The present invention relates to a microorganism of the genus Escherichia having enhanced L-tryptophan productivity, which has been modified to express yeast anthranilate phosphoribosyltransferase in order to be able to produce L-tryptophan at high concentration, and to a method for producing L-tryptophan, comprising a step of culturing the microorganism. The microorganism of the genus Escherichia can produce L-tryptophan, and thus can be advantageously used in the pharmaceutical industry and the feed industry, particularly for animal feed.

L-tryptophan, a kind of essential amino acid, has been widely used as a feed and food additive. L-tryptophan is generally produced by fermentation using microorganisms of the genus Corynebacterium, Bacillus or Escherichia, and variant thereof. L-tryptophan is biosynthesized from chorismic acid which is a common intermediate for the synthesis of aromatic amino acids. Specifically, L-tryptophan is biosynthesized by the action of five enzymes, which are synthesized by the tryptophan operon trpEDCBA, on chorismic acid produced through the common shikimic acid pathway that starts from phosphoenolpyruvate and D-erythrose-4-phosphate. First, anthranilate synthase (TrpE-TrpD complex) acts on chorismic acid to synthesize anthranilic acid, then anthranilate phosphoribosyltransferase (TrpD) acts on it to synthesize N-(5′-phosphoribosyl)-anthranilate. Then, phosphoribosylanthranilate isomerase (TrpC) and indole-3-glycerol phosphate synthase (TrpC) act on the N-(5′-phosphoribosyl)-anthranilate to synthesize indole-3-glycerol-phosphate, then tryptophan synthase (TrpB-TrpA complex) acts on it to synthesize L-tryptophan (FIG. 1; Bonggaerts et al., Metab Eng, 3, 289-300, 2001).
In E. coli, a protein encoded by a complex of the trpE and trpD genes forms anthranilate synthase to synthesize anthranilic acid. The synthesized anthranilic acid reacts with 5-phosphoribosyl 1-pyrophosphate (PRPP) by anthranilate phosphoribosyltransferase encoded by the trpD gene, thereby synthesizing N-(5′-phosphoribosyl)-anthranilate.
Herein, the protein encoded by the trpD gene acts as anthranilate synthase in combination with the protein encoded by the trpE gene or acts alone as anthranilate phosphoribosyltransferase, and a wild-type E. coli strain maintains the balance of such two actions.
In a wild-type E. coli strain, the concentration of PRPP that is used as a cofactor in intracellular tryptophan biosynthesis is about 180 μM (Bennett et al., Nat Chem Biol, 5, 595-599, 2009). In an L-tryptophan-producing strain with enhanced biosynthesis of anthranilic acid, the extracellularly accumulated concentration of anthranilic acid is at the maximum value, whereas the intracellular concentration of PRPP is greatly lower than the concentration of anthranilic acid. Low PRPP concentration acts as a limiting factor in the production of N-(5′-phosphoribosyl)-anthranilate to reduce the overall synthesis rate of L-tryptophan and increase the intracellular and extracellular accumulation of anthranilic acid. Thus, the use of an anthranilate phosphoribosyltransferase having higher affinity for PRPP makes it possible to prevent the intracellular and extracellular accumulation of anthranilic acid and to increase the biosynthesis rate of L-tryptophan.
Among previous reports on improvement in L-tryptophan-producing strains, a technology of enhancing the biosynthesis pathway while maintaining the balance of anthranilate synthase and anthranilate phosphoribosyltransferase activities has not yet been reported.
According to studies, the Km value of E. coli for PRPP is 50, whereas the Km value of yeast for PRPP is about 22.4±2.6 (Hommel et al., Eur J Biochem, 180, 33-40, 1989). Thus, the affinity of yeast anthranilate phosphoribosyltransferase for PRPP is higher than that of E. coli anthranilate phosphoribosyltransferase. Thus, it is expected that the use of yeast anthranilate phosphoribosyltransferase will have greater effects on the prevention of the intracellular and extracellular accumulation of anthranilic acid and an increase in the biosynthesis of L-tryptophan in microorganisms with enhanced L-tryptophan biosynthesis pathways.
During an attempt to enhance the chorismic acid biosynthesis pathway and trp operon pathway in E. coli in order to produce a large amount of industrially useful L-tryptophan, the present inventors have found that, as the above two pathways are enhanced, anthranilic acid is accumulated intracellularly and extracellularly, and for this reason, abnormal culture appears. Accordingly, the present inventors have continued to study under the expectation that enhancement of the expression of anthranilate phosphoribosyltransferase in microorganisms having an enhanced L-tryptophan biosynthesis pathway can prevent the intracellular and extracellular accumulation of anthranilic acid and increase the biosynthesis of L-tryptophan, thereby completing the present invention.

Microorganisms having L-tryptophan productivity and a method for production of L-tryptophan using same


A NAND gate circuit system that provides for adjustable pulse width that comprises eight transistors arranged so that a signal can propagate through the transistors in series, the transistors consisting of at least one N-channel and at least one P-channel transistor.

The present invention relates generally to address and data transition detection. This technique is commonly used to reduce power consumption, especially in Static Random Access Memory devices (SRAM).
Conventional transition detection circuits generally consist of an exclusive OR gate and multiple inverters (See FIG. 1 and 2 for circuit diagrams). One input terminal of the exclusive OR gate is connected directly to the input line. The other input terminal is connected to the output of a series of inverters connected together. This series of inverters is positioned between the input line and the second input terminal to the exclusive OR gate. When the address or data input changes, the exclusive-OR gate generates a pulse whose width equals the delay caused by the series of inverters (See FIG. 3 for the timing diagram of the circuit of the circuit diagram of FIG. 2, which was provided by the SPICE simulation program).
These conventional transition detection circuits have several disadvantages. In particular, the parameters of the transition boundaries of the pulse are inconsistent, as the pulse width is non-adjustable and the pulse is extremely sensitive to noise. The width of the pulse, the slope of the transitional boundaries of the pulse, and the circuit's immunity to noise ultimately affect the speed of the extended circuit.
Regarding the adjustable pulse width, the number of additional inverters in series can be changed to adjust the pulse width. These adjustments generally occur in multiples of two, in order to maintain the proper polarity. The total number of inverters is generally an odd number. (FIG. 1 and 2 demonstrates the variable lengths of these inverter chains. FIG. 1 has one inverter in series. FIG. 2 has nine inverters in series.) Regarding the transitional boundaries, the slope of the transitional boundaries is small, which slows down the operation of the entire system. Regarding the sensitivity of these traditional circuits to noise, changes in the IN signal translates to direct changes in the OUT signal. If the IN signal is noisy, the OUT signal is noisy as well. These traditional circuits tend to be extremely sensitive to noisy inputs (See FIG. 4 for a for the timing diagram for the circuit diagram presented in FIG. 2 for a noisy input signal, which is provided by the SPICE simulation of the circuit).

Gate circuits in transition detection input buffers


A semiconductor device includes: a lead frame; an IC element mounted on a main face of the lead frame; an inductor mounted on a back face of the lead frame; and a resin body configured to seal the lead frame, the IC element and the inductor, wherein the inductor and the lead frame are closely contacted with each other, wherein the IC element is disposed at a position corresponding to an center axis of the inductor, wherein the inductor and the IC element are electrically connected to each other, and wherein wiring of main current flowing through the IC element is disposed between terminals of the inductor.

There is a semiconductor device including a DC-DC converter as a power converter for converting a power source voltage to a predetermined operating voltage. In such a semiconductor device, a SON-type (Small Outline Non-leaded type) semiconductor device with a small size and a low profile has been generally known in which an inductor (coil), IC chip and capacitor are mounted on a main face of a frame. (See JP-A-2007-318954)

Semiconductor device having an inductor mounted on a back face of a lead frame


In the method according to the present invention, a transmit power for each eigenbeam in a set of eigenbeams forming at least a portion of a multiple transmit antenna system is determined based on noise associated with each eigenbeam in the set of eigenbeams. The set of eigenbeams is for transmitting a number of parallel complex Gaussian channels.

