Described herein is a computer implemented method of measuring the determining the Left Ventricular Ejection Fraction (LVEF) of a patient. The S Wave, P Wave, R Wave and T Wave are continually measured using an ECG apparatus. The LVEF is computed as a function of S Wave, P Wave, R Wave and T Wave. The system described herein includes an ECG apparatus and an analytical computing device for computing the LVEF.

According to the American Heart Association, Left Ventricular Ejection Fraction (LVEF) is defined as the measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. It is the most common method for assessment of systolic function.
LVEF measurement is one of the hallmarks in diagnosis and prognosis of heart failure patients. In many cardiology emergencies such as Acute Myocardial Infarction and acute Congestive Cardiac Failure, there is an urgency to measure the LVEF since treatment plans often depend on it.
At present, the standard method of assessing LVEF is by conducting an Echocardiography, using the modified Quinones Equation. Hence, LVEF can only be assessed as snapshots rather than as a continuous parameter.
LVEF can be determined using several invasive and non-invasive imaging modalities, either subjectively by visual estimation or objectively by quantitative methods i.e., echocardiography, magnetic resonance imaging (MRI), computed tomography (CT), gated equilibrium radionuclide angiography (commonly referred to as multiple-gated acquisition [MUGA] scan) and gated myocardial perfusion imaging with either single-photon emission computed tomography (SPECT) or positron emission tomography (PET). LVEF can also be measured non-invasively using the 'first-pass' radionuclide technique, but this technique is rarely performed in the current era. However, none of these have the advantage of continuous monitoring. Also, the above mentioned are much more expensive than ECG and require trained professionals, whereas ECG lead placements require very basic training. In this application, the abbreviations ECG and EKG are used interchangeably, and both refer to electrocardiography. The abbreviations vary across different countries, but universally have the same meaning.

Determining LVEF using electrocardiographic signals


A quality value for a carbon ceramic brake disc (2) in a vehicle is measured by means of a measuring device (3) installed in the vehicle. The measuring device (3) with a coil (10) is located at a distance (d) from the brake disc (2) in order avoid direct physical contact with the brake disc. The impedance of the coil (10) is measured for at least two frequencies. The resulting measurement values that correlate to impedance values are introduced into a mathematical model in order to eliminate the dependence of the unknown distance (d) and to obtain a quality value dependent on the conductivity of the brake disc (2).

A "carbon ceramic brake disc" is a brake disc comprising a carbon ceramic material, wherein the carbon ceramic material comprises a ceramic matrix as well as carbon fibers embedded in the matrix.
In such carbon ceramic brake discs an oxidation of the carbon fibers and therefore wear occurs due to high operating temperatures. This wear cannot be reliably recognized by mere optical inspection. An improved recognition of wear is achieved by inductive methods of measurement. The principle used in this type of measurements is based on eddy current damping; either using two coils (EP 1 387 166) operating continuously, or one or two coils in pulsed operation (DE 10 2008 051 802). In these documents, the excellent correlation between the inductive measurement and a gravimetric determination of the wear is disclosed. A conventionally traded Profometer (www.proceq.com) is used as measuring device. Using this type of techniques, it is not necessary to disassemble the brake disc for measurement.
US 2013/0015849 describes a method for measuring the wear of a carbon ceramic brake disc, where a housing holding a plurality of coils is held against the brake disc.
All these techniques, which are based on determining a quality value dependent on the inductance of the brake disc, are designed for offline measurements where the measuring device is not permanently built into the vehicle, e.g. for measurements at a garage, where the vehicle is at rest, or for measurements of brake discs outside a vehicle. The measuring device is brought into physical contact with the brake disc and a parameter depending on the impedance of the coil(s) is measured.
It is found that this type of measuring device is poorly suited for being a permanent installation in the vehicle.

Method and device for determining wear of a carbon ceramic brake disc in a vehicle by impedance measurements


An optical measurement device for measurement of chemical and/or biological samples comprises an illumination means (16) for illuminating the sample (20) to be measured. Further, an optics means (22) is provided for imaging a sample area in an image field (10). A first partial area (12) of the image field is covered by a first detector (28), and a second partial area (14) of the image field (10) is covered by a second detector (34). Thus, it is possible to change between two measurement methods without switching or to perform two measurements on a sample at the same time.

