Disclosed is an anastomosis catheter, for achieving a tissue to tissue or synthetic graft to tissue attachment. The catheter includes a plurality of deployable tissue anchors, which may be laterally deployed into surrounding tissue. The anchors may be used to achieve end to end or end to side anastomoses. Methods are also disclosed.

The present invention relates to methods and devices for performing anastomosis. More particularly, the present invention relates to methods and devices for performing tissue-to-tissue or synthetic graft-to-tissue vascular anastomosis under either direct or transluminal access.
Anastomosis is the union or joinder of one hollow vessel or structure to another so that the interior of the vessels communicate with one another. There are generally two types of vascular anastomosis: end-to-end and end-to-side. In an end-to-end anastomosis, the severed end of a first vessel or an end of a synthetic graft is coupled, usually by suturing or stapling, to the severed end of a second vessel. In the context of a synthetic vascular graft, the ends and possibly intermediate portions of the graft may be secured to the wall of the vessel without removing a portion of the native vessel. In an end-to-side anastomosis, the severed end of a first vessel or an end of a synthetic graft is connected around an opening cut into the side of a second vessel.
Anastomoses are performed in a variety of anatomies, such as between airways, blood vessels, bowels, and urogenital lumens. The procedure for connecting blood vessels is referred to as vascular anastomosis. One of the best known surgical procedures utilizing vascular anastomosis is the coronary bypass. In the context of coronary artery disease, the flow of oxygenated blood to the myocardium of the heart is inhibited by a stenosis or obstruction in the coronary artery. This flow can be improved by providing a coronary artery bypass graft (xe2x80x9cCABGxe2x80x9d) between the aorta and a point in the coronary artery distal to the stenosis. Typically, a section of vein from the leg is removed and attached at one end to the aorta and at the other end to the coronary artery utilizing end-to-side anastomosis. Such grafts are known as saphenous coronary artery bypass grafts. Alternatively, synthetic grafts can be utilized to effect the bypass.
While the typical coronary bypass procedure favorably affects the incidence and severity of angina in patients with coronary artery disease, a variety of risks are associated with such procedures. Among them are mortality, myocardial infarction, postoperative bleeding, cerebrovascular accident, arrhythmias, wound or other infection, aortic dissection and limb ischemia. Furthermore, the vein grafts deteriorate over time, thereby resulting in the recurrence of angina, myocardial infarction and death. In addition, the costs of such procedures are relatively high and the patient recovery relatively long.
In an attempt to overcome such problems, a number of alternative approaches have been developed. For example, artery to artery bypass procedures have been utilized in which an arterial source of oxygenated blood-such as the left internal mammary artery (xe2x80x9cLIMAxe2x80x9d), right internal mammary artery (xe2x80x9cRIMAxe2x80x9d), or right internal thoracic artery (xe2x80x9cRITAxe2x80x9d)xe2x80x94is severed and anastomosed to the obstructed coronary artery distally to the stenosis or occlusion. More recently, other arteries have been used in such procedures, including the inferior epigastria arteries and gastroepiploic arteries. In general, artery to artery bypass procedures have demonstrated a better patency rate as compared with autologous vein or synthetic grafts.
While vascular anastomosis can be effective, and sometimes life-saving procedures, traditionally available techniques have been associated with a number of complications. For example, conventional techniques for performing vascular anastomosis generally require an extensive incision in the patient""s body. Such operations are traumatic to the patient, involve a lengthy recovery, and a relatively high risk of infection or other complications.
In the context of coronary bypass surgery, for example, the bypass graft or artery-to-artery procedure is traditionally performed using an open chest procedure. In particular, each procedure involves the necessity of a formal 20 to 25 cm incision in the chest of the patient, severing the sternum and cutting and peeling back various layers of tissue in order to give access to the heart and arterial sources. As a result, these operations typically require large numbers of sutures or staples to close the incision and 5 to 10 wire hooks to keep the severed sternum together. Furthermore, such procedures leave an unattractive scar and are painful to the patient. Most patients are out of work for a long period after such an operation and have restricted movement for several weeks. Such surgery often carries additional complications such as instability of the sternum, post-operative bleeding and mediastinal infection. Above all, open procedures are associated with long recuperation times.
Due to the risks attendant to such procedures, there has been a need to develop procedures which minimize invasion of the patient""s body tissue and resulting trauma. In this regard, limited open chest techniques have been developed in which the coronary bypass is carried out using an abdominal (subxyphoid) approach or, alternatively, a xe2x80x9cChamberlainxe2x80x9d incision (an approximately 8 cm incision at the sternocostal junction), thereby lessening the operating area and the associated complication rate. While the risks attendant to such procedures are generally lower than their open chest counterparts, there is still a need for a minimally invasive surgical technique. Nevertheless, each of these techniques is thoracotomic, requiring an incision to be made in the chest wall through which conventional surgical instruments are introduced to perform conventional coronary bypass surgery.
In order to reduce the risk of patient mortality, infection, and other complications associated with surgical techniques, it is advantageous and desirable to utilize endoscopic and thoracoscopic surgical techniques. Such procedures usually involve the use of surgical trocars to puncture the abdomen or chest, thereby facilitating access to a body cavity through the cannula and a relatively small opening in the patient""s body. Typically, such trocars have a diameter of about 3 mm to 15 mm. Surgical instruments and other devices such as fiber optic cameras can be inserted into the body cavity through the cannula. Advantageously, the use of trocars minimizes the trauma associated with many surgical procedures.
Another application involves the implantation and/or attachment of synthetic vascular grafts. Tubular vascular grafts comprising polytetrafluoroethylene (PTFE), Dacron, or other fabric materials may be implanted in a vessel to span a diseased or damaged site. In this application, the diseased portion of the vessel is merely isolated by directing blood flow through the graft. This may be accomplished by attaching the proximal end and distal end of the graft to the vessel wall proximally and distally of the diseased site. In some circumstances, portions of the graft in between the proximal and distal ends are preferably also attached to the vessel wall, to maintain patency throughout the graft. One application of such grafts is to treat abdominal aortic aneurysms, by implanting either a straight segment graft or a Y shaped xe2x80x9cbifurcationxe2x80x9d graft at the bifurcation of the lower abdominal aorta and the left and right iliac arteries.
When vascular anastomoses are performed, the goal is to achieve a sufficiently leak-proof connection between tubular structures. Typically, such connections in a CABG procedure are established using suturing techniques. Suturing of vascular structures, however, is a tedious and time consuming process. Furthermore, current suturing techniques are not possible using transluminal access, and are not readily adapted for endoscopic use, where the surgeon""s freedom of access and movement are limited. Thus, there is a need for an alternative to current suturing techniques that would expedite the anastomosis procedure, and that can be readily adapted for transluminal or endoscopic use.
Various stapling techniques are also known for providing anastomotic connections between organs, such as in intestinal and colorectal anastomosis. Due to the size of these devices, however, they are not easily adapted for use with vascular organs in general, and particularly not for transluminal or endoscopic techniques.
Surgical clips have also been developed, which are intended to facilitate the anastomosis of vascular structures. In this technique, the vascular tissues are approximated, partially everted, and then clipped by applying the arms of the surgical clip over the everted tissue and securing the clip so as to hold the tissue together without penetrating the interior wall of the vessel. Nevertheless, in order to properly utilize these clips, the tissues should be everted. A transluminal approach is thus not readily possible using this technique.
Thus, notwithstanding the various efforts in the prior art, there remains a need for methods and devices for performing vascular anastomoses which minimize the risk of infection, trauma, and other complications associated with conventional surgery, and, in particular, which can be utilized transluminally or in conjunction with an endoscopic technique for vascular anastomosis.
There is provided in accordance with one aspect of the present invention, a method of attaching a tubular graft to a vessel wall. The method comprises the steps of positioning a tubular graft within a vessel, and positioning a tissue anchor deployment catheter at a first position within the graft, the deployment catheter comprising a first plurality of tissue anchors. The anchors are thereafter advanced into the vessel wall, to secure the graft to the vessel wall. In one embodiment, the advancing the anchors step comprises advancing the anchors through the graft and into the vessel wall. Preferably, the advancing the anchors step comprises advancing at least four anchors into the vessel wall. In one embodiment, the positioning a graft step comprises positioning a tubular PTFE graft. Preferably, the method further comprises the step of advancing a catheter to a second position within the graft, and advancing a second plurality of anchors into the vessel wall. This may be accomplished using a second plurality of anchors, carried by the catheter.
In accordance with another aspect of the present invention, there is provided a method of attaching a first tubular structure to a second tubular structure in a patient. The method comprises the steps of identifying a first tubular structure in the patient, and positioning a second tubular structure in communication with the first tubular structure. An anchor deployment catheter is positioned within at least one of the first and second tubular structures. A plurality of tissue anchors are deployed from the catheter and through at least one of the first and second tubular structures, to attach the first tubular structure to the second tubular structure. The first tubular structure may be an artery or a vein, and the second tubular structure may be a graft. The graft may be autologous vessel tissue, a homograft, a xenograft, or a prosthetic tubular graft.
In accordance with a further aspect of the present invention, there is provided an anastomosis catheter. The anastomosis catheter comprises an elongate flexible body, having a proximal end and distal end. At least one tissue anchor support is provided on the body, moveable between an axial orientation and an inclined orientation. An anchor is movably carried by the anchor support. The anchor comprises a body, having at least one proximal engagement surface for resisting distal travel of the body through the tissue and at least one distal engagement surface for resisting proximal travel of the body through tissue.
In one embodiment, the tissue anchor support comprises a tube. The tube comprises a proximal section, a distal section and a hinge in-between the proximal section and the distal section. An actuator is preferably connected to the distal section, so that proximal retraction of the actuator with respect to the catheter body advances the anchor support from the axial position to the inclined position. Preferably, the catheter further comprises an introducer removably connected to the anchor for driving the anchor into the tissue. Preferably, the catheter comprises from about four anchor supports to about eight anchor supports.
In accordance with another aspect of the present invention, there is provided a method of tacking a tubular graft to a vessel wall. The method comprises the steps of identifying a tubular graft which has been previously positioned within a vessel. A tissue anchor deployment catheter is positioned within the graft, the deployment catheter comprising at least one tissue anchor. The anchor is thereafter advanced into the vessel wall, to secure the graft to the vessel wall.
Further features and advantages of the present invention will become apparent to those of skill in the art in view of the detailed description of preferred embodiments which follows, when considered together with the attached drawings and claims.