Antennas are part of some of the more critical components of a communication system, and in particular, wireless communication systems. In wireless communication systems, communication signals that are transmitted by antennas over traffic channels and signaling channels will at some point propagate through the air and be received by other antennas. Thus, part of or all of the medium of the traffic and signaling channels is the air itself. The traffic channels are communication channels through which users of the wireless communication system convey (i.e., transmit and/or receive) communication signals to each other. The communication signals typically carry information being conveyed between users. The signaling channels are communication channels through which signals that facilitate the control, maintenance and management of the communication system are conveyed. The signaling signals are typically transmitted by system equipment and user equipment. System equipment are various communication equipment owned, controlled and operated by a system operator or provider. Examples of system operators include local telephone companies and Internet service providers. User equipment are equipment that are typically owned and operated by users of the communication system. Examples of user equipment include cellular phones, wireless personal computers and pagers.
As the communication signals propagate through the air, they are adversely affected by various anomalies that distort such signals and cause part or all of the information being carried by said signals to be received erroneously. The quality of the communication channels can greatly affect the communication system's throughput. The throughput is the amount of information that is received without any errors for a given period of time. The various anomalies of a communication channel can adversely affect any one or all of a signal's parameters; some of these parameters include signal amplitude, signal phase, signal frequency. The signals are transmitted by transmit antennas and received by receive antennas. It should be noted that the antennas are often designed to operate as both transmit and receive antennas. To reduce the anomalous effects of a communication channel, communication systems often employ a feedback technique where a receive antenna transmits channel quality feedback information to a transmit antenna allowing the transmit antenna to modify, in some fashion, one or more of the signal's parameters. The channel quality feedback information is information about how transmitted signals are affected by the communication channel through which they have propagated. The signals propagating through the communication channel can therefore be manipulated so as to be less vulnerable to the various channel anomalies; thus the adverse effects of the channel are effectively reduced thus increasing throughput. Also, to increase system throughput, the communication system can use more than one transmit antenna and more than one receive antenna for the same or different signals.
Suppose, there are two transmit antennas and two receive antennas. The same information is transmitted by both transmit antennas. Although, the signals carry the same information, they may have different parameters. Therefore, the signals may be affected differently by the communication channel. Even when the signals carry the same information and have the same parameters, they may still be affected differently by the communication channel. One feedback technique used by many communication systems is to have the receive antennas transmit channel quality feedback information to the transmit antenna informing the transmit antennas about the quality of the transmitted signals. The parameters of the transmitted signal least adversely affected by the communication channel is then used in ensuing transmissions by the transmit antennas in an effort to improve the quality of the received signals.
Another technique is to pre-modify (or pre-process) the transmit signals based on the channel quality feedback information received by the transmit antennas from the receive antennas. The pre-modification (or pre-processing) compensates for the anomalies that the transmitted signals experience as they propagate through the communication channel. The channel quality feedback information may be based on measurements of previously transmitted signals or measurements of various channel parameters from signals transmitted over the signaling channel. A signal that is typically transmitted over the signaling channel and measured by the system is the pilot signal. Many wireless communication systems have a pilot signal that, among other purposes, serves to signal the presence of system equipment.
Yet, another technique is to measure the amount of energy contained in the two receive signals and send that information back to the transmit antennas. The parameters of the signal having the higher measured energy will be used for the next transmission. In all of the above feedback techniques, a rather brute force method is used to determine which set of signal parameters will allow a transmitted signal to be relatively less adversely affected by the communication channel. These brute force methods require a relatively large amount of information to be fed back to the transmit antennas. Further, the channel quality feedback information is continuously being sent back to the transmit antennas. Many communication systems have limited bandwidth for their signaling channels through which other critical information are conveyed. It may not, therefore, be practical to send all of the feedback information. Also, because the communication channel is a continually varying dynamic system, it may not be possible to efficiently and quickly modify the transmit signal to reduce its vulnerability to the channel anomalies.
Some communication systems attempt to characterize the communication channel mathematically so as to be able to develop more comprehensive channel quality feedback information that can sufficiently track the variations in the communication channel. For example, the communication channel can be modeled as an Eigenspace represented by an eigenvector matrix whose elements are complex numbers each of which is a basic unit that represents one or more measured parameters of the communication channel. The measured parameters of the channel include, for example, the effect of the channel on a signal's amplitude, the effect of the channel on a signal's phase and the effect of the channel on a signal's frequency. The measured channel parameters are also called channel parameters. For example suppose a signal is transmitted with an amplitude of 0 db, but such signal is received with a measured amplitude of −3 dB. The channel parameter for amplitude is thus −3 dB. When more than one transmitter and receiver are used, a channel parameter matrix can be generated from measured channel parameters.
A channel matrix can thus be formed from measurements of channel parameters. Again suppose, there are two transmit antennas (T1 and T2) and two receive antennas (R1 and R2). The channel parameter measurement at receive antenna R1 due to a signal transmitted by transmit antenna T1 is designated h11. The channel parameter measurement at receive antenna R2 due to a signal transmitted by transmit antenna T1 is designated h12. The channel parameter measurement at receive antenna R1 due to a signal transmitted by transmit antenna T2 is designated h21. The channel parameter measurement at receive antenna R2 due to a signal transmitted by transmit antenna T2 is designated h22. The measured channel parameters are elements of the channel matrix H, where:
  H  =      [                                        h            11                                                h            12                                                            h            21                                                h            22                                ]  and where h11,h12,h21, and h22 are complex numbers having complex conjugates h11*, h12*, h21* and h22*. A channel correlation matrix is obtained by performing a Hermitian operation on the channel matrix and pre-multiplying the channel matrix with this Hermitian matrix. The Hermitian operation is a well known matrix mathematical conversion in which all of the elements of the matrix are changed to their complex conjugates and the transpose of the complex conjugate matrix is performed. Thus the Hermitian matrix of channel matrix H is H+ where H+=[H*]T. The channel correlation matrix is designated as S where S≡H+H.
The elements of the channel correlation matrix, S, are related to eigenvalues and eigenvectors which can be obtained by a well known procedure called an eigenvalue decomposition, Applied Linear Algebra, 2d edition, Ben Noble, James W. Daniel, Prentice Hall Inc., 1977 and 1969, ISBN 0-13-041343-7. First it is recognized that S=ΣΛΣ+ where Σ is the eigenvector matrix. Σ is a unitary matrix meaning that Σ+Σ=ΣΣ+=I where I is an identity matrix. Λ is a diagonal eigenvalue matrix whose elements are eigenvalues and Σ is a matrix whose columns are eigenvectors or equivalently eigenbeams. For a 2×2 system (i.e., two transmit antennas and two receive antennas):
  Λ  =      [                                        λ            1                                    0                                      0                                      λ            2                                ]  where elements λ1 and λ2 are the eigenvalues; and Σ=[e1 e2] where e1 and e2 are eigenvectors which are the columns of the eigenvector matrix. Also, for a 2×2 system,
  I  =            [                                    1                                0                                                0                                1                              ]        .  Because S is known and I is a known constant matrix, the eigenvalues (i.e., λ) are obtained by solving the following equation:det[S−λI]=0where det represents the determinant operation. The values for Σ are then obtained by solving the equation Se=λe; i.e., because S is known and λ is known, e can be determined. Once the eigenvectors are obtained, channel quality feedback information—represented in terms of the eigenvectors—is sent or fed back to the transmit antennas to allow these antennas to modify the transmit signals so as to reduce the distortion experienced by these signals.
The channel quality feedback information in the form of eigenvalues and/or eigenvectors represents a relatively large amount of information that is to be periodically transmitted over band-limited signaling channels of the communication system. Further, many times some of the channel information being transmitted in the form of eigenvalues and/or eigenvectors are not as accurate in their characterization of the communication channel. In other words, there are certain eigenvalues that more accurately represent the communication channel characteristics than other eigenvalues.
In a single-transmit-single-receive antenna system, the transmission power can be determined using the well known procedure called the water-filling approach. However, for a multiple-transmit-multiple-receive antenna system, this method will not work simply because the channels between different antennas are interfering with each other. In this case, it is usually assumed that the same transmit power is given for each eigenbeam. Artificial ways of providing different transmit power to different eigenbeams is possible but this involves experimental fine tuning to determined the amount of power should be given and is usually not very effective.

Method of determining transmit power for transmit eigenbeams in a multiple-input multiple-output communications system


A system for slowing down the speed of flying objects by applying electrodynamic and aerodynamic braking forces. The system is comprised of plurality of stubs, where each stub is made of dielectric material surrounded by metal foil and another metal foil is inserted in the middle of the stub, where the outer metal foil and the inner metal foil are isolated from each other, so that they form a capacitor. Each stub is stored in a barrel before being used. When activated, the stubs are stretched from the barrel as a tail behind the flying object. The area of the stub generates aerodynamic drag. The stub capacitor is charged by a generator so that free electrons are present in the outer metal layer of the stub. The electric field produced by these charges interacts with ions in the atmosphere.

Since the dawn of aviation aircraft crashes have been much publicized. Today air travel is considered one of the safest, and yet we are still in awe when a civilian aircraft crashes down. This is mainly due to the large number of people that inhabit each of these flights. The problem was, and remains, that once airborne, a damaged aircraft cannot land as regularly but crashes down or performs an emergency landing. These two options may cause injuries or massive loss of life. To this day no system has been invented that could help mitigate the damage and allow an airborne aircraft, once damaged or malfunctioned, to reasonably safely land on the ground or water, with minimal damage.
Such systems, of course, have been suggested before. One such system used in the commercial market is intended for the recovery of small single engine planes. This system, produced by BRS Aerospace, uses a single parachute that deploys if the aircraft departs controlled flight. This method, though, is only applicable to small aircraft that fly at slow speed and the breaking force delivered by the parachute is not as strong as one necessary to slow a jet airliner.
U.S. Pat. No. 8,123,170 "Recovery and Rescue System for Aircraft" describes a system intended for small aircraft. This system, it is mentioned, can be upgraded to fit larger jets up to business jets. This patent describes the use of a single sail that automatically launches in an emergency. The use of a sail has its advantages of the sudden breaking power of a parachute, but the system does not offer a complete solution to all aircraft and is generally limited to small aircrafts.
U.S. Pat. No. 6,761,334 "Aircraft Passenger Safety Module" describes a system were the passengers in an airliner will sit in a module that can be separated in the event of an emergency. After the separation, parachutes can open to allow for the safe landing of the passenger module. This system will require an elaborate construction and pyrotechnics to fit into existing airframes (if possible). In addition, the use of parachutes in high capacity, high weight, high flying and high-speed jet planes can be as dangerous as a crash. Using a parachute at high speeds can cause a breaking force that could tear the module apart or even injure or kill the passengers inside it. A successful method must first slow down the plane and only open the parachutes when it is safe to do so.
US Pat. Publication No. 2008/0142635 "Aircraft Safety System" describes a system of parachutes designed to help safely down an airliner during an emergency. In this patent, the aircraft's wings are taken off and landed separately from the body, thus reducing the weight of the aircraft. However, again, the single use of parachutes for breaking purposes can be very dangerous in highflying high-speed airliners. This patent also includes a fuselage to facilitate a gentler touchdown of the aircraft, even without the deployed landing gear.
U.S. Pat. No. 5,826,827 "Air-Chute Safety System" describes yet another recovery patent that uses several parachutes to help land a jetliner in an emergency. This system, again, uses only parachutes for the recovery operation.
U.S. Pat. No. 7,523,891 "Safety Pre-Impact deceleration System For Vehicles" describes a rescue system comprised of inflatable airbags that enables to smoothly decelerate the speed of the air vehicle. Another method described in the patent is the use of canopy with orifices that can be controlled. In addition, airbags are inflated around the vehicle to ease the landing impact.
The major deficiency in the above-described patents is that the deceleration is very high, at a level that can harm people within the vehicle.
Space craft reentering the atmosphere fly at a very high speed, and they have no means for reducing their speed before entering the atmosphere. Hence they have to protected against high temperature which is generated during the reentrancy. The weight of the heat protection means constitutes significant part of the weight of the vehicle.
Thus, a different approach that will assure gradual slowdown of the vehicle's speed is required both for air vehicles within the atmosphere and for air vehicles in space before reentering the atmosphere.

