For use with a top drive power unit supported for connection with a well string in a well bore to selectively impart longitudinal and/or rotational movement to the well string, a feeder for supplying a pumpable substance such as cement and the like from an external supply source to the interior of the well string in the well bore without first discharging it through the top drive power unit including a mandrel extending through a sleeve which is sealably and rotatably supported thereon for relative rotation between the sleeve and mandrel. The mandrel and sleeve have flow passages for communicating the pumpable substance from an external source to discharge through the sleeve and mandrel and into the interior of the well string below the top drive power unit. The unit can include a packing injection system, clamp, and novel packing configuration.

In top drive rigs, the use of a top drive unit, or top drive power unit is employed to rotate drill pipe, or well string in a well bore. Top drive rigs can include spaced guide rails and a drive frame movable along the guide rails and guiding the top drive power unit. The travelling block supports the drive frame through a hook and swivel, and the driving block is used to lower or raise the drive frame along the guide rails. For rotating the drill or well string, the top drive power unit includes a motor connected by gear means with a rotatable member both of which are supported by the drive frame.
During drilling operations, when it is desired to "trip" the drill pipe or well string into or out of the well bore, the drive frame can be lowered or raised. Additionally, during servicing operations, the drill string can be moved longitudinally into or out of the well bore.
The stem of the swivel communicates with the upper end of the rotatable member of the power unit in a manner well known to those skilled in the art for supplying fluid, such as a drilling fluid or mud, through the top drive unit and into the drill or work string. The swivel allows drilling fluid to pass through and be supplied to the drill or well string connected to the lower end of the rotatable member of the top drive power unit as the drill string is rotated and/or moved up and down.
Top drive rigs also can include elevators are secured to and suspended from the frame, the elevators being employed when it is desired to lower joints of drill string into the well bore, or remove such joints from the well bore.
At various times top drive operations, beyond drilling fluid, require various substances to be pumped downhole, such as cement, chemicals, epoxy resins, or the like. In many cases it is desirable to supply such substances at the same time as the top drive unit is rotating and/or moving the drill or well string up and/or down, but bypassing the top drive's power unit so that the substances do not damage/impair the unit. Additionally, it is desirable to supply such substances without interfering with and/or intermittently stopping longitudinal and/or rotational movement by the top drive unit of the drill or well string.
A need exists for a device facilitating insertion of various substances downhole through the drill or well string, bypassing the top drive unit, while at the same time allowing the top drive unit to rotate and/or move the drill or well string.
One example includes cementing a string of well bore casing. In some casing operations it is considered good practice to rotate the string of casing when it is being cemented in the wellbore. Such rotation is believed to facilitate better cement distribution and spread inside the annular space between the casing's exterior and interior of the well bore. In such operations the top drive unit can be used to both support and continuously rotate/intermittently reciprocate the string of casing while cement is pumped down the string's interior. During this time it is desirable to by-pass the top drive unit to avoid possible damage to any of its portions or components.
The following U.S. patents are incorporated herein by reference: U.S. Pat. No. 4,722,389.
While certain novel features of this invention shown and described below are pointed out in the annexed claims, the invention is not intended to be limited to the details specified, since a person of ordinary skill in the relevant art will understand that various omissions, modifications, substitutions and changes in the forms and details of the device illustrated and in its operation may be made without departing in any way from the spirit of the present invention. No feature of the invention is critical or essential unless it is expressly stated as being "critical" or "essential."


A protection element comprises a ring-shape gate electrode, an N+ drain region inside the ring-shape gate electrode, an N+ source region outside, and a shield plate electrode. The ring gate and source regions are connected to ground via a through-hole, and the drain region is connected to an external pad. The shield plate electrode is connected to ground or to a power supply. Element isolation is achieved by the shield plate electrode, without forming a LOCOS or other element isolation oxide layer. By this means, blocking of thermal conduction by an oxide layer can be avoided to improve the heat dissipation and ESD resistance of the protection element.

1. Field of the Invention
This invention relates to a semiconductor circuit device and, more particularly, to a semiconductor circuit device comprising a protection element to protect the circuit from ESD and so on.
2. Description of a Related Art
In a semiconductor circuit device, it is necessary to electrically isolate each element in order that no electrical interference occurs between the plurality of elements formed on the substrate or within the substrate. There are increasingly strict demands for semiconductor circuit devices with higher integration levels, greater functionality, faster speed, and lower power consumption, and various element isolation techniques have been proposed in the past. One of the most representative element isolation methods is the LOCOS (LOCal Oxidation of Silicon) structure. In the LOCOS method, elements are isolated by forming a thermal oxide layer between elements on the substrate, using a nitride film as a mask. By performing such oxidation, the oxidation progresses toward the silicon substrate interior, and a buried oxide layer (LOCOS) is formed.
The STI (Shallow Trench Isolation) method is known as another element isolation technique. In the STI method, a groove or trench is formed in silicon by dry etching, and after filling the trench with SiO2, CMP (Chemical Mechanical Polishing) is used to remove SiO2 formed outside the trench. An isolation structure is thereby formed in which a flat oxide layer is buried only in the trench. Compared with a LOCOS structure, STI makes possible smaller isolation widths, thus greatly contributing to higher device densities.
The SOI (Silicon On Insulator) structure is known as an isolation technique which includes the substrate itself. A SOI structure comprises a device formed in a silicon thin film (SOI layer) on an insulating layer. In a bulk CMOS device, a P/N-type MOS transistor is isolated by a well layer; but an SOI-MOS device is isolated by the Si supporting substrate and a buried oxide layer, as shown in FIG. 8. A device in which the SOI layer is made thin and the body area below the channel is completely depleted is called a fully depleted SOI device; a device having an area which is not depleted to the bottom of the body area is called a partially depleted SOI device. FIG. 8 shows one example of the structure of a partially depleted SOI device. In this structure, each element is isolated by, for example, a LOCOS oxide layer, and the operating area (SOI layer) is completely isolated by an insulator.
The SOI structure is effective for solving problems such as latch-up and parasitic junction capacitance, and greatly contributes to increases in device density and speed and to reduced power consumption. However, the buried oxide layer causes some problems. While the buried oxide layer provides electrical isolation, it also impedes thermal conduction, greatly reducing heat dissipation. This effect cannot be ignored, particularly for elements with high current densities.
An NMOS device with the gate connected to ground (GGNMOS, Gate-Grounded NMOS) is known as a protective element which prevents internal breakdown in a circuit due to ESD (Electro-Static Discharge). ESD gives rise to a surge voltage pulse between an external connection pad and the internal circuit due to contact of the semiconductor circuit device with, for example, human skin or equipment. A GGNMOS element prevents application of a surge voltage to a gate electrode of the internal circuit by passing a current between the external pad and the ground line as a result of breakdown between source and drain. In the SOI structure of a protective element, there is the problem that thermal conduction is impeded by the buried oxide layer, so that the temperature of the ESD protective element rises sharply due to the surge current, and the ESD withstand voltage of the ESD protection element itself is reduced.
Consequently, proposals have been made to resolve the heat dissipation problems of SOI elements (see for example U.S. Pat. No. 6,352,882). Polysilicon plugs penetrating the buried oxide layer are formed on the substrate, connecting the MOSFET device region with the silicon substrate of an opposite polarity type. The polysilicon plugs are in contact with the MOSFET device source or drain, and comprise the function of diffusing positive or negative ESD. At the same time, the polysilicon plugs comprise the function of diffusing heat, and can prevent thermal breakdown of the element. However, such a structure has the problem of involving complicated manufacturing processes.
On the other hand, a shield plate isolation method is known as a technique for electrically isolating elements (see for example Japanese Unexamined Patent Application Publication No. 11-126899). This technique provides, for example, an oxide layer and a shield plate electrode so as to surround the element. By applying a reverse bias voltage to the shield plate, extension of the depletion layer outside the region surrounded by the shield plate electrode is prevented, and electrical isolation of elements is achieved.
However, such shield plate electrodes have not been studied from the standpoint of thermal problems on an SOI substrate (or in SOI elements). In particular, the problem of thermal breakdown in elements used for input protection, and their relation to shield plate electrodes, have not received any study. Further, the devices disclosed in the above references comprise straight gate electrodes intersecting with the shield plate electrode; there is a considerable possibility that this intersection portion may also constitute a major problem with respect to ESD. Or, because the diffusion layer connected to the external terminal is isolated by the shield plate electrode, the discharge path cross-sectional area is small, and the amount of ESD is small.
In a transistor used as a protection element, in order to render uniform the current distribution, a gate electrode structure comprising a waffle-shape pattern layout has been proposed (see for example Japanese Unexamined Patent Application Publication No. 6-112482). By means of a waffle-shape pattern gate electrode, the current density of the breakdown current flowing between source and drain is made uniform, so that the electrostatic breakdown intensity of the protection element can be enhanced. However, the problems of such gate electrode structures and of drops in electrostatic resistance due to heat of the protection element have not yet received any study.

Semiconductor circuit device including a protection circuit


A method is disclosed. The method includes one or more light field cameras recording image data of a substrate during printing to the substrate and a control unit processing the image data received from the one or more light field cameras to identify defect areas in the substrate.

In the high speed print production systems, relatively small variations in substrate (e.g., paper) web alignment, paper movement and surface contour can be critical. The same can be said for a print verification system (PVS) that verifies the print on the back-end of a print production system.
Predictable operations and final quality are affected by attributes such as proper web tension, paper to ink-jet head gap, localized deformity (e.g., cockle), flutter and other mechanical anomalies that affect paper. Various means are currently in use to control and detect these aspects of the print or PVS system. Nonetheless, these mechanisms are static (e.g., tension gauge) or limit sensing (e.g., light beam make/break). The nature of the (paper) web, however, is such that simple edge or threshold sensing is insufficient.
Accordingly, an improved detection mechanism is desired.