For the microscopic optical examination of samples, various measurement methods exist which provide different kinds of information. Either image or point measurements can be performed. In image measurements, generally, the value of a physical quantity is recorded in dependence on the measurement site. The measurement of this physical quantity is performed either at numerous different points or measurement sites in parallel, or respectively only at one point, and the site of this point, i.e. the measurement site, will be varied. The latter is often referred to as a "screening" of the sample surface. In this case, each individual measurement has to be performed very fast so that the image measurement can be concluded within an acceptable length of time.
Examples of useful image measurement methods are: bright-field, dark-field, total-internal-reflection, fluorescence, 2-photon-fluorescence, fluorescence-lifetime, fluorescence-emission-spectroscopy, polarization and fluorescence-polarization microscopy. Further, these methods can be performed by use of different detectors such as e.g. line cameras or surface cameras, and, in part, these detectors can be used both in conventional and confocal arrangements.
In point measurements, contrary to image measurement, the measurement is carried out only at one site on the sample, or the site information is not evaluated, or an averaging including a large number of measurement sites is performed (conventional measurement by use of a large-surfaced detector). Correspondingly, the individual measurement may be both more complex and more time-consuming. The complexity can relate both to the measurement apparatus and the data obtained (e.g. complete spectra). For instance, in the fluorescence correlation spectroscopy (FCS) point measurement method, the fluctuation of a fluorescence signal coming from a small volume is recorded over a longer period of time, and the signal is used to derive information on photophysical, chemical and physical properties of fluorescent particles and molecule in this volume. In these measurements, it is often assumed beforehand that the volume observed is representative of the sample. This will of course largely apply to homogenous samples but only to a restricted extent if also structured components occur in the sample. Useful point measurement methods are—although the following examples are not exhaustive—FCS, FIDA, fluorescence-emission, fluorescence-excitation and fluorescence-absorption spectroscopy, fluorescence-lifetime spectroscopy and fluorescence-anisotropy measurements, as described in numerous scientific and technical publications. The measurements can often be performed both in a conventional and a confocal arrangement.
For the characterization of substances with regard to possible pharmaceutical and medical uses, it is often reasonable and necessary to carry out an examination by use of image and point measurement methods alike. Then, information on all components can be extracted from samples containing homogeneous as well as structured components. By way of example, it could be examined in what manner a sample comprising cells which are assumed to release certain molecules into the solution surrounding them, will react on an added test substance. With the FCS method, the possible occurrence of a biochemical reaction in the solution can be detected while fluorescence microscopy makes it possible to examine the cell layer and to obtain indications e.g. of a possible toxic nature of the test substance.
In multi-channel microscopy, a sample can be subjected to imaging measurement methods for performing a plurality of measurements of the same sample region under different measurement conditions or with different detectors. Thereby, for instance, there is determined the distribution of different fluorophobes in the sample, which differ from each other with regard to their photophysical properties such as e.g. the excitation and emission spectra and/or the fluorescence lifetime.
As to the devices wherein image measurement methods are combined with point measurement methods, mention should be made of the FCS apparatus for intracellular FCS by Brock (see e.g. Brock, "Fluorescence Correlation Microscopy and Quantitative Microsphere Recruitment Assay", dissertation, 1999). This apparatus comprises a fluorescence microscope which has been retrofitted to include the components required for FCS. The selection among the measurement methods of microscopy or FCS is realized by a hinged mirror arranged in the path of rays.
To begin with, such a mechanical switching of the path of rays by means of a hinged mirror entails the necessity to determine the positions of the different measurement volumes relative to each other. High-throughput applications are subject to the additional necessity to perform this switching cycle a large number of times, thus causing mechanical wear of the constructional components. This wear process particularly affects a predefined relative position of the measurement volumes so that this position would have to be redefined at regular intervals. In certain cases, even the complete switching unit has to be replaced because of wear. Especially in high-throughput applications, a disadvantage is caused by the loss of measurement time due to the switching process, resulting in a decrease of the obtainable sample throughput.
So-called laser scanning microscopes (LSM) generate a two-dimensional image of a sample by sequential screening of the object plane with a single small measurement volume. Based on the knowledge on the position of the measurement volume at each point of time and on the corresponding picked-up measurement value, an image of this plane can be generated. Possible signals for this purpose include reflection and fluorescence intensity but also anisotropy and fluorescence anisotropy. In microscopes of the above type, a combination with point measurement methods such as e.g. the fluorescence emission spectroscopy is relatively simple since only the movement of the measurement volume need be eliminated for obtaining a sufficient measurement time.
When using laser scanning microscopes, a disadvantage resides in the relatively long measurement times for the individual images. A use of such microscopes for high-throughput screening will thus not be possible because the required short measurement times with sufficient signal quality cannot be obtained. In short measurement times, the measurement results will have only a small signal-to-noise ratio, so that an averaging has to be performed over several images. This averaging is carried out for improving the signal-to-noise ratio and therefore is necessary in case of short measurement times for an individual image. In case of long measurement times, a sufficient signal-to-noise ratio can be obtained also without averaging. This in turn will increase the measurement time. Further, the laser scanning microscope is restricted to the use of relatively complex image-generating methods.
To be able to distinguish a plurality of fluorophores in a microscope on the basis of their excitation and emission spectra, special optical filters, chromatic cameras and imaging spectrographs are used in multi-channel microscopes.
Normally, when optical filters are used, at least three filters will be employed. The first filter determines the excitation wavelength range, the second filter is a dichromatic mirror which reflects the excitation light and transmits the emission light (or vice versa). In front of the detector, a further filter is inserted, transmitting only the emission range. For the detection of different fluorophores, the possibility exists to exchange all three filters, according to the standardized routine when using commercially available microscopes. Alternatively, a single filter set can be arranged for a plurality of colorants if the excitation and emission wavelengths are sufficiently remote from each other, as is the case e.g. for the colorants DAPI, FITC and TRITC. If these colorants have to be recorded separately, a color film or a color CCD camera can be used. Likewise suited is a monochrome camera in combination with a selectable excitation spectrum, as performed e.g. in the so-called Pinkel filter sets. Filter sets also offer the opportunity to distinguish colorants from each other on the basis of their Stokes shift. In this manner, different colorants can be excited by the same wavelength and will differ from each other by the different displacement of the emission spectrum.
In multi-channel microscopes, it is frequently required to exchange one or several filters between the individual measurements. When using high-throughput systems, this causes considerable disadvantages, such as e.g. wear of components or losses in measurement time due to the switching times. Systems adapted to detect a plurality of colorants simultaneously are restricted to mere few combinations of colorants because the emission spectra must be sufficiently different and must not overlap with the excitation spectra of the other colorants. Further, the manufacture of such optical filters which are suited for a plurality of colorants is very complex so that a change towards other colorants is impeded by the considerable expenses for development and manufacture. This imposes heavy restrictions on the selection of the possible colorants. This disadvantage affects also systems which are based on spectrographs since also these require that the excitation light be attenuated. Further, imaging spectrographs are not particularly suited to record an image of the sample because the recording times—and possibly also the processing times—are frequently as long as several seconds.
It is an object of the invention to provide a device and a method for the measurement of chemical and/or biological samples which make it possible to perform different measurements of a sample, particularly through an image measurement method and a point measurement method, in a simple manner.

Device and method for optical measurement of chemical and/or biological samples


A tamper evident closure for an open container having an outwardly projecting container finish proximate to the container opening is disclosed. The closure comprises a hollow body which includes a tamper evidencing means. The tamper evidencing means is hinged within the body so that removal of the closure from the container requires engagement of the tamper evidencing means with the projecting finish. This engagement results in outward displacement of the tamper evidencing means and creates a visual impression.

1. Field Of The Invention
This invention relates to tamper evidencing caps and containers which provide visual evidence of prior cap removal. More particularly, the present invention relates to a tamper evidencing cap and container with an automatic indicator which becomes visually apparent when the cap is removed for the first time.
2. Description Of The Related Art
A variety of tamper evidencing devices have been developed. Such devices are especially useful for containers that hold food or medicine. These devices generally seek to allow the consumer to visually determine container tampering prior to use. See for example, my own prior U.S. Pat. No. 4,771,923. Other examples of tamper evidencing means are shown in the following patents; U.S. Pat. Nos.: 3,673,761; 4,480,761; 4,506,795; 4,595,110; 4,595,547; 4,598,833; 4,591,062; 3,957,169; 1,875,431; 3,335,889; 4,573,601; UK Pat. No. 974,564; Italian Pat. No. 527065; and French Pat. No. 1,268,937


To simplify a configuration for increasing an amount of information on an observation space, taken image acquisition means of an image processing system acquires taken images that have been taken by image taking means, which is movable in a real space. Observation space information acquisition means acquires, based on changes in position of a feature point cloud in the taken images, observation space information including three-dimensional coordinates of the feature point cloud in an observation space. Machine learning means acquires, based on machine learning data on a feature of an object, additional information on a feature of a photographed object shown in the taken images. Integration means integrates the observation space information and the additional information.