An electroacoustic driver includes a diaphragm, a diaphragm drive system and a diaphragm suspension. The diaphragm system is configured to subject the diaphragm to a motion, wherein the diaphragm suspension is configured to guide the diaphragm. The diaphragm drive system includes an active element configured to actively influence the motion of the diaphragm.

An electroacoustic driver typically comprises a lightweight diaphragm which may have a circle- or square-shape, as well as a basket, a diaphragm drive system and a diaphragm suspension. The diaphragm suspension is configured to guide the diaphragm along its motion, wherein the diaphragm drive system is configured to subject the diaphragm to the motion or to an oscillation in order to produce a sound in response to an electric audio signal. The diaphragm is typically deflected by using a coil electromagnet acting on a permanent magnet, wherein the coil is coupled to the diaphragm and the permanent magnet is attached to the basket. The diaphragm suspension elastically mounting the diaphragm and the basket may comprise a spider arranged in the middle of the diaphragm and a surround arranged at an edge region of same. The spider and the surround are typically made by a fabric or a rubber which are passive elements. Each of the passive elements may have a spring stiffness influencing the restoring force counteracting to the excursion of the diaphragm. However, such suspensions often cause deficiencies in sound quality because the surround and/or the spider may typically provide a restoring force having a non-linear characteristic. Therefore, there is the need for an approved approach.

Fraunhofer-Gesellschaft zur Foerderung der angewandten Forschung e.V.


A road surface friction coefficient calculator is to detect a coefficient of friction on a road surface. A braking force calculator is to detect the braking force of a vehicle. A decelerating calculator is to determine whether the vehicle transitions to a decelerating travel mode. The pulley pressure controller is to control pulley pressure in a belt-driven continuously variable transmission. The pulley pressure controller is to increase the pulley pressure by an additional amount when the decelerating calculator determines the vehicle transitions to the decelerating travel mode while the coefficient of friction detected by the road surface friction coefficient calculator is equal to or lower than a reference value. The pulley pressure controller is to reduce the additional amount when the braking force calculator detects an increase in the braking force in the decelerating travel mode.

1. Field
The present disclosure relates to a pulley pressure control apparatus for a belt-driven continuously variable transmission.
2. Description of the Related Art
Pulley pressure for a drive pulley and a driven pulley of a belt-driven continuously variable transmission is controlled for the following purposes: increasing or decreasing pulley-groove widths to change the transmission gear ratio and preventing slippage of an endless belt on the pulleys. Slippage of the endless belt is caused by an increase in torque transmitted between the endless belt and the pulleys. Thus, to prevent the slippage of the endless belt, pulley pressure is increased when the torque transmitted by the endless belt is large and decreased when the torque transmitted by the endless belt is small.
When driving wheels are braked on a road surface with a low coefficient of friction (hereinafter also referred to as a low μ road surface), the endless belt slips on the pulleys, easily causing lock-up of the driving wheels. Thus, the slippage of the endless belt needs to be prevented by making the pulley pressure larger on a low μ road surface than on a high μ road surface (hereinafter also referred to as a high μ road surface). However, excessive increase in the pulley pressure unnecessarily increases load on a hydraulic pressure generator such as an oil pump, and in turn, increases the fuel consumption of an engine that drives the hydraulic pressure generator.
Regarding this problem, Japanese Unexamined Patent Application Publication No. 2013-127287 aims to achieve both prevention of slippage of the endless belt and reduction in the load on the hydraulic pressure generator, by calculating pulley pressure necessary for preventing slippage of the endless belt on a high μ road surface and pulley pressure necessary for preventing slippage of the endless belt on a low μ road surface and employing the larger one of these pulley pressures in absolute value.

Pulley pressure control apparatus for belt-driven continuously variable transmission


Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reduction of resistance to the treatment, prevention, and/or diagnosis of diseases characterized by the formation of cancers. Embodiments include methods of treating cancer, comprising the steps of: providing a patient diagnosed with cancer with a therapeutic regime that includes at least one therapeutically effective dose of at least one agent that reduces the activity of at least one DNA damage/repair pathway. Other embodiments include methods of treating cancer, comprising the steps of: treating a patient diagnosed with cancer with a combination of therapeutic agents that includes at least one therapeutically effective anti-cancer agent and at least one compound that reduces the activity of at least one DNA damage/repair pathway. Yet other embodiments include methods of reducing resistance to a genotoxic therapeutic, comprising the steps of: treating a patient at least one therapeutically effective dose of at least one agent that reduces at least one DNA damage/repair pathway.

