemisia annua L., also known as qinghao or sweet wormwood, is a pervasive weed that has been used for many centuries in Chinese traditional medicine as a treatment for fever and malaria. Its earliest mention, for use in hemorrhoids, occurs in the Recipes for 52 Kinds of Diseases found in the Mawangdui Han dynasty tomb dating from 168 B.C. Nearly five hundred years later Ge Hong wrote the Zhou Hou Bei Ji Fang (Handbook of Prescriptions for Emergency Treatments) in which he advised that a water extract of qinghao was effective at reducing fevers. In 1596, Li Shizhen, the famous herbalist, wrote that chills and fever of malaria can be combated by qinghao preparations. Finally, in 1972, Chinese chemists isolated from the leafy portions of the plant the substance responsible for its reputed medicinal action. This crystalline compound, called qinghaosu, also referred to as QHS or artemisinin, is a sesquiterpene lactone with an internal peroxide linkage.
Artemisinin is a member of the amorphane subgroup of cadinenes and has the following structure (I). ##STR2##
Artemisinin or QHS was the subject of a 1979 study conducted by the Qinghaosu Antimalarial Coordinating Research Group involving the treatment of 2099 cases of malaria (P. vivax and P. falciparum in a ratio of about 3:1) with different dosage forms of QHS, leading to the clinical cure of all patients. See, Qinghaosu Antimalarial Coordinating Research Group, Chin. Med J, 92:811 (1979). Since that time artemisinin has been used successfully in many thousand malaria patients throughout the world including those infected with both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. Assay of artemisinin against P. falciparum in vitro revealed that its potency is comparable to that of chloroquine in two Hanian strains (Z. Ye, et al., J. Trad. Chin. Med., 3:95 (1983)) and of mefloquine in the Camp (chloroquine-susceptible) and Smith (chloroquine-resistant) strains, D. L. Klayman, et al., J. Nat. Prod., 47:715 (1984).
Although artemisinin is effective at suppressing the parasitemias of P. vivax and P. falciparum, the problems encountered with recrudescence, and the compound's insolubility in water, led scientists to modify artemisinin chemically, a difficult task because of the chemical reactivity of the peroxide linkage which is believed to be an essential moiety for antimalarial activity.
Reduction of artemisinin in the presence of sodium borohydride results in the production of dihydroartemisinin (II-1) or DHQHS, (illustrated in structure II below), in which the lactone group is converted to a lactol (hemiacetal) function, with properties similar to artemisinin. Artemisinin in methanol is reduced with sodium borohydride to an equilibrium mixture of .alpha.- and .beta.-isomers of dihydroartemisinin. The yield under controlled conditions is 79% (artemisinin, 0.85M with NaBH.sub.4 6:34M, 7:5 equivalents in methanol, 12 L at 0-5.degree. C. for about 3 hours followed by quenching with acetic acid to neutrality at 0-5.degree. C. and dilution with water to precipitate dihydroartemisinin), A. Brossi, et al., Journal of Medicinal Chemistry, 31:645-650 (1988). Using dihydroartemisinin as a starting compound a large number of other derivatives, such as, ##STR3##
1 R=H
2 R=CH.sub.3 PA0 3 R=CH.sub.2 CH.sub.3 PA0 4 R=COCH.sub.2 CH.sub.2 COON.sub.a PA0 5 R=CH.sub.2 C.sub.6 H.sub.4 COOH PA0 6 R=CH.sub.2 C.sub.6 H.sub.4 COON.sub.a ##STR4##
artemether (compound II-2), arteether (II-3), sodium artesunate (II-4), artelinic acid (II-5), sodium artelinate (II-6), dihydroartemisinin condensation by-product (II-7) and the olefinic compound, structure III, ##STR5##
have been produced.
Artemether (II-2) is produced by reacting .beta.-dihydroartemisinin with boron trifluoride (BF.sub.3) etherate or HCl in methanol:benzene (1:2) at room temperature. A mixture of .beta.- and .alpha.-artemether (70:30) is obtained, from which the former is isolated by column chromatography and recrystallized from hexane or methanol, R. Haynes, Transactions of the Royal Society of Tropical Medicine and Hygiene, 88(1): S1/23-S1/26 (1994). For arteether (II-3), (Brossi, et al., 1988), the .alpha.-isomer is equilibrated (epimerized) to the .beta.-isomer in ethanol:benzene mixture containing BF.sub.3 etherate. Treatment of dihydroartemisinin with an unspecified dehydrating agent yields both the olefinic compound, (III), and the dihydroartemisinin condensation by-product (II-7), formed on addition of dihydroartemisinin to (III), M. Cao, et al., Chem. Abstr., 100:34720k (1984). Until recently, the secondary hydroxy group in dihydroartemisinin (II-1) provided the only site in an active artemisinin-related compound that had been used for derivatization. See B. Venugopalan, "Synthesis of a Novel Ring Contracted Artemisinin Derivative," Bioorganic & Medicinal Chemistry Letters, 4(5):751-752 (1994).