In recent years, there has been investigated a technology of analyzing taken images that have been taken by a camera, and reproducing a view of a real space in an observation space. In Non Patent Literature 1, for example, there is described a technology called "simultaneous localization and mapping (SLAM)" of generating, based on changes in position of a feature point cloud in taken images that have been taken by an RGB camera (so-called "monocular camera") including no depth camera, a 3D map including three-dimensional coordinates of the feature point cloud in the observation space. Moreover, in Non Patent Literature 2, for example, there is described a technology of generating a 3D map based on taken images that have been taken by an RGB-D camera including an RGB camera and a depth camera.

Image processing system, image processing method, and program


An apparatus, system, and related methods for multi-bounce material property detection and signal amplification are provided. The apparatus has a first acoustic transducer positioned on an exterior sidewall of a pipe or container carrying or holding a quantity of fluid therein. An acoustic signal is transmitted by the first acoustic transducer into the sidewall of the pipe from an exterior surface thereof. With material detection, at least a portion of the acoustic signal reflects off an interior surface of the sidewall of the pipe. The reflected acoustic signal is received at the second acoustic transducer on the exterior sidewall of the pipe. The reflected acoustic signal provides an indication of a material property of the pipe or a material within the pipe. With signal amplification, the second acoustic transducer transmits a phase synchronized second acoustic signal to the first acoustic signal, where the second acoustic signal amplifies the first acoustic signal.

Pipes and pipelines are commonly used in a variety of industries to transport fluids. For instance, water pipes transport potable and sewer water in urban areas, pipes are used to transport chemicals within factories, and pipelines are used within the oil and gas industry for transporting petroleum products within refineries or between various locations. To monitor the fluid within the pipes and pipeline, conventional technologies such as pressure gauges and various sensors are commonly used. More recently, acoustic-based sensors have been used to monitor the fluid or determine characteristics of the fluid.
For instance, acoustic signals are commonly used in assessing fluids and other materials within containers, such as containers and pipelines used to store oil and gas within the petroleum industry. There are many reasons to use acoustic waves for measurements of fluids or materials in a container or other type of enclosure. For instance, some containers are not easily accessible, such as underground storage tanks and large, multi-story fuel storage containers. Acoustic waves for measurements are also especially useful for metal enclosures and other non-transparent enclosures that encapsulate potentially hazardous materials, such as oil, gas, fuel, and various chemicals at different temperatures. These may be prevalent in processing plants, nuclear power stations, power grid transformers, and refineries.
In use, an acoustic sensor or transducer is positioned proximate to the container and an acoustic signal is transmitted into the container sidewall. The coupling of the transducer to the container is usually designed to minimize the impact of mounting the transducer to the container. When the signal crosses the sidewall of the container from the outside of the container to the inside, it loses significant amounts of energy, especially when the signal reaches the impedance barrier at the inside surface of the container sidewall. The loss of signal energy at the acoustic impedance barrier inside surface of the container sidewall is determined by one or more properties of the fluid material inside the container, as well as the properties of the material forming the sidewall of the container, and the temperature. For instance, in case of dense liquids, like crude oil, almost 80% to 90% of the energy of the acoustic wave is lost crossing the impedance barrier between crude oil and the sidewall of the container. Less dense liquids and gasses are prone to blocking even mode energy at the impedance barrier on the inside of the container.
In the case of liquids flowing through a pipeline, the fluid materials being transported often have a noticeably different acoustic impedance from the material used to form the pipeline wall, often a metal material, such as cast iron, steel, aluminum, or similar materials. This difference in acoustic impedance leads to significant reflection of an acoustic or ultrasound wave of an acoustic sensor which crosses this impedance barrier, and as a result, the strength of the transmitted signal into fluid can be lower than desired. With petroleum products specifically, this problem occurs due to petroleum paraffin wax deposits forming on the inside of the pipeline wall. Similarly, with gasses flowing through a pipe, the impedance barrier on the inside surface of the pipe wall can reflect most of the signal back into the pipe wall, thereby preventing accurate signal transmission.
Thus, a heretofore unaddressed need exists in the industry to address the aforementioned deficiencies and inadequacies.

In-wall multi-bounce material property detection and acoustic signal amplification


A semiconductor device that includes an integrated circuit and an HBM structure formed on different semiconductor substrates is provided. The HBM structure may include input or output or input/output circuitry coupled to the integrated circuit and protection structures coupled to the input or output or input/output circuitry. In an embodiment, the integrated circuit may include input or output or input/output structures spaced across an area of the integrated circuit. The input or output or input/output circuitry of the HBM structure may be coupled to the input or output or input/output structures of the integrated circuit. A method for developing a design for an HBM structure is also provided. The method may include coupling an HBM structure formed on a first semiconductor substrate to an integrated circuit formed on a second semiconductor substrate. The method may also include testing the HBM structure and altering the HBM design based on the testing.