Fatty acid synthase (FASN) is a key mammalian enzyme required for de novo synthesis of palmitate. FASN expression and activity is largely suppressed by sufficient dietary fat in most normal non-adipose tissues, but abnormally elevated in many human cancer cells elevated level of activity of this enzyme in cancer cells is associates with poor prognosis. FASN's association with poor prognosis may derive in part from FASN functioning to elevate in drug resistance during chemotherapy. Indeed, it has been found that FASN expression and/or activity was increased in drug-selected and resistant breast and pancreatic cancer cells. It was also found that FASN over-expression causes cellular resistance to DNA-damaging drugs such as doxorubicin and mitoxantrone but not to microtubule modulators such as vinblastine and paclitaxel. Decreased ceramide production following doxorubicin treatment via suppressing tumor necrosis factor (TNF)-α production was believed to be one of the mechanisms of FASN-induced resistance to doxorubicin.
The observation that FASN increases resistance to genotoxic drugs prompted an investigation to determine if FASN over-expression may up-regulate DNA damage response/repair pathways. As reported herein this hypothesis was tested with a focus on repair of DNA double strand breaks (DSBs), which are thought to be induced by anticancer drugs such as doxorubicin, mitoxantrone, and ionizing radiation. In mammalian cells, DSBs are repaired mainly via homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. NHEJ is the predominant form of DSB repair because it appeasrs to occur during all phases of cell cycle while HR only initiates at the late G1 and S phases. NHEJ repair of DSB was studied and it was found that FASN up-regulates NHEJ activity and repair of DSB by increasing PARP-1 expression via increasing the expression of specific protein 1 (SP1) and reducing the expression of NF-κB which bind to the same composite element in the PARP-1 promoter. Furthermore, lipid-deprivation suppresses SP1 expression, which could be rescued by palmitate supplementation. These findings indicated that FASN may up-regulate DNA repair mechanisms by increasing PARP-1 expression via NF-κB and SP1, which in turn contributes to cellular resistance to genotoxic anticancer treatments. Thus, lipid metabolism likely plays an important role in cancer cell survival against genotoxic insults by regulating DNA repair pathways.
The findings disclosed herein reveals a potential molecular pathway on how FASN causes drug and radiation resistance and contributes to poor clinical prognosis of cancer diseases. FASN is the sole cytosolic enzyme responsible for de novo lipid synthesis, required for cancer cell survival but not for most normal non-adipose tissues. The finding that FASN regulates DNA repair by regulating SP1 and NF-κB in cancer cell response to anticancer treatments will have profound impact on designing treatment strategies. It also helps establish FASN as a target for therapeutic discovery to sensitize drug and radiation resistance. FASN is crucial for cancer cell survival and associates with poor prognosis. FASN over-expression has been found to cause resistance to genotoxic insults. Here, it was found that FASN suppresses NF-κB but increases SP1 expression. NF-κB and SP1 bind to a composite element in the PARP-1 promoter in a mutually exclusive manner and regulate PARP-1 expression. Up-regulation of PARP-1 by FASN in turn increases Ku protein recruitment and DNA repair. Furthermore, lipid-deprivation suppresses SP1 expression, which could be rescued by palmitate supplementation. However, lipid deprivation or palmitate supplementation had no effect on NF-κB expression. Thus, FASN may regulate NF-κB and SP1 expression using different mechanisms. While not wishing to be bound by this theory, FASN may regulate cellular response against genotoxic insults by up-regulating PARP-1 and DNA repair via NF-κB and SP1.
A first embodiment includes a method of treating cancer, steatosis, and/or diabetes, comprising the steps of: providing a patient diagnosed with cancer, steatosis, and/or diabetes with a therapeutic regime that includes at least one therapeutically effective dose of at least one agent that reduces the activity of at least one DNA damage/repair pathway. Some embodiments include a composition for use in treating cancer, steatosis, and/or diabetes comprising at least one therapeutically effective dose of at least one agent that reduces the activity of at least one DNA damage/repair pathway.
A second embodiment includes the method and/or the composition of the first embodiment, wherein the at least one agent that reduces the activity of the at least one DNA damage/repair pathway comprises a fatty acid synthase (FASN) inhibitor, a poly ADP ribose polymerase (PARP) inhibitor, a specific protein 1 (SP1) inhibitor, FASN siRNA, PARP siRNA, and/or SP1 siRNA.
A third embodiment includes the method and/or the composition of any one of the first and the second embodiments, wherein the therapeutic regime further includes comprises at least one proton pump inhibitor.
A fourth embodiment includes the method and/or the composition of any one of the first to the third embodiments, wherein the at least one agent is a proton pump inhibitor (PPI) selected from the group consisting of: omeprazole, PRILOSEC®, lansoprazole, PREVACID®, dexlansoprazole, DEXILENT®, rabeprazole, ACIPHEX®, pantoprazole, PROTONIX®, esomeprazole, NEXIUM®, and ZEGARID®, anaprazole, tenatoprazole, ilaprozole, and/or metabolites thereof, and/or R- or S-enantiomers thereof, and/or a pharmaceutically acceptable salt thereof.
A fifth embodiment includes the method and/or the composition of any one of the first to the fourth embodiments, wherein the at least one agent that reduces the activity of the at least one DNA damage/repair pathway is a poly ADP ribose polymerase (PARP) inhibitor selected from the group consisting of: olaparib, niraparib, iniparib, talazoparib, veliparib, and rucaparib.
A sixth embodiment includes a method of treating cancer, steatosis, and/or diabetes, comprising the steps of: treating a patient diagnosed with cancer, steatosis, and/or diabetes with a combination of therapeutic agents that includes at least one therapeutically effective anti-cancer agent and at least one compound that reduces the activity of at least one DNA damage/repair pathway. Some embodiments include a composition for use in treating cancer, steatosis, and/or diabetes comprising at least one therapeutically effective anti-cancer agent and at least one compound that reduces the activity of at least one DNA damage/repair pathway.
A seventh embodiment includes the method and/or the composition of the sixth embodiment, in which the at least one compound that reduces the up-regulation of a DNA damage/repair pathway acts by reducing the activity of PARP-1 and/or by affecting the activity of NF-κB pathway and/or SP1 activity.
An eighth embodiment includes the method and/or the composition of any one of the sixth and the seventh embodiments, in which the at least one compound that reduces the activity of the DNA damage repair activity comprises a fatty acid synthase (FASN) inhibitor, a poly ADP ribose polymerase (PARP) inhibitor, a specific protein 1 (SP1) inhibitor, FASN siRNA, PARP siRNA, and/or SP1 siRNA.
A ninth embodiment includes the method and/or the composition of any one of the sixth to the eighth embodiments, in which the combination of therapeutic agents further includes at least one proton pump inhibitor.
A tenth embodiment includes the method and/or the composition of any one of the sixth to the ninth embodiments, wherein the at least one agent is a proton pump inhibitor selected from the group consisting of: omeprazole, PRILOSEC®, lansoprazole, PREVACID®, dexlansoprazole, DEXILENT®, rabeprazole, ACIPHEX®, pantoprazole, PROTONIX®, esomeprazole, NEXIUM®, and ZEGARID®, anaprazole, tenatoprazole, ilaprozole, and/or metabolites thereof, and/or R- or S-enantiomers thereof, and/or a pharmaceutically acceptable salt thereof.
An eleventh embodiment includes the method and/or the composition of any one of the sixth to the tenth embodiments, in which the at least one agent reduces the activity of the DNA damage/repair pathway is a poly ADP ribose polymerase inhibitor selected from the group consisting of: olaparib, niraparib, iniparib, talazoparib, veliparib, rucaparib, and/or metabolites thereof, and/or R- or S-enantiomers thereof, and/or a pharmaceutically acceptable salt thereof.
A twelfth embodiment includes the method and/or the composition of any one of the sixth to the eleventh embodiments, wherein the at least one anti-cancer treatment induces DNA double strand breaks (DSBs).
A thirteenth embodiment includes the method and/or the composition of any one of the sixth to the twelfth embodiments, wherein the at least one anti-cancer treatment comprises treatments with doxorubicin, bleomycin, vinblastine, paclitaxel, mitoxantrone, cisplatine, H2O2, UVB, ionizing radiation, and/or DNA-damaging radiotherapy.
A fourteenth embodiment includes a method of reducing resistance to a genotoxic therapeutic, comprising the steps of: treating a patient at least one therapeutically effective dose of at least one agent that reduces at least one DNA damage/repair pathway. Some embodiments include a composition for use in reducing resistance to a genotoxic therapeutic comprising at least one therapeutically effective dose of at least one agent that reduces at least one DNA damage/repair pathway.
A fifteenth embodiment includes the method and/or the composition of the fourteenth embodiment, wherein the at least one agent comprises a fatty acid synthase (FASN) inhibitor, a proton pump inhibitor (PPIs), a poly ADP ribose polymerase (PARP) inhibitor, a specific protein 1 (SP1) inhibitor, FASN siRNA, PARP siRNA, and/or SP1 siRNA.
A sixteenth embodiment includes the method and/or the composition of any one of the fourteenth and the fifteenth embodiments, further includes administering at least one proton pump inhibitor to the patient.
A seventeenth embodiment includes the method and/or the composition of any one of the fourteenth to the sixteenth embodiments, in which the at least one proton pump inhibitor is selected from the group consisting of: omeprazole, PRILOSEC®, lansoprazole, PREVACID®, dexlansoprazole, DEXILENT®, rabeprazole, ACIPHEX®, pantoprazole, PROTONIX®, esomeprazole, NEXIUM®, and ZEGARID®, anaprazole, tenatoprazole, ilaprozole, and/or metabolites thereof, and/or R- or S-enantiomers thereof, and/or a pharmaceutically acceptable salt thereof.
An eighteenth embodiment includes the method and/or the composition of any one of the fourteenth to the seventeenth embodiments, wherein the at least one agent is a poly ADP ribose polymerase (PARP) inhibitor selected from the group consisting of: olaparib, niraparib, iniparib, talazoparib, veliparib, and rucaparib.
A nineteenth embodiment includes the method and/or the composition of any one of the fourteenth to the eighteenth embodiments, wherein the genotoxic therapy induces DNA double strand breaks (DSBs).
A twentieth embodiment includes the method and/or the composition of any one of the fourteenth to the nineteenth embodiments, wherein the at least one genotoxic therapy is selected from the group consisting of: doxorubicin, bleomycin, vinblastine, paclitaxel, mitoxantrone, cisplatine, H2O2, UVB, ionizing radiation and DNA-damaging radiotherapy. Some embodiments include the method of any one of the preceding embodiments, wherein the patient is treated with chemotherapy or hormonal therapy.
A twenty first embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein the at least one therapeutically effective anti-cancer agent includes at least one agent comprising a DNA-damaging drug, a cross-linker, an anthracycline, an antimitotic, an anti-metabolite, an ER antagonist and/or agonist, a GnRH antagonist and/or agonist, an aromatase inhibitor, and/or a HER2 inhibitor. Some embodiments include the method of any one of the preceding embodiments, wherein the patient includes humans, animals, and/or tissues thereof, and/or cells thereof.
A twenty second embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein the at least one therapeutically effective anti-cancer agent includes at least one agent comprising a DNA-damaging drug, a cross-linker, an anthracycline, an antimitotic, an ER antagonist and/or agonist, an aromatase inhibitor, and/or a HER2 inhibitor.
