The invention relates to a method and a kit for the diagnosis of endometriosis using blood and endometrial leukocyte markers or a combination thereof. The marker is a surface antigen from endometrial or blood leukocytes.

(a) Field of the Invention
The invention relates to a method and a kit for the diagnosis of endometriosis using blood and endometrial leukocyte markers.
(b) Description of Prior Art
Endometriosis is one of the most common gynecological disorders, affecting up to 15% of women within reproductive age. It is closely associated with severe pelvic pain, dysmenorrhea, dyspareunia, infertility and several other symptoms such as intraperitoneal bleeding, back pain, constipation and/or diarrhea. It is a major threat to physical, psychological and social integrity of the patients.
Endometriosis is characterized by the implantation and growth of endometrial cells (which normally constitute the lining of the uterus) in extra-uterine sites such as the peritoneal cavity. Although the etiology and pathogenesis of endometriosis remain mainly unclear, the theory of retrograde menstruation is the most widely accepted to explain the presence of ectopic endometrial cells in the peritoneal cavity. However, this phenomenon occurs in most women and, thus, several other factors must be invoked to explain the implantation of endometrial cells and the subsequent development of endometriotic lesions. It is generally believed that initiation of endometriosis implies a complex cascade of events requiring several essential features. Retrogradely seeded endometrial cells must remain viable, be capable of adhering to the mesothelium and of proliferating. Local degradation of the extracellular matrix, as well as extensive vascularization, are also believed to play an essential role in promoting the invasion of the peritoneal cavity by endometrial cells. Furthermore, once implanted, ectopic endometrial cells must have the capacity to counteract the cytolytic action of the immune system. Indeed, this is supported by the observation of several immunological abnormalities in patients with endometriosis.
At present, direct visualization of the endometriotic lesions under surgical procedures (laparascopy or laparotomy) is the golden standard and the only reliable method available to diagnose endometriosis. However, this method is highly invasive (i.e. surgery under general anesthesia), costly (i.e. direct cost and indirect cost due to convalescence) and requires a well-trained surgeon who has the ability to identify endometriotic lesions with a variety of appearances. The type of lesions, their size and their localization will determine the stage of the disease (stage I minimal, stage II mild, stage III moderate, stage IV severe). However, there is still no clear consensus on how these parameters correlate with the stage of the disease and the prognostic of endometriosis. In addition, early or minimal endometriosis (which can involve microlesions) can be hardly diagnosed by surgical methods, as they are unlikely to be detected by direct visualization. Indeed, several studies have reported microscopic endometriotic lesions that were not detected laparoscopically. Because the diagnosis of endometriosis by surgical procedures is difficult, costly and invasive, in some cases, several physicians and patients tend to avoid it or at least seriously delay it. Hence, the length of time between the onset of symptoms and the diagnosis can be as long as 8 to 12 years. The possibility to diagnose endometriosis at an early stage would certainly improve the efficacy of the treatments, and reduce dramatically the number of years during which patients endure acute or chronic pain.
Imaging methods such as transvaginal ultrasound and magnetic resonance imaging have been designed for the diagnosis of endometriosis. However, these techniques can only be reliable for the detection of large ( greater than 1 cm diameter) endometriomas lesions detected among a very small proportion of patients with endometriosis. Moreover, the high cost of these techniques has limited their use for the diagnosis of endometriosis.
Serum proteins such as CA-125 and placental protein-14 have been proposed as diagnostic markers for endometriosis. Elevated levels of CA-125 have been observed in serum, menstrual effluent and peritoneal fluid of patients with endometriosis. However, these markers, when used alone, are of very limited value for a diagnosis test. Indeed, these markers are not suitable for screening or diagnostic purposes because they provide poor sensitivity. Furthermore, levels of CA-125 and placental protein-14 vary according to several factors such as the assay, the stage of the disease and the menstrual cycle. Finally these markers are known to be modulated by conditions other than endometriosis.
High concentrations of antibodies to endometrial antigens were found in the serum of patients with endometriosis, and thus were proposed as markers for a diagnostic test (International patent application publications WO 94/28021 and WO 92/18535). However, the levels of specificity and sensibility with these tests remain very low. In most cases, the antigens recognized by these antibodies are still poorly characterized or yet totally unknown.
In U.S. Pat. No. 5,478,725, low levels of xcex1vxcex23 integrin expression in endometrial samples during the secretory phase of the menstrual cycle is described as a predictor of endometriosis in infertile but not in fertile patients with endometriosis. This observation was associated with milder form of endometriosis (stages I and II) only and, thus, is not useful to detect advanced stages of the disease. Moreover, this method yielded a specificity of 91% but a very low sensitivity (38%).
Taking into account that a number immunological abnormalities have been reported in patients with endometriosis, it is conceivable that the proportion of leukocyte populations and/or their activation status may be modulated during the course of the disease and, thus, may provide some diagnostic value. Previous flow cytometric studies have shown that some T lymphocyte subpopulations (CD8+, CD45+/HLADR+, CD45+/CD3+/HLADR+or CD3+/CD25+) can be slightly modulated in the peritoneal fluid of subjects with endometriosis relative to normal controls (Oosterlyncck D. J., et al., Am J reprod. Immunol., 31: 25-31, 1994; Becker J. L., et al., Am J Reprod. Immunol., 34: 179-187, 1995; Wu M. Y., et al., Am. j. Reprod. Immunol. 35: 510-516, 1996). However, these observations have limited value for the diagnosis of endometriosis because peritoneal fluid collection is an invasive, non-conventional procedure. Proportions of leukocyte populations have also been studied in peripheral blood and endometrium of patients with endometriosis. Wu et al., (supra) have reported a modest but significant decrease in the proportion of CD3+ T lymphocytes expressing either CD69 or CD25 activation marker in the blood of patients with advanced endometriosis but not in patients with mild stage of endometriosis or normal controls. This difference was observed in advanced cases of endometriosis only and it was too modest to be used as a diagnostic marker. In contrast, Oosterlynck et al., (Oosterlyncck D. J., et al., Am J reprod. Immunol., 31: 25-31, 1994) and Ho et al. (Ho H. N., et al., Hum Reprod., 97: 2528-2533, 1997) reported no significant difference in term of T lymphocyte subpopulations when comparing endometriosis subjects with normal controls. These inconsistent results may be explained by the very low number of samples tested in these studies.