The potency of various artemisinin-derivatives in comparison to artemisinin as a function of the concentration at which the parasitemia is 90 percent suppressed (SD.sub.90) was reported by D. L. Klayman, "Qinghaosu (Artemisinin): An Antimalarial Drug from China," Science 228:1049-1055 (1985). Dr. Klayman reported that the olefinic compound III is inactive against P. berghei-infected mice, whereas the dihydroartemisinin condensation by-product (II-7) has an SD.sub.90 of 10 mg/Kg in P. berghei-infected mice. Thus, the dihydroartemisinin ether dimer proved to be less potent than artemisinin, which has an SD.sub.90 of 6.20 mg/Kg. Following, in order of their overall antimalarial efficacy, are the three types of derivatives of dihydroartemisinin (II-1) that have been produced: (artemisinin)<ethers (II, R=alkyl)<esters [II, R=C(=O)-alkyl or -aryl]<carbonates [II,R=C(=O)O-alkyl or -aryl].
Other rational design of structurally simpler analogs of artemisinin has led to the synthesis of various trioxanes, some of which possess excellent antimalarial activity. Posner, G. H., et al., reported the chemistry and biology of a series of new structurally simple, easily prepared, racemic 1,2,4-trioxanes (disclosed in U.S. Pat. No. 5,225,437 and incorporated herein by reference) that are tricyclic (lacking the lactone ring present in tetracyclic artemisinin I) and that are derivatives of trioxane alcohol IV ##STR6##
having the relative stereochemistry shown above. Especially attractive features of trioxane alcohol IV are the following: (1) its straightforward and easy preparation from cheap and readily available starting materials, (2) its availability on gram scale, and (3) its easy one-step conversion, using standard chemical transformations, into alcohol derivatives such as esters and ethers, without destruction of the crucial trioxane framework. See, Posner, G. H., et al., J. Med. Chem., 35:2459-2467 (1992), incorporated herein by reference. The complete chemical synthesis of artemisinin and a variety of other derivatives is reviewed by Sharma, R. P., et al., Heterocycles, 32(8):1593-1638 (1991), and is incorporated herein by reference.
Metabolic studies by Baker, et al., demonstrated that .beta.-arteether (II-3), one of the antimalarial derivatives discussed previously, was rapidly converted by rat liver microsomes into dihydroartemisinin (II-1). See Baker, J. K., et al., Biol. Mass Spect., 20: 609-628 (1991). This finding and the fact that the most effective artemisinin derivatives against malaria have been ethers or esters of (II-1) suggest that they were prodrugs for (II-1). The controlled slow formation of (II-1), however, is not desirable in view of its short half-life in plasma (less than two hours) and relatively high toxicity.
The successful synthesis of anticancer and antiviral drugs by replacing a carbon-nitrogen bond in nucleosides by a carbon--carbon bond (C-nucleosides) prompted the preparation of several 10-alkyldeoxoartemisinins, V, ##STR7##
wherein R is 1-allyl, propyl, methyl, or ethyl. Typically, these syntheses involved five or six steps and the reported yields were only about 12 percent. See, Jung, M., et al., Synlett., 743-744 (1990); and Haynes, R. K., et al., Synlett., 481-484 (1992).
Heterolytic cleavage of the peroxide O- 13 O bond via S.sub.N 2 attack of nucleophiles is well documented., see Adam, W. et aL, J. Am. Chem. Soc., 114:5591 (1992) and Razuvaev, G. A., et al., T. G. In Organic Peroxides; D. Swern, Ed., John Wiley & Sons, N.Y., 3:141-270, (1972). For example, tert-butyl ethers are conveniently prepared by Grignard nucleophilic attack on the O--O bond in tert-butyl peresters, see Lawesson, S.-O., et al., J. Am. Chem. Soc., 81:4230, (1959). Also, 3,3-disubstituted-1,2-dioxetanes react with organolithium reagents primarily via S.sub.N 2 O--O bond cleavage (with regioselective attack at the sterically less encumbered O atom) to form .beta.-hydroxy ethers (Adam, W., et al., Chem. Ber, 125:235, (1992)) and bicyclic endoperoxides likewise react with lithium and magnesium organometallics to produce O--O bond-cleaved hydroxy ethers. See, Schwaebe, M. K., et al., Tetrahedron Lett., 37:6635 (1996). When a dialkyl peroxide O---O bond is sterically hindered, then nucleophilic attack by a reactive organometallic reagent is made more difficult; an excellent example of this phenomenon leading to chemoselective nucleophilic addition of an organolithium reagent to the aldehyde carbonyl group in a peroxy aldehyde. See, Dussault, P., et al., T. J. Org. Chem., 58:5469 (1993) and Dussault, P., Synlett, 997 (1995). 1,2,4-Trioxanes in the artemisinin family undergo peroxide O--O bond cleavage when exposed to dimethylcopperlithium and to trityllithium; in these two cases, however, single-electron-reductive cleavage of the peroxide bond is likely occurring. See, Posner, G. H. et al., J. Am. Chem. Soc., 114:8328 (1992). Sodium borohydride chemoselectively reduces artemisinin (I) into its lactol (II-1), but more potent lithium aluminum hydride reduces both the lactone carbonyl group and the trioxane O--O bond. See, Wu, Y, et al, Youji Huaxue, 153, (1986); Chem. Abstr. 1986, 105, 191426n.
