A diaphragm structure includes a ceramic substrate having at least one window portion and a thin diaphragm laminated onto the ceramic substrate so as to cover the window portion, wherein only a part of an interface between the ceramic substrate and the thin diaphragm is joined to form a joint of the diaphragm. A diaphragm structure is free from instability caused by a breakage or deformation of a partition wall between window portions upon punching or laminating even if a diaphragm structure employs a design in which dimensions of a diaphragm portion is maintained and simultaneously a distance between diaphragm portions is made narrow to restrain a surface area excluding a diaphragm portion of a diaphragm structure or a design in which a plurality of diaphragm portion having various configurations and dimensions are disposed.

The present invention relates to a diaphragm structure. Particularly, the present invention relates to a ceramic diaphragm structure having a thin diaphragm in a hollow portion and a joint portion of the diaphragm in a hollow portion having a special configuration.
There has conventionally been used a diaphragm structure as a member or the like constituting various kinds of sensors. The diaphragm structure has a substrate having at least one window portion and a thin film material having flexibility so as to cover the window portion. In recent years, the diaphragm structure has had particular usefulness as a piezoelectric/electrostrictive actuator.
For example, as a member constituting a sensor, a diaphragm portion of the diaphragm structure detects a flexing displacement and vibrations received from a subject to be measured by a proper detecting means. When the diaphragm structure is used as a member constituting a piezoelectric/electrostrictive actuator, a diaphragm portion of the diaphragm structure is deformed, displaced and vibrates by the piezoelectric/electrostrictive actuator, thereby generating sound or pressure in a pressurizing chamber formed inside the diaphragm structure.
Such a diaphragm structure is produced by unitarily combining a substrate as a supporter and a film member providing a diaphragm. In view of reliability, thermal resistance, anti-corrosive ability and the like, it was considered to constitute such a diaphragm structure by unitarily firing a ceramic body. The present inventors have proposed in Japanese Patent Application 62-129360 (Japanese Patent Lid-Open 63-292032) a pressure detecting apparatus or a piezoelectric/electrostrictive actuator, each of which uses a ceramic diaphragm structure obtained by being unitarily fired.
As shown in FIG. 9, such a ceramic diaphragm structure is generally obtained by firing unitary laminate composed of a first green substrate 10 having window portions 10a and a second green substrate 9 having a thin planar shape. Alternatively, as necessary, such a ceramic diaphragm is obtained by firing unitary laminate composed of the green substrates 9, 10 and another substrate such as a third green substrate 11 having throughholes 11a in communication with the window portions 10a.
If the third green substrate 11 does not have any throughhole 11a, thereby closing off the cavities, problems are caused by rising air pressure in each cavity when thermally treated, or the like, in a manufacturing process. Each of the throughholes 11a has a role of avoiding such problems. For example, when the diaphragm structure is used for a speaker, the throughhole 11a has a function of adjusting a volume of air flow and a back pressure.
There are various kinds of requirements for an element of a sensor, a speaker, an actuator, a filter, a condenser array, and the like. The requirements are increasing a surface area of a moving portion occupying a part of a surface of an element (decreasing a surface area of a stationary portion), high efficiency and miniaturization of an element by means of highly dense disposition of a plurality of moving portions, conformability to a complicated modification of a design, disposition of a plurality of driving portions each having different properties in one clement. Particularly in the case of a sensor, an element having a large surface area of a stationary portion increases a sensing loss, thereby lowering a sensing ability.
Therefore, as shown in FIG. 10, a partition wall between window portions 13a, 17a of the first ceramic substrate 13, 17 was changed from a thick one 13c to a thin one 17c (D2.ltoreq.D1) without changing a distance between the partition walls (L1=L2), thereby restraining a surface area excluding diaphragm portions (D1-D4) of a diaphragm structure by decreasing a distance between diaphragm portions with maintaining dimensions of diaphragm portions.
However, there are some problems in the diaphragm structure in which a surface area excluding diaphragm portions is restrained by decreasing a distance between moving portions by reducing a thickness of the partition wall.
First, since the partition wall 17c formed between window portions is thin, a rigidity of the first ceramic green sheet decreases. Therefore, there sometimes happens a distortion of an inner wall of a window portion, i.e., a partition wall 17c, or a burr upon punching a window portion 17a, thereby giving an unstable configuration of a diaphragm structure to be obtained.
Second, since a die for machine punching must typically have a fine configuration, the die is prone to abrasion and a short life span, and the cost for maintaining the die increases, which makes a diaphragm structure expensive, in addition to an unstable configuration of the diaphragm structure.
Third, a partition wall 17c is crushed and deformed by a pressure of lamination upon handling after punching, particularly when ceramic green sheets are laminated by being pressurized. Therefore, a diaphragm cannot have a stable configuration.
Other problems are that a diaphragm structure cannot be produced with high precision, or that various types with only a small order number cannot be produced, in view of the demand for conformity to a modification of a design of a diaphragm structure or for disposition of a plurality of diaphragm portions having various configurations.
Accordingly, the present invention is directed to providing a diaphragm structure which maintains a rigidity inherent in ceramic green sheets have in a producing process and a configuration of a diaphragm of a completed diaphragm structure and which has a smaller rate of surface area occupied by a portion excluding diaphragm portions. Further, the diaphragm structure is produced rapidly at a low cost even if a design is changed complexly or a design requires disposition of a plurality of diaphragm portions each having an individual configuration in one substrate.


A nonvolatile memory device and method for fabricating the same are provided. The nonvolatile memory device includes an active region; a source region formed in the active region; a source line formed on the source region and electrically connected with the source region, to cross over the active region; word lines aligned at each sidewall of the source line to cross over the active region in parallel with the source line; and a charge storage layer interposed between the word lines and the active region. Since the word lines are formed at both sides of the source line using an anisotropic etch-back process, without photolithography, the area of a unit cell can be reduced.

1. Field of the Invention
The present invention relates to semiconductor devices, and more particularly, to a nonvolatile memory device and a method for fabricating the same.
2. Discussion of the Related Art
A nonvolatile memory device may be a floating gate type device or a charge trap type device. A floating gate nonvolatile memory device is an example of a flash memory device while a charge trap nonvolatile memory device is an example of a silicon-oxide-nitride-oxide-silicon, or SONOS, memory device. The charge-trap device has a MOS transistor structure in which a multilevel charge storage layer is used as a gate insulating layer. The charge-trap device is thereby enabled to have writing and erasing voltages lower than those of the floating-gate device. Therefore, the charge-trap device can be operated at lower power, with a smaller area for a peripheral circuit, e.g., a voltage pump. The charge-trap device can also be operated with higher reliability due to its use of a spatially isolated insulating layer for storing charges.
FIGS. 1A and 1B illustrate a related art nonvolatile memory device having a multilevel charge storage layer.
Referring to FIGS. 1A and 1B, a device isolation film 12 is formed in a semiconductor substrate 10 to define a plurality of parallel active regions. Word lines 16 are formed above the active regions by interposing a charge storage layer 14. The word lines 16 pass above the device isolation film 12, that is, above the surface of the semiconductor substrate 10, to cross over the active regions. Source/drain regions 18s and 18d are respectively formed in the active regions at both sides of the word lines 16. The source region 18s is formed between two adjacent word lines 16. Each source region 18s is connected with another source regions 18s of other active regions where there is no formation of the device isolation film 12. Common source lines, to which a plurality of source regions are connected, are formed between and in parallel with the word lines 16. By contrast, each drain region 18d is isolated between formations of the device isolation film 12, such that the formation of each drain region is restricted to an active region. A sidewall insulating film 20 forms spacers at sidewalls of the word lines 16.
The word lines may be patterned by a photolithographic process, and after their formation, the common source lines are formed by etching the device isolation film using the word lines as an etching mask. Then, impurity ions are implanted. Therefore, any desired reduction in the width of each word line and each source line is inherently limited. The limitations restrict attempts to increase the integration of a nonvolatile memory device by reducing the unit cell size.

Method for fabricating nonvolatile memory device


Disclosed herein is a display device using a field inversion driving system, the display device being formed by arranging pixels each including an electrooptic element in a form of a matrix and inverting polarity of a display signal to be written to each of the pixels in field periods, the display device including: double-speed converting means for converting an input display signal into a double-speed display signal having a field frequency twice a field frequency of said display signal; and crosstalk correcting means for correcting crosstalk in a second field of two fields as a unit of said double-speed display signal generated by said double-speed converting means, using information of the first field.