1. Field of the Invention
This invention relates to electrostatic discharge protection of integrated circuit devices, and more particularly, to an electrostatic discharge protection device that is decoupled from an integrated circuit device.
2. Description of the Related Art
The following descriptions and examples are not admitted to be prior art by virtue of their inclusion within this section.
Integrated circuit devices such as common silicon integrated circuits typically have delicate construction that is susceptible to damage by voltage spikes such as voltage spikes caused by electrostatic discharge. Such voltage spikes may occur in various situations such as during manufacturing of an integrated circuit, handling of the integrated circuit after packaging, and handling of a board after assembly such as during use of the board. There are a number of models that may be used to describe such damage to an integrated circuit device. For example, the human body model (HBM) describes a voltage spike condition caused by electrostatic discharge from a human body to an integrated circuit device. For an integrated circuit device to be commercially viable, it has to be protected against this condition except under special circumstances such as when manufacturers and customers specifically agree on the lack of such protection. This agreed upon lack of HBM protection is necessary because lack of this protection may require special handling of the integrated circuit device that complicates logistics, increases handling costs, and increases the probability of damaging the device.
To protect against electrostatic discharge, a silicon die typically includes protection circuitry (or an xe2x80x9cHBM structurexe2x80x9d) that will divert or otherwise dissipate the energy caused by a voltage spike. In this manner, the core logic circuitry of the die may not be damaged by the voltage spike. An HBM structure is the xe2x80x9cfirst line of defensexe2x80x9d for input/output (I/O) cells. Therefore, the structure is integrated into the die and is adjacent to or outside of the I/O cells through which the die interacts with the external environment (i.e., through device pins).
Development of the HBM structure, however, is usually difficult as development hinges upon understanding of process technology and how its various underlying factors interact so that an adequate structure can be developed. An adequate HBM structure also has to react fast to a voltage spike (i.e., it has to react faster than the internal circuitry) to be effective. In addition, HBM structures have to dissipate relatively large amounts of energy. On the other hand, an HBM structure cannot present an undue burden to I/O cells in areas such as current consumption and capacitance as these factors affect the performance of the device.
There are several disadvantages of currently available HBM structures. For example, the electrical design of an HBM structure is difficult to develop correctly without some experimentation due to lack of means of accurate simulations. In particular, the electrical design of an HBM structure may be difficult to develop if a new process is being used for the die. In addition, the practice of integrating an HBM structure into the base die, where the logic and regular I/O circuitry reside, may cause revision of the entire die if the HBM structure is inadequately designed. Such revision may be especially problematic if the revision of the die is solely required due to the HBM structure because the expensive tape-out of the die adds no value to the performance or functionality of the device. Additionally, while an optimal HBM structure is desired for a device, the fact that its revision causes expensive revision of the entire die and re-tape-out discourages experimentation of HBM structures thereby hindering HBM structure design. Furthermore, an HBM structure may enlarge the size of the integrated circuit die thereby increasing die cost and making a die revision for any reason more expensive than it would be without the HBM structure. Revision of an HBM structure if an existing one is inadequate requires re-layout of the device that often goes beyond the structure itself. For example, such revision may affect the I/O cell layout of the device. This revision and/or re-layout may delay product launch and increase the product development time and cost.
Accordingly, it may be advantageous to develop an HBM structure that allows revision of the HBM structure without revision of the entire die and/or re-tape-out or re-layout of the entire device, allows less problematic and less expensive revision such that better HBM structures may be developed, reduces the size of the die thereby reducing cost of the die and revision of the die for any reason, reduces product development time and costs, and allows reuse of the HBM structure for various integrated circuits.
The problems outlined above may be in large part addressed by an embodiment of a semiconductor device including an integrated circuit and an HBM structure formed on separate semiconductor substrates. Various embodiments described herein may reduce, and even eliminate, problems such as HBM structure-induced integrated circuit latch-up, integrated circuit partitioning problems due to the HBM structure, and product delay due to HBM structure development. In addition, if an integrated circuit and an HBM structure are formed on different semiconductor substrates, then the die size of the integrated circuit may be reduced thereby reducing integrated circuit manufacturing costs. There are several additional advantages to the various embodiments as described herein.
In an embodiment, the integrated circuit may be formed on a first semiconductor substrate. The HBM structure may be formed on a second semiconductor substrate. The integrated circuit may include, for example, logic circuitry, charged-device model (CDM) structures, other circuitry typically included in an application specific integrated circuit (ASIC), and optionally portions of the input/output cells of the integrated circuit. The HBM structure may include input or output or input/output circuitry coupled to the integrated circuit. In an embodiment, the HBM structure may also include input/output cells of the integrated circuit. The input or output or input/output circuitry may be included in the input/output cells. The HBM structure may also include protection structures coupled to the input or output or input/output circuitry. The semiconductor device may also include a package substrate to which the first and second semiconductor substrates may be connected directly or through a pair of back to back diodes. The protection structures of the HBM structure may be further coupled to signal traces of the package substrate. In this manner, the protection structures may be configured to protect the input/output cells of the integrated circuit from electrostatic discharge that may be conducted through the signal traces.
In an embodiment, the input or output or input/output circuitry of the HBM structure may be coupled to the integrated circuit by wire bonding. In an alternative embodiment, the input or output or input/output circuitry of the HBM structure and the integrated circuit may be coupled to a signal trace within the package substrate by wire bonding. In a further embodiment, the input or output or input/output circuitry of the HBM structure and the integrated circuit may be connected to a signal trace within the package substrate by solder bumps. According to yet another embodiment, the semiconductor device may also include two or more HBM structures. Each of the two or more HBM structures may include a portion of the input or output or input/output circuitry and protection structures coupled to the portion of the input or output or input/output circuitry.
Latch-up and other problems associated with the HBM structure may be reduced, and even eliminated, by an HBM structure de-coupled from the integrated circuit. For example, when the HBM structure is integrated into the integrated circuit as is currently done, the HBM structure and the integrated circuit are formed on a common substrate. Typically, HBM structures are large in size. In this manner, a large number of minority carriers may be injected from the HBM structure to the integrated circuit. Such carrier flow may cause latch-up in the integrated circuit in the event of a sudden large current flow during device operation. Currently, to reduce latch-up of the integrated circuit, the input/output portion of the HBM structure may be isolated from the integrated circuit by inserting complex guard ring structures between the HBM portion and the integrated circuits. Carriers, however, may still flow from the HBM structure to the integrated circuit across the common substrate. In embodiments as described herein, however, minority carrier flow from the HBM structure into the integrated circuit may be greatly reduced because the HBM structure and the integrated circuit are formed on different semiconductor substrates. Therefore, latch-up of the integrated circuit may be reduced due to the limited carrier flow from the HBM structure into the integrated circuit.
In addition, different manufacturing processes may be used to form the HBM structure and the integrated circuit because the HBM structure and the integrated circuit are not formed on the same semiconductor substrate. In this manner, the HBM structure may be formed using a processing technology different from that used to form the integrated circuit. For example, the integrated circuit may be formed using advanced processing technology with relatively fine line width and a relatively large number of layers of metal. In contrast, the HBM structure, due to simpler design, may be formed using more traditional technology with larger line width and fewer metal layers. As such, devices of the integrated circuit may have substantially different average critical dimensions than devices of the HBM structure. In addition, the HBM structure may have a different number of layers than the integrated circuit. Therefore, forming the HBM structure with more traditional technology may lower overall costs of the device.
Another embodiment relates to a semiconductor device that also includes an integrated circuit and an HBM structure formed on different semiconductor substrates. The HBM structure may be formed on a second semiconductor substrate. In this embodiment, the integrated circuit may be formed on a first semiconductor substrate. The integrated circuit may include input or output or input/output structures spaced across an area of the integrated circuit. The area may include a central portion of the integrated circuit and a peripheral portion of the integrated circuit. In an embodiment, the input or output or input/output structures may not be surrounded by guard rings. Guard rings may include a continuous ring of n-diffusion in an n-well connected to VDD and a ring of p-diffusion in a p-well connected to VSS to collect minority carriers thereby reducing flow of the carriers into a portion of the substrate occupied by the integrated circuit. Guard rings, however, require a relatively large area of the substrate and increase the difficulty of designing an integrated circuit having input/output cells not only at the periphery of the integrated circuit but also proximate a central portion of the integrated circuit. Therefore, eliminating such guard rings reduces the difficulty of silicon partitioning.
Moreover, as the speed of an integrated circuit increases, wire bonding and placing inputs or outputs or input/outputs proximate the periphery of the integrated circuit, but not proximate the central portion of the integrated circuit, may not be adequate for such integrated circuits. For example, isolating the HBM structure to protect the integrated circuit by limiting the input or output or input/output locations within the integrated circuit may result in inefficient use of die space and reduced performance of such high speed integrated circuits. De-coupling the HBM structure and the integrated circuit may, therefore, reduce, and even eliminate, such concerns.
The HBM structure may include input or output or input/output circuitry coupled to the input or output or input/output structures of the integrated circuit. In an embodiment, the input or output or input/output structures may be self-aligned to the input or output or input/output circuitry. For example, the semiconductor device may include a package substrate to which the first and second semiconductor substrates may be connected. The first and second semiconductor substrates may be connected to the package substrate in a flip chip stacked ball grid array configuration. Therefore, in such an embodiment, input or output or input/output structures may be spaced across the area of the integrated circuit at convenient positions and at positions that may increase circuit performance without constructing complicated tapping to isolate the HBM structure from the integrated circuit. In addition, the HBM structure may include protection structures coupled to the input or output or input/output circuitry.
A further embodiment relates to a method for developing a design for an HBM structure. The method may include forming an HBM structure having an initial HBM design on a first semiconductor substrate. The method may also include coupling the first semiconductor substrate to a package substrate and coupling the HBM structure to an integrated circuit coupled to the package substrate. The integrated circuit may be formed on a second semiconductor substrate. In addition, the method may include testing the HBM structure. The method may further include altering the initial HBM design based on the testing.
In an embodiment, the method may include forming an additional HBM structure having the altered initial design without altering a design of the integrated circuit. The method may also include forming an additional HBM structure having the altered initial design without altering manufacturing of the integrated circuit. In an embodiment, the method may include altering a design of the integrated circuit without further altering the initial design of the HBM structure. Altering an HBM structure die does not require altering an integrated circuit die and vice versa because the die are formed on separate semiconductor substrates. Altering one of the die, instead of both die, will reduce re-layout time and costs associated with re-layout of both die.
The method may also include forming an additional HBM structure having the altered initial design without manufacturing an additional integrated circuit Therefore, such embodiments may reduce the costs of manufacturing another integrated circuit on the same die as the additional HBM structure. Furthermore, because the HBM structure may be manufactured separately from the integrated circuit, the HBM structure may be used to protect other integrated circuits and perhaps at a reduced cost. In another embodiment, the method may further include using the HBM structure until an additional HBM structure having the altered initial design can be formed and coupled to the integrated circuit. In this manner, if the HBM structure will sufficiently protect a new integrated circuit product, the HBM structure may be used as an interim solution for the new integrated circuit product while an optimal HBM structure is being developed for the new product thereby reducing product delay. As such, the new product may be shipped as an HBM protected device while the development of the HBM structure continues. Such a method may also be used for integrated circuits having an integrated HBM structure.
Additional HBM structures may be experimentally tested as described herein. ESD structures such as an HBM structure are often difficult to develop without some experimentation. For example, an adequate HBM structure is often difficult to determine prior to experimentation because an adequate design of the structure often requires process technology characterization, which may be difficult to obtain without taping out the integrated circuit. Determining an adequate HBM structure may be particularly difficult if the integrated circuit process technology includes new processes and/or technologies. The development of such structures also tends to be performed proximate the end of the product design cycle. Therefore, developing an HBM structure separately from an integrated circuit may reduce the development time for the HBM structure thereby speeding product launch.