System and method for braking flying objects


A sheet transporting device includes a drive roller including a high rigidity roller having a surface coated with ceramic particles and a follower roller including an elastic roller having a surface coated with a low friction material. A sheet of printing medium is nipped and fed by the drive roller and the transporting roller.

1. Field of the Invention
This invention relates to a sheet transporting device for transporting a sheet of printing medium, such as regular paper, coated paper, overhead projector sheet, glossy paper, and glossy film. More specifically, such a sheet transporting device may be used for a printer.
Generally, known sheet transporting devices use a pair of rubber rollers, where one of the paired rollers is a drive roller and the other is a follower roller. This arrangement causes a number of problems with sheet transporting accuracy, especially if the drive roller is formed with a rubber roller. First, it is difficult to produce a rubber roller with an accurately dimensioned outside diameter. Second, rubber rollers wear quickly and the thermal expansion of the roller is large. Finally, the coefficient of friction of the roller may be markedly reduced by paper powder, dust and chemicals of coated paper, which attach to the surface of the roller.
A sheet transporting device that attempted to solve the above problems is disclosed in Unexamined Japanese Patent Application No. Hei. 4-140247. In this sheet transporting device, the drive roller is a metal roller with a surface that has been subjected to a blasting process and has a highly accurate outside diameter, and the follower roller is an elastic roller, the surface of which is coated with silicon. According to such a sheet transporting device, because the friction coefficient of the elastic roller is small, the roller pair exhibits a low resistance to paper transportation, and further, the use of the rigid roller blasting process ensures stable transportation of the printing medium.
This sheet transporting device, however, may suffer from other disadvantages. For example, during the blasting process, the raised edges or peaks of the irregular surface of the metal drive roller are easily plastically deformed. As a result, when the printing medium is a film, the coefficient of friction of the paired rollers is insufficient, and transporting accuracy is decreased. Additionally, the paired rollers are easily worn, and, hence, their durability is low.
As such, there is a need for a sheet transporting device that is durable, and accurately and reliably feeds printing media, including media such as films.


An analyzing model creating apparatus includes an interval acquiring part to acquire intervals of a plurality of parts that are mounted on a PCB for an electronic equipment, from design data of the PCB, a comparing part to compare a minimum part interval between the parts and a first mesh size which is preset, and a computing part to compute a value which is ½ the minimum part interval between the parts as a second mesh size if the minimum part interval between the parts is less than 2 times the first mesh size. A generating part is provided to generate an analyzing model of the printed circuit board based on the second mesh size.

1. Field of the Invention
The present invention generally relates to analyzing model creating apparatuses and methods and computer-readable storage media, and more particularly to an analyzing model creating apparatus and an analyzing model creating method which create a Finite Element Method (FEM) model suited for evaluating a part bonding strength of a part that is mounted on a Printed Circuit Board (PCB), and to a computer-readable storage medium which stores a program for causing a computer to realize functions of such an analyzing model creating apparatus.
2. Description of the Related Art
Recently, due to the reduced weight and size of portable electronic equipments, it is becoming increasingly important from the point of design to secure the part bonding strength of the part that is mounted on the PCB which is assembled within the portable electronic equipment. There are proposals to improve the efficiency with which the portable electronic equipments are developed, by evaluating a virtual part bonding strength by a numerical simulation using the Finite Element Method (FEM).
Because the parts mounted on the PCB of the portable electronic equipment are extremely small, an evaluation method which directly evaluates a solder bonding part by forming a detailed mesh model of the parts is unsuited in this case. For this reason, an evaluation method which is generally employed fixes rectangular part meshes of a simple part model on PCB meshes in a joining contact state, and evaluates a PCB stress or distortion in a periphery of the part in order to indirectly evaluate the load on the part. More particularly, the part and the board are respectively divided into meshes from a three-dimensional model of the PCB, and a node located on a part mounting surface is fixed to a mesh surface of the board using a joining type contact definition, in order to create a FEM model.
Three-dimensional models of the PCB are proposed in Japanese Laid-Open Patent Applications No. 2005-115859 and No. 2006-91939, for example.
Conventionally, most of the three-dimensional models of the mounting parts have a simple block shape, and it is relatively easy to create the meshes. However, because the number of meshes is large, there was a problem in that a large number of processes are required to create the meshes.
On the other hand, the division of the board into the meshes and the division of the evaluation target part into the meshes are performed independently, and the meshes of the board and the meshes of the evaluation target part are fixed using the joining type contact definition. For this reason, the size and direction (or orientation) of an evaluation target element 12 may differ depending on the position in the periphery of the evaluation target part as shown in FIG. 1. Consequently, a relative error of approximately 30%, for example, is generated in the evaluation result depending on the manner in which the PCB model is created. FIG. 1 is a diagram for explaining the conventional FEM model. In FIG. 1, (a) shows a plan view of the FEM model, and (b) shows a portion of the evaluation target part of the FEM model. In FIG. 1, a reference numeral 10 denotes a mesh model of the board, and a reference numeral 11 denotes a mesh model of the evaluation target part.

Analyzing model creating apparatus and method, and computer-readable storage medium to create a model using a minimum part interval between parts


A graphical interface for generating configuration files. Many computer programs require configuration files. These files specify parameters which the program will use. One example of a parameter is the resolution of a video display, which the program will use to display output. The invention provides a graphical interface which allows a user to select parameters from menus, and test the generated configuration file. In one form of the invention, speech synthesis of break-out instructions are provided during testing.

X Windows Program
FIG. 1 shows a central computer 3, commonly called a server, and four other computers 6, commonly called clients. The server 3 is frequently designed to run the operating system UNIX, such as that available from AT & T Corporation as product number UNIX SVR4 MP-RAS, version 3.0.
Each client 6 runs its own X Windows Server 12, which is a program which handles mouse and keyboard input, and other tasks, and which can be viewed as an interface for dealing with the UNIX program running on the server 3. (The fact that this program, called a "server," runs on a computer called a "client," which interacts with another computer called a "server" is a possible source of confusion, but this terminology has become accepted in the industry, and is beyond the Inventor's control.)

Method and system for generating a configuration file using an X-windows server configuration tool


The present invention relates to a virus-derived particle comprising one or more Cas protein(s), as well as to kits and methods using the same for altering a target nucleic acid.