Based on these published precedents, it seemed that it would be very difficult to find any reactive organometallic reagents that would add chemoselectively to the lactone carbonyl group (less electrophilic than an aldehyde) of trioxane lactone artemisinin (I) without also cleaving the trioxane O--O bond. In fact, exposing artemisinin to 1.2 equivalent of phenyllithium in THF at -78.degree. C. produced at least three major products (not characterized).
Over the past thirty years only a few drugs isolated from higher plants have yielded clinical agents, the outstanding examples being vinblastine and vincristine from the Madagascan periwinkle, Catharanthus roseus, etoposide, the semi-synthetic lignan, from Mayapple Podophyllum peltatum and the diterpenoid taxol, commonly referred to as paclitaxel, from the Pacific yew, Taxus brevifolia. Of these agents, paclitaxel is the most exciting, recently receiving approval by the Food and Drug Administration for the treatment of refractory ovarian cancer. Since the isolation of artemisinin, there has been a concerted effort by investigators to study other therapeutic applications of artemisinin and its derivatives.
National Institutes of Health reported that artemisinin is inactive against P388 leukemia. See NCI Report on NSC 369397 (tested on Oct. 25, 1983). Later anticancer studies that have been conducted on cell line panels consisting of 60 lines organized into nine, disease-related subpanels including leukemia, non-small-cell lung cancer, colon, CNS, melanoma, ovarian, renal, prostate and breast cancers, further confirm that artemisinin displays very little anticancer activity. A series of artemisinin-related endoperoxides were tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolum (MTT) assay, H. J. Woerdenbag, et al., "Cytotoxicity of Artemisinin-Related Endoperoxides to Ehrlich Ascites Tumor Cells," Journal of Natural Products, 56(6):849-856 (1993). The MTT assay, used to test the artemisinin-related endoperoxides for cytotoxicity, is based on the metabolic reduction of soluble tetrazolium salts into insoluble colored formazan products by mitochondrial dehydrogenase activity of the tumor cells. As parameters for cytotoxicity, the IC.sub.50 and IC.sub.80 values, the drug concentrations causing respectively 50% and 80% growth inhibition of the tumor cells, were used. Artemisinin (I) had an IC.sub.50 value of 29.8 .mu.M. Derivatives of dihydroartemisinin (II-1) being developed as antimalarial drugs (artemether (II-2), arteether (III-3), sodium artesunate (II-4), artelinic acid (II-5) and sodium artelinate (II-6)), exhibited a somewhat more potent cytotoxicity. Their IC.sub.50 values ranged from 12.2 .mu.M to 19.9 .mu.M. The dihydroartemisinin condensation by-product dimer (II-7), disclosed previously by M. Cao, et al., 1984, was the most potent cytotoxic agent, its IC.sub.50 being 1.4 .mu.M. At this drug concentration the condensation by-product (II-7) is approximately twenty-two times more cytotoxic than artemisinin and sixty times more cytotoxic than dihydroartemisinin (II-1), the parent compound.
While artemisinin and its related derivatives (II-6) discussed above demonstrated zero to slight antiproliferative and antitumor activity, it has been discovered that a class of artemisinin dimer compounds exhibits antiproliferative and antitumor activities that are, in vitro, equivalent to or greater than known antiproliferative and antitumor agents. See, U.S. Pat. No. 5,677,468 incorporated herein by reference. Unfortunately, while the in vitro results of these artemisinin compounds are encouraging these compounds do not appear to have significant antitumor activity on the treatment of tumor cells in mice.
There is still a need, therefore, to develop methods for the formation of hydrolytically stable C-10 carbon-substituted artemisinin compounds and structural analogs thereof having antimalarial, and antiproliferative and antitumor activities that are equivalent to or greater than those of known antimalarial, and antiproliferative and antitumor agents, respectively, wherein the method does not result in cleavage of the trioxane O--O bond.