Method of providing HBM protection with a decoupled HBM structure


Embodiments of the invention provide a method for querying performance counter data on a massively parallel computing system, while minimizing the costs associated with interrupting computer processors and limited memory resources. DMA descriptors may be inserted into an injection FIFO of a remote compute node in the massively parallel computing system. Upon executing the DMA operations described by the DMA descriptors, performance counter data may be transferred from the remote compute node to a destination node.

1. Field
Embodiments of the invention relate generally to parallel processing and more particularly to a technique for using a DMA reflect operation to unobtrusively query remote performance data.
2. Description of the Related Art
Powerful computers may be designed as highly parallel systems where the processing activity of hundreds, if not thousands, of processors (CPUs) are coordinated to perform computing tasks. These systems are highly useful for a broad variety of applications, including financial modeling, hydrodynamics, quantum chemistry, astronomy, weather modeling and prediction, geological modeling, prime number factoring, and image processing (e.g., CGI animations and rendering), to name but a few examples.
International Business Machines (IBM) has developed one family of parallel computing systems under the name Blue Gene®. The various Blue Gene architectures provide a scalable, parallel computer system. For instance, the Blue Gene/P system may be configured with a maximum of 256 racks, housing 8,192 node cards and 884,736 PowerPC 450 processors. The Blue Gene/P architecture has been successful and on Nov. 12, 2007, IBM announced that a Blue Gene/P system at Jülich Research Centre reached an operational speed of 167 Teraflops (167 trillion floating-point operations per second), making it the fastest computer in Europe at that time. Further, as of June 2008, the Blue Gene/P installation at Argonne National Laboratory achieved a speed of 450.3 Teraflops, making it the then third fastest computer in the world.
The compute nodes in a parallel system typically communicate with one another over multiple communication networks. For example, the compute nodes of a Blue Gene/P system are interconnected using five specialized networks. The primary communication strategy for the Blue Gene/P system is message passing over a torus network (i.e., a set of point-to-point links between pairs of nodes). The torus network allows application programs developed for parallel processing systems to use high level interfaces such as Message Passing Interface (MPI) and Aggregate Remote Memory Copy Interface (ARMCI) to perform computing tasks and distribute data among a set of compute nodes. Of course, other message passing interfaces have been (and are being) developed. Other parallel architectures also use MPI and ARMCI for data communication between compute nodes connected via a variety of network topologies. Typically, MPI messages are encapsulated in a set of packets which are transmitted from a source node to a destination node over a communications network (e.g., the torus network of a Blue Gene system).
Additionally, the compute nodes may contain various FIFOs in their local memory. For instance, the nodes may contain an injection FIFO in which commands may be stored. The node may monitor the injection FIFO to determine when commands have been added to the FIFO. For instance, a head pointer and a tail pointer may be used to monitor the FIFO. When the FIFO contains one or more commands, the node may then begin to execute those commands. The nodes may also contain other FIFOs, such as FIFOs containing data to be written to memory.