This invention relates to a lockup structure of mobile hard drive, and comprises a base plate for receiving a hard drive, a lock member having a block sheet, a base frame having a through hole for mounting the lock member, and a spiral arm. At a free end of the spiral arm comprises a protruding block for locating into the base plate and a notch for positioning the block sheet of the lock member, and at a fixing end comprises a position block mounted into a shell. Thus, when in locking position, the spiral arm cannot be pushed outwardly and the position block can prevent the base plate from withdrawing from the shell, therefore, a wrong withdrawal will be avoided.

1. Field of the Invention
The present invention relates to a lockup structure of mobile hard drive, particularly to the lock member and the spiral arm are assembled at two sides of the base plate, as the spiral arm is in locking position, the notch at the free end of the spiral arm is used for position the block sheet of the lock member, and the position block at fixing end of the spiral arm is located in the fixed slot of the shell to get positioned and prevent a wrong withdrawal.
2. Description of the Related Art
Following to the advancement and popularity of computer technology, computers have entered into our daily life. The great development of computer industry has resulted in types of functions of computer, furthermore, along with broad application of computers, a lot of data such as personnel photo, bank accounts, password or database, R&D data and commercial secrets of company are stored in the hard drive of the computers. In case of the computer is attacked by virus and damaged by people, data stored in the computer would be destroyed, thus, the data saved in the computer have to backup.
However, due to large quantity of data and small capacity of the portable USB disk, so that it is impossible to backup data saved in the hard drive. Although the built-in hard drive has enough capacity to backup the data, however, it is difficult to disassemble quickly and is also inconvenient to carry with after disassembly, thus, some manufacturers developed the mobile hard drive.
Referring to FIG. 9, a chamber A1 is made in an external shell A, and a open A11 is set at one side of the chamber A1. Meanwhile, a mobile device B can be mounted in the chamber A1. The mobile device B comprises a rotating and displacing handle B1 at front side thereof, furthermore, a hard drive B2 is installed in the mobile device B, and a connection port B3 at rear side of the mobile device B for connecting with hard drive B2 to transform different types of connection interfaces for hard drive B2. Therefore, the mobile device B can be used for disengaging the hard drive B2 from the external shell A quickly.
Although the mobile hard drive is characterized by quick installation and easy disengagement, however, as the mobile hard drive is inserted into the computer, if the user bumps or disengages accidentally, or while transporting, the hard drive may be drop off since the mobile hard drive is not fixed in the external shell. Therefore, how to overcome the above disadvantages of the mobile hard drive is the objective of the relevant manufacturers.


A method for forming an integrated circuit (IC) is presented. The method includes providing a wafer having a substrate prepared with a photoresist layer. The photoresist layer is processed by passing a radiation from an exposure source of a lithography tool through a mask having a pattern. The process parameters of the lithography tool are determined by performing a pattern matching process. The photoresist layer is developed to transfer the pattern on the mask to the photoresist layer.

Lithographic best condition, such as best focus or best energy, is generally determined by Focus Exposure Matrix (FEM) approach. However, the analysis of FEM (Bossung Curve to ED-windows) requires complicated software code. Thus, extracting the best focus and exposure settings of a lithography tool requires purchase of expensive software to perform automated FEM analysis. Moreover, this solution is difficult to be integrated into inline Statistical Process Control (SPC) or Automated Process Control (APC) system.
From the foregoing discussion, it is desirable to provide a simplified and cost saving method to determine the process condition of a lithography tool. It is also desirable to provide a method to determine the process condition of a lithography tool which can be integrated into inline SPC or APC system.

Determination of lithography tool process condition


A method of monitoring cardiac dysfunction, such as pericardial effusion, is disclosed. The method uses an indwelling probe inserted within a coronary sinus or a chamber or vessel of the heart, the probe having motion sensing means configured to sense motion of the probe based on movement of the wall of the coronary sinus or other chamber or vessel. Data is obtained from the motion sensing means and processed to monitor for cardiac dysfunction. The monitoring can be in real-time and can utilise one or more three-axis accelerometers. In some embodiments, two or more three-axis accelerometers are spaced longitudinally along an elongate body of the probe, which can increase accuracy and reliability of monitoring.

Monitoring of cardiac wall motion is important in many clinical cardiac procedures. As the number and complexity of percutaneous intracardiac procedures continues to increase and a variety of new technologies for structural heart disease and electrophysiology interventions are introduced, the risk of periprocedural injury to the heart also increases. Many of these procedures have in common the need for intraprocedural anticoagulation and a number require transseptal puncture to access the heart.
Percutaneous based catheterisation is the most rapidly growing technique in the field of interventional cardiology for diagnosing and treating diseases in the heart. Perforation or full-thickness injury of the heart wall during catheterisation procedures occurs at a rate of approximately 1 to 6% clinically depending on the aetiology and complexity of the procedure. This often leads to pericardial effusion, which involves the ejection of blood or fluid from within the perforated (or injured) cardiac chamber into the pericardial space, and more seriously cardiac tamponade, which is the crushing of the heart due to an accumulation of blood or fluid in the pericardial space, thus preventing the heart from beating. Both conditions lead to a loss of contractile function of the heart wall.
Monitoring cardiac function is also desirable for coronary intervention procedures. Coronary intervention is a procedure which aims to restore blood flow to an occluded artery of the heart via intravascular deployment of a balloon designed to distend the artery or deploy a stent. The act of ballooning in coronary interventions temporarily causes cardiac ischemia (lack of oxygen due to interrupted coronary blood flow). This may lead to impaired cardiac function, such as loss of contractility of the heart wall, and could contribute to sudden cardiac death.
Monitoring cardiac function may also be desirable for cardiac ablation procedures. It is well recognised that blood volume pressure of the heart may increase due to the overload of physiological normal saline (irrigation) during cardiac ablation procedures. The increased blood volume pressure can have adverse effects on cardiac wall motion, leading to complications during the procedure.
In the electrophysiology setting, an increased risk of pericardial effusion may be associated with intracardiac or epicardial arrhythmia ablations of any chamber of the heart, placement of biventricular pacemakers, and implantable cardioverter-defibrillators.
Implantable cardioverter-defibrillators (ICDs) or pacemakers are often implanted in patients at risk of cardiac arrhythmias or to enable cardiac rate control (pacing) in patients with cardiac dysfunction. The modality of treatment by such devices is achieved by electrical stimulation of the heart muscle via an electrode imbedded within the heart wall. Under certain situations, cardiac electrical stimulation by such devices may be ineffective when physiological changes to the heart occur, such as ischemia or heart failure, which may result in loss of contractile function of the heart wall and may lead to potentially life threatening circumstances. As such, effective delivery of therapy from ICDs or pacemakers depends upon accurate measurement of intrinsic cardiac activity.
Current methods used to monitor cardiac activity, particularly pericardial effusion and cardiac tamponade, involve hemodynamic monitoring (blood pressure measurement), echocardiographic assessment, and fluoroscopic assessment. Hemodynamic assessment, which is often performed continuously in cardiac procedures, has low sensitivity to early changes in cardiac contractility. Current imaging modalities involving x-ray and ultrasound are also limited as they are often utilised reactively to hemodynamic compromise and not proactively.
Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each claim of this application.

Methods and apparatuses for monitoring cardiac dysfunction


In a conventional DRAM, a decrease in the capacitance of a capacitor causes an error in reading data. A plurality of memory blocks MB is connected to one bit line BL_m. Each memory block MB includes a sub bit line SBL, a plurality of memory cells, and a precharge transistor. The drain of a transistor of the memory cell is connected one of the bit line BL_m and the sub bit line SBL, whereas a capacitor of the memory cell is connected to the other one of the bit line BL_m and the sub bit line SBL. The capacitance of the sub bit line SBL is sufficiently low; thus, a potential change due to electric charges of the capacitor of the memory cell can be amplified by an amplifier circuit AMP without an error and the amplified signal can be output to the bit line.