Genome editing using targetable nucleases is an emerging technology for the precise genome modification of organisms ranging from bacteria to plants and animals, including humans. Its attraction is that it can be used for almost all organisms in which targeted genome modification has not been possible with other kinds of methods.
Improving protocols for expressing exogenous proteins within human cells is of major interest for research and medical purposes. In spite of the constant evolution of transfection methods and performances of viral vectors, the efficiency of these approaches can vary dramatically, especially in primary cells that are highly sensitive to modifications of their environment and may be altered in response to transfection agents/vectors. Moreover, delivering genetic information through the transfer of a coding integrative/non-integrative DNA may be responsible for adverse effects like the induction of unwanted stress signals or the unexpected insertion of an exogenous gene within the cellular genome, which is a serious issue for therapeutic applications, particularly in stem cells.
Recent approaches to targeted genome modification—zinc-finger nucleases (ZFNs) and transcription-activator like effector nucleases (TALENs)—have enabled researchers to generate permanent mutations by introducing double-stranded breaks to activate repair pathways. The capacity of designed nucleases, like ZFN and TALENs, to generate DNA double-stranded breaks at desired positions in the genome has created optimism for therapeutic translation of locus-directed genome engineering. However, these approaches are costly and time-consuming to engineer, limiting their widespread use, particularly for large scale, high-throughput studies.
More recently, a new tool based on a totally distinct and specific system, namely bacterial CRISPR-associated protein-9 nuclease (Cas9) from Streptococcus pyogenes has generated considerable interest.
To achieve site-specific DNA recognition and cleavage, Cas9 must be complexed with both a crRNA and a separate trans-activating crRNA (tracrRNA or trRNA), that is partially complementary to the crRNA (11). The tracrRNA is required for crRNA maturation from a primary transcript encoding multiple pre-crRNAs.
During the cleavage of target DNA, the HNH and RuvC-like nuclease domains cut both DNA strands, generating double-stranded breaks (DSBs) at sites defined by a 20-nucleotide guide sequence within an associated crRNA transcript that base pairs with the target DNA sequence. The HNH domain cleaves the target DNA strand that is complementary to the guide RNA, while the RuvC domain cleaves the non-complementary strand. The double-stranded endonuclease activity of Cas9 also requires that a short conserved sequence, (2-5 nts) known as protospacer-associated motif (PAM), follows immediately 3′-of the crRNA complementary sequence.
The simplicity of the type II CRISPR nuclease, with only three required components (Cas9 along with the crRNA and trRNA) made this system amenable to adaptation for genome editing. This potential was realized in 2012 by the Doudna and Charpentier laboratories (Jinek et al., 2012, Science, Vol. 337: 816-821). Based on the type II CRISPR system described previously, a simplified two-component system was developed by combining trRNA and crRNA into a single synthetic single guide RNA (sgRNA). The sgRNA-programmed Cas9 was shown to be as effective as Cas9 programmed with separate trRNA and crRNA in guiding targeted gene alterations.
Mainly, three different variants of the Cas9 nuclease have been adopted in genome-editing protocols. The first is wild-type Cas9, which can site-specifically cleave double-stranded DNA, resulting in the activation of the double-strand break (DSB) repair machinery. DSBs can be repaired by the cellular Non-Homologous End Joining (NHEJ) pathway (Overballe-Petersen et al., 2013, Proc Natl Acad Sci USA, Vol. 110: 19860-19865), resulting in insertions and/or deletions (indels) which disrupt the targeted locus. Alternatively, if a donor template with homology to the targeted locus is supplied, the DSB may be repaired by the homology-directed repair (HDR) pathway allowing for precise replacement mutations to be made (Overballe-Petersen et al., 2013, Proc Natl Acad Sci USA, Vol. 110: 19860-19865; Gong et al., 2005, Nat. Struct Mol Biol, Vol. 12: 304-312).
Cong and colleagues (Cong et al., 2013, Science, Vol. 339: 819-823) took the Cas9 system a step further towards increased precision by developing a mutant form, known as Cas9D10A, with only nickase activity. This means that Cas9D10A cleaves only one DNA strand, and does not activate NHEJ. Instead, when provided with a homologous repair template, DNA repairs are conducted via the high-fidelity HDR pathway only, resulting in reduced indel mutations (Cong et al., 2013, Science, Vol. 339: 819-823; Jinek et al., 2012, Science, Vol. 337: 816-821; Qi et al., 2013 Cell, Vol. 152: 1173-1183). Cas9D10A is even more appealing in terms of target specificity when loci are targeted by paired Cas9 complexes designed to generate adjacent DNA nicks (Ran et al., 2013, Cell, Vol. 154: 1380-1389).
The third variant is a nuclease-deficient Cas9 (Qi et al., 2013 Cell, Vol. 152: 1173-1183). Mutations H840A in the HNH domain and D10A in the RuvC domain inactivate cleavage activity, but do not prevent DNA binding. Therefore, this variant can be used to target in a sequence-specific manner any region of the genome without cleavage. Instead, by fusing with various effector domains, dCas9 can be used either as a gene silencing or activation tools. Furthermore, it can be used as a visualization tool by coupling the guide RNA or the Cas9 protein to a fluorophore or a fluorescent protein.
Following its initial demonstration in 2012 (9), the CRISPR/Cas9 system has been widely adopted by the scientific community. It has already been successfully used to target important genes in many cell lines and organisms, including human (Mali et al., 2013, Science, Vol. 339: 823-826), bacteria (Fabre et al., 2014, PLoS Negl. Trop. Dis., Vol. 8:e2671.), zebrafish (Hwang et al., 2013, PLoS One, Vol. 8:e68708.), C. elegans (Hai et al., 2014 Cell Res. doi: 10.1038/cr.2014.11.), bacteria (Fabre et al., 2014, PLoS Negl. Trop. Dis., Vol. 8:e2671.), plants (Mali et al., 2013, Science, Vol. 339: 823-826), Xenopus tropicalis (Guo et al., 2014, Development, Vol. 141: 707-714.), yeast (DiCarlo et al., 2013, Nucleic Acids Res., Vol. 41: 4336-4343.), Drosophila (Gratz et al., 2014 Genetics, doi:10.1534/genetics.113.160713), monkeys (Niu et al., 2014, Cell, Vol. 156: 836-843.), rabbits (Yang et al., 2014, J. Mol. Cell Biol., Vol. 6: 97-99.), pigs (Hai et al., 2014, Cell Res. doi: 10.1038/cr.2014.11.), rats (Ma et al., 2014, Cell Res., Vol. 24: 122-125.) and mice (Mashiko et al., 2014, Dev. Growth Differ. Vol. 56: 122-129.). Several groups have now taken advantage of this method to introduce single point mutations (deletions or insertions) in a particular target gene, via a single gRNA. Using a pair of gRNA-directed Cas9 nucleases instead, it is also possible to induce large deletions or genomic rearrangements, such as inversions or translocations. A recent exciting development is the use of the dCas9 version of the CRISPR/Cas9 system to target protein domains for transcriptional regulation, epigenetic modification, and microscopic visualization of specific genome loci.
The CRISPR/Cas9 system requires only the redesign of the crRNA to change target specificity. This contrasts with other genome editing tools, including zinc finger and TALENs, where redesign of the protein-DNA interface is required. Furthermore, CRISPR/Cas9 enables rapid genome-wide interrogation of gene function by generating large gRNA libraries for genomic screening.
Thus, the CRISPR/Cas9 technology can be easily adapted to any gene of interest and may offer unchallenged possibilities to alter genes (knock-out, knock-in, introduction of precise mutations). Its spread in the scientific community is amazingly rapid and has triggered a recent burst of scientific communications using it.
CRISPR's delivery is commonly performed by DNA transfection or through the use of viral vectors encoding Cas9, both methods being convenient but limited to certain cell types as well as being rather intrusive. Furthermore, maintenance of Cas9 expression for a long period is possibly toxic and at best not necessary, since Cas9-mediated cleavage occurs rapidly (Jinek et al., 2013, eLife, Vol. 2, e00471) and could even be toxic on long term. Other approaches have succeeded in exploiting recombinant Cas9 and synthetic RNAs to transfer the RNPc by Proteo transfection or by physical microinjection but these CRISPRs systems remain limited to target fragile primary cells.
There is a need in the art for improved tools and methods for gene editing by using CRISPR/Cas technology.

Methods and products for genetic engineering

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)


A puzzle for printing on a printer having rollers in its paper feed path, such as a personal computer printer. The puzzle is a semirigid but flexible sheet having at least one blank side serving as means for printing on by the printer. The sheet is sufficiently flexible to negotiate through the rollers of the printer. The sheet has a plurality of die-cuts defining pieces. The die-cuts intersect at intersections. The intersections have nicks for separating each cut at its intersection, and for maintaining rigidity of the sheet during printing.

The inventor has long sold, through Compoz-A-Puzzle Inc., jigsaw puzzles, which have been die-cut in such a way that the puzzle pieces remain intact as a single sheet of cardboard until the puzzle is bent sufficiently to break "nicks" in the die-cut cardboard and to allow the pieces to separate. "Nicks" are uncut portions of the cardboard along the cuts. The uncuts or nicks are made by nicking blades of the cutting die that perforates the cardboard to cut the puzzle pieces.


A hydrogen gas detecting material, which changes in light absorption characteristics when exposed to an atmosphere containing hydrogen, and the coating method are characterized in that (1) the principal component of the hydrogen gas detecting material is tungsten oxide, (2) palladium is deposited on the surface of the tungsten oxide, (3) the tungsten oxide is coated on a substrate by a sputtering method involving a controlled oxygen pressure, and (4) the temperature of the substrate during coating with the tungsten oxide is room temperature (20° C.).

In recent years, global warming due to the emission of greenhouse gases (CO2, etc.) associated with mass consumption of fossil fuels has posed a problem. In response, the realization of an energy supply system relying minimally on fossil fuels has been necessitated. A system for electric power supply by a hydrogen fuel cell, in particular, is an electric power supply system which does not discharge CO2 as an environmental load. Technologies for its coating are under study in many fields as an infrastructure for realizing hydrogen society aimed at sustained development. However, hydrogen as a fuel is a combustible gas involving explosion, and its handling requires a careful safety monitor. For this purpose, the development of an inexpensive detecting method, which safely detects leaking trace hydrogen, becomes one of the most important challenges in realizing hydrogen society. The trace of leaking hydrogen has hitherto been monitored using a hydrogen detector, or by confirming the amount of hydrogen consumption. However, prompt pinpointing of the location of leakage is difficult. Much labors and time are usually spent on the pinpointing. The general hydrogen gas detector measures a change in electrical resistance on the surface of a semiconductor due to the adsorption of hydrogen. Since an explosion is caused by ignition of hydrogen at the power circuit in general hydrogen gas detector, it has been problematic in terms of safety. Under these circumstances, proposals have been made for hydrogen leakage detecting methods (have been proposed) in which hydrogen leakage detecting paints containing fine particles (particle size: 1 μm or less) comprising palladium oxide or tungsten oxide, or hydrogen gas detecting materials coated with such paints are applied or stuck to a location suspected of hydrogen leakage (Patent Documents 1 to 3). Judgment of hydrogen leakage by the paint is based on the visual confirmation of the site of discoloration of palladium oxide or tungsten oxide by the adsorption of leaking hydrogen. Thus, this method is a hydrogen leakage detecting method which facilitates pinpointing of the location of leakage and has high safety.
However, the paint is applied as a film by a chemical manufacturing process using wide varieties of chemicals, including a strongly acidic aqueous solution, a strongly basic aqueous solution, and a harmful organic solvent. Thus, its manufacturing cost is high, and it is also problematical in terms of load on the surrounding environment and environmental sanitation for an operator. In recent years, moreover, there has been a concern about the effect on humans of inhalation of, or exposure to, fine particles with a particle size of 1 μm or less. The production and handling of such paints are not preferred for environmental sanitation for the operator.    Patent Document 1: JP-A-4-279681    Patent Document 2: JP-A-8-253742    Patent Document 3: JP-A-2005-345338

Hydrogen gas detecting material and the coating method


A device for drilling controlled directional wells comprises a central hollow element and three hollow tubular elements connected thereto out-of-line with respect to each other. The first hollow tubular element connected by a thread to the spindle and the central hollow element, are each provided with a contact segmental section, thereby forming a pair of contact segmental sections. The sections are disposed on the opposite sides with respect to the meridian plane of the spindle in the bending plane of the drill string and at a distance L between the nearest edges of the contact segmental sections along the central axis of the first element. L≧D, where D is the spindle outer diameter. The contact segmental section of the first element is deviated from the meridian plane of the spindle in the bending plane of the drilling string in an opposite direction with respect to the reaction torque of a drilling bit.