Several studies have investigated whether leukocytes are also modulated in eutopic endometrium from patients with endometriosis. Results arising from these studies are contradictory, probably due to the fact that in most cases the methods used were only semi-quantitative and the number of samples tested were very low. For instance, by means of immunohistochemistry, Ota et al. (Ota H., et al., Am J Reprod. Immunol., 35: 477-482, 1996) have reported that the number of CD3+, CD4+, or CD8+ T lymphocytes, cells bearing adhesion molecules (i.e. ICAM-1, LFA-1, CD2) or CD68+ cells were upregulated in the endometrium of patients with endometriosis compared with infertile controls. In contrast, several other studies using similar techniques have reported no difference in the proportion of T lymphocyte subsets (Klentzeris L. D., et al., Eur. J Obstet gynecol Reprod Biol., 63:41-47, 1995; Jones R. K., et al., Fertil Steril, 66:81-89, 1996). In addition, a decrease in CD3 positive T cells has been shown by flow cytometry analysis but no difference in the proportion of CD4+, CD8+ stromal leukocytes in the endometrium of patients with endometriosis compared with fertile controls. When these observations are tentatively used in a diagnostic test, they give only low levels of sensibility and specificity because of a significant overlap between the groups.
Therefore, the diagnostic methods presented in the literature so far do not solve the problems encountered with the diagnosis of endometriosis by surgical procedures. It thus remains imperative to be provided with a less invasive, cheaper and reliable method that could allow detection of females suffering from endometriosis as early as possible.
One aim of the present invention is to provide a less invasive, cheaper and reliable method that could allow detection of females suffering from endometriosis as early as possible.
In accordance with the present invention there is provided a specific blood and/or endometrial leukocyte marker for endometriosis selected from the group consisting of CD3+, CD4+, CD5+, CD8+, CD13+, CD14+, CD20+, CD36+, CD44+, CD56+, CD57+, CD69+, CD122+, HLADR+, CD16+, CD45RA+, CD45RO+, CD56xe2x88x92CD122+, CD3+CD4xe2x88x92CD69+, CD3xe2x88x92CD8+HLADRxe2x88x92, CD3+CD4+, CD3+CD4xe2x88x92, CD3xe2x88x92CD4xe2x88x92, CD3+CD5+, CD3xe2x88x92CD5+, CD3xe2x88x92CD5xe2x88x92, CD3+CD8+, CD3+CD8xe2x88x92, CD3xe2x88x92CD8xe2x88x92, CD3+CD16+, CD3xe2x88x92CD16+, CD3+CD16xe2x88x92, CD3+CD20xe2x88x92, CD3xe2x88x92CD20xe2x88x92, CD3+CD44xe2x88x92, CD3xe2x88x92CD44+, CD3xe2x88x92CD44xe2x88x92, CD3+CD45RAxe2x88x92, CD3xe2x88x92CD45RAxe2x88x92, CD3+CD45RA+, CD3+CD45RO+, CD3xe2x88x92CD45RO+, CD3+CD45ROxe2x88x92, CD3+CD56xe2x88x92, CD3xe2x88x92CD56xe2x88x92, CD3+CD57xe2x88x92, CD3xe2x88x92CD57+, CD3xe2x88x92CD57xe2x88x92, CD3+CD69xe2x88x92, CD3+CD69+, CD3xe2x88x92CD69+, CD3+CD122xe2x88x92, CD3+HLADR+, CD3+HLADRxe2x88x92, CD3xe2x88x92HLADR+, CD3xe2x88x92HLADRxe2x88x92, CD4+CD13+, CD4+CD13xe2x88x92, CD4xe2x88x92CD13+, CD4+CD14xe2x88x92, CD4xe2x88x92CD14xe2x88x92, CD4xe2x88x92CD16xe2x88x92, CD4xe2x88x92CD36+, CD4+CD45RAxe2x88x92, CD4xe2x88x92CD45RAxe2x88x92, CD4+CD45RO+, CD4+CD45ROxe2x88x92, CD4xe2x88x92CD45RO+, CD4+CD69xe2x88x92, CD4xe2x88x92CD69+, CD4xe2x88x92CD69xe2x88x92, CD4+HLADRxe2x88x92, CD4-HLADR+, CD8xe2x88x92CD44+, CD8xe2x88x92CD44xe2x88x92, CD8+CD69xe2x88x92, CD8+HLADRxe2x88x92, CD8xe2x88x92HLADRxe2x88x92, CD13+CD16xe2x88x92, CD13xe2x88x92CD16+, CD13+CD44+, CD13xe2x88x92CD44xe2x88x92, CD13+CD45ROxe2x88x92, CD13xe2x88x92CD45RO+, CD13xe2x88x92CD69+, CD13xe2x88x92CD122+, CD13xe2x88x92CD122xe2x88x92, CD13+HLADR+, CD13xe2x88x92HLADR+, CD14+CD13+, CD14+CD13xe2x88x92, CD14+CD16xe2x88x92, CD14+CD44+, CD14xe2x88x92CD44xe2x88x92, CD14+CD45RO+, CD14xe2x88x92CD69xe2x88x92, CD14+CD122xe2x88x92, CD14+HLADR+, CD14xe2x88x92HLADR+, CD20xe2x88x92CD5+, CD20xe2x88x92CD5xe2x88x92, CD20+CD44xe2x88x92, CD20xe2x88x92CD44+, CD20xe2x88x92CD44xe2x88x92, CD20xe2x88x92CD69+, CD20xe2x88x92CD69xe2x88x92, CD20+HLADR+, CD20xe2x88x92HLADR+, CD20xe2x88x92HIADRxe2x88x92, CD36xe2x88x92HLADR+, CD56xe2x88x92CD16+, CD56xe2x88x92CD16xe2x88x92, CD56xe2x88x92CD44xe2x88x92, CD56+CD69xe2x88x92, CD56xe2x88x92CD69+, CD56xe2x88x92CD69xe2x88x92, CD56+CD122+, CD56+CD122xe2x88x92, CD56xe2x88x92CD122xe2x88x92, CD56+HLADR+, CD57xe2x88x92CD44+, CD57xe2x88x92CD44xe2x88x92, CD3xe2x88x92CD4xe2x88x92CD44+, CD3xe2x88x92CD4+CD45RAxe2x88x92, CD3xe2x88x92CD4xe2x88x92CD45RA+, CD3xe2x88x92CD4xe2x88x92CD45RAxe2x88x92, CD3xe2x88x92CD4xe2x88x92CD45RO+, CD3xe2x88x92CD8xe2x88x92CD44+, CD3+CD8+CD69xe2x88x92, CD3+CD8+HLADRxe2x88x92, CD3+CD8xe2x88x92HLADR+, CD3+CD8xe2x88x92HLADRxe2x88x92, CD3xe2x88x92CD8xe2x88x92HLADRxe2x88x92, CD3+CD20xe2x88x92CD5+, CD3+CD20xe2x88x92CD5xe2x88x92, CD3xe2x88x92CD20xe2x88x92CD5xe2x88x92, CD3+CD56+CD16+, CD3+CD56xe2x88x92CD16+, CD3+CD56xe2x88x92CD16xe2x88x92, CD3xe2x88x92CD56+CD16+, CD3xe2x88x92CD56+CD16xe2x88x92, CD3+CD56xe2x88x92CD44+, CD3+CD56xe2x88x92CD44xe2x88x92, CD3+CD56xe2x88x92CD122+, CD3+CD56xe2x88x92CD122xe2x88x92, CD3xe2x88x92CD56+CD122+, CD3xe2x88x92CD56xe2x88x92CD122xe2x88x92, CD3xe2x88x92CD56xe2x88x92HLADRxe2x88x92, CD3xe2x88x92CD57+CD44xe2x88x92, CD3xe2x88x92CD57xe2x88x92CD44+, CD3xe2x88x92CD57xe2x88x92CD44xe2x88x92, CD3+CD57xe2x88x92HLADR+, CD4xe2x88x92CD13+CD16+, CD4xe2x88x92CD13xe2x88x92CD16+, CD4xe2x88x92CD13xe2x88x92CD16xe2x88x92, CD14+CD13+CD16b+, CD14+CD13+CD16bxe2x88x92, CD14+CD13xe2x88x92CD16bxe2x88x92, CD14xe2x88x92CD13xe2x88x92HLADR+, CD14xe2x88x92CD13xe2x88x92HLADRxe2x88x92, CD14+CD20+CD44+, CD14+CD20+CD44xe2x88x92, CD14+CD20xe2x88x92CD44+, CD14+CD20xe2x88x92CD44xe2x88x92, CD14xe2x88x92CD20+CD44xe2x88x92, ratio CD3/CD45RO, Ratio CD13/CD3, Ratio CD13/CD8, Ratio CD14/CD3, and Ratio CD14/CD8.
Also in accordance with the present invention, there is provided a diagnostic method for the detection of endometriosis in a patient sample. The method comprises the step of detecting at least one specific marker as described above, whereby detection of this specific marker is indicative of endometriosis.
Further in accordance with the present invention, there is provided a diagnostic method for the detection of endometriosis in a patient sample. The method comprises the step of detecting at least two different surface antigens from blood or endometrial leukocytes, whereby detection of at least two different surface antigens is indicative of endometriosis.
In accordance with a further embodiment of the invention, there is provided a diagnostic method for the detection of endometriosis in a patient sample. The method comprises the step of detecting a specific marker combination for endometriosis as defined above, whereby detection of this combination is indicative of endometriosis.
Further in accordance with the present invention, there is provided a diagnostic kit for the detection of endometriosis. The kit comprises an antibody specific for the specific maker as described above. Preferably, the kit comprises at least two different antibodies, each specific for different surface antigens as defined in the specific marker combination defined above. Most preferably, the specific marker combination of the diagnostic kit is selected from the combination described below in Tables 1 and 2.
For the purpose of the present invention, the following symbol xe2x80x9c/xe2x80x9d is intended to mean a ratio between an expression in front of the symbol and another expression after the symbol.