1. Field of the Invention
The present invention relates to a memory device using a semiconductor.
2. Description of the Related Art
Terms used in this specification will be briefly explained. First, when one of a source and a drain of a transistor is called a drain, the other is called a source in this specification. That is, they are not distinguished depending on the potential level. Therefore, a portion called a source in this specification can be alternatively referred to as a drain.
In this specification, "connection" means a structure in which effective direct current can be supplied at least temporarily. Therefore, a state of connection means not only a state of direct connection but also a state of indirect connection through a circuit element such as a wiring or a resistor, in which direct current can be supplied. It does not matter whether a circuit is actually designed so that direct current is supplied thereto.
For example, in the case where a switching element is provided between two nodes, direct current can be supplied in a certain condition (i.e., only when the switch is on); therefore, the structure can be expressed as "the nodes are connected to each other". On the other hand, in the case where only a capacitor is provided between two nodes, effective direct current cannot be supplied through the capacitor; therefore, the structure can be expressed as "the nodes are not connected to each other".
Similarly, in the case where only a diode is provided between nodes, direct current can be supplied when the potential of one of the nodes is higher; therefore, the structure can be expressed as "the nodes are connected to each other". In this case, even if potentials with which current does not flow are supplied to the two nodes because of the circuit design (in which case current does not actually flow between the two nodes through the diode), the structure is expressed as "the nodes are connected to each other" in this specification.
For example, in the case where a node A is in contact with a source of a transistor and a node B is in contact with a drain of the transistor, direct current can flow between the node A and the node B depending on the potential of a gate; thus, the structure is expressed as "the node A and the node B are connected to each other".
On the other hand, in the case where the node A is in contact with the source of the transistor and a node C is in contact with the gate of the transistor, effective direct current cannot flow between the node A and the node C regardless of the potentials of the source, drain, and gate of the transistor; thus, the structure is expressed as "the node A and the node C are not connected to each other".
In the above description, effective direct current refers to current excluding unintentional current such as leakage current. Note that the value of effective direct current is not defined by its amount (absolute value) and sometimes depends on circuits. That is, in some cases, a low current of 1 pA can be effective current in one circuit, whereas a higher current of 1 μA is not considered as effective current in another circuit.
Needless to say, in one circuit having an input and an output (e.g., an inverter), the input and the output are not necessarily connected to each other. Using the inverter as an example, the input and the output are not connected to each other in the inverter.
When the term "connect" is used in this specification, there is a case in which a physical connection is not clear in an actual circuit and a wiring is only extended. For example, in a circuit composed of insulated-gate field-effect transistors (hereinafter simply referred to as transistors), one wiring serves as gates of a plurality of transistors in some cases. In this case, one wiring that branches into gates may be illustrated in a circuit diagram. In this specification, the expression "a wiring is connected to a gate" may be used even in such a case.
Further, in this specification, in referring to a specific row, column, or position in a matrix, a reference sign is accompanied by a sign denoting coordinates as follows, for example: "precharge transistor PTr_n_m", "bit line BL_m" and "sub bit line SBL_n_m". When one element has a function relating to a plurality of rows or columns, the element may be represented by, for example, "amplifier circuit AMP_n/n+1_m".
On the other hand, when the row, column, or location of a component is not specified, when components are collectively treated, or when the location of a component is obvious, the following expressions may be used, for example: "precharge transistor PTr", "bit line BL", and "sub bit line SBL", or simply "precharge transistor", "bit line", and "sub bit line".
A DRAM whose memory cell includes one transistor and one capacitor can be highly integrated, has no limit on the number of write cycles in principle, and can perform write and read operations at relatively high speed; thus, such a DRAM is used in many kinds of electronic devices. In a DRAM, data is stored by accumulating electric charges in a capacitor of each memory cell and is read by releasing the electric charges to a bit line and amplifying a small potential change of the bit line (see Patent Document 1).
Capacitance (parasitic capacitance) exists between adjacent bit lines and between a bit line and a wiring (a word line and the like) intersecting with each other. The capacitance of the bit line is usually much higher than that of a capacitor. If the capacitance of the bit line is extremely higher than that of the capacitor, a potential change of the bit line when the electric charges accumulated in the capacitor is released to the bit line becomes extremely small, causing an error in amplifying a potential difference between the bit line and a reference potential. Accordingly, the capacitance of the capacitor is desirably 10% or higher of the capacitance of the bit line.
A capacitor in a miniaturized DRAM is formed to have a trench with a depth of as much as several micrometers or a stack with a height of as much as several micrometers, which increases difficulties in processing. Thus, it is necessary to reduce memory capacitance. Accordingly, an increase in the off-state resistance of a transistor of a memory cell has been suggested (see Patent Documents 2 and 3); at the same time, an error due to a decrease in the capacitance of a capacitor, described above, needs to be avoided.
Further, by miniaturization of a DRAM, variations in threshold voltages among transistors are increased. This is due to statistical fluctuation of dopant concentration. In a DRAM, a small potential change due to electric charges released from a capacitor of a memory cell to a bit line is amplified by a sense amplifier; however, when variations in threshold voltages among transistors included in the sense amplifier are increased, an error occurs at the time of amplification. The potential change of the bit line needs to be large so that the error is avoided.
To reduce power consumption and suppress short channel effect, a power supply voltage tends to be reduced; however, a potential change of a bit line at the time of reading is reduced by half if voltage for writing becomes half. On the other hand, there is also a problem in that reading accuracy is decreased with the reduction in power supply voltage since the lower limit of the potential change which can be amplified is almost fixed.
In order to solve these problems, a method is proposed in which bit lines are provided with sub bit lines and a sense amplifier of a flip-flop circuit type is connected to each of the sub bit lines so that data is read by comparison of the capacitance between the sub bit line and the capacitor (see Patent Document 4).
However, the semiconductor memory device disclosed in Patent Document 4 is applicable to folded-bit-line DRAMs, but not applicable to open-bit-line DRAMs, which are more highly integrated. In fact, the semiconductor memory device disclosed in Patent Document 4 has a problem in the degree of integration when being applied to a highly integrated device.
The sense amplifier of a flip-flop circuit type is apt to fail to work properly when the capacitance of the sub bit line is low. In general, the potential of an object with a low capacitance greatly changes because of effects of noise. A conventional DRAM has a capacitance of bit line of several hundred femtofarads; based on the simplest assumption, when the capacitance of sub bit line is several femtofarads, a potential change due to noise is increased a hundredfold.
In the sense amplifier of a flip-flop circuit type, a small potential difference of about 0.1 V is amplified in an early stage of amplification. In this case, when a potential change other than by signals becomes 0.1 V or higher, an error occurs. For example, in a conventional DRAM, the capacitance of a bit line (or a sub bit line) is high, so that a potential change other than by signals can be 1 mV; however, if the capacitance of the bit line (or the sub bit line) (plus the capacitance of one capacitor) is one hundredth or less of that in the conventional DRAM, the potential change other than by signals is 0.1 V or more.
In other words, in the semiconductor memory device disclosed in Patent Document 4, an error at the time of reading is apt to occur when the capacitance of the sub bit line is greatly reduced. In the semiconductor memory device disclosed in Patent Document 1, an extremely high off-state resistance of a transistor is not expected and the capacitance of the sub bit line and the capacitance of one capacitor are expected to be as high as several hundreds of femtofarads or more and as high as several tens of femtofarads or more, respectively; therefore, Patent Document 1 does not disclose any solution to the case where the capacitance of the capacitor is several ten of femtofarads or lower, for example.

Semiconductor memory device including amplifier circuit

Semiconductor Energy Laboratory Co., Ltd.


The present invention relates to improvements in therapy and prevention of conditions characterized by an elevated level of eosinophil leukocytes, i.e. conditions such as asthma and other chronic allergic diseases. A method is provided for down-regulating interleukin 5 (IL5) by enabling the production of antibodies against IL5 thereby reducing the level of activity of eosinophils. The invention also provides for methods of producing modified IL5 useful in this method as well as for the modified IL5 as such. Also encompassed by the present invention are nucleic acid fragments encoding modified IL5 as well as vectors incorporating these nucleic acid fragments and host cells and cell lines transformed therewith. The invention also provides for a method for the identification of IL5 analogues which are useful in the method of the invention as well as for compositions comprising modified IL5 or comprising nucleic acids encoding the IL5 analogues. The preferred embodiment of the present invention entails the use of variants of IL5, where foreign T helper epitopes are introduced so as to induce production of cross-reactive antibodies capable of binding to autologous IL5.