This patent is subject to a terminal disclaimer.

Query performance data on parallel computer system having compute nodes

International Business Machines Corporation


Each of a plurality of substantially co-linear alignments has a score. Each alignment may comprise a starting alignment that has been diagonally extended to meet a length requirement. Dynamic programming is performed in interalignment regions between the extended alignments to generate a corresponding set of interalignment scores. Alignment scores and interalignment scores are summed to generate a score for the entire chain of alignments. This process is repeated for multiple chains. Chains of alignments are ranked by chain score and are displayed to a user. In one embodiment, additional dynamic programming is performed at the head and tail of each chain to increase the chain score when possible. An integrated circuit that performs the method at high speed in hardware is disclosed. Techniques are disclosed that reduce the amount of interalignment dynamic programming. The method increases sensitivity and gives an order of magnitude speed improvement over NCBI-BLAST.

The size of genomic sequence databases are currently growing at an exponential rate. Today, a typical genomic (DNA) database contains the sequence for billions of nucleotides. As a result, searching a genomic sequence database to find a sequence that correlates to an query sequence is often extremely computationally intensive.
Various sequence similarity searching algorithms are currently used to identify DNA and amino acid sequences within a genomic sequence database that have a correlation to a query sequence. Generally speaking, sequence searching algorithms may be classified as one of two types, namely global comparison methods and local comparison methods. Global comparison methods search a database sequence for the occurrence of an entire query sequence. Although such methods have a high degree of accuracy, they tend to be extremely slow. On the other hand, local comparison methods, such as NCBI-Blast and FastA, are faster than global comparison methods. Local comparison methods identify similar subsequences based on similar k-tuples of nucleic or amino acids.
Local comparison methods typically employ dynamic programming evaluations in order to find an optimal solution to a given search. Not surprisingly, the significant contributor to search time for such local comparison algorithms is the dynamic programming evaluations. Indeed, dynamic programming evaluations account for about 76% of the processing time of a typical NCBI-Blast search. Thus, although local comparison methods may be faster than global comparison methods, such methods are still quite computationally intensive.
A local comparison method is therefore sought that is less computationally intensive than methods such as NCBI-Blast and FastA. An apparatus is desired that performs a local comparison algorithm in less time than the search time of current searches employing local comparison methods.

Apparatus for calculating scores for chains of sequence alignments


Some embodiments include apparatuses and methods including memory cells and a control unit to store information in a portion of the memory cells and to generate an entry associated with the information. The information is associated with a logical address recognized by a host. The entry includes an indicator indicating that the information is to be preserved for a creation of an image of information associated with logical addresses in a logical address space recognized by the host.

Many electronic systems, such as desktop and laptop computers, servers, data storage system, and other electronic devices or systems, have memory to store information (e.g., data). Some conventional systems may include techniques to capture certain information stored in a memory device at a particular time. Some of these techniques, however, may be time consuming, may employ complicated information management, or both.

Logical address history management in memory device


A method of forming cell bitline contact plugs is disclosed in the present invention. After providing a semiconductor substrate with a first region and a second region, cell bitline contacts are formed at the first region. After forming bitline pattern openings at the second region, poly spacers are formed on sidewalls of the cell bitline contacts and the bitline pattern openings. A substrate contact and a gate contact are then formed within the openings at the second region. After forming a trench around each of the substrate contact and the gate contact by performing an etching process, cell-bitline contact plugs, a substrate contact plug, and a gate contact plug are formed.

1. Field of the Invention
The present invention relates to semiconductor process integration and, more particularly, to a method of forming a bitline contact plug with a higher part and a lower part.
2. Description of the Related Art
Continued shrink of the dimensions of integrated circuits places more imperative requirements on creating contact openings, which are applied to form contact plugs to the integrated circuits. Particularly, the dynamic random access memory (DRAM) devices require certain integration practice to achieve the fabrication of the contact plugs, especially the bitline contact plugs, of which purpose to connect CMOS devices and memory cells.
For the concern of junction leakage, some of traditional bitline contact plugs of memory cells were made of N-doped polysilicon. The polysilicon plugs would form a continuously-distributed N-type junction, which would cause relatively lower junction leakage. However, concerning the DRAMS devices with a design rule of less than 140 nm, especially in the cases of deep sub-micron DRAM devices, a material with lower electrical resistivity is needed for the cell contact plugs. In other word, N-doped polysilicon may not be a good choice for forming the bitline contact plugs at the cell region.
However, the traditional metal plugs, such as tungsten plugs, are also not a good option for forming the bitline contact plugs at the cell region. That's because the junction leakage between the metal material and the semiconductor substrate is much larger than the junction leakage in the case of polysilicon contact plugs.
Furthermore, it is also an issue in the integration process of fabricating a contact plugs to create an opening with a dimension smaller than the minimum width of the design rule. The Japanese patent with number JP07-169755 illustrated an example to achieve this goal.


An electromagnetic relay system is constituted by containing an electromagnetic relay arranged in a case and including a coil, a movable contact and a plurality of fixed contacts, a positive terminal and a negative terminal formed to project from the case, and load terminals formed to project from the case and connectable to a motor. An electric current flowing in the motor is controlled by controlling an electric current flowing in the coil. A ground line extended from the coil is connected to the negative terminal via a coil spring in the case.