Method and diagnostic kit for diagnosis of endometriosis


A method for soil moisture retrieval using multi-channel collaboration algorithm and passive microwave radiometry including: establishing mathematical relationship formula between brightness temperatures at any two channels according to microwave radiative transfer equation; collecting actual brightness temperatures of core channel and collaborative channels; selecting parameters to be retrieved including soil moisture value; giving a series of estimated values of parameters to be retrieved, calculating a series of predicted brightness temperatures of collaborative channels according to actual brightness temperature of core channel, microwave radiative transfer equation and mathematical relationship formula, comparing predicted brightness temperatures with actual brightness temperature, and determining soil moisture value.

The remote sensing observation of soil moisture mainly depends on a microwave remote sensing technology. Especially, the soil moisture at a global scale can be obtained by a space-borne passive microwave radiometer within 2 to 3 days. At present, the soil moisture retrieval algorithms are generally developed for specific satellite payload configurations, which can be divided into the following three categories: (1) a reverse solution based on the radiative transfer equation; (2) an iterative solution based on the radiative transfer equation; and (3) an analytical solution with certain indices from microwave observations. The above-mentioned retrieval algorithms comprise the following disadvantages and limitations: methods (1) and (2) require auxiliary data to assist in the retrieval process. For example, prior information on vegetation, such as the vegetation water content from the auxiliary optical images have to be used to account for vegetation effects in the reverse solution of the method (1) to derive the soil moisture. In the iterative retrieval solution of the method (2), the differences between radiative transfer model simulations and satellite observations are minimized through a certain cost function to obtain a solution result of soil moisture. Because a situation of multiple minima (multiple solutions) are prone to occur in this process, the auxiliary data is generally used as an initial value or as upper and lower bounds of unknown parameters to constrain the retrieval results. The method (3) is used for performing an analytical solving of the radiative transfer equation. There are many parameters in the radiative transfer equation that affect observed brightness temperature of the Earth land surfaces. The model has to be simplified to obtain an analytical solution. Generally, it is assumed that the vegetation effects are polarization independent or there is no vegetation scattering effects. In fact, these assumptions and neglections are not in line with the actual situation, so the retrieval results of soil moisture are inconsistent with the ground-based observations. Therefore, a technical solution that can overcome the above deficiencies at least in some ways is urgently needed.