The present invention relates to improvements in therapy and prevention of conditions characterized by an elevated level of eosinophil leukocytes, i.e. conditions such as asthma and other chronic allergic diseases. More specifically, the present invention provides a method for down-regulating interleukin 5 (IL5) by enabling the production of antibodies against IL5 thereby reducing the level of activity of eosinophils. The invention also provides for methods of producing modified IL5 useful in this method as well as for the modified IL5 as such. Also encompassed by the present invention are nucleic acid fragments encoding modified IL5 as well as vectors incorporating these nucleic acid fragments and host cells and cell lines transformed therewith. The invention also provides for a method for the identification of IL5 analogues which are useful in the method of the invention as well as for compositions comprising modified IL5 or comprising nucleic acids encoding the IL5 analogues.
Asthma is a common disease of the airways, affecting about 10% of the population. The present treatments is primarily based on the administration of steroids and represents a market value exceeding well over a billion dollars. For yet unknown reasons the incidence and morbidity of asthmatics have increased worldwide over the past two decades. Today, an improved understanding of the immunological mechanisms involved in asthmatic conditions combined with an explosive development in biotechnology provides a new basis for the development of alternative and perhaps better strategies for treatment.
A general feature in the pathogenesis of asthma and other chronic allergic diseases has proven to be elevated numbers of eosinophils, especially in the bronchial mucosa of the lungs. Upon activation eosinophils secrete a number of mediators that are actively involved in the inflammatory airway response. In the activation of eosinophils, interleukin 5 (IL5) plays an important role.
IL5 is a cytokine found in many mammalian species and among others both the human and the murine gene for IL5 have been cloned (Tanabe et al., 1987, Campbell et al., 1988). The human gene consists of four exons with three introns positioned at chromosome 5 and codes for a 134 amino acid residue precursor, including a 19 amino acid N-terminal leader sequence which has the amino acid sequence set forth in SEQ ID NO: 62. Posttranslational cleavage generates the mature 115 amino acid residue protein (SEQ ID NO: 1). The murine IL5 (mIL5) gene similarly codes for a 133 amino acid residue pre-cursor with a 20 amino acid leader sequence which has the amino acid sequence set forth in SEQ ID NO: 64. The processed mature mIL5 is thus 113 amino acid residues long (SEQ ID NO: 12), missing two N-terminal amino acid residues by alignment with human IL5. The amino acid sequences of hIL5 and mIL5 are 70% identical compared to 77% at nucleotide level of the coding regions (Azuma et al., 1986). Higher similarity was reported within human primates; 99% identity is reported for the coding regions of the human and the Rhesus monkey nucleotide sequences (Villinger et al., 1995).
The human amino acid sequence has two potential N-glycosylation sites and the murine three. Human IL5 has been shown to be both N-glycosylated as well as O-glycosylated at Thr 3. Studies of hIL5 has demonstrated that the glycosylation is not necessary for the biological activity even though the stability seems to be affected by de-glycosylation (Tominaga et al., 1990; Kodama et al., 1993).
Structure of IL5
The active IL5 is a homo-dimer and the 3-dimensional structure of recombinant hIL5 has been determined by X-ray crystallography (Milburn et al., 1993). The 2 monomers are organised in an antiparallel manner and covalently bound by two interchain disulfide bridges (44-87xe2x80x2 and 87-44xe2x80x2), thus engaging all 4 cysteines of the 2 monomers.
The secondary structure of the monomers consists of 4 xcex1-helices (A-D) intermitted by 3 linking regions (loops) including two short stretches of xcex2-sheets. This 4xcex1 helix bundle is known as the xe2x80x9ccommon cytokine foldxe2x80x9d, which has also been reported for IL-2, IL-4, GM-CSF, and M-CSF. But all these are monomers and the homodimer-structure in which the D-helix completes the 4xcex1 helix motif of the opposite monomer is unique to IL5.
The native monomers alone has been shown to be biologically inactive (for reviews see Callard and Gearing, 1994; Takutsu et al., 1997). It is nevertheless possible to produce a modified recombinant biologically active monomer by inserting 8 additional amino acid residues in loop 3, connecting the helices C and D. This enables helix D to complete the 4 helix structure within one polypeptide chain and thus enable the monomer to interact with its receptor (Dickason and Huston, 1996; Dickason et al., 1996).
The IL5 receptor is primarily present on eosinophils and it is composed of an xcex1-chain and a xcex2-chain. The xcex1-chain of the receptor is specific for IL5 and the xcex2-chain, which assure high-affinity binding and signal transduction, is shared with the hetero-dimer receptors for IL-3 and GM-CSF. The sharing of a receptor component could be the reason for the cross-competition seen between IL5, IL-3 and GM-CSF (for review, see Lopez et al., 1992). However, it was recently demonstrated that the regulation of the IL5R is distinct from the regulation of the IL-3R and the GM-CSFR, further indicating a highly specialised role of IL5 in the regulation of the eosinophilic response (Wang et al., 1998).
The C-terminal part of IL5 seems to be important in both binding to the IL5R and for the biological activity, since removal of more than two C-terminal amino acid residues results in a decline in both the binding affinity to the IL5 R and in the biological activity in an IL5 bioassay (Proudfoot et al., 1996). Other residues have also been found to be important for binding to the receptor, such as Glu12, which is involved in binding to the xcex2-chain, while the Arg90 and Glu109 residues are involved in the binding to the xcex1-chain of the receptor. In general, binding to the IL5R seems to occur in regions overlapping helices A and D, where helix D is primarily responsible for the binding to the specific IL5R xcex1-chain (Graber et al., 1995; Takastsu et al., 1997).
IL5""s Homology to Other Proteins
The two 4-helix domain motifs seen in the homodimer has strikingly similar secondary and tertiary structure as compared to the cytokine fold found in GM-CSF and M-CSF, IL-2, IL-4 and human and porcine growth hormone (Milburn et al., 1993). However, even though striking similarities are also observed in the intron/exon organisation and position of cysteines (Tanabe et al., 1987; Cambell et al., 1988) suggesting a phylogenetic relationship with IL-2, IL-4 and GM-CSF, no significant homology with any of these or other cytokines is observed from the amino acid sequence.
Biological Activity of IL5
IL5 is mainly secreted by fully differentiated Th2 cells, mast cells and eosinophils (Cousins et al., 1994; Takutsu et al., 1997). It has been shown to act on eosinophils, basophiles, cytotoxic T lymphocytes and on murine B cells (Callard and Gearing, 1994; Takutsu et al., 1997). The effects of IL5 on human cells are still a matter of controversy. Augmentation of immunoglobulin synthesis under certain circumstances and binding to a variety of human B cell lines have been demonstrated. Even though mRNA for the hIL5R has been found in human B-cells, the actual presence of the receptor on these cells has still to be verified (Baumann and Paul, 1997; Huston et al., 1996).
The actions of IL5 on eosinophils include chemotaxis, enhanced adhesion to endothelial cells, activation and terminal differentiation of the cells. Furthermore it has been demonstrated that IL5 prevents mature eosinophils from apoptosis (Yamaguchi et al., 1991). These findings have contributed to the present concept of IL5 as being the most important cytokine for eosinophil differentiation (Corrigan and Kay, 1996; Karlen et al., 1998).
Physiologically, IL5 and its associated eosinophil activation is considered to serve a protective role against helminthic infections and possibly against certain tumours, since these diseases are typically accompanied by peripheral blood eosinophilia (Takutsu et al., 1997; Sanderson et al., 1992). It is, however, somewhat speculative as in two studies the authors failed to show any effect beside eosinophil down-regulating following administration of antibodies against IL5 on the immunity (e.g. IgE levels) against Nippostrongylus braziliensis or Schistosoma mansoni in mice infected with these parasites (Sher et al., 1990; Coffman et al., 1989).
IL5 Transgenic and xe2x80x9cKnock-outxe2x80x9d Animals
Studies of transgenic mice expressing IL5 or knock-out mice deficient for IL5 have given further knowledge of the physiological role of IL5.
Several IL5 transgenic mice have been reported:
A transgenic mouse expressing the IL5 gene in T cells was reported to have an increased white blood cell level characterised by expansion of B220+ B lymphocytes and profound eosinophilia. This was accompanied by a massive peritoneal cavity cell exudate dominated by eosinophils and infiltration of eosinophils in nearly all organ systems (Lee et al., 1997a).
Another transgenic mouse, expressing the IL5 gene under control of a metallothionin promoter was characterised by an increase in the serum levels of IgM and IgA, a massive eosinophilia in peripheral blood and many other organs accompanied by the expansion of a distinctive CD5+ B cell population, which produce auto-antibodies (Tominaga et al., 1991).
A third study involved a transgenic mouse constitutively expressing IL5 in the lungs. These animals developed pathophysiological changes resembling those of human asthma, including eosinophil invasion of peribronchial spaces, epithelial hypertrophy and increased mucus production. Furthermore, development of airway hyper responsiveness was seen in the absence of antigens (Lee et al., 1997b).
IL5-deficient mice (xe2x80x98knock-outxe2x80x99 mice) have also been studied. These mice (C57BL/6) have no obvious signs of disease and are fertile. The immunoglobulin levels and the specific antibody responses to DNP-OVA were normal. Basal levels of eosinophils are produced, but are 2-3 times lower than in control animals, indicating that eosinophils can be produced in the complete absence of IL5. When these mice were infected with Mesocestoides corti the eosinophilia normally seen was abolished and this absence of eosinophilia did not affect the worm burden produced by this parasite (Kopf et al., 1996).
In a study by Foster et al. (1996), the effect of IL5 knock-out on a common model of atopic airway inflammation was investigated. Sensitisation and aerosol challenge of mice with ovalbumin normally result in airway eosinophilia, airway hyperreactivity to xcex2-methacholin and extensive lung damage analogous to that seen in asthma. In the IL5 deficient mice the eosinophilia, airway hyperreactivity and lung damage were abolished. When IL5 expression in these mice was reconstituted, the aero-allergen induced eosinophilia and airway dysfunction were restored.
Pathophysiologic Role of IL5
Asthma affect about 10% of the population worldwide and for yet unknown reasons the incidence and morbidity have increased over the past two decades (Ortega and Busse, 1997). It is a chronic airway disease characterised by recurrent and usually reversible air flow obstruction, inflammation and hyper responsiveness (Moxam and Costello, 1990). This produces symptoms of wheezing and breathlessness, which in severe cases can be fatal.
The animal experiments referred to above using transgenic mice constitutively expressing IL5 in the lungs (Lee et al., 1997a) and the IL5 deficient xe2x80x9cknock-outxe2x80x9d mice (Foster et al., 1996) strongly implicate a crucial role of IL5 in the pathogenesis of asthma. Further evidence supporting this can be deduced from several studies including asthmatic individuals.
Eosinophilia has been identified in bronchoalveolar lavage (BAL) fluid and in bronchial mucosal biopsies of subjects with asthma and correlates with disease severity. Several eosinophil products have been identified in the BAL fluid of patients with asthma and numbers of peripheral blood eosinophils correlate with asthma severity (Ortega and Busse 1997).
IL5 serum concentration was found to be elevated (median concentration 150 pg/ml) in 15 out of 29 patients with chronic severe asthma as compared to control subjects (Alexander et al., 1994).
In another study involving both non-atopic and atopic asthmatics, it was found that an enhanced IL5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and non-atopic asthma (Mori et al., 1997).
Other results also indicate that IL5 has a distinct role in other atopic diseases. Allergen induced systemic episodes in individuals with allergic rhinitis has recently been shown to correlate to allergen induced IL5 synthesis rather than IgE (Ohashi et al., 1998). The correlation of atopic reactions is also demonstrated in a study by Barata et al. (1998) in which a significant expression of IL5 by T-cells in a cutaneous late phase reaction is demonstrated.
These and other results have led several authors as Corrigan and Kay (1996), Danzig and Cuss (1997) to identify and recommend IL5 as a primary target in the development of a better treatment for asthma and atopic diseases involving eosinophilic inflammation. Chronic tissue damaging hypereosinophilia induced by parasitic infection, topical pulmonary eosinophilia and hypereosinophilic syndrome are examples of other pathogenic conditions that could be addressed by IL5 down regulation.
In vivo Demonstration of the Role of IL5
In several studies with rodent models of asthma it has been shown that treatment with monoclonal antibodies against IL5 (anti-IL5 mAb) results in dose-related inhibition of eosinophilia, as compared to non-treated controls (Nagai et al., 1993a and b; Chand et al., 1992; Coeffier et al., 1994; Kung et al., 1995; Underwood et al., 1996). In the study by Nagai et al. (1993a) the effect was also observed by treating the sensitised Balb/c mice with soluble IL5 receptor xcex1.
In one study with Balb/c mice (Hamelmann et al., 1997) and four studies with guinea pigs it was additionally shown that anti-IL5 mAb could inhibit airway hyperreactivity elicited with various substances in antigen sensitised animals (Mauser et al., 1993; Akutsu et al., 1995; van Oosterhout et al., 1995 and 1993). In some of the studies beneficial effects (cf. table 1) of the anti-IL5 mAb treatment were also observed microscopically (Mauser et al., 1993; Akutsu et al., 1995; Kung et al., 1995). Importantly, in the study by Kung et al. (1995) a reduction of pulmonary inflammation in B6D2F1 mice was seen both when anti-IL5 mAb was administered hours before antigen challenge and also when administered up to five days after antigen challenge, indicating that the effect of anti-IL5 mAb may be both prophylactic and therapeutic for airway inflammation. This effect, however, was not observed by Underwood et al. when guinea pigs were given anti-IL5 mAb two hours after antigen challenge (Underwood et al., 1996).
In a study using a monkey model of asthma, Mauser et al. (1995) reported an inhibition of airway hyper reactivity after antigen challenge, when rat anti mouse-IL5 mAb was given 1 hour before antigen challenge. In addition, there was 75% reduction in the number of eosinophils in bronchoalveolar lavage (BAL) of antibody treated animals, as compared to non-treated controls. The effects on eosinophilia and hyperresponsiveness of anti-IL5 mAb was seen for up to three months after treatment (Mauser et al., 1995). Regarding allergic hyperresponsiveness, the results from studies by Nagai et al. (1993a and 1993b) document no reduction in hyperresponsiveness in conjunction to a reduction of eosinophil numbers in BAL.
All anti-IL5 mAb in vivo experiments mentioned so far have been done with rat-anti-mouse monoclonal antibodies. Egan et al. (1995) have reported experiments using humanised rat-anti-human IL5 monoclonal antibodies, called Sch 55700. These mAbs, inhibited lung lavage eosinophilia by 75% at a dose of 0,3 mg/kg when administered to sensitised monkeys. When Sch 55700 was given at 1 mg/kg in allergic mice, inhibition of airway eosinophilia was also observed.
Treatment of Asthma at Present and in the Future
The current treatment of asthma is, as mentioned, corticosteroids which, by their anti-inflammatory action, are the most powerful drugs. Besides this, xcex22 agonists and methyl xanthine derivatives which all cause bronchodilation, and disodium chromoglycate which xe2x80x98stabilisesxe2x80x99 mast cells, thereby preventing mediator release, all have proven beneficial in asthma patients (Ortega and Busse 1997).
Future treatment of asthma may as discussed above include anti-IL5 mAbs. Celltech in corporation with Schering Plough have anti-IL5 mAb in phase I clinical trial for treatment of asthma. However, treatment with monoclonal antibodies entails a number of drawbacks. First of all, the development and production costs for a safe mAB (e.g. a humanised mAB) are very high, resulting in an expensive therapeutic product for the end user. Second, mABs have the disadvantageous characteristic seen from a patient point of view that they have to be administered with relatively short intervals. Third, by nature mABs exhibit a narrow specificity against one single epitope of the antigen. And, finally, mABs (even humanised) are immunogenic, leading to an increasingly fast inactivation of administered antibodies as treatment progresses over time.
Also use of antisense IL5 oligonucleotides for antisense therapy has been suggested by the company Hybridon for the treatment of asthma, allergies and inflammation. However, the antisense technology has proven to be technically difficult and, in fact, conclusive evidence of the feasibility of antisense therapy in humans has not yet been established.
Finally, WO 97/45448 (Bresagen Limited/Medvet Science) proposes the use of xe2x80x9cmodified and variant forms of IL5 molecules capable of antagonising the activity of IL5xe2x80x9d in ameliorating, abating or otherwise reducing the aberrant effects caused by native or mutant forms of IL5. The antagonizing effect is reported to be the result of the variant forms of IL5 binding to the low affinity a chain of IL5R but not to the high affinity receptors; in this way the variants compete with IL5 for binding to its receptors without exerting the physiological effects of IL5.
Other atopic diseases involving eosinophilic inflammation are treated with either the symptomatica mentioned for asthma or immune therapy (IT) using hyposensitization with allergen extracts. The latter type of treatment is known to be effective against allergies against one or a few antigens, whereas IT is not feasible in the treatment of multiple allergies. Furthermore, the time scale for obtaining clinical improvement in patients susceptible to treatment is very long for conventional IT.
Thus, in spite of existing and possible future therapies for chronic allergic diseases such as asthma, there is a definite need for alternative ways of treating and ameliorating this and other chronic allergic diseases.
The object of the present invention is to provide novel therapies against chronic allergic conditions (such as asthma) characterized by eosinophilia. A further object is to develop an autovaccine against IL5, in order to obtain a novel treatment for asthma and for other pathological disorders involving chronic airway inflammation.
The T-cell derived cytokine IL5 has, as mentioned above, a crucial role in orchestrating the eosinophilic response, affecting both the production, the localisation and the activation of eosinophils. As IL5 has not otherwise been reported to have a central role in the development of a protective immune response, this particular cytokine is in the opinion of the inventors an attractive therapeutic target for the treatment of asthma.
The general aim according to the present invention is to decrease the pathogenic levels of eosinophils in the airways of the asthma patient by down-regulating of the IL5 levels, since eosinophils depend on IL5 for attraction and activation. The result of a decreased eosinophil number in the airway mucosa would be a concomitant decrease in the airway inflammation, corresponding to a clinical improvement in the asthmatic patient.
The potential effect of such an approach has already been demonstrated in studies using anti IL5 monoclonal antibodies in animal models of airway inflammation, cf. the xe2x80x9cPREAMBLE TO EXAMPLESxe2x80x9d.
This current invention, however, takes the results obtained through passive immunisation one step further by using the approach of generating an active immune response through the concept of autovaccination. To the best of the inventor""s knowledge, such an approach has never been suggested before.
The advantage of treating asthmatics with an IL5 autovaccine, as compared to current treatment with corticosteroids etc., is a reduction and/or elimination of side effects and most likely a better effect in terms of duration. When compared to anti-IL5 mAbs, the effect of an induced polyclonal Ab response is expected to be superior to passively injected monoclonal immunoglobulins since the polyclonal response has a broader specificity. Improvements with respect to administration regimen are also expected (since effective autovaccines described herein typically would require a maximum of 2-6 administrations per year).
When compared to hyposensitization, the present invention offers the attractive aspect of being non-specific; this is especially relevant when dealing with multi-allergic patients.
Thus, in its broadest and most general scope, the present invention relates to a method for in vivo down-regulation of interleukin 5 (IL5) activity in an animal, including a human being, the method comprising effecting presentation to the animal""s immune system of an immunologically effective amount of
at least one IL5 polypeptide or subsequence thereof which has been formulated so that immunization of the animal with the IL5 polypeptide or subsequence thereof induces production of antibodies against the IL5 polypeptide, and/or
at least one IL5 analogue wherein is introduced at least one modification in the IL5 amino acid sequence which has as a result that immunization of the animal with the analogue induces production of antibodies against the IL5 polypeptide.
The most attractive aspect of this approach is that e.g. asthma can be controlled by periodic but not very frequent immunizations, in contrast to a therapeutic approach which involves administration of anti-IL5 or molecules having a binding affinity to IL5 analogous therewith. It is expected that 1-4 annual injections with an immunogenic composition according to the invention will be sufficient to obtain the desired effect, whereas administration of other inhibitors of IL5 activity does or will require daily, or at least weekly, administrations.
The invention also relates to IL5 analogues as well as to nucleic acid fragments encoding a subset of these. Also immunogenic compositions comprising the analogues or the nucleic acid fragments are part of the invention.
The invention also relates to a method of identifying analogues of IL5 as well as a method for preparing a composition comprising the IL5 analogues.