Known is a gerotor type motor, comprising a hollow housing, a multiple-lead gear-rotored mechanism that is positioned in said housing and includes a coaxially disposed stator, and a rotor positioned within the stator, and also a spindle that is coupled, via a drive shaft, to the rotor and positioned within the spindle housing, the motor and spindle housings being interconnected using a bent substitute having threads on its edges [RU Patent 2149971, E 21B4/02, 7/08, 1999].
In this prior-art design the motor and spindle housings are connected to the bent substitute by means of threaded enclosures; the rotor and spindle being interconnected by the drive shaft using threaded adapters; the inner cavity of one of the threaded enclosures is provided with an annular bead, which bead accommodates a ring; the ring inner diameter is provided with a gap with respect to the drive shaft, and value of said gap does not exceed that of the substitute outer diameter; the bent substitute, on its edges, has threads having the crossing axes; and the longest distance between said threads axes is equal to the rotor s eccentricity with respect to the stator.
A disadvantage of this known design is as follows: setting of another angle value, and compensating of the lateral force imparted by the drilling bit using the reactive moment occurring on the substitute, the bent drilling string s motor and spindle, need disengagement of the motor from the spindle so that to enable replacement of the substitute.
Another disadvantage of this known design consists in an incomplete utilization of the possibilities for compensating the lateral force imparted by the drilling bit (at a certain value of angle on the substitute), and in a narrow range of said force, as the longest distance between the crossing threads axes does not exceed the value of the rotor eccentricity with respect to the stator.
This circumstance does not allow to compensate the positive and negatives peaks of fluctuations of the axial load on the drilling bit, and to maintain the optimum axial load on the drilling bit by preserving the axial load current values without loss of stability of a slanted-directional bent drilling string.
Known is the angle regulator, consisting of a central hollow element and three hollow mutually misaligned tubular elements connected with said central element, each of which three tubular elements has an inner through opening, wherein the inner hollow tubular element being disposed in the centre between the first and second elements, and the first and second tubular elements being connected to the inner hollow tubular element by the threads provided on their edges that face one another, the first and second tubular elements being connected by a thread to the gerotor type motor housing [U.S. Pat. No. 5,343,966, E 21B7/08, 1994].
In this known design, the first or second tubular elements are intended to connect the gerotor type motor housing to the spindle or a drill pipe, the central and inner hollow tubular elements being interconnected by a splined joint, and providing for re-setting of a new angle value when a drilling string is lifted, without disengagement from the downhole motor.
A disadvantage of this prior-art design is the lack of compensation of the lateral force imparted by the drilling bit by the use of the reactive moment occurring on the angle regulator, motor and spindle of a bent drilling string, during penetration through a well bottom heterogeneity.
In these circumstances, optimisation of penetration wells is difficult to achieve due to the difficulty to correct for the component of the lateral force exerted on the drilling bit, which force brings about the reactive bending moment that changes its direction (sign) when a slanted-directional bent drilling string loses its stability (see Gazovaya Promyshlennost Journal [Gas Industry], February 1998, pp. 42-44).
This difficulty affects accuracy of sinking the inclined wells due to the unforecastable component of the lateral force exerted on the drilling bit, so that drilling parameters cannot be optimized, and in particular the optimum axial load acting on the drilling bit cannot be maintained by preserving the axial load current values without loss of stability of the bent drilling string.
The art most pertinent to the claimed design is a regulator of an angle and reactive moment of a gerotor type motor, comprising:
a central hollow element and three hollow tubular elements connected to said central hollow element;
each of which the hollow tubular elements having a through opening;
a first tubular hollow element having one axis;
a second tubular hollow element having another axis;
an inner hollow element being disposed in the centre between the first and second elements, and having a third axis;
wherein the first and second tubular elements being connected to the inner hollow element by the threads provided on the edges facing one another;
the first hollow tubular element being connected to a spindle by a thread;
the second hollow tubular element being connected to the motor housing by a thread;
the central hollow element being connected to the inner hollow element by splines;
the inner hollow element having threads on its edges, the threads have axes that cross one another and the central axis;
the longest distance between said threads axes is the double value of the rotor eccentricity with respect to the gerotor type motor stator;
the longest distance between its central axis and axes of any of the threads on its edges being equal to the rotor eccentricity with respect to the gerotor type motor stator (U.S. Pat. No. 2,186,923, E 21B4/02, 7/08, 2000].
A disadvantage of this known design is an incomplete utilisation of a possibility to increase the deviation angle and improve penetrating capability of the gerotor type motor having a spindle and drilling bit in a bent drilling string by compensation of the resultant radially-unbalanced force generated during rotation of a drilling bit in a borehole.
In this prior-art design, the regulator has not its own contact segmental sections, which sections would improve stability of a bent drilling string, for example—any sections that would be provided at different sides with respect to the string bend plane and would ensure the continuous contact with the borehole wall in time of drilling, and also would further increase accuracy of penetration into a well bottom heterogeneity by way of providing an optimum axial load on the drilling bit, without loss of stability of the bent drilling string.

Regulator of angle and reactive moment of a gerotor type motor having a spindle and drilling bit in a bent drilling string

Obschestvo S Ogranichennoi Otvetstvennostyu'Tirma “Radius-Servis”


A universal white room disposed at the distal end of an access arm of a launch pad service tower utilizes multiple interchangeable modular rooms of varying shapes, sizes and configurations to interface with access points on multiple differently configured launch vehicles and/or payload(s). The interchangeable modular rooms attach to a common portal in the white room allowing a single white room to be used. The modular rooms may be stationary relative to the white room or movable relative to the white room.

Prior to launch, a launch vehicle and associated upper stage are positioned on a launch pad. A launch vehicle and upper stage may be positioned on the launch pad for several weeks prior to launch. The upper stage contains a payload that may include supplies for a space station, instrumentation and/or one or more spacecraft, for example, satellites. Typically, a vertical mast is positioned adjacent to the launch vehicle and assists in securing the launch vehicle in its vertical orientation. Umbilicals extending from the mast interconnect the ground-based systems and the launch vehicle-based systems, which disconnect upon liftoff of the launch vehicle. Because cryogenic propellant is typically used, propellant from remote sources is continuously loaded into propellant tanks to maintain pressures at appropriate levels. Launch vehicle electronic and avionics systems are also interconnected to ground systems while the launch vehicle is on the launch pad.
A service tower may also be located proximate to the launch vehicle and upper stage at the launch pad. In the case of a manned mission, the service tower facilitates crew access to the upper stage or spacecraft to be carried into space by the launch vehicle. In the case of manned or unmanned missions, the service tower also facilitates loading of and/or access to cargo or payloads carried on the upper stage. Sensitive electronic equipment within the launch vehicle and/or upper stage may need regular monitoring and attention. Certain payloads, for example, live organisms, may need to be added at the last moment prior to launch. The service tower typically moves away from the launch vehicle prior to lift off.
The service tower will have one or more access arms or catwalks that extend from the service tower to the launch vehicle and/or the upper stage. The access arms extend to and retract from the launch vehicle. A small enclosed room, known as a white room, may be located at the distal end of the access arm proximate the launch vehicle or upper stage while the launch vehicle is positioned on the launch pad. The white room provides a staging area for personnel accessing the launch vehicle and/or upper stage prior to launch. The room takes its name from the white paint first used in NASA's Project Gemini. In this room astronauts and attendants make final preparations before entering the upper stage spacecraft. Alternatively, from this room, scientists and/or technicians may access payload or cargo to perform maintenance, system checks, or to add, remove or swap out payload. In some instances, payload includes living organisms, such as mice, which can only be added shortly prior to liftoff.
As illustrated in FIG. 1, launch vehicles 10 and associated upper stages 12, come in a variety of shapes and sizes. Depicted are representations of an Antares, Athena II, Ariane V, Atlas II, Delta IV, Titan IV and Saturn V, respectively. The payload carried by these launch vehicles may be for a single mission having a single payload or may be multiple independent payloads each having a different purpose or mission. External booster rockets 14 may be added to a launch vehicle to provide added thrust to deliver heavier payloads. Also, because payloads can vary, the height and diameter of the upper stage may vary to accommodate different sized or multiple payloads. For example, compare the upper stage payload fairings 16 for the Titan and Atlas II. There may also be a need to access the launch vehicle, in addition to a payload. Accordingly, there may be more than one access point associated with the launch vehicle and payload, and each access point(s) may be at different distances and elevations relative to the service tower. For example, access points may be located on a vertical cylindrical surface or on a sloped conical surface, or the access points may be at different heights measured from the ground. For at least these reasons, an access arm extending from a service tower must be able to extend different distances from the service tower and the white room positioned at the end of the catwalk must interface with launch vehicles and/or upper stages of different shapes. Until now, a different white room was separately built for each different launch vehicle or launch vehicle configuration.
Current white rooms are designed to fit just one launch vehicle or launch vehicle configuration (for example, the space shuttle white room could only interface with the space shuttle). Extensive modification would be needed to a typical access arm or white room to allow the access arm to interface with one or more different launch vehicles or launch vehicle configurations that are launching from the same launch pad. Moreover, those modifications could take a long time to complete which could remove the launch pad from active launches and interfere with launch activities. A common white room design, in combination with interchangeable modules that interface with the end of the white room, allows a quick modification to allow an access arm to interface with many different launch vehicles or launch vehicle configurations that are launching from the same launch pad, without interfering with the launch cadence of the launch pad.