The present invention relates to an electromagnetic relay system for controlling an electric current flowing in a load by controlling an electric current flowing in a coil of a relay means.
An electromagnetic relay system of a related art, for example, an electromagnetic relay system for controlling an operation of a winch or the like mounted on an ATV (All Terrain Vehicle), is constituted by containing an electromagnetic relay comprising two coils and a plurality of fixed terminals in a substantially hermetically closed case made of a resin and including a plurality of terminals formed by being projected from the case. In the electromagnetic relay system, a motor as a drive source of the winch or the like regularly rotates when an electric current is flowed in one of the coils, and the motor reversely rotates when the electric current is flowed in the other of the coils.
Further, specifically, the electromagnetic relay system comprises a positive terminal and a negative terminal both connectable to a power source of a battery or the like arranged at the ATV and a load terminal connectable to the motor for driving the winch. The electromagnetic relay system further comprises control wirings extended from a change over switch separately arranged and connected to respectives of the coils of the respective electromagnetic relays. The electromagnetic relay system is constituted to be able to arbitrarily rotate regularly and reversely the motor by selectively making currents flow to the respectives of the coils at the respective electromagnetic relays via the control wirings.
Meanwhile, according to the above-described electromagnetic relay system of the related art, whereas one end of the coil constituting the electromagnetic relay is connected to the control wiring, a ground line extended from the coil is extended from the case to an external portion and a front end thereof is connected to the negative terminal. That is, according to the coil constituting the electromagnetic relay, when the electric current flows from the control wiring, the electric current reaches to the negative terminal via the ground line and is grounded therefrom.
However, since the above-described electromagnetic relay system of the related art is constituted by extending the ground line of the coil constituting the electromagnetic relay from the case to the external portion and connecting the ground line to the negative terminal and therefore, it is necessary to form a through hole for inserting the ground line through the case and it is necessary to fit a grommet or to fill a resin for waterproofing the through hole.


Compounds of the formula: ##STR1## are useful as anti-cancer, anti-obesity, anti-diabetic, anti-coronary agents, anti-aging agents, anti-hypolipidemic agents and anti-autoimmune agents.