A linking arm assembly incorporating an improved connection between an elongated rod portion and an engagement element such as a ball stud or the like adapted to join the linking arm to another structure. The linking arm assembly may incorporate an improved ball and socket connection. The socket may include an arrangement of flexible rib elements that are compressed when the ball stud is inserted so as to bias against the ball during use.

In many operational environments one or more linking arm assemblies may be operatively connected to a structure for use in monitoring the position of that structure relative to a defined reference position. In many of these linking arm assemblies, a rod extends between a pair of socket heads or other attachment elements at either end of the rod. The attachment element at one end of the rod is attached to a ball stud or other engagement element at the structure to be monitored, and the attachment element at the other end is operatively connected to a reference structure or is allowed to articulate in a defined manner. The rod may include one or more sensors which monitor the relative positions of the ends. Changes in spacing and/or relative position of the ends can thus be monitored, thereby indicating changes in position. The linking arm assembly is not generally required to carry a significant load. However, the linking arm assembly may be subjected to substantial vibration and high frequency articulating movement during use. Such linking arm assemblies may be used in conjunction with a vehicle computer to monitor headlight leveling, suspension ride height and the like. By way of example only, a linking arm assembly in accordance with the present disclosure may find application as a vehicle ride height sensor linkage. Such a linkage establishes a connection between the vehicle's moveable suspension and a sensor, such as a wheel sensor or the like, which provides position information to an electronic control unit. Of course, such assemblies may likewise be used for any number of other purposes as well.
In some prior linking arms, establishing and maintaining a secure connection between the linking arm and the attached socket structures has required relatively complex assembly practices. Accordingly, a linking arm assembly which promotes secure connection between components while reducing the complexity of the assembly process represents a useful advancement over the current art.