White room modular system for launch vehicles


The present invention relates to a flexible sheet having a composite structure for stabilizing coatings, comprising a first layer of fiber material and a second layer of fiber material impregnated by a first and a second impregnating material, respectively, and a body layer set between said first layer and said second layer according to a general sandwich structure, where the body layer consists of a third material. The first and the second impregnating materials and the third material constituting the body layer are polymeric materials presenting a substantial affinity, so that the flexible sheet has a physically heterogeneous and chemically homogeneous structure.

In the laying of a flooring, as in the case of a wall coating, it is necessary for the substrate on which the flooring or wall coating is laid to be as flat as possible. It is moreover advantageous for the coating—whether this be in the form of a carpet, parquet, marble or ceramic tiles, or any other type of material—to be isolated from the substrate, the aim being to prevent any infiltration of moisture from the substrate itself, which could damage the coating, as well as to obtain a heat-insulating effect, i.e., reducing any heat losses.
In order to meet the needs outlined above, there have been available on the market for some time now flexible sheets made of synthetic material—referred to as stabilizing sheets—which are used as base for the laying of the coating. Said sheets are principally used for stabilizing floorings, i.e., they are set between the substrate to be coated and the final coating.
One of such stabilizing sheets is marketed by the present applicant under the commercial name EVERLAY and forms the subject of the Italian patent application No. 67797-A/85 in the name of the present applicant.
The sheet EVERLAY consists of a core layer of material made of silica-fibers (also commonly referred to as glass fibers) and two layers of plastic material applied on the opposite faces of the core layer.
This type of product, which has been used and marketed for some time now, has proved to be altogether satisfactory from the operative and functional points of view. It is, however, precisely the widespread use of this material that has shown that there is still further room for improvement; for example, as regards release into the environment of part of the silica fibers which make up the core layer (there being an increasing tendency to avoid this kind of phenomenon) and/or as regards other functional aspects and features of use.

Synthetic material sheet for stabilizing coverings


A sense amplifier control circuit for use in a semiconductor memory device is provided which comprises a sense amplifier comprising first transistors of a first conductivity type connected in the form of a latch type differential amplifier, a set driver corresponding to the sense amplifier and the set driver comprising a second transistor of a second conductivity type for connecting the common source line of the latch type differential amplifier to a restore power supply line.

This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 2001-000475, filed Jan. 5, 2001, the entire contents of which are incorporated herein by reference.
1. Field of the Invention
Some conventional semiconductor memory devices use a sense amplifier consisting of a latch type differential amplifier circuit. The circuit arrangement of a conventional differential amplifier will be described below in terms of a sense amplifier section for amplifying the bit-line potential in a dynamic random access memory (DRAM) as an example.
2. Description of the Related Art
The sense amplifier section shown in FIG. 1 includes a bit line pair /BL less than 2 greater than  and BL less than 2 greater than  ( less than 2 greater than  is illustrated by example), an equalizer and multiplexer (EQLandMUX) 101, an N-channel sense amplifier (NSA) 102, an NSA common source line 103, an NSA set driver 104, and a DQ gate 105. The equalizer comprises N-channel transistors (hereinafter referred to as NFETs) Q11, Q12, and Q13. The multiplexer comprises NFETs Q14 and Q15. The NSA 102 comprises NFETs Q16 and Q17. The NSA common source line 103 provides a xe2x80x9c0xe2x80x9d write potential VBLL (e.g., Vss) to the common sources of the NFETs Q16 and Q17 in the NSA 102. The NSA set driver 104 provides VBLL to the NSA common source line 103. The DQ gate 105 comprises NFETs Q18 and Q19.
To the right of the DQ gate 105 are further provided a P-channel sense amplifier (PSA) 106, a PSA common source line 107, and a PSA set driver 108. The PSA 106 comprises P-channel transistors (hereinafter referred to as PFETs) Q20 and Q21. The PSA common source line 107 transfers a xe2x80x9c1xe2x80x9d write potential (e.g., VBLH) to the common sources of the transistors Q20 and Q21 in the PSA 106, and the PSA set driver 108 provides VBLH to the PSA common source line 107. Furthermore, the PSA 106 is followed by a multiplexer comprised of NFETs Q22 and Q23 and an equalizer comprised of NFETs Q24, Q25 and Q26.
Such a sense amplifier as described above is provided for each bit line pair; thus, as shown in the lower portion of FIG. 1, the same circuit is also provided for /BL less than 0 greater than  and BL less than 0 greater than  ( less than 0 greater than  is merely exemplary). The VBLH/2 power supply lines on the right and left supply the equalized potential VBLH/2 to the bit line pairs. CSL denotes a column select signal line. Though not shown, memory cells, each consisting of a cell capacitor and a cell transistor, are connected on the opposite sides of the sense amplifier section to each bit line pair.
The major part of the sense amplifier of FIG. 1 is formed from the NSA 102 and PSA 106 each of which has its transistors cross-coupled to the bit line pair. The common source line 103 of the NSA 102 is connected by the NSA set driver 104 consisting of an NFET to a bit line restore power supply line at the xe2x80x9c0xe2x80x9d write potential VBLL (e.g., Vss). The common source line 107 of the PSA 106 is connected by the PSA set driver 108 consisting of a PFET to a bit line restore power supply line at the xe2x80x9c1xe2x80x9d write potential VBLH.
With the conventional sense amplifier, as described above, the NSA set driver is formed of an NFET and the PSA set driver is formed of a PFET. At sense time, latch signals NSET and bPSET are set high and low, respectively, thereby amplifying a small potential difference between the bit lines to set the bit line BL (or the /BL) at xe2x80x9c1xe2x80x9d write potential on the high potential side and the bit line /BL (or the BL) at xe2x80x9c0xe2x80x9d write potential on the low potential side, respectively.
According to an aspect of the present invention there is provided a sense amplifier control circuit for use in a semiconductor memory device comprising: a sense amplifier comprising first transistors of a first conductivity type connected in the form of a latch type differential amplifier; a set driver corresponding to the sense amplifier; and the set driver comprising a second transistor of a second conductivity type for connecting the common source line of the latch type differential amplifier to a restore power supply line.

Sense amplifier control circuit of semiconductor memory device


A reproduction method for a multi-level optical recording medium according to the present invention rotates an optical recording medium, on which recording data has been recorded according to a multi-level recording method which sets several levels for light reflectivity of virtual recording cells, emits a reproduction laser beam towards the optical recording medium, and reproduces the recording data based on an electric signal generated in accordance with a received level of reflected light, the method setting the emission power of the reproduction laser beam in a range of 1.0 mW to 2.5 mW inclusive when the optical recording medium is rotated at a linear velocity in a range of 9 m/s to 25 m/s inclusive. By doing so, it is possible to improve the read accuracy for recording data while suppressing the reproduction deterioration of the optical recording medium to a level where deterioration effectively does not occur.

At present, as optical recording media, binary optical recording media constructed so that binary data can be recorded by forming pits by irradiation with a recording laser beam and the binary data can be reproduced based on the presence/absence of such pits are in widespread use. Due to demands in recent years for improvements to the recording density of optical recording media, research has been conducted into a recording method that adjusts the focused beam diameter of a recording laser beam to record recording data at a high density.
On the other hand, aside from methods that adjust the focused beam diameter, the development of multi-level optical recording media where one out of a plurality of marks with different meanings can be recorded in each virtual recording cell is also progressing. With such multi-level optical recording media, a characteristic is used whereby, for example, an altered part (hereinafter also referred to as a "recording mark") where the light transmissivity is lowered appears in one part of a virtual recording cell that is being recorded upon on the optical recording medium due to an irradiated amount of the recording laser beam being switched between several levels, and the proportion of an entire virtual recording cell taken up by a recording mark varies according to the irradiated amount of the recording laser beam. That is, when a reproduction laser beam is irradiated onto this multi-level optical recording medium, an effect is caused by the light transmissivity in virtual recording cells in which the above-described recording marks have been formed, resulting in there being several levels (for example, five levels) of light reflectivity for the reproduction laser beam. Accordingly, by associating the respective light reflectivity levels with respective data contents, it is possible to record one out of a plurality of data in one virtual recording cell. Here, the expression "light transmissivity" refers to the proportion of the reproduction laser beam irradiated onto a virtual recording cell that passes through the virtual recording cell, and the expression "light reflectivity" refers to the proportion of the reproduction laser beam irradiated onto a virtual recording cell that passes through the virtual recording cell, is reflected off a reflective layer of the multi-level optical recording medium, and then passes back through the virtual recording cell and exits to the periphery of the multi-level optical recording medium.
When reproducing recording data recorded on this multi-level optical recording medium (hereinafter this is also referred to as "multi-level reproduction"), the recording data is reproduced by specifying the light reflectivity of a virtual recording cell irradiated with the reproduction laser beam as a first, second, third, etc., level out of a plurality of light reflectivity levels. Here, in order to record recording data (recording marks M) at an even higher density than a normal binary optical recording medium, the size of the virtual recording marks S on a multi-level optical recording medium is set so as to be smaller than the pits on a binary optical recording medium. Also, the reading speed (i.e., read number of recording marks) per unit reproduction time should be set higher for a multi-level optical recording medium than a normal binary optical recording medium and the standard rotational speed (that is, a linear velocity when recording and reproduction are carried out at 1× speed) is set higher than the standard rotational speed of a normal binary optical recording medium. This means that during multi-level reproduction, in the case where the irradiation power of a reproduction laser beam is set at a similar level as the irradiation power (in this case, 0.7 mW or below) of the reproduction laser beam set for a normal binary optical recording medium, the ratio ("C/N", also referred to below as "SNR") of a noise component included in the reflected light increases, which can lead to a decrease in the read accuracy for recording data and to the occurrence of tracking errors when the medium is rotated at high speed. Accordingly, the present inventors tried to solve the above problems by increasing the irradiation power of the reproduction laser beam during multi-level reproduction.