A twenty third embodiment includes the method and/or the composition of any one of the twenty first and twenty second embodiments, wherein the at least one therapeutically effective anti-cancer agent includes at least one agent comprising carboplatin, cisplatin, cyclophosphamide, epirubicin, doxorubicin, liposomal doxorubicin, docetaxel, paclitaxel, vinorelbine, capecitabine, gemcitabine, fluorouracil, methotrexate, fulvestrant, tamoxifen, goserelin, leuprolide, anastrozole, exemestane, letrozole, trastuzumb, and/or metabolites thereof, and/or a pharmaceutically acceptable salt thereof.
A twenty fourth embodiment includes the method and/or the composition of any one of the twenty first and twenty second embodiments, wherein the at least one therapeutically effective anti-cancer agent includes at least one agent comprising carboplatin, cisplatin, cyclophosphamide, epirubicin, doxorubicin, liposomal doxorubicin, docetaxel, paclitaxel, vinorelbine, fulvestrant, tamoxifen, anastrozole, exemestane, letrozole, trastuzumb, and/or metabolites thereof, and/or a pharmaceutically acceptable salt thereof.
A twenty fifth embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein cancer includes bone cancer, brain cancer, breast cancer, endocrine cancer, gastrointestinal cancer, gynegologic cancer, head and neck cancer, hematologic cancer, lung cancer, prostate cancer, renal cell carcinoma, skin cancer, urologic cancer, and/or rare cancers. Consistent with this embodiment, wherein cancer includes breast cancer.
A twenty sixth embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein at least one therapeutically effective anti-cancer agent and at least one compound that reduces the activity of at least one DNA damage/repair pathway exhibits synergy. In these embodiments, the at least one compound that reduces the activity of at least one DNA damage/repair pathway includes, but is not limited to, a fatty acid synthase (FASN) inhibitor, a proton pump inhibitor (PPI), a poly ADP ribose polymerase (PARP) inhibitor, a specific protein 1 (SP1) inhibitor, FASN siRNA, PARP siRNA, SP1 siRNA, and/or any combination thereof. Consistent with these embodiments, the synergistic composition comprises at least one proton pump inhibitor (PPI) and at least one PARP inhibitor, and the ratio between the at least one proton pump inhibitor (PPI) and at least one PARP inhibitor is from about 100:1 to about 1:100, from about 80:1 to about 1:80, from about 70:1 to about 1:70, from about 50:1 to about 1:50, from about 30:1 to about 1:30, from about 20:1 to about 1:20, from about 15:1 to about 1:15, from about 10:1 to about 1:10, from about 5:1 to about 1:5, from about 3:1 to about 1:3, from about 3:1 to about 1:1, and/or from about 1:1 to about 1:3. Some embodiments include the synergistic composition comprising the at least one proton pump inhibitor (PPI) and at least one PARP inhibitor and the ratio between the at least one proton pump inhibitor (PPI) and at least one PARP inhibitor is about 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, and/or 2:1. Some synergistic compositions comprise a poly ADP ribose polymerase (PARP) inhibitor including, but is not limited to, olaparib, niraparib, iniparib, talazoparib, veliparib, and rucaparib; and a proton pump inhibitor including, but is not limited to, omeprazole, PRILOSEC®, lansoprazole, PREVACID®, dexlansoprazole, DEXILENT®, rabeprazole, ACIPHEX®, pantoprazole, PROTONIX®, esomeprazole, NEXIUM®, and ZEGARID®, anaprazole, tenatoprazole, ilaprozole, and/or metabolites thereof, and/or R- or S-enantiomers thereof, and/or a pharmaceutically acceptable salt thereof; or any combinations thereof.
Consistent with these embodiments, the synergistic composition comprises lansoprazole and olaparib, and the ratio between lansoprazole and olaparib is from about 100:1 to about 1:100, from about 80:1 to about 1:80, from about 70:1 to about 1:70, from about 50:1 to about 1:50, from about 30:1 to about 1:30, from about 20:1 to about 1:20, from about 15:1 to about 1:15, from about 10:1 to about 1:10, from about 5:1 to about 1:5, from about 3:1 to about 1:3, from about 3:1 to about 1:1, and/or from about 1:1 to about 1:3. Some embodiments include the synergistic composition comprising lansoprazole and olaparib, wherein the ratio between lansoprazole and olaparib is about 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, and/or 2:1.
In other embodiments, the synergistic composition comprises lansoprazole and doxorubicin (or IR), and the ratio between lansoprazole and doxorubicin (or IR) is from about 100:1 to about 1:100, from about 80:1 to about 1:80, from about 70:1 to about 1:70, from about 50:1 to about 1:50, from about 30:1 to about 1:30, from about 20:1 to about 1:20, from about 15:1 to about 1:15, from about 10:1 to about 1:10, from about 5:1 to about 1:5, from about 3:1 to about 1:3, from about 3:1 to about 1:1, and/or from about 1:1 to about 1:3. Some embodiments include the synergistic composition comprising lansoprazole and doxorubicin (or IR), wherein the ratio between lansoprazole and doxorubicin (or IR) is about 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, and/or 2:1.
A twenty seventh embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein the at least one proton pump inhibitor is an R-enantiomer. Some embodiments include the method and/or the composition of any one of the preceding embodiments, wherein the at least one proton pump inhibitor is 5-hydroxy lansoprazole sulfide.
A twenty eighth embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein the patient is diagnosed with type-1 and/or type-2 diabetes.
A twenty ninth embodiment includes the method and/or the composition according to any one of the preceding embodiments, wherein the therapeutically effective dose of the at least one proton pump inhibitor is on the order of between about 0.01 mg to about 200 mg and the dose of the compound is administered to the patient at least once per day. In some embodiments, the therapeutically effective dose of the at least one proton pump inhibitor includes, but is not limited to, on the order of between: about 0.01 mg to about 150 mg; about 0.01 mg to about 100 mg; about 0.01 mg to about 80 mg; about 0.01 mg to about 60 mg; about 0.05 mg to about 100 mg; about 0.05 mg to about 80 mg; about 0.05 mg to about 50 mg; about 0.1 mg to about 100 mg; about 0.1 mg to about 50 mg; about 0.2 mg to about 100 mg; about 0.2 mg to about 50 mg; about 0.5 mg to about 100 mg; about 0.5 mg to about 50 mg; about 100 mg to about 200 mg; about 100 mg to about 150 mg; and/or any combination thereof. Consistent with these embodiments, the therapeutically effective dose of the at least one proton pump inhibitor includes, but not limited to, on the order of between: about 0.01 mg/m2 to about 100 mg/m2; about 0.01 mg/m2 to about 80 mg/m2; about 0.01 mg/m2 to about 50 mg/m2; about 0.01 mg/m2 to about 25 mg/m2; about 0.05 mg/m2 to about 100 mg/m2; about 0.05 mg/m2 to about 80 mg/m2; about 0.05 mg/m2 to about 50 mg/m2; about 80 mg/m2 to about 150 mg/m2; about 80 mg/m2 to about 120 mg/m2; and/or any combination thereof.
A thirtieth embodiment includes the method and/or the composition according to any one of the preceding embodiments, wherein the therapeutically effective dose of the at least one anti-cancer agent is on the order of between about 0.01 mg to about 200 mg and the dose of the compound is administered to the patient at least once per day. In some embodiments, the therapeutically effective dose of the at least one anti-cancer agent includes, but is not limited to, on the order of between: about 0.01 mg to about 150 mg; about 0.01 mg to about 100 mg; about 0.01 mg to about 80 mg; about 0.01 mg to about 60 mg; about 0.05 mg to about 100 mg; about 0.05 mg to about 80 mg; about 0.05 mg to about 50 mg; about 0.1 mg to about 100 mg; about 0.1 mg to about 50 mg; about 0.2 mg to about 100 mg; about 0.2 mg to about 50 mg; about 0.5 mg to about 100 mg; about 0.5 mg to about 50 mg; about 100 mg to about 200 mg; about 100 mg to about 150 mg; and/or any combination thereof. Consistent with these embodiments, the therapeutically effective dose of the at least one anti-cancer agent includes, but not limited to, on the order of between: about 0.01 mg/m2 to about 100 mg/m2; about 0.01 mg/m2 to about 80 mg/m2; about 0.01 mg/m2 to about 50 mg/m2; about 0.01 mg/m2 to about 25 mg/m2; about 0.05 mg/m2 to about 100 mg/m2; about 0.05 mg/m2 to about 80 mg/m2; about 0.05 mg/m2 to about 50 mg/m2; about 80 mg/m2 to about 150 mg/m2; about 80 mg/m2 to about 120 mg/m2; and/or any combination thereof.
A thirty first embodiment includes the method and/or the composition according to any one of the preceding embodiments, wherein the therapeutically effective dose of the poly ADP ribose polymerase (PARP) inhibitor is on the order of between about 0.01 mg to about 200 mg and the dose of the compound is administered to the patient at least once per day. In some embodiments, the therapeutically effective dose of the poly ADP ribose polymerase (PARP) inhibitor includes, but is not limited to, on the order of between: about 0.01 mg to about 150 mg; about 0.01 mg to about 100 mg; about 0.01 mg to about 80 mg; about 0.01 mg to about 60 mg; about 0.05 mg to about 100 mg; about 0.05 mg to about 80 mg; about 0.05 mg to about 50 mg; about 0.1 mg to about 100 mg; about 0.1 mg to about 50 mg; about 0.2 mg to about 100 mg; about 0.2 mg to about 50 mg; about 0.5 mg to about 100 mg; about 0.5 mg to about 50 mg; about 100 mg to about 200 mg; about 100 mg to about 150 mg; and/or any combination thereof. Consistent with these embodiments, the therapeutically effective dose of the poly ADP ribose polymerase (PARP) inhibitor includes, but not limited to, on the order of between: about 0.01 mg/m2 to about 100 mg/m2; about 0.01 mg/m2 to about 80 mg/m2; about 0.01 mg/m2 to about 50 mg/m2; about 0.01 mg/m2 to about 25 mg/m2; about 0.05 mg/m2 to about 100 mg/m2; about 0.05 mg/m2 to about 80 mg/m2; about 0.05 mg/m2 to about 50 mg/m2; about 80 mg/m2 to about 150 mg/m2; about 80 mg/m2 to about 120 mg/m2; and/or any combination thereof.
A thirty second embodiment includes the method and/or the composition according to any one of the preceding embodiments, wherein the therapeutically effective dose of the at least one agent that reduces the activity of the at least one DNA damage/repair pathway is on the order of between about 0.01 mg to about 200 mg and the dose of the compound is administered to the patient at least once per day. In some embodiments, the therapeutically effective dose of the at least one agent that reduces the activity of the at least one DNA damage/repair pathway includes, but is not limited to, on the order of between: about 0.01 mg to about 150 mg; about 0.01 mg to about 100 mg; about 0.01 mg to about 80 mg; about 0.01 mg to about 60 mg; about 0.05 mg to about 100 mg; about 0.05 mg to about 80 mg; about 0.05 mg to about 50 mg; about 0.1 mg to about 100 mg; about 0.1 mg to about 50 mg; about 0.2 mg to about 100 mg; about 0.2 mg to about 50 mg; about 0.5 mg to about 100 mg; about 0.5 mg to about 50 mg; about 100 mg to about 200 mg; about 100 mg to about 150 mg; and/or any combination thereof. Consistent with these embodiments, the therapeutically effective dose of the at least one agent that reduces the activity of the at least one DNA damage/repair pathway includes, but not limited to, on the order of between: about 0.01 mg/m2 to about 100 mg/m2; about 0.01 mg/m2 to about 80 mg/m2; about 0.01 mg/m2 to about 50 mg/m2; about 0.01 mg/m2 to about 25 mg/m2; about 0.05 mg/m2 to about 100 mg/m2; about 0.05 mg/m2 to about 80 mg/m2; about 0.05 mg/m2 to about 50 mg/m2; about 80 mg/m2 to about 150 mg/m2; about 80 mg/m2 to about 120 mg/m2; and/or any combination thereof.
A thirty third embodiment includes the method and/or the composition of any one of the preceding embodiments, wherein the patient is treated by suppressing DNA damage repair via inhibiting FASN activity and PARP1 expression.
A thirty fourth embodiment includes the method and/or the composition of any one of the preceding embodiments, the patient includes, but is not limited to, African American and/or Caucasian patients.