A radio communication apparatus includes a device for sequentially discriminating whether or not different frequency channels are open or occupied and generating channel-condition signals representative thereof during each of cycles of a channel scan. The channel-condition signals correspond to the channels respectively. A device holds the channel-condition signals and thereafter outputs the channel-condition signals. A device detects a variation between a current channel-condition signal and a preceding channel-condition signal in respect of each of the channels. The current channel-condition signal is currently generated by the discriminating device. The preceding channel-condition signal is outputted from the holding device. A device detects whether or not a given identification signal is present in the channel where the detected variation occurs.

1. Field of the Invention
This invention relates to a radio communication apparatus such as a radio communication transceiver of the multi channel access (MCA) type.
2. Description of the Prior Art
Some communication stations use conventional MCA-type radio communication transceivers which automatically find an open or unoccupied channel from a plurality of channels and which perform communication via the open channel. In cases where such a MCA-type transceiver of a station is required to transmit an information signal, a transmitter side of the transceiver scans channels to find an open channel. When the open channel is found, the transmitter side transmits the information signal via the open channel. In cases where the station is in a stand-by mode, a receiver side of the transceiver scans the channels to detect a related identification (ID) signal.
During the stand-by channel scan, the receiver side checks whether or not a channel is occupied by a signal having an electric field stronger than a given level. When the channel is unoccupied, the scanning process advances to a subsequent channel and the receiver side performs a similar check with respect to the subsequent channel. Such checks are reiterated sequentially for respective channels until an occupied channel is found. In the case where an occupied channel is found, the receiver side determines whether or not a related ID signal is present in the received signal. When the related ID signal is present, the associated transmitter side is activated to transmit an answer signal via the channel. When the related ID signal is absent, the scanning process advances to a subsequent channel and the receiver side performs the previously-mentioned check with respect to the subsequent channel.
In cases where the number of the channels is large, such a conventional stand-by channel scan tends to take a considerable length of time to find a related identification signal.

Matsushita Electric Industrial Co., Ltd.


An image forming apparatus having both an image data carrying member for carrying and forwarding image data rendered into a visible image by a developer and a device requiring high voltage in the form of a unit separable from a body of the image forming apparatus, wherein, inside the separable unit are a high voltage generator for the device and an electrically conductive member, the high voltage generator being disposed within the image data carrying member, the electrically conductive member being interposed between the image data carrying member and the high voltage generator and between the device and the high voltage generator, insulating members being interposed between the electrically conductive member and the image data carrying member and between the electrically conductive member and the device, the electrically conductive member being grounded.

The present invention relates to image forming apparatuses such as electrophotographic copying machines and printers. More particularly, the present invention is directed to an image forming apparatus having image data carrying members such as a photoreceptor, a transfer material carrying member, and an intermediate transfer body for carrying and forwarding image data rendered visible by a developer as well as high voltage requiring devices such as dischargers and chargers and contained in a unit that can be separated from the body of the image forming apparatus.
Conventional image forming apparatuses such as electrophotographic copying machines and printers use a transfer unit that is separable from the image forming apparatus body. Such a transfer unit contains: image data carrying members such as a photoreceptor, a transfer material carrying member, and an intermediate transfer body for carrying and forwarding image data rendered visible by a developer; devices such as a transfer corotron and adhesion corotron that require high voltage; and the like. A high voltage generating power supply for these high voltage requiring devices is usually disposed on the image forming apparatus body side and is connected to these devices through a high power cable and several junction connectors. However, this type of arrangement often requires that signal lines and the like run adjacent to the high power lines, and in this case, noise infiltrates into the signal lines from the high power lines, often causing erroneous operation.
To overcome this problem, a solution is disclosed in Japanese Patent Unexamined Publication No. 62-187371. According to this solution, a high voltage generating power supply is disposed within the transfer unit, so that the high voltage cable and junction connectors connected to the image forming apparatus body side can be eliminated to thereby prevent such noise-induced erroneous operation.
However, while there is no description in Japanese Patent Unexamined Publication No. 62-187371, it has been found out that desired current is not provided due to current leak at the high voltage line and junction connectors and that this impairs the image quality. In addition, if the transfer unit employs an endless belt, by only arranging a high voltage generating power supply inside the loop of the endless belt, a sufficient distance between the endless belt and the high voltage generating power supply cannot be provided due to the design restriction that a large thicknesswise space is not usually provided for the endless belt unlike the transfer drum. As a result, various problems are encountered.


A high hardness silicon nitride sintered body which includes 10.about.50% of a .alpha.-Si.sub.3 N.sub.4 per total weight of silicon nitride and has a Knoop hardness of not less than 15.5 Gpa, and is use as a bearing material or the like.

1. Field of the Invention
This invention relates to a silicon nitride sintered body having high hardness and strength.
2. Related Art Statement
Recently, there have been various advanced attempts for using ceramics as structural materials for machines and the like, by utilizing the lightweight properties, thermal resistance, abrasion resistance and so on inherent to ceramics.
Particularly, it is known that when the ceramics are used as a bearing material, it is important to grasp the rolling fatigue life of the ceramic material. In order to enhance the rolling fatigue life, it is important to utilize materials having high strength.
Under such circumstances, there have hitherto been known a method of producing high density silicon nitride by converting a greater part of .alpha.-type silicon nitride (Si.sub.3 N.sub.4) into .beta.-type silicon nitride, and the like. These techniques aim to provide high strength silicon nitride products.
However, the inventors have made studies from all angles with respect to the bearing material and confirmed that it is favorable to include a given amount of .alpha.-type silicon nitride in the bearing material in order to enhance the rolling fatigue life among, as well as other properties required for use in the bearing material or the like. That is, it has been found that the hardness can be increased and the high strength can be maintained by including a given amount of .alpha.-type silicon nitride and the improved rolling fatigue life is first obtained by this synergistic action, and consequently the invention has been accomplished.

High hardness silicon nitride sintered bodies


A safety apparatus of a seat for a vehicle with a height adjustment device may include a height link that has one end rotatably connected to a seat rail bracket and the other end fixed to a rear hinge pipe, a restriction link that may be disposed at a side of the height link and has one end pivotally coupled to the seat rail bracket, wherein the restriction link may be elastically biased away from the height link, a first anti-rotation mechanism that may be disposed at the height link and the restriction link to restrict rotation of the height link when a front of the height link rotates upward in a front collision, and a second anti-rotation mechanism that may be disposed at the height link and the restriction link to restrict rotation of the height link when a rear of the height link rotates upward in a rear collision.

1. Field of the Invention
The present invention relates to a safety apparatus of a seat for a vehicle with a height adjustment device. More particularly, it relates to a safety apparatus of a seat for a vehicle with a height adjustment device that protect a passenger as safely as possible by restricting rotation of a seat cushion frame in a collision.
2. Description of Related Art
In general, a seat of a vehicle includes a seat cushion supporting the passenger's lower body, a seat back supporting the upper body, and a headrest supporting the head and neck, in which the frames of the seat cushion and the seat back are a seat cushion frame and a seat back frame, respectively.
The seat cushion frame, as shown in FIG. 1, is divided into an inner seat cushion frame 1 and an outer seat cushion frame 2, the inner seat cushion frame 1 and the outer seat cushion frame 2 are connected by a front hinge pipe 3 and a rear hinge pipe 4.
A height adjustment device that makes it possible to adjust the height of the seat cushion frame includes a pumping device and a rack bar 6, I which the pumping device 5 and the rack bar 6 are mounted only on the outer seat cushion frame 2.
The inner seat cushion frame 1 and the outer seat cushion frame 2 are connected rotatably with respect to a seat rail bracket 9 by a front link 7 and a rear link 8 such that the eight of the seat cushion frame can be adjusted, and the seat rail bracket 9 is combined with a movable rail 11 of the seat rail and the movable rail 11 can move along a fixed rail 12.
Therefore, when the height of the outer seat cushion frame 2 is adjusted by operating the height adjustment device composed of the pumping device 5 and the rack bar 6, the operational force is transmitted to the inner seat cushion frame 1 through the front hinge pipe 3 and the rear hinge pipe 4, such that the outer seat cushion frame 2 and the inner seat cushion frame 1 adjust together the height.
However, in a seat equipped with the height adjustment device having the configuration of the related art, although the outer seat cushion frame 2 restricts the rotation of the front link 7 and the rear link by the restricting force of the height adjustment device composed of the pumping device 5 and the rack bar 6, but the inner seat cushion frame 1 is not provided with a specific mechanism for restriction the rotation of the front link 7 and the rear link 8, such that in a front collision or a rear collision, the inner seat cushion frame 1 is moved up or down by the rotation of the front link 7 and the rear link 8, and accordingly, the passenger in the seat is unbalanced at the inner and outer sides of the seat and severely injured.
The description provided above as a related art is just for helping understanding the background of the present invention and should not be construed as being included in the related art known by those skilled in the art.
The information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Safety apparatus of seat for vehicle with height adjust device


A joined article in which a first metal member made of a tungsten carbide base cemented carbide and a second metal member made of a martensitic stainless steel having a carbon equivalent of 2.5 to 3.5 and containing 0.030 mass % or less of sulfur are joined. The martensitic stainless steel having the carbon equivalent of 2.5 to 3.5 is preferably at least one selected from the group consisting of SUS431, SUS420J1, SUS420J2, SUS410, SUS410J1, S-STAR, PROVA-400, HPM38, STAVAX ESR, and SUS403 in the joined article. There is disclosed a joined article in which the lowering of the strength of a second metal member around a joining interface thereof is prevented.