Method and device for soil moisture retrieval using multi-channel collaborative algorithm and passive microwave radiometry

Aerospace Information Research Institute, Chinese Academy of Sciences


The additional voltage drop across a guard diode against supply polarity inversion in an integrated bridge circuit for driving an external load and employing two high-side NPN power switches driven by two PNP transistors, all monolithically integrated using a junction-type isolation technique, is substantially eliminated by connecting the emitters of the two PNP drive transistors directly to the positive rail, i.e. to the anode of the guard diode. Integrated PNP transistors are per se intrinsically protected against polarity inversion and when so connected permit to reduce the overall voltage drop across the driving bridge circuit. Using a Zener diode as the guard diode and a second Zener diode connected in opposition to the first Zener between the cathode thereof and the negative supply rail an additional spike protection of the circuit's components is implemented.

1. Field of the invention
The present invention relates to an integrated circuit employing NPN power transistors for DC driving an external load, particularly an electric motor, and having a protection against an accidental inversion of polarity of the supply.
2. Description of the prior art
Full-bridge or half-bridge output driving stages, monolithically integrated by employing a junction isolation technique for bidirectional DC driving of motors by means of integrated power switches, are known and widely used. In these integrated power stages the N-type transistors (bipolar NPN or N-channel MOS transistors) are much more efficient than P-type transistors. In practice bridge or half-bridge circuits for high level currents may be economically implemented in an integrated form only if the power switching transistors are of the N-type.
A typical integrated bridge circuit of this kind is shown in FIG. 1. The positive pole of the supply is switched, respectively by the two (high side) NPN power transistors TN1 and TN2, on two output terminals 1 and 2, across which the motor M to be driven is connected. The bridge circuit is completed by two (low side) power transistors TN3 and TN4 which are driven so as to connect to the negative supply pole (ground) the output terminals 1 and 2, respectively. It is also a common practice to drive the two high side switches TN1 and TN2 by means of the two drive PNP transistors TP5 and TP6, respectively, to the base of which the respective drive signals are fed.
The presence of a parasitic diode (respectively D1 and D2 in the circuit diagram of FIG. 1) between an N-type collector C and the P-type substrate S connected to ground of the integrated circuit is intrinsic to such an integrated structure employing a junction-type isolation of an NPN transistor depicted in FIG. 3. In the perspective sectional view of the integrated structure of an NPN transistor of FIG. 3, the presence of this parasitic diode D1 (D2) is schematically shown by means of the relative graphic symbol. The hatched portions of the cross section identify P-type regions while the non-hatched portions identify N-type regions.
Should the supply polarity be accidentally inverted, these parasitic diodes D1 and D2 of the integrated NPN transistors TN1 and TN2 become directly biased and the current passing through these diodes may reach destructive levels.
In order to overcome this problem it is known in the art to use a circuit, such as the one depicted in FIG. 2, wherein a polarity guard diode D3 is employed, which when the supply is accidentally applied with an inverted polarity remains reverse biased thus preventing current flow.
This known solution is not free of drawbacks. In fact, by observing the circuit of FIG. 1, it is easily recognizable that the total voltage drop of the load driving bridge circuit is given by the following expression (for a first diagonal of the bridge): EQU VCE.sub.SAT (TP5)+VBE(TN1)+VCE.sub.SAT (TN4)
or (for the other diagonal of the bridge): EQU VCE.sub.SAT (TP6)+VBE(TN2)+VCE.sub.SAT (TN3)
while in the case of the circuit provided with the guard diode of FIG. 2, the total voltage drop of the circuit is similarly given by the expression (for a first diagonal): EQU V.sub.F (D3)+VCE.sub.SAT (TP5)+VBE(TN1)+VCE.sub.SAT (TN4)
or (for the other diagonal): EQU V.sub.F (D3)+VCE.sub.SAT (TP6)+VBE(TN2)+VCE.sub.SAT (TN3).
It is evident that the use of a diode D3 for protection against polarity inversion of the supply penalizes the electrical efficiency of the circuit by introducing an additional voltage drop V.sub.F (D3) which, in a normal operating condition may be comprised between about 600 mV and 1.2 V.

Bridge circuit having polarity inversion protection means entailing a reduced voltage drop


A flexible touch panel includes a touch sensor unit disposed on a flexible substrate. The flexible touch panel includes a transparent conductive layer, a first transparent conductive oxide layer, and a second transparent conductive oxide layer that are sequentially deposited and sequentially contact each other.

Field
Exemplary embodiments relate to a flexible touch panel and a manufacturing method of the flexible touch panel.
Discussion of the Background
A touch panel is an apparatus which recognizes a touch by a pen or a user's finger and has been recently used as a means which is disposed on a display panel, such as an organic light emitting diode display or a liquid crystal display, to input a signal to a display device.
The touch panel includes a substrate and a touch sensor unit which is positioned on the substrate to recognize a touch.
Recently, the substrate has been formed of a flexible film and the touch sensor unit has been formed of metal mesh or silver nanowire (AgNW), and as a result, a touch panel that is entirely flexible has been developed.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the inventive concept, and, therefore, it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

Flexible touch panel and method for manufacturing flexible touch panel


A new electrostatic discharge protection device is achieved. A p-well region is in a semiconductor substrate. An n+ region in the p-well region is connected to a first voltage supply. An n-well region in the p-well region is spaced from the n+ region such that a depletion region will extend therebetween during normal operation. A p+ region in the n-well region is connected to a second voltage supply of greater value than the first voltage supply during normal operation. Current is conducted through the n+ region to the p+ region during an electrostatic discharge event.