This invention relates to novel steroids and more particularly to androsterone derivatives useful as anti-cancer, anti-obesity, anti-diabetic, and hypolipidemic agents and useful in combatting coronary diseases.
Dehydroepiandrosterone (DHEA) and DHEA-sulfate are major adrenal secretory products in humans. The plasma concentration of DHEA-sulfate, which next to cholesterol, is the most abundant steroid in humans, undergoes the most marked age-related decline of any known steroid.
Although DHEA-sulfate is the main precursor of placental estrogen and may be converted into active androgens in peripheral tissue, there is no obvious biological role for either DHEA or DHEA-sulfate in the normal individual. Several retrospective and prospective studies suggest that women with sub-normal levels of these steroids may be predisposed to develop breast cancer. For example, see Brownsey, et al., "Plasma dehydroepiandrosterone sulfate levels in patients with benign and malignant breast disease," Eur. J. Cancer, 8, 131-137 (1972); Bulbrook, et al., "Relation between urinary androgen and corticoid excretion and subsequent breast cancer," Lancet, 2, 395-398 (1971); Rose, et al., "Plasma dehydroepiandrosterone sulfate, androstenedione and cortisol, and urinary free cortisol excretion in breast cancer," Eur. J. Cancer, 13, 43-47 (1977); Wang, et al., "Studies of the sulfate esters of dehydroepiandorsterone and androsterone in the blood of women with breast cancer," Eur. J. Cancer, 10, 477-482 (1974); and Zumoff, et al., "Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer," Cancer Research, 41, 3360-3363, Sept., 1981.
It has also been established that DHEA is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). For example, see Oertel, et al., "The effects of steroids on glucose-6-phosphate dehydrogenase," J. Steroid Biochem., 3, 493-496 (1972) and Marks, et al., "Inhibition of mammalian glucose-6-phosphate dehydrogenase by steroids," Proc. Nat'l Acad. Sci, U.S.A., 46, 477-452 (1960). Moreover, Yen, et al., "Prevention of obesity in A.sup.vy /a mice by dehydroepiandrosterone," Lipids, 12, 409-413 (1977), reported that long-term administration of DHEA to VY-A.sup.vy /a mice prevented the development of obesity without suppressing appetite.
Furthermore, it is also known that the long-term treatment of C3H mice with DHEA, in addition to reducing weight gain without suppressing appetite, markedly inhibits spontaneous breast cancer development and may delay the rate of aging. It has been observed that DHEA antagonizes the capacity of the tumor promoter, 12-0-tetradecanoylphorbol-13-acetate, to stimulate .sup.3 H-thymidine incorporation in mouse epidermis and in a cultured rat kidney epithelial cell line. See, Schwartz, "Inhibition of spontaneous breast cancer formation in female C3H-A.sup.vy /a mice by long-term treatment with dehydroepiandrosterone, Cancer Res., 39, 1129-1132 (1979); and Schwartz, et al., "Dehydroepiandrosterone: an anti-obesity and anti-carcinogenic agent," Nut. Cancer 3, 46-53 (1981).
Ben-David, et al., "Anti-hypercholesterolemic effect of dehydroepiandrosterone in rats," Proc. Soc. Expt. Biol. Med., 125, 1136-1140 (1967) have observed that DHEA treatment has an anti-hypercholesterolemic effect in mice, while Coleman, et al. (Diabetes 31, 830, 1982) report that administration of DHEA produces a marked hypoglycemic effect in C57BL/KsJ-db/db mice. The latter authors suggest that the therapeutic effect of DHEA might result from its metabolism to estrogens.
It is further known that DHEA and 16.alpha.-bromoepiandrosterone are inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes and that 16.alpha.-bromoepiandrosterone is a more potent inhibitor of mammalian G6PDH than DHEA. See, Schwartz, et al. Carcinogensis, Vol. 2 No. 7, 683-686 (1981).
While DHEA has been found effective in the afore-described manners, there is however, evidence of an estrogenic effect after prolonged administration. DHEA is not an estrogen per se but is well known to be convertible into estrogens. In addition, the therapeutic dose of DHEA is rather high. It would therefore be highly desirable to provide steroids, which while having the same afore-described advantage of DHEA are more potent and do not produce an estrogenic effect.
Besides DHEA, other steroids are known in the art.
Great Britain Patent No. 989,503 to Burn, et al. discloses 6,16.beta.-dimethyl-3.beta.-hydroxyandrost-5-en-17-ones. These compounds are disclosed to be useful as possessing pituitary inhibiting action.
U.S. Pat. No. 2,833,793 to Dodson, et al. discloses 1.beta.,3.beta.-dihydroxy-5-androsten-17-one as an androgenic and anabolic agent.
U.S. Pat. No. 2,911,418 to Johns, et al. discloses 16.alpha.-chloro-3.beta.-hydroxyandrost-5-en-17-one and 3.beta.-hydroxy-16.alpha.-iodoandrost-5-en-17-one as an anti-androgen.
Goldkamp, et al. in U.S. Pat. No. 3,148,198 disclose that 16.alpha.,16.beta.-difluoro-3.beta.-hydroxyandrost-5-en-17-one possess androgenic properties.
French Application No. FR-A 2,317,934 discloses the following compounds:
3.beta.-hydroxy-16.xi.-methylandrost-5-en-17-one PA0 3.beta.-hydroxy-16.xi.-ethylandrost-5-en-17-one PA0 3.beta.-hydroxy-16.xi.-isopropylandrost-5-en-17-one PA0 (a) 3.beta.-iodo-.DELTA..sup.5 -6-methyl-17-oxoandrostene PA0 (b) 3.beta.-chloro-.DELTA..sup.5 -6-methyl-17-oxoandrostene PA0 (c) 3.beta.-hydroxy-.DELTA..sup.5 -6-methyl-17-oxoandrostene PA0 3.beta.-hydroxy-16.alpha.-bromo-5.alpha.-androstan-17-one PA0 3.beta.-hydroxy-16.alpha.-chloro-5.alpha.-androstan-17-one PA0 3.beta.-hydroxy-16.alpha.-fluoro-5.alpha.-androstan-17-one PA0 3.beta.-hydroxy-16.alpha.-iodo-5.alpha.-androstan-17-one PA0 3.beta.-hydroxy-16.alpha.-bromoandrost-5-ene-17-one PA0 16.alpha.bromoandrostan-17-one PA0 3.beta.-hydroxy-16.alpha.-chloro-5.alpha.-androstan-17-one, PA0 3.beta.-hydroxy-16.alpha.-fluoro-5.alpha.-androstan-17-one, PA0 3.beta.-hydroxy-16.alpha.-bromo-5.alpha.-androstan-17-one, PA0 3.beta.-hydroxy-16.alpha.-iodo-5.alpha.-androstan-17-one. PA0 3.beta.-hydroxy-5.alpha.-androstan-17-one PA0 3.beta.-hydroxy-5.beta.-androstan-17-one PA0 3.alpha.-hydroxy-5.alpha.-androstan-17-one PA0 11.beta.-hydroxy-5.alpha.-androstan-17-one PA0 3.alpha.-hydroxy-4.alpha.-methyl-5.alpha.androstan-17-one PA0 3.alpha.-hydroxy-7.alpha.-methyl-5.alpha.androstan-17-one PA0 3.beta.-hydroxy-7.alpha.-methyl-5.beta.androstan-17-one PA0 3.beta.-hydroxy-16.alpha.-bromo-5.alpha.androstan-17-one PA0 3.beta.-chloro-5.alpha.-androstan-17-one.
U.S. Pat. No. 3,976,691 discloses the following compounds: ##STR2##
U.S. Pat. No. 3,471,480 to Fritsch, et al. discloses the following compounds which are useful as progestational agents:
Hanson, et al. in Perkin Transactions I, 1977, pp. 499-501, disclose 3.beta.,4.beta.-dihydroxyandrost-5-en-17-one. No utility is disclosed.
Chemical Abstract 89:105866b discloses that 3.beta.-hydroxy-5.alpha.-androstan-17-one can be hydroxylated in the 15.alpha.-position. Furthermore, said reference teaches that hydroxylation of 3.beta.-hydroxy-5.alpha.androsten-17-one gave both the 7.alpha. and 7.beta.-hydroxyisoandrosterones.
Numazawa, et al. in Steroids, 32, 519-527 disclose 3.beta.,16.alpha.-dihydroxyandrost-5-en-17-one. No utility is disclosed.
DE-A-2,035,738 discloses 7.alpha.-Methyl-3.beta.-hydroxy-5-androsten-17-one and 6,7.alpha.-dimethyl-3.beta.-hydroxy-5-androsten-17-one.
DE-A No. 2 705917 discloses 3.beta.,16.beta.-dihydroxy-5-androsten-17-one.
The Annual Report of the Fels Research Institute, pp. 32-33, (1979-1980) discloses the following compounds as having tumor-preventive, anti-obesity and anti-aging qualities:
Abou-Gharbia, et al. in Journal of Pharmaceutical Sciences, 70, 1154-1156 (1981) disclose the syntheses of:
Pashko, et al. in Carcinogenesis, 2, 717-721 (1981) disclose that 16.alpha.-Br-epiandrosterone is more active than DHEA in inhibiting G6PDH and in reducing the rate of [.sup.3 H] thymidine incorporation into mouse breast epithilum and epidermis. The authors suggest that this compound may be useful in suppressing breast cancer development.
Neef, et al. in Journal of Org. Chem., 43, 4679-4680 disclose the syntheses of 3.beta.-hydroxy-16.alpha.-methyl-5-androsten-17-one and 3.beta.-hydroxy-16.beta.-methyl-5-androsten-17-one.
Robinson, et al. in Journal of Org. Chem., 28, 975-980 (1963) disclose the synthesis of 3.beta.-hydroxy-16.alpha.,16.beta.-difluoro-5-androsten-17-one, and 16-formyl-5-androstene-3.beta.ol-17-one.
Raineri, et al. in Biochemistry, 9, 2233-2243 (1970) tested the inhibitory activity of the following steroids on NADP and NAD linked activity of glucose 6-phosphate dehydrogenase:
Gordon, et al. in Cancer Research 46, 3389-3395 (1986) disclose that DHEA, 16.alpha.-bromoepiandrosterone, epiandrosterone, 3.beta.-hydroxy-5.alpha.-pregnan-20-one, 5.alpha.-androstan-17-one and 5.alpha.-androstan-3.beta.,16.alpha.-diol-17-one are inhibitors of glucose 6-phosphate dehydrogenase. Furthermore, said reference discloses that testosterone, 17.beta.-Estradiol, 5-androstene-3.beta.,17.beta.diol, dehydroepiandrosterone-3-sulfate and 5.alpha.-androstan-17.beta.-ol are noninhibitors of glucose-6-phosphate dehydrogenase. The reference suggests that there is a general correlation between the structure requirements for blocking differentiation to adipocytes and inhibiting glucose-6-phosphate dehydrogenase.
Julian, et al. in JACS, 70, 3872-3876 (1948) discloses the preparation of 16-dimethylaminomethyldehydroisoandrosterone and 16-methylenedehydroisoandrosterone acetate.
Ross, et al. in J. Chem. Soc., 25, (1945) disclose the synthesis of 16-isopropylidene-5-androstene-17-one.
Peat in U.S. Pat. No. 4,028,052 discloses compositions containing the following compounds as the active ingredient: ##STR3## wherein R.sub.1 is O or OH and R.sub.2 is O, or OH; and which may contain one double bond in ring A and/or ring B or tocopherol.
The compounds are alleged to be useful in treating rhemumatoid arthritis, osteoarthritis and arthritas associated with psoriases and with lupus and other auto-immune diseases and also for treating non-specific joint pain associated with stress.

16-substituted androstanes and 16-substituted androstenes