1. Field of the Invention
The present invention relates to a joined article and a die for forming a honeycomb structure. More particularly, it relates to a joined article and a die for forming a honeycomb structure in which the lowering of strength around a joining interface is prevented.
2. Description of the Related Art
Heretofore, a joined article of a tungsten carbide base cemented carbide and a stainless steel is used in a die for forming a ceramic honeycomb structure (a honeycomb structure forming die), a precision mold, a die, a plug and the like.
As the honeycomb structure forming die, for example, there is used a die including a joined article (a die base member) obtained by joining a plate-like member made of the stainless steel and provided with back holes for introducing a forming material, and a plate-like member made of the tungsten carbide base cemented carbide and provided with slits connected to the back holes to form the forming material into a lattice-like shape (e.g., see JP-A-2006-051682 and JP-A-2007-181976).
In the honeycomb structure forming die, one surface of the die base member is usually provided with the slits each having a width corresponding to the thickness of each partition wall of a honeycomb structure and having a lattice-like shape or the like, and the opposite surface (the other surface) thereof is provided with the back holes connected to the slits and having large open areas. Moreover, the back holes are usually provided in positions where the slits intersect with one another (e.g., the intersecting positions of the formed lattice-like slits), and both the back holes and the slits arc connected to one another in the die base member. Therefore, a forming material such as a ceramic material introduced from the back holes moves from the back holes having comparatively large inner diameters to the narrow slits, and is extruded as a formed honeycomb structure article from openings of the slits. Thus, slit portions are narrow, and hence a high pressure is applied to the slit portions when the ceramic material passes through the slit portions, whereby the slit portions have an easily worn structure. On the other hand, in the honeycomb structure forming die including the slits formed in the member made of the tungsten carbide base cemented carbide having a high wear resistance, the tungsten carbide base cemented carbide is used to improve the wear resistance.


Wireless communication between two electronic devices may be used to determine a distance between the two devices, even in the presence of an otherwise-disruptive attacker. A wireless receiver system of one device may receive a true wireless ranging signal from a first transmitting device and a false wireless ranging signal from an attacker. The wireless receiver system may correlate the wireless signals with a known preamble sequence and perform channel estimation using the result, obtaining a channel impulse response for the wireless signals. The wireless receiver system may filter the channel impulse response for the plurality of wireless signals by removing at least part of the channel impulse response due to the false wireless ranging signal while not removing at least part of the channel impulse response due to the true wireless ranging signal. The receiver system may perform a wireless ranging operation using the filtered channel impulse response.

This disclosure relates to systems and methods for securely identifying a wireless channel in a shortest free-space path between a transmitting device and a receiving device.
This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present techniques, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
Many electronic devices, such as smartphones and computers, include antennas that are used for various forms of wireless communication. Some electronic devices may benefit from determining an accurate estimate of proximity to another electronic device using wireless signals. This may be accomplished by calculating a time-of-flight estimation for a wireless signal sent over a wireless channel of the shortest free-space path between a transmitting device and a receiving device. A simple way to determine the wireless channel of the shortest free-space path involves identifying the wireless channel between the receiving device and the transmitting device that provides the strongest signal. However, the strongest signal may not always represent the shortest free-space path between the receiving device and the transmitting device. In some cases, an obstruction—such as a person—may be positioned in the shortest free-space path between the receiving device and the transmitting device. This may lower the signal strength of the wireless channel of the shortest free-space path. Meanwhile, a wireless channel in a non-direct path, such as a reflection off a wall that goes around the obstruction, could provide a stronger signal. In cases like these, then, signal strength alone may not accurately identify the shortest free-space path between the receiving device and the transmitting device.
Since the signal strength does not always indicate the wireless channel of the shortest free-space path between the receiving device and the transmitting device, identifying the shortest free-space path may involve identifying the wireless channel with the signal having the earliest arrival time. For example, the signal from the transmitting device may include a defined preamble that can be used to determine which of the possible channels provides the earliest signal, even if the earliest signal is not the strongest signal. While this may allow the receiving device to accurately identify the proximity to the transmitting device in many cases, an attacker could provide a spoofed signal using the defined preamble. The spoofed signal could appear, from the perspective of the receiving device, to be earlier than the signal from the actual shortest free-space path. In this way, an attacker could cause the receiving device to misidentify the shortest free-space path between the receiving device and the transmitting device, which could thereby cause the receiving device to calculate a false proximity.


This invention relates to a method and device to produce esterified, olefinated/esterified, or thermochemolytic reacted bio-oils as fuels. The olefinated/esterified product may be utilized as a biocrude for input to a refinery, either alone or in combination with petroleum crude oils. The bio-oil esterification reaction is catalyzed by addition of alcohol and acid catalyst. The olefination/esterification reaction is catalyzed by addition of resin acid or other heterogeneous catalyst to catalyze olefins added to previously etherified bio-oil; the olefins and alcohol may also be simultaneously combined and catalyzed by addition of resin acid or other heterogeneous catalyst to produce the olefinated/esterified product.