(1) Field of the Invention
The invention relates to a device for protecting integrated circuits from electrostatic discharge (ESD), and more particularly, to a novel diode device for ESD protection in multiple supply applications.
(2) Description of the Prior Art
The fabrication of disparate functions onto single integrated circuit chips often requires that more than one voltage supply be used. For example, an integrated circuit device may have a low voltage section wherein very small MOS logic transistors are powered from a low voltage supply. This same integrated circuit device may contain analog circuits or input/output (I/O) circuits that are powered by a high voltage supply. In these cases, special design and layout consideration must be used to handle these differing voltage supplies on the chip. In addition, interface circuits, such as level shifting circuits, provide special challenges to insure that the integrated circuit device is not damaged during normal operation or during special transient conditions.
Electrostatic discharge (ESD) is of particular concern for integrated circuits containing more than one voltage supply. ESD events occur primarily due to handling of the integrated circuit by machines or by people. During an ESD event, a large electrostatic potential can develop between pins of the device. When the potential is discharged, energy is dissipated within the device and can result in catastrophic damage to the chip. ESD protection devices are designed on each input and output pin to provide conductive paths between the pin and ground or the pin and the voltage supply during the large voltage transient associate with the ESD event. These protection devices are typically sufficient to protect the I/O pads of the single supply chip. However, when more than one voltage supply pin is used, the ESD protection devices must be modified or additional protection structures must be added.
Referring now to FIG. 1, a partial top view of a prior art integrated circuit device 10 is illustrated. In this device 10, three pads 12, 14, and 16 are shown. In this case, the device 10 uses two voltage supplies, VCC1 and VCC2. In normal operation, the VCC1 voltage is connected to the VCC1 pad 16 and the VCC2 voltage is connected to the VCC2 pad 14. An additional ESD protection device 22 is added to the integrated circuit device 10. This additional ESD protection device 22 is illustrated as a diode 22. The third pad, GND 12, is connected to the ground reference for the system using the integrated circuit device.
Referring now to FIG. 2, a cross-section of an exemplary diode protection device is shown. This device comprises a p-well region 26 in the semiconductor substrate. In practice, the entire semiconductor substrate may be a lightly doped p-type region 26. The p-well region 26 is connected to the GND pad 32. An n-well region 34 is formed in the p-well region 26. An n+region 42 and a p+ region 38 are formed in the n-well region. The n+ region 42 is connected to the VCC1 supply 44, and the p+ region 38 is connected to the VCC2 supply 40. A p-n junction is formed by the p+ region 38 and the n-well region 34. This p-n junction forms the p-n diode 22 that is shown in both FIGS. 1 and 2. This diode structure 22 provides isolation between the VCC2 supply 40 and the VCC1 supply 44 assuming that VCC2 is greater than VCC1 by an amount of less than the diode turn on voltage (Vt) that is typically about 0.7 Volts. When an ESD event occurs, the diode provides a current path between the voltage supply pins that protects the internal circuitry from damage. A distinct disadvantage of the device of FIG. 2 is that VCC2 supply can only be a maximum of about 0.7 Volts greater than the VCC1 supply.
Referring now to FIG. 3, the useful operating range of the diode device of FIG. 2 can be extended by creating a string of diodes. In this prior art device, two n-well regions 66 and 78 are formed. A first diode 80 is formed in the first n-well region 66 by the p-n junction formed by the p+ region 62 and the n-well region 66. The p-terminal 62 of the first diode 80 is connected to the higher voltage source, VCC264. The n-terminal, formed as the n+ regions 58, of the first diode 80 is connected to the p-terminal 74 of the second diode 88. The n-terminal, formed by the n+ regions 70, of the second diode 88 is then connected to the lower voltage source, VCC172. Note that the presence of the n-well regions 66 and 78 in the p-well region 48 actually creates a chain of two p-n-p transistors with two diode drops between VCC2 and VCC1. This means that the diode string configuration allows for the VCC2 voltage to exceed the VCC1 voltage by two diode drops, or about 1.4 Volts.
Referring now to FIG. 4, the prior art diode string concept is shown in the general configuration wherein a large string of p-n-p transistors 112, 116, 120, and 124 are used in the case where a large voltage difference exists between VCC2100 and VCC1104. The diode string approachs used in FIGS. 3 and 4 have the disadvantage of requiring a lot of area to form the separate n-well regions for each stage of the string. In addition, the conductivity of the diodes during an ESD event is not optimal.
Several prior art inventions describe ESD devices and circuits. U.S. Pat. No. 6,002,568 to Ker et al discloses an ESD circuit using silicon controlled rectifier (SCR) devices. U.S. Pat. No. 5,898,205 to Lee teaches an ESD protection circuit where conventional CMOS protection transistors are capacitively-coupled to improve performance. U.S. Pat. No. 6,011,681 to Ker et al discloses a circuit using bi-directional SCR devices to provide current discharge paths between separate power supplies. U.S. Pat. No. 5,530,612 to Maloney teaches ESD protection circuits using biased diode strings and cantilevered diode strings. U.S. Pat. No. 5,747,834 to Chen et al discloses a bipolar SCR with an adjustable holding voltage wherein the device is entirely constructed in an n-well and uses a buried layer.
A principal object of the present invention is to provide an effective and very manufacturable integrated circuit device for protecting the integrated circuit from electrostatic discharge (ESD) events.
A further object of the present invention is to provide an ESD protection device that is effective as a discharge path between voltage supply pins on the same integrated circuit device.
A yet further object of the present invention is to provide an ESD protection device that is suitable for applications wherein a large voltage difference exists between the voltage supply pins.
A still further object of the present invention is to provide an ESD protection device that is suitable for large voltage differences between the voltage supply pins and that can be integrated in a single n-well of small area.
In accordance with the objects of this invention, a new electrostatic discharge protection device is achieved. A p-well region is in a semiconductor substrate. An n+ region in the p-well region is connected to a first voltage supply. An n-well region in the p-well region is spaced from the n+ region such that a depletion region will extend therebetween during normal operation. A p+ region in the n-well region is connected to a second voltage supply of greater value than the first voltage supply during normal operation. Current is conducted through the n+ region to the p+ region during an electrostatic discharge event.

Taiwan Semiconductor Manufacturing Company


An electromagnetic relay includes an electromagnetic part, a movable iron piece, a contact driving part, a contact which is opened and closed by driving the contact driving part with a card disposed between the movable iron piece and the contact driving part. Particularly, the card is disposed between the insulating wall and the contact driving part, a driving projection projected onto an inward surface side opposed to the insulating wall of the card is inserted in and projected from a manipulation hole made in the insulating wall, and the driving projection of the card is pressed by the movable iron piece that is operated based on excitation and demagnetization of the electromagnetic part.