Combination drug therapy reduces PARP-1 related DNA repair and increases the efficacy of genotoxic agents

INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION


A health suit for improving sweating and tanning in various weather conditions includes a transparent material that is configured to allow ultraviolet rays and infrared energy to pass through the material and penetrate the skin with minimal deflection or absorption by the material. The health suit may also include an anti-fog layer or other set of anti-fogging features, moisture absorbing material, and a heat retention feature to improve sweating and tanning in various weather conditions.

The therapeutic and cosmetic effects of exposing a person's body to sunlight are well known. Sunlight, for example, is an important source of a body's ability to produce Vitamin D. Currently, millions of people in the world suffer from various diseases or conditions that may be exacerbated by lack of adequate exposure to sunlight, or ameliorated by additional exposure to sunlight. These conditions may include diabetes, elevated blood pressure, heart disease, multiple sclerosis, osteomalacia, osteoporosis, psoriasis, rickets, seasonal affective disorder, tooth decay, tuberculosis and cancer. However, due to seasonal changes or weather conditions, the benefits of sunlight are not always available.
Several methods have been used to increase our exposure to light such as, for example, using artificial UV rays in tanning salons or using transparent clothing garments outdoors that allow natural sun light to penetrate the garment in cold/cool seasons while still providing thermal protection against the cold. Other garments like rain coats or similar PVC or plastic garments that are slightly transparent are available, but they are not made specifically to allow ultraviolet rays to penetrate the outer layer in order to maximize health benefits.
The benefits of body sweating have also been explored, for example, for detoxification and weight loss purposes, improved absorption of vitamin D and lowering of blood pressure. The most widely used methods to stimulate body sweating has been through physical activity or use of clothing garments that facilitate sweating such as layered reducing garment and sweat suits. These garments trap body heat and block wind creating a sauna effect to facilitate weight loss. However, these garments are opaque and are not useful for tanning purposes.
Current health suits do not adequately provide health and tanning benefits to a user at the same time. Therefore, a garment that can effectively stimulate body sweating and tanning for a user at the same time would be desirable. The positive effects of the sun exposure and of the sweating may be found to be amplified by the combination of the two effects in the health suit described herein. For example, a wearer may lose weight as its body works to cool itself. The increased body heat from the tanning aspects of the health suit may further increase a wearer's heart rate, thus increasing cardiac output and also metabolic rates. Consequently a wearer may then burn additional calories increasing the health effects sought through the sweating aspects. Further, a wearer may have health benefit from vitamin D absorption from sunlight. The increase in skin pore openings or improved blood circulation that may result from the sweating aspects of the health suit may improve the tanning aspects of the suit as well, further increasing a wearer's ability to absorb vitamin D more effectively and enhance melanin production and skin pigmentation through the wearer's increased pore openings.

Health suit with improved health and tanning benefits in various weather conditions


In an environment in which many types of drivers are installed, it is cumbersome for a user to select a desired printer from a printer list displayed on a screen, after the user has issued a printing instruction from an application. In an information processing apparatus in the present invention, data which is received from an application in response to an instruction from a user is spooled as intermediate data, printers which are connected to the apparatus itself are retrieved after the instruction from the user, an installation process and creation of a print queue are performed for a printer driver which is compatible with a printer selected from found printers, the intermediate data is passed to the printer driver, and a printing process is performed. Then, a deletion candidate is decided in the created print queues, and the print queue which is the deletion candidate is deleted.

1. Field of the Invention
The present invention relates to an information processing apparatus, and more particularly, to a system in which printing can be efficiently performed by only specifying a printer to be used, from placed printers, by a user at the time of the printing.
2. Description of the Related Art
Conventionally, in order to use a peripheral device such as a printer from a host computer, generally, a particular device driver which is compatible with the peripheral device needs to be incorporated in the host computer. A user or an administrator has been forced to perform installation work for previously checking information on an IP address or the like required for incorporating the device driver before printing, finding a compatible device driver from the Internet, and placing the device driver.
Consequently, in recent years, "universal driver" (generic printer driver), which is a common device driver that can be used regardless of a type of the peripheral device, has been researched and developed. For example, HP Universal Print Driver Series for Windows-overview and features (http://h20338.www2.hp.com/hpsub/cache/342988-0-0-225-121.html) discloses a method of issuing a printing instruction from an application to the generic printer driver, subsequently selecting a network printer that can perform output, and perform printing. According to this method, all printers which the generic printer driver is compatible with can be used by only previously incorporating the generic printer driver in an information processing apparatus.
However, since the generic printer driver shown in the above described article generates and transmits a command which can be processed by using common functions included in all the compatible printers, functions are limited in comparison with a case where the printing is performed by using a dedicated printer driver which is specialized in each printer. Moreover, basically, the printing cannot be performed for a printer of a type which cannot process a format of the command transmitted by the generic printer driver.
When the user performs the printing for the printer, the user issues the printing instruction from the application, selects a desired printer from a printer list displayed on a screen, and designates printing settings or the like. Here, the printer list displayed on the screen is displayed corresponding to a printer driver which has been installed and for which a print queue has been created.
For the user, depending on a document to be printed or the like, it is desirable to perform the printing depending on occasions, such as in a case where the generic printer driver as described above is used to simply perform the printing, and in a case where a dedicated printer is used to perform the printing. Therefore, in a host computer used by the user, such a situation can occur in which many types of drivers are installed and mixed. Furthermore, there is also an environment in which many types of printer drivers can be installed in the host computer by plug-and-play or the like without the user's intent.
In this way, in the environment in which many types of drivers are installed, it is cumbersome for the user to select the desired printer from the printer list displayed on the screen, after the user has issued the printing instruction from the application. Particularly, as described above, there are also printer drivers, such as the generic printer driver and the dedicated printer driver, which transmit a print job to the same printer but are different in functions. Thus, it is very difficult for the user to select a printer for performing the printing while taking full advantage of the functions included in the printer.
Therefore, an object of the present invention is to provide a method of managing device drivers so that the selection of the printer at the time of the printing may not be cumbersome, in such an environment in which many types of device drivers are installed in the host computer without the user's intent.

Information processing apparatus and method thereof


Apparatuses, systems, and methods are disclosed for use in or with firearms. A firearm barrel trunnion includes a rear portion shaped to couple to a receiver for a firearm. The trunnion includes a front portion shaped to couple to a handguard for the firearm and to support the handguard without the handguard contacting other components of the firearm. A bore is formed within the trunnion, and is shaped to receive a barrel for the firearm.

Designs for many AK-47 type rifles prioritize quick, low-cost production methods over accuracy. Stamped sheet metal construction and high clearances between parts may result components not being aligned the same way from shot to shot. Also, contact between the barrel and other components may push the barrel in different directions (e.g., due to force on a handguard attached to the barred), or may interfere with barrel harmonics, so that the barrel vibrates or oscillates differently from shot to shot. Despite these accuracy problems, modern warfighters who need to fire accurately may want to use AK-47 type rifles for a variety of reasons, such as to utilize widely available interchangeable parts, or in circumstances when the distinctive sound of an AK-47 is expected.


A hardfacing composition essentially consisting of from about 50 to 75 percent by weight of a carbide phase having a particle size distribution of ±20% or less of a median particle size; and from about 25 to 50 percent by weight of binder phase is disclosed. Drill bits having such hardfacing compositions disposed thereon are also disclosed.

1. Field of the Invention
Embodiments disclosed herein relate generally to compositions which provide improved hardfacing materials for use in drill bits or other earth boring cutting tools.
2. Background Art
Historically, there have been two types of drill bits used drilling earth formations, drag bits and roller cone bits. Roller cone bits include one or more roller cones rotatably mounted to the bit body. These roller cones have a plurality of cutting elements attached thereto that crush, gouge, and scrape rock at the bottom of a hole being drilled. Several types of roller cone drill bits are available for drilling wellbores through earth formations, including insert bits (e.g. tungsten carbide insert bit, TCI) and "milled tooth" bits. The bit bodies and roller cones of roller cone bits are conventionally made of steel. In a milled tooth bit, the cutting elements or teeth are steel and conventionally integrally formed with the cone. In an insert or TCI bit, the cutting elements or inserts are conventionally formed from tungsten carbide, and may optionally include a diamond enhanced tip thereon.
The term "drag bits" refers to those rotary drill bits with no moving elements. Drag bits are often used to drill a variety of rock formations. Drag bits include those having cutting elements or cutters attached to the bit body, which may be a steel bit body or a matrix bit body formed from a matrix material such as tungsten carbide surrounded by an binder material. The cutters may be formed having a substrate or support stud made of carbide, for example tungsten carbide, and an ultra hard cutting surface layer or "table" made of a polycrystalline diamond material or a polycrystalline boron nitride material deposited onto or otherwise bonded to the substrate at an interface surface.
Typically, a hardfacing material is applied, such as by arc or gas welding, to the exterior surface of the steel components (e.g., milled teeth or steel bit body) to improve the wear resistance of the area of the bit (or other downhole tools needing body protection. The hardfacing material typically includes one or more metal carbides, which are bonded to the steel components by a metal alloy ("binder alloy"). In effect, the carbide particles are suspended in a matrix of metal forming a layer on the surface of the steel. The carbide particles give the hardfacing material hardness and wear resistance, while the matrix metal provides fracture toughness to the hardfacing.
Many factors affect the durability of a hardfacing composition in a particular application. These factors include the chemical composition and physical structure (size and shape) of the carbides, the chemical composition and microstructure of the matrix metal or alloy, and the relative proportions of the carbide materials to one another and to the matrix metal or alloy. The metal carbide most commonly used in hardfacing is tungsten carbide. Small amounts of tantalum carbide and titanium carbide may also be present in such material, although these other carbides may be considered to be deleterious.
Many different types of tungsten carbides are known based on their different chemical compositions and physical structure. Three types of tungsten carbide commonly typically used in hardfacing drill bits are cast tungsten carbide, macro-crystalline tungsten carbide, carburized tungsten carbide, and cemented tungsten carbide (also known as sintered tungsten carbide).
Cemented tungsten carbide refers to a material formed by mixing particles of tungsten carbide, typically monotungsten carbide, and particles of cobalt or other iron group metal, and sintering the mixture. In a typical process for making cemented tungsten carbide, small tungsten carbide particles, e.g., 1-15 microns, and cobalt particles are vigorously mixed with a small amount of organic wax which serves as a temporary binder. An organic solvent may be used to promote uniform mixing. The mixture may be prepared for sintering by forming the mixture into granules or particles such as by pressing through a screen, or tumbling and then screened to obtain more or less uniform particle size.
Such green particles are then heated in a vacuum furnace to first evaporate the wax and then to a temperature near the melting point of cobalt (or the like) to cause the tungsten carbide particles to be bonded together by the metallic phase. After sintering, the compacts are crushed and screened for the desired particle size. Similarly, the sintered particles, which tend to bond together during sintering, are gently churned in a ball mill with media to separate them without damaging the particles. Some particles may be crushed to break them apart. These are also screened to obtain a desired particle size. The crushed cemented carbide is generally more angular than the particles which tend to be rounded.
Another type of tungsten carbide is macro-crystalline carbide. This material is essentially stoichiometric tungsten carbide created by a thermite process. Most of the macro-crystalline tungsten carbide is in the form of single crystals, but some bicrystals of tungsten carbide may also form in larger particles. Single crystal stoichiometric tungsten carbide is commercially available from Kennametal, Inc., Fallon, Nev.
Carburized carbide is yet another type of tungsten carbide. Carburized tungsten carbide is a product of the solid-state diffusion of carbon into tungsten metal at high temperatures in a protective atmosphere. Sometimes, it is referred to as fully carburized tungsten carbide. Such carburized tungsten carbide grains usually are multi-crystalline, i.e., they are composed of tungsten carbide agglomerates. The agglomerates form grains that are larger than the individual tungsten carbide crystals. These large grains make it possible for a metal infiltrant or an infiltration binder to infiltrate a powder of such large grains. On the other hand, fine grain powders, e.g., grains less than 5 μm, do not infiltrate satisfactorily. Typical carburized tungsten carbide contains a minimum of 99.8% by weight of tungsten carbide, with a total carbon content in the range of about 6.08% to about 6.18% by weight.
Regardless of the type of hardfacing material used, designers continue to seek improved properties (such as improved wear resistance, thermal resistance, etc.) in the hardfacing materials. Unfortunately, increasing wear resistance usually results in a loss in toughness, or vice-versa.
Accordingly, there exists a continuing need for improvements in hardfacing materials.