Bio-Oil Characteristics
Fast pyrolysis is a process that can produce pyrolysis oil, often termed bio-oil, from any lignocellulosic biomass type. Bio-oil is produced by fast pyrolysis of small biomass particles at 400° C. to 650° C. in the absence of oxygen. The yield of bio-oil is relatively high at 60% to 80% dry weight basis. Bio-oil chemical properties vary with the feedstock, but woody biomass typically produces a mixture of 30% water, 30% phenolics, 20% aldehydes and ketones, 15% alcohols and 10% miscellaneous compounds.
As a fuel, bio-oil has potential environmental advantages because combusted bio-oil produces half the NOX and no SOX when compared to petroleum fuels. Because bio-oil is produced from renewable biomass, it is considered to be CO2 neutral. Bio-oil can be burned directly in engines. Electricity has been produced by bio-oil fueled diesel engines, and turbines have been specially modified to successfully burn bio-oil. However, some properties of bio-oil such as lower octane, acidity, immiscibility with hydrocarbons, viscosity change over time and a distinctive odor have prevented its commercialization as a fuel to date, other than for use in pilot and demonstration projects. Researchers have unanimously concluded that some form of upgrading of raw bio-oils is required prior to utilization for fuel.
Bio-oil can contain up to 45 percent oxygen which is responsible for most of the various negative properties described. Bio-oil catalytic hydrodeoxygenation (HDO) has been investigated using various catalysts and has resulted in reducing or eliminating some of the negative properties of bio-oils due to the elimination of oxygen and/or reduction of double bonds and aldehyde and keto groups. Several groups of researchers are utilizing various catalysts to produce HDO bio-oil. However, approximately 3 wt % of hydrogen is required to apply HDO and nearly 30% of energy contained in the original raw bio-oil is lost in the process. Another potential upgrading process, referred to herein as esterification for the purpose of this patent, provides considerably higher yields and does not require the expense of hydrogen and the capital outlay for hydrotreating infrastructure.
Bio-Oil Upgrading Via Alcohols Addition
Bio-oil primarily contains reactive hydroxyl, carbonyl and carboxylic groups which undergo etherification and esterification reactions during storage. These condensation reactions generally increase the molecular weight and are responsible for bio-oil viscosity increase over time that makes raw bio-oil difficult to store. The problem of polymerization of the bio-oil can be minimized if these reactions are controlled. Researchers have demonstrated that these polymerization reactions can be slowed by reacting alcohols with the reactive sites of the oligomers present in the bio-oil. These alcohols have been shown to restrict the continuation of the polymerization reaction to increase bio-oil stability. The monofunctional alcohols can react with the acidic compounds present in the bio-oil to form polyesters which may again undergo esterification reactions with alcohol to form low molecular weight materials. Similarly, aldehydes and ketones can be changed to their corresponding acetals and ketals by reacting with alcohol, and this reaction will act to block the reactive sites and restrict the polymerization reactions which are responsible for the temporal increase in bio-oil viscosity (Diebold and Czernik 1997).
Further research was performed in 2000 (Boucher et al.) to determine the influence of alcohol's addition to stabilize and upgrade bio-oil produced from tree bark feedstock. The upgrading was practiced to produce a potential fuel for gas turbines. The methanol addition improved some properties of the raw bio-oil. Viscosity was reduced, higher heating value (HHV) was increased significantly to 32 MJ/kg, and accelerated aging was significantly reduced. The improvement of properties resulting from methanol addition correlate to those found by other investigators who have added alcohols to stabilize or improve the fuel value of raw bio-oils.
Esterification Via Alcohol and Catalyst Addition
"Esterification" will be referenced in this disclosure as the catalyzed reaction of the bio-oil organic acids and other compounds with alcohols. Reactions, such as etherification, acetalization, ketalization and others are known to occur as a result of the catalyzed esterification of alcohols combined with bio-oil. The term esterification, as used herein, will be utilized to simplify the description of our invention, but it is understood that all reactions resulting from a combination of alcohol, bio-oil and an esterifying catalyst are being referenced with the term "esterification" as applied in this disclosure. The chemical combinations of alcohol and acid catalyst to produce an esterification reaction with the carboxylic acids prevalent in bio-oil have been shown to decrease bio-oil acidity, as well as to convert aldehydes to acetals. While the esterification reaction has been shown to improve most bio-oil properties, the reaction also produces a significant amount of water from the reaction (Tang et al., 2009; Xiong et al., 2009; Peng et al., 2008; Peng et al., 2009; Tang et al., 2008; Deng et al., 2009; Zhang et al., 2006). This increased water acts to reduce the total energy yield from addition of alcohol and from the higher heating value provided by the esters, acetals and ketals resulting from the reaction.
Radlein et al. (1995, 1997) provided an early esterification reaction example by dissolving freshly produced pyrolytic tar in 51.6 wt % of ethanol. The water content of this high viscosity bio-oil was 1.74%. Therefore, the organic fraction of the tar was 46.7%. Molecular sieve media and 1.4 wt % of sulfuric acid comprised the reacted mixture. The mixture was kept at room temperature for a few hours. The formation of acetals and esters were detected by GC/MS analysis within a few minutes of the mixing. After two hours' reaction time, the amount of ethanol and water had both decreased significantly. The water content was 0.28%, whereas the amount of ethanol remaining in the mixture was 35.9 wt %. Higher amounts of ethyl acetate, acetyl formate and diethoxyacetal of hydroxyacetaldehyde were detected. All of these esterification reactions produced water in the reaction medium. However, the lower amount of water produced by this experiment indicated that the molecular sieve media removed significant amounts of both the water resulting from condensation reactions and a portion of the water initially present in the raw bio-oil.
Moens and Czernik (2008) performed esterification experiments with a stoichiometric, or excess, amount of alcohol. The product was a two-phase compound. One phase (39 wt %) was a distillate containing water, acids and other carbonyl groups. The upgraded phase (63 wt %) was a semi-solid with low acidity and reduced oxygen with a water content of zero. This route to esterified bio-oil appears to provide low yield and a product of such high viscosity that it is unusable as a heating fuel.
Hitten et al. (2009) published results of ethanol injection into a slow pyrolysis reactor. These practitioners attached the cross pipe carrying the pyrolysis vapors from the main pyrolyzer reactor tube to the condenser train. While the cross pipe leading to the reaction vessel was heated to 450° C., the reaction vessel itself was not heated. For this reason, the pyrolysis vapors inside the reaction vessel partially condensed in the reaction vessel such that the alcohol spray introduced into the reaction vessel necessarily contacted condensed vapors in liquid bio-oil form, as well as reacting with the pyrolysis vapors. Therefore, the Hitten et al. device, developed for application to a fast pyrolysis reactor, differs from the novel device and method of our invention in that, by our method, alcohol is injected into the hot vapor stream well prior to condensation of pyrolysis vapors.
Xiong et al. (2008) esterified bio-oil organic acids by application of a dicatopmoc ionic liquid (C6(mim)2-HSO4) rather than the traditional acid catalyst. A two-phase liquid was obtained which was separated to provide a 49% yield of upgraded product. The properties of the upgraded fraction were improved to provide an HHV of 24.6 MJ/kg, an increased pH to 5.1 from 2.9, and a reduction of water content to 8.2% from 29.8%. GC/MS analysis confirmed esterification of organic acids to esters. The loss of 51% of the total reaction products in the form of a discarded aqueous fraction, however, will likely hinder any commercialization of this process.
Therefore, past practitioners have upgraded bio-oil by combining alcohols with bio-oils or by catalyzing bio-oil/alcohol mixtures to produce esterification reactions. The esterification reactions have all been described as increasing bio-oil water content to some degree. This water has usually been left in the final esterified bio-oil, but, in this case, it acts to reduce total HHV and partially reduces the energy increase obtained from production of esters, acetals and ketals. Alternatively, water removal has been achieved by discarding any aqueous fraction that may be produced simultaneously with the upgraded fraction; utilization of a water adsorbent to remove water produced by esterification has also been practiced.
Thermochemolysis with Tetramethyl Ammonium Hydroxide
Tetramethyl ammonium hydroxide (TMAH) thermochemolysis is pyrolysis combined with methylation of the polar groups evolved from the degradation of bio-polymers. Reaction of TMAH in the presence of alcohol produces methyl derivatives by hydrolysis, as well as by methanolysis. TMAH thermochemolysis, in the presence of methanol, can also convert completely/partially phenols to their corresponding methyl derivatives (Challinor 2001).
TMAH thermochemolysis of phenolic and lignin model compounds containing a β-5 linkage provided the methylated stilbenes as major products (Kuroda et al. 2002). Another group of researchers used furaldehyde, benzaldehyde, hydroxybenzaldehyde, methoxybenzaldehyde, di-methoxybenzaldehyde and vanillin as model compounds for TMAH thermochemolysis and found that TMAH not only acts as the methylating agent, but also reacts with the aldehydes according to Cannizzaro reaction. An in-situ methylation of the reaction products formed the corresponding esters and ethers (Tanczos et al. 1997). The product distribution indicated that the pyrolytic process involved two sequential reactions. At first, the aldehydes form an equimolar amount of corresponding alcohols and carboxylic acids; in the second step, methylation occurs. TMAH is an excellent methylating agent at high temperature. Therefore, the benzyl alcohols are converted to their corresponding ether, and the tetramethylammonium salt of the carboxylic acid decomposes to the methyl ester.
For better understanding of the TMAH thermochemolysis process, synthetic and natural lignins were pyrolyzed in the presence of TMAH. Coniferyl alcohol dimethyl ether, erythro/threo-1-(3,4-dimethoxyphenyl)-1,2,3-trimethoxypropane, and pinoresinol dimethylether were identified from GC/MS analysis. Phenolic models and lignin end units having β-5 structure gave methylated stilbene products during the TMAH-thermochemolysis process (Kuroda et al. 2002 2006).
13C labeled TMAH was also used for the thermochemolysis study of synthetic lignin dimer model compounds. The mechanistic study showed a number of base catalyzed rearrangement and elimination reactions to the lignin dimer, resulting in the methylation of alcohols and phenols to methyl ethers (Filley et al. 1999).
The comparison between the compounds released by Py-GC/MS with and without the application of TMAH of non-woody lignin samples was performed by a group of researchers (Del Rio et al. 2007). Pyrolysis of lignin in presence of TMAH undergoes β-O-4 ether bond cleavage and forms methylated aldehydes, ketones and acids. Presence of TMAH also initiated the high-temperature saponification of esters of p-hydroxycinnamic acid. Cleavage of the ether linkage at C-4 resulted in the methylation of free carboxyl and hydroxyl groups.
The TMAH thermochemolysis of levoglucosan and levoglucosan acetate formed the methyl ester of saccharinic acid, methyl acetate, methyl levoglucosan and other compounds. The thermochemolysis of cellulose produced methyl esters of pentanoic acid and butanoic acid (Schwarzinger et al. 2002). Pyrolysis of cellulose and lignin in the presence of TMAH produced a significant amount of aromatic acid and fatty acid methyl esters (Gauthier et al., 2003). The TMAH thermochemolysis fully converted the model aliphatic acid to its corresponding methyl esters (Joll et al., 2002). TMAH thermochemolysis of lignin produced some completely methylated compounds, such as 1,2-dimethoxybenzene, 3,4-dimethoxytoluene, 4-ethyl-1,2-dimethoxybenzene, 1,2,4-trimethoxybenzene, 1,2-dimethoxy-4-(2-propenyl)benzene, 3,4-dimethoxybenzoic acid, methyl ester and others (Klingberg et al, 2005).
As described, TMAH thermolysis has been employed to methylate various organic compounds and to assist in identifying the chemical structures of lignins and other biopolymers. TMAH thermochemolysis to convert bio-oil acids and their corresponding esters and ethers has not been performed by past practitioners.
Fractionation of Raw Bio-Oil to Produce a Pyroligneous Fraction Prior to Esterification or Olefination
Marker and Petri (2008) disclose a method by which water fractionation is applied to obtain the pyroligneous and aqueous fractions as previously described. These inventors propose production of gasoline or diesel hydrocarbons from the pyroligneous fraction by two stages: hydrotreating followed by hydrocracking. It is proposed that the aqueous fraction be reformed to hydrogen which is then input to the hydrotreating and hydrocracking process. The fractionation into pyroligneous and aqueous fractions may be performed by any method, but water fractionation is the preferred method. The pyroligneous fraction produced by this process is highly viscous, and processing this thick bio-oil fraction in hydrotreating reactors is expected to be problematic. Marker and Petri (2008) did not propose esterification, esterification followed by olefination, or simultaneous olefination/esterification to reduce the viscosity of the pyroligneous fraction to allow practical hydrotreating.
Olefination of Esterified Bio-Oil or Simultaneous Olefination/Esterification of Bio-Oil
The olefination of bio-oil model compounds and bio-oil has been attempted with limited success due to the immiscibility of olefin hydrocarbons with the water emulsion that comprises bio-oil (Yang et al. 2010; Zhang et al 2010). However, upgrading of bio-oil by olefinating esterified bio-oil, or by simultaneous esterification and olefination of bio-oil, combined with alcohol has not been reported.
As discussed previously, the esterification of bio-oil produces an upgraded product with improved properties. However, water content is increased significantly. Suggested methods to remove this water include utilization of molecular sieves as adsorbents. This method is likely to be prohibitively expensive, and recycling or disposal of utilized molecular sieve material may be problematic.

Method to upgrade bio-oils to fuel and bio-crude