1. Technical Field
The present invention relates to an electromagnetic relay.
2. Related Art
Conventionally, Japanese Unexamined Patent Publication No. 2003-115248 discloses an electromagnetic relay. The electromagnetic relay includes: a substantially C-shaped flat-plate yoke that includes a body part extending in a horizontal direction and leg parts extending downward from both ends of the body part; an insulating winding frame that includes a winding body part attached to the body part, and an exciting coil being wound around the winding body part; an armature that includes a horizontal part, a turning shaft part, and a vertical part, the horizontal part extending in the horizontal direction, an insulating actuating piece being provided in the horizontal part, the turning shaft part extending from one end side of the horizontal part toward an extending direction of one of the leg parts, the vertical part extending from the other end side of the horizontal part, the vertical part coming into contact with the other leg part when the exciting coil is excited; an insulating base housing that includes a recessed portion or a hole while supporting the leg parts of the yoke, the recessed portion or the hole receiving a shaft piece formed at a lower end of the turning shaft part of the armature; and a movable contact piece and a fixed contact piece that are attached to the base housing while disposed below the exciting coil and between the leg parts of the yoke, the movable contact piece and the fixed contact piece coming into contact with each other by a pressing force of the actuating piece. In the electromagnetic relay, the base housing includes an insulating wall extending between the exciting coil and the armature and a second insulating wall that interrupts the movable and fixed contact pieces and the armature, and the actuating piece presses the movable contact piece through a hole made in a substantially central portion of the second insulating wall.
As illustrated in FIG. 6, in the conventional electromagnetic relay, an armature 60 reciprocatably turned by excitation and demagnetization of an exciting coil 56 and an actuating piece (card) 64 are integrally reciprocated, a movable contact piece 21 is driven by the actuating piece 64 to bring and separate the movable contact into contact with and from the fixed contact.
However, in the conventional electromagnetic relay, it is necessary to obliquely assemble a projection part 65 of the actuating piece 64 outsert-molded in the armature 60 in a rectangular hole 15 made in a base 10. For this reason, it is troublesome to assemble the projection part 65 in the rectangular hole 15, which results in low assembly workability. Additionally, it is necessary to make the rectangular hole 15 in large size. Therefore, a desired insulating distance cannot be ensured, and an insulating characteristic is degraded. It is also necessary to make the rectangular hole 15 in large size compared with a section of the projection part 65, which results in a problem in that an abrasion powder generated by an operation of the armature 60 easily passes through the rectangular hole 15 to generate an insulation failure. The present invention has been devised to solve the problems described above, and an object thereof is to provide an electromagnetic relay having the excellent assembly workability, the excellent insulating characteristic, and the hard-to-generate insulation failure.


A pressure compensated solenoid valve with fluid flow force balancing is provided. The solenoid valve includes an armature and a valve plunger arranged to transport hydraulic fluid from a supply end of a valve plunger to an upper end of the armature facilitating a resultant upper fluid force that acts upon the upper end of the armature to balance a resultant lower fluid force that acts on the supply end of the valve plunger. The solenoid valve includes a poppet that is configured as a pressure-relief valve for maintaining a minimum fluid pressure within an actuation fluid gallery. An inlet fluid force of the poppet is balanced by an outlet fluid force of the poppet.

Variable valve lift (VVL) and variable valve timing (VVT) systems of internal combustion (IC) engines often manage hydraulic fluid flow, leakage or pressure within a network of fluid galleries to vary the output of these respective systems. This type of hydraulic fluid management is typically handled by a solenoid valve which can be precisely controlled by an electronic controller such as an engine control unit (ECU). A solenoid valve that consistently functions throughout the varying operating conditions of the IC engine is critical to the accuracy and performance of many VVL and VVT systems.

Pressure compensated solenoid valve with fluid flow force balancing


A medical report generation apparatus includes a key image selection unit that selects, as a key image representing a diagnostic characteristic feature, a slice image generated based on three-dimensional medical image data obtained by imaging a subject, a selected position input unit that inputs a selected position in the key image, a supplementary image determination unit that determines, based on the key image and the selected position, a slice image that includes the selected position and represents a cross section different from a cross section represented by the key image, as a supplementary image, in the three-dimensional medical image data, and a medical report generation unit that generates a medical report including the key image and information for identifying the supplementary image.

1. Field of the Invention
The present invention relates to a medical report generation apparatus, a medical report generation method and a medical report generation program for generating a medical report about image-based diagnosis of a patient.
2. Description of the Related Art
In image-based diagnosis in medical fields, a person in charge of generating a medical report reads and interprets a medical image obtained by imaging a patient, and generates the medical report that describes position information about a region of interest judged to be important for diagnosis, and to which a key image including the region of interest is attached. Further, a doctor or the like checks the generated medical report to diagnose the patient.
However, when only the key image attached to the medical report and the position information about the region of interest described in the medical report are provided, the information is insufficient for a doctor or the like in some cases to diagnose a patient while accurately recognizing the region of interest, such as the position and the size of a diseased part or the like. In such cases, the doctor or the like needs to obtain a supplementary image by manually retrieving an image in which the region of interest is recognizable from images of the patient obtained by imaging. That may impose time and work on the doctor or the like.
Japanese Unexamined Patent Publication No. 2010-182179 (Patent Document 1) discloses an apparatus that makes a doctor easily recognize the location of a lesion by generating and displaying a lesion location image representing the location of the lesion in a schematic diagram. The lesion location image is generated based on report data including information about the position of the lesion and schematic image data representing the schematic diagram illustrating the structure of an anatomical region in which the lesion is present.
Japanese Unexamined Patent Publication No. 2005-327302 (Patent Document 2) discloses an apparatus that displays a key image, which is a key for image-based diagnosis, and an image related to the key image in a medical report when a user displays and checks report data. The image related to the key image is generated from a picture archiving and communication system (PACS), based on report data generated by attaching the key image and an image processing parameter set necessary to generate the key image to the medical report, by using the image processing parameter set necessary to generate the key image or an image processing parameter set obtained by modifying the image processing parameter set necessary to generate the key image.
However, the method disclosed in Patent Document 1 indicates the location of a lesion in the schematic diagram. Therefore, the position of an actual region, skeleton or the like of a patient and an anatomical position in the schematic diagram do not sufficiently match with other. Hence, comparison has been difficult in some cases. Further, in the method disclosed in Patent Document 2, when a user displays and checks the medical report, the user needs to specify an image to generate and display the image related to the key image. Therefore, there has been a problem that selection of the image related to the key image is not easy for a user who is not used to an operation for appropriately changing an image processing parameter set and an operation for selecting the image related to the key image.