Hardfacing compositions for earth boring tools


A superior catalyst for the oxychlorination of C.sub.2 hydrocarbon feeds comprises a mixture of copper chloride and alkali metal chloride, for instance, potassium chloride, and preferably also magnesium chloride, which mixture is deposited on an alumina support having a surface area in excess of 20 and less than 100 m.sup.2 /g. The thermal stability of such a catalyst composition can be further improved by incorporating 0.2 to 5 percent silica in the alumina support. The use of such microspheroidal catalyst in the production of perchloroethylene and trichloroethylene by oxychlorination of a C.sub.2 hydrocarbon feed in a fluidized bed reactor results in particularly good process efficiencies in terms of high HCl conversion, and good flexible selectivity to specifically desired product, reduced burning, long on-stream times, and relatively low corrosion rates.

1. Field of the Invention
The invention relates to the production of perchloroethylene and trichloroethylene by catalytic oxychlorination of C.sub.2 hydrocarbons or their partially chlorinated derivatives, to catalysts useful in such oxychlorination processes, and to processes for making such catalysts.
2. General Background and Summary of the Prior Art
Perchloroethylene, C.sub.2 Cl.sub.4, and trichloroethylene, C.sub.2 HCl.sub.3, are chlorinated hydrocarbons which have been widely used as solvents in dry cleaning textiles, in degreasing metal parts, in various solvent extraction processes, in compounding rubber cements, and in various other operations. Perchloroethylene is relatively stable, so its use is currently much less severely restricted by anti-pollution regulations than is the use of most other chlorinated solvents. Trichloroethylene is a potentially valuable intermediate for manufacturing chlorofluorocarbon replacements which are less damaging to the atmospheric ozone layer.
It has been common to produce perchloroethylene simultaneously with trichloroethylene by catalytic oxychlorination of ethane, ethylene or a partially chlorinated derivative thereof, i.e., by reacting such a feedstock with chlorine or hydrogen chloride and air or oxygen at a suitable elevated temperature in the presence of a suitable solid catalyst, the catalyst being maintained in the reaction zone either as a fixed bed or, more preferably, as a fluidized bed.
Typically, such oxychlorination catalysts are compositions that comprise a catalytic amount of a metal having a variable valence, notably copper, as well as an alkali metal, notably potassium, supported on a suitable carrier. Carriers used commercially in the past have included highly calcined Fuller's earth (an adsorbent clay) such as "Florex" or, preferably, synthetic activated aluminas. See, for instance, U.S. Pat. No(s). 3,267,162, 3,296,319 and 4,463,200. Fuller's earth is essentially a porous magnesium-aluminum silicate containing small proportions of oxides of iron, calcium, potassium and titanium. By contrast, synthetic activated alumina consists essentially of alumina with virtually no significant impurities or at the most only a very small proportion of silica.
Researchers working on catalytic oxychlorination processes in the prior art have in some instances expressed a preference for the use of low-surface-area alumina as catalyst supports, i.e., for supports having a surface area below 10 m.sup.2 /g or more especially between 2 and 5 m.sup.2 /g (as in U.S. Pat. No. 4,124,534), while in other instances they have expressed a preference for high-surface-area alumina as catalyst supports, i.e., for supports having a surface area of at least 100 m.sup.2 /g (as in U.S. Pat. No. 4,463,200). Low-surface-area supports have been recommended mainly because they were thought to result in higher HCl conversions and lower carbon burning (see, for instance, U.S. Pat. No. 3,427,359 and French Patent No. 1,386,023), whereas high-surface-area supports have been recommended because they were thought to contribute to an increased selectivity of the reaction toward the production of perchloroethylene as the desired product and a reduced formation of undesirable 1,1,2-trichloroethane and unsymmetrical tetrachloroethane, as indicated in U.S. Pat. No. 4,463,200.
However, catalysts comprising a low-surface-area support have been found to be relatively unstable in that such supports possess only a relatively small number of binding sites for retaining the active metal salts in the composition, and the resulting loss of the metal salts from such catalysts has been found to constitute a significant factor in causing corrosion of the metal reactors in which such oxychlorination reactions are generally carried out. In addition, especially when low-surface-area supports such as diatomaceous earth or other silica-aluminas are used, high selectivities to perchloroethylene and trichloroethylene are not obtained at reasonable temperatures.
On the other hand, catalysts comprising a high-surface-area support, especially when used at temperatures near or above 400.degree. C. which are required to obtain good selectivity for the production of perchloroethylene and trichloroethylene, cause substantial oxidation of the feed material with a concomitant formation of unwanted carbon oxides, especially when ethane or ethylene are used as the feed, and in particular under conditions favoring the production of trichloroethylene.

Manufacture of perchloroethylene and trichloroethylene by catalytic oxychlorination, and improved catalysts therefor


A surface mountable resistor chip assembly, containing an integral heat sink, convective cooling provision exhibits higher continuous-mode power ratings than prior art surface mount resistors having comparable printed circuit board footprints. The preferred embodiments are also configured so as to reduce transient thermal impedance in a manner to exhibit increased power rating under short duration overload conditions. The assembly includes a housing with passages, holes or slotted openings, for the chip assembly and for air flow therethrough, and electrically conductive paths to bring the chip electrical connections out to pads on the housing arranged to make electrical connections to a printed circuit board.

1. Field of the Invention
The present invention relates to surface mounted resistors and more particularly to high power dissipating surface mounted resistors.
2. Background Information
The use of power resistors in electronic circuits is well known. Such products are produced by dozens of vendors, with ratings of a few watts up to thousands of watts, involving hundreds of physical configurations. Over the past 15-20 years there has been significant growth in the use of surface mount components, with power resistors not immune to that trend. Driving this trend has been the desire for manufacturers and consumers to have functionality in ever-decreasing equipment size or, conversely, more functionality in the same size.
The pressure to lower cost has been an additional impetus since surface mount manufacturing techniques, being highly automated in nature, are particularly conducive to high throughput and high repeatability. Electronic assembly has steadily progressed to where more and more components, previously used only in their through-hole (components mounted with their leads extending through the printed circuit board) version, are becoming available as surface mountable versions.
This is another way of saying that surface-mount assembly, originally associated with low-power circuits, is increasingly being expected to accommodate higher-power functions. Viewed from a circuit designer's standpoint, surface mount only requires a major space consideration on one side of a printed circuit board while a through-hole part has an impact on available space on both sides of the PC board: on one side for the component itself and on the other for the protrusion of leads. That is to say. a surface-mount component, aside from its many other size and reliability advantages, minimizes the need for what is called "mixed technology: that is, the use of one manufacturing process for one side of the PC board and a different process for components affixed to the other side of the PC board.
The continued acceleration of such trends in compactness and automation has led to the introduction of surface-mount power resistors by many firms. In the simplest case, the device is a standard resistor chip, with perhaps a larger size, so that it can handle up to a watt. Above that power level, many firms have adapted a mainstay of more traditional through-hole power resistor technology; that is, a winding of resistive wire, to create wire-wound surface mount types.
U.S. Pat. No. 4,672,358 owned by Ohmite discloses a power resistor with its core of traditional design but with its leads arranged for surface mounting. Similar products are offered by many firms, e.g. Vishay, IRC, KOA, Panasonic. These power resistor s are offered with dissipation up to 5 watts.
Typically, even though wire wound power resistors are wound "non-inductively," there is some unwanted residual inductance. In high frequency applications, such inductance is a limitation. The present invention inherently minimizes the inductance.
In the U.S. Pat. No. 4,672,358 patent, the power resistor is placed down flush with the PC board surface. This is a limitation of the patent and limits the power resistor to about 50% of its stated rating. If the power resistor transmits too much heat to a circuit board, that circuit board will not pass safety-agency rating criteria. For example, a power resistor rated for a maximum temperature of 250 degrees C. (Celsius) might be operating safely at 200 degrees, but the PC board below it, being at perhaps 175 degrees C., is far above its safety-agency rating, which is typically about 100 degrees C. and 150 degrees C. for some types of fire resistant boards. U.S. Pat. No. 5,291,175 describes these considerations.
Another thermal consideration involves certain types of power resistors used in "dynamic-braking" applications. In such applications, the resistor can be subject to high current for a short period of time. U.S. Pat. No. 5,710,494 describes such applications and the principles involved. In a typical continuous-mode operation, the maximum temperature rating determines the power dissipated. If the temperature rises above that maximum, the resistor may fail. Such a rating can be influenced by the resistor surface area, the ambient temperature and cooling effects of air turbulence in the immediate vicinity of the resistor.
In a short-duration, high-current mode, however, the power dissipated in a resistor may be much higher that the listed rating and the maximum temperature not reached. This is because other parameters, namely, the mass and specific heat of the resistor control the temperature rise for short duration events. The mass acts like a shock absorber to short bursts of power. Therefore, in short-duration, high-current applications, such as dynamic braking, capacitive-discharge circuits, power supply inrush limiters etc., it is possible to have a small resistor do the job of a much larger one if the relationship of surface area, ambient temperature, air turbulence, pulse-current duration and material mass are understood wherein the temperature rise remains below the resistors rating.
In cases where it is possible to have the mass, as just referenced, in the form of a thermally conductive metal, such as aluminum or copper, it is possible to obtain substantially higher dissipation in a relatively small resistor assembly. Such higher dissipation is achieved by making use of the very low value of what is called transient thermal impedance, a term long associated with power semi-conductors. International Rectifier Corp. Application Note 949, entitled "Current Ratings of a Power Semiconductor," 1999; and a paper by Chan Su Yun, entitled, "Static and Dynamic thermal Behavior of IGBT Power Modules," dated Jun. 9, 2000 and available on the Internet at: www.iis.ee.ethz.ch/csyun/papers/thesis/node71.html are incorporated herein by reference. These references describe the principles involved.
A paper by the present inventor entitled, "Cooling a High Density DC-DC Converter Impacts Performance and Reliability," published in PCIM Magazine (now Power electronics magazine), November 1999, pages 60-66 describes in detail heat removal from a power semiconductor chip whereby that heat travels from the chip through a series of barriers on its way to an ultimate cooling medium. This reference is also incorporated herein by reference. The carefully configured heat removal system described in this paper is used in preferred embodiments of the present invention to maximize power handling in both continuous and high-power transient modes.