Multi-level optical recording medium reproducing method and reproducing device


A lever device includes an elongated body and a double-sided stretch releasing adhesive attached to the body, whereby the body can be firmly adhesively bonded to a surface and cleanly removed from the surface without damaging the surface by stretching the adhesive. The device may include a base, a body member pivotally connected with the base, and stretch releasing adhesive arranged to attach the base and/or body member to a surface or object. The base may be pivotally connected with an end of the body member or to the middle of the body member.

Stretch releasing adhesive tapes are a class of high performance pressure-sensitive adhesives that combine strong holding power with clean removal and no surface damage. Stretch releasing adhesive tapes are characterized by their ability to be cleanly removed from a surface without damaging the surface by stretching the tape. A commercially available double-sided stretch releasing adhesive is the product sold under the trade designation COMMAND adhesive by 3M Company, St. Paul, Minn. This product is currently manufactured as discrete strips with one end of the strip including a non-adhesive pull tab to facilitate stretching of the strip during removal. Stretch releasing adhesives are useful in a wide variety of assembling, joining, attaching, and mounting applications.
Levers are simple machines capable of producing a mechanical advantage which find application in many well known devices. Common examples of levers include scissors, nut crackers, and tweezers. For certain lever devices, it is desirable to attach the lever to a surface. For example, U.S. Pat. No. 4,877,277 (Leopoldi) discloses a lever adapter for a door knob for aiding arthritic patients in rotating the door knob. The lever adapter is attached to the door knob by a concave, arcuate member having a layer of adhesive. U.S. Pat. No. 4,352,476 (Meeks) discloses a cable clamp including a lever. The cable clamp includes a double-sided adhesive tape for attaching the clamp to a work piece. These devices, however, have limited uses and suffer from other limitations and drawbacks.
There is therefore a need for a versatile lever device that can be easily attached to and removed from a surface or work piece and can be used to generate tensile or compressive forces or torque depending on the particular end use application. It would therefore be desirable to provide a simple and inexpensive lever device that can be used to produce tension, compression, or torque and that can be securely fastened to a surface and readily removed therefrom without damaging the surface or leaving unwanted residue.


A microbiological heap leaching simulation process wherein material, representative of ore in a heap, is microbiologically leached in a housing and the temperature of the material at a plurality of locations in the housing is monitored and controlled to reduce heat loss from the housing.

This invention relates generally to the microbiological leaching of ore in a heap and is concerned, more particularly, with the simulation of certain aspects thereof.
In a microbiological heap leaching application mined ore is crushed and agglomerated with acid and nutrients. Oxygen and carbon dioxide are supplied to the ore to provide an environment for organism growth and to promote the oxidising conditions required for mineral degradation.
Normally the acidic solution is applied to the top of the ore heap and is allowed to percolate downwardly while the oxygen and carbon dioxide are supplied in the form of air introduced to the bottom of the heap. The air flowing upwardly and the acidic solution flowing downwardly, through the heap, are counter-current transport media which interact at different points of the heap allowing oxygen transfer, species migration and a heat exchange mechanism within the heap.
It is known that a heap leaching process is temperature-dependent with determining factors including the ore type and the microorganisms which are used for the leaching. For example, the acidic solubilisation of copper from copper oxide ores, chalcocitic ores and other secondary copper sulphide bearing ores, at low temperatures, may result in an acceptable recovery of the metal. On the other hand minerals such as enargite, carrollite and chalcopyrite are slow leaching at low temperatures (below 30° C.) and leaching at these temperature results in poor metal extraction which, in most instances, is uneconomical.
The enhanced oxidation of the sulphide components of minerals of the aforementioned type, by microbiological action, is an exothermic reaction which releases substantial amounts of energy, a process which must be correctly managed to obtain effective metal recovery.
It is difficult and expensive to monitor conditions inside a commercially operated heap due, primarily, to the size of a typical heap and the amount and type of material it contains.

Method of and apparatus for simulating a biological heap leaching process


The present invention involves an artificial nose having an array comprising at least a first dye and a second dye in combination and having a distinct spectral response to an analyte. In one embodiment, the first and second dyes are from the group comprising chemoresponsive dyes, and the second dye is distinct from the first dye. In one embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phthalocyanine, and salen, or their metal complexes. In another embodiment, the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes. The present invention is particularly useful in detecting metal ligating vapors. Further, the array of the present invention can be connected to a visual display device.

There is a great need for olfactory or vapor-selective detectors (i.e., "artificial noses") in a wide variety of applications. For example, there is a need for artificial noses that can detect low levels of odorants and/or where odorants may be harmful to humans, animals or plants. Artificial noses that can detect many different chemicals are desirable for personal dosimeters in order to detect the type and amount of odorants exposed to a human, the presence of chemical poisons or toxins, the spoilage in foods, the presence of flavorings, or the presence of vapor emitting items, such as plant materials, fruits and vegetables, e.g., at customs portals.
Conventional artificial noses have severe limitations and disadvantages and are not considered generally useful for such purposes. Limitations and disadvantages of conventional artificial noses include their need for extensive signal transduction hardware, and their inability to selectively target metal-coordinating vapors and toxins. In addition, artificial noses which incorporate mass sensitive signal transduction or polar polymers as sensor elements are susceptible to interference by water vapor. This limitation is significant in that it can cause variable response of the detector with changes ambient humidity. See F. L. Dickert, O. Hayden, Zenkel, M. E. Anal. Chem. 71, 1338 (1999).
Initial work in the field of artificial noses was conducted by Wilkens and Hatman in 1964, though the bulk of research done in this area has been carried out since the early 1980's. See, e.g., W. F. Wilkens, A. D. Hatman. Ann. NY Acad. Sci., 116, 608 (1964); K. Pursaud, G. H. Dodd. Nature, 299, 352-355 (1982); and J. W. Gardner, P. N. Bartlett. Sensors and Actuators B, 18-19, 211-220 (1994).
Vapor-selective detectors or "artificial noses" are typically based upon the production of an interpretable signal or display upon exposure to a vapor emitting substance or odorant (hereinafter sometimes referred to as an "analyte"). More specifically, typical artificial noses are based upon selective chemical binding or an interface between a detecting compound of the artificial nose and an analyte or odorant, and then transforming that chemical binding into a signal or display, i.e., signal transduction.
Polymer arrays having a single dye have been used for artificial noses. That is, a series of chemically-diverse polymers or polymer blends are chosen so that their composite response distinguishes a given odorant or analyte from others. Examples of polymer array vapor detectors, including conductive polymer and conductive polymer/carbon black composites, are discussed in: M. S. Freund, N. S. Lewis, Proc. Natl. Acad. Sci. USA 92, 2652-2656 (1995); B. J. Doleman, R. D. Sanner, E. J. Severin, R. H. Grubbs, N. S. Lewis, Anal. Chem. 70, 2560-2564 (1998); T. A. Dickinson, J. White, J. S. Kauer, D. R. Walt, Nature 382, 697-700 (1996)(polymer array with optical detection); A. E. Hoyt, A. J. Ricco, H. C. Yang, R. M. Crooks, J. Am. Chem. Soc. 117, 8672 (1995); and J. W. Grate, M. H. Abraham, Sensors and Actuators B 3, 85-111 (1991).
Other interface materials include functionalized self-assembled monolayers (SAM), metal oxides, and dendrimers. Signal transduction is commonly achieved with mass sensitive piezoelectric substrates, surface acoustic wave (SAW) transducers, or conductive materials. Optical transducers (based on absorbance or luminescence) have also been examined. Examples of metal oxide, SAM, and dendrimer-based detectors are discussed in J. W. Gardner, H. V. Shurmer, P. Corcoran, Sensors and Actuators B 4, 117-121 (1991); J. W. Gardner, H. V. Shurmer, T. T. Tan, Sensors and Actuators B 6, 71-75 (1992); and R. M. Crooks, A. J. Ricco, Acc. Chem. Res. 31, 219-227 (1998). These devices also use a single dye.
Techniques have also been developed using a metalloporphyrin for optical detection of a specific, single gas such as oxygen or ammonia, and for vapor detection by chemically interactive layers on quartz crystal microbalances. See A. E. Baron, J. D. S. Danielson, M. Gouterman, J. R. Wan, J. B. Callis, Rev. Sci. Instrum. 64, 3394-3402 (1993); J. Kavandi, et al., Rev. Sci. Instrum. 61, 3340-3347 (1990); W. Lee, et al., J. Mater. Chem. 3, 1031-1035 (1993); A. A. Vaughan, M. G. Baron, R. Narayanaswamy, Anal Comm. 33, 393-396 (1996); J. A. J. Brunink, et al., Anal. Chim. Acta 325, 53-64 (1996); C. Di Natale, et al., Sensors and Actuators B 44, 521-526 (1997); and C. DiNatale, et al., Mat. Sci. Eng. C 5, 209-215 (1998). However, these techniques either require extensive signal transduction hardware, or, as noted above, are limited to the detection of a specific, single gas. They are also subject to water vapor interference problems, as discussed previously.
While typical systems to date have demonstrated some success in chemical vapor detection and differentiation, these systems have focused on the detection of non-metal binding or non-metal ligating solvent vapors, such as arenes, halocarbons and ketones. Detection of metal-ligating vapors (such as amines, thiols, and phosphines) has been much less explored. Further, while some single porphyrin based sensors have been used for detection of a single strong acid, there is a need for sensor devices that will detect a wide variety of vapors.
To summarize, there are a number of limitations and drawbacks to typical artificial noses and single porphyrin based sensors. As noted above typical artificial noses are not designed for metal binding and metal ligating vapors, such as amines, thiols, and phosphines. Further, typical artificial noses require extensive signal transduction hardware, and are subject to interference from water vapor. As noted above, single porphyrin based sensors have been used for detection of a single strong acid, but cannot detect a wide variety of vapors. Thus, there is a need for new artificial noses and methods that overcome these and other limitations of prior artificial noses and single porphyrin based sensors and methods.