Medical report generation apparatus, method and program


A plastic lens barrel includes an object-end portion, an image-end portion and a tube portion. The object-end portion has an object-end outer surface, an object-end opening and an object-end inner surface, wherein one end of the object-end inner surface is connected to the object-end outer surface and surrounds the object-end opening. The image-end portion has an image-end outer surface and an image-end opening. The tube portion connected object-end portion and the image-end portion, and includes a plurality of tube inner surfaces. At least one of the tube inner surfaces and the object-end inner surface includes a plurality of annular convex structures. Each of the annular convex structures surrounds a central axis of the plastic lens barrel. A cross-sectional plane of each annular convex structure passing through the central axis includes a peak point and two valley point.

Technical Field
The present disclosure relates to a plastic lens barrel and an imaging lens module. More particularly, the present disclosure relates to a plastic lens barrel and an imaging lens module applicable to portable electronic devices.
Description of Related Art
In recent years, the portable electronic devices have been developed rapidly, such as smart devices, tablets and so on. These portable electronic devices have been full of daily lives of modern people, and the camera module loaded on the portable electronic devices thrives on it. The demand for quality of the camera module increases along with the advances in technology. Therefore, the camera module needs to be improved not only on the quality of the optical design but manufacturing assembling precision.
FIG. 10 is a schematic view of an imaging lens module 10 applied to camera module in the conventional art. In FIG. 10, the imaging lens module 10 includes a lens barrel 11 and a plurality of optical elements 12 (such as lens elements, light shielding sheets), wherein the optical elements 12 are disposed in the lens barrel 11. The lens barrel 11 is made by an injection molding, and an inner surface thereof is arranged with a plurality of stepped structures 11a. However, each of the stepped structures 11a does not have obvious peak point and valley points, the positions 11b, and 11c thereof projecting on the optical axis overlap to each other. Hence, the image would be affected by the stray light, so as to affect the image quality.

Plastic lens barrel, imaging lens module and electronic device


Systems and methods for establishing direct communication between a server system and a video game controller are described. The systems and methods include the video game controller and a computing device. An application is executed by the server system when a session is established by the computing device with the server system. Once the application is executed, the video game controller is used to send an identifier to the server system. The server system verifies the identifier to pair the session with the video game controller. When the video game controller is paired with the session, the video game controller can be used to change a state of a virtual scene that is displayed on the computing device or on a display screen.

Generally, a game is accessed for play via a game console. The game console is coupled to a game controller. A gamer connects the game console to a television. The game or an update for the game is downloaded from a server to the game console and the gamer plays the game using the game controller.
It is in this context that embodiments described in the present disclosure arise.


The application relates to compounds of Formula (I′):

STK4 (also known as MST1) is a serine-threonine kinase that is part of the Hippo signaling pathway. STK4 is involved in multiple cellular processes including proliferation, trafficking, apoptosis, immune response and stress response (Cottini, F., et al., Nat. Med., 20 (6), 599-606 (2014); Salojin, K. V., et al., PLoS One, 9(5), e98151 (2014); Ardestani, A., et al., Nat. Med., 20 (4), 385-397, (2014)). STK4 reactivates the Hippo mediator YAP1 thereby triggering apoptosis in hematologic malignancies characterized by high levels of DNA damage. DNA double-strand break (DSB) followed by activation of DNA damage response in cancers occurs in premalignant and malignant conditions. However, progression to malignancy is prevented in precancerous settings by senescence and apoptotic responses until the tumor suppressor TP53 (p53) is inactivated, thereby triggering genomic instability and enhancing tumor cell growth.
Recently, it has been shown that hematologic malignancies, including multiple myeloma, lymphoma, and leukemia, contain pervasive DNA damage that leads to activation of a p53-independent proapoptotic network centered on relocalization of ABL1 kinase. Unlike normal cells in which ABL1 kinase triggers cell death with the Hippo pathway co-activator YAP1, low levels of YAP1 in hematologic malignancies prevent nuclear ABL1-induced apoptosis (Cottini, F., et al., Nat. Med., 20 (6), 599-606, (2014)).
Downregulation of STK4 with specific shRNAs has been shown to lead to a robust increase of YAP1 protein levels compared to scrambled shRNA. Inactivation of serine-threonine kinase 4 (STK4) has also been shown to restore YAP1 levels triggering cell death in vitro and in vivo demonstrating that YAP1 is under the control of STK4. Inhibition of STK4 with small molecule inhibitors has the potential to be a treatment for cancers and other disorders. Known STK4 inhibitors have demonstrated poor kinase selectivity, cell penetration and pharmacokinetic properties. For these reasons, there remains a need for novel and potent small molecule STK4 inhibitors.

STK4 inhibitors for treatment of hematologic malignancies

Abstract: which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.


A hot gas heat treat system is employed to cool mix in a hopper and a freezing cylinder and to heat the mix for pasteurization. A hopper liquid line solenoid valve at the inlet of the hopper and a cylinder liquid line solenoid valve at the inlet of the freezing cylinder each control the flow of refrigerant to the expansion valves which further control the flow of refrigerant that flows around the hopper and the freezing cylinder, respectively. A hopper hot gas solenoid valve at the inlet of the hopper and a cylinder hot gas solenoid valve at the inlet of the freezing cylinder control the flow of refrigerant from the compressor that flows around the hopper and the freezing cylinder. The system further includes a hot gas bypass valve that is opened when only the hopper is being cooled to provide additional load to the compressor. An EPR valve is positioned proximate to the hopper discharge to vary the temperature of the refrigerant exchanging heat with the hopper. A CPR valve is employed to control the inlet pressure of the compressor by reducing the amount of hot refrigerant flowing into the compressor suction. The system further includes a TREV valve to allow for liquid refrigerant injection to the compressor suction to control excessive compressor discharge during the cool cycle.

The present invention relates generally to a refrigeration system used in a frozen dessert system that includes a hopper heat exchanger and a cylinder heat exchanger that each contain a frozen dessert mix and have a respective expansion device, and a valve is positioned between each of the respective expansion devices and a heat rejecting heat exchanger to control a flow of refrigerant from the heat rejecting heat exchanger and into the hopper heat exchanger and the cylinder heat exchanger.
A refrigeration system is employed to cool a mix in a frozen dessert system. The frozen dessert system typically includes a hopper which stores the mix and a freezing cylinder that cools and mixes air into the mix prior to serving. The freezing cylinder is cooled by a refrigeration system. Refrigerant is compressed in a compressor to a high pressure and high enthalpy. The refrigerant then flows through a condenser where the refrigerant rejects heat and is cooled. The high pressure low enthalpy refrigerant is then expanded to a low pressure. After expansion, the refrigerant flows through the tubing encircling the freezing cylinder, accepting heat from and cooling the freezing cylinder, and therefore the mix. After cooling the freezing cylinder, the refrigerant is at a low pressure and high enthalpy and returns to the compressor for compression, completing the cycle.
The hopper is cooled by a separate glycol system that wraps around the hopper and the freezing cylinder. The glycol that flows around the freezing cylinder is cooled by the freezing cylinder. The cooled glycol then flows around the hopper to cool the mix in the hopper. To meet food safety standards, the mix in the hopper must be kept below 41xc2x0 F.
The mix is also pasteurized every night to kill any bacteria. The mix is heated for approximately 90 minutes to obtain a temperature of at least 150xc2x0 F. The mix is kept over 150xc2x0 F. for 30 minutes, and then cooled back to 41xc2x0 F. within 120 minutes. The mix is heated by heating the glycol with an electrical heater. As the heated glycol flows around the hopper and the freezing cylinder, the heat in the glycol is transferred to the freezing cylinder and the hopper, warming the mix.
A drawback to this system is that both the freezing cylinder and the hopper are coupled by the glycol system. During cooling, when the cooled glycol flows around and exchanges heat with the hopper, the glycol is heated by the hopper. When the glycol later flows around the freezing cylinder again, the heat in the glycol heats the freezing cylinder, melting the mix in the freezing cylinder.
Additionally, during heating, the glycol first flows around and heats the freezing cylinder. As the glycol rejects heat to the freezing cylinder, the glycol is cooled. When this glycol flows around the hopper, it is less effective in heating the hopper as the glycol has already been cooled by the freezing cylinder. Therefore, it takes longer to heat the hopper, resulting in a long pasteurization cycle which requires over three hours to complete. As the pasteurization cycle changes the flavor of the mix, a longer pasteurization cycle can affect the flavor of the frozen dessert.
Hot gas heating systems have been used in the prior art, but did not allow for individual control of the cooling of the hopper and the cylinder. Therefore, both the hopper and cylinder were cooled at the same time and could not be cooled separately. If only one of the hopper and the freezing cylinder required cooling, the other would have to be cooled as well. As the suction lines of the hopper and the freezing cylinder of the prior art are also not de-coupled, it is difficult to vary the pressure, and hence the temperature, of the refrigerant in the hopper and the freezing cylinder. To achieve the best dessert product quality, it is desirable to have the refrigerant cooling the mix in the hopper be at a different temperature and pressure than the refrigerant freezing the mix in the freezing cylinder. Another drawback of the prior art hot gas system is also that there is a low system capacity as an undersized compressor is employed to attain compressor reliability.
The hot gas heat treat system of the present invention includes a hopper which stores mix for making a frozen product. The mix flows from the hopper into a freezing cylinder for cooling and mixing with air. The refrigerant is compressed in a compressor and then cooled by a condenser and changes to a liquid. The refrigerant is then split into two paths, one flowing to the freezing cylinder and one flowing to the hopper. The refrigerant flowing to the freezing cylinder is expanded to a low pressure by an AXV expansion valve and then accepts heat from the freezing cylinder to cool the mix in the freezing cylinder. The refrigerant flowing to the hopper is expanded to a low pressure by a TXV expansion valve and then accepts heat from the hopper to cool the mix in the hopper. The refrigerant flowing to the hopper is between 22xc2x0 and 24xc2x0 F to keep the mix in the hopper between 37xc2x0 and 39xc2x0 F. After cooling the freezing cylinder and the hopper, the refrigerant is at a low pressure and high enthalpy and returns to the compressor for compression.
A liquid line solenoid valve is positioned at the inlet of each of the hopper and the freezing cylinder to control the flow of cool high pressure liquid refrigerant from the condenser to the hopper and the freezing cylinder. A hot gas solenoid valve is positioned at each of the inlet of the hopper and the freezing cylinder to control flow of hot gaseous refrigerant from the compressor discharge to the hopper and the freezing cylinder. When the system is in the cooling mode, the liquid line solenoid valves are opened and the hot gas solenoid valves are closed to allow the flow of high pressure liquid refrigerant to cool the mix in the hopper and the freezing cylinder. When the system is in the heating mode for nightly repasteurization, both the hot gas solenoid valves are opened and the liquid line solenoid valves are closed to allow the hot gaseous refrigerant to warm the mix in the hopper and the freezing cylinder.
When only the hopper is being cooled, not enough load is provided on the compressor, affecting compressor reliability. A hot gas bypass valve is opened to allow refrigerant gas from the compressor discharge to flow to the compressor suction to increase compressor load. Preferably, a solenoid valve is employed in series with the hot gas bypass valve to prevent leakage of refrigerant through the hot gas bypass valve.
An EPR valve is positioned proximate to the hopper discharge to maintain the evaporator pressure of the hopper, and therefore the temperature of the refrigerant flowing through the hopper. A CPR valve limits the inlet pressure of the compressor by reducing the amount of refrigerant flowing into the compressor suction. A solenoid valve proximate to the discharge of the freezing cylinder is closed when the freezing cylinder is not being cooled to prevent warm refrigerant from migrating around the freezing cylinder.
The system further includes a TREV valve to allow for liquid refrigerant injection to the compressor suction to control excessive compressor discharge during the cool cycle. When the compressor discharge temperature approaches 230xc2x0 F., the TREV valve is opened to allow the high pressure liquid refrigerant from the condenser to flow into the compressor suction, cooling the compressor suction and therefore the compressor discharge.
These and other features of the present invention will be best understood from the following specification and drawings.