Surface mounted resistor with improved thermal resistance characteristics


A method and apparatus for efficient network scanning that selects candidate frequencies based upon the frequency bands that were noted as being active during a previous network scan. A mobile device performs a full network scan on power up or on radio cycle and determines the available active bands. This information is stored as active band information on the device. When the device loses coverage on a selected one of the bands, then it identifies a candidate frequency based upon the stored active band information and attempts to locate a suitable network on the candidate band.

Many wireless devices are capable of communicating with wireless networks on more than one frequency band. Wireless networks in different countries or regions often have different frequency bands available for wireless communication services. In particular, North American systems typically have 850 MHz band and/or 1900 MHz band and European systems typically have 900 MHz band and/or 1800 MHz band. Devices that are capable of communicating on more than one frequency band require a mechanism and method for scanning supported frequency bands and selecting a suitable network.
One option is to perform an exhaustive network scan to search for suitable networks on all frequency bands supported by the device. This process is typically performed by many wireless devices upon power cycle and/or radio cycle; however scanning all frequency bands exhaustively is expensive in terms of battery power. A device sometime loses coverage on one frequency band and needs to re-establish a connection with a wireless network as quickly and efficiently as possible. In these circumstances, an exhaustive network scan consumes time and battery power.
Accordingly, some devices base their search for active frequency bands upon the country in which the device was most recently connected. For example, if the device had established communications on a 900 MHz band, it may choose to assume it is located in a country supporting the European network frequency plan. Therefore, it may assume that the frequency bands that will be available are the usual 900 MHz and/or 1800 MHz bands. Thus, the device may limit its search for suitable networks to these two likely co-existing frequency bands, if these two bands are supported by the device.
There are some circumstances in which this technique fails to locate the available networks unless a power cycle or radio cycle is performed. In some countries or regions suitable networks may be available on frequency bands associated with both network frequency plans. For example, in the border regions of some countries a device may be capable of connecting to wireless providers in either of two countries, each of which may be on a different network frequency plan. Therefore, the device may have available to it suitable networks providing, for example, 850 MHz, 900 MHz, and 1800 MHz bands. It would be advantageous to have a method and system for efficiently locating suitable networks on available supported frequency bands in such a situation.

This patent is subject to a terminal disclaimer.

Method and apparatus for efficient network scanning


An exercise device including one or more weight stacks moveably supported on a frame. Each weight stack includes one or more weight plates that may be selectively engaged by way of a dial arrangement operably coupled with the weight stack. The dial arrangement is connected with a selection member that extends through a selection aperture in the weight plates. Each selection aperture defines a unique contour with at least one engaging surface, such as a tab. The selection member has corresponding protrusions adapted to engage the engaging surface of the weight plate. Each dial arrangement may be configured so that the weight stack may only be actuated when the selection member is properly positioned so that the protrusions properly engage the engaging surfaces. By adjusting the dial setting, the selection member is rotated so that one or more of the various protrusions engage associated engaging surfaces in order to engage some combination of weight plates. Upon actuation (i.e., exercise), the selected weights are engaged and moved when the selection member is properly orientated.

Exercise weight stacks are well known in the art and prevalent in the exercise equipment industry. Generally speaking, a plurality of weights or plates are arranged in a stack and maintained in alignment by guide members or rods. A desired amount of weight is engaged by selectively connecting a selector rod to the appropriate weight in the stack. The selector rod and/or the uppermost weight in the stack are/is connected to at least one force receiving member by means of a connector. The engaged weight is lifted up from the stack in response to movement of the force receiving member.
Some examples of weight stacks, their applications, and/or features are disclosed in U.S. Pat. No. 3,912,261 to Lambert, Sr. (discloses an exercise machine which provides weight stack resistance to a single exercise motion); U.S. Pat. No. 5,263,915 to Habing (discloses an exercise machine which uses a single weight stack to provide resistance to several different exercise motions); U.S. Pat. No. 4,900,018 to Ish III, et al. (discloses an exercise machine which provides weight stack resistance to a variety of exercise motions); U.S. Pat. No. 4,878,663 to Luquette (discloses an exercise machine which has rigid linkage members interconnected between a weight stack and a force receiving member); U.S. Pat. No. 4,601,466 to Lais (discloses bushings which are attached to weight stack plates to facilitate movement along conventional guide rods); U.S. Pat. No. 5,374,229 to Sencil (discloses an alternative to conventional guide rods); U.S. Pat. No. 4,878,662 to Chern (discloses a selector rod arrangement for clamping the selected weights together into a collective mass); U.S. Pat. No. 4,809,973 to Johns (discloses telescoping safety shields which allow insertion of a selector pin but otherwise enclose the weight stack); U.S. Pat. No. 5,000,446 to Sarno (discloses discrete selector pin configurations intended for use on discrete machines); U.S. Pat. No. 4,546,971 to Raasoch (discloses levers operable to remotely select a desired number of weights in a stack); U.S. Pat. No. 5,037,089 to Spagnuolo et al. (discloses a controller operable to automatically adjust weight stack resistance); U.S. Pat. No. 4,411,424 to Barnett (discloses a dual-pronged pin which engages opposite sides of a selector rod); U.S. Pat. No. 1,053,109 to Reach (discloses a stack of weight plates, each having a slide which moves into and out of engagement with the weight plate or top plate above it); and U.S. Pat. No. 5,306,221 to Itaru (discloses a stack of weight plates, each having a lever which pivots into and out of engagement with a selector rod), all of which are incorporated herein by reference.


A method for maintaining data integrity of a storage device is provided. A request is received to create an access monitoring session for a data range on a volume of the storage device. A session identification (ID) is determined for the access monitoring session for data range on the volume. An entry is created in an access monitoring session table for the session ID, and the entry adds the access monitoring session with session ID for the data range on the volume to the access monitoring session table. Request parameters are included in the request to create the access monitoring session. The request parameters denote access to the data range on the volume for the session ID and are stored in the access monitoring session table. Access is controlled to the data range on the volume for the session ID based on request parameters stored in the access monitoring session table.

Exemplary embodiments of the present invention relate to storage, and more specifically, to data integrity of external storage devices.
External storage (also referred to as a secondary storage device) is any device that temporarily stores information and external storage is generally not permanently fixed inside a computer. A direct access storage device, or DASD, is any secondary storage device which has relatively low access time for all its capacity. The DASD is accessed by a computer system. Historically, IBM® introduced the term to cover three different device types: disk drives, magnetic drums, and data cells. Modern DASD most commonly means but is not limited to large disk arrays utilizing, e.g., RAID (Redundant Array of Independent Disks) schemes. A disk array is a disk storage system which contains multiple disk drives. It is differentiated from a disk enclosure, in that an array has cache memory and advanced functionality, like RAID and virtualization. Components of a typical disk array include disk array controllers, cache memories, disk enclosures, power supplies, etc. Typically a disk array provides increased availability, resiliency and maintainability by using additional, redundant components (controllers, power supplies, fans, etc.), often up to the point when all single points of failure (SPOFs) are eliminated from the design. Typically, disk arrays are divided into categories: network attached storage (NAS) arrays, storage area network (SAN) arrays, and/or storage virtualization as understood by one skilled in the art.
In a computer system with one or more host systems (computers) connected to one or more external storage systems, loss of data integrity for data on external storage devices can occur if the wrong data (data residing at the wrong external storage location) is accidentally updated ("clobbered"). Similarly, loss of data integrity can occur if the correct data is updated at the wrong time.

Data integrity mechanism for external storage devices

International Business Machines Corporation


First and second bit lines are arranged on one side of each sense amplifier while third and fourth bit lines are arranged on the other side thereof. A first dummy cell is connected to either the first bit line or the second bit line. In addition, a second dummy cell is connected to either the third bit line or the fourth bit line. When a memory cell connected to the first bit line is selected, the second dummy cell is simultaneously selected. On this occasion, the first bit line is connected to a first terminal of the sense amplifier, and the third bit line and the fourth bit line are connected to a second terminal of the sense amplifier. Potentials of the first and second terminals are differentially amplified. On the other hand, when a memory cell connected to the third bit line is selected, the first dummy cell is simultaneously selected. On this occasion, the third bit line is connected to the second terminal of the sense amplifier, and the first bit line and the second bit line are connected to the first terminal of the sense amplifier. The potentials of the first and second terminals are differentially amplified.