This patent is subject to a terminal disclaimer.

Colorimetric artificial nose having an array of dyes and method for artificial olfaction

The Board of Trustees of the University of Illinois


A nonvolatile semiconductor memory device includes a memory cell array which includes a memory cell string including a plurality of memory cells each having a variable resistor element and a switching element having a current path with one end and the other end, between which the variable resistor element is connected, the plurality of memory cells having current paths thereof being connected in series, the memory cell array further including a first select element connected to one end of a current path of the memory cell string, and a second select element connected to the other end of the current path of the memory cell string, a bit line which is electrically connected to one end of a current path of the first select element, and a source line which is electrically connected to one end of a current path of the second select element.

1. Field of the Invention
The present invention relates to a nonvolatile semiconductor memory device and a data erase/write method thereof, and is applied, for example, to a ReRAM (resistive memory) using a variable resistor element in which a resistance value varies depending on the direction of a voltage that is applied.
2. Description of the Related Art
In recent years, studies have been made on the application of, e.g. a ReRAM (resistive memory) using a variable resistor element in which a resistance value varies depending on the direction of a voltage that is applied. As disclosed in, for instance, Jpn. Pat. Appln. KOKAI Publication No. 2004-272975 and S.Q. Liu, N. J. Wu, A. Ignatiev (App, Phy, Lett, 76, 19 (2000), such a phenomenon was found that when a voltage pulse is applied to a thin film, which becomes a variable resistor element, the resistance value of the thin film remarkably varies depending on the direction (sign) of the pulse voltage, and this phenomenon is applied to memories.
Jpn. Pat. Appln. KOKAI Publication No. 2004-272975 discloses an example of a nonvolatile semiconductor memory device using a variable resistor element. In the structure of KOKAI No. 2004-272975, however, only one select transistor (Si), which selects a series-connected memory cell section (memory cell string) (2), is provided in association with each series-connected memory cell section (2).
Thus, there is a tendency that the direction of the voltage that is to be applied to the variable resistor element cannot be changed, and data erase (reset) cannot be executed in units of the series-connected memory cell section (memory cell string) (2).

Nonvolatile semiconductor memory device and data erase/write method thereof


Methods for identifying disease-specific markers, in particular breast cancer markers, by electrophoretically separating serum albumin complexes in a biological sample on a membrane are provided. Electrophoretic separation profiles representing different diseases or different cancer stages can be produced, and used in the diagnosis, prognosis and treatment of these diseases. Methods for identification of a cancer peptide fragment comprising a cancer peptide motif are provided. Also provided are breast cancer and other cancer markers and antibodies that specifically recognize these markers.

Blood is a rich and readily accessible source for the detection of diagnostic markers and therapeutic targets in many human diseases. Currently, however, only a handful of plasma proteins are routinely used in the clinic for diagnostic purposes. It is generally established that these low-abundance proteins contain most of the useful biomarkers, including those that are produced by specific diseases such as cardiovascular diseases, neurological disorders, autoimmune diseases, and cancer, but these low abundance proteins are difficult to detect because they are often masked by high-abundance proteins, particularly serum albumin. In serum and plasma, the quantities of high-abundance proteins and some low-abundance proteins span over 10 orders of magnitude. For example, low-abundance proteins such as growth factors and cytokines are present in one millionth to one trillionth of the abundant proteins.
Serum albumin, the most abundant protein in serum typically present at 45-50 mg/ml, constitutes about 55% of total serum protein. Albumin functions as a scaffold for binding proteins, lipids, small molecules in the intracellular space and has been found to form associations with peptide hormones such as insulin and glucagon; serum amyloid A, interferons, bradykinin, the amino-terminal peptide of HIV-1, gp41, the 14-kDa fragment of streptococcal protein G, and others. In order to carry out such diverse functions, it is likely that serum albumin population is heterogeneous and contains many different albumin complexes. Technologies currently available such as two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) developed by O'Farrel (O'Farrel, P., (1975) J. Biol. Chem. 250: 4007-4021) do not allow separation of protein complexes because they were carried out under denaturing conditions which dissociated the serum albumin complexes.
Due to the wide range of protein concentrations and high structural complexity of the constituent proteins, analysis of the proteome of plasma and serum represents a challenge. At present, low-abundance proteins can only be detected for further analysis by removal of abundant proteins to decrease both dynamic concentration range and complexity.
One approach for removing the most abundant plasma proteins, yielding an enriched pool of low-abundance proteins, is immunoaffinity chromatography (Gallent, S R., (2008) Methods Mol. Biol. 421:53-60). Although this method has increased the number of detectable proteins in plasma/serum analysis, it has several major drawbacks. First, up to 90% of potential protein biomarkers are known to be associated with the highly abundant carrier proteins in blood such as serum albumin. Depletion of the high-abundance proteins often removes many potentially important marker proteins. In addition, some low-abundance proteins may be retained in the column through nonspecific binding, resulting in their loss from the flow-through fractions. Extensive sample handling also increases the chance of sample loss and protein degradation, resulting in substantial sample-to-sample variation. The depletion process is also time-consuming and the immunoaffinity columns are rather expensive.
Realizing that most of potential protein biomarkers are likely to be associated with the highly abundant carrier proteins in blood such as serum albumin, a different approach for partial enrichment of the low-abundance proteins is to capture serum albumin onto a solid support followed by selectively eluting the low-abundance proteins with solvents. However, serum albumin is composed of mixtures of complexes and selective removal of bound proteins based on affinity without first resolving the albumin complexes will have difficulty in obtaining the low-abundance proteins. Most of proteins detected by this procedure were abundant proteins present naturally and not related to the specific disease.
Diseases such as cancer are caused by, for example, DNA damage (i.e., mutation) in genes that regulate cell growth and division. It is often characterized by the production of abnormal proteins. Because of the difficulties indicated above it is virtually impossible to isolate the low-abundance disease proteins. Compounding the problem for their detection is the fact that in many diseased cells, these disease-associated proteins are degraded by proteolytic enzymes, generating peptide fragments that are subsequently released into the bloodstream. Being low molecular weight in nature, these peptide fragments generally have a half-life of only several hours and most of them are cleared from circulation by the kidney (Lowenthal et al. (2005) Clinical Chemistry 51: 1933-45). However, some of these peptide fragments have high affinity for serum albumin which has a rather long half-life of about 19 days. By their association with serum albumin to form complexes the longevity of these disease-related peptide fragments can be increased by approximately 60 to 100-fold (Dennis et al. (2002) J. Biol. Chem. 277: 35035-43).
Breast cancer is the second most common cause of cancer death in women in the United States and is also a cause of disability, psychological trauma, and economic loss. Breast cancer morbidity increases significantly if it is not detected early in its progression. Early detection of breast cancer before symptoms appear is highly desirable. Even so, it is estimated that between 15 to 25% of women with early stage breast cancer are currently missed by mammography particularly if they have dense breasts. The challenge is to address the inherent limitations of mammography by developing a simple blood test procedure that can detect early stage breast cancer and potentially enhance treatment and enhance the potential survival of the patient.

Serum markers associated with early and other stages of breast cancer

Temple University of The Commonwealth System of Higher Education


A filter device includes a filter housing (10), a filter inlet (12), a filter outlet (14), and a filter element (16). The filter element divides a filter area (18) into two partial areas (20, 22). One partial filter areas is conical in form with the cross-section of that partial area (20) being tapered from the filter inlet (12) to the filter outlet (14). The partial areas are separated from each other by the filter element. This arrangement results in an optimum residence time distribution inside the filter device at a uniform flow rate, which is particularly useful for highly viscous fluids such as polymer melts or similar.

Filter devices, such as those disclosed in U.S. Pat. Nos. 4,964,984, 4,169,795, 4,052,315, 4,043,918, and in GB 2 075 364), are readily obtainable on the market in a multiplicity of embodiments. The structure of the filter elements, which filter impurities out of a fluid, is determined by the manufacturer. Filter elements of higher quality have a multilayer meshed structure which may rest at least on one supporting fabric to enable the structure to resist higher pressure or pressure peaks.
In principle, it is desirable to arrive at uniform flow behavior inside the filter space during the filtration process, while avoiding dead spaces. The requirements set for the desired behavior increase as the viscosity of the fluid increases, especially if liquefied polymer materials or polymer solutions are to be filtered.
U.S. Pat. No. 3,817,377 discloses a generic filter device, in particular one for separation of impurities from hot thermoplastic polymer material. In one embodiment of the conventional filter device shown in FIGS. 4 and 5 of that patent, a conical filter element subdivides a conical filter space into two conical subspaces. The conicities of the two subspaces extend constantly in opposite directions but to different extents, that is, with different cross-sections relative to one point of reference. The diameter of the filter element is measured from the filter outlet in the direction of the filter inlet more or less constantly. The resulting conicity of the filter element is referred to the longitudinal direction of the filter outlet. The bounding walls following the subspaces as housing elements have a conical orientation comparable to that of the filter element, so that the conventional solution applied for this purpose is complex in structure. Control of flow, which is unfavorable from the viewpoint of energy, is obtained because of the different cross-sectional patterns referred to one point of comparison, especially in the case of high-viscosity fluids.