1. Field of the Invention
The present invention relates to a display device and a driving method of a display device, and particularly to an active matrix type display device formed by two-dimensionally arranging pixels each including an electrooptic element in the form of a matrix and a driving method of the display device.
2. Description of the Related Art
A display device formed by arranging pixels each including an electrooptic element in the form of a matrix, for example an active matrix type liquid crystal display device formed by two-dimensionally arranging pixels each including a liquid crystal cell, the liquid crystal cell being used as an electrooptic element, in the form of a matrix generally employs an alternating-current driving system that inverts the polarity of a display signal in certain periods with a common potential Vcom as a center in order to prevent degradation of liquid crystal and image burn-in in an alignment layer due to continuous application of a direct-current voltage of the same polarity to the liquid crystal.
FIGS. 13A and 13B are diagrams of assistance in explaining a field inversion driving system that inverts the polarity of a display signal in field periods. FIG. 13A shows, for example, a pixel arrangement of four rows and four columns. FIG. 13B shows a driving waveform for each pixel in the pixel arrangement.
This field inversion driving system has a problem of degradation in display quality due to a so-called vertical crosstalk caused by a leak of pixel transistors for switching liquid crystal cells. Specifically, as shown in FIG. 14, when a normally white type liquid crystal display device (a liquid crystal display device that decreases transmittance as voltage applied to liquid crystal is raised), for example, displays a black window on a gray background, a problem occurs in pixels in gray areas 02 and 03 situated in a direction of vertical scanning (top-to-bottom direction) of a black area 01 in that the pixels in the area 02 over the black area 01 appear darker than original gray and the pixels in the area 03 under the black area 01 appear lighter than the original gray.
The problem of this vertical crosstalk occurs because field inversion driving switches between positive polarity driving and negative polarity driving in field units, and thereby changes potentials between the common electrodes of pixels, source wiring, and gates, resulting in a difference between an amount of leakage (amount of crosstalk) of pixel transistors in the upper area 02 and an amount of leakage (amount of crosstalk) of pixel transistors in the lower area 03.
Making more concrete description, when the pixels are written with a positive polarity (or a negative polarity) in a certain field, and written with a negative polarity (or a positive polarity) in a next field, in a stage of writing the black area 01, the polarity of a row being written and the polarity of the upper area 02 are the same negative polarity, whereas the polarity of the lower area 03 yet to be written remains the positive polarity of the previous field.
Thus, with respect to a potential to be written to the black area 01, the polarity of a potential retained by the pixels in the upper area 02 is different from the polarity of a potential retained by the pixels in the lower area 03, resulting in a difference between the amounts of leakage of the pixel transistors in the upper area 02 and the lower area 03. Therefore, the upper area 02 over the black area 01 appears darker than the original gray, and the lower area 03 under the black area 01 appears lighter than the original gray.
To deal with degradation in display quality due to such a vertical crosstalk in related art, image data for each pixel is corrected such that even when the potential of a pixel electrode is changed with a potential change, the potential of the pixel electrode coincides with an average potential within a frame when it is assumed that the change in the potential of the pixel electrode does not occur (see for example, Japanese Patent Laid-Open No. 2005-077508. Hereinafter refer to as Patent Document 1.).
Also known is a technique that uses a memory (line memory) having a capacity for one scanning line, stores a sum of information for one vertical column in a previous field, and corrects image data for each pixel in a present field using the information stored in the line memory (see for example, Japanese Patent Laid-Open No. 2000-330093. Hereinafter refer to as Patent Document 2).

Display device and driving method of display device


A zirconia based ceramic material having improved and well-balanced mechanical strength and toughness consists essentially of 0.5 to 50 vol % of Al.sub.2 O.sub.3 having an average grain size of 2 .mu.m or less and the balance of a partially stabilized zirconia having an average grain size of 5 .mu.m or less. The partially stabilized zirconia consists essentially of 8 to 12 mol % of CeO.sub.2, 0.05 to 4 mol % of TiO.sub.2 and the balance of ZrO.sub.2. Fine Al.sub.2 O.sub.3 grains having an average grain size of 1 .mu.m or less are dispersed within the grains of the partially stabilized zirconia at a dispersion ratio. The dispersion ratio is defined as a ratio of the number of Al.sub.2 O.sub.3 grains dispersed within the grains of the partially stabilized zirconia relative to the number of the entire Al.sub.2 O.sub.3 grains dispersed in the ceramic material, and at least 2% in the present invention. The ceramic material can be made by the following process. A first constituent formed of the partially stabilized zirconia is mixed with a second constituent formed of Al.sub.2 O.sub.3 to obtain a mixture. The mixture is molded into a desired shape, and then sintered in the air under an atmospheric pressure to obtain the ceramic material.

1. Field of the Invention
The present invention is directed to a zirconia based ceramic material having excellent mechanical strength and toughness, and also a process of making the same product.
2. Disclosure of the Prior Art
A partially stabilized zirconia, which is obtained by the addition of a preferable amount of a stabilizer such as yttrium oxide (Y.sub.2 O.sub.3), cerium oxide (CeO.sub.2), magnesium oxide (MgO), or the like., to zirconia (ZrO.sub.2), has been well known as a ceramic material having higher mechanical strength and toughness than another popular ceramic materials such as alumina (Al.sub.2 O.sub.3), silicon carbide (SiC), silicon nitride (Si.sub.3 N.sub.4), or the like. The partially stabilized zirconia possesses a unique mechanism for improving the mechanical strength and toughness. That is, a phase transformation from metastable tetragonal zirconia to stable monoclinic zirconia is caused under a stress concentration, for example, at the tip of a crack developed in the partially stabilized zirconia. Since such a transformation, which is usually called as a stress induced phase transformation, is accompanied with a volume expansion of about 4%, a further progress of the crack in the partially stabilized zirconia can be effectively prevented. For example, a partially stabilized zirconia containing Y.sub.2 O.sub.3 as the stabilizer exhibits a mechanical strength of 1000 MPa or more. Particularly, it is already known that a ceramic material comprising Al.sub.2 O.sub.3 grains as a dispersing phase and the partially stabilized zirconia containing Y.sub.2 O.sub.3 as a matrix exhibits a higher mechanical strength of 2400 to 3000 MPa. However, these ceramic materials provide a relatively low mechanical toughness which is in a range of 5 to 6 MPa m.sup.1/2 and not always enough to use as structural and machine parts. On the other hand, a partially stabilized zirconia containing CeO.sub.2 as the stabilizer exhibits a high mechanical toughness of 10 to 20 MPa m.sup.1/2. Additionally, the partially stabilized zirconia containing CeO.sub.2 is capable of stably maintaining the metastable tetragonal zirconia at a temperature range of 200.degree. C. to 400.degree. C., and particularly keeping the mechanical strength even under a hydrothermal condition. The partially stabilized zirconia containing Y.sub.2 O.sub.3 exhibits a low temperature degradation of mechanical strength at the temperature range of 200.degree. C. to 400.degree. C. When the partially stabilized zirconia containing Y.sub.2 O.sub.3 is kept at the temperature range for an extended time period, most of tetragonal zirconia included in the partially stabilized zirconia containing Y.sub.2 O.sub.3 is transformed to monoclinic zirconia accompanying with the volume expansion of about 4%. By the volume expansion, micro cracks are developed in the partially stabilized zirconia containing Y.sub.2 O.sub.3, so that the mechanical strength is decreased. In addition, the tetragonal-to monoclinic phase transformation is accelerated under the hydrothermal condition, so that the mechanical strength is considerably decreased. Thus, the partially stabilized zirconia containing CeO.sub.2 exhibits a higher mechanical strength than the partially stabilized zirconia containing Y.sub.2 O.sub.3 at the above temperature range, and particularly under the hydrothermal condition. However, the mechanical strength of the partially stabilized zirconia containing CeO.sub.2 is in a range of 600 to 800 MPa at a room temperature, which is lower than that of the partially stabilized zirconia containing Y.sub.2 O.sub.3. Therefore, by improving mechanical strength of the partially stabilized zirconia containing CeO.sub.2, more expanded application fields will be expected as a material overcoming the low temperature degradation of the mechanical strength of the widely-used partially stabilized zirconia containing Y.sub.2 O.sub.3. In other words, a zirconia based ceramic material having improved and well-balanced mechanical strength and toughness is desired.
Japanese Early Patent Publication KOKAI! No. 5-246760 discloses a zirconia based composite material comprising a matrix of a partially stabilized zirconia containing 5 to 30 mol % of CeO.sub.2 and a secondary phase of at least one selected from Al.sub.2 O.sub.3, SiC, Si.sub.3 N.sub.4, B.sub.4 C, carbides, nitrides and borides of elements of groups IVa, Va, VIa of the periodic table. Fine grains of the secondary phase are dispersed within grains as well as in grain boundaries of the partially stabilized zirconia matrix. When the content of CeO.sub.2 is more than 30 mol %, the mechanical strength of the composite material is lowered due to the increase of cubic zirconia in the matrix. When the content of CeO.sub.2 is less than 5 mol %, a formation of metastable tetragonal zirconia in the matrix is not enough. The composite material contains 0.5 to 50 vol % and more preferably 2.5 to 30 vol % of the secondary phase.
Japanese Early Patent Publication KOKAI! No. 63-144167 discloses the following ceramic materials (a) to (c):
(a) a ceramic material comprising 45-94.75 mol % of ZrO.sub.2, 5-45 mol % of TiO.sub.2 and 0.25-10 mol % of a rare earth oxide selected from the group consisting of Gd.sub.2 O.sub.3, Yb.sub.2 O.sub.3, Nd.sub.2 O.sub.3, Tb.sub.2 O.sub.3, Pr.sub.2 O.sub.3, Dy.sub.2 O.sub.3, Ho.sub.2 O.sub.3, Sm.sub.2 O.sub.3, and Er.sub.2 O.sub.3 ;
(b) a ceramic material comprising 48-94.75 mol % of ZrO.sub.2, 5-45 mol % of TiO.sub.2 and 0.25-7 mol % of Y.sub.2 O.sub.3 ;
(c) a ceramic material comprising 35-93.5 mol % of ZrO.sub.2, 5-45 mol % of TiO.sub.2 and 1.5-20 mol % of CeO.sub.2.
For example, in the ceramic material (a), a grain growth of tetragonal zirconia is prevented by adding a small amount of the rare earth oxide to a partially stabilized zirconia containing TiO.sub.2 as the stabilizer, so that the mechanical properties are improved. In addition, this prior art discloses that grains of cubic zirconia and/or zirconium titanate (ZrTiO.sub.4) are effective to prevent the grain growth of tetragonal zirconia. These ceramic materials (a) to (c) can be used as a dispersing phase to reinforce a ceramic matrix such as alumina, mullite, or the like. For example, a ceramic composite consisting of about 5 vol % of the ceramic material and the balance of the ceramic matrix may be useful as a material improving mechanical properties of the ceramic matrix.
Japanese Patent Publication KOKOKU! No. 64-7029 discloses a ceramic material comprising 61 to 87 wt % of ZrO.sub.2, 11 to 27 wt % of CeO.sub.2 and 20 wt % or less of Al.sub.2 O.sub.3. The ceramic material mainly contains tetragonal zirconia, in which CeO.sub.2 forms a solid solution with ZrO.sub.2. 20% or less of the entire zirconia crystals in the ceramic material is monoclinic zirconia and/or cubic zirconia. This prior art discloses that a sintered body produced by preparing a mixture of ZrO.sub.2, CeO.sub.2 and Al.sub.2 O.sub.3 with the above composition and sintering the mixture exhibits a mechanical strength comparable to a sintered body in ZrO.sub.2 -Y.sub.2 O.sub.3 system. This prior art also indicates that the ceramic material may contains 2 wt % or less of SiO.sub.2, TiO.sub.2 and Fe.sub.2 O.sub.3, etc., as impurities. That is, since a ZrO.sub.2 powder used in this prior art is prepared by treating a zircon sand containing the impurities with an acid to obtain an acid chloride of zirconium, and performing a heat-treatment to the acid chloride, there is a probability of remaining a small amount of the impurities in the ZrO.sub.2 powder. On the other hand, when the content of Al.sub.2 O.sub.3 is more than 20 wt %, a sintering temperature of the ceramic material is raised, so that the grain growth of the zirconia crystals is enhanced. By such a grain growth, variations in mechanical strength of the ceramic material are increased.
Thus, various attempts have been made to improve the mechanical properties of the zirconia based ceramic material.

Process of making zirconia based ceramic material


The present invention discloses a method of treating, preventing or ameliorating tumor growth by administering a therapeutic agent that selectively inhibits dipeptidyl peptidase including fibroblast activation protein and dipeptidyl peptidase 8/9 in combination with an immune checkpoint inhibitor. The method specifically discloses use of Talabostat in combination with an immune checkpoint inhibitor, its pharmaceutical composition and process of preparing such composition.

Cancer is a multistep process that begins with minor pre-neoplastic changes, which may progress to neoplasia, the neoplastic lesions possibly developing an increasing capacity for invasion, growth, metastasis, and heterogeneity. Current therapies for the treatment of cancer involve surgery, hormonal therapy, radiation therapy, chemotherapy and immunotherapy. Immunotherapy for the treatment of cancer has evolved alongside our improved understanding of immune system. In particular, an appreciation of the ability of cancer cells to subvert the antitumor immune response has provided a rationale for the development of novel immunotherapies that target immune checkpoints responsible for the tumor cells escaping detection and destruction by the immune system. Such immune escape mechanisms are mediated either directly by the tumor cells or by the tumor microenvironment. Tumor cells are known to express membrane proteins, secreted products, enzymes, anti-inflammatory cytokines, and chemokines to produce changes in their genome that aid in immune evasion and immune inhibition. At the same time, a key role is played by the tumor microenvironment.
Immune checkpoint molecules such as PD-1, PD-L1, CTLA-4 are cell surface signaling receptor play an important role in modulating the T-cell response in the tumor microenvironment. Tumor cells have been shown to utilize these checkpoints to their benefit by up regulating their expression and activity. Therefore, immune checkpoint inhibitors have been developed which can unleash the immune system's cancer-destroying properties. Recent discoveries have identified immune checkpoints or targets like, PD-1, PD-L1, PD-L2, CTLA4, TIM3, LAG3, CCR4, OX40, OX40L, IDO, and A2AR as proteins responsible for immune evasion, acting as brakes of the immune system. Specific immune checkpoint inhibitors, including antibodies against CTLA-4, PD-1 receptor or its ligand PD-L1 have produced impressive results in the clinic in a range of cancers, leading to FDA approvals for YERVOY® (Ipilimumab; CTLA-4 antagonist), OPDIVO® (Nivolumab; PD-1 antagonist) and KEYTRUDA® (Pembrolizumab; PD-1 antagonist) in multiple tumor indications and with ongoing registration trials in many more. As immune checkpoint inhibitors, could show activity in many or most tumor types, it is estimated that the market for this type of therapy could grow to >$100 billion by 2020.
Unfortunately, checkpoint inhibitors suffer from several limitations. Only a minority of patients treated with checkpoint inhibitors exhibit robust anti-tumor responses, and most responses are partial and temporary. Many patients initially respond, but then relapse due to the emergence of resistant pathways, which may occur due to many reasons, mainly the generation by the tumor cells that form a non-immune permissive micro-environment to overcome the action of the immune-checkpoint inhibitors; the so called "non-inflamed" tumors or either T cells have not been recruited to the tumor site or because even if present, they are not activated. In these cases, just releasing the brake is not enough to achieve the full anti-tumor potential of the immune system. Moreover, the cancer immunity cycle comprises of several steps and the current hypothesis is that combinations of various inhibitors acting at different stages in this cycle will permit to optimize immune-oncology therapies and improve efficacy to a wider population and reduce resistance.
This hypothesis has received its first validation by the recent approval of the combination of the two checkpoint inhibitors Ipilimumab and Nivolumab, which act on various sites in the cancer immunity cycle, which increased the response rate in melanoma patients from the 11% and 32% seen with the respective monotherapy to 60% with the combination. Unfortunately, this combination has the major drawback of high toxicity, as many patients experience unusual toxicities related to an excessive immune response leading to pneumonitis, hepatitis, colitis and other immune related disorders. It is also not known yet whether this combination will increase response rate in other tumors beside melanoma. Therefore, current research in carcinogenesis has been directed to identifying the use of therapeutic agents acting as immunomodulators, which impact the tumor or the tumor microenvironment. Various databases, conferring the details, relating to genomic, proteomic, and bioinformatics have been used to identify such individual targets that should be synergistically targeted for a better treatment response. The inventors of the present invention utilize the target dipeptidyl peptidase (DPP) which specifically includes FAP and DPP 8/9, a dipeptidyl peptidase linked to immune-evasion.
The analysis revealed the existence of several approaches to target dipeptidyl peptidase (DPP) that specifically include FAP and DPP 8/9. Various approaches include small molecules, antibodies, engineered peptides, engineered receptors, autologous immune enhancement approach or siRNA, preferred is the small molecule approach, i.e. small molecule inhibitor such as Talabostat. This clinically validated immunomodulatory small molecule plays important role in immune evasion and regulates both innate and/or acquired immunity.
Talabostat also known as PT-100 (Val-boroPro; L-valinyl-L-boroproline), was originally developed by Point Therapeutics, during 2000 to 2007. It is an orally available synthetic selective inhibitor of dipeptidyl peptidases like FAP and DPP8 and DPP9. The stereoisomer of the Talabostat molecule disclosed in the U.S. Pat. No. 6,825,169 while its oral formulation such as tablet, capsule, lozenges is disclosed in the U.S. Pat. No. 7,265,118.
U.S. Pat. No. 6,949,514 assigned to Point Therapeutics, Inc. discloses a method of treating abnormal mammalian cell proliferation by administration of Talabostat. WIPO Publication No. WO 2007058957 assigned to Point Therapeutics, Inc. discloses a combination of Talabostat with at least one cytokine such as IL-2, Interferon, G-CSF, or GM-CSF. These cytokines are not immune-checkpoint inhibitors, although they stimulate the immune system but do not remove the brakes, therefore the present invention is entirely different from this disclosure.
U.S. Pat. No. 6,890,904 assigned to Point Therapeutics, Inc. discloses a combination of Talabostat with at least one anti-cancer drug. However, these therapies of Talabostat alone or in combination with cytokine or chemotherapeutic agents are not effective for the treatment of cancer and in the clinical trials of pancreatic and lung cancer. Talabostat was unable to meet primary as well as secondary endpoints.
WIPO Publication No. WO2007059099 assigned to Point Therapeutics, Inc. discloses a combination of Talabostat with Pemetrexed or Erlotinib or Docetaxel. It further discloses that the combination therapy further comprises the administration of a cancer antigen such as B7-H1. However, WO′099 does not provide any disclosure for the combination of Talabostat with immune checkpoint inhibitors.
EP Patent No. 2,782,994 assigned to Trustees of Tufts College discloses ARI-4175 compound or other compounds that inhibit the activity of mammalian DASH serine proteases alone or in combination with immunotherapies for the treatment of cancer wherein compound is not val-boro-pro. Hence, EP'994 focuses on the use of compound ARI-4175 for treating cancer wherein Talabostat is disclaimed. However, the present invention focuses on use of Talabostat in combination with immune checkpoint inhibitors.
Talabostat shows various adverse events and the most common adverse events are edema/peripheral swelling, hypotension, hypovolemia, and dizziness. These adverse events as well as insufficient primary and secondary outcomes in the clinical trials may lead to withdrawal of Talabostat molecule.
The novel discovery in this regard includes a selective dipeptidyl peptidase (DPP) inhibitor in combination with an immune checkpoint inhibitor comprised of several elements. Firstly, the combination therapy is surprisingly more effective at sub-therapeutic doses. In addition, DPP inhibitor has been shown to induce edema, which is also a major toxicity associated with chemotherapeutic agents and therefore the combination with chemotherapeutic agent induces additive, potentially synergistic toxicity which results in discontinuation and limited efficacy. Immune checkpoint inhibitor does not have edema as relevant toxicity so this new combination approach would not have the limitation observed with the previous combination.
The final element consists of the identification of the novel combination (i.e. selective DPP inhibitor and an immune checkpoint inhibitor) that possess the strong additive/synergistic mechanism of action.
To sum up, the inventors of the present invention have come up with a combination of a selective DPP inhibitor such as Talabostat with immune checkpoint inhibitor to overcome the problems in the prior arts that may enhance or prolong the anti-tumor and immunomodulatory effects of immune checkpoint inhibitor, leading to breakdown of tumor microenvironment, enhancing infiltration and attack by immune cells, converting non-immunogenic tumor to immunogenic tumor, enabling a subject to respond to a non-responsive cancer or reducing the dose or toxicity of Talabostat and/or immune checkpoint inhibitor.
Accordingly, it is an object of the present invention to provide improved methods with a novel combination for the treatment of cancer.

Approach for treatment of cancer via immunomodulation by using talabostat


The present invention discloses a mating ring, a primary ring, and associated mechanical seal having superior heat transfer and wear characteristics. According to an exemplary embodiment of the present invention, one or more dimples are formed onto the cylindrical outer surface of a mating ring sidewall and/or a primary ring sidewall. A stationary mating ring for a mechanical seal assembly is disclosed. Such a mating ring comprises an annular body having a central axis and a sealing face, wherein a plurality of dimples are formed into the outer circumferential surface of the annular body such that the exposed circumferential surface area of the annular body is increased. The texture added to the sidewall of the mating ring yields superior heat transfer and wear characteristics.

Mechanical face seals are used to control leakage from pumps, mixers, agitators, and the like. Seals are among the most crucial components of industrial machinery. If a seal fails prematurely, it can have significant economic and environmental consequences.
A basic mechanical seal is a mechanically loaded device consisting of a rotating (primary) ring and stationary (mating) ring, having lapped faces that operate in close proximity under hydraulic pressure from fluid containment as well as the spring force that pushes the rings together to minimize the leakage between the rotating shaft and the stationary housing. A common material used in primary rings is carbon graphite, and ceramic, stainless steel, tungsten carbide and silicon carbide are popular materials for use in mating rings. Coolant (flush fluid) may be supplied to lubricate and remove heat from the interface between the two rings.
Most mechanical seals fail long before they wear out, with high temperatures identified as some of the main causes of their failure. Heat is generated at the interface as the primary ring rubs against the mating ring during operation. Too much heat can cause thermal distortions on the seal face and accelerate wear, and thus increase the leak path. Further, heat effects are known to be responsible for thermo-elastic instabilities (TEI) that occur due to high speeds and high loads, particularly if the seal material is prone to heat checking. These instabilities give rise to the formation of macroscopic hot spots on the seal faces interface. Hot spots may expand relatively more than adjacent areas, causing higher local pressures that act on the surface and generate more frictional heating. This is analogous to a positive feedback loop in a control system, causing thermally induced instability.
Both conduction and convection heat transfer play a significant role on the performance of a mechanical seal. Since heat conduction occurs as heat flows through the primary ring and mating ring, the thermal conductivity of these materials is important. In addition, heat generated at the interface between the mating and rotating ring is dissipated into the flush fluid through the process of convective heat transfer. In order to remove the heat generated at the faces very quickly, a high heat transfer coefficient and/or a larger wetted area is needed. Heat transfer from seal face is mostly dissipated through axial and radial directions. Therefore, increasing the wetted area in the axial and radial directions can be considered for improving heat transfer. However, an increase in the surface area is not always possible due to space and/or design limitations. Therefore, new heat transfer augmentation techniques are needed to reduce interface temperature.
There are many heat transfer augmentation techniques employed in the engineering field, such as pin fins, rib turbulators, and dimpled surfaces. Dimples may be defined as pits, bores, holes, or any other depressions formed into a surface. Dimples can be easily fabricated using such techniques as a laser engraving machine, which can quickly "burn" textures on different material from carbides to metals, or any other suitable technique. Arrays of surface dimples are used in wide variety of practical applications such as electronics cooling, heat exchangers, turbine blade internal cooling passages, etc. However, most of studies on utilizing dimpled surfaces in mechanical seals consider turbulent flows at high Reynolds numbers while studies pertaining to thermal performance for dimpled surfaces in laminar flows are, quite rare.
Some studies have examined the placement of dimples on the active surface of the mating ring of a mechanical seal. While such placement may achieve a desired effect on the friction generated between the mating ring and the stationary ring, texturing the active surface of the mating ring may create an additional load-carrying capacity with each dimple such that the summation of all of them could created a lifting force. Such a lifting force may separate the faces and thus create a leak path and thus render the seal ineffective. Further, considering a seal in which the active surface has been lapped to within 2 helium light bands (a common practice), adding dimples to the active surface would require a second lapping step after the dimples are added, thus introducing a greater expense and complexity to the manufacturing process. Additionally, other recent studies suggest that adding dimples or otherwise texturing the active surface of the mating ring may lead to increased wear.
Other recent studies regarding the use of dimple textures in mechanical seals are associated with an internal cooling process whereby the coolant is pumped through small channels with dimpled surfaces. However, such designs likely require potentially drastic changes to existing seal configurations, the flush plan, and/or the use of additional auxiliary parts in order to accommodate the internal cooling process. Accordingly, there is currently an unfilled need for a mechanical seal with superior heat transfer and wear characteristics that nevertheless functions with conventional mechanical seal configurations.

Board of Supervisors of Louisiana State University and Agricultural and Mechanical College


Embodiments of the present disclosure provide for the synchronous distribution real-time and historical farming data to user client devices via shared and personal interface rooms. In some embodiments, multiple users can be connected to a shared interface room corresponding to a data collection device to view real-time and historical farming data simultaneously. The shared interface room can then broadcast farming data to each user whenever real-time farming data is received. Historical farming data can be determined based on a pair of timestamps corresponding to data collection device activity and user activity. When one of the connected users requests to view historical farming data, the historical farming data can be provided to the requesting user via a personal interface room.

Advancements in farming machinery have provided users with access to valuable machine and agronomic data ("farming data") that is generated or collected by the farming machinery and other sensors to provide valuable analytical insights into farmland, machine efficiencies, harvest yields, farming methodologies, and more. Users—such as farmers—often benefit from accessing this data as quickly as possible in order to make informed decisions.
However, conventional systems often require a user to manually export farming data from farming machines and sensors, translate the farming data and then present the farming data for analysis and consumption. For example, in some conventional systems, the user must connect a universal serial bus ("USB") drive to a terminal in the farming machine and export the data to the USB drive. As the farming data is often stored in a proprietary format, the user must then upload the data to a proprietary or third-party system to translate the farming data, which can require several hours or days to complete. Although the user can access the farming data in this way, the process is time consuming and may provide the user with valuable information only after the time period to make a decision has passed.

This patent is subject to a terminal disclaimer.

Real-time and historical farming data distribution system


A system for analyzing a chemical reaction provides control of the temperature and volume of the reagents to improve the accuracy and precision in quantitative measurements of specific proteins and other immunochemistries in body fluids. The reaction occurs in a cuvette within a nephelometric optics module. A sensor senses the temperatures of reaction buffer liquids as they flow into the cuvette, and a heat exchanging device increases or decreases the temperatures of the buffer liquids. A control circuit responsive to the temperature sensor controls the heat exchanging device to maintain the temperature of the buffer liquids and the cuvette within a selected temperature range. The system may also include a sample pickup station, a sample probe for withdrawing a selected sample from the sample pickup station, a sample preparation station, and transport device for carrying said sample from the sample preparation station to the reaction cuvette. The system may include an antibody pickup station, an antibody probe for withdrawing an antibody from the antibody pickup station, an antibody preparation station, and antibody transport device for carrying the antibody from the antibody preparation station to the reaction cuvette.

The invention relates generally to immunochemistry analyzing apparatus and methods and particularly to rate nephelometric techniques for analyzing precipitate forming reactions between antigens and antibodies.
Certain analytes, such as proteins, in body fluids may be detected by monitoring chemical reaction between the analytes and antibodies produced in goats, rabbits, etc. In particular, polyvalent protein antigens in sera may react with their corresponding antibodies to produce precipitates. Such antibodies are called precipitins, and their reactions are called immunoprecipitin reactions. In these reactions the amount of precipitate is a function of either the antibody concentration or the antigen concentration, depending upon the relative concentrations of the antigen and antibody.
Nephelometry involves measuring the intensity of light scattered by particles in suspension in a cell when a beam of light is passed through the cell. Rate nephelometry is the monitoring of the rate of change of the amount of light scattered as a reaction proceeds. The resulting complexing and consequent changing scattered light intensity occurs at a rate that increases gradually at first. The rate then increases rapidly until it reaches a peak rate before it decreases to zero as either the antibody or the antiqen is depleted.
The analyzer electronics derives the peak value of the rate of change from the scattered light signal. For these purposes, an antigen-antibody immunoprecipitin reaction is conducted in an optically transparent sample container or vial. An excitation system directs a beam of light into the sample container, and a detection system measures light scattered at a forward angle from the precipitate. The detected nephelometric, or light scatter, signal is differentiated to provide a function indicated of the rate. The peak value of the rate is indicative of the concentration of the desired antigen or antibody.
Although less sensitive than enzyme immunoassay, fluorescent immunoassay and radioimmunoassay, nephelometry and rate nephelometry provide the most convenient and direct method for measuring most clinically significant proteins. Nephelometric measurements require no labels and provide direct real time monitoring of the antigen-antibody reaction.
The basis for nephelometric determination of antigens and antibodies is the formation of molecular aggregates when the bivalent antibody molecules combine with multivalent antigen molecules. When the connections of the antigens and antibodies are near equivalence, considerable cross linking occurs between the molecules. Antibody molecules bridge between antigen molecules to link several antigen molecules and many antibody molecules into large molecular aggregates that from a precipitate.
These molecular aggregates, after attaining molecular weights of about 3 million or greater, scatter an appreciable amount of light, which may be monitored with various means for detecting light. When the antibody is present in considerable excess, only small scattering centers develop because each antigen tends to have its sites saturated with antibody molecules. The probability that a single antibody molecules will from a bridge between two antigen molecules is small. The reaction forms complexes of the form Ag(Ab).sub.m, where Ag represents the antigen, Ab represents the antibody and m is the valency of the antigen; but larger complexes do not form. No precipitation occurs in extreme antibody excess.
In the case of antigen excess, each antibody molecule has both of its sites occupied by different molecules. Complexes of the form (Ag).sub.2 Ab form, but there are insufficient antibody molecules to bridge between the antigen molecules to form a cross linked lattice.
In the case of antibody excess, or low antigen concentration, no free antigen molecules appear in the supernatent, and an increasing amount of precipitation occurs as antigen is added to the sample. On a plot of peak rate versus antigen concentration, the peak rate increases from zero to a maximum and then decreases from the maximum with further increases in antigen concentration. On the ascending portion of the curve, at lower antigen concentrations, there is an excess of antibody. As further antigen is added, the system moves into antigen excess such that the antigen ties up all the antibody molecules without cross linking. There is a decrease in the total amount of precipitation, and no free antibody is found in the supernatent.
The double valued nature of the functional relationship between the antigen concentration and the amount of precipitate formed presents problems in measurement because a given amount of precipitate can correspond to both a low amount and a high amount of antigen. The measuring range in nephelometry is preferably on the ascending region of the curve where there is an excess amount of antibody. Only measurements in the ascending region of the curve provide reliable data on the amount of antigen present in a sample. Clinical applications of nephelometry generally require analysis of a large number of samples. Therefore, the time required for measuring each sample is an important consideration.
After a measurement has been made in the ascending portion of the curve, it is necessary to verify that the peak rate obtained was valid. The time required for this verification is called the peak verify time. If it is determined that a measured peak rate corresponds to a higher antigen concentration on the descending portion of the curve in antigen excess, it is necessary to dilute the sample and remeasure the rate for the sample. The dilutions and remeasuring are repeated until a peak rate in antibody excess is obtained. After an acceptable peak rate measured in antibody excess is derived from the diluted sample, the corresponding antigen concentration is scaled upward by the appropriate dilution factor to determine the actual antigen concentration of the original sample.
There are several publications describing nephelometric assay of antigen-antibody reactions and addressing the problems encountered in determining the antigen or antibody excess condition of such reactions. These publications include: (1) Savory et al., Kinetics of the lgG-anti-lgG Reaction as Evaluated by Conventional and Stopped-flow Nephelometry, Clin. Chem., 20, 1071 (1974); (2) Buffone et al., Use of a Laser-equipped Centrifugal Analyzer for Kinetic Measurement of Serum lgG. Clin. Chem., 20, 1320 (1974); (3) Buffone et al., Evaluation of Kinetic Light Scattering as an Approach to the Measurement of Specific Proteins With the Centrifugal Analyzer. I. Methodology. Clin. Chem., 21. 1731 (1975); (4) Buffone et al., Evaluation of Kinetic Light Scattering as an Approach to the Measurement of Specific Proteins With the Centrifugal Analyzer. II. Theoretical Considerations. Clin. Chem., 21, 1735 (1975); (5) Tiffany et al., Specific Protein Analysis by Light-scatter Measurement With a Miniature Centrifugal Fast Analyzer. Clin. Chem., 20, 1055 (1974); (6) Anderson et al., A Rate Nephelometer for Immunoprecipitin Measurement of Specific Serum Proteins in Automated Immunoanalysis, 2, R. F. Ritchie, Ed., Marcel Dekker, New York (1978), pp 409-469; and (7) Sternburg, Monitoring the Precipitin Reaction Using Rate Nephelometry, ACPR 27, April, (1984).
Savory et al., Clin. Chem., 20, 1071 (1974) and Buffone et al., Clin. Chem., 20, 1320 (1974) disclose a two-point semi-kinetic method for measuring specific proteins by deriving the average rate of change of scatter between two fixed times. These references disclose the scatter intensity rises more rapidly in comparison with the end value that it approaches in antigen excess than in antibody excess. These references neither disclose nor suggest any method for utilizing such behavior for determining an excess of antibody or antigen.
Buffone et al., Clin. Chem., 21. 1731 (1975) and Buffone et al., Clin. Chem., 21, 1735 (1975) disclose that consideration of later time intervals with the use of both PBS and PEG-PBS demonstrate no unique characteristics on which differentiation of either antigen or antibody excess samples could be used and that the kinetic procedure cannot directly detect antigen excess. Therefore, although the fundamental properties of antigen-antibody reactions are disclosed, these references fail to disclose kinetic methods for determining antigen or antibody excess.
Tiffany et al., Clin. Chem., 20, 1055 (1974) reports a study of kinetic and equilibrium measurement of antigen-antibody reactions and the achievement of better precision with equilibrium measurements. Tiffany et al. disclose a method for determining antigen excess for equilibrium measurements by measuring a change in equilibrium light scatter intensity caused by the post-addition of a small quantity of antibody into the reaction cell after the primary antigen-antibody reaction has reached equilibrium. If the primary antigen-antibody reaction proceeded in an antigen excess condition, and additional antibody is injected into the reaction cell containing the equilibrated reaction components, the excess antigen reacts with the injected antibody and produces a significant change in scatter intensity. On the other hand, if the primary antigen-antibody reaction proceeded in antibody excess, subsequent injection of the additional antibody produces an insignificant response.
Although determination of antigen or antibody excess by post addition of reactant into the primary reaction is a reliable technique, it is time consuming to perform. Consequently, a time delay is introduced while waiting for the primary reaction to reach equilibrium before the post addition step.
U.S. Pat. No. 4,157,871 to Anderson et al. discloses several kinetic methods for determining antigen excess. In one such method, the peak rate value and the elapsed time from the start of a reaction to occurrence of the peak rate are graphed as functions of increasing antigen concentration for a fixed antibody concentration. A coordinate transformation is used to derive a single valued function, derived from the peak rate and the time thereto, for distinguishing antigen excess.
In a second method disclosed by U.S. Pat. No. 4,157,871 the rate signal, which is the first derivative of the nephelometric signal, is differentiated to generate the second derivative of the nephelometric signal. The elapsed time from the start of the reaction to the occurrence of the peak of the rate signal is determined together with the time difference between the peak value of the rate signal and the peak value of the second derivative signal. A ratio that distinguishes between antigen excess and antibody excess is established by dividing the elapsed time to the peak rate by the time difference between the peak values of the first and second derivative signals.
U.S. Pat. No. 4,204,837 to Sternberg et al. discloses a method of nephelometric analysis of antigen-antibody reactions to determine whether the reaction is in an antigen excess or antibody excess condition. A first reaction between antigen and antibody reaction components is initiated, and the rate of change of a nephelometric signal is derived from the reaction to develop a rate signal. The peak value of the rate signal provides a measure of the antigen concentration. Sternberg et al. disclose that the rate signal provides kinetic information for may samples from which the antigen or antibody excess condition of the first reaction can be determined without requiring a further step of post-addition of antigen or antibody to the reaction.
Sternberg et al. disclose normal measuring range of peak values between upper and lower thresholds that defines an ambiguous zone for peak values for which a reaction may be in either antigen or antibody excess. Samples having peak heights greater than the threshold can immediately be eliminated for being greater than the normal measuring range, i.e. rejected as being clearly in antigen excess, or as being in near equivalence whether on the antibody or antigen side of the kinetic equivalence point. Sternberg et al. disclose that samples having a peak height lower than the lower threshold are regarded as being clearly on the antibody excess portion of the response curve since it is unlikely that antigen excess samples in a physiological feasible range will exhibit peak heights lower than the lower threshold. The method of Sternberg et al. does not require a post addition step for samples exhibiting peak values below the lower threshold for determining the antigen or antibody excess condition. Similarly, samples exhibiting peak heights above the threshold do not require post-addition. Such samples are rejected, and the reaction is repeated at a higher dilution, or lower concentration, of antigen. The step of post addition for determining the antigen or antibody excess condition is required only for samples having peak heights in the ambiguous zone.
U.S. Pat. No. 4,322,216 to Lillig et al. discloses a method and apparatus for conveying liquids to and from a reaction cell in an automated sample handling instrument. Lillig et al. disclose a track and one or more cars mounted thereon. One car carries a sample to a diluting well; a second car transfers the diluted sample to a reaction cell; and a third car transfers a reagent to the reaction cell. Sensors on the track detect when the cars are properly positioned relative to a plurality of slots in the track.

Automatic immunochemistry analyzing apparatus and method


A fluoropropene composition comprising Z-1,3,3,3-tetrafluoropropene, E-1,3,3,3-tetrafluoropropene, 1,1,3,3,3-pentafluoropropene, 2,3,3,3-tetrafluoropropene, and optionally 1,1,1,3,3-pentafluoropropane wherein the 2,3,3,3-tetrafluoropropene being present in an amount of 0.00001 to 1.0%. A method of producing the fluoropropene, methods for using the fluoropropene and the composition formed are also disclosed.

The fluorocarbon industry has been working for the past few decades to find replacement refrigerants for the ozone depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) being phased out as a result of the Montreal Protocol. The solution for many applications has been the commercialization of hydrofluorocarbon (HFC) compounds for use as refrigerants, solvents, fire extinguishing agents, blowing agents and propellants. These new compounds, such as HFC refrigerants, HFC-134a and HFC-125 being the most widely used at this time, have zero ozone depletion potential and thus are not affected by the current regulatory phase-out as a result of the Montreal Protocol.
In addition to ozone depleting concerns, global warming is another environmental concern in many of these applications. Thus, there is a need for compositions that meet both low ozone depletion standards as well as having low global warming potentials. Certain hydrofluoroolefin compositions are believed to meet both goals. Thus, there is also a need for economical manufacturing processes that provide these compositions.
HFO-1234ze (CF3CH═CHF) and HFO-1234yf (CF3CF═CH2), both having zero ozone depletion and low global warming potential, have been identified as potential refrigerants. U.S. Pat. No. 7,862,742 discloses compositions comprising HFO-1234ze and HFO-1234yf. U.S. Pat. No. 9,302,962 discloses methods for making HFO-1234ze. The disclosures of U.S. Pat. Nos. 7,862,742 and 9,302,962 are hereby incorporated by reference in their entirety.
Catalytic dehydrofluorination of HFC-245fa in general produces a mixture of both the E-isomer as well as the Z-isomer of HFC-1234ze. Depending on the particular catalyst chosen, the amount of the Z-isomer can vary between 15% to 23%. Dehydrofluorination in the liquid phase using aqueous solutions of caustic or other strong bases also produces mixture of both isomers. Although the ratio of the two isomers can be shifted somewhat by temperature, about 13% to about 15% of the Z-isomer is typically formed. As the E-isomer is the most useful for refrigeration applications, after separation of the E-isomer from the Z-isomer, the Z-isomer is typically either isomerized to the E-isomer in a separate step or converted back to 245fa through addition of hydrogen fluoride. Both alternatives require additional steps which add cost.
There is a need in this art for a process that can produce compositions of HFO-1234ze and HFO-1234yf that minimizes or eliminates the need for purification or separation steps for removing excess quantities of HFO-1234yf. In particular, there is a need in this art for an economical process that produces compositions comprising HFO-1234ze, HFO-1225zc and HFO-1234yf wherein the amount of HFO-1225zc and HFO-1234yf are each greater than zero and less than about 1 mole percent and wherein the total amount of HFO-1225zc and HFO-1234yf is less than about 1 mole percent.

HFO-1234ze, HFO-1225zc and HFO-1234yf compositions and processes for producing and using the compositions


A fuse device for a cable in vehicles, includes a current strength sensor having an evaluation circuit connected downstream, and a severing device for the cable. The severing device disconnecting the cable when a current strength exceeds a limiting value. The sensor, evaluation circuit, and severing device are located in a housing in which a section of the cable also runs.

The invention relates to a fuse device and, more particularly, to a fuse device for a cable in motor vehicles with a current strength sensor, an evaluation circuit connected downstream of the current strength sensor, and a severing device for severing the cable at a current strength that lies above a limiting value.
A known fuse device is described in German Patent document DE 41 10 240 C. The sensor, evaluation circuit, and severing device are spatially separate from one another. The sensor is located above an exposed portion of the cable separate from the severing device. Separate lines run between the sensor and the evaluation circuit on the one hand, and between the evaluation circuit and the severing device on the other hand. The design of the known fuse device is therefore expensive and especially prone to problems that can disadvantageously occur in the especially critical case of an accident. The connecting leads between the sensor and the severing device and the evaluation circuit are exposed to the risk of damage or destruction. This can lead to an ineffectiveness of the known fuse device at precisely the time of a critical situation such as an accident as mentioned above.
There is therefore needed a fuse device of the abovementioned type such that it is characterized by a simple design and high effectiveness.
These needs are met according to the present invention by fuse device for a cable in motor vehicles with a current strength sensor, an evaluation circuit connected downstream of the current strength sensor, and a severing device for severing the cable at a current strength that lies above a limiting value. The sensor, evaluation circuit, and severing device are located in a housing in which a section of the cable also runs.
Advantageously, the compact design of the fuse device according to the invention means, first of all, that there is no danger of its destruction, especially in an accident. At the same time, the design results in a definite reduction, if not complete elimination, of functional problems, specifically during an accident. The fuse device can be located at any point, for example directly behind or integrated with the positive terminal of a vehicle battery, or directly behind or integrated with a battery support. The compact design of the fuse device also influences the cost. In contrast to known fuse devices, there are definite cost advantages which make it possible to use the fuse device in a multiple manner in a cable to monitor for example a plurality of line sections that are especially at risk.
Advantageous embodiments of the invention are characterized by: 1) further reduction of the wire cost; 2) the possibility of replacing the fuse device after the severing device has operated, without performing extensive repairs on the cable for that purpose; 3) the possibility of performing this repair in an especially prompt and inexpensive manner; 4) further reduction in the size of the total structure and, hence, in the manufacturing costs; 5) achieving a further cost reduction by multiple use of the current sensor; 6) an additional possibility of replacing the fuse device without great expense; 7) when the current load is high as a result of operation, the possibility of preventing activation of the severing device (typically when starting an internal combustion engine); and 8) the possibility of adjusting the triggering threshold for the severing device to the changing current loads on the cable.
The possibility of adjusting the triggering threshold for the severing device to the changing current loads on the cable offers a wide variety of possibilities. Thus, it is not only possible to take into account load fluctuations occurring in rapid sequence and to quickly modify the triggering threshold for the severing device, but also to take into account loads related to operations that vary from one vehicle to another, and which are caused, for example, by the use of different electrical consumption devices. It is also possible to take into account a change in the current load that occurs during long-term operation as the result of slowly changing electrical properties of various electrical consumers. Such a phenomenon is comparable with long-term drift and can be recognized, for example, by differentiation of the current changes, for example in addition to or directly during defined loads on the cable.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Fuse device for a cable in motor vehicles

Bayerische Motoren Werke Aktiengellschaft


A method and apparatus are disclosed for generating a quadrature signal that may be used to modulate and/or demodulate communication signals transmitted between communication devices. A quadrature signal generator may include a control block, a mixer, and a filter. The control block may generate a reference signal and a filter control signal based on an input clock signal. The mixer may generate a mixer output signal based on the input clock signal and the reference signal. The filter, controlled by the filter control signal, may filter the mixer output signal to suppress a band of frequencies within the mixer output signal.

Communication devices may transmit and receive communication data through a communication medium. In one example, the communication medium may be a wireless communication medium where the communication data (e.g., radio frequency signal) is transmitted and received by communication devices according to a wireless communication protocol. Example wireless communication protocols may include IEEE 802.11 protocols and Bluetooth protocols according to the Bluetooth Special Interest Group. In another example, the communication medium may be a wired communication medium where the communication data is transmitted and received according to a wire-based communication protocol. Some example wire-based protocols may include an Ethernet® protocol and/or a Powerline Communications protocol described by the HomePlug 2.0 specification. In yet another example, the communication medium may be a hybrid combination of both wired and wireless communication mediums.
Some communication protocols may use quadrature signals to transmit and/or receive the communication data through the communication medium. For example, a communication protocol may use an in-phase (I) clock signal and a quadrature (Q) clock signal (sometimes referred to as a local oscillator signal) to encode and/or decode the communication data. In some communication devices, the generated I and Q clock signals may include one or more unwanted signals that may interfere with the performance of the communication device. For example, unwanted harmonics of the I and Q clock signals may undesirably couple into a sensitive receive and/or transmit circuit and interfere with the transmission and/or reception of the communication data.
Thus, there is a need to improve the generation of signals (such as I and Q clock signals) and suppress and/or reduce unwanted signals associated therewith to improve the performance of the communication device.


In a sewing machine, a needle and a work fabric are relatively moved in X and Y directions according to driving data indicative of a needle location. An external ROM, which functions as an external memory, preliminarily stores compressed stitch data or compressed display data, and also preliminarily stores a program for converting the compressed stitch data into the driving data indicative of the needle location or a program for converting the compressed display data into dot pattern data. The manner of compression of the stitch data and the display data is not limited, thereby improving the flexibility of the external memory.

1. Field of the Invention
The present invention relates to an external memory for an electronically controlled sewing machine and, more particularly, to such an external memory for converting compressed stitch data for stitch patterns into driving data for a driving motor provided in the sewing machine and outputting the driving data to the sewing machine or for converting compressed display data to be used for pattern display into dot data to be displayed on a display and outputting the dot data to the sewing machine.
2. Description of Related Art
In a conventional electronically controlled sewing machine, stitch data for a plurality of stitch patterns, such as character patterns and figure patterns corresponding to code numbers of the stitch patterns, are preliminarily stored in a nonvolatile memory such as a ROM provided in a control device, and a desired stitch pattern selected by operating a pattern select key, such as a ten-key, is sewn on a work fabric.
In connection with a recent electronically controlled sewing machine having been practically applied, a ROM card (pattern card), for example, is prepared to store stitch data for many stitch patterns in every kind of pattern, so as to sew many stitch patterns of various kinds. The ROM card storing a desired stitch pattern is adapted to be mounted to a body of the sewing machine. The desired stitch pattern in the ROM card is selected to read stitch data for this stitch pattern, and the stitch pattern is sewn on a work fabric. In this case, the ROM card preliminarily stores stitch data only, and a control program for reading the stitch data is stored in a ROM provided in a control device of the sewing machine.
There has been proposed in U.S. Pat. No. 4,388,883 that a stitch pattern is divided into many blocks and stitch data of the stitch pattern is stored in a compressed condition from position data of apexes of the blocks and the number of stitches in the blocks. Accordingly, it is considered that the stitch data in the ROM card may be stored in a compressed condition by various compression techniques, so as to store many stitch patterns.
In the case where the stitch data of stitch patterns are stored in a compressed condition in the ROM card, and where the control program for reading the stitch data is stored in the ROM of the control device in the sewing machine, it is necessary to identify a data structure of the stitch data of stitch patterns stored in the ROM of the control device in the sewing machine with a data structure of the stitch data of stitch patterns stored in the ROM card. Therefore, compression of the stitch data of stitch patterns stored in the ROM card or change of the compressed condition in the ROM card is limited by the data structure of the stitch data stored in the ROM of the control device, that is, by the data read control program stored in the ROM of the control device. Furthermore, when the data structure of the stitch data stored in the ROM of the control device in the sewing machine is changed, it is necessary to change the data structure of the stitch data stored in the ROM card.

External memory for electronically controlled sewing machine


This invention includes methods of depositing a silicon dioxide comprising layer in the fabrication of integrated circuitry, and to methods of forming trench isolation in the fabrication of integrated circuitry. In one implementation, a method of depositing a silicon dioxide comprising layer in the fabrication of integrated circuitry includes flowing an aluminum containing organic precursor to a chamber containing a semiconductor substrate effective to deposit an aluminum comprising layer over the substrate. An alkoxysilanol is flowed to the substrate comprising the aluminum comprising layer within the chamber effective to deposit a silicon dioxide comprising layer over the substrate. At least one halogen is provided within the chamber during at least one of the aluminum containing organic precursor flowing and the alkoxysilanol flowing under conditions effective to reduce rate of the deposit of the silicon dioxide comprising layer over the substrate than would otherwise occur under identical conditions but for providing the halogen. Other implementations are contemplated.

One commonly used material in the fabrication of integrated circuitry is silicon dioxide. Such might be utilized as essentially 100% pure, or in combination with other materials, including property-modifying dopants. Accordingly, silicon dioxide might be utilized as a mixture with other materials in forming a layer or layers, and may or may not constitute a majority of a given layer.
In certain instances of integrated circuitry fabrication, a substrate in process might have outwardly exposed surfaces of different compositions. Further in some instances, it is desirable to selectively deposit a material over one substrate area, as opposed to another substrate area. In some instances, it might be desirable to in a blanketing manner deposit a silicon dioxide comprising (or other) layer of substantially uniform thickness over a substrate. In other instances, it might be desirable to in a blanketing manner deposit such a layer to be thicker over one area than over another area.

Method of depositing a silicon dioxide-comprising layer in the fabrication of integrated circuitry


A frequency band configuration apparatus and method of a half-duplex system and a communication system. The method includes: determining a half-duplex frequency band, and receiving configuration information of the half-duplex frequency band; and receiving indication information for reconfiguring the half-duplex frequency band transmitted by a network device; the indication information indicates that the half-duplex frequency band is used for both uplink transmission and downlink transmission. Hence, it is supported that the half-duplex frequency band can be configured as both an uplink frequency band and a downlink frequency band at the same time, a cell capacity is not limited too much, and cases where uplink and downlink capacities are relatively large can be well supported.

In an existing half-duplex system, a frequency band is configured as either a time division duplex (TDD) band or a frequency division duplex (FDD) band. Specifically, the TDD band is allocated for DL and UL transmission in different time slots by using a carrier frequency (such as f1), while the FDD band includes two different carrier frequencies (such as f1 and f2), which are allocated for DL and UL transmission, respectively. In this sense, user equipments (UEs) in the same cell can be served in either DL or UL transmission over the same carrier at the same time.
It should be noted that the above description of the background is merely provided for clear and complete explanation of this disclosure and for easy understanding by those skilled in the art. And it should not be understood that the above technical solution is known to those skilled in the art as it is described in the background of this disclosure.

Frequency band configuration apparatus, method and communication system


A network element (NE) for a communications network, particularly for a synchronous digital communications system, is disclosed. It comprises a controller (CT) which contains a processor (CPU) for executing an access request (REQ), a memory (MEM) in which managed objects (MO) are stored, and an access unit (ACC) for receiving the access request (REQ). The controller controls the network element by means of the managed objects (MO). The managed objects are images of the static and dynamic properties of resources of the network element (NE). The memory (MEM) stores a service profile (PRO) which contains information about access rights to the managed objects (MO). Before executing the access request (REQ), the processor (CPU) checks whether access rights to managed objects (MO) needed to execute the access request (REQ) are present. This permits more flexible and less error-prone management of the access rights to managed objects, particularly during communication between managed objects.

This invention relates to a network element as set forth in the preamble of claim 1, to a method of controlling a network element as set forth in claim 7, and to a controller for a network element as set forth in the preamble of claim 9.
Network elements are pieces of equipment in a communications network which serve, for example, to establish connections within the network, provide access to the network, switch connections in the network, or change the format of messages which are transmitted in the network. In a synchronous digital communications network based on the synchronous digital hierarchy (SDH) or in Synchronous Optical Networks (SONETs), the network elements include crossconnects, add/drop multiplexers, and line multiplexers.
Such network elements contain a controller for controlling and monitoring network-element-specific functions. In an article by S. Colombo et al, xe2x80x9cTechnologie der SDH-Netzelemente: die Software-Platformxe2x80x9d, Elektrisches Nachrichtenwesen, 4th Quarter 1993, pp. 322-328, it is described that network elements operate and are controlled in accordance with an object-oriented specification which was defined by international standards committees such as CCITT (now ITU-T), ETSI, or ANSI. Functions of the network elements are described and implemented in the form of managed objects (MO).
Managed objects are real life imagesxe2x80x94and thus descriptions of static and dynamic propertiesxe2x80x94of physical or virtual components (resources) of the network element. In CCITT Recommendation X.720 (01/92), a managed object is defined as an abstraction of data processing and data processing resources (e.g., protocol state machines, connections, and modems) for the purposes of management.
According to the above article by S. Colombo et al, the controller of a network element comprises:
processor hardware consisting of CPU, memory, and permanent (xe2x80x9cpersistentxe2x80x9d) storage;
a processor platform with OSI stack, operating system, data management, interprocess communication, and defense functions;
a so-called framework, which has a common application program interface (API) for managed object implementation; and
a number of network element functions which are implemented by managed objects.
The xe2x80x9cframeworkxe2x80x9d incorporates an attribute library, which provides services for accessing the managed objects, such as SET, GET, REPLACE, CREATE or DELETE. It further provides an interobject communication service, which controls communication between different managed objects.
A disadvantage of this approach is that access rights, which determine which access services are permitted for the individual managed objects, have to be taken into account in the programming of the network element functions in each individual case and encoded into the source code of the object classes (applications). This is complicated and prone to error.
It is an object of the invention to provide a network element, a controller for a network element, and a method of controlling a network element which permit more flexible and less error-prone management of the access rights of managed objects.
This object is attained with respect to the network element by the features of claim 1, with respect to the method by the features of claim 7, and with respect to the controller by the features of claim 9. Further advantageous aspects of the invention are defined in the dependent claims.
The invention simplifies the management of access rights during communication between managed objects.
A particular advantage of the invention is that the functionality of a network element can be extended or restricted without making any changes to hardware and software, simply by loading new service profiles. This makes it possible to provide a network element version with standard functions and a version with extended functions using identical hardware and software.
A further advantage of the invention is that by means of service profiles it is possible to hide entire managed-object classes from one or more user groups and to make this class accessible by, and thus xe2x80x9cvisiblexe2x80x9d to, only one particular user group, for example.

Method of controlling a network element using a service profile and apparatus of the same


A semiconductor memory apparatus includes a data bus inversion (DBI) section configured to receive a plurality of input data and decide whether to invert or output, without an inversion, the plurality of input data depending upon logic levels of the plurality of data, and further configured to generate a plurality of inversion data based on the decision; and a data output section configured to receive the plurality of inversion data, invert or output, without an inversion the plurality of inversion data in response to a mode signal, and generate a plurality of output data.

1. Technical Field
The present invention relates to a semiconductor memory apparatus, and, more particularly, to a semiconductor memory apparatus which adopts a data bus inversion scheme and a method for reading data stored in a semiconductor memory apparatus.
2. Related Art
As the data processing speeds of a central processing unit (CPU) and a graphic processing unit (GPU) gradually increase, semiconductor memory apparatuses operating at high frequencies are necessarily demanded in the art. However, in the case of semiconductor memory apparatuses operating at a high frequency band, the performance of the semiconductor memory apparatuses may be degraded due to the noise of data. In order to cope with this problem, a method has been proposed, in which data driver strength is increased or a semiconductor memory apparatus is designed in consideration of a clock margin. Nevertheless, the problems caused due to the fact that noise is generated and misoperation occurs due to the increase in the number of data switching times at a high frequency band, have not been solved yet.
Under this situation, a data bus inversion (DBI) scheme capable of minimizing the number of data switching times has been adopted. In the DBI scheme, a decision is made for how many data among data having a preset number of bits, for example, 8-bit data, cause current flow through a transistor constituting a data output buffer. As a result of the decision, if the data having logic values for causing current flow constitutes a majority, the logic values of the data are inverted so that current consumption can be reduced. For instance, when the data output buffer comprises a PMOS transistor, if the number of data having a low logic level among 8-bit data is less is than 5, the data are applied to the data output buffer without being inverted in the logic levels thereof. If the number of data having a low logic level is 5 or greater, the data are applied to the data output buffer by being inverted in the logic levels thereof.
FIG. 1 is a block diagram illustrating the schematic configuration of a conventional semiconductor memory apparatus. The conventional semiconductor memory apparatus 10 includes a DBI decision section 11 and a data output section 12. The DBI decision section 11 is enabled by receiving an enabled mode signal 'mode' from a mode register set. The DBI decision section 11 receives data 'GIO<0:7>' transmitted from a data input and output line, and generates a decision signal 'flag' for deciding whether to invert the data, depending upon the logic levels of the data 'GIO<0:7>'. The data output section 12 has a plurality of data output drivers DQ1 through DQ8. The data output section 12 receives the data 'GIO<0:7>' transmitted from the data input and output line and the decision signal 'flag' and decides whether to output the data by inverting the data or without inverting the data. If the mode signal 'mode' is enabled, the decision signal 'flag' is transmitted to a chipset which is connected with the semiconductor memory apparatus 10. Therefore, even though inverted data is outputted, the chipset can sense that the data having the logic levels opposite to those of the inverted output data are correct output data.
However, in the conventional semiconductor memory apparatus 10, because the decision as to whether to invert data is not made until operations of the data output section 12 occur, and then the data is inverted depending upon the result of the decision, a problem occurs in that current consumption may increase due to toggling of data input and output lines for transmitting the data. Also, in the conventional art, there is a problem that, due to the difficulties in interfacing among the semiconductor memory apparatus and the chipset, only when the mode signal 'mode' inputted from the mode register set indicates a DBI mode, the data inversion may be performed. When the mode signal 'mode' indicates a normal mode, the data inversion may not be performed.

Semiconductor memory apparatus and a method for reading data stored therein


A transceiver, comprising an interface for receiving at least one message, a display unit provided to assume at least one switched-on operating state and at least one switched-off operating state, a message indicator indicating a receipt of a message by a unit of a signal, independent of the operating state of the display unit, wherein the message is associated with at least one message parameter, and a unit for evaluating the message parameter with the signal provided as a function of evaluation of the message parameter.

Mobile radio systems, for example mobile radio systems that function according to the GSM standard (group spéciale mobile), are designed to allow subscribers to the mobile radio network to send and receive short messages. One example of such a short message service is the so-called SMS service (short message service). In typical mobile telephones, the recipient of a short message of this kind is notified of its arrival by a corresponding indication on the display of the telephone.


A motor-pump unit is provided that has at least two internal gearwheel pumps axially aligned that are driven off of the rotor of the electric motor. The rotor of the electric motor is U-shaped and is concentrically disposed about the pump. The web of the U-shape is disposed in the region of the rotational axis with internal toothing that meshes with pinions of the at least two internal gearwheel pumps.

1. Field of the Invention
The present invention relates to a motor-pump unit having an electric motor and a pump. The motor and the pump are interlocked with each other.
2. Description of the Related Art
A motor-pump unit having a pump surrounded concentrically by a rotor/stator is shown in WO 01/73295.
DE 195 38 278 A1 describes a motor-pump unit. The rotor of the electric motor is simultaneously the impeller of the pump.
EP 0 611 887 A1 describes another motor-pump unit. Although the rotor of the motor is a separate component, it is connected in a torsionally rigid fashion with the cylinder block of a reciprocating pump.
These types of units reduce space. However, these units still have room for improvement.


A glove with enhanced gripping capabilities that makes maintaining a grip for a user, less taxing and less fatiguing for the user's hand and forearm muscles. More particularly, a grip-enhancing glove, and method for maintaining a grip, which enables a user to maintain a prolonged grip without incurring undesirable effects.

1. Field of Invention
The present invention relates to a glove with enhanced gripping capabilities that makes maintaining a grip for a user, less taxing and less fatiguing for the user's hand and forearm muscles. More particularly, the present invention entails a grip-enhancing glove and a method for maintaining a grip that enables a user to maintain a prolonged grip without incurring undesirable effects, as described herein.
2. Background and Related Art
Many sports and other activities require a participant to maintain a prolonged grip around a generally cylindrical object, such as a handle bar. Unfortunately, maintaining such a grip often fatigues the sports participant or user's hand and forearm muscles. In fact, to create a strong grip requires great strength from multiple muscles. Specifically, to form a grip, the flexor muscles of the forearm pull the flexor tendons in the hand. The large amount of tension generated in these muscles and forearm causes hypertrophy, which occurs when the muscles grow in size and fictional capacity to meet the demands placed on it. Thus, prolonged grips and the inability to maintain them becomes a limiting factor for users participating in activities requiring prolonged grips.
Moreover, certain activities cause premature hand and muscle fatigue and consequent grip failure. Grip failure occurs where there is constant direct pressure countering the grip, which eventually forces the grip to open. For example, if a user is strength training and using either a hanging bar or lifting a dumbbell, pressure is continually exerted on the palm of the hand. Eventually, if the force is big enough, it causes the hand to open and the grip to release. Another example involves a user who grips a motorcycle handlebar. While riding, a motorcycle rider, must exert great forces in order to grip and maintain the grip. Specifically, the rider exerts force to hold the bar, must endure the vibration of the bar, and maintain a steady grip for long distance rides. The rider must also vary the pressure to which he or she grips the handlebar, further fostering muscle fatigue.
Many users wear gloves to alleviate the wear and tear on their hands that results from users making prolonged grips. Gloves with non-slip surfaces also provide enhanced gripping capabilities and greater grip strength. However, the problem remains unresolved, and there exists a need, for a glove or method for maintaining a prolonged grip, which enables a user to maintain a grip for an extended period of time, without incurring the undesirable effects of hand wear and tear and hand and forearm muscle fatigue. Moreover, there exists the need for a glove that postpones hand, forearm and muscle fatigue and allows a user to maintain a grip for greater lengths of time and under greater pressures than are possible with available gloves.

Grip enhancing glove and method for maintaining a grip that enables a user to maintain a prolonged grip without incurring undesirable effects


An ultrasonic Doppler blood flow measuring apparatus comprises a plurality of frame memories for storing information pieces about a blood flow speed in a unit of frame, circuits for comparing blood flow speed information pieces at corresponding addresses on the plurality of frame, memories and determining a speed difference, a circuit for comparing the speed difference with a predetermined threshold value and determining a blood flow at the corresponding address as an arterial flow when the speed difference exceeds the threshold value but as a venous flow when the speed difference is below the threshold value, and a circuit for displaying the determined arterial and venous flows in different colors.

The present invention relates to an ultrasonic Doppler blood flow measuring apparatus in which an ultrasonic wave is transmitted to and received from a subject to provide a reflected echo signal and a signal caused to undergo a Doppler shift by a blood flow is derived from the reflected echo signal to display blood flow information two-dimensionally and more particularly to an ultrasonic blood flow measuring apparatus capable of determining which of arterial and venous flows a blood flow in a region of interest belongs to and displaying arterial and venous flows in coloring fashion.
A conventional ultrasonic Doppler blood flow measuring apparatus of this type comprises, as shown in FIG. 5, a probe 1 for transmitting and receiving an ultrasonic wave to and from a subject, an ultrasonic wave transmitting/receiving circuit 2 for controlling the probe 1 so as to cause it to transmit and receive the ultrasonic wave and amplifying a received reflected wave signal, a Doppler demodulating circuit 3 for deriving a frequency signal, caused to undergo a Doppler shift by a blood flow in the subject, from the reflected echo signal produced from the ultrasonic wave transmitting/receiving circuit 2, a blood flow speed calculation circuit 4 for calculating a blood flow speed in the subject by using the frequency signal from the Doppler demodulating circuit 3, a blood flow speed frame memory unit 5 for storing blood flow speed information from the blood flow speed calculation circuit 4, a color signal conversion and display circuit 6 for receiving data from the blood flow speed frame memory unit 5 and converting it into a color signal complying with a blood flow state, and an image display 7 for receiving the color signal from the color signal conversion and display circuit 6 to perform a coloring display. An ultrasonic wave is transmitted from the probe 1 to a vessel of the region of interest in the subject, and a Doppler shift frequency of an ultrasonic wave reflected from red blood corpuscles in the vessel and received is measured to obtain blood flow information which in turn is displayed two-dimensionally on the image display 7.
In the conventional ultrasonic Doppler blood flow measuring apparatus as above, data from the blood flow speed frame memory unit 5 is inputted to the color signal conversion and display circuit 6 and converted into a color signal complying with a blood flow speed to ensure that for example, a blood flow approaching the probe 1 can be coloring-displayed in a color of red system and a blood flow departing from the probe 1 ca be coloring-displayed in a color of blue system but any display as to which of arterial and venous flows the displayed blood flow belongs to cannot be obtained. In other words, the difference of directions of the blood flow can be determined and displayed in coloring fashion but it is impossible to determine which of arterial and venous flows the blood flow belongs to and to display a determined arterial or venous flow discriminatively in coloring fashion.
Under the circumstances, in the event that a blood flow is interrupted for some abnormal causes in a region of interest where a great number of vessels run complicatedly, for example, in the liver or kidney, a doctor or the like sometimes is not permitted to execute correct diagnosis if he does not know which of arterial and venous flows the blood flow in question belongs to. In such an event, the doctor or the like is forced to execute diagnosis while considering which of arterial and venous flows the blood flow portion where abnormality is occurring belongs to on the basis of knowledge of anatomy. Accordingly, it takes a long time to execute diagnosis and efficiency is degraded. In addition, the doctor or the like sometimes arises the individual difference in diagnostic judgment and correct diagnosis cannot be done.

Ultrasonic doppler blood flow measuring apparatus