1. Field of the Invention
The present invention relates generally to semiconductor memory devices, and more particularly, to a semiconductor memory device in which high-speed access can be made even if integration density is increased.
2. Description of the Prior Art
FIG. 1 is a block diagram showing the entire structure of a conventional collectively erasable type of electrically erasable and programmable read-only memory (referred to as flush EEPROM hereinafter).
In FIG. 1, the flush EEPROM includes a plurality of memory cell arrays 31. Each of the memory cell arrays 31 is provided with a column decoder/Y gate 32. In addition, the plurality of memory cell arrays 31 are provided with a common row decoder 33. A column address signal is applied to the plurality of column decoder/Y gates 32 from a Y address buffer 34. A row address signal is applied to the row decoder 33 from an X address buffer 35. On the other hand, sense amplifier/write drivers 36 are connected to the column decoder/Y gates 32 through I/O lines I/O, respectively. A common input/output buffer 37 is connected to the plurality of sense amplifier/write drivers 36.
A chip enable signal CE, a write enable signal WE and an output enable signal OE.pi.are externally applied to a control signal input buffer 38. The control signal input buffer 38 is responsive to the signals for applying a control signal to a write/read timing generating circuit 39. The write/read timing generating circuit 39 is responsive to this control signal for generating various timing signals, to control a writing operation and a reading operation.
Each of the memory cell arrays 31 includes a plurality of memory cells arranged in a matrix as described below. The row decoder 33 is responsive to the row address signal applied from the X address buffer 35 for selecting one row in the memory cell arrays 31. The column decoder/Y gates 32 are responsive to the column address signal applied from the Y address buffer 34 for selecting columns in the memory cell arrays 31, respectively Data are read out from memory cells respectively provided at intersections of the rows and the columns, amplified by respective sense amplifiers in the sense amplifier/write drivers 36, and outputted through the input/output buffer 37.
FIG. 2 is a circuit diagram showing a structure of one of the memory cell arrays 31 included in the flush EEPROM shown in FIG. 1.
In FIG. 2, a plurality of memory cells MC are arranged in a matrix in the memory cell array 31. A bit line BL is arranged in each column of the plurality of memory cells MC. The memory cells MC have their drains connected to the bit line BL. The bit lines BL are connected to an I/O line I/O through N channel MOS transistors Q31, respectively. The plurality of transistors Q31 constitute a Y gate included in each of the column decoder/Y gates 32 shown in FIG. 1. Each of the transistors Q31 has its gate connected to a column decoder 32a included in each of the column decoder/Y gates 32. In addition, a word line WL is provided in each row of the plurality of memory cells MC. The memory cells MC have their control gates connected to the word line WL. A plurality of word lines WL are connected to a row decoder 33. All the memory cells MC have their sources connected to ground through a source line SL and an N channel MOS transistor Q32. The transistor Q32 has its gate receiving an erase signal ERS. On the other hand, a current detecting type sense amplifier 40 included in each of the sense amplifier/write drivers 36 is connected to the I/O line I/O.
FIG. 3 is a cross sectional view showing a memorY transistor constituting a memory cell MC, and FIG. 4 is a diagram showing an equivalent circuit of the memory transistor.
The memory transistor comprises a source 41, a drain 42, a floating gate 43 and a control gate 44. Data "1" or "0" is stored in the memory transistor depending on whether or not electrons are stored in the floating gate 43. More specifically, when electrons are stored in the floating gate 43, the threshold voltage of the memory transistor becomes high. Consequently, if and when a predetermined voltage is applied to the control gate 44, a path between the source 41 and the drain 42 is rendered non-conductive. Contrary to this, when electrons are emitted from the floating gate 43, the threshold voltage of the memory transistor becomes low. Consequently, if a predetermined voltage is applied to the control gate 44, the path between the source 41 and the drain 42 is rendered conductive. Thus, an on or off state of the memory transistor corresponds to data "0" or "1" to be stored.
Description is now made on an erasing operation, a writing operation and a reading operation of the flush EEPROM shown in FIG. 2.
In the erasing operation, as shown in FIG. 5A, a high voltage V.sub.PP is applied to all the bit lines BL, and all the word lines WL are grounded. On this occasion, the erase signal ERS is brought to an "L" level, so that the transistor Q32 is rendered non-conductive, whereby the source line SL remains electrically floating. Consequently, as shown in FIG. 5B, electrons stored in the floating gate 43 in the memory transistor are emitted into the drain 42 by a tunnel phenomenon. As a result, the threshold voltage of the memory transistor becomes low. In the above described manner, data stored in all the memory cells MC are simultaneously erased.
In the writing operation, as shown in FIG. 6A, the high voltage V.sub.PP is applied to a selected bit line BL and a selected word line WL. On this occasion, the erase signal ERS is brought to an "H" level. As a result, the transistor Q32 is turned on, so that the source line SL is grounded. Consequently, as shown in FIG. 6B, avalanche breakdown occurs in the vicinity of the drain 42 in the memory transistor, so that hot electrons are injected into the floating gate 43. Therefore, the threshold voltage of the memory transistor becomes high. In the above described manner, data is written to a memory cell MC enclosed by a broken line in FIG. 6A.
Description is now made on the reading operation of the flush EEPROM. In FIG. 2, any of the plurality of word lines WL is selected by the row decoder 33, so that an "H" level potential is applied to the word line. In addition, any of the plurality of transistors Q31 is selected by the column decoder 32a, so that the "H" level potential is applied to a gate of the selected transistor. Thus, one memory cell MC is selected. The current detecting type sense amplifier 40 connected to the I/O line I/O determines whether or not a current flows from a drain to a source of the selected memory cell MC.
FIG. 7 is a circuit diagram showing the current detecting type amplifier 40 shown in FIG. 2. The current detecting type sense amplifier 40 is disclosed in, for example, Japanese Patent Laying-Open Gazette No. 170097/1987.
The sense amplifier 40 comprises a current-voltage converting circuit 40a for converting to a voltage signal a current corresponding to data stored in a memory cell MC, and an inverter circuit 40b for inverting the converted voltage signal. The current-voltage converting circuit 40a comprises P channel MOS transistors Q41 and Q42 and N channel MOS transistors Q43, Q44 and Q45.
First, in the reading operation, when the memory cell MC is rendered conductive, a potential of a node N11 becomes approximately 1.0 V in a steady state. Consequently, the transistor Q43 is slightly turned on, so that a potential of a node N12 becomes approximately 2 V. Therefore, the transistors Q44 and Q45 are slightly turned on. However, since the on-resistance of the transistor Q42 is set to be larger than that of the transistor Q45, a potential of a node N13 becomes approximately the same (i.e., 1.0 V) as the potential of the node N11.
Then, in the reading operation, when the memory cell MC is rendered non-conductive, the potential of the node N11 becomes approximately 1.1 V. Consequently, the potential of the node N12 becomes approximately 1.8 V, so that the potential difference between a gate and a source of each of the transistors Q44 and Q45 becomes approximately 0.7 V. Thus, the transistors Q44 and Q45 are turned off, so that the potential of the node N13 is pulled up to 5 V.
When the size of a memory cell is decreased as the semiconductor memory device is made finer and the integration density thereof is increased, a current (cell current) flowing through the memory cell is reduced. In order to detect this reduced cell current, the sensitivity of the current detecting type sense amplifier must be increased. However, when the size of a load transistor, (for example, the transistor Q42 shown in FIG. 7) in the sense amplifier is decreased in order to increase the sensitivity of the sense amplifier, the access time is delayed, so that the reading operation is not speeded up.
On the other hand, Japanese Patent Laying-Open Gazette No. 73300/1986 discloses a semiconductor memory device using a differential amplifier circuit. In this semiconductor memory device, a pair of bit lines 51 and 52 are connected to both sides of a differential amplifier circuit 59, as shown in FIG. 8. A plurality of memory cells 55A (only one memory cell is illustrated in FIG. 8) and one dummy cell 58A are connected to the bit line 51, and a plurality of memory cells 55B (only one memory cell is illustrated in FIG. 8) and one dummy cell 58B are connected to the bit line 52.
At the time of the reading operation, the bit lines 1 and 52 are charged to a power-supply potential V.sub.DD When one of the memory cells 55A connected to the bit line 1 is selected, the dummy cell 58B connected to the bit line 52 is simultaneously selected. Consequently, if data "1" is stored in the selected memory cell 55A, a potential on the bit line 51 remains at the power-supply potential V.sub.DD. On the contrary, if data "0" is stored in the selected memory cell 55A, the bit line 51 is discharged to a ground potential. On the other hand, respective conductances of the dummy cells 58A and 58B are set smaller than those of the memory cells 55A and 55B storing data "0" and larger than those of the memory cells 55A and 55B storing data "1". Thus, when the dummy cell 58B is selected, the bit line 52 is discharged. The change in potential on the bit line 52 becomes gentler than that appearing when data "0" is read out to the bit line 51. Consequently, a potential difference appears between the bit lines 51 and 52. This potential difference is differentially amplified by the differential amplifier circuit 59.
In this semiconductor memory device, since the current detecting type sense amplifier is not employed unlike the conventional flush EEPROM shown in FIGS. 1 and 2, the above described problems do not occur.
However, in the semiconductor memory device shown in FIG. 8, the respective conductances of the dummy cells 58A and 58B must be set to one-half of the respective conductances of the memory cells 55A and 55B. Such setting of parameters of the dummy cells 58A and 58B involves difficulty in manufacturing techniques.
Furthermore, in the semiconductor memory device shown in FIG. 8, one differential amplifier circuit 59 is provided for each pair of bit lines 51 and 52. Therefore, when a pitch between the bit lines is decreased as the semiconductor memory device is made finer and the integration density thereof is increased, a space becomes small in which the differential amplifier circuit 59 is arranged, so that the layout becomes difficult.
Additionally, in the semiconductor memory device shown in FIG. 8, the bit lines 51 and 52 are precharged to the power-supply potential V.sub.DD (about 5 V) before reading out data. Consequently, the power-supply potential V.sub.DD is applied to respective drains of the memory cells 55A and 55B, so that the potential difference between a floating gate storing electrons and the drains is increased. As a result, electrons are liable to be emitted from the floating gate to the drains by the tunnel phenomenon, whereby data holding characteristics of the memory cells 55A and 55B ar liable to be adversely affected.

Semiconductor memory device having reading operation of information